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12,200 | 28,497,108 | Although not statistically significant ( P = 0.06 ) , by meta-regression , in the absence of ROSE , FNB showed a relatively better diagnostic adequacy .
The absence of ROSE was associated with a higher SMD , i. e. , in the presence of an onsite pathologist , FNA required relatively fewer passes to establish the diagnosis than in the absence of an onsite pathologist .
Conclusions There is no significant difference in the diagnostic yield between FNA and FNB , when FNA is accompanied by ROSE .
However , in the absence of ROSE , FNB is associated with a relatively better diagnostic adequacy in solid pancreatic lesions .
Also , FNB requires fewer passes to establish the diagnosis | Background The diagnostic yield of endoscopic ultrasound ( EUS ) guided fine-needle aspiration ( FNA ) is variable , and partly dependent upon rapid onsite evaluation ( ROSE ) by a cytopathologist .
Second generation fine-needle biopsy ( FNB ) needles are being increasingly used to obtain core histological tissue sample s. Aims Studies comparing the diagnostic yield of EUS guided FNA versus FNB have reached conflicting conclusions .
We therefore conducted a systematic review and meta- analysis to compare the diagnostic yield of FNA with FNB , and specifically evaluating the diagnostic value of ROSE while comparing the two types of needles . | OBJECTIVE To assess and compare the quality of nonstructured and structured abstract s of original research articles in three medical journals . DESIGN Blind , criterion-based observational study . SAMPLE R and om sample of 300 abstract s ( 25 abstract s per journal each year ) of articles published in the British Medical Journal ( BMJ ) , the Canadian Medical Association Journal and the Journal of the American Medical Association ( JAMA ) in 1988 and 1989 ( nonstructured abstract s ) and in 1991 and 1992 ( structured abstract s ) . MAIN OUTCOME MEASURES The quality of abstract s was measured against 33 objective criteria , which were divided into eight categories ( purpose , research design , setting , subjects , intervention , measurement of variables , results and conclusions ) . The quality score was determined by dividing the number of criteria present by the number applicable ; the score varied from 0 to 1 . RESULTS The overall mean quality scores for nonstructured and structured abstract s were 0.57 and 0.74 respectively ( p < 0.001 ) . The frequency in meeting the specific criteria was generally higher for the structured abstract s than for the nonstructured ones . The mean quality score was higher for nonstructured abstract s in JAMA than for those in BMJ ( 0.60 v. 0.54 , p < 0.05 ) . The scores for structured abstract s did not differ significantly between the three journals . CONCLUSIONS The findings support recommendations that promote the use of structured abstract s. Further studies should be performed to assess the effect of time on the quality of abstract s and the extent to which abstract s reflect the content of the articles BACKGROUND AND STUDY AIMS Histological examination of core tissue sample s may have advantages over cytology in endoscopic ultrasound (EUS)-guided sampling . We aim ed to evaluate the feasibility and efficiency of a new 22 G core biopsy needle . PATIENTS AND METHODS Consecutive patients with a pancreatic mass lesion or peri-intestinal lymphadenopathy sequentially underwent fine needle biopsy with both a newly developed 22 G core needle ( the FNB needle ) and a st and ard 22 G fine needle aspiration ( FNA ) needle , in r and omized order . RESULTS In 144 patients , mean age 48 years ( ± st and ard deviation [ SD ] 14 ; range 18 - 82 ) , with 145 lesions ( mean lesion size 39 ± 15 mm , range 15 - 99 ) , EUS-guided sampling was technically feasible with both needles in all patients . Mean number of passes to obtain sufficient tissue was 1.2 ± 0.5 with the core needle vs. 2.5 ± 0.9 with the st and ard needle ( P < 0.001 ) . FNB specimens were adequate for evaluation in 125 ( 86.2 % ) vs. 127 ( 87.6 % ) with FNA ( P = 0.72 ) . Among 139 patients available for follow-up , FNB provided a correct diagnosis in 110 ( 79.1 % ) and FNA in 112 ( 80.6 % ) ( P = 0.73 ) . Sensitivity , specificity , positive and negative predictive values , and accuracy for diagnosis of malignancy were 90 % , 100 % , 100 % , 93 % , 96 % for FNB and 77 % , 100 % , 100 % , 85 % , 92 % for FNA , respectively ( P > 0.05 ) . CONCLUSION FNB with the new 22 G core needle was technically feasible , efficient and comparable to FNA with a st and ard needle . The core needle required fewer passes to provide an adequate sample , offering potentially shorter procedure time Background : Endoscopic ultrasound (EUS)-guided fine needle aspiration ( FNA ) with bedside cytopathology is the gold st and ard for assessment of pancreatic , subepithelial , and other lesions in close proximity to the gastrointestinal tract , but it is time-consuming , has certain diagnostic limitations , and bedside cytopathology is not widely available . Aims : The goal of this study is to compare the diagnostic yield of EUS-guided FNA with on-site cytopathology and EUS-guided core biopsy . Methods : Twenty-six patients with gastrointestinal mass lesions requiring biopsy at a tertiary medical center were included in this retrospective analysis of a prospect i ve cohort . Two core biopsies were taken using a 22 gauge needle followed by FNA guided by a bedside cytopathologist at the same endoscopic session . The diagnostic yield and test characteristics of EUS core biopsy and EUS FNA with bedside cytopathology were examined . Results : The mean number of passes was 3.2 for FNA , and the mean procedure time was 39.4 minutes . The final diagnosis was malignant in 92.3 % . Sensitivity and specificity were 83 % and 100 % , respectively , for FNA , and 91.7 % and 100 % , respectively , for core biopsy . Diagnostic accuracy was 92.3 % for FNA and 84.6 % for core biopsy . The two approaches were in agreement in 88.4 % with a kappa statistic of 0.66 ( 95 % confidence interval 0.33 – 0.99 ) . Conclusions : An approach using two passes with a core biopsy needle is comparable to the current gold st and ard of FNA with bedside cytopathology . The performance of two core biopsies is time-efficient and could represent a good alternative to FNA with bedside cytopathology The specific needle sizes/types used in performing endoscopic ultrasound-guided fine needle aspirations ( EUS-FNA ) vary . The HD ProCore ( ™ ) is a 22-gauge beveled needle allowing for core biopsy along with aspiration material . In this study we compare this needle with a st and ard 22-gauge needle . Between April 1 , 2011 and November 15 , 2011 , 18 patients undergoing EUS-FNA using the HD ProCore ( ™ ) needle were compared to a control group of 18 cases using the st and ard 22-gauge needle . Smears were assessed for : three-dimensional clusters , thick obscuring clusters , monolayer sheets , cellularity , crowded obscuring single cells , blood , and nuclear staining . Cell blocks were assessed for cellularity and presence of diagnostic material . Records were review ed for the overall adequacy , number of FNA passes , and patient follow-up . Overall , the two needle groups demonstrated similar results for the cytology parameters , amount of diagnostic cell block material , adequacy , and accuracy . The mean number of passes to achieve adequacy varied between the groups [ 2.94 for the st and ard 22-gauge needle group versus 2.11 for the beveled needle group ( P=0.03 ) ] with no meaningful difference in case duration between needle groups . No complications were reported . The beveled EUS needle affords similar cytologic interpretability , adequacy , diagnostic accuracy , and amount of cell block material as a st and ard needle . There was a statistically significant trend toward fewer passes to achieve adequacy with the beveled EUS-FNA needle . Therefore , the EUS-FNA needle with a lateral bevel is a diagnostically similar alternative to st and ard endoscopy needles , the possibility that this beveled needle may improve per pass adequacy requires further verification Background and aims : Endoscopic ultrasound‐guided fine needle aspiration ( EUS‐FNA ) has a diagnostic accuracy of 70–90 % , depending on the site under evaluation . In order to improve EUS‐guided tissue sampling a novel 19‐gauge trucut‐type needle has been design ed to obtain core biopsies during EUS . We prospect ively evaluated the safety and accuracy of EUS‐FNA alone versus combined EUS‐FNA and trucut needle biopsy ( TNB ) in patients referred to our Unit over a 3‐year period BACKGROUND AND STUDY AIMS The aims of this study were : firstly , to determine the usefulness of endoscopic ultrasound-guided fine-needle aspiration ( EUS-FNA ) in obtaining tissue diagnosis of intramural and extraintestinal lesions ; secondly , to assess the immediate , acute , and 30-day complications in these patients ; and thirdly , to assess the impact of the tissue diagnoses on patient management . PATIENTS AND METHODS All EUS-FNAs of extraintestinal mass lesions and intramural gastrointestinal tumors over a 26-month period were evaluated prospect ively . The reference st and ards for the final diagnosis were surgery ( n = 20 ) , repeat imaging ( n = 12 ) , clinical follow-up ( n = 4 ) , or death from disease ( n = 2 ) . Four patients were lost to follow-up . RESULTS Forty-two consecutive patients ( 24 men , 18 women ; mean age 59.7 years ) underwent EUS-FNA of extraintestinal mass lesions and intramural gastrointestinal tumors . Previous attempts at tissue diagnosis had failed in 52.4 % of the patients . The EUS-FNA cytological diagnoses included : 17 gastrointestinal stromal tumors , five esophageal cancers , five rectal cancers , one bronchogenic cyst , one foregut duplication cyst , and 13 other miscellaneous diagnoses . The mean number of passes needed to reach a diagnosis was 3.9 ( + /- 2.2 ) . The mean follow-up period was 13.1 months . The sensitivity , specificity , positive predictive value , negative predictive value , and accuracy of EUS-FNA of extraintestinal and intramural tumors were 97 % , 100 % , 100 % , 90 % , and 98 % , respectively . No major complications were encountered . CONCLUSIONS EUS-FNA is a safe and accurate method that can provide a tissue diagnosis in intramural and extraintestinal mass lesions , especially when other modalities have failed . EUS-FNA significantly affects the management of patients by allowing them to be allocated to appropriate treatment and by avoiding the need for more invasive procedures to obtain tissue diagnosis Abstract Objective . Endoscopic ultrasonography (EUS)-guided fine-needle aspiration ( EUS-FNA ) may facilitate tissue sampling for histopathological diagnosis of subepithelial tumors ( SETs ) in the gastrointestinal ( GI ) tract . However , immunohistochemistry is not always feasible using EUS-FNA sample s due to the low quality of specimens often obtained by aspiration . This study aim ed to compare the use of 22-gauge ( G ) EUS-guided fine-needle biopsy ( EUS-FNB ) with 22 G EUS-FNA for core sampling used for histopathological examination , including immunohistochemistry , in patients with GI SETs . Methods . Twenty-eight patients with GI SETs ≥2 cm in size were prospect ively enrolled at five university hospitals in Korea between January and June 2013 . They were r and omized to undergo either EUS-FNB or EUS-FNA . Results . A total of 22 patients was finally analyzed in this study : 10 and 12 patients underwent EUS-FNA and EUS-FNB , respectively . Compared to the EUS-FNA group , the EUS-FNB group had a significantly lower median number of needle passes to obtain macroscopically optimal core sample s ( 4 vs. 2 , p = 0.025 ) ; higher yield rates of macroscopically and histologically optimal core sample s with three needle passes ( 30 % vs. 92 % , p = 0.006 ; 20 % vs. 75 % , p = 0.010 , respectively ) ; and a higher diagnostic sufficiency rate ( 20 % vs. 75 % , p = 0.010 ) . No technical difficulties were encountered in either group . Conclusions . This study shows that EUS-FNB has a better ability to obtain histological core sample s and a higher diagnostic sufficiency rate than EUS-FNA and that EUS-FNB is a feasible , safe , and preferable modality for adequate core sampling for histopathological diagnosis of GI SETs Endoscopic ultrasound-guided fine-needle aspiration ( EUS-FNA ) is widely used for diagnosis of pancreatic lesions . The Echotip Procore Needle ( Wilson-Cook Medical ) is a new 22 G fine biopsy needle ( FNB ) for obtaining core biopsy material at time of EUS . This study aim ed to compare the technical and diagnostic performance of conventional FNA and FNB . Thirty-two patients met the design criteria for this prospect i ve paired cohort study . All lesions sample d were solid ( non-cystic ) pancreatic masses by EUS appearance . Patients were r and omized to receive FNA or FNB by first attempt . A cytopathologist performed on-site evaluations . Sample s were assessed for accuracy of diagnosis , cellularity , contamination , and sufficiency for ancillary studies . Technical and diagnostic performances were compared . Compared to FNA , there was a statistically significant decreased ability of FNB to achieve a diagnosis ( FNA 93.8 % , FNB 28.1 % , P < 0.001 ) . FNB was diagnostically superior to FNA in 1 of 32 cases . Technical failures were observed in five cases due to resistance to advancement of the FNB needle . Regarding operator perceived ease-of-use , FNA outperformed FNB ( P < 0.001 ) . Eight cases had insufficient FNB material to survive tissue processing . There was no significant difference in mean specimen cellularity between devices . FNA sample s showed an increased amount of contaminant ( P = 0.036 ) but were more sufficient for ancillary studies ( P = 0.502 ) . Although deemed comparable to FNA when providing material for cytology , the pledged advantage of FNB acting like a core biopsy needle was not apparent in our series . Additional studies are needed before routine adoption of 22 G FNB can be recommended BACKGROUND There is a lack of prospect i ve , r and omized studies comparing the diagnostic yield and complication rates of 22-gauge and 25-gauge needles during EUS-FNA of solid pancreatic masses . OBJECTIVES Our primary aim was to compare the diagnostic yield of 22-gauge and 25-gauge needles . Secondary aims included determining the number of needle passes performed , ease of needle passage , and complications . DESIGN Prospect i ve , r and omized study . SETTING Tertiary referral centers at Yale University School of Medicine , New Haven , Connecticut , and Virginia Piper Cancer Institute , Minneapolis , Minnesota . PATIENTS Patients with a suspected solid pancreatic mass from February 2007 to June 2008 were enrolled . INTERVENTIONS Patients were r and omized to EUS-FNA with a 22-gauge or 25-gauge needle . MAIN OUTCOME MEASUREMENTS A diagnostic result was defined as cytology findings positive for malignant cells . RESULTS A total of 131 patients were enrolled : EUS-FNA was performed with a 22-gauge needle in 64 patients and with a 25-gauge needle in 67 patients . Cytology was diagnostic in 120 ( 91.6 % ) of 131 patients overall : 56 ( 87.5 % ) of 64 with 22-gauge needles and 64 ( 95.5 % ) of 67 with 25-gauge needles ( no statistically significant difference was found between the 2 groups ; P=.18 ) . A similar number of passes was performed in both arms ( mean [ SD ] 2.6 [ 1.2 ] each ; P=.96 ) . There were no complications in either group . LIMITATION A larger number of patients is needed to determine small differences in diagnostic yield . CONCLUSIONS This is the first prospect i ve , r and omized trial comparing 22-gauge and 25-gauge needles in EUS-FNA of solid pancreatic masses . We achieved equally high diagnostic yields by using a similar number of passes , showing that 25-gauge needles are an effective alternative to 22-gauge needles BACKGROUND To overcome limitations of cytology , biopsy needles have been developed to procure histologic sample s during EUS . OBJECTIVE To compare 22-gauge ( G ) FNA and 22 G biopsy needles ( FNB ) for EUS-guided sampling of solid pancreatic masses . DESIGN R and omized trial . SETTING Tertiary-care medical center . PATIENTS This study involved 56 patients with solid pancreatic masses . INTERVENTION Sampling of pancreatic masses by using 22 G FNA or 22 G FNB devices . MAIN OUTCOME MEASUREMENTS Compare the median number of passes required to establish the diagnosis , diagnostic sufficiency , technical performance , complication rates , procurement of the histologic core , and quality of the histologic specimen . RESULTS A total of 28 patients were r and omized to the FNA group and 28 to the FNB group . There was no significant difference in median number of passes required to establish the diagnosis ( 1 [ interquartile range 1 - 2.5 ] vs 1 [ interquartile range 1 - 1 ] ; P = .21 ) , rates of diagnostic sufficiency ( 100 % vs 89.3 % ; P = .24 ) , technical failure ( 0 vs 3.6 % ; P = 1.0 ) , or complications ( 3.6 % for both ) between FNA and FNB needles , respectively . Patients in whom diagnosis was established in passes 1 , 2 , and 3 were 64.3 % versus 67.9 % , 10.7 % versus 17.9 % , and 25 % versus 3.6 % , respectively , for FNA and FNB cohorts . There was no significant difference in procurement of the histologic core ( 100 % vs 83.3 % ; P = .26 ) or the presence of diagnostic histologic specimens ( 66.7 % vs 80 % ; P = .66 ) between FNA and FNB cohorts , respectively . LIMITATIONS Only pancreatic masses were evaluated . CONCLUSION Diagnostic sufficiency , technical performance , and safety profiles of FNA and FNB needles are comparable . There was no significant difference in yield or quality of the histologic core between the 2 needle types BACKGROUND AND STUDY AIMS An endoscopic ultrasound (EUS)-guided fine needle biopsy ( EUS-FNB ) device using a core biopsy needle was developed to improve diagnostic accuracy by simultaneously obtaining cytological aspirates and histological core sample s. We prospect ively compared the diagnostic accuracy of EUS-FNB with st and ard EUS-guided fine needle aspiration ( EUS-FNA ) in patients with solid pancreatic masses . PATIENTS AND METHODS Between January 2012 and May 2013 , consecutive patients with solid pancreatic masses were prospect ively enrolled and r and omized to undergo EUS-FNB using a core biopsy needle or EUS-FNA using a st and ard aspiration needle at a single tertiary center . The specimen was analyzed by onsite cytology , Papanicolaou-stain cytology , and histology . The main outcome measure was diagnostic accuracy for malignancy . The secondary outcome measures were : the median number of passes required to establish a diagnosis , the proportion of patients in whom the diagnosis was established with each pass , and complication rates . RESULTS The overall accuracy of combining onsite cytology with Papanicolaou-stain cytology and histology was not significantly different for the FNB ( n = 58 ) and FNA ( n = 58 ) groups ( 98.3 % [ 95 % CI 94.9 % - 100 % ] vs. 94.8 % [ 95 % CI 91.9 % - 100 % ] ; P = 0.671 ) . Compared with FNA , FNB required a significantly lower median number of needle passes to establish a diagnosis ( 1.0 vs. 2.0 ; P < 0.001 ) . On subgroup analysis of 111 patients with malignant lesions , the proportion of patients in whom malignancy was diagnosed on the first pass was significantly greater in the FNB group ( 72.7 % vs. 37.5 % ; P < 0.001 ) . CONCLUSIONS The overall accuracy of FNB and FNA in patients with solid pancreatic masses was comparable ; however , fewer passes were required to establish the diagnosis of malignancy using FNB.This study was registered on the UMIN Clinical Trial Registry ( UMIN000014057 ) BACKGROUND AND STUDY AIMS A new core biopsy needle for endoscopic ultrasound (EUS)-guided sampling has recently been developed . The aim of this prospect i ve multicenter study was to compare this needle with a st and ard needle in patients with solid pancreatic masses . PATIENTS AND METHODS Consecutive patients with solid pancreatic masses referred to 17 centers for EUS-guided sampling were included . Each patient had two passes with a st and ard 22 G needle and a single pass with a 22 G core needle performed in a r and omized order . Sample s from both needles were separately processed for liquid-based cytology and cell-block preparation and were assessed independently by two blinded expert pathologists . The primary endpoint was the accuracy of the detection of malignancy . The reference st and ard was based on further cytohistological analysis obtained under ultrasound or computed tomography scanning , endoscopic or surgical guidance , and /or by clinical follow-up with repeated imaging examinations for at least 12 months . The secondary endpoints were the rate of technical failure and the quality of the cytohistological sample s obtained . RESULTS Of the 80 patients included ( 49 men ; mean age 67.1 ± 11.1 ) , 87.5 % had final malignant diagnoses ( adenocarcinoma n = 62 , 77.5 % ) . There was no difference between the needles in diagnostic accuracy ( st and ard needle 92.5 % vs. core needle 90 % ; P = 0.68 ) or technical failure . Both pathologists found the overall sample quality significantly better for the st and ard needle ( expert 1 , P = 0.009 ; expert 2 , P = 0.002 ) . CONCLUSIONS The diagnostic accuracy of EUS sampling for solid pancreatic masses using st and ard and core needles seems comparable but with a better overall histological sample quality for the former . Clinical Trial.gov identifier : NCT01479803 Objectives Endoscopic ultrasound-guided fine-needle aspiration ( EUS-FNA ) using st and ard needles has a high diagnostic value in the evaluation of solid pancreatic masses . Fenestrated needles have been developed to improve the quality of EUS-guided tissue sampling by providing core biopsies ( FNB ) . Methods Patients with solid pancreatic masses of > 2 cm were prospect ively included in our study and r and omized to receive EUS sampling , using either a st and ard 22 G FNA or a 22 G Procore ® FNB needle . The main study endpoint was the number of needle passes required to obtain a diagnosis in more than 90 % of cases . Results We included 100 patients ( male = 63 , female = 37 ; mean age = 68.4 years ) in our study . We found that 88 % of the lesions were malignant , with a mean size of 32 mm . A sample adequate for diagnosis was obtained in more than 90 % of cases after the second needle pass in the FNB group , versus the third needle pass in the FNA group . Slide cellularity and presence of tissue microfragments were significantly higher in the FNB group . Sensitivity for the diagnosis of malignancy was 88.4 % versus 97.8 % for the EUS-FNA and EUS-FNB group , respectively , while specificity for both techniques was 100 % . No complications were recorded . Conclusions Although the accuracy of both needle types for proving malignancy was similar , a lower number of passes was required with the FNB needles to achieve the same contributive sample rate as with the FNA needles . FNB also improved the histopathological quality of specimens , suggesting an overall superiority of FNB sampling |
12,201 | 12,729,430 | Advanced Cardiac Life Support programs sponsored by the AHA also provide supplemental instruction and testing on abnormal cardiac rhythm recognition in emergency setting s. Successful completion of residency , board certification , and Advanced Cardiac Life Support training are one reasonable method of objective documentation that a physician is competent to interpret bedside ECGs in routine and emergency setting s , pending additional outcomes -based research .
Cardiologists also demonstrate greater accuracy than noncardiologists in ECG interpretation during st and ardized examinations of ECG interpretation when minimal history is given ( 15 ) . | This guideline from the American College of Physicians presents supporting evidence and makes specific recommendations on training , initial competency evaluation , and maintenance of competency for interpretation of the 12-lead resting electrocardiogram ( ECG ) .
Other organizations have provided consensus-based guidance on ECG interpretation .
The Accreditation Council for Graduate Medical Education Residency Review Committee for Internal Medicine issued guidelines stating that residents should be given an opportunity to develop competency in interpretation of ECGs but did not specify how to achieve this goal ( 2 ) .
The American Board of Internal Medicine does not require a minimum number of supervised ECG interpretations to take the internal medicine board certification examination ( 3 ) .
The American College of Cardiology ( ACC ) and American Heart Association ( AHA ) published consensus-based guidelines for attaining , testing , and maintaining competency in ECG interpretation .
A 2001 statement by the ACC/AHA recommended interpretation of 500 ECGs under supervision to attain initial competency ( 4 ) .
Several features of the current literature on ECG interpretation make valid conclusions difficult .
Typically , noncardiologists or trainees are compared to an expert electrocardiographer gold st and ard .
The proportion of abnormal diagnoses correctly identified is then reported .
The clinical significance of the differences between cardiologists and noncardiologists is uncertain because intra-interpreter reliability varies , even among cardiologists ( 6 , 7 ) .
As many trials test comprehensive detection of ECG abnormalities , the sensitivity of physicians ' detection of any given disorder is often uncertain .
Specificity and the implication s of false-positive interpretations are infrequently reported .
Studies examining comprehensive ECG analysis show that , although major interpretation errors are common ( 4 % to 33 % ) , adverse patient outcomes result ing from these errors are rare , typically occurring in less than 1 % of interpretations ( 1 ) .
Computer interpretation of ECGs is a common feature of many ECG acquisition devices .
However , comparisons of the accuracy of computer ECG analysis with that of expert electrocardiographers show that only 0 % to 94 % of disorders are classified correctly ; arrhythmias are the most problematic diagnosis ( 6 , 7 , 10 , 11 ) .
Therefore , computer ECG analysis should be considered a helpful adjunct to , but not a substitute for , physician interpretation in clinical decision making .
The skill of noncardiologist physicians in interpreting ECGs of patients not under their care remains uncertain .
Research has suggested that noncardiologists are more affected by the context of the patient 's clinical history and the automated computer interpretation than are cardiologists when interpreting an ECG ( 8 , 13 , 14 ) . | This study was design ed to assess whether a self- study interactive computer program is more effective than weekly seminars for teaching fundamental skills of electrocardiographic interpretation to junior medical students . Forty-two students were assigned to the computer and 41 to the seminar group . A test was given to each participant at the beginning and end of each rotation . The computer group used a computer-assisted learning program , and the seminar group met weekly with a cardiologist to review electrocardiograms . Attendance at a minimum of 80 % of the seminars or completion of 80 % of the computer-assisted learning program was required for inclusion in the statistical analysis . The mean difference in test scores before and after study was 5.69 for the computer group and 4.36 for the seminar group ( P less than .02 by one-tailed t-test ) . These results indicate that the computer group performed significantly better than the seminar group . We believe this difference to be educationally important To examine the effect of clinical history on the electrocardiogram ( ECG ) interpretation skills of physicians with different levels of expertise , we r and omly allocated to an ECG test package 30 final-year medical students , 15 second-year internal medicine residents , and 15 university cardiologists at university-affiliated teaching hospitals . All participants interpreted the same set of 10 ECGs . Each ECG was accompanied by a brief clinical history suggestive of the correct ECG diagnosis , or the most plausible alternative diagnosis , or no history . Provision of a correct history improved accuracy by 4 % to 12 % compared with no history , depending on level of training . Conversely , a misleading history compared with no history reduced accuracy by 5 % for cardiologists , 25 % for residents , and 19 % for students . Clinical history also affected the paticipants ’ frequencies of listing ECG features consistent with the correct diagnosis and features consistent with the alternative diagnosis ( allp values < .05 ) . For physicians at all levels of expertise , clinical history has an influence on ECG diagnostic accuracy , both improving accuracy when the history suggests the correct diagnosis , and reducing accuracy when the history suggests an alternative diagnosis We assessed the performance of diagnostic electrocardiogram ( ECG ) interpretation by the computer program MEANS and by research physicians , compared to cardiologists , in a physician-based study . To establish a strategy for ECG interpretation in health surveys , we also studied the diagnostic capacity of three scenarios : use of the computer program alone ( A ) , computer program and cardiologist ( B ) , and computer program , research physician , and cardiologist ( C ) . A stratified r and om sample of 381 ECGs was drawn from ECGs collected in the Rotterdam Study ( n = 3057 ) , which were interpreted both by a trained research physician using a form for structured clinical evaluation and by MEANS . All ECGs were interpreted independently by two cardiologists ; if they disagreed ( n = 175 ) the ECG was judged by a third cardiologist . Five ECG diagnoses were considered : anterior and inferior myocardial infa rct ion ( MI ) , left and right bundle branch block ( LBBB and RBBB ) , and left ventricular hypertrophy ( LVH ) . Overall , sensitivities and specificities of MEANS and the research physicians were high . The sensitivity of MEANS ranged from 73.8 % to 92.9 % and of the research physician ranged from 71.8 % to 96.9 % . The specificity of MEANS ranged from 97.5 % to 99.8 % and of the research physician from 96.3 % to 99.6 % . To diagnose LVH , LBBB , and RBBB , use of the computer program alone gives satisfactory results . Preferably , all positive findings of anterior and inferior MI by the program should be verified by a cardiologist . We conclude that diagnostic ECG interpretation by computer can be very helpful in population -based research , being at least as good as ECG interpretation by a trained research physician , but much more efficient and therefore less expensive OBJECTIVES To determine whether access to a computer generated electrocardiogram ( ECG ) report can reduce errors of interpretation by senior house officers ( SHOs ) in an accident and emergency department . METHODS Ten SHOs were asked to interpret 50 ECGs each : 25 with computer generated reports , 25 without . Their answers , and the computer generated reports , were compared with a “ gold st and ard ” produced by two experienced clinicians . The primary outcome measure was the proportion of major errors of interpretation . RESULTS The computer reading system made two major errors ( 4 % , 95 % confidence interval ( CI ) 1.1 % to 13.5 % ) compared with the gold st and ard . Access to the computer report did not significantly reduce major errors among SHOs ( 46 ( 18.4 % ) with report v 56 ( 22.4 % ) without , odds ratio 0.64 , 95 % CI 0.36 % to 1.14 % , p=0.13 ) or improve the proportion completely correct ( 104 ( 41.6 % ) with reportv 91 ( 36.4 % ) without , odds ratio 1.43 , 95 % CI 0.88 to 2.33 , p=0.15 ) . CONCLUSIONS SHOs have a high error rate when interpreting ECGs , which is not significantly reduced by access to a computer generated report . Junior doctors should continue to seek expert senior help when they have to interpret a difficult ECG Objective . To evaluate the effect of computer-assisted interpretation of electrocardiograms ( ECGs ) on diagnostic decision making by primary care physicians . Design . R and omized controlled trial . Setting . Primary care physicians ' outpatient clinics in or near the Minneap olis/St . Paul metropolitan area . Participants . Forty family physicians and general internists who were members of either of two large consortia of clinics . Intervention . Subjects evaluated ten clinical vignettes accompanied by ECGs and reported their diagnostic impressions . The vignettes were based on actual patient visits . Half of the subjects received ECGs with computer-generated reports , the other half received the same ECGs without reports . Main outcome measures . ECG reading time ; agreement with the clinical diagnosis ; agreement with the computer report ; diagnostic confidence . Results . The subjects receiving the reports were more likely to agree with the clinical diagnoses of the original cases , particularly for two vignettes in which the diagnoses were uncommon and were mentioned in the reports . The subjects receiving the reports were also more likely to make diagnoses that were consistent with the reports , even when the reports were erroneous . Those receiving the reports spent , on average , 15 seconds less time looking at each ECG , a 25 % decrease . Conclusions . In simulated cases , primary care physicians appear to use computer interpre tations of ECGs when available , as shown by enhanced diagnostic accuracy and modestly reduced time spent reading the tracings . However , erroneous reports may mislead physi cians . Since the effects of computerized ECG interpretation do not appear to have been uniformly favorable in this mock- clinical setting , it will be important to evaluate the effects of this technology in actual practice . Key words : computer-assisted diagnosis ; computer-as sisted decision making ; physician decision making ; electrocardiogram . ( Med Decis Making 1995;15:107 - 112 The present study compares the on-site interpretation of an admission electrocardiogram ( ECG ) with core laboratory results in a large , multicenter trial of 516 patients diagnosed with unstable angina pectoris or non-Q-wave myocardial infa rct ion . The local investigators evaluated the admission ECG regarding ST-T changes before the ECGs were sent to the core laboratory for blinded interpretation . The strength of agreement between the observations was described by kappa statistics . There was a poor agreement regarding identification of ST-segment elevation , with 17 patients identified by the local investigator versus 92 by the core laboratory ( kappa = 0.05 ) . There was a fair agreement on ST-segment depression with 158 patients diagnosed on-site versus 64 by the core laboratory ( kappa = 0.38 ) . Identification of T-wave inversion demonstrated good agreement with 306 patients diagnosed on-site versus 280 by the core laboratory ( kappa = 0.63 ) . A moderate agreement regarding identification of a normal ECG was found with 101 patients on-site versus 135 in the core laboratory ( kappa = 0.42 ) . Independent variables , including peak creatine kinase-MB and 30-day outcome , were more closely related to core laboratory results than the local investigator 's interpretation of the admission ECG . Thus , in the present study , considerable differences were demonstrated between the on-site interpretation of the admission ECG and the blinded evaluation performed in the core laboratory regarding relatively simple electrocardiographic variables . The results suggest that more widespread use of independent evaluation of clinical data should be incorporated in future clinical trials In this study we have examined the ability of senior house officers in the Accident and Emergency ( A&E ) Department to interpret electrocardiographs ( ECGs ) and tested the value of a single seminar and guidelines on interpretation . We prospect ively audited ECG interpretation taken from notes over a two-month period and repeated this audit following a single seminar by a consultant cardiologist and after the issue of guidelines . A formal test of interpretation of a set of 20 ECGs by senior house officers in A&E was also carried out . 245 case notes were review ed and in one third the ECG was interpreted incorrectly by senior house officers in A&E but incorrect clinical management followed in only 3.2 % of cases . Following the intervention , 242 case notes were review ed and serious misinterpretations were halved as was the number of patients mismanaged as a result ( 1.7 % ) . In conclusion , formal training in ECG interpretation can reduce serious errors |
12,202 | 11,034,778 | REVIEW ER 'S CONCLUSIONS Intravenous prostagl and in is no more efficient than intravenous oxytocin for the induction of labour but its use is associated with higher rates of maternal side effects and uterine hyperstimulation than oxytocin .
No conclusions can be drawn form the comparisons of combination of prostagl and in F2 alpha and oxytocin compared to oxytocin alone or extra amniotic and intravenous prostagl and in E2 | BACKGROUND Intravenous prostagl and in E2 and F2 alpha can be used to induce labour .
The use of intravenous prostagl and ins in this context has been limited by perceived unacceptable maternal side effect profiles .
This is one of a series of review s of methods of cervical ripening and labour induction using st and ardised methodology .
OBJECTIVES To determine the effects of intravenous prostagl and in for third trimester cervical ripening or induction of labour .
This involves a two-stage method of data extraction . | OBJECTIVE To clarify the safety of elective induction of labor at 39 weeks of gestation . STUDY DESIGN Prospect i ve r and omized study . SUBJECTS AND METHODS Uncomplicated nulliparas ( N = 194 ) were r and omly assigned at 36 weeks of gestation . Labor was electively induced in 63 women at 39 weeks of gestation in the active management group ( I group , N = 98 ) . Spontaneous labor onset was expected with semi-weekly nonstress test ( NST ) and amniotic fluid index ( AFI ) by 42 weeks of gestation in the expectant group ( E group , N = 96 ) . Perinatal events were compared between the 2 groups . RESULTS A significantly higher incidence of meconium-stained amnios ( 19.4 % vs 3.2 % ) and fetal resuscitation ( 16.7 % vs 4.8 % ) was found in the E group than in the I group . Also , although a significantly higher incidence of epidural analgesia was noted in the I group ( 89 % ) than in the E group ( 54 % ) ( labor onset > or = 39 weeks , N = 72 ) , the duration of the 1st stage was shorter in I group and the duration of the 2nd stage was not significantly different . No other significant difference was noted between the 2 groups in terms of the rate of C-section , blood loss , incidence of pathological FHR , birth weight , Apgar score , umbilical arterial pH , or admission to NICU . CONCLUSION Active management of labor at 39 weeks could be made as safely as expectant management with modified biophysical profile monitoring A total of 85 women with antepartum fetal death between 14 and 42 weeks gestation was r and omly assigned to one of two regimens of intravenous infusion of the prostagl and in analogue 16‐phenoxy‐17 , 18 , 19 , 20‐tetranor‐PGE2‐methylsulphonamide ( sulprostone ) for inducing labour . Women received either 1 μg/min until delivery or the commonly recommended treatment of 1500 μg in 8 h followed by another , identical course of treatment if delivery did not occur within 24 h. The 1 μg/min dose schedule used half the amount of prostagl and in and result ed in statistically significantly fewer gastrointestinal side‐effects compared with the conventional treatment . All women were delivered vaginally and there were no differences in induction‐to‐delivery intervals between the two treatments . Sulprostone infused at a rate of 1 μg/min result ed in a 50 % chance of being delivered within 12 h and a 90 % chance of being delivered within 24 h , with an overall frequency of side‐effects of 20 % Using a r and omized double-blind research design , the efficacy and safety of intravenous prostagl and in F2a ( PF ) and oxytocin ( O ) for inducing labor were compared in term pregnant women . The results show that successful induction depends upon the condition of the cervix , and for comparable groups there was no difference for PF or O. The PF failures occurred in patients who were significantly more obese . The incidence of uterine hypertonus , hot flashes and vein phlebitis was increased significantly in the PF group but there was no difference in the incidence of fetal bradycardia , nausea , vomiting or diarrhea . The infants delivered vaginally were of similar weight and had similar 1- and 5-minute Apgar scores . Laboratory toxicity studies , before and after infusions ( complete blood count , uric acid , bilirubin , SGOT , and blood urea nitrogen ) , were similar for the two drug groups , except that hemoglobin levels postinfusion were significantly higher in the O group . The incidence of cesarean section was significantly increased in the PF group and these sections were done for uterine hypertonus and /or fetal bradycardia . Caution should be exercised before prostagl and in Fα solutions are used routinely to induce labor at term A comparison has been made between the effectiveness of infusing prostagl and in F2a with Syntocinon for the induction of labour , in the presence of intact membranes A double blind trial of prostagl and in E2 and oxytocin given by intravenous infusion after amniotomy for induction of labour in 100 primigravidae with unfavourable induction features is reported . No clear‐cut advantage of either drug emerged although PGE2was perhaps superior when the cervix was highly unfavourable . Prostagl and in E2appeared to produce less deleterious effects on the fetus but was associated with a higher incidence of maternal side effects . The automatic Cardiff Infusion apparatus was found to be a safe means of PGE2infusion and to have advantages over the use of non‐automatic techniques both for PGE2 and for oxytocin infusion One hundred consecutive women with singleton pregnancies and primary rupture of membranes ( PROM ) after 36 weeks of gestation were included in a prospect i ve , r and omized trial of intravenous infusion of oxytocin ( up to 30 mIU/min ) versus low‐dose prostagl and in F2α(PGF2αup to 6.0 μg/min ) . Cesarean section was performed in 12 patients because of suspected disproportion or intra‐uterine asphyxia . Effective contractions or labor progress failed to become established within 8 hours in another 4 women stimulated with PGF2α and 2 stimulated by oxytocin . The stimulation delivery time ( hours ) for the remaining 82 women treated with PGF2α or oxytocin , respectively was 8.7 against 12.1 for initial Bishop score < 5 ( p<0.01 ) , ( Mann‐Whitney test ) , 7.2 vs. 7.1 for Bishop score 5–8 and 5.7 vs. 4.2 for Bishop score > 8 . Patients with initial Bishop score < 5 seemed to need analgetics less often when treated with PGF2α than with oxytocin . Frequencies of side effects and instrumental deliveries as well as the fetal outcome were similar for the two treatment schedules . The results of the study suggest that low‐dose PGF2α infusion may be the more appropriate treatment for women with an unfavorable initial Bishop score A double-blind study was conducted to determine the effects of prostagl and in F2 alpha on the levels of estriol and progesterone in the peripheral venous blood during term pregnancy and to compare the effects of PGF2 alpha with that produced by oxytocin . 32 multiparous volunteers in the last 4 weeks of pregnancy were r and omly assigned to 1 of 2 groups the first group of 12 women receiving oxytocin for labor induction and the 2nd group of 20 women receiving PGF2 alpha . The subjects in both groups were of comparable age parity . and weight . 3 inductions failed in the oxytocin group compared to 8 in the PGF2 alpha group . As the process of delivery itself may alter plasma steroid levels both groups were further subdivided into those subjects who delivered and those who did not deliver . The data suggest that neither oxytocin nor PGF2 alpha given intravenously to term pregnant women for labor induction significantly altered the plasma levels of estriol or progesterone In a group of 20 matched primigravid patients labour was induced by forewater amniotomy followed by intravenous oxytocin ( Syntocinon ) administered in escalating doses . Ten of these patients , in a double-blind trial , also received prostagl and in E2 infused simultaneously with the oxytocin . In the combined prostagl and in-oxytocin group there was a noticeable reduction in the dosage of oxytocin required to produce effective uterine action , and the duration of labour was also reduced . No side effects were observed PGEM concentration was determined radioimmunologically in a non-pregnant woman in whom PGE2 was infused intravenously at increasing dosage and in women in whom labour was induced by various methods for local application of PGE2 . There was excellent correlation between the amount of PGE2 infused intravenously and the levels of PGEM determined in the peripheral plasma . The following methods of local application of PGE2 were included in the study : 0.4 mg PGE2 gel placed retroamnially by means of a balloon catheter ; 0.4 and 0.5 mg PGE2 gel applied endocervically ; 1.5 mg PGE2 given pericervically through a portio adapter and 3 mg PGE2 placed intravaginally in form of a single vaginal tablet ; also included was a control group where only vaginal examination was performed . Blood was withdrawn before , and then 30 minutes , 1 , 2 and 3 hours after PGE2 administration . Mean levels of PGEM in the maternal peripheral plasma showed no change within or between the various groups , with the exception of one patient in the portio adapter group where hyperstimulation occurred . After removal of the adapter PGEM levels dropped to baseline values . It is concluded from the present study that local application of doses currently used to soften the cervix and /or induce labour at term does not give rise to PGEM concentrations in the maternal blood of the same magnitude as achieved by intravenous PGE2 administration A comparison has been made between the effectiveness of infusing prostagl and in E2 with Syntocinon for the induction of labour in the presence of intact membranes . Rapid titration schedules were used to induce an early uterine response . All 15 subjects receiving prostagl and in E2 achieved cervical dilatation , whereas this occurred in only 9 out of 15 patients receiving Syntocinon Abstract Prostagl and ins E 2 and F 2 α and synthetic oxytocin were studied for efficacy and side effects in a double-blind protocol for the induction of labor at term in 100 women . That an inducibility scoring index should be part of each clinical oxytocin trial is evidence d by the fact that erroneous conclusions would have been drawn if it had not been used . All patients who were classified as having " easy inductions " were delivered independent of which drug they received ; however , the 3 categories of grade d " difficult inductions " reflected success rates from 93.3 to 40 per cent , depending upon difficulty of induction . Synthetic oxytocin and prostagl and in F 2 α were found to be equally efficacious in the difficult groups although more cases will be required to allow significant statistical analysis . Except for an increased incidence of innocuous uterine hypertonus , no significant side effects of prostagl and in infusions were noted A double-blind trial of oxytocin ( Syntocinon ) and prostagl and in E2 ( PGE2 ) in the induction of labor in 300 patients result ed in equally high success rates for both drugs . 73 % of the patients in each group were delivered or achieved a 6 cm dilatation of the cervix within 12 hours of the start of infusion . The patients were not matched for factors known to affect labor and thus no statistical analysis of the results was attempted . In the successful cases there were no maternal complications of treatment . ( authors |
12,203 | 30,468,950 | The results of the review suggest that mindfulness may be particularly useful for preventing distracted driving . | Mindfulness has been identified as a potentially effective intervention for reducing road trauma .
In this paper , we report on the results of a systematic review which examined the evidence regarding the relationship between mindfulness and road safety . | Objective : The principal objective of the present work was to examine the effects of mind state ( mind-w and ering vs. on-task ) on driving performance in a high-fidelity driving simulator . Background : Mind-w and ering is thought to interfere with goal -directed thought . It is likely , then , that when driving , mind-w and ering might lead to impairments in critical aspects of driving performance . In two experiments , we assess the extent to which mind-w and ering interferes with responsiveness to sudden events , mean velocity , and headway distance . Method : Using a car-following procedure in a high-fidelity driving simulator , participants were probed at r and om times to indicate whether they were on-task at that moment or mind-w and ering . The dependent measures were analyzed based on the participant ’s response to the probe . Results : Compared to when on-task , when mind-w and ering participants showed longer response times to sudden events , drove at a higher velocity , and maintained a shorter headway distance . Conclusion : Collectively , these findings indicate that mind-w and ering affects a broad range of driving responses and may therefore lead to higher crash risk . Application : The results suggest that situations that are likely associated with mind-w and ering ( e.g. , route familiarity ) can impair driving performance Task unrelated thought ( TUT ) refers to thought directed away from the current situation , for example a daydream . Three experiments were conducted on healthy participants , with two broad aims . First , to contrast distributed and encapsulated views of cognition by comparing the encoding of categorical and r and om lists of words ( Experiments One and Two ) . Second , to examine the consequences of experiencing TUT during study on the subsequent retrieval of information ( Experiments One , Two , and Three ) . Experiments One and Two demonstrated lower levels of TUT and higher levels of word-fragment completion whilst encoding categorical relative to r and om stimuli , supporting the role of a distributed re source in the maintenance of TUT . In addition the results of all three experiments suggested that experiencing TUT during study had a measurable effect on subsequent retrieval . TUT was associated with increased frequency of false alarms at retrieval ( Experiment One ) . In the subsequent experiments TUT was associated with no advantage to retrieval based on re collection , by manipulating instructions at encoding ( Experiment Two ) , and /or at retrieval ( Experiment Three ) . The implication s of the results of all three experiments are discussed in terms of recent accounts of memory retrieval and conscious awareness Previous studies have found that mindfulness training reduces overgeneral memories and increases autobiographical memory specificity ( e.g. , [ Williams , J. M. G. , Teasdale , J. D. , Segal , Z. V. , & Soulsby , J. ( 2000 ) . Mindfulness-based cognitive therapy reduces overgeneral autobiographical memory in formerly depressed patients . Journal of Abnormal Psychology , 109 , 150 - 155 ] ) . However , little work has investigated the mechanisms underlying this effect . The present study explored the role of executive processes as a mediator of MBCT effects in an unselected sample . An autobiographical memory task , a cognitive inhibition task , a motor inhibition task , a cognitive flexibility task and a motor flexibility task were administered before and after intervention . Compared to matched controls , MBCT participants showed increased autobiographical memory specificity , decreased overgenerality , and improved cognitive flexibility capacity and capacity to inhibit cognitive prepotent responses . Mediational analyses indicated that changes in cognitive flexibility partially mediate the impact of MBCT on overgeneral memories . Results are discussed in terms of Conway 's [ 2005 . Memory and the self . Journal of Memory and Language , 53 , 594 - 628 ] autobiographical memory model |
12,204 | 31,294,378 | Corticosteroid therapies ( including budesonide ) can be used as induction , but not maintenance therapies .
Among immunosuppressants , thiopurines should not be used for induction , but can be used for maintenance therapy for selected low-risk patients .
Parenteral methotrexate was proposed for induction and maintenance therapy in patients with corticosteroid-dependent CD .
Biologic agents , including tumor necrosis factor antagonists , vedolizumab , and ustekinumab , were recommended for patients failed by conventional induction therapies and as maintenance therapy .
The consensus group was unable to clearly define the role of concomitant immunosuppressant therapies in initiation of treatment with a biologic agent . | Background & Aims Crohn 's disease ( CD ) is a lifelong illness with substantial morbidity , although new therapies and treatment paradigms have been developed .
We provide guidance for treatment of ambulatory patients with mild to severe active luminal CD . | BACKGROUND Oral budesonide 9 mg/day represents first-line treatment of mild-to-moderately active ileocolonic Crohn 's disease . However , there is no precise recommendation for budesonide dosing due to lack of comparative data . A once-daily ( OD ) 9 mg dose may improve adherence and thereby efficacy . METHODS An eight-week , double-blind , double-dummy r and omised trial compared budesonide 9 mg OD versus 3 mg three-times daily ( TID ) in patients with mild-to-moderately active ileocolonic Crohn 's disease . Primary endpoint was clinical remission defined as CDAI < 150 at week 8 ( last observation carried forward ) . RESULTS The final intent-to-treat population comprised 471 patients ( 238 [ 9 mg OD ] , 233 [ 3 mg TID ] ) . The confirmatory population for the primary endpoint analysis was the interim per protocol population ( n=377 ; 188 [ 9 mg OD ] , 189 [ 3 mg TID ] ) , in which the primary endpoint was statistically non-inferior with budesonide 9 mg OD versus 3 mg TID . Clinical remission was achieved in 71.3 % versus 75.1 % , a difference of -3.9 % ( 95 % CI [ -14.6 % ; 6.4 % ] ; p=0.020 for non-inferiority ) . The mean ( SD ) time to remission was 21.9 ( 13.8 ) days versus 21.4 ( 14.6 ) days with budesonide 9 mg OD versus 3 mg TID , respectively . In a sub population of 122 patients with baseline SES-CD ulcer score ≥1 , complete mucosal healing occurred in 32.8 % ( 21/64 ) on 9 mg OD and 41.4 % ( 24/58 ) on 3 mg TID ; deep remission ( mucosal healing and clinical remission ) was observed in 26.6 % ( 17/64 ) and 32.8 % ( 19/58 ) of patients , respectively . Treatment-emergent suspected adverse drug reactions were reported in 4.6 % of 9 mg OD and 4.7 % of 3 mg TID patients . CONCLUSIONS Budesonide at the recommended dose of 9 mg/day can be administered OD without impaired efficacy and safety compared to 3 mg TID dosing in mild-to-moderately active Crohn 's disease BACKGROUND & AIMS Osteoporosis frequently occurs in Crohn 's disease , often because of corticosteroids . Budesonide as controlled release capsules is a locally acting corticosteroid with low systemic bioavailability . We investigated its effects on bone compared with prednisolone . METHODS In 34 international centers , 272 patients with Crohn 's disease involving ileum and /or colon ascendens were r and omized to once daily treatment with budesonide or prednisolone for 2 years at doses adapted to disease activity . One hundred eighty-one corticosteroid-free patients had active disease ( 98 had never received corticosteroids , corticosteroid naive ; 83 had received corticosteroids previously , corticosteroid exposed ) , and 90 had quiescent disease , receiving long-term low doses of corticosteroids , corticosteroid-dependent ; in 1 patient , no efficacy data were obtained . Bone mineral density and fractures were assessed in a double-blinded fashion ; disease activity , side effects , and quality of life were monitored . RESULTS Neither the corticosteroid-free nor the corticosteroid-dependent patients treated with budesonide differed significantly in bone mineral density from those receiving prednisolone . However , corticosteroid-naive patients receiving budesonide had smaller reductions in bone mineral density than those on prednisolone ( mean , -1.04 % vs -3.84 % ; P = .0084 ) . Treatment-emergent corticosteroid side effects were less frequent with budesonide . Efficacy was similar in both groups . CONCLUSIONS Treatment with budesonide is associated with better preserved bone mass compared with prednisolone in only the corticosteroid-naive patients with active ileocecal Crohn 's disease . In both the corticosteroid-free and corticosteroid-dependent groups , budesonide and prednisolone were equally effective for up to 2 years , but budesonide caused fewer corticosteroid side effects BACKGROUND Budesonide is a steroid with low systemic effect and high effectiveness in the treatment of Crohn 's Disease ( CD ) . Beclomethasone dipropionate ( BDP ) is also a steroid with the same systemic effects , but it has been never investigated in CD . MATERIAL / METHODS To evaluate the effectiveness and tolerability of BDP versus budesonide in treating CD , we enrolled 30 consecutive patients affected by mild-to-moderate non-fistulizing , non-obstructive Crohn 's disease ( CDAI < or = 250 ) ( 13 M and 17 F , mean age : 33.4 years , range : 16 - 71 years ) in whom this diagnosis was made for the first time . The patients were r and omly treated for 8 weeks with budesonide 9 mg/day ( group A , 15 patients ) or with BDP 10 mg/day ( group B , 15 patients ) . RESULTS Of group A patients , 13/14 ( on intention to treat ( i-t-t ) : 86.67 % ) showed response to budesonide and 10/14 ( on i-t-t . : 66.66 % ) were in remission after 8 weeks of treatment . In group B patients , 10/14 ( on i-t-t : 66.66 % ) showed response to BDP and 8/14 ( on i-t-t : 53.33 % ) were in remission after 8 weeks of treatment ( p<0.001 ) . Budesonide was also faster in the time to obtain symptomatic remission ( p = n.s . ) and was better in improving IBDQL ( p<0.05 ) . Regarding side effects , two group A patients ( 6.66 % ) and three group B patients ( 10 % ) experienced mild-to-moderate side effects which were transitory and did not require any specific treatment or stopping the treatment . CONCLUSIONS BDP seems to be less effective than budesonide in treating CD , probably due to better the pharmacokinetic properties of budesonide Adalimumab is approved for use in patients with moderate to severe Crohn 's disease ( CD ) or ulcerative colitis ( UC ) who have not achieved disease control with conventional therapies including corticosteroids and /or immunomodulators ( IMM ) BACKGROUND & AIMS The aim of this study was to evaluate the usefulness of short-term infliximab combined with azathioprine ( AZA ) or 6-mercaptopurine ( 6-MP ) in steroid-dependent Crohn 's disease patients . METHODS Patients with active disease despite prednisone given for more than 6 months were eligible and were stratified as follows : the failure stratum consisted of patients receiving AZA/6-MP at a stable dose for more than 6 months , and the naive stratum consisted of patients not treated previously with AZA/6-MP . Patients were r and omized to infliximab 5 mg/kg or placebo at weeks 0 , 2 , and 6 . All patients were treated with AZA/6-MP maintained at a stable dose throughout the 52 weeks of the study . The primary end point was remission off steroids at week 24 . RESULTS Among the 113 enrolled patients ( 55 in the failure stratum ) , 57 were assigned to infliximab . At week 24 , the success rate ( intent-to-treat analysis ) was higher in the infliximab group than in the placebo group ( 57 % vs 29 % ; P = .003 ) ; at weeks 12 and 52 , the corresponding rates were 75 % vs 38 % ( P < .001 ) and 40 % vs 22 % ( P = .04 ) , respectively . In each stratum , the success rate was significantly higher in the infliximab group at weeks 12 and 24 , and a trend was found at week 52 . In the failure stratum , only 27 % of the patients in the infliximab group were still in remission off steroids , compared with 52 % in the naive stratum . Steroid resistance was less common and the cumulative dose of prednisone was lower in the infliximab group . CONCLUSIONS Infliximab plus AZA/6-MP is more effective than AZA/6-MP alone in steroid-dependent Crohn 's disease patients BACKGROUND TNF inhibitors have improved treatment of Crohn 's disease , ulcerative colitis , spondyloarthritis , rheumatoid arthritis , psoriatic arthritis , and chronic plaque psoriasis , but are expensive therapies . The aim of NOR-SWITCH was to examine switching from originator infliximab to the less expensive biosimilar CT-P13 regarding efficacy , safety , and immunogenicity . METHODS The study is a r and omised , non-inferiority , double-blind , phase 4 trial with 52 weeks of follow-up . Adult patients on stable treatment with infliximab originator treated in a hospital setting for at least 6 months were eligible for participation . Patients with informed consent were r and omised in a 1:1 ratio to either continued infliximab originator or to switch to CT-P13 treatment , with unchanged dosing regimen . Data were collected at infusion visits in 40 Norwegian study centres . Patients , assessors , and patient care providers were masked to treatment allocation . The primary endpoint was disease worsening during 52-week follow-up . 394 patients in the primary per- protocol set were needed to show a non-inferiority margin of 15 % , assuming 30 % disease worsening in each group . This trial is registered with Clinical Trials.gov , number NCT02148640 . FINDINGS Between Oct 24 , 2014 , and July 8 , 2015 , 482 patients were enrolled and r and omised ( 241 to infliximab originator , 241 to CT-P13 group ; one patient was excluded from the full analysis and safety set for CT-P13 ) and 408 were included in the per- protocol set ( 202 in the infliximab originator group and 206 in the CT-P13 group ) . 155 ( 32 % ) patients in the full analysis set had Crohn 's disease , 93 ( 19 % ) had ulcerative colitis , 91 ( 19 % ) had spondyloarthritis , 77 ( 16 % ) had rheumatoid arthritis , 30 ( 6 % ) had psoriatic arthritis , and 35 ( 7 % ) had chronic plaque psoriasis . Disease worsening occurred in 53 ( 26 % ) patients in the infliximab originator group and 61 ( 30 % ) patients in the CT-P13 group ( per- protocol set ; adjusted treatment difference -4·4 % , 95 % CI -12·7 to 3·9 ) . The frequency of adverse events was similar between groups ( for serious adverse events , 24 [ 10 % ] for infliximab originator vs 21 [ 9 % ] for CT-P13 ; for overall adverse events , 168 [ 70 % ] vs 164 [ 68 % ] ; and for adverse events leading to discontinuation , nine [ 4 % ] vs eight [ 3 % ] , respectively ) . INTERPRETATION The NOR-SWITCH trial showed that switching from infliximab originator to CT-P13 was not inferior to continued treatment with infliximab originator according to a prespecified non-inferiority margin of 15 % . The study was not powered to show non-inferiority in individual diseases . FUNDING Norwegian Ministry of Health and Care Services Background : Vedolizumab is a gut-selective & agr;4&bgr;7 integrin antagonist for the treatment of moderately to severely active Crohn 's disease ( CD ) . Aims of this study were to characterize the efficacy and safety of vedolizumab induction and maintenance therapy in patients who were naïve to tumor necrosis factor-alpha ( TNF-&agr ; ) antagonist therapy ( TNF-naïve ) or who had discontinued TNF-&agr ; antagonist therapy because of inadequate response ( i.e. , primary nonresponse ) , loss of response , or intolerance ( collectively classified as the TNF-failure population ) . Methods : Post hoc analyses of the efficacy data for 516 TNF-naïve and 960 TNF-failure patients from the GEMINI 2 and GEMINI 3 trials were evaluated at weeks 6 , 10 , and 52 and included clinical remission ( CD Activity Index [ CDAI ] score ⩽150 ) , enhanced clinical response ( ≥100-point decrease from baseline in CDAI score ) , durable clinical remission ( remission at ≥80 % of visits ) , and corticosteroid-free remission . Adverse events were summarized for the TNF-naïve and TNF-failure subgroups by treatment received . Results : Among patients who responded to vedolizumab induction at week 6 , 48.9 % of TNF-naïve and 27.7 % of TNF-failure patients were in remission with vedolizumab at week 52 ( versus 26.8 % and 12.8 % with placebo ) . Clinical efficacy was similar between the different types of TNF-&agr ; antagonist failure or the number of prior TNF-&agr ; antagonists failed . Safety profiles were similar in both sub population s. Conclusions : Vedolizumab had increased efficacy over placebo in CD patients irrespective of TNF-&agr ; antagonist treatment history . Overall , rates of response and remission were numerically higher in patients receiving vedolizumab as a first biologic than in patients who had experienced TNF failure Background There is a need for better , less-invasive disease activity indices that provide a representative assessment of endoscopic disease activity . We developed a new clinical score that incorporates the Harvey-Bradshaw index [ HBI ] with modified patient-reported outcomes [ PROp ] and physician [clinician]-reported outcomes [ PROc ] and assessed its ability to measure endosopic disease activity in ileocolonic Crohn 's disease [ CD ] . Methods A cohort of 88 CD patients undergoing colonoscopy was accrued in a prospect i ve fashion . In total , 48 of the subjects were CD cases and 40 had already undergone a post-operative ileocolonic resection [ post-op CD ] . Each patient underwent multiple , endoscopist-blinded assessment s including : HBI score , a PROp question asking for patient perception of disease activity status , a PROc question for clinician perception of disease activity status and C-reactive protein [ CRP ] . Active endoscopic disease was defined as Simple Endoscopic Score for CD [ SES-CD ] ≥ 3 for CD subjects and Rutgeerts score > i1 for post-op CD subjects . Results Clinical remission as defined by the HBI did not accurately reflect endoscopic remission as defined by the SES-CD ( area under the curve [ AUC ] = 0.54 ) . Combining the HBI with PROp and PROc scores and then further adding CRP significantly improved the correlation with SES-CD [ AUC = 0.78 and AUC = 0.88 , respectively , p < 0.00001 ] . In post-op CD , HBI-defined remission also performed poorly against endoscopic remission defined by the Rutgeerts score [ AUC = 0.52 ] . Combining HBI with PROp and the PROc scores and then further adding CRP did not significantly improve the model [ AUC = 0.65 and AUC = 0.61 , respectively , p = NS ] . Conclusion In CD , the HBI correlates poorly with endoscopic disease activity . However , the HBI-PRO score , which incorporated PROp , PROc , CRP and HBI , significantly improved its ability to predict endoscopic activity in ileocolonic CD without prior surgery The aim of this study was to evaluate the accuracy of multidetector CT in patients with Crohn ’s disease ( CD ) relapse after ileocolic resection compared with endoscopy . Thirty-four patients were studied by endoscopy and multidetector CT , after oral administration of polyethylene glycol solution ( n = 21 ) or after administration of methylcellulose via nasojejunal tube ( n = 13 ) . In CT examinations we evaluated the presence of mural thickening , target sign , perienteric str and ing , comb sign , fibrofatty proliferation and complications . Endoscopic results were classified in accordance with Rutgeerts score ( from 0 to 4 ) . The statistical evaluations were carried out by using Fisher ’s exact text and χ2 testing ( p < 0.05 , statistically significant difference ) . Sensitivity , specificity and accuracy of the CT were 96.9 % , 100 % and 97 % , respectively . We found a statistically significant correlation between an endoscopic score of 4 and the CT signs of target sign , perienteric str and ing , comb sign and fibrofatty proliferation , and between scores 1 and 2 and mucosal hyperdensity without or with mural thickening , respectively ( p < 0.05 ) . Moreover , only CT identified the presence of jejunal and proximal ileum disease in two and three patients , respectively , and fistulas in three patients . CT is a reliable method in the diagnosis of CD relapse and shows agreement with the approved endoscopic Rutgeerts score Background : C‐reactive protein ( CRP ) is a traditional nonspecific marker of inflammation , with Crohn 's disease ( CD ) being associated with a strong CRP response . Thus far , no clear cutoff values have been determined . The authors ' aim was to investigate whether high‐sensitivity (hs)‐CRP is useful for the identification disease phenotype , active disease , and relapse during follow‐up , using a classification based on the hs‐CRP value at diagnosis . Methods : In all , 260 well‐characterized , unrelated , consecutive CD patients ( male/female : 120/140 ; duration : 7.0 ± 6.1 years ) , with a complete clinical follow‐up , were included . Hs‐CRP , clinical activity according to the Harvey – Bradshaw Index , and clinical data ( disease phenotype according to the Montreal Classification , extraintestinal manifestations , smoking habits , medical therapy , and surgical events ) were prospect ively collected between January 1 , 2008 and June 1 , 2010 . Medical records prior to the prospect i ve follow‐up period were analyzed retrospectively . Results : In all , 32.3 % of CD patients had normal hs‐CRP at diagnosis . Elevated hs‐CRP at diagnosis was associated with disease location ( P = 0.002 ) , noninflammatory disease behavior ( P = 0.058 ) , and a subsequent need for later azathioprine/biological therapy ( P < 0.001 and P = 0.024 ) , respectively . The accuracy of hs‐CRP for identifying patients with active disease during prospect i ve follow‐up was good ( area under the curve [ AUC ] : 0.82 , cutoff : 10.7 mg/L ) . AUC was better in patients with an elevated hs‐CRP at diagnosis ( AUC : 0.92 , cutoff : 10.3 mg/L ) . In Kaplan – Meier and Cox‐regression analyses , hs‐CRP was an independent predictor of 3‐ ( P = 0.007 ) or 12‐month ( P = 0.001 ) clinical relapses for patients in remission who had elevated hs‐CRP at diagnosis . In addition , perianal involvement ( P = 0.01 ) was associated with the 12‐month relapse frequency . Conclusions : Our data suggest that hs‐CRP positivity at diagnosis is associated with disease location and behavior , and in patients who are hs‐CRP positive at diagnosis , is an accurate marker of disease activity and a predictor of short‐ and medium‐term clinical flare‐ups during follow‐up . ( Inflamm Bowel Dis 2012 BACKGROUND & AIMS This study evaluated the efficacy and safety of adalimumab , a fully human , anti-tumor necrosis factor monoclonal antibody administered subcutaneously , in the maintenance of response and remission in patients with moderate to severe Crohn 's disease ( CD ) . METHODS Patients received open-label induction therapy with adalimumab 80 mg ( week 0 ) followed by 40 mg ( week 2 ) . At week 4 , patients were stratified by response ( decrease in Crohn 's Disease Activity Index > or = 70 points from baseline ) and r and omized to double-blind treatment with placebo , adalimumab 40 mg every other week ( eow ) , or adalimumab 40 mg weekly through week 56 . Co- primary end points were the percentages of r and omized responders who achieved clinical remission ( Crohn 's Disease Activity Index score < 150 ) at weeks 26 and 56 . RESULTS The percentage of r and omized responders in remission was significantly greater in the adalimumab 40-mg eow and 40-mg weekly groups versus placebo at week 26 ( 40 % , 47 % , and 17 % , respectively ; P < .001 ) and week 56 ( 36 % , 41 % , and 12 % , respectively ; P < .001 ) . No significant differences in efficacy between adalimumab eow and weekly were observed . More patients receiving placebo discontinued treatment because of an adverse event ( 13.4 % ) than those receiving adalimumab ( 6.9 % and 4.7 % in the 40-mg eow and 40-mg weekly groups , respectively ) . CONCLUSIONS Among patients who responded to adalimumab , both adalimumab eow and weekly were significantly more effective than placebo in maintaining remission in moderate to severe CD through 56 weeks . Adalimumab was well-tolerated , with a safety profile consistent with previous experience with the drug BACKGROUND & AIMS Treatment with immunosuppressive thiopurines such as azathioprine is associated with an increased risk of leukemogenesis . We assessed the risk of myeloid disorders , such as acute myeloid leukemia and myelodysplastic syndromes , in a large cohort of patients with inflammatory bowel disease ( IBD ) in France . METHODS We performed a prospect i ve observational study of 19,486 patients with IBD enrolled in the Cancers Et Surrisque Associé aux Maladies inflammatoires intestinales En France ( CESAME ) study from May 2004 through June 2005 ; patients were followed through December 31 , 2007 . The incidence of myeloid disorders in the general population , which was used for reference , was determined from the French Network of Cancer Registries . RESULTS During 49,736 patient-years of follow-up , 5 patients were diagnosed with incident myeloid disorders ( 2 with acute myeloid leukemia and 3 with myelodysplastic syndromes ) . Four of these patients had been exposed to thiopurines ( 1 with ongoing treatment and 3 with past exposure ) . The risk of myeloid disorders was not increased among the overall IBD population , compared with the general population ; the st and ardized incidence ratio ( SIR ) was 1.80 ( 95 % confidence interval [ CI ] , 0.58 - 4.20 ) . The risk of myeloid disorders was not increased among patients with IBD and ongoing thiopurine treatment ( SIR , 1.54 ; 95 % CI , 0.05 - 8.54 ) , but patients with past exposures to thiopurines had an increased risk of myeloid disorders ( SIR , 6.98 ; 95 % CI , 1.44 - 20.36 ) . CONCLUSIONS Past exposure to thiopurines increases the risk of myeloid disorders 7-fold among patients with IBD . This finding should be considered when initiating thiopurine therapy , so risks and benefits can be calculated The response of active Crohn 's disease to sulphasalazine ( 4 - 6 g per day ) has been studied in a placebo-controlled trial . The study was carried out at two hospitals . From August 1977 to August 1979 all patients with established Crohn 's disease were examined for their eligibility for the trial . A nine-item index of inflammatory activity was used as the primary measure of response . The variables in this index were serum albumin , ESR , body weight released to height , abdominal mass , temperature , stool consistency , bowel resection , and extraintestinal symptoms related to Crohn 's disease . A favourable response to therapy was defined as a decrease of the activity index with 25 % or more at the end of the trial period , compared with the initial value . Twenty-six patients ( 13 in each treatment group ) have been followed up for six months . The response of active Crohn 's disease to sulphasalazine was significantly better than to placebo BACKGROUND & AIMS Immunomodulator therapy is effective for patients with Crohn 's disease ( CD ) but has not been shown to affect disease progression , presumably because it is given too late after diagnosis . We compared the efficacy of early treatment ( within 6 months after diagnosis ) with azathioprine versus conventional management of patients at high risk for disabling disease . METHODS We performed an open-label trial of adults with a diagnosis of CD for less than 6 months who were at risk for disabling disease . From July 2005 to November 2010 , patients at 24 French centers were r and omly assigned to treatment with azathioprine ( 2.5 mg ∙ kg(-1 ) ∙ day(-1 ) , n = 65 ) or conventional management ( azathioprine only in cases of corticosteroid dependency , chronic active disease with frequent flares , poor response to corticosteroids , or development of severe perianal disease ) ( n = 67 ) . The primary end point was the proportion of trimesters spent in corticosteroid-free and anti-tumor necrosis factor (TNF)-free remission during the first 3 years after inclusion . RESULTS During the 3-year follow-up period , 16 patients in the azathioprine group were switched to mercaptopurine or methotrexate therapy because of intolerance or poor efficacy . Forty-one patients in the conventional management group required immunosuppressant therapy ( 61 % ; median time to first prescription , 11 months ) . In the azathioprine group , a median 67 % of trimesters were spent in remission ( interquartile range , 11%-85 % ) compared with 56 % in the conventional management group ( interquartile range , 29%-73 % ) ( P = .69 ) . Among secondary outcomes , a higher cumulative proportion of patients in the azathioprine group were free of perianal surgery than in the conventional management group ( 96 % ± 3 % and 82 % ± 6 % at month 36 , respectively ; P = .036 ) . The cumulative proportion of patients free of intestinal surgery and anti-TNF therapy did not differ between groups . CONCLUSIONS Based on results from a clinical trial , administration of azathioprine within 6 months of diagnosis of CD was no more effective than conventional management in increasing time of clinical remission . Clinical trials.gov , Number NCT00546546 Thiopurine methyltransferase ( TPMT ) catalyzes thiopurine S-methylation , an important metabolic pathway for drugs such as 6-mercaptopurine . Erythrocyte ( RBC ) TPMT activity was measured in blood sample s from 298 r and omly selected subjects . Of the subjects , 88.6 % were included in a subgroup with high enzyme activity ( 13.50 + /- 1.86 U , mean + /- SD ) , 11.1 % were included in a subgroup with intermediate activity ( 7.20 + /- 1.08 U ) , and 0.3 % had undetectable activity . This distribution conforms to Hardy-Weinberg predictions for the autosomal codominant inheritance of a pair of alleles for low and high TPMT activity , TPMT(L ) and TPMT(H ) , with gene frequencies of .059 and .941 , respectively . If RBC TPMT activity is inherited in an autosomal codominant fashion , then subjects homozygous for TPMT(H ) would have high enzyme activity , subjects heterozygous for the two alleles would have intermediate activity , and subjects homozygous for TPMT(L ) would have undetectable activity . The segregation of RBC TPMT activity among 215 first-degree relatives in 50 r and omly selected families and among 35 members of two kindreds and one family selected because they included prob and s with undetectable RBC enzyme activity were also compatible with the autosomal codominant inheritance of RBC TPMT . For example , in eight matings between subjects with intermediate activity ( presumed genotype TPMT(L)TPMT(H ) ) and subjects with high activity ( presumed genotype TPMT(H)TPMT(H ) ) , 47 % ( 8/17 ) of the offspring had intermediate activity . This value is very similar to the 50 % figure expected on the basis of autosomal codominant inheritance ( chi(2 ) ( [ 1 ] ) = .059 ) . Further experiments are required to determine whether this genetic polymorphism for an important drug metabolizing enzyme may represent one factor in individual variations in sensitivity to thiopurines Objective To explore the risk of new or recurrent cancer among patients with IBD and previous cancer , exposed or not to immunosuppressants . Design Among the 17 047 patients of the CESAME prospect i ve observational cohort who were enrolled from May 2004 to June 2005 , and followed-up until December 2007 , we identified 405 patients with cancer diagnosed previous to study entry . We calculated the rates of incident cancer in patients with or without previous cancer , and we assessed by survival analysis and nested case-control study the impact of immunosuppressants on the risk of incident new or recurrent cancer in patients with previous cancer . Results The rate of incident cancer was 21.1/1000 patient-years ( PY ) and 6.1/1000 PY in patients with and without previous cancer , respectively . The multivariate-adjusted HR of incident cancer between patients with and without previous cancer was 1.9 ( 95 % CI 1.2 to 3.0 , p=0.003 ) . Among patients with previous cancer , the rates of new and recurrent cancers were , respectively , 13.2/1000 PY and 6.0/1000 PY in the 312 patients who were not taking immunosuppressant at the time of study entry , and 23.1/1000 PY and 3.9/1000 PY in the 93 patients treated with immunosuppressants at study entry . There was no significant association between the exposure to immunosuppressants and the risk of new or recurrent cancer . Conclusions Patients with IBD with a history of cancer are at increased risk of developing any ( new or recurrent ) cancer , with a predominant incidence of new cancers . Treatment with immunosuppressants has no overall major impact per se on this risk Objective Although the reasons for secondary loss of response to infliximab ( IFX ) maintenance therapy in Crohn ’s disease vary , dose intensification is usually recommended . This study investigated the cost-effectiveness of interventions defined by an algorithm design ed to identify specific reasons for therapeutic failure . Design R and omised , controlled , single-blind , multicentre study . 69 patients with secondary IFX failure were r and omised to IFX dose intensification ( 5 mg/kg every 4 weeks ) ( n=36 ) or interventions based on serum IFX and IFX antibody levels using the proposed algorithm ( n=33 ) . Predefined co- primary end points at week 12 were proportion of patients responding ( Crohn 's Disease Activity Index ( CDAI ) decrease ≥70 , or ≥50 % reduction in active fistulas ) and accumulated costs related to treatment of Crohn ’s disease , expressed as mean cost per patient , based on the Danish National Patient Registry for all hospitalisation and outpatient costs in the Danish healthcare sector . Results Costs for intention-to-treat patients were substantially lower ( 34 % ) for those treated in accordance with the algorithm than by IFX dose intensification : € 6038 vs € 9178 , p<0.001 . However , disease control , as judged by response rates , was similar : 58 % and 53 % , respectively , p=0.81 ; difference 5 % ( −19 % to 28 % ) . For per- protocol patients , treatment costs were even lower ( 56 % ) in the algorithm-treated group ( € 4062 vs € 9178 , p<0.001 ) and with similar response rates ( 47 % vs 53 % , p=0.78 ; difference −5 % ( −33 % to 22 % ) ) . Conclusions Treatment of secondary IFX failure using an algorithm based on combined IFX and IFX antibody measurements significantly reduces average treatment costs per patient compared with routine IFX dose escalation and without any apparent negative effect on clinical efficacy . Trial Registration No NCT00851565 Objective To assess whether a combination of adalimumab and ciprofloxacin is superior to adalimumab alone in the treatment of perianal fistulising Crohn 's disease ( CD ) . Design R and omised , double-blind , placebo controlled trial in eight Dutch hospitals . In total , 76 CD patients with active perianal fistulising disease were enrolled . After adalimumab induction therapy ( 160/80 mg week 0 , 2 ) , patients received 40 mg every other week together with ciprofloxacin 500 mg or placebo twice daily for 12 weeks . After 12 weeks , adalimumab was continued . Follow-up was 24 weeks . Primary endpoint ( clinical response ) was defined as 50 % reduction of fistulas from baseline to week 12 . Secondary endpoints included remission ( closure of all fistulas ) , Perianal Crohn 's Disease Activity Index , Crohn 's Disease Activity Index ( CDAI ) and Inflammatory Bowel Disease Question naire ( IBDQ ) . Results Clinical response was observed in 71 % of patients treated with adalimumab plus ciprofloxacin and in 47 % treated with adalimumab plus placebo ( p=0.047 ) . Likewise , remission rate at week 12 was significantly higher ( p=0.009 ) in the combination group ( 65 % ) compared with adalimumab plus placebo ( 33 % ) . Combination treatment was associated with a higher mean CDAI change and mean IBDQ change at week 12 ( p=0.005 and p=0.009 , respectively ) . At week 24 , no difference in clinical response between the two treatment groups was observed ( p=0.22 ) . No difference in safety issues was observed . Conclusions Combination therapy of adalimumab and ciprofloxacin is more effective than adalimumab monotherapy to achieve fistula closure in CD . However , after discontinuation of antibiotic therapy , the beneficial effect of initial coadministration is not maintained . Trial registration Clinical Trials.gov Identifier : NCT00736983 Abstract Objective : The infliximab biosimilar CT-P13 ( Remsima ® , Inflectra ® ) was approved in Europe for the treatment of inflammatory bowel disease ( IBD ) based on extrapolation of data from patients with rheumatic disease . Because there are limited published reports on clinical outcomes for IBD patients treated with CT-P13 , we monitored responses to induction treatment with this biosimilar in patients with Crohn ’s disease ( CD ) or ulcerative colitis ( UC ) in centres across the Czech Republic . Material and methods : Fifty-two patients with CD ( n = 30 ) or UC ( n = 22 ) were treated with 5 mg/kg CT-P13 for up to 14 weeks . Effectiveness of therapy was evaluated with the Crohn ’s Disease Activity Index ( CDAI ) or the Mayo Scoring System ( MSS ) in patients with CD or UC , respectively , before and after 14 weeks . Additional goals were to evaluate weight changes , serum C-reactive protein ( CRP ) levels , and complications/adverse events . Results : In patients with CD , remission ( CDAI < 150 ) was achieved in 50.0 % of cases , and partial response ( ≥70-point decrease in CDAI score from baseline ) in the remaining 50.0 % . In patients with UC , remission ( total score on partial Mayo index ≤2 points ) was achieved in 40.9 % of cases , partial response ( ≥2-point decrease in partial Mayo score from baseline ) in 54.5 % , and no response in 4.5 % . There were statistically significant improvements in CDAI , MSS and CRP serum levels after 14 weeks of therapy , and body weight increased . Four adverse events were identified ( n = 1 each ) : lower-extremity phlebothrombosis , herpes labialis , pneumonia and allergic reaction . Conclusions : This prospect i ve observational study provides evidence of the effectiveness of CT-P13 in IBD The Crohn 's Disease Activity Index ( CDAI ) is a measure of disease activity based on symptoms , signs and a laboratory test . The US Food and Drug Administration has indicated that patient reported outcomes ( PROs ) should be the primary outcome in r and omised controlled trials for Crohn 's disease ( CD ) BACKGROUND Ustekinumab , a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23 , was evaluated as an intravenous induction therapy in two population s with moderately to severely active Crohn 's disease . Ustekinumab was also evaluated as subcutaneous maintenance therapy . METHODS We r and omly assigned patients to receive a single intravenous dose of ustekinumab ( either 130 mg or approximately 6 mg per kilogram of body weight ) or placebo in two induction trials . The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor ( TNF ) antagonists or had unacceptable side effects . The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred . Patients who completed these induction trials then participated in IM-UNITI , in which the 397 patients who had a response to ustekinumab were r and omly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab ( either every 8 weeks or every 12 weeks ) or placebo . The primary end point for the induction trials was a clinical response at week 6 ( defined as a decrease from baseline in the Crohn 's Disease Activity Index [ CDAI ] score of ≥100 points or a CDAI score < 150 ) . The primary end point for the maintenance trial was remission at week 44 ( CDAI score < 150 ) . RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo ( in UNITI-1 , 34.3 % , 33.7 % , and 21.5 % , respectively , with P≤0.003 for both comparisons with placebo ; in UNITI-2 , 51.7 % , 55.5 % , and 28.7 % , respectively , with P<0.001 for both doses ) . In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks , 53.1 % and 48.8 % , respectively , were in remission at week 44 , as compared with 35.9 % of those receiving placebo ( P=0.005 and P=0.04 , respectively ) . Within each trial , adverse-event rates were similar among treatment groups . CONCLUSIONS Among patients with moderately to severely active Crohn 's disease , those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo . Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy . ( Funded by Janssen Research and Development ; Clinical Trials.gov numbers , NCT01369329 , NCT01369342 , and NCT01369355 . ) BACKGROUND Reports of an increased risk of lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease are controversial . We assessed this risk in a prospect i ve observational cohort study . METHODS 19,486 patients with inflammatory bowel disease , of whom 11,759 ( 60.3 % ) had Crohn 's disease and 7727 ( 39.7 % ) had ulcerative colitis or unclassified inflammatory bowel disease , were enrolled in a nationwide French cohort by 680 gastroenterologists , who reported details of immunosuppressive therapy during the observation period , cases of cancer , and deaths . The risk of lymphoproliferative disorder was assessed according to thiopurine exposure . Median follow-up was 35 months ( IQR 29 - 40 ) . FINDINGS At baseline , 5867 ( 30.1 % ) of patients were receiving , 2809 ( 14.4 % ) had discontinued , and 10,810 ( 55.5 % ) had never received thiopurines . 23 new cases of lymphoproliferative disorder were diagnosed , consisting of one case of Hodgkin 's lymphoma and 22 cases of non-Hodgkin lymphoproliferative disorder . The incidence rates of lymphoproliferative disorder were 0.90 per 1000 ( 95 % CI 0.50 - 1.49 ) patient-years in those receiving , 0.20/1000 ( 0.02 - 0.72 ) patient-years in those who had discontinued , and 0.26/1000 ( 0.10 - 0.57 ) patient-years in those who had never received thiopurines ( p=0.0054 ) . The multivariate-adjusted hazard ratio of lymphoproliferative disorder between patients receiving thiopurines and those who had never received the drugs was 5.28 ( 2.01 - 13.9 , p=0.0007 ) . Most cases associated with thiopurine exposure matched the pathological range of post-transplant disease . INTERPRETATION Patients receiving thiopurines for inflammatory bowel disease have an increased risk of developing lymphoproliferative disorders . FUNDING Programme Hospitalier de Recherche Clinique National ( AOM05157 ) , Association François Aupetit , Délégation Inter-régionale de la Recherche clinique Ile de France-Assistance Publique Hôpitaux de Paris ( AP-HP ) , Ligue contre le Cancer , and Fonds de Recherche de la Société Nationale Française de Gastro-entérologie BACKGROUND & AIMS Selective blockade of lymphocyte-vascular endothelium interactions in the gastrointestinal tract is a promising therapeutic strategy for inflammatory bowel disease . This r and omized , double-blind , controlled trial assessed the efficacy and safety of MLN0002 , a monoclonal antibody targeting the alpha4beta7 integrin , in patients with active Crohn 's disease . METHODS Patients were r and omized to receive MLN0002 2.0 mg/kg ( n = 65 ) , MLN0002 0.5 mg/kg ( n = 62 ) , or placebo ( n = 58 ) by intravenous infusion on days 1 and 29 . The primary efficacy end point was clinical response ( > or=70-point decrement in the Crohn 's Disease Activity Index [ CDAI ] score ) on day 57 . Secondary end points were the proportions of patients with clinical remission ( CDAI score < or=150 ) and with an enhanced clinical response ( > or=100-point decrement in CDAI ) . Human anti-human antibody levels were measured . RESULTS Clinical response rates at day 57 were 53 % , 49 % , and 41 % in the MLN0002 2.0 mg/kg , MLN0002 0.5 mg/kg , and placebo groups . Clinical remission rates at day 57 were 37 % , 30 % , and 21 % , respectively ( P = .04 for the 2.0 mg/kg vs placebo comparison ) . At day 57 , 12 % and 34 % of patients in the 2.0- and 0.5-mg/kg groups had clinical ly significant human anti-human antibody levels ( titers > 1:125 ) . There was one infusion-related hypersensitivity reaction . The most common serious adverse event was worsening of Crohn 's disease . CONCLUSIONS This phase 2 study was suggestive of a dose-dependent beneficial effect of MLN0002 therapy on clinical remission . MLN0002 was well tolerated in patients with active Crohn 's disease Abstract Objectives : The occurrence of thiopurine-related adverse events ( AEs ) may complicate the management of patients with inflammatory bowel disease ( IBD ) . We aim ed to evaluate the tolerability of thiopurines in a current IBD setting . Material s and methods : All consecutive patients who started a treatment with azathioprine ( AZA ) from January 2010 to March 2016 were entered in a prospect ively maintained data base , and the AEs which led to the permanent discontinuation of the drug were reported . Results : Two hundred and fifty three patients were included . Median total follow-up was 32 months ( range : 0.2–75 months ) . At the end of the study , AZA was discontinued in 160 patients ( 63.2 % ) . The main reason leading to drug withdrawal was the occurrence of AEs ( 109/160 patients [ 68.1 % ] ; cumulative incidence among the entire cohort : 43.1 % ) . Overall , the most frequent AEs leading to treatment withdrawal were nausea ( 31/253 patients , 12.3 % ) and subjective symptoms , i.e. , poorly defined side effects such as fatigue , headache and muscle pain ( 20/253 patients , 7.9 % ) . Among the 109 AZA-intolerant patients , a switch to 6-mercaptopurine ( 6-MP ) was performed in 44 cases ( 40.4 % ) . At the end of follow-up , 6-MP was discontinued in 35/44 patients ( 79.5 % ) , mostly due to AEs ( 29/35 patients , 82.8 % ) . Azathioprine-induced hepatic and pancreatic toxicity was associated with male gender ( p = .01 and p = .03 , respectively ) , and occurrence of nausea with Crohn ’s disease ( p = .04 ) . Conclusions : Our real-life prospect i ve cohort showed the higher cumulative incidence of thiopurine withdrawal due to AEs reported to date . Switching from AZA to 6-MP was often ineffective OBJECTIVES : The objective of this study was to contribute long-term safety data for infliximab and other therapies in Crohn 's disease ( CD ) . METHODS : We prospect ively evaluated CD patients enrolled in the large , observational Crohn 's Therapy , Re source , Evaluation , and Assessment Tool registry , established to compare infliximab safety with conventional nonbiological medications in CD . RESULTS : A total of 6,273 patients were enrolled and evaluated on or before 23 February 2010 ; 3,420 received infliximab ( 17,712 patient-years ; 89.9 % received ≥2 infusions ) and 2,853 received other-treatments-only ( 13,251 patient-years ) . Mean length of patient follow-up was 5.2 years . More infliximab- than other-treatments-only-treated patients had moderate-to-severe ( 30.6 % vs. 10.7 % ) or severe-to-fulminant ( 2.5 % vs. 0.6 % ) disease severity ( P<0.001 ) . In the year before enrollment , more infliximab- than other-treatments-only-treated patients required surgical intervention ( 17.4 % vs. 13.6 % ) , medical hospitalization ( 14.2 % vs. 8.8 % ) , prednisone ( 47.8 % vs. 31.4 % ) , immunomodulators ( 52.0 % vs. 32.1 % ) , and narcotic analgesics ( 17.3 % vs. 9.1 % ) . Patient mortality was similar for infliximab- and other-treatments-only-treated patients ( 0.58 vs. 0.59/100 patient-years ) . In multivariate logistic regression analyses , treatment with prednisone ( hazard ratio (HR)=2.14 , 95 % confidence interval (CI)=1.55 , 2.95 ; P<0.001 ) or narcotic analgesics ( HR=1.79 , 95 % CI=1.29 , 2.48 ; P<0.001 ) and age ( HR=1.08 , 95 % CI=1.07 , 1.09 ; P<0.001 ) were associated with increased mortality risk . Neither infliximab nor immunomodulator treatment was associated with increased mortality risk . Factors independently associated with serious infections included moderate-to-severe disease activity ( HR=2.24 , 95 % CI=1.57 , 3.19 ; P<0.001 ) , narcotic analgesic treatment ( HR=1.98 , 95 % CI=1.44 , 2.73 ; P<0.001 ) , prednisone therapy ( HR=1.57 , 95 % CI=1.17 , 2.10 ; P=0.002 ) , and infliximab treatment ( HR=1.43 , 95 % CI=1.11 , 1.84 ; P=0.006 ) . CONCLUSIONS : Mortality was similar between infliximab- and other-treatments-only-treated CD patients . An increased risk of serious infection with infliximab was observed , although CD severity and use of prednisone or narcotic analgesics carried higher risks BACKGROUND & AIMS The marijuana plant Cannabis sativa has been reported to produce beneficial effects for patients with inflammatory bowel diseases , but this has not been investigated in controlled trials . We performed a prospect i ve trial to determine whether cannabis can induce remission in patients with Crohn 's disease . METHODS We studied 21 patients ( mean age , 40 ± 14 y ; 13 men ) with Crohn 's Disease Activity Index ( CDAI ) scores greater than 200 who did not respond to therapy with steroids , immunomodulators , or anti-tumor necrosis factor-α agents . Patients were assigned r and omly to groups given cannabis , twice daily , in the form of cigarettes containing 115 mg of Δ9-tetrahydrocannabinol ( THC ) or placebo containing cannabis flowers from which the THC had been extracted . Disease activity and laboratory tests were assessed during 8 weeks of treatment and 2 weeks thereafter . RESULTS Complete remission ( CDAI score , < 150 ) was achieved by 5 of 11 subjects in the cannabis group ( 45 % ) and 1 of 10 in the placebo group ( 10 % ; P = .43 ) . A clinical response ( decrease in CDAI score of > 100 ) was observed in 10 of 11 subjects in the cannabis group ( 90 % ; from 330 ± 105 to 152 ± 109 ) and 4 of 10 in the placebo group ( 40 % ; from 373 ± 94 to 306 ± 143 ; P = .028 ) . Three patients in the cannabis group were weaned from steroid dependency . Subjects receiving cannabis reported improved appetite and sleep , with no significant side effects . CONCLUSIONS Although the primary end point of the study ( induction of remission ) was not achieved , a short course ( 8 weeks ) of THC-rich cannabis produced significant clinical , steroid-free benefits to 10 of 11 patients with active Crohn 's disease , compared with placebo , without side effects . Further studies , with larger patient groups and a nonsmoking mode of intake , are warranted . Clinical Trials.gov , NCT01040910 BACKGROUND & AIMS Few prospect i ve data are available to support the clinical relevance of mucosal healing in patients with Crohn 's disease . This study examined whether complete healing , determined by endoscopy , predicts a better outcome in Crohn 's disease . METHODS One-hundred thirty-three newly diagnosed and treatment-naïve Crohn 's disease patients were given either a combination of immunosuppressive therapy ( azathioprine ) and 3 infusions of infliximab or treatment with conventional corticosteroids . Patients given azathioprine were given repeated doses of infliximab for relapses , patients given corticosteroids were given azathioprine in cases of corticosteroid dependency and infliximab only if azathioprine failed . A representative subset of 49 patients from the initially r and omized cohort underwent ileocolonoscopy after 2 years of therapy . Correlation analysis was performed between different clinical parameters including endoscopic activity ( Simple Endoscopic Score ) and clinical outcome 2 years after this endoscopic examination . Data were available from 46 patients 3 and 4 years after therapy began . RESULTS Complete mucosal healing , defined as a simple endoscopic score of 0 after 2 years of therapy , was the only factor that predicted sustained , steroid-free remission 3 and 4 years after therapy was initiated ; it was observed in 17 of 24 patients ( 70.8 % ) vs 6 of 22 patients with lesions detected by endoscopy ( 27.3 % , Simple Endoscopic Score > 0 ) ( P = .036 ; odds ratio = 4.352 ; 95 % confidence interval , 1.10 - 17.220 ) . Fifteen of 17 patients with mucosal healing at year 2 maintained in remission without further infliximab infusions during years 3 and 4 ( P = .032 ; odds ratio = 4.883 ; 95 % confidence interval , 1.144 - 20.844 ) . CONCLUSIONS Complete mucosal healing in patients with early-stage Crohn 's disease is associated with significantly higher steroid-free remission rates 4 years after therapy began OBJECTIVE Corticosteroids are effective in acute Crohn 's disease ( CD ) . The present study assessed the effectiveness and safety of oral pH-modified release budesonide ( BUD ) in patients with active CD in comparison with 6-methylprednisolone ( MPred ) . DESIGN This was a prospect i ve multicentre , r and omized , double-blind , double-dummy study . METHODS A total of 67 patients with active CD ( CDAI > 150 ) were included . Patients were treated with 3 x 3 mg BUD ( n = 34 ) or MPred ( n = 33 ) according to a weekly tapering schedule ( 48 - 32 - 24 - 20 - 16 - 12 - 8 mg ) . The primary aim was remission of CD ( CDAI < 150 and decrease by at least 60 points from baseline ) after eight weeks . RESULTS Baseline demographics , disease activity and localization of CD in the small bowel and the colon were similar in both treatment groups . On an intention-to-treat basis 19/34 patients in the BUD group ( 55.9 % ) and 24/33 patients in the MPred group ( 72.7 % ) were in remission after eight weeks ( P = 0.237 ) . Therapy failed in 15/34 patients ( 44.1 % ) of the BUD group and in 9/33 patients ( 27.3 % ) of the MPred group . The mean CDAI decreased from 262 + /- 50 to 118 + /- 69 in the BUD-group and from 262 + /- 81 to 95 + /- 61 in the Mored group ( P = 0.183 , final CDAI BUD vs. MPred ) . Steroid-related side effects appeared in 28.6 % of the patients in the BUD group and in 69.7 % of the patients in the Mored group ( P = 0.0015 ) . CONCLUSIONS Oral pH-modified release budesonide ( 3 x 3 mg/day ) is almost as effective as a conventional corticosteroid in patients with active CD but causes significantly less corticosteroid-related side effects BACKGROUND The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn 's disease are unknown . METHODS In this r and omized , double-blind trial , we evaluated the efficacy of infliximab monotherapy , azathioprine monotherapy , and the two drugs combined in 508 adults with moderate-to-severe Crohn 's disease who had not undergone previous immunosuppressive or biologic therapy . Patients were r and omly assigned to receive an intravenous infusion of 5 mg of infliximab per kilogram of body weight at weeks 0 , 2 , and 6 and then every 8 weeks plus daily oral placebo capsules ; 2.5 mg of oral azathioprine per kilogram daily plus a placebo infusion on the st and ard schedule ; or combination therapy with the two drugs . Patients received study medication through week 30 and could continue in a blinded study extension through week 50 . RESULTS Of the 169 patients receiving combination therapy , 96 ( 56.8 % ) were in corticosteroid-free clinical remission at week 26 ( the primary end point ) , as compared with 75 of 169 patients ( 44.4 % ) receiving infliximab alone ( P=0.02 ) and 51 of 170 patients ( 30.0 % ) receiving azathioprine alone ( P<0.001 for the comparison with combination therapy and P=0.006 for the comparison with infliximab ) . Similar numerical trends were found at week 50 . At week 26 , mucosal healing had occurred in 47 of 107 patients ( 43.9 % ) receiving combination therapy , as compared with 28 of 93 patients ( 30.1 % ) receiving infliximab ( P=0.06 ) and 18 of 109 patients ( 16.5 % ) receiving azathioprine ( P<0.001 for the comparison with combination therapy and P=0.02 for the comparison with infliximab ) . Serious infections developed in 3.9 % of patients in the combination-therapy group , 4.9 % of those in the infliximab group , and 5.6 % of those in the azathioprine group . CONCLUSIONS Patients with moderate-to-severe Crohn 's disease who were treated with infliximab plus azathioprine or infliximab monotherapy were more likely to have a corticosteroid-free clinical remission than those receiving azathioprine monotherapy . ( Clinical Trials.gov number , NCT00094458 . Objectives : Biomarkers , endoscopy and imaging tests can identify patients at increased risk for early recurrence of symptomatic inflammatory bowel disease ( IBD ) . However , patients may be unwilling to accept additional medical therapy risks related to therapy escalation to avoid a future disease relapse . We sought to quantify IBD patients ’ willingness to accept medication risk to avoid future disease relapse . Methods : We conducted a discrete-choice experiment among 202 patients with IBD who were offered choices of therapies with varying risks of lymphoma and infection , and varying time to next IBD relapse . R and om parameters logit was used to estimate patients ’ willingness to accept tradeoffs among treatment features in selecting medication therapy to avoid future disease relapse . Results : To avoid a disease relapse over the next 5 years , IBD patients were willing to accept an average of a 28 % chance of a serious infection ; and an average of 1.8 % chance of developing lymphoma . These results did not significantly change when patients were offered 10 years until their next disease relapse , but were lower ( 11 and 0.7 % , respectively ) when offered 1.5 years until the next disease relapse . Patients with active disease symptoms were significantly less willing to accept medication risk for time in remission . Conclusions : IBD patients are willing to accept high levels of lymphoma and serious infection risk to maintain disease remission . These preferences are congruent with the treatment paradigms emphasizing mucosal healing and early aggressive therapy and highlight patients ’ strong preferences for therapies result ing in durable remission of at least 5 years BACKGROUND AND AIMS Current treatments for Japanese patients with active Crohn 's disease have not proved optimal , and new treatment options are required . The present study therefore evaluated the efficacy and tolerability of oral budesonide in Japanese patients with mild-to-moderate active Crohn 's disease . METHODS In this multicentre , double-blind , r and omized , parallel-group , Phase II study , patients ( 18 - 65 years ) with baseline Crohn 's Disease Activity Index ( CDAI ) score≥200 were r and omized to once-daily ( od ) oral budesonide 9 mg or 15 mg , or matching placebo , for 8 weeks . Concomitant therapy with sulfasalazine or 5-aminosalicylic acid , and nutritional therapy , was allowed . The rate of remission ( defined as CDAI score≤150 ) after 8 weeks ' treatment ( primary variable ) , health-related quality of life ( assessed using the Inflammatory Bowel Disease Question naire [ IBDQ ] ) , and tolerability were assessed . RESULTS 77 patients were r and omized and 63 completed the study . The proportion of budesonide-treated patients with remission after 8 weeks ' treatment was higher compared with placebo ( 23.1 % , 28.0 % , and 11.5 % for budesonide 9 mg , 15 mg , and placebo , respectively ; no significant difference ) . The mean change from baseline to week 8 in CDAI total score ( -48.0 , -58.2 , and -27.2 , respectively ) and IBDQ total score ( 10.8 , 23.2 , and 6.5 , respectively ) was greater for budesonide-treated patients than placebo recipients . While budesonide 9 mg and 15 mg demonstrated similar efficacy , budesonide 9 mg caused fewer drug- and glucocorticosteroid-related adverse events and less adrenal suppression . CONCLUSIONS Oral budesonide 9 mg od ( for up to 8 weeks ) may offer a new treatment option for Japanese patients with mild-to-moderate active Crohn 's disease Background and Aim Many patients with quiescent Crohn ’s disease are maintained on long-term treatment with azathioprine ( AZA ) , but controlled data are limited . We aim ed to evaluate the efficacy of AZA therapy for more than 4 years to maintain clinical remission . Methods We performed a r and omized double-blind placebo-controlled AZA withdrawal trial with a follow-up period of 24 months . Patients had to have continuous AZA therapy ≥4 years without exacerbation of disease during the 12 months before enrollment , and a Crohn ’s disease activity index < 150 at baseline . Patients were r and omized to continue on AZA or switch to placebo . The primary endpoint was time to clinical relapse during follow-up . Results After inclusion of 52 patients , the trial was stopped prematurely due to slow recruitment . During the 2-year follow-up , clinical relapse occurred in 4 of 26 ( 15 % ) patients on continued AZA and in 8 of 26 ( 31 % ) patients on placebo . Time to clinical relapse averaged 22.3 months ( 95 % CI 20.6–24.0 ) on AZA and 19.2 months ( 95 % CI 16.4–22.1 ) on placebo ( p = 0.20 ) . According to life-table analysis , the proportion of patients in remission after 12 and 24 months was 96 ± 4 and 86 ± 7 % in patients receiving AZA versus 76 ± 8 and 68 ± 9 % in patients receiving placebo ( month 12 , p = 0.035 ; month 24 , p = 0.30 ) . A higher AZA dose at enrollment was an independent predictor for relapse ( p < 0.05 ) . Conclusions AZA withdrawal result ed in a significantly increased relapse risk after 1 year and a nonstatistically significant trend for relapse after 2 years . Our results are in line with previous observations BACKGROUND The endoscopic sub study of the ACCENT I ( A Crohn 's Disease Clinical Trial Evaluating Infliximab in a New Long-term Treatment Regimen ) Crohn 's disease trial examined the effects of infliximab on mucosal inflammation and mucosal healing , and assessed their impact on outcomes . DESIGN ACCENT I was a r and omized , double-blind , parallel group study . SETTING This study took place at multiple centers in North America , Europe , and Israel . MAIN OUTCOME MEASUREMENTS Ileocolonoscopic examinations were performed at weeks 0 , 10 , and 54 . Complete mucosal healing was defined as the absence of all mucosal ulcerations . The end point of principal interest was the proportion of patients r and omized as responders with mucosal healing at week 10 . The proportion of responders who demonstrated mucosal healing at week 54 or at both weeks 10 and 54 is also summarized . Changes in Crohn 's disease endoscopic index of severity ( CDEIS ) scores from baseline to week 10 and 54 were calculated for all patients in this sub study . RESULTS Complete mucosal healing by week 10 occurred in significantly more week 2 responders who had received 3 doses of infliximab compared with a single dose ( 31 % vs. 0 % , p = 0.010 ) . A significantly higher proportion of week 2 responders in the combined scheduled maintenance group had complete mucosal healing at week 54 compared with the episodic group ( 50 % vs. 7 % , p = 0.007 ) . The results for all patients are consistent with those for week 2 responders only . Significantly greater improvement in the CDEIS occurred with scheduled maintenance compared with episodic treatment at week 10 ( p < /= 0.001 ) and week 54 ( p = 0.026 ) . Notably , no strong relationship between clinical remission and complete mucosal healing was found . Overall , mucosal healing appeared to correlate with fewer hospitalizations , although these results were not statistically significant . CONCLUSIONS Scheduled infliximab maintenance therapy result ed in more improvement in mucosal ulceration and in higher rates of mucosal healing . There was a numerical trend for patients with better mucosal healing to have a lower rate of Crohn 's disease-related hospitalizations BACKGROUND Although corticosteroids are highly effective in improving symptoms of Crohn 's disease , they may have substantial toxicity . In some patients , attempts to discontinue corticosteroids are unsuccessful . METHODS We conducted a double-blind , placebo-controlled multicenter study of weekly injections of methotrexate in patients who had chronically active Crohn 's disease despite a minimum of three months of prednisone therapy . Patients were r and omly assigned to treatment with intramuscular methotrexate ( 25 mg once weekly ) or placebo for 16 weeks . The patients also received prednisone ( 20 mg once a day ) , which was tapered over 10 weeks unless their condition worsened . The primary outcome measure was clinical remission at the end of the 16-week trial . Remission was defined by the discontinuation of prednisone and a score of < or = 150 points on the Crohn 's Disease Activity Index . RESULTS A total of 141 patients were r and omly assigned in a 2:1 ratio to methotrexate ( 94 patients ) or placebo ( 47 patients ) . After 16 weeks , 37 patients ( 39.4 percent ) were in clinical remission in the methotrexate group , as compared with 9 patients ( 19.1 percent ) in the placebo group ( P = 0.025 ; relative risk , 1.95 ; 95 percent confidence interval , 1.09 to 3.48 ) . The patients in the methotrexate group received less prednisone overall than those in the placebo group ( P = 0.026 ) . The mean ( + /- SE ) score on the Crohn 's Disease Activity Index after 16 weeks of treatment was significantly lower in the methotrexate group ( 162 + /- 12 ) than in the placebo group ( 204 + /- 17 , P = 0.002 ) . The changes in quality -of-life scores and serum orosomucoid concentrations were similar . In the methotrexate group , 16 patients ( 17 percent ) withdrew from treatment because of adverse events ( including asymptomatic elevation of serum aminotransferase in 7 and nausea in 6 ) , as compared with 1 patient ( 2 percent ) in the placebo group . CONCLUSIONS In a group of patients with chronically active Crohn 's disease , methotrexate was more effective than placebo in improving symptoms and reducing requirements for prednisone BACKGROUND & AIMS Tumor necrosis factor ( TNF ) is a pivotal cytokine in intestinal inflammation . Controlled trials using a chimeric anti-TNF antibody ( infliximab ) have shown its efficacy in refractory Crohn 's disease . METHODS Endoscopic and histological response to infliximab was investigated in a multicenter , r and omized , double-blind , and placebo-controlled trial including 30 patients with active Crohn 's disease undergoing ileocolonoscopy before and 4 weeks after intravenous administration of 5 , 10 , or 20 mg/kg of infliximab or placebo as a single infusion . Lesions were scored by means of the vali date d Crohn 's Disease Endoscopic Index of Severity ( CDEIS ) . Endoscopic biopsy specimens were taken during both procedures from 9 of 30 patients and scored by a single gastrointestinal pathologist . RESULTS CDEIS scores decreased significantly in most infliximab-treated patients without an apparent dose response . No endoscopic improvement was observed in the placebo group . The changes in CDEIS correlated highly with those of the Crohn 's Disease Activity Index . At a histological level , disappearance of the inflammatory infiltrate was observed in infliximab-treated patients but not in placebo-treated ones ; however , architectural changes persisted in most patients . Strictures developed in several patients . CONCLUSIONS Clinical improvement after infliximab therapy in active Crohn 's disease is accompanied by significant healing of endoscopic lesions and disappearance of the mucosal inflammatory infiltrate BACKGROUND & AIMS We investigated the efficacy of adalimumab for inducing and maintaining mucosal healing in patients with Crohn 's disease ( CD ) . METHODS A r and omized , double-blind , placebo-controlled trial ( extend the safety and efficacy of adalimumab through endoscopic healing [ EXTEND ] ) evaluated adalimumab for induction and maintenance of mucosal healing in 135 adults with moderate to severe ileocolonic CD . The baseline degree of mucosal ulceration was documented by ileocolonoscopy . All patients received induction therapy ( subcutaneous adalimumab 160/80 mg at weeks 0/2 ) . At week 4 , patients were r and omly assigned to groups given 40 mg adalimumab or placebo every other week through week 52 . Open-label adalimumab was given to patients with flares or no response , starting at week 8 . Mucosal healing was reassessed by ileocolonoscopy at weeks 12 and 52 . RESULTS Twenty-seven percent of patients receiving adalimumab had mucosal healing at week 12 ( the primary end point ) versus 13 % given placebo ( P = .056 ) . At week 52 , rates of mucosal healing were 24 % and 0 , respectively ( P < .001 ) . Remission rates , based on the Crohn 's Disease Endoscopic Index of Severity , were 52 % for adalimumab and 28 % for placebo at week 12 ( P = .006 ) and 28 % and 3 % , respectively , at week 52 ( P < .001 ) . Rates of clinical remission based on the Crohn 's Disease Activity Index were greater among patients given continuous adalimumab therapy versus placebo at weeks 12 ( 47 % vs 28 % ; P = .021 ) and 52 ( 33 % vs 9 % ; P = .001 ) . Five serious ( 1 during induction and 4 during open-label therapy ) and 3 opportunistic infections ( 1 in each group during double-blind therapy and 1 during open-label therapy ) were reported ( n = 135 ) . CONCLUSIONS Following induction therapy with adalimumab , patients with moderately to severely active CD who continue to receive adalimumab are more likely to achieve mucosal healing than those given placebo Objective : To assess the efficacy , tolerability , and safety of CT-P13 ( Remsima ® ) in patients with Crohn ’s disease ( CD ) or ulcerative colitis ( UC ) . Methods : This was a prospect i ve observational study performed in a single center in Norway . Patients with CD ( n = 46 ) or UC ( n = 32 ) received CT-P13 ( 5 mg/kg ) by intravenous infusion at weeks 0 , 2 , and 6 . Efficacy end points included remission at week 14 , measured by a Harvey-Bradshaw Index score of ≤4 or partial Mayo score of ≤2 . Levels of the inflammatory markers C-reactive protein and calprotectin were measured . Adverse events up to week 14 were also recorded . Results : Seventy-nine percent of CD and 56 % of UC patients achieved remission at week 14 . Significant reductions in C-reactive protein and calprotectin occurred between baseline and week 14 . There were no unexpected adverse events reported during the study . Conclusion : CT-P13 is efficacious and well tolerated in patients with CD or UC BACKGROUND & AIMS Tumor necrosis factor blockade has been shown to be an effective treatment strategy in Crohn 's disease ( CD ) . Adalimumab is a human immunoglobulin G1 ( IgG(1 ) ) monoclonal antibody targeting tumor necrosis factor ( TNF ) . A r and omized , double-blind , placebo-controlled , dose-ranging trial was performed to evaluate the efficacy of adalimumab induction therapy in patients with CD . METHODS A total of 299 patients with moderate to severe CD naive to anti-TNF therapy were r and omized to receive subcutaneous injections at weeks 0 and 2 with adalimumab 40 mg/20 mg , 80 mg/40 mg , or 160 mg/80 mg or placebo . The primary endpoint was demonstration of a significant difference in the rates of remission at week 4 ( defined as a Crohn 's Disease Activity Index score < 150 points ) among the 80 mg/40 mg , 160 mg/80 mg , and placebo groups . RESULTS The rates of remission at week 4 in the adalimumab 40 mg/20 mg , 80 mg/40 mg , and 160 mg/80 mg groups were 18 % ( P = .36 ) , 24 % ( P = .06 ) , and 36 % ( P = .001 ) , respectively , and 12 % in the placebo group . Adverse events occurred at similar frequencies in all 4 treatment groups except injection site reactions , which were more common in adalimumab-treated patients . CONCLUSIONS Adalimumab was superior to placebo for induction of remission in patients with moderate to severe Crohn 's disease naive to anti-TNF therapy . The optimal induction dosing regimen for adalimumab in this study was 160 mg at week 0 followed by 80 mg at week 2 . Adalimumab was well tolerated Summary : Adrenocorticotrophic hormone ( ACTH ) and corti‐costeroids have no maintenance values for inflammatory bowel disease but serve to reduce the severity of disease . The effec‐tiveness of intravenous corticotrophin versus hydrocortisone in ulcerative colitis has been determined including whether previous steroid therapy influenced the better response to one rather than the other , but no such studies have ever been done in Crohn 's disease . Eighty‐eight patients hospitalized with moderate‐to‐severe Crohn 's disease ( Present‐Korelitz [ P‐K ] Index ‐3 to ‐2 and the International Organisation for the Study of Inflammatory Bowel Disease‐Crohn 's & Colitis Foundation of America [ IOIBD‐CCFA ] Index , mean 14 , range 5‐23 ) were treated in a prospect i ve , r and omized , double‐blind clinical trial to receive either continuous intravenous infusion of 120 U/day of ACTH ( 44 patients ) or hydrocortisone 300 mg/day ( 44 patients ) . Patients were also subdivided into those who received oral steroids during the 30 days prior to intravenous therapy and those who had not . Response was followed on a daily basis and tabulated at 3 , 5 , and 10 days . Patients were followed from 1‐3 years to determine the later status . After 10 days of intravenous therapy 36 of 44 patients ( 82 % ) who received ACTH and 41 of 44 patients ( 93 % ) who received hydrocortisone fully responded ( P‐K index + 3 and IOIBD‐CCFA Index mean of 3 ) . At the end of the study , response to intravenous ACTH and hydrocortisone was not statistically different whether or not patients received oral steroids during the 30 days prior to admission , although the response to IV ACTH tended to be faster at 3 days in those who had received previous steroid therapy . Intravenous ACTH and hydrocortisone are equally effective in achieving therapeutic goals in patients with Crohn 's disease who have not achieved results with oral medications . Moreover the response rate was high ( mean 88 % ) , serving to buy time for establishment of successful maintenance programs of treatment with oral 5‐ASA and immunosuppressive drugs for 69 % of patients at 1‐3 years BACKGROUND & AIMS We evaluated etanercept , a human soluble tumor necrosis factor receptor : Fc fusion protein , for the treatment of active Crohn 's disease . METHODS Forty-three patients with moderate to severe Crohn 's disease were enrolled in an 8-week placebo-controlled trial . Patients were r and omized to subcutaneous etanercept 25 mg or placebo twice weekly . The primary outcome measure was clinical response at week 4 , defined as a decrease in the baseline Crohn 's Disease Activity Index score > or = 70 points or a Crohn 's Disease Activity Index score < 150 points . RESULTS At week 4 , 39 % of etanercept-treated patients had clinical response as compared with 45 % of placebo-treated patients ( P = 0.763 ) . The frequency of common adverse events including headache , new injection site reaction , asthenia , abdominal pain , Crohn 's disease-related anemia , and skin disorders was similar in both groups . Likewise , the frequency of severe or serious adverse events was similar in both groups . CONCLUSIONS Subcutaneous etanercept at a dose of 25 mg twice weekly is safe , but not effective , for the treatment of patients with moderate to severe Crohn 's disease . The dose of etanercept administered in this study is that approved for rheumatoid arthritis . Higher doses or more frequent dosing may be required to attain a response in patients with active Crohn 's disease BACKGROUND At present only one large controlled study has indicated that parenteral methotrexate may be effective in chronic active Crohn 's disease ( CD ) . AIM To evaluate the effectiveness of oral methotrexate in chronic steroid-dependent CD . PATIENTS Patients with active CD , who have received steroids and /or immunosuppressives for at least 4 months during the preceding 12 months and with a current Harvey-Bradshaw index of > or = 7 were studied . METHODS Methotrexate ( 12.5 mg weekly ) or 6-mercaptopurine ( 50 mg daily ) , or placebo were given during the 9 months of the trial in addition to steroids and 5-aminosalicylic acid as clinical ly indicated . RESULTS Eighty-four patients were included ( methotrexate , 26 patients ; 6-mercaptopurine , 32 patients ; placebo , 26 patients ) . The proportion of patients entering first remission as well as the proportions of patients relapsing after first remission were not significantly different between the groups . The mean Harvey-Bradshaw index and the mean monthly steroid dose were also similar . However , when each patient was evaluated as his or her own control , the reduction in steroid dose , the general well being , and the reduction in abdominal pain were significantly better in the methotrexate treated patients . CONCLUSIONS Methotrexate at a weekly oral dose of 12.5 mg was found to be moderately better than 6-mercaptopurine and placebo in patients with chronic active CD BACKGROUND AND AIMS Biosimilar infliximab CT-P13 is approved for all indications of the originator product in Europe . Prospect i ve data on its efficacy , safety , and immunogenicity in inflammatory bowel diseases are lacking . METHODS A prospect i ve , nationwide , multicentre , observational cohort was design ed to examine the efficacy , safety , and immunogenicity of CT-P13 infliximab biosimilar in the induction treatment of Crohn 's disease [ CD ] and ulcerative colitis [ UC ] . Demographic data were collected and a harmonised monitoring strategy was applied . Early clinical remission , response , and early biochemical response were evaluated at Week 14 , steroid-free clinical remission was evaluated at Week 30 . Therapeutic drug level was monitored using a conventional enzyme-linked immunosorbent assay . RESULTS In all , 210 consecutive inflammatory bowel disease [ 126 CD and 84 UC ] patients were included in the present cohort . At Week 14 , 81.4 % of CD and 77.6 % of UC patients showed clinical response and 53.6 % of CD and 58.6 % of UC patients were in clinical remission . Clinical remission rates at Week 14 were significantly higher in CD and UC patients who were infliximab naïve , compared with those with previous exposure to the originator compound [ p < 0.05 ] . Until Week 30 , adverse events were experienced in 17.1 % of all patients . Infusion reactions and infectious adverse events occurred in 6.6 % and 5.7 % of all patients , respectively . CONCLUSIONS This prospect i ve multicentre cohort shows that CT-P13 is safe and effective in the induction of clinical remission and response in both CD and UC . Patients with previous infliximab exposure exhibited decreased response rates and were more likely to develop allergic reactions One hundred forty-two patients with active colonic or ileocolonic Crohn 's disease were included in a multicenter prospect i ve study . Data collection included 28 clinical , biological , and endoscopic items ; the latter were recorded according to a st and ardized colonoscopic protocol ; a previously vali date d endoscopic index of severity was calculated . Oral prednisolone ( 1 mg/kg body wt per day ) was started and maintained until clinical remission and for at least 3 and at most 7 wk . A second clinical biological and endoscopic evaluation was then performed . At initial colonoscopy , mucosal lesions were , by decreasing order of frequency , superficial ulcerations , deep ulcerations , mucosal edema , erythema , pseudopolyps , aphthoid ulcers , ulcerated stenosis , and nonulcerated stenosis ( 93 % , 74 % , 48 % , 44 % , 41 % , 35 % , 10 % , 8 % , and 2 % of cases , respectively ) . No correlation was found between the clinical activity index and any of the endoscopical data ( lesion frequency and surface , endoscopic severity index ) . Ninety-two percent of patients underwent clinical remission within 7 wk of treatment . None of the 28 clinical biological and endoscopical items collected just before treatment could predict clinical response to steroids . Only 38 of the 131 patients in clinical remission were also in endoscopic remission . In conclusion , ( a ) the description and severity of colonoscopic lesions in active Crohn 's disease have been quantified ; ( b ) no correlation exists between clinical severity and nature , surface , or severity of endoscopic lesions ; ( c ) Oral prednisolone ( 1 mg/kg body wt per day ) induces a clinical remission in 92 % of patients within 7 wk ; ( d ) resistance to steroids can not be predicted from the data collected before treatment onset ; and ( e ) only 29 % of patients in clinical remission also achieve endoscopic remission The outcome of the first steroid treatment course was prospect ively studied in a regional cohort of 196 patients with Crohn 's disease diagnosed 1979 - 1987 . The immediate outcome after 30 days , and the prolonged outcome 30 days after treatment had stopped , are described . In all 109 patients treatment was analysed . Complete remission was obtained in 48 % , partial remission in 32 % , and no response in 20 % within 30 days of treatment . Among primary responders ( complete and partial remission ) , 55 % remained in prolonged response after treatment had finished , while 45 % relapsed or could not be withdrawn from treatment within one year . Localisation of disease , age , sex or clinical symptoms did not significantly correlate with outcome , which can be summarised as prolonged steroid response in 44 % , steroid dependency in 36 % , and steroid resistant in 20 % of the patients BACKGROUND Most patients who have active Crohn 's disease are treated initially with corticosteroids . Although this approach usually controls symptoms , many patients become resistant to or dependent on corticosteroids , and long exposure is associated with an increased risk of mortality . We aim ed to compare the effectiveness of early use of combined immunosuppression with conventional management in patients with active Crohn 's disease who had not previously received glucocorticoids , antimetabolites , or infliximab . METHODS We did a 2-year open-label r and omised trial at 18 centres in Belgium , Holl and , and Germany between May , 2001 , and January , 2004 . We r and omly assigned 133 patients to either early combined immunosuppression or conventional treatment . The 67 patients assigned to combined immunosuppression received three infusions of infliximab ( 5 mg/kg of bodyweight ) at weeks 0 , 2 , and 6 , with azathioprine . We gave additional treatment with infliximab and , if necessary , corticosteroids , to control disease activity . 66 patients assigned to conventional management received corticosteroids , followed , in sequence , by azathioprine and infliximab . The primary outcome measures were remission without corticosteroids and without bowel resection at weeks 26 and 52 . Analysis was by modified intention to treat . This trial was registered with Clinical Trials.gov , number NCT00554710 . FINDINGS Four patients ( two in each group ) did not receive treatment as per protocol . At week 26 , 39 ( 60.0 % ) of 65 patients in the combined immunosuppression group were in remission without corticosteroids and without surgical resection , compared with 23 ( 35.9 % ) of 64 controls , for an absolute difference of 24.1 % ( 95 % CI 7.3 - 40.8 , p=0.0062 ) . Corresponding rates at week 52 were 40/65 ( 61.5 % ) and 27/64 ( 42.2 % ) ( absolute difference 19.3 % , 95 % CI 2.4 - 36.3 , p=0.0278 ) . 20 of the 65 patients ( 30.8 % ) in the early combined immunosuppression group had serious adverse events , compared with 19 of 64 ( 25.3 % ) controls ( p=1.0 ) . INTERPRETATION Combined immunosuppression was more effective than conventional management for induction of remission and reduction of corticosteroid use in patients who had been recently diagnosed with Crohn 's disease . Initiation of more intensive treatment early in the course of the disease could result in better outcomes BACKGROUND The efficacy of vedolizumab , an α4β7 integrin antibody , in Crohn 's disease is unknown . METHODS In an integrated study with separate induction and maintenance trials , we assessed intravenous vedolizumab therapy ( 300 mg ) in adults with active Crohn 's disease . In the induction trial , 368 patients were r and omly assigned to receive vedolizumab or placebo at weeks 0 and 2 ( cohort 1 ) , and 747 patients received open-label vedolizumab at weeks 0 and 2 ( cohort 2 ) ; disease status was assessed at week 6 . In the maintenance trial , 461 patients who had had a response to vedolizumab were r and omly assigned to receive placebo or vedolizumab every 8 or 4 weeks until week 52 . RESULTS At week 6 , a total of 14.5 % of the patients in cohort 1 who received vedolizumab and 6.8 % who received placebo were in clinical remission ( i.e. , had a score on the Crohn 's Disease Activity Index [ CDAI ] of ≤150 , with scores ranging from 0 to approximately 600 and higher scores indicating greater disease activity ) ( P=0.02 ) ; a total of 31.4 % and 25.7 % of the patients , respectively , had a CDAI-100 response ( ≥100-point decrease in the CDAI score ) ( P=0.23 ) . Among patients in cohorts 1 and 2 who had a response to induction therapy , 39.0 % and 36.4 % of those assigned to vedolizumab every 8 weeks and every 4 weeks , respectively , were in clinical remission at week 52 , as compared with 21.6 % assigned to placebo ( P<0.001 and P=0.004 for the two vedolizumab groups , respectively , vs. placebo ) . Antibodies against vedolizumab developed in 4.0 % of the patients . Nasopharyngitis occurred more frequently , and headache and abdominal pain less frequently , in patients receiving vedolizumab than in patients receiving placebo . Vedolizumab , as compared with placebo , was associated with a higher rate of serious adverse events ( 24.4 % vs. 15.3 % ) , infections ( 44.1 % vs. 40.2 % ) , and serious infections ( 5.5 % vs. 3.0 % ) . CONCLUSIONS Vedolizumab-treated patients with active Crohn 's disease were more likely than patients receiving placebo to have a remission , but not a CDAI-100 response , at week 6 ; patients with a response to induction therapy who continued to receive vedolizumab ( rather than switching to placebo ) were more likely to be in remission at week 52 . Adverse events were more common with vedolizumab . ( Funded by Millennium Pharmaceuticals ; GEMINI 2 Clinical Trials.gov number , NCT00783692 . ) Background : Vitamin D ( 25(OH)D ) deficiency occurs in active Crohn 's disease ( CD ) and may be secondary to reduced sunlight exposure and oral intake . Vitamin D – binding protein ( VDBP ) levels , however , fluctuate less with season and sunlight . The aim , therefore , was to examine patients with CD in remission and determine any associations between VDBP , serum 25(OH)D , and the calculated free 25(OH)D concentrations with the risk of disease flare . Methods : Subjects were identified from prospect ively maintained inflammatory bowel disease data bases at 3 teaching hospitals in Australia . Patients were in steroid-free clinical remission at the time of blood draw and were followed for at least 12 months . Total and epimer-25(OH)D3 , VDBP concentrations , and genotypes were determined . Results : A total of 309 patients with CD ( 46 % men ) met the inclusion criteria . A disease flare occurred in 100 ( 32.4 % ) . Serum 25(OH)D3 was deficient ( < 50 nmol/L ) in 36 ( 12 % ) and insufficient ( 50–75 nmol/L ) in 107 ( 35 % ) patients . Total , free , and epimer-25(OH)D3 serum levels did not predict disease flare . Higher VDBP concentrations , however , significantly correlated with increased risk of disease flare ( hazard ratio 1.2 , 95 % CI , 1.0–1.5 ) . On multivariate analysis , VDBP concentration , low albumin , and medication-induced remission were significantly more associated with disease flare . VDBP genotypes were significantly associated with 25(OH)D and VDBP concentrations but not disease flare . Conclusions : Vitamin D deficiency was uncommon in our patients with CD in remission , and serum 25(OH)D3 did not predict disease flare , whereas higher VDBP concentrations were significantly associated with disease flare . Further investigations to explore the possible mechanisms for this association are warranted BACKGROUND Studies in animals and an open-label trial have suggested a role for antibodies to tumor necrosis factor alpha , specifically chimeric monoclonal antibody cA2 , in the treatment of Crohn 's disease . METHODS We conducted a 12-week multicenter , double-blind , placebo-controlled trial of cA2 in 108 patients with moderate-to-severe Crohn 's disease that was resistant to treatment . All had scores on the Crohn 's Disease Activity Index between 220 and 400 ( scores can range from 0 to about 600 , with higher scores indicating more severe illness ) . Patients were r and omly assigned to receive a single two-hour intravenous infusion of either placebo or cA2 in a dose of 5 mg per kilogram of body weight , 10 mg per kilogram , or 20 mg per kilogram . Clinical response , the primary end point , was defined as a reduction of 70 or more points in the score on the Crohn 's Disease Activity Index at four weeks that was not accompanied by a change in any concomitant medications . RESULTS At four weeks , 81 percent of the patients given 5 mg of cA2 per kilogram ( 22 of 27 patients ) , 50 percent of those given 10 mg of cA2 per kilogram ( 14 of 28 ) , and 64 percent of those given 20 mg of cA2 per kilogram ( 18 of 28 ) had had a clinical response , as compared with 17 percent of patients in the placebo group ( 4 of 24 ) ( p<0.001 for the comparison of the cA2 group as a whole with placebo ) . Thirty-three percent of the patients given cA2 went into remission ( defined as a score below 150 on the Crohn 's Disease Activity Index ) , as compared with 4 percent of the patients given placebo ( P=0.005 ) . At 12 weeks , 41 percent of the cA2-treated patients ( 34 of 83 ) had had a clinical response , as compared with 12 percent of the patients in the placebo group ( 3 of 25 ) ( P=0.008 ) . The rates of adverse effects were similar in the groups . CONCLUSIONS A single infusion of cA2 was an effective short-term treatment in many patients with moderate-to-severe , treatment-resistant Crohn 's disease Needing a single index of degree of illness in Crohn 's disease , the National Cooperative Crohn 's Disease Study group collected data prospect ively from 187 visits of 112 patients with Crohn 's disease of the small bowel , colon , or both . Information on 18 predictor variables was gathered at each visit . In addition , the attending physician rated his over-all evaluation of how well the patient was doing and compared the patient 's status with that at the previous visit . A multiple regression computer program was utilized to derive an equation for prediction of the physician 's over-all ratings from a subset of the predictor variables fulfilling a combination of constraints . This equation , numerically simplified and utilizing eight selected variables , is the Crohn 's Disease Activity Index . Index values of 150 and below are associated with quiescent disease ; values above that indicate active disease , and values above 450 are seen with extremely severe disease BACKGROUND AND AIMS The efficacy of azathioprine for Crohn 's disease under adalimumab treatment remains obscure . METHODS In an open-labelled prospect i ve study , we evaluated the efficacy of adalimumab with and without azathioprine in patients with active Crohn 's disease , who were naïve to biologics and thiopurines . The patients were r and omly assigned to subcutaneous administration of adalimumab [ monotherapy group ] or to exactly the same schedule of adalimumab with azathioprine [ 25 - 100 mg daily ] [ combination group ] for 52 Weeks . The primary endpoint was clinical remission at WWeek 26 . We also evaluated the score for simple endoscopic severity of Crohn 's disease before the therapy and at WWeeks 26 and 52 . RESULTS A total of 176 patients were r and omized to either the monotherapy group [ n = 85 ] or to the combination group [ n = 91 ] . Eighteen patients [ 21.2 % ] from the monotherapy group and 7 patients [ 7.7 % ] from the combination group withdrew owing to active disease , and 15 patients [ 16.5 % ] from the combination group and 1 patient [ 1.2 % ] from the monotherapy group withdrew due to side effects of the medications . Non-responder imputation analysis revealed that the remission rate at WWeek 26 did not differ between the monotherapy group and the combination group [ 71.8 % vs 68.1 % ; OR 0.84 , p = 0.63 ] . The rate of endoscopic improvement at WWeek 26 was significantly higher in the combination group [ 84.2 % , n = 57 ] than in the monotherapy group [ 63.8 % , n = 58 ] [ p = 0.019 ] . CONCLUSION The clinical efficacy of a combination of adalimumab and azathioprine at WWeek 26 did not differ from that of adalimumab monotherapy in patients with Crohn 's disease naïve to both medications Background : Oral methotrexate and folic acid are partly absorbed by a common intestinal transporter BACKGROUND In patients with Crohn 's disease , the efficacy of ustekinumab , a human monoclonal antibody against interleukin-12 and interleukin-23 , is unknown . METHODS We evaluated ustekinumab in adults with moderate-to-severe Crohn 's disease that was resistant to anti-tumor necrosis factor ( TNF ) treatment . During induction , 526 patients were r and omly assigned to receive intravenous ustekinumab ( at a dose of 1 , 3 , or 6 mg per kilogram of body weight ) or placebo at week 0 . During the maintenance phase , 145 patients who had a response to ustekinumab at 6 weeks underwent a second r and omization to receive subcutaneous injections of ustekinumab ( 90 mg ) or placebo at weeks 8 and 16 . The primary end point was a clinical response at 6 weeks . RESULTS The proportions of patients who reached the primary end point were 36.6 % , 34.1 % , and 39.7 % for 1 , 3 , and 6 mg of ustekinumab per kilogram , respectively , as compared with 23.5 % for placebo ( P=0.005 for the comparison with the 6-mg group ) . The rate of clinical remission with the 6-mg dose did not differ significantly from the rate with placebo at 6 weeks . Maintenance therapy with ustekinumab , as compared with placebo , result ed in significantly increased rates of clinical remission ( 41.7 % vs. 27.4 % , P=0.03 ) and response ( 69.4 % vs. 42.5 % , P<0.001 ) at 22 weeks . Serious infections occurred in 7 patients ( 6 receiving ustekinumab ) during induction and 11 patients ( 4 receiving ustekinumab ) during maintenance . Basal-cell carcinoma developed in 1 patient receiving ustekinumab . CONCLUSIONS Patients with moderate-to-severe Crohn 's disease that was resistant to TNF antagonists had an increased rate of response to induction with ustekinumab , as compared with placebo . Patients with an initial response to ustekinumab had significantly increased rates of response and remission with ustekinumab as maintenance therapy . ( Funded by Janssen Research and Development ; CERTIFI Clinical Trials.gov number , NCT00771667 . ) BACKGROUND & AIMS A small placebo-controlled trial reported the efficacy of mercaptopurine therapy for children newly diagnosed with Crohn 's disease , yet little is known about the efficacy of early thiopurine therapy in adults . METHODS We performed a prospect i ve double-blind trial of adult patients with a recent ( < 8 weeks ) diagnosis of Crohn 's disease . Patients were r and omly assigned to groups given azathioprine ( 2.5 mg · kg(-1 ) · day(-1 ) , n = 68 ) or placebo ( n = 63 ) at 31 hospitals from February 2006 to September 2009 . Corticosteroids but no other concomitant medications were allowed for control of disease activity . The primary measure of efficacy was sustained corticosteroid-free remission . RESULTS After 76 weeks of treatment , 30 patients treated with azathioprine ( 44.1 % ) and 23 given placebo ( 36.5 % ) were in sustained corticosteroid-free remission ( difference of 7.6 % ; 95 % confidence interval , -9.2 to 24.4 % ; P = .48 ) . The rates of relapse ( defined as Crohn 's Disease Activity Index score > 175 ) and corticosteroid requirements were similar between groups . A post hoc analysis of relapse , defined as a Crohn 's Disease Activity Index score > 220 , showed lower relapse rates in the azathioprine group than in the placebo group ( 11.8 % vs 30.2 % ; P = .01 ) . Serious adverse events occurred in 14 patients in the azathioprine group ( 20.6 % ) and 7 in the placebo group ( 11.1 % ) ( P = .16 ) . A larger percentage of patients in the azathioprine group had adverse events that led to study drug discontinuation ( 20.6 % ) than in the placebo group ( 6.35 % ) ( P = .02 ) . CONCLUSIONS In a study of adults with Crohn 's disease , early azathioprine therapy was no more effective than placebo to achieve sustained corticosteroid-free remission but was more effective in preventing moderate to severe relapse in a post hoc analysis . EudraCT 2005 - 001186 - 34 BACKGROUND & AIMS Methotrexate and infliximab are effective therapies for Crohn 's disease ( CD ) . In the combination of maintenance methotrexate-infliximab trial , we evaluated the potential superiority of combination therapy over infliximab alone . METHODS In a 50-week , double-blind , placebo-controlled trial , we compared methotrexate and infliximab with infliximab alone in 126 patients with CD who had initiated prednisone induction therapy ( 15 - 40 mg/day ) within the preceding 6 weeks . Patients were assigned r and omly to groups given methotrexate at an initial weekly dose of 10 mg , escalating to 25 mg/week ( n = 63 ) , or placebo ( n = 63 ) . Both groups received infliximab ( 5 mg/kg of body weight ) at weeks 1 , 3 , 7 , and 14 , and every 8 weeks thereafter . Prednisone was tapered , beginning at week 1 , and discontinued no later than week 14 . The primary outcome was time to treatment failure , defined as a lack of prednisone-free remission ( CD Activity Index , < 150 ) at week 14 or failure to maintain remission through week 50 . RESULTS Patients ' baseline characteristics were similar between groups . By week 50 , the actuarial rate of treatment failure was 30.6 % in the combination therapy group compared with 29.8 % in the infliximab monotherapy group ( P = .63 ; hazard ratio , 1.16 ; 95 % confidence interval , 0.62 - 2.17 ) . Prespecified subgroup analyses failed to show a benefit in patients with short disease duration or an increased level of C-reactive protein . No clinical ly meaningful differences were observed in secondary outcomes . Combination therapy was well tolerated . CONCLUSIONS The combination of infliximab and methotrexate , although safe , was no more effective than infliximab alone in patients with CD receiving treatment with prednisone . ClincialTrials.gov number , NCT00132899 BACKGROUND & AIMS There is an increasing need for new treatments for patients with Crohn 's disease ( CD ) in whom previous therapy with tumor necrosis factor ( TNF ) antagonists has failed . We performed a placebo-controlled , phase 3 , double-blind trial to evaluate the efficacy and safety of vedolizumab , an antibody against the integrin α4β7 , as induction therapy . METHODS Patients with moderately to severely active CD ( CD activity index [ CDAI ] score , 220 - 400 points ) were assigned r and omly to groups given vedolizumab ( 300 mg ) or placebo intravenously at weeks 0 , 2 , and 6 . The primary analysis involved 315 patients with previous TNF antagonist failure ( ie , an inadequate response to , loss of response to , or intolerance of ≥1 TNF antagonists ) ; we determined the proportion of patients in clinical remission ( CDAI , ≤150 points ) at week 6 . Secondary analyses evaluated outcomes at weeks 6 and 10 in this population and in the overall population ( N = 416 ) , which included patients naive to TNF antagonist therapy ( n = 101 ) . RESULTS Among patients who had experienced previous TNF antagonist failure , 15.2 % of those given vedolizumab and 12.1 % of those given placebo were in remission at week 6 ( P = .433 ) . At week 10 , a higher proportion of this population given vedolizumab was in remission ( 26.6 % ) than those given placebo ( 12.1 % ) ( nominal P = .001 ; relative risk , 2.2 ; 95 % confidence interval , 1.3 - 3.6 ) . A higher proportion of patients with previous TNF antagonist failure given vedolizumab also had a CDAI-100 response ( ≥100-point decrease in CDAI score from baseline ) at week 6 than those given placebo ( 39.2 % vs 22.3 % ; nominal P = .001 ; relative risk , 1.8 ; 95 % confidence interval , 1.2 - 2.5 ) . Adverse event results were similar among all groups . CONCLUSIONS Vedolizumab was not more effective than placebo in inducing clinical remission at week 6 among patients with CD in whom previous treatment with TNF antagonists had failed . The therapeutic benefits of vedolizumab in these patients were detectable at week 10 . Clinical Trials.gov number : NCT01224171 Background Elective switching between anti-tumour necrosis factor ( TNF ) agents not necessarily dictated by efficacy or tolerability occurs in clinical practice . A study was undertaken to evaluate prospect ively the impact of elective switching of patients with Crohn 's disease well controlled with intravenous infliximab to subcutaneous adalimumab in a controlled trial . Methods An open-label r and omised single-centre trial recruited 73 patients with ongoing response to at least 6 months of scheduled maintenance infliximab . Patients were r and omised to continue intravenous 5 mg/kg infliximab or to switch to subcutaneous adalimumab 80 mg at baseline followed by 40 mg every other week for 1 year . Dose optimisation was allowed for intermittent flares , and patients with loss of response or intolerance could cross over to the alternative treatment group . Tolerability , patient preference and efficacy of both treatment options were the primary outcomes . Results Dose optimisation or interruption of treatment occurred in 17/36 patients ( 47 % ) in the adalimumab group and in 6/37 patients ( 16 % ) in the infliximab group ( p=0.006 ) . One patient interrupted infliximab treatment and 10 patients interrupted adalimumab treatment ( p=0.003 ) , mostly for loss of tolerance . Overall , patients preferred adalimumab treatment . All five serious adverse events were related to complicated Crohn 's disease and occurred in patients r and omised to adalimumab . Injection site reactions were more frequent than infusion reactions ( 8 vs 1 , p=0.01 ) , but only the latter caused cessation of further dosing . Anti-TNF serum levels were stable throughout the 1-year period in both groups . Conclusion Elective switching from infliximab to adalimumab is associated with loss of tolerance and loss of efficacy within 1 year . Adherence to the first anti-TNF agent is recommended BACKGROUND There is currently little evidence about what treatment objectives most interest patients with inflammatory bowel disease ( IBD ) . AIMS To determine patient preferences regarding IBD treatment objectives , specially the attributes they value most and the symptoms to be controlled as a priority . METHODS Prospect i ve , observational , anonymous study conducted in 117 out patients with Crohn 's disease or ulcerative colitis . RESULTS The most important treatment objectives from the patients ' perspective were : improving quality of life ( 40.2 % of patients ) , and completely resolving symptoms ( 33.3 % ) . Only 12.8 % of patients indicated having a completely normal colonoscopy as a preferred objective . The symptoms the patients considered to be most important when prioritizing their control were : abdominal pain ( 23.1 % of patients ) , and bowel movement urgency ( 17.1 % ) . The preferred treatment objectives were similar for Crohn 's disease and ulcerative colitis patients . CONCLUSIONS Improving quality of life and completely controlling symptoms are the priority treatment objectives for IBD patients , with abdominal pain being the most important symptom . Conversely , therapeutic objective target goals proposed by physicians , such as healing the mucosal lesions , are not a priority for most patients . This indicates that there are discrepancies between patient and physician expectations , which should be taken into account if a patient-centered care model is to be implemented |
12,205 | 18,843,665 | Reported adverse events were mainly mild and transient , and occurred at similar rates with 1000 mg paracetamol and placebo .
A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain , for a period of about four hours , and is associated with few , mainly mild , adverse events | BACKGROUND This is an up date d version of the original Cochrane review published in Issue 1 , 2004 - this original review had been split from a previous title on ' Single dose paracetamol ( acetaminophen ) with and without codeine for postoperative pain ' .
The last version of this review concluded that paracetamol is an effective analgesic for postoperative pain , but additional trials have since been published .
This review sought to evaluate the efficacy and safety of paracetamol using current data , and to compare the findings with other analgesics evaluated in the same way .
OBJECTIVES To assess the efficacy of single dose oral paracetamol for the treatment of acute postoperative pain . | The purpose of the present investigation was to compare the analgesic efficacy of flurbiprofen , a nonsteroidal anti-inflammatory drug , which is a phenyl propionic acid derivative , with acetaminophen and placebo in 63 adult out patients with moderate to severe dental pain following periodontal surgery . After surgery was completed under local anesthesia , the patients received under double-blind conditions an envelope containing four tablets of either flurbiprofen 100 mg , acetaminophen 500 mg , or placebo and they were instructed to take one tablet every 6 hours when postoperative pain reached moderate to severe intensity . To determine analgesic efficacy and patients recorded pain intensity on a scale of 0 to 3 . Patients were allowed to remedicate after 1 hour if pain was not reduced . Flurbiprofen was shown to possess an adequate analgesic effect superior to either placebo ( P less than 0.005 ) or acetaminophen ( P less than 0.01 ) in the parameters studied . Our results seem to further support earlier data obtained with the drug in dental patients with postoperative pain after the surgical removal of impacted third molars ; therefore , it is concluded that flurbiprofen used as directed is a new alternative for the proper treatment of pain following periodontal surgery BACKGROUND The purpose of this r and omized double-blind study was to compare the efficacy and safety of propacetamol 2 g ( an i.v . acetaminophen 1 g formulation ) administered as a 2-min bolus injection ( n=50 ) or a 15-min infusion ( n=50 ) with oral acetaminophen 1 g ( n=50 ) or placebo ( n=25 ) for analgesia after third molar surgery in patients with moderate to severe pain after impacted third molar removal . METHODS All patients were evaluated for efficacy during the initial 6 h period after treatment administration ( T(0 ) ) and for safety during the entire week after T(0 ) . RESULTS The onset of analgesia after propacetamol was shorter ( 3 min for bolus administration , 5 min for 15-min infusion ) than after oral acetaminophen ( 11 min ) . Active treatments were significantly better for all parameters ( pain relief , pain intensity , patient 's global evaluation , duration of analgesia ) than placebo ( P<0.05 ) . Adverse events were more frequent after propacetamol , especially pain at the injection site . Propacetamol bolus result ed in a much higher incidence of local adverse events than the infusion ( propacetamol bolus 90 % vs propacetamol infusion 52 % ) with no clinical ly significant benefits in terms of analgesic efficacy . CONCLUSION I.V. propacetamol , administered as a 15-min infusion , is a fast-acting analgesic agent . It is more effective in terms of onset of analgesia than a similar dose of oral acetaminophen Abstract Variability in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size In a double‐blind , r and omized , single‐dose trial the analgesic contribution of acetaminophen , 1000 mg , and codeine , 60 mg , was determined . The study was a 2 × 2 factorial experiment in which 120 patients suffering from pain as a result of oral surgery rated their pain intensity and pain relief for up to 5 hours after a single dose of one of : 1000 mg acetaminophen , 60 mg codeine , 1000 mg acetaminophen plus 60 mg codeine , or placebo . The factorial analysis showed that both 1000 mg acetaminophen and 60 mg codeine made a statistically significant ( P < 0.05 ) contribution to the analgesic effectiveness of the combination on all measures of efficacy ( sum of pain intensity differences , largest pain intensity difference , total pain relief , largest pain relief , and time to remedication ) . The incidence of adverse effects did not appear to differ among the treatments , including placebo To determine the relative analgesic efficacy of ibuprofen 400 mg and acetaminophen 1000 mg , we conducted a single-dose , double-blind , placebo-controlled , r and omized clinical trial using a st and ard assay for analgesic agents , the dental pain model . At regular intervals over 6 hours , 184 patients who had undergone dental impaction surgery rated pain intensity and relief on categorical scales and pain half-gone on a dichotomous nominal scale ; a categorical overall evaluation was completed at the end of 6 hours . Both active agents were effective compared to placebo . Ibuprofen 400 mg was more effective than acetaminophen 1000 mg for Sum Pain Intensity Difference ( SPID ) , Total Pain Relief ( TOTPAR ) , sum pain half-gone , and overall evaluation ( P less than .05 to P less than .001 ) . The time-effect curves demonstrated a greater peak effect and longer duration of action for ibuprofen 400 mg compared to acetaminophen 1000 mg . Side effects were reported in five ibuprofen patients , 11 acetaminophen-treated patients , and seven placebo patients . Based on the results of this clinical study , we conclude that ibuprofen 400 mg is a safe and more effective analgesic than acetaminophen 1000 mg for patients with acute pain A double-blind , placebo-controlled trial was carried out in 299 patients suffering from post-episiotomy pain to compare the analgesic effectiveness and tolerance of single doses of 500 mg dipyrone and 500 mg paracetamol . Assessment s of pain relief over a 6-hour period showed that dipyrone produced significantly better results than placebo within half an hour of intake and maintained this superiority throughout the 6 hours . It also afforded consistently better pain relief than paracetamol and was significantly more effective at the 6-hour assessment . Side-effects were few and mild Lysine clonixinate ( LC ) , an effective and well tolerated non-morphinic analgesic whose mechanism of action is basically due to the inhibition of cyclo-oxygenase , was assessed with a double-blind r and omized dummy design versus paracetamol ( P ) on 200 patients suffering from pain after minor dental surgery . Patients received according to their needs 1 or 2 tablets of 125 mg lysine clonixinate or 500 mg paracetamol every 8 h during 48 h or until pain relief . Both groups , each composed of 100 patients , were comparable in terms of demographic conditions ( t test ) , initial symptoms ( chi-square test ) , characteristics of the extracted dental pieces , surgical complications and wound treatment ( chi-square test ) . Pain intensity scores and daily average intake of tablets ( 3.4/day ) documented in the patients ' diary revealed no statistically significant differences between the two treatments ( chi-square test ) . It was found that spontaneous pain measured using a visual analogue scale ( VAS ) decreased significantly in both treatment groups at the 24-h control examination . The following values were observed in the LC group : baseline 4.38 + /- 1.7 ; 24-h * 1.20 + /- 1.4 ; 48-h * 0.36 + /- 1.2 . In the P group the values were : baseline 4.28 + /- 1.6 ; 24-h * 1.11 + /- 1.4 ; 48-h * 0.30 + /- 0.7 ( * p < 0.05 ) . Other variables like facial swelling and night pain , evaluated on a score from 0 to 4 and symptom presence or absence respectively , showed a similar response . ( ABSTRACT TRUNCATED AT 250 WORDS Background : A r and omized , double‐blind , placebo‐controlled single oral dose study was done in order to examine whether codeine has an additive analgesic effect to that of paracetamol for moderate and strong postoperative pain after abdominal surgery . The maximum recommended single dose of paracetamol 1000 mg ( Paracet ® ) was compared with a combination of a submnximal dose of paracetamol 800 mg plus codeine 60 mg ( Paralgin forte ® ) and placebo for pain relief after Caesarean section in 125 patients 1 Dipyrone 1.0 g , paracetamol 1.0 g and placebo were compared in a double-blind parallel group study in patients with episiotomy pain . 2 Patients were stratified according to severity of initial pain ( severe or moderate ) and the three treatments were r and omized for each of these two groups . 3 Two-hundred and sixty-four patients entered the study : five patients were excluded from analysis ; 127 patients had ' severe ' pain , 132 ' moderate ' pain . 4 Both drugs were more effective than placebo , and dipyrone was significantly more effective than paracetamol , particularly where initial pain was severe . 5 The efficacy of dipyrone 1.0 g was compared with paracetamol 1.0 g in relieving pain after tooth extraction . 6 Ninety patients entered the study and 87 were analyzed without stratification according to initial pain severity . 7 Dipyrone was consistently and significantly more effective than paracetamol at every assessment & NA ; There is uncertainty over whether the patient group in which acute pain studies are conducted ( pain model ) has any influence on the estimate of analgesic efficacy . Data from four recently up date d systematic review s of aspirin 600/650 mg , paracetamol 600/650 mg , paracetamol 1000 mg and ibuprofen 400 mg were used to investigate the influence of pain model . Area under the pain relief versus time curve equivalent to at least 50 % maximum pain relief over 6 h was used as the outcome measure . Event rates with treatment and placebo , and relative benefit ( RB ) and number needed to treat ( NNT ) were used as outputs from the meta‐analyses . The event rate with placebo was systematic ally statistically lower for dental than postsurgical pain for all four treatments . Event rates with analgesics , RB and NNT were infrequently different between the pain models . Systematic difference in the estimate of analgesic efficacy between dental and postsurgical pain models remains unproven , and , on balance , no major difference is likely The efficacy of diclofenac sodium ( Voltarol ) with and without paracetamol in the control of post-surgical dental Summary Acetylsalicylic acid(ASA ) was compared with paracetamol(P ) in a double-blind crossover study , in which essentially the same operation was performed on two separate occasions in 32 healthy patients , who required surgical removal of bilateral “ identically ” impacted wisdom teeth . Sixteen patients were given the drugsboth before and after(b & a-group ) the operations ( 0.5 g on the pre-operative evening , followed by 0.5 g × 4 for 3 days ) ; the other 16 patients did not start treatment until 2 hoursafter(a-group ) the operations . A number of objective and subjective factors were assessed , including swelling , bleeding , pain and preference , and were used to make comparisons of the pre- , per- and post-operative courses . About 50 % greater post-operative swelling was associated withASA compared toP , either if medication was begun prior to surgery or if the drugs were given only after operation . In theb & a-group , interference with platelet function and prolonged pre-operative bleeding time were produced byASA ( 8.9 vs 6.5 min ) , but the per-operative blood loss was not significantly increased ( 7.8 vs 7.4 ml ) . In both groupsASA tended to increase post-operative bleeding and the formation of haematomas and ecchymoses . There was no noticeable difference betweenASA and P with respect to pain score , but the preference scores showed a tendency to favourP in both groups . It appears that in circumstances with acute tissue injuries , P should be preferred toASA , if post-traumatic swelling and bleeding are to be prevented or reduced In a double-blind study of patients suffering from pain after surgery , fenoprofen 200 mg and paracetamol 500 mg was compared with each drug given separately and with a placebo . There was a significant difference between the combination and the placebo , whereas , separately , the drugs were only marginally better than the placebo in relieving pain . There was a significant linear trend indicating a better clinical result as the number of active components in the regimen was increased In a clinical trial conducted on women suffering from postpartum pain , 600 mg of acetaminophen proved as effective an analgesic as similar doses of acetophenetidin or acetylsalicylic acid . A new statistical technique for analyzing analgesic response is described 1 In a double-blind crossover study , essentially the same operation was performed on two separate occasions in 24 healthy patients . 2 On one occasion they were given paracetamol ( Panadol ) 1 g four times daily for 2 d , then 0.5 g four times daily for the next 2 d ; on the other , they were given placebo tablets . 3 Several objective and subjective assessment s were recorded for a paired comparison of the postoperative courses . 4 Significantly less swelling was measured after the operation when paracetamol was given ; on day 3 it averaged 71 % of that with placebo . This reduction in postoperative swelling was greater than the reduction previously obtained with ibuprofen and oxyphenbutazone using the same clinical model . 5 With paracetamol , a tendency was noted towards reduced local inflammatory temperature increase and less postoperative bleeding . 6 The results of this clinical trial agree with recent findings in animals studies which show paracetamol to be anti-inflammatory . 7 The pain and preference scores were clearly in favour of paracetamol . Adequate pain relief with paracetamol may require doses as high as 1 g three to four times daily . 8 The results obtained in this model with bilateral oral surgery suggest that in situations in which there are tissue lesions caused by surgery or injury , paracetamol may be preferable to acetylsalicylic acid if swelling and bleeding are to be prevented or reduced A double blind trial to study the effects of analgetics was carried out in patients suffering from pain after third molar osteotomy . 204 patients were evaluated after r and om allocation to treatment with paracetamol 500 mg and paracetamol 500 mg plus codeine 30 mg . Statistical evaluation revealed a tendency for better analgesia using the combination of paracetamol and codeine . For further studies an exact stratification for sex and age is necessary . Sample sizes of 150 patients are necessary for each parameter Abstract A previously established relationship for deriving dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics has been tested using an independent data set . Individual patient information from 18 RCTs of parallel‐group design in acute postoperative pain ( after abdominal , gynaecological and oral surgery ) was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with > 50%maxTOTPAR for the different treatments . The relationship between the measures was investigated in 85 treatments with over 3400 patients . In 80 of 85 treatments ( 94 % ) agreement between calculated and actual number of patients with > 50%maxTOTPAR was within four patients per treatment and in 72 ( 85 % ) was within three ( average of 40 patients per treatment , range 21–58 patients ) . Summing the positive and negative differences between actual and calculated numbers of patients with > 50%maxTOTPAR gave an average difference of 0.30 patients per treatment arm . Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events , such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data in acute pain studies enables data published as means to be used for quantitative systematic review s which require data in dichotomous form We assessed the quality of assessment and reporting of adverse effects in r and omized , double-blind clinical trials of single-dose acetaminophen or ibuprofen compared with placebo in moderate to severe postoperative pain . Reports were identified by systematic search ing of a number of bibliographic data bases ( e.g. , MEDLINE ) . Information on adverse effect assessment , severity and reporting , patient withdrawals , and anesthetic used was extracted . Compliance with former guidelines for adverse effect reporting was noted . Fifty-two studies were included ; two made no mention of adverse effects . No method of assessment was given in 19 studies . Twenty trials failed to report the type of anesthetic used , eight made no mention of patient withdrawals , and nine did not state the severity of reported adverse effects . Only two studies described the method of assessment of adverse effect severity . When all adverse effect data were pooled , significantly more adverse effects were reported with active treatment than with placebo . For individual adverse effects , there was no difference between active ( acetaminophen 1000 mg or ibuprofen 400 mg ) and placebo ; the exception was significantly more somnolence/drowsiness with ibuprofen 400 mg . Ninety percent of trials reporting somnolence/drowsiness with ibuprofen 400 mg were in dental pain . All studies published after 1994 complied with former guidelines for adverse effect reporting . Different methods of assessing adverse effects produce different reported incidence : patient diaries yielded significantly more adverse effects than other forms of assessment . We recommend guidelines for reporting adverse effect information in clinical trials Two-hundred six out patients with postoperative pain after the surgical removal of impacted third molars were r and omly assigned on a double-blind basis to receive oral doses of ketorolac tromethamine 10 and 20 mg , ibuprofen 400 mg , acetaminophen 600 mg , a combination of acetaminophen 600 mg plus codeine 60 mg , or placebo . Using a self-rating record , subjects rated their pain and its relief hourly for 6 hours after medicating . All active medications were significantly superior to placebo . Analgesia was similar for ketorolac 10 and 20 mg and ibuprofen 400 mg ; however , these treatments were superior to acetaminophen alone and the acetaminophen-codeine combination . The analgesic effect of each active medication was significant by hour 1 and persisted for 5 - 6 hours . The data suggest a plateau in ketorolac 's analgesic efficacy at the 10-mg level . Repeat-dose data indicated that on the day of surgery ketorolac 10 and 20 mg and ibuprofen 400 mg were superior to acetaminophen 600 mg ; ketorolac 20 mg was also superior to acetaminophen-codeine . Differences among active medications were not significant when data for the entire postoperative period ( days 0 - 6 ) were evaluated . The frequency of adverse effects was similar for the active medications A double-blind evaluation of the clinical effectiveness of a single dose of naproxen , ibuprofen , and acetaminophen was performed on 98 patients who had undergone periodontal surgery . A statistically significant difference was found when the effect of these medications was compared with that of a placebo , but no statistically significant difference was found among these three drugs . No side effects result ed from the use of these medications The aims of this study were to test the hypotheses that the type of 3rd molar removal determines baseline pain and that baseline pain influences analgesic assay sensitivity . Three groups of patients were studied : ( i ) 100 patients that had one fully erupted maxillary 3rd molar extracted ; ( ii ) 95 patients that had one lower impacted 3rd molar surgically removed ; and ( iii ) 98 patients that had two ipsilateral impacted 3rd molars surgically removed . In a r and omized , double-blind fashion , the patients received ( every third hour , three times ) either : ( i ) paracetamol 1 g ; ( ii ) paracetamol 1 g plus codeine 60 mg ; or ( iii ) placebo . Baseline pain intensity ( 100 mm Visual Analogue Scale ) was significantly lower after extraction ( 8 mm ( 2 - 20 ) ) ( = median ( 25th -75th percentile ) than after surgical removal of one 3rd molar ( 35 mm ( 15 - 57 ) ) , which was significantly lower than pain intensity after surgical removal of two 3rd molars ( 49 mm ( 24 - 82 ) ) . Analgesic effects of the active test drugs were superior to placebo . Paracetamol with and without codeine could be distinguished in patients after surgical removal of one 3rd molar . In conclusion , baseline pain was related to the degree of surgical trauma , but large inter-individual variation in baseline pain intensity reduced the ability to distinguish between paracetamol with and without codeine This double‐blind , r and omized , parallel , placebo‐controlled study evaluated the analgesic effects of single oral doses of 30 mg nalbuphine , 650 mg acetaminophen , and the contribution of each to the efficacy of their combination in 128 hospitalized patients with postoperative pain . Subjective reports of patients evaluated each hour for 6 hours were used as indices of analgesic response . Both nalbuphine and acetaminophen were significantly superior to placebo for most measures of total and peak analgesia . The interaction contrast between nalbuphine and acetaminophen was not significant for any analgesic measurements , indicating an additive effect of the components . The combination was the most effective treatment , followed by nalbuphine , acetaminophen , and placebo . Effects of the combination were significantly different from those of acetaminophen at 4 , 5 , and 6 hours and from those of placebo at 1 to 6 hours . There was no significant difference in the frequency or intensity of side effects among the groups . The combination of nalbuphine and acetaminophen appears to be a therapeutically useful combination & NA ; Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events — such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data , at least in acute pain models , indicates that more meaningful overviews or meta‐ analysis may be possible . This study investigated the relationship between continuous and dichotomous analgesic measures in a set of individual patient data , and then used that relationship to derive dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics . Individual patient information from 13 RCTs of parallel‐group and crossover design in acute postoperative pain was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with greater than 50 % pain relief ( > 50%maxTOTPAR ) for the different treatments . The relationship between the measures was investigated in 45 actual treatments and 10 000 treatments simulated using the underlying actual distribution ; 1283 patients had 45 separate treatments . Mean % maxTOTPAR correlated with the proportion of patients with > 50%maxTOTPAR ( r2 = 0.90 ) . The relationship calculated from all the 45 treatments predicted to within three patients the number of patients with more than 50 % pain relief in 42 of 45 treatments , and 98.8 % of 10 000 simulated treatments . For seven effective treatments , actual numbers‐needed‐to‐treat ( NNT ) to achieve > 50%maxTOTPAR compared with placebo were very similar to those derived from calculated data Two hundred male and female patients underwent a variety of oral surgical procedures and were treated qfterwards in four test groups . They took a combination of orphenadrine ( 25 mg ) and acetaminophen ( 325 mg ) , either drug alone , or placebo . A double-blind study design was used . All patients had moderately severe baseline pain intensity ; post-treatment pain relief was recorded at 30 minutes , one , two , four and six hours . A back-up analgesic ( codeine-ASA ) was made available if needed . Pain intensity difference ( PID ) and sums of pain intensity difference ( SPID ) were calculated using established analgesic study techniques . Statistical analyses indicated better analgesic efficacy in both PID and SPID scores for the orphenadrine-acetaminophen combination over the three other treatments . This was evident at 30 minutes and continued through the sixth hour . Each active drug , in turn , was also significantly better throughout than placebo for pain relief . Sub-groups in each treatment regimen required additional pain relief prior to six hours , with significantly more placebo than orphenadrine-acetaminophen patients needing remedication . Side-effect incidence was very low and r and omly distributed among the four In a double‐blind , placebo‐controlled , single‐dose , parallel‐group study , oral doses ( 5 , 10 and 25 mg ) of the prostagl and in synthetase inhibitor bromfenac were compared with acetaminophen ( 1000 mg ) and placebo for postoperative orthopedic pain . Analgesic measurements were made by nurse observers by use of st and ard verbal rating and visual analog scales . For most pain intensity and pain relief measurements , 1000 mg acetaminophen was statistically superior to placebo , demonstrating assay sensitivity , and 10 and 25 mg doses of bromfenac were statistically better than both placebo and 5 mg bromfenac for ordinal and analog ratings of pain intensity and pain relief ; 25 mg bromfenac produced significantly longer time to remedication than acetaminophen . The 5 mg dose of bromfenac was statistically superior to placebo for some measures , including remedication time . There were no untoward adverse effects or alterations in vital signs . Overall , 10 mg bromfenac produced analgesia equivalent to that of 1000 mg acetaminophen in this pain context Although both acetaminophen and oxycodone are commonly used analgesics , they were not available as a combination until recently . Since oxycodone is not available as a single entity , there is no archival or even anectodal information on the efficacy and safety of this combination . The purpose of this study was to evaluate the relative efficacy of various doses of the combination that could be used in dental situations . The single-dose efficacy and safety of acetaminophen 500 mg . , oxycodone 5 mg . , acetaminophen 500 mg . + oxycodone 5 mg . , acetaminophen 1,000 mg . + oxycodone 5 mg . , acetaminophen 1,000 mg . + oxycodone 10 mg . , and placebo were compared in out patients who experienced moderate to severe pain after surgical removal of inpacted third molars . Analgesic data were analyzed by analysis of variance and Duncan 's multiple range test . All active treatments were superior to placebo , with the high-ratio combination being the most efficacious . This treatment also had the highest incidence of limiting side effects . A positive dose-effect relationship was evident for both acetaminophen 500 mg . and 1,000 mg . and for oxycodone 5 mg . and 10 mg In a double blind study in Hong Kong Chinese , 250 mg of diflunisal , 500 mg of paracetamol or placebo were given for post-operative pain relief following 77 third molar surgical procedures . The intensity of pain was recorded on a visual analogue scale . The first and second doses of paracetamol reduced pain significantly more than placebo , while this was true only for the second dose of diflunisal . There was no significant difference in pain reduction with the first and second dose of paracetamol , when compared with the first and the second dose of diflunisal . In this study in Hong Kong Chinese , neither the dose nor the interval between ingestion of the analgesic tablets in patients , who needed analgesics for postoperative pain , were significantly different to that reported before in non-Chinese , in contrast to the popular belief that Chinese patients have higher pain thresholds . However , a higher proportion of Chinese than that reported in non-Chinese did not need any analgesics for relief of postoperative pain Objective To compare the efficacy of soluble aspirin 900 mg and paracetamol 1,000 mg in patients with postoperative pain after third molar surgery . Design A r and omised , placebo controlled , double-blind study . Setting Day stay units of Oral and Maxillofacial Surgery at Cardiff Dental Hospital and Hexham General Hospital , Northumberl and .Subjects and methods One hundred and sixty-seven ( 104 female ) patients who required the removal of their impacted third molars under general anaesthesia . Intervention In the early postoperative period , patients were medicated with either a single dose of soluble aspirin 900 mg , solid paracetamol 1,000 mg or placebo . Main outcome measures Pain intensity was measured on 100 mm visual analogue scales at 0 , 5 , 10 , 15 , 20 , 30 , 45 , 60 , 90 , 120 and 240 minutes after dosing . Other efficacy variables evaluated included time to rescue medication and an overall assessment of the study medication efficacy by the patient on completion of the study . Results One hundred and sixty-seven patients consented to take part in the study , but only 153 were medicated . Of the 14 patients not treated , 10 failed to develop sufficient pain to enter the study , two withdrew consent , one had an adverse reaction to the general anaesthetic and one was a protocol violator . Over the four hour investigation period , patients treated with soluble aspirin reported significantly less pain when compared with those treated with paracetamol ( mean difference in AUC0 - 240 = -2001 , 95 % CI −3893 to −109 , p=0.038 ) and placebo ( mean difference in AUC0 - 240 = -3470 , 95 % CI −5719 to −1221 , p=0.003 ) . Similarly , at 20 and 30 minutes after dosing , patients in the soluble aspirin group were reporting significantly less pain than those in the paracetamol treatment group ( mean difference in pain intensity : at 20 minutes −7.9 , 95 % CI −15.3 to −0.6 , p=0.035 ; at 30 minutes −10.6 , 95 % CI −18.6 to −2.6 , p=0.010 ) . There were no significant differences between treatment groups with respect to the number of patients requiring rescue medication , however the time to dosing was significantly longer for those taking soluble aspirin when compared with placebo ( hazard ratio 2.34 , 95 % CI 1.41 to 3.88 , p<0.001 ) . Conclusion The findings from this study showed that soluble aspirin 900 mg provides significant and more rapid analgesia than paracetamol 1,000 mg in the early postoperative period after third molar surgery In this factorial study , 148 out patients with pain after oral surgery were r and omly assigned , on a double-blind basis , a single oral dose of acetaminophen 650 mg , phenyltoloxamine 60 mg , a combination of acetaminophen 650 mg with phenyltoloxamine 60 mg , or placebo . Using a self-rating record , subjects rated their pain and its relief hourly for 6 hours after medication . Measures of total and peak analgesia were derived from these subjective reports . The acetaminophen effect was significant for every measure of total and peak analgesia . The phenyltoloxamine effect was not significant for any measure of analgesia . Although efficacy was lower for the acetaminophen-phenyltoloxamine combination than for acetaminophen alone , for every variable , the contrast for interaction was not statistically significant . The results of this study differ from those of previous studies in patients with headache and musculoskeletal pain . All adverse effects were transitory and consistent with the known pharmacologic profiles of the study medications or the backup analgesic A double-blind r and omised cross-over study to compare 2 regimes of paracetamol and diflunisal for postoperative pain relief following 3rd molar surgery was design ed . 35 patients received one of the regimes at one visit and the alternative at the other visit . Both drugs , namely a single dose of 500 mg of diflunisal given preoperatively or 2 doses of 1000 mg of paracetamol , given preoperatively and 4 h postoperatively , produced adequate pain relief , without the need for supplementary analgesics during the 10-h test period . The differences in the mean overall pain scores in the 2 regimes were not statistically significant In a double‐blind study with the use of subjective reports of patients as indices of analgesia , we compared the analgesic effect of oral nalbuphine and acetaminophen and determined the contribution of each to the efficacy of their combination . In this parallel 2 × 2 factorial study , 129 in patients after surgery were r and omly assigned to treatment with a single oral dose of nalbuphine hydrochloride ( 30 mg ) , acetaminophen ( 650 mg ) , the combination of nalbuphine ( 30 mg ) and acetaminophen ( 650 mg ) , or placebo . In the factorial analysis , both the nalbuphine and acetaminophen effects were significant for virtually every measure of total and peak analgesia , whereas the interaction contrast was not significant for any measure of analgesic effect . This indicates that the analgesic effect of the combination represents the additive effect of its constituents and is consistent with the results of studies of combinations of codeine and other opioids with aspirin or acetaminophen . There were few adverse effects other than sedation , which occurred twice as frequently in patients treated with nalbuphine as in those receiving acetaminophen or placebo . Our data suggest that this combination should prove at least as effective as any currently marketed narcotic‐containing combination . Since nalbuphine has less dependence liability than narcotics and exhibits a ceiling on respiratory depression , its combination with acetaminophen should also be safer than comparable narcotic combinations The analgesic efficacy of single 500- and 1,000-mg doses of diflunisal ( Dolobid ) , a new nonsteroidal anti-inflammatory analgesic , was compared in a double-blind study with that of acetaminophen , 600 mg , the combination of acetaminophen , 600 mg , with codeine phosphate , 60 mg , and placebo in 159 oral surgery out patients . Using a self-rating record , patients rated their pain and its relief hourly for 12 hours after medication . Both doses of diflunisal were significantly more effective than acetaminophen alone and produced peak analgesia comparable to that of the acetaminophen-codeine combination . Diflunisal proved to have an unusually long duration of analgesic action . Acetaminophen and the combination were significantly superior to placebo through hours 2 and 5 , respectively ; both doses of diflunisal were significantly superior through the end of the 12-hour observation period . None of the active treatments produced more side effects than the placebo Summary A double-blind r and omized trial was carried out in 90 male patients suffering from pain after meniscectomy . The patients received a single dose of paracetamol 1 000 mg plus codeine 60 mg , paracetamol 1 000 mg , codeine 60 mg , or placebo . The tablets were taken when needed after surgery and the postoperative pain was recorded on a visual analogue scale . Over a period of 4 h the efficacy of the drugs was calculated in terms of pain intensity , pain intensity difference and percentage pain reduction . The greatest effect was obtained in patients taking the paracetamol plus codeine combination . Statistical analysis was carried out by use both of parametric and non-parametric procedures . The results suggest that pain reduction is a valuable measurement of analgesic efficacy and that non-parametric assumptions are preferable in the statistical analysis of analgesic activity A double-blind , placebo-controlled , parallel-group study was performed to compare the analgesic activity of the combination of 650 mg acetaminophen plus 60 mg phenyltoloxamine citrate with that of 650 mg acetaminophen alone . Two hundred female in patients who had severe pain associated with a recent episiotomy procedure were r and omly assigned to receive a single dose of one of the two active treatments or a placebo . Analgesia was assessed over a 6-hour period . Treatments were compared on the basis of st and ard subjective scales for pain intensity and relief , a number of derived variables based on these data and two global measures . For essentially all measures , the two active treatments were significantly superior to the placebo control . The combination was significantly superior to acetaminophen alone for all analgesic measures including SPID , TOTAL , and global ratings . The results of this study demonstrate that 60 mg phenyltoloxamine produces significant augmentation of the analgesic activity of 650 mg acetaminophen in postepisiotomy pain A single-dose , double-blind , r and omized clinical trial was conducted to examine the relative analgesic efficacy of ibuprofen 400 mg ( n = 36 ) , acetaminophen 1000 mg ( n = 37 ) , and placebo ( n = 38 ) in postpartum patients who had moderate to severe pain after episiotomy . At regular intervals over 4 hours , patients evaluated pain severity and relief on categorical scales and completed a categorical overall evaluation at the end of the trial . Both active agents were effective compared with placebo ( P less than .05 ) . Ibuprofen 400 mg was more effective than acetaminophen 1000 mg for the sum of pain intensity difference , total pain relief , and reduction of pain by more than 50 % ( P less than .05 ) , suggesting a more rapid onset of action and a more prolonged effect by ibuprofen 400 mg . No adverse effects were reported . Based on the results of this conventional postpartum episiotomy pain model , both agents are considered efficacious and ibuprofen 400 mg is a more effective analgesic for the relief of acute pain than acetaminophen 1000 mg This r and omized , double-blind , placebo-controlled study compared the time to onset of analgesia and the analgesic efficacy of two formulations of acetaminophen 1000 mg -- an effervescent solution and tablet -- in 242 patients with moderate or severe pain following dental surgery . Onset of analgesia was determined using a two-stopwatch procedure . Analgesia was assessed over a 4-hour period . Treatments were compared using st and ard indexes of pain intensity and pain relief and summary measures . Both acetaminophen formulations were significantly more effective than their corresponding placebo for all efficacy assessment s. The median time to onset of analgesia was significantly shorter with effervescent acetaminophen ( 20 minutes ) compared to tablet acetaminophen ( 45 minutes ) . During the first 45 minutes after administration , effervescent acetaminophen was significantly more effective at each scheduled assessment time than tablet acetaminophen . The median time to meaningful pain relief was significantly shorter with effervescent acetaminophen ( 45 minutes ) compared to tablet acetaminophen ( 60 minutes ) . At 4 hours after administration , the pain relief was significantly better with tablet acetaminophen than with effervescent acetaminophen . No other significant differences were observed between the active treatments . In conclusion , effervescent acetaminophen produces a significantly faster onset of analgesia than tablet acetaminophen 1 . A placebo-controlled , double-blind , r and omized trial was carried out to evaluate the efficacy of single doses of racemic ketoprofen 12.5 and 25 mg and paracetamol 500 and 1000 mg in patients with post-operative pain after third molar surgery over a 6 h investigation period . 2 . Outcome variables included overall pain scores ( AUC(0,360 min ) , maximum pain relief , pain relief at 1 h after dosage and the number of patients taking escape analgesics . 3 . Overall pain scores ( AUC(0,360 min ) were significantly lower for all active treatments when compared to placebo ( P < 0.01 ) . 4 . Both ketoprofen treatments and patients treated with paracetamol 1000 mg reported significantly greater pain relief ( P < 0.01 ) and a later time to taking escape analgesics ( P < 0.01 ) than patients medicated with placebo . 5 . At 1 h after dosage , pain scores were significantly less ( P < 0.01 ) after both doses of ketoprofen when compared with placebo . 6 . Single doses of ketoprofen 12.5 and 25 mg , together with paracetamol 1000 mg are effective analgesics for treating post-operative pain after third molar surgery . These treatments provide up to 4 h of pain relief after this surgical procedure AIMS To evaluate the effect of a 3-day regimen of ibuprofen 600 mg x 4 on acute postoperative swelling and pain and other inflammatory events after third molar surgery compared with a traditional regimen of paracetamol 1000 mg x 4 . METHODS A controlled , r and omized , double-blind , cross-over study where 36 patients ( 26 females , 10 males ) with mean age 23 ( range 19 - 27 ) years acted as their own controls . All patients were subjected to surgical removal of bilateral third molars . After one operation the patients received tablets of ibuprofen 600 mg x 4 for 3 days . After the other operation they received an identical regimen of paracetamol 1000 mg tablets . Swelling was objective ly measured ( mm ) with a st and ardized face bow and the patients scored their pain intensity ( PI ) on a 100-mm visual analogue scale . RESULTS There was no statistically significant difference between paracetamol and ibuprofen treatment with respect to effect on acute postoperative swelling . Swelling after paracetamol on the third postoperative day was 1.8 % less than that after ibuprofen . Mean ( 95 % CI ) difference between treatments was -0.3 ( -4.7 , 4.1 ) mm . On the sixth postoperative day swelling after ibuprofen was 2.3 % less than that after paracetamol . Mean ( 95 % CI ) between treatments was 0.2 ( -2.4 , 2.8 ) mm . There was no statistically significant difference in pain intensity between the paracetamol and the ibuprofen regimen on the day of surgery . The mean ( 95 % CI ) difference between the treatments for summed pain intensity on the day of surgery ( SUMPI 3.5 - 11 ) was 3.31 ( -47.7 , 54.3 ) mm . Two patients developed fibrinolysis of the blood clot ( dry socket ) after receiving ibuprofen while none did this after paracetamol treatment . There was no noticeable difference between treatments with respect to appearance of haematomas/ecchymoses or adverse effects which all were classified as mild to moderate . CONCLUSIONS A 3-day regimen of ibuprofen 600 mg x 4 daily does not offer any clinical advantages compared with a traditional paracetamol regimen 1000 mg x 4 daily with respect to alleviation of acute postoperative swelling and pain after third molar surgery Acetaminophen ( APAP ) 1000 mg , APAP 2000 mg , the combination of APAP 1000 mg plus codeine phosphate 60 mg ( APAPCOD ) , and placebo ( PBO ) were compared in a 6-hour , r and omized , single-dose , double-blind , parallel-group analgesic trial . All active treatments were statistically superior ( p less than 0.05 ) to placebo for 4 hours after medication with respect to pain intensity ( PI ) and pain intensity difference ( PID ) , and up to 3 hours regarding pain relief ( PAR ) . The combination scored better than all other treatments on the summary analgesic efficacy measures sum PI ( SUMPI ) , sum PID ( SPID ) , and total PAR ( TOTPAR ) . The combination was statistically superior to APAP 1000 mg on SUMPI , TOTPAR and maximum PAR ( MAXPAR ) . Acetaminophen 2000 mg showed marginal numerical superiority over 1000 mg for SUMPI , but was not statistically superior for any summary efficacy measure . The 2000-mg dose was numerically inferior to APAPCOD for every summary efficacy measure and statistically inferior regarding SPID and MAXPAR . We concluded that codeine 60 mg added to acetaminophen 1000 mg offers analgesic advantages , and acetaminophen reaches an analgesic ceiling effect at 1000 mg using the dental pain model The purpose of this double-blind , r and omized , parallel , multiple-dose study was to compare the efficacy and safety of flurbiprofen with acetaminophen with codeine phosphate in the 96-hr postoperative period following foot surgery . Analysis of mean pain intensity and mean pain relief for the patients not requiring rescue medication did not reveal any significant differences between treatment groups . There were also no significant differences between treatment groups with respect to patient and investigator global evaluations of therapy . The incidence of termination of the study because of side effects was higher for the acetaminophen with codeine group A controlled , r and omized , double-blind crossover study , in which the patients acted as their own controls , was carried out to test the efficacy of naproxen 500 mg x 2 versus acetaminophen 1000 mg x 4 for 3 days on the postoperative course following third molar surgery . Acetaminophen reduced the mean swelling on the 3rd postoperative day by 22.4 % ( p = 0.023 ) compared to that after naproxen . On the 6th postoperative day , there was 20.9 % less mean swelling with naproxen ( p = 0.44 ) , although the total swelling measurements were much less than those measured on the 3rd postoperative day . Summed pain intensity ( SUMPI3.5 - 11 ) on the day of surgery revealed no statistically significant difference between the acetaminophen or naproxen regimen with the exception of 0.5 hours ( p = 0.002 ) and 1 hour ( p = 0.009 ) after first medication when acetaminophen gave less pain than naproxen . Since the drug regimens were different , summed PI for the first acetaminophen dose interval ( SUMPI3.5 - 6 ) and the first naproxen dose interval ( SUMPI3.5 - 9 ) was calculated . There was a tendency toward a statistically significant difference in favor of acetaminophen for SUMPI3.5 - 6 ( p = 0.055 ) but no statistically significant difference ( p = 0.41 ) between the treatments with respect to SUMPI3.5 - 9 . Naproxen was statistically superior ( p < or = 0.002 ) to acetaminophen at 08:00 , 12:00 , and 16:00 hours on the 1st postoperative day and at 08:00 hours on the 2nd postoperative day , when the pain intensity level was lower than that on the day of surgery . A 3-day acetaminophen regimen reduces acute postoperative swelling better than naproxen on the 3rd postoperative day after third molar surgery but not on the 6th postoperative day when the total swelling is less This single-dose , double-blind , parallel-group , single-site study compared ibuprofen lysine 400 mg with acetaminophen 1000 mg and placebo in 240 patients with moderate-to-severe postoperative dental pain . The relative onset of analgesic response , overall analgesic efficacy , duration of effect , and safety were assessed over a 6-hour postdose period . Analgesic efficacy was assessed by patient self-rating of pain intensity , pain relief , time to meaningful pain relief , need for additional analgesic medication , and patient global evaluation . Both ibuprofen lysine 400 mg and acetaminophen 1000 mg were significantly ( P < or = 0.05 ) more effective than placebo . Ibuprofen lysine had a significantly ( P < or = 0.05 ) faster onset of action with greater peak and overall analgesic effect than did effect than did acetaminophen . All treatments were generally well tolerated Two hundred ninety-eight patients with post-operative pain after the surgical removal of an impacted third molar were r and omly assigned , on a double-blind basis , to receive a single oral dose of piroxicam 20 mg , or piroxicam-beta-cyclodextrin equivalent to 20 mg piroxicam , or paracetamol 500 mg , or placebo . Using a semi-quantitative self-rating scale , patients rated their pain and its relief at 30-min intervals for the first 2 h , and then hourly for 4 h after treatment administration . All active medications were reported to be significantly superior to placebo . The three active drugs were comparable for the degree of analgesia up to the third hour , after which the effect of paracetamol decreased significantly as compared to piroxicam-beta-cyclodextrin and piroxicam . Piroxicam-beta-cyclodextrin and paracetamol were more rapid than piroxicam in inducing analgesia . The tolerability for the active drugs was comparable to that for placebo Our objective was to determine the value of caffeine in combination with acetaminophen in the relief of pain from uterine cramping , episiotomy , and third molar extraction . In the dental study , 173 patients received two or four tablets of 500 mg acetaminophen or the combination of 500 mg acetaminophen and 65 mg caffeine . In the three postpartum studies , 1345 patients received one , two , or three tablets of acetaminophen , the combination , or a placebo . The mean scores for the summary variable percent sum of the pain intensity differences ( % SPID ) were higher in all for the combination than for acetaminophen alone , and in two studies the null hypothesis of no differences was rejected . The relative potency estimates for % SPID were 1.9 , 1.8 , and 1.3 for the three studies in which bioassays could be performed and the pooled relative potency was 1.7 with a 95 % confidence interval of 1.1 to 3.1 . The results were essentially the same among pain models and among patient groups with similar habitual caffeine consumption . Onset of analgesia was also faster with the combination . We conclude that caffeine enhances the analgesic efficacy of acetaminophen In a double-blind , r and omized controlled trial among 500 post-partum patients experiencing moderate to severe pain , a single oral dose of an aspirin/caffeine combination ( 800 mg aspirin , 65 mg caffeine ) provided significantly more pain relief at 2 hours than did a higher dose of an acetaminophen/aspirin combination ( 648 mg acetaminophen , 648 mg aspirin ) and a higher dose of acetaminophen alone ( 1000 mg acetaminophen ) . At 3 and 4 hours , the acetaminophen/aspirin combination as well as the aspirin/caffeine combination were significantly superior to acetaminophen alone . At all times , all three drugs were significantly superior to placebo . There were no clinical ly significant adverse reactions . These results provide evidence of a potentiating effect of caffeine on aspirin 's analgesic potency A double-blind clinical study of analgesic drugs was conducted involving 47 healthy adults requiring removal of 90 bony impacted m and ibular third molars . The analgesic effect of paracetamol plus codeine ( P + C ) 350 + 20 mg was compared to that of acetylsalicylic acid ( ASA ) 500 mg and placebo . A st and ardized surgical procedure under local anesthesia was used . Insufficient analgesic effect was noted in 16 % of the ASA group and in 69 % of the placebo group but in none in the P+C group . On the first postoperative day , patients given P+C suffered less pain compared with those given ASA ( P less than 0.01 ) . No relationship could be demonstrated between the type of impaction and intensity of pain . Trismus , however , was found to be associated with difficulty of extirpation . Drowsiness and an increased sleeping tendency were the main side effects found in the P+C group . The incidence of secondary hemorrhage was high in the ASA group , compared with the P+C group a significance of 0.01 less than P less than 0.05 was found on various postoperative days . Registration of swelling revealed less postoperative edema in the P+C group than in the ASA group ( 0.01less thanPless than0.05 ) . The main conclusion from this study is that the analgesic effect of P+C orally administered after a specific oral surgical procedure is superior to ASA and placebo . P+C also appears to have a more marked antiphologistic effect than ASA PURPOSE The analgesic efficacy of 50 and 100 mg flurbiprofen was compared with acetaminophen 650 mg , acetaminophen 650 mg plus codeine 60 mg , and placebo . PATIENTS AND METHODS Subjects undergoing the surgical removal of impacted third molars were r and omly administered one of the five treatments after the onset of moderate to severe postoperative pain . Pain intensity , pain relief , and side effects were evaluated for 6 hours after drug administration . RESULTS Both doses of flurbiprofen result ed in significant analgesia in comparison with placebo , acetaminophen , and acetaminophen plus codeine as measured by pain intensity difference , pain relief , and global evaluation . The greatest incidence of side effects occurred in the group receiving acetaminophen plus codeine , and the fewest side effects were reported by subjects administered flurbiprofen . CONCLUSION The results of this study indicate that flurbiprofen is more effective and causes fewer effects than acetaminophen and codeine when used for post-operative dental pain , in ambulatory patients INTRODUCTION Acute postoperative pain is a common experience in oral surgery practice . Non-steroidal anti-inflammatory drugs ( NSAIDs ) are quite effective against mild to moderate pain and they are generally better suited in ambulatory out patients than narcotic analgesics . The analgesic activity of piroxicam , a well known NSAID has been documented in many pain states . Piroxicam can be administered once daily because of its long half-life , but its absorption in the gastrointestinal tract is slow as it is its onset of action . Piroxicam-beta-cyclodextrin ( PBCD ) is a new formulation of piroxicam which is the product of supermolecular encapsulation of piroxicam with the cyclic oligosaccharide beta-cyclodextrin . PBCD is absorbed much faster than st and ard piroxicam , and its action as an analgesic is consequently more rapid . The purpose of this study was to assess the efficacy and the rapidity of action of piroxicam-beta-cyclodextrin in comparison with st and ard piroxicam , paracetamol and placebo following surgical extraction of impacted third molars . MATERIAL S AND METHODS The study population was composed of 32 patients of both sexes and in good health . To be included into the study , patients must have had third molar removal result ing in acute post-surgical pain of at least moderate intensity . The patients were then r and omly assigned to one of four treatment groups . PBCD 20 mg tablets ; piroxicam 20 mg capsules ; paracetamol 500 mg tablets , or placebo . The study was conducted according to a double-blind , double-dummy design . Pain intensity and pain relief were recorded at 0.5 , 1 , 1.5 , 2 , 3 , 4 hours after a single dose of the study drugs , by means of a Keele-type rating scale . Rescue analgesics were not allowed before one and a half hour after taking the study drugs . A global evaluation of study drugs was expressed by patients at the end of the observation period . RESULTS Treatment groups were homogeneous for demographic characteristics of the patients and for pain intensity at the time of medication with study drugs . All patients who received placebo requested supplemental analgesics , while none of the patients treated with the active drugs needed rescue analgesics . PBCD and paracetamol were comparable for their analgesic effect , while the time lag before a significant reduction of pain intensity with piroxicam was longer . Piroxicam and PBCD were superior to paracetamol because they showed a substantial analgesic effect through the 4-hour study duration , while paracetamol did not induce a complete relief from pain . DISCUSSION One of the most commonly utilized model for the evaluation of analgesics is the third molar extraction pain . Our study clearly differentiated between active drugs and placebo . Furthermore , while PBCD and paracetamol showed a rapid effect , piroxicam was slow in inducing pain relief . The analgesic and anti-inflammatory activity of PBCD and piroxicam brought about the resolution of pain and inflammation consequent to the dental extraction . Paracetamol , a pure analgesic , was not equally active and pain persisted , even if at a low grade , throughout the observation period ; probably this was due to local inflammation and edema . The results of our study appear to confirm the pharmacokinetic data on PBCD , which showed that therapeutic blood levels are reached faster with PBCD than with the st and ard piroxicam formulation . This results should be confirmed in studies with an adequate number of patients & NA ; A data base of r and omised clinical trials ( RCTs ) in pain research published from 1950 to 1990 was created following an extensive literature search . By applying a refined MEDLINE search strategy from 1966 to 1990 and by h and ‐ search ing more than 1 000 000 pages of a total of 40 biomedical journals published during the period 1950–1990 , more than 8000 RCTs were identified . The RCTs were published in more than 800 journals and over 85 % appeared between 1976 and 1990 . If the trend of the last 15 years persists , a total of more than 15 000 RCTs will be published in pain relief by the year 2000 . A detailed description of methods to ensure efficient use of re sources during the identification , retrieval and management of the information in pain relief and other fields is given . Emphasis is made on the importance of refining MEDLINE search strategies , on the use of volunteers to h and ‐ search journals and on careful monitoring of each of the steps of the process . The potential uses of the data base to guide clinical and research decisions are discussed In a r and omized double‐blind study , 120 patients with moderate to strong pain after surgical removal of wisdom teeth were given the following in single oral doses : 100‐mg enteric‐coated diclofenac tablets ; 1 g acetaminophen ( INN , paracetamol ) ; 1 g acetaminophen plus 60 mg codeine ; 100‐mg enteric‐coated diclofenac tablets plus 1 g acetaminophen ; or 100‐mg enteric‐coated diclofenac tablets plus 1 g acetaminophen plus 60 mg codeine . Patients recorded pain intensity and pain relief for 8 hours . Upside assay sensitivity was confirmed because acetaminophen plus codeine was superior to acetaminophen . Diclofenac plus acetaminophen with and without codeine had superior analgesic effect compared with diclofenac , acetaminophen , or acetaminophen plus codeine . Addition of 60 mg codeine increased the degree of side effects . These results support the clinical practice of combining diclofenac with acetaminophen for acute pain . Of clinical importance are superior and prolonged analgesia and fewer side effects after enteric‐coated diclofenac tablets plus acetaminophen compared with acetaminophen plus codeine In a single-dose , parallel group , r and omized block treatment allocation study , the relative analgesic efficacy of flurbiprofen , a nonsteroidal antiinflammatory drug , was compared to acetaminophen 650 mg with codeine 60 mg , zomepirac sodium 100 mg , and placebo . A total of 226 post-surgical dental patients ( 146 females and 80 males ) participated in the study . Flurbiprofen in 50 mg and 100 mg dosages demonstrated effective analgesic activity with the 100 mg dosage being at least as effective as the acetaminophen/codeine combination . The results of this study support previous work on flurbiprofen AIMS To compare the efficacy and safety of diclofenac-K ( 12.5 mg ) vs paracetamol ( 500 mg ) and placebo given in a flexible dosage regimen to treat pain result ing from extraction of impacted third molar teeth . METHODS This was a 2-day , double-blind , double-dummy , r and omized , parallel-group , placebo-controlled study of diclofenac-K ( 12.5 mg ) tablets vs paracetamol ( 500 mg ) tablets and placebo in patients with moderate or severe pain within 8 hours of extraction of impacted third molars . RESULTS After the first 2-tablet dose , patients took on average 2.5 additional tablets of diclofenac-K or 2.4 tablets of paracetamol , almost all as 1-tablet doses . Most placebo patients discontinued by taking rescue medication ( ibuprofen 200 mg ) on the first day . Pain relief after the initial dose of diclofenac-K ( 2 x 12.5 mg ) was superior to placebo ( P < .01 for all efficacy outcomes ) and comparable to paracetamol ( 2 x 500 mg ) . About 30 % of patients in each active treatment group took rescue medication during the study , compared to 78 % on placebo . About 70 % in each active treatment group considered the overall pain relief to be " some , " " a lot , " or " complete " compared to only 15 % on placebo . The incidence of adverse events in each active treatment group was low and comparable between the treatments . CONCLUSION An initial double-dose of diclofenac-K ( 2 x 12.5 mg ) or paracetamol ( 2 x 500 mg ) adequately relieved the most intense postoperative pain , and the flexible multiple dose regimen ( 1 or 2 tablets ) maintained adequate pain relief thereafter . Most patients needed only 1-tablet doses following the initial 2-tablet dose Codeine , a relatively weak oral narcotic agent , is the most frequently prescribed oral opiate drug . It is also frequently utilized as a control drug in comparative analgesic efficacy studies . These studies are often single dose analysis of pain relief following surgery or childbirth . We conducted a single dose , post-operative analysis of 116 patients who were r and omly assigned to receive codeine 60 mg , acetaminophen 600 mg , the combination of codeine and acetaminophen at these doses , or a placebo . Only the combination agent was uniformly superior to placebo . Codeine 60 mg was not consistently superior to placebo in this post-operative single dose analysis . A review of the literature confirms the difficulty in unequivocally establishing the value of codeine as an analgesic , in acceptable oral doses , in the single dose setting . Previous reports , however , suggest that the multiple doses of codeine may afford adequate analgesia . Interpretation of single dose studies with extrapolation to repeated dosing in the practice setting is difficult This double-blind , r and omized , parallel-group study compared the analgesic efficacy and safety of single doses of (R)- ketoprofen 25 mg and 100 mg to that of acetaminophen 1,000 mg and placebo in 177 patients experiencing moderate to severe pain after surgical removal of their impacted third molars . Both (R)- ketoprofen 100 mg and acetaminophen 1,000 mg were significantly ( P < 0.05 ) more efficacious than placebo for all summary analgesic measures . Other than a more rapid analgesic onset ( 45 minutes versus 60 minutes ) for acetaminophen 1,000 mg , (R)- ketoprofen 100 mg and acetaminophen 1,000 mg were statistically equivalent to each other . The 25 mg dose of (R)- ketoprofen appeared to approach the analgesic threshold dose , being numerically but not statistically superior to placebo for all summary measures . There were no serious adverse events observed in this study , with the overall incidence of side effects being somewhat less in the (R)- ketoprofen groups than in the acetaminophen 1,000 mg group . (R)- Ketoprofen possesses analgesic activity and an acceptable side-effect profile in the oral surgery pain model The purpose of this paper was to evaluate the contribution of low dosages of codeine and caffeine when added to acetaminophen . Subjects were dental out patients undergoing oral surgery involving bone removal . This was a single-dose , parallel group , double-blind assay evaluting 99 subjects . The treatment groups were acetaminophen 1000 mg , acetaminophen 1000 mg + codeine 16 mg + caffeine 30 mg and placebo . The results demonstrated that both active treatments were superior to placebo . Overall , the combination was slightly better than acetaminophen alone . The advantage of the combination appeared more evident in the " severe " baseline pain group One-hundred twenty-eight out patients with postoperative pain after the surgical removal of impacted third molars were r and omly assigned , on a double-blind basis , to receive oral doses of ketorolac tromethamine 10 mg , aspirin 650 mg , a combination of acetaminophen 600 mg plus codeine 60 mg , or placebo . Using a self-rating record , subjects rated their pain and its relief hourly for 6 hours after medicating . All active medications were significantly superior to placebo . The acetaminophen-codeine combination was significantly superior to aspirin for peak analgesia . Ketorolac was significantly superior to aspirin for every measure of total and peak analgesia , and significantly superior to acetaminophen-codeine for measures of total effect . The analgesic effect of ketorolac was significant by hour 1 and persisted for 6 hours . Repeat-dose data also suggested that ketorolac 10 mg was superior to aspirin 650 mg and acetaminophen-codeine on the day of surgery . Differences among the active medications were trivial for the postoperative days 1 - 6 analyses . The frequency of adverse effects was over 4 times greater for acetaminophen-codeine than for ketorolac or aspirin Abstract One way to ensure adequate sensitivity for analgesic trials is to test the intervention on patients who have established pain of moderate to severe intensity . The usual criterion is at least moderate pain on a categorical pain intensity scale . When visual analogue scales ( VAS ) are the only pain measure in trials we need to know what point on a VAS represents moderate pain , so that these trials can be included in meta‐ analysis when baseline pain of at least moderate intensity is an inclusion criterion . To investigate this we used individual patient data from 1080 patients from r and omised controlled trials of various analgesics . Baseline pain was measured using a 4‐point categorical pain intensity scale and a pain intensity VAS under identical conditions . The distribution of the VAS scores was examined for 736 patients reporting moderate pain and for 344 reporting severe pain . The VAS scores corresponding to moderate or severe pain were also examined by gender . Baseline VAS scores recorded by patients reporting moderate pain were significantly different from those of patients reporting severe pain . Of the patients reporting moderate pain 85 % scored over 30 mm on the corresponding VAS , with a mean score of 49 mm . For those reporting severe pain 85 % scored over 54 mm with a mean score of 75 mm . There was no difference between the corresponding VAS scores of men and women . Our results indicate that if a patient records a baseline VAS score in excess of 30 mm they would probably have recorded at least moderate pain on a 4‐point categorical scale To test the hypothesis that the postoperative abdominal pain of tubal occlusion is mediated by prostagl and ins , the effects of meclofenamate , a potent inhibitor of cyclooxygenase , on postoperative analgesia and incidence of abdominal pain were compared with those of acetaminophen , a weak inhibitor of prostagl and in activity . One hundred patients undergoing tubal occlusion under local anesthesia were studied . The patients were r and omly divided into four equal groups : control ; acetaminophen , 1300 mg ; meclofenamate , 100 mg ; meclofenamate , 200 mg . The fallopian tubes were occluded by electrocautery in 47 patients and by application of Falope rings in 53 patients . Both acetaminophen and meclofenamate provided substantial analgesia for 4 hours after the operation ( p less than 0.05 ) . Meclofenamate reduced the incidence of abdominal pain by one half ( p less than 0.02 ) , but acetaminophen did not . These results suggest that a portion of pain relief achieved by meclofenamate may be due to suppression of myosalpingian and /or myometrial contractions , a process mediated by prostagl and ins BACKGROUND Ibuprofen liquigel is a solubilized potassium ibuprofen 200-mg gelatin capsule formulation that was approved for over-the-counter use in 1995 . OBJECTIVE This study compared the analgesic efficacy and tolerability of ibuprofen liquigel 200 mg , ibuprofen liquigel 400 mg , acetaminophen caplets 1000 mg , and placebo in patients experiencing moderate or severe pain after surgical removal of impacted third molars . METHODS This r and omized , double-blind , parallel-group , 6-hour study was conducted in 210 patients experiencing moderate or severe postoperative pain . Ratings of pain intensity and pain relief were recorded every 15 minutes for the first hour , at 90 and 120 minutes , and then hourly through hour 6 . The onsets of first perceptible relief and meaningful relief were recorded using 2 stopwatches . An analysis of variance model was employed to test for significant differences ( P < or = 0.05 ) between treatment groups with respect to pain relief , pain intensity difference , total pain relief ( TOTPAR ) , and summed pain intensity difference ( SPID ) . Stopwatch measures were analyzed using the Cox proportional hazards model . Drug tolerability was assessed by monitoring the occurrence of adverse events . RESULTS During the first 2 hours of the study ( TOTPAR 2 and SPID 2 ) , all active treatments were significantly more efficacious than placebo ( P < 0.001 ) , with ibuprofen liquigel 200 and 400 mg significantly more efficacious than acetaminophen 1000 mg ( P < 0.05 and P < 0.01 , respectively ) . For the entire duration of the study ( TOTPAR 6 and SPID 6 ) , only the 2 doses of ibuprofen liquigel were significantly more efficacious than placebo ( P < 0.001 ) . Ibuprofen liquigel 200 and 400 mg were also significantly more efficacious than acetaminophen 1000 mg on the summary measures TOTPAR 6 and SPID 6 ( P < 0.01 and P < 0.001 , respectively ) . Analysis of the stopwatch data revealed that all active treatments displayed significantly more rapid onsets to confirmed first perceptible relief ( P < 0.001 to < 0.05 ) and meaningful relief ( P < 0.001 to < 0.01 ) than did placebo , with ibuprofen liquigel 400 mg displaying a significantly more rapid onset to meaningful relief than acetaminophen 1000 mg ( P < 0.05 ) and a significantly more rapid onset to confirmed first perceptible relief than acetaminophen 1000 mg ( P < 0.001 ) and ibuprofen liquigel 200 mg ( P < 0.01 ) . All adverse events were considered mild or moderate , with an overall incidence of 11.5 % in the ibuprofen liquigel 200-mg group , 6.8 % in the ibuprofen liquigel 400-mg group , 19.0 % in the acetaminophen 1000-mg group , and 25.9 % in the placebo group . CONCLUSIONS Ibuprofen liquigel provided greater peak and overall analgesic effects and a more rapid onset to analgesia than did acetaminophen 1000 mg In a r and omized , double-blind , multiple-dose , parallel study of 107 patients , the safety and analgesic efficacy of single and multiple doses of orally administered ketorolac tromethamine ( 10–40 mg/day ) were compared with orally administered paracetamol ( 1000–4000 mg/day)/codeine ( 60–240 mg/day ) for treating moderate to severe pain after gynaecological surgery . Both drugs effectively reduced pain intensity . After the first dose of medication , over 90 % of the patients in each treatment group reported pain reduction of at least 50 % . The mean time until additional medication was requested was over 6 h for both groups . No statistically significant differences in analgesic efficacy were observed in the two treatment groups . Ketorolac tromethamine-treated patients reported a total of 62 adverse events ( 17 considered drug-related ) and the paracetamol/codeine-treated patients reported 65 ( 20 considered drug-related ) ; the adverse event profiles of the two treatment regimens were similar . Thus , both the single and the multiple doses of ketorolac tromethamine ( 10 mg ) alleviated moderate to severe pain after gynaecological surgery as safely and efficaciously as paracetamol ( 1000 mg)/codeine ( 60 mg ) Summary A new sequential test has been used to compare the effect of paracetamol and placebo on uterine cramping . Paracetamol was significantly superior to placebo at the 5 % level . 75 patients were included in the trial , whereas in a fixed sample study 90 patients would have been required to obtain the same significance level and power . The magnitude of the difference in treatment effect was estimated following the sequential test . In addition to the effect on uterine pain , which was the primary variable , the effect on episiotomy pain was also estimated . Paracetamol was also superior to placebo against the episiotomy pain This prospect i ve study compared the effectiveness of nine medications and a placebo in controlling pain following obturation . A total of 588 patients who required root canal obturation were included . After obturation of root canals , each patient took one of the medications , salicylic acid ( 2 x 250 mg ) , acetaminophen ( 2 x 250 mg ) , ibuprofen ( 2 x 250 mg ) , ketoprofen ( 2 x 250 mg ) , acetaminophen ( 2 x 250 mg ) plus codeine ( 2 x 250 mg ) , penicillin ( 2 x 250 mg ) , erythromycin base ( 2 x 250 mg ) , penicillin plus ibuprofen ( 2 x 250 mg ) , methylprednisolone ( 2 x 250 mg ) plus penicillin ( 2 x 250 mg ) , or a placebo , every 6 h for 72 h. All medications were encapsulated in identical capsules . The patients registered their degree of discomfort on a visual analogue scale of 0 to 9 . Statistical analysis of the data showed that the incidence of postoperative pain after obturation is lower than that following complete cleaning and shaping ( 5.83 % versus 21.76 % ) . In addition , there was no significant difference between the effectiveness of the various medications and placebo tablets in controlling postoperative pain following obturation Eighty-eight out patients with postoperative pain after the surgical removal of impacted third molars were r and omly assigned , on a double-blind basis , to receive a single , oral dose of flurbiprofen 100 mg , acetaminophen 600 mg , a combination of acetaminophen 600 mg with codeine 60 mg , or placebo . Using a self-rating record , subjects rated their pain and its relief hourly for 12 hours after medicating . Estimates of sum of pain intensity differences , peak pain intensity differences , total relief , peak relief , and hours of 50 % relief were derived from these subjective reports . Flurbiprofen and the acetaminophen-codeine combination were significantly superior to placebo for every measure of total and peak analgesia and significantly superior to acetaminophen alone for most measures of efficacy . Based on the 12-hour data , acetaminophen alone did not differ significantly from placebo ; however , it was superior to placebo for measures of total effect based on the 4-hour data . Flurbiprofen was significantly superior to the acetaminophen codeine combination with respect to the number of hours until remedication . All medications had manifested an effect by hour 1 ; analgesia persisted for 12 hours for flurbiprofen , 6 hours for acetaminophen-codeine , and 3 hours for acetaminophen alone . The frequency of adverse effects was similar for the active medications The relative analgesic efficacy and safety of single oral doses of 50 and 100 mg of flurbiprofen ( Ansaid , Upjohn ) were compared with 100 mg of zomepirac sodium , 650 mg of acetaminophen plus 60 mg of codeine , 650 mg of acetaminophen alone , and placebo in a r and omized , double-blind , parallel-group study . A total of 182 patients entered the study with moderate pain from a third molar extraction and were evaluated for six hours . For many efficacy variables , all active treatments were significantly ( p less than or equal to 0.05 ) more effective than placebo . The two doses of flurbiprofen gave approximately similar results , suggesting a plateau effect above 50 mg . With the exception of relief at one hour , there were no significant differences between zomepirac and either dose of flurbiprofen . However , the mean response with zomepirac was greater than with either 50 or 100 mg of flurbiprofen during the first four hours and lower during the last two hours . The analgesic effects of acetaminophen alone were not significantly different from acetaminophen in combination with codeine . At the first hour , acetaminophen plus codeine led to significantly better pain relief than did 100 mg of flurbiprofen . After the first hour , flurbiprofen result ed in greater mean scores than acetaminophen alone or acetaminophen plus codeine , and these differences were significant at the fifth and sixth hours . Five patients had adverse reactions while receiving acetaminophen , acetaminophen plus codeine , or placebo . There were no adverse effects with flurbiprofen or zomepirac Pharmacological management of pain for acute and chronic conditions has been guided by a scientific underst and ing of peripheral and central acting mechanisms for the control of inflammation as well as pain . Oral surgery pain is a reliable model to reference the effectiveness of commonly used analgesics such as ibuprofen and acetaminophen . A total of 706 patients who were experiencing moderate to severe pain received a single dose of ibuprofen , acetaminophen , or placebo . After 6 hours , the degree of pain relief and tolerance was assessed . Ibuprofen has important implication s for postoperative pain in clinical practice The present r and omized double-blind study was performed to investigate the analgesic effects of single doses of suprofen ( alpha-methyl-4-(2-thienylcarbonyl)benzene acetic acid ; Suprol ) 200 mg , suprofen 400 mg paracetamol ( APAP , acetaminophen ) 650 mg , and combination suprofen 100 mg + APAP 650 mg versus placebo . The five treatment groups were homogeneous as to their demographic features and comprised 28 - -32 subjects each . Data for a total of 146 patients were evaluated . There were statistically significant differences between the therapeutic effect of the test preparations containing active substance on the one h and and placebo and the other h and . Of the active substances , the best results were obtained with the combination suprofen 100 mg + APAP 650 mg , followed by suprofen 400 mg and APAP 650 mg ; there were hardly any differences in the results obtained with the two latter substances . Suprofen 200 mg ranked third . Statistical significance was only seen for the parameter pain intensity ( SPID ) on comparison of suprofen 100 mg + APAP 650 mg versus suprofen 200 mg . Side effects , homogeneously distributed over the treatment groups , were observed in four cases In a r and omized , double-center , double-blind , parallel group study the analgesic effect of a single dose of paracetamol ( 1000 mg ) and acetyl salicylic acid ( 1000 mg ) was compared with placebo in patients with moderate to severe postoperative pain following the surgical removal of a wisdom tooth . The most important finding was the statistically significantly shorter period until the onset of the action of paracetamol as against acetyl salicylic acid Ketoprofen ( Orudis ) is a nonsteroidal anti‐inflammatory drug that is currently approved in the United States for the management of mild to moderate pain . The objective of this trial was to determine the effectiveness of orally administered ketoprofen in the management of severe postoperative pain . This r and omized , double‐blind parallel study compared the efficacy and safety of single doses of 100 mg or 50 mg ketoprofen , the combination of 650 mg acetaminophen plus 10 mg oxycodone hydrochloride , 650 mg acetaminophen , or placebo in 240 patients with severe postoperative pain after cesarean section . Analgesia for the first dose was assessed over an 8‐hour period . Multiple doses of 100 mg or 50 mg ketoprofen and the combination at half the dose ( 325 mg acetaminophen plus 5 mg oxycodone ) were also assessed for up to 7 days . The 100 and 50 mg doses of ketoprofen and the combination were statistically superior to acetaminophen and placebo for many analgesic measures . A dose response was observed between the two doses of ketoprofen , with the 100 mg dose providing significantly greater analgesia over the lower dose . Ketoprofen , 100 mg , was at least as effective as the combination and its effects lasted longer , with the exception of hour 1 when the combination was superior . Remedication time for the group receiving 100 mg ketoprofen was significantly longer than for the other treatment groups . Significantly more patients who took repeated doses of the combination ( 84 % ) than those who took either dose of ketoprofen ( 70 % ) had adverse effects . Ketoprofen at both dose levels was shown to be effective , long‐lasting , and well tolerated , and it should be considered as a viable option for the management of moderate to severe postoperative pain Ibuprofen is a peripherally acting nonsteroidal anti-inflammatory drug indicated fo ranalgesia , antipyresis , and various arthritic conditions . A solubilized 200 mg liquigel formulation of ibuprofen has been shown to have a more rapid rate of absorption compared with ibuprofen 200 mg tablets . Ibuprofen liquigels have a kinetic profile similar to ibuprofen suspension , with both a higher Cmax and an earlier tmax than any solid tablet . The objective of this single-dose , double-blind , triple-dummy , parallel-group study was to assess the time to onset of relief and overall analgesic efficacy of liquigel ibuprofen 400 mg , ketoprofen 25 mg compared with acetaminophen 1000 mg , and placebo in 239 patients with moderate or severe pain following third molar extraction s. Treatments were compared over 6 hours using st and ard scales for pain intensity and relief and stopwatch onset of meaningful relief . All active treatments provided meaningful relief significantly faster compared with placebo . Ibuprofen provided significantly faster relief compared with acetaminophen and ketoprofen . By the end of the study ( 6 h ) , onset of meaningful relief was achieved by 36 % , 99 % , 96 % , and 88 % of the patients in the placebo , ketoprofen , ibuprofen , and acetaminophen groups , respectively . The median times to onset of relief were > 6 hours for placebo , 25.5 minutes for ketoprofen , 24.2 minutes for ibuprofen , and 29.9 minutes for acetaminophen . In addition , both ibuprofen and ketoprofen showed statistical superiority over acetaminophen at earlier time points on the time-effect curves for pain relief and pain intensity difference . Consistent results were seen with respect to the 6-hour summary efficacy variables : the three active treatments were significantly better than placebo , and ibuprofen was significantly better than both acetaminophen and ketoprofen . Liquigel ibuprofen 400 mg was shown to provide faster relief and superior overall efficacy compared with ketoprofen 25 mg , acetaminophen 1000 mg , and placebo . No serious adverse effects were reported in this single-dose study |
12,206 | 26,852,297 | In addition , periodontal therapy also had benefits on long-term gastric H. pylori eradication .
AUTHORS ' CONCLUSIONS Overall , periodontal therapy could increase the efficiency of H. pylori eradication and the non-recurrence rate of gastricH. pylori . | BACKGROUND Helicobacter pylori is estimated to affect about half the world 's population and is considered as the main cause of chronic gastritis and peptic ulcer disease .
Eradication of H. pylori infection accelerates ulcer healing and prevents relapse , reducing incidence of H. pylori-related gastric diseases .
Numerous studies have provided evidence that the oral cavity could be a potential reservoir for H. pylori .
The presence of oralH. pylori might affect the efficiency of eradication therapy and act as a causal force for its recurrence .
Conversely , other investigators have indicated that the colonization and growth of H. pylori differs between the oral cavity and the stomach .
Considering the open debate on the topic , it 's necessary to clarify whether periodontal therapy is an effective adjunctive treatment for gastric H. pylori infection .
OBJECTIVES To assess the effects of periodontal therapy plus eradication therapy versus eradication therapy alone for gastric H. pylori infection .
The secondary objective is to compare the non-recurrence rate at long-term follow up in different treatment groups . | The sensitivity of H. Pylori to antibiotic treatment is well known . Politherapy ( omeprazole or pantoprazole or ranitidine , amoxicillin and /or azithromycin and /or clarithromycin , metronidazole and bismuth citrate ) notably changed the percentage of H. pylori eradication but rarely resolutive . Periodontal pockets treatment with topic metronidazole , calcium sulphate and potassium sulphate result ed active against bacteria included in periodontal pockets leading to a long-term H. pylori eradication ( two years follow-up ) Background and Aims Helicobacter pylori ( H. pylori ) is an important pathogen in gastritis , peptic ulcer and possibly gastric cancer , but several questions remain unanswered . Particularly how the organism is transmitted and what is the relationship between oral presence of H. pylori and the gastric infection . Accordingly , we aim ed to characterize the H. pylori in oral cavity and to evaluate its relationship to gastric H. pylori infection . Material s and Methods Out of total 100 screened for H. pylori infection female subjects ( 40 to 85 y ) , 49 patients ( pts ) , who had positive 13C-urea breath test ( UBT ) and dyspeptic symptoms , agreed for 1 week regimen of triple anti-H. pylori therapy . The presence of H. pylori in oral cavity was assessed using bacterial culture from saliva and gingival pockets . Gastric H. pylori infection was estimated using capsulated 13C-urea breath test and plasma anti-H. pylori IgG and saliva IgA antibodies . In addition , plasma gastrin , ghrelin , and pepsinogen I were measured by radioimmunoassay . In selected patients , gastroscopy was additionally performed and gastric biopsy sample s were taken for H. pylori r and om amplification of polymorphic DNA genetic profiling . Results The triple therapy result ed in gastric H. pylori eradication in 79 % pts , along with significant decrease of plasma gastrin combined with an increase in plasma ghrelin and pepsinogen I ( PgI ) levels and a marked alleviation of dyspeptic symptoms . In contrast to gastric effects , the eradication therapy failed to cause any changes in the presence of H. pylori in oral cavity . Moreover no relationship was observed between the presence of H. pylori in oral cavity and the gastric H. pylori eradication . In line with these findings , no relationship between gastric and oral H. pylori was found using genetic profiling by r and om amplification of polymorphic DNA . Conclusions H. pylori was detected both in the oral cavity and the stomach but oral H. pylori had no relation to gastric H. pylori and remained unaffected by eradication of gastric H. pylori This study was design ed to compare differentprimer sets for PCR analysis of H. pylori in the sameseries of 40 dental plaque sample s. Three pairs ofprimers , HPU1/HPU2 , HP1/HP2 , and EHC-U/EHC-L , directed to the urease A gene , 16S rRNA gene , or 860-bpDNA of H. pylori , respectively , were used . Our results demonstrate that EHC-L/EHC-U were moRespecific and sensitive for H. pylori added to saliva or dental plaque than HPU1/HPU2 and HP1/HP2 . Thedetection rates for H. pylori DNA in dental plaque sample s from r and omly selected adult patients from theDental Clinic of the University of Ulm were 26.5 % ( 9/34 ) for HPU1/HPU2 , 78.9 % ( 30/38 ) for HP1/HP2 , and 100 % ( 40/40 ) for EHC-U/EHC-L ( P < 0.001 ) . Nested PCRusing primers directed to the 860-bp DNA of H. pylorifurThe r confirmed the presence of H. pylori DNA ( 40/40 ) in all these sample s. Our results indicate that primers EHC-U/EHC-L are to be recommendedfor PCR detection of H. pylori in the oralcavity BACKGROUND Two triple therapies with lansoprazole (LPZ)/amoxicillin (AMPC)/clarithromycin ( CAM ) for eradication of Helicobacter pylori were studied in multicenter , double-blind fashion to evaluate the eradication rate of H. pylori and safety of eradiation treatment in Japanese patients with H. pylori-positive active gastric ulcers or duodenal ulcers . METHODS Patients were r and omly chosen for the control treatment of LPZ 30 mg twice a day ( b.i.d . ; Group A-LPZ-only ) or the test treatments of LPZ 30 mg plus AMPC 750 mg and CAM 200 mg b.i.d . ( Group B-LAC200 ) and LPZ 30 mg , AMPC 750 mg and CAM 400 mg b.i.d . ( Group C-LAC400 ) . All eradication treatments lasted for a period of 7 days . Successful eradication was assessed by culture and gastric histology 1 month after completion of the ulcer treatment . RESULTS The eradication rates of H. pylori in the full analysis set were 0 % in Group A-LPZ-only , 87.5 % in Group B-LAC200 and 89.2 % in Group C-LAC400 for gastric ulcer and , 4.4 % in Group A-LPZ-only , 91.1 % in Group B-LAC200 and 83.7 % in Group C-LAC400 for duodenal ulcer . The eradication rates of Group B-LAC200 and Group C-LAC400 were 89.2 % ( 95 % CI : 84.8 - 93.7 % ) and 86.4 % ( 95%CI : 81.5 - 91.3 % ) in total in the full analysis set , 89 % ( 95 % CI : 84.3 - 93.7 % ) and 85.3 % ( 95%CI : 80.1 - 90.5 % ) in the per protocol set . The eradication rates in Groups B-LAC200 and group C-LAC400 were statistically significantly higher than the rate in Group A-LPZ-only for both gastric ulcer and duodenal ulcer patients ( p < .0001 for both ) . CONCLUSION A satisfactorily high H. pylori eradication rate was obtained in Japanese ulcer patients with the triple therapy regimen consisting of LPZ 30 mg , AMPC 750 mg , and CAM 200 mg b.i.d OBJECTIVE To determine whether antimicrobial therapy for Helicobacter pylori infection accelerates the healing of duodenal ulcers . DESIGN Single-blind , r and omized , controlled trial . SETTING Veterans Affairs hospital . PARTICIPANTS One hundred and five patients with endoscopically verified duodenal ulcers . INTERVENTION Patients received either ranitidine , 300 mg/d , or ranitidine , 300 mg/d , plus " triple therapy " ( 2 g/d of tetracycline , 750 mg/d of metronidazole , and 5 or 8 bismuth subsalicylate tablets per day ) . Triple therapy was administered for only the first 2 weeks of ulcer treatment . MEASUREMENTS Videoendoscopic assessment of ulcer status was done until ulcer healing was complete . Evaluations were done after 2 , 4 , 8 , 12 , and 16 weeks of therapy . MAIN RESULTS Ulcer healing was more rapid in patients receiving ranitidine plus triple therapy than in patients receiving ranitidine alone ( P less than 0.01 ) . The cumulative percentages of patients with healed ulcers in the group receiving ranitidine plus triple therapy and in the group receiving ranitidine alone were as follows : 37 % and 18 % after week 2 ; 74 % and 53 % after week 4 ; 84 % and 68 % after week 8 ; 96 % and 80 % after week 12 ; and 98 % and 84 % after week 16 . CONCLUSION Combined therapy with anti-H. pylori agents and ranitidine was superior to ranitidine alone for duodenal ulcer healing . Our results indicate that H. pylori plays a role in duodenal ulcer disease BACKGROUND The goal of this study was to see whether Helicobacter pylori ( H. pylori ) in the oral cavity might adversely affect the outcome of eradication therapy for gastric H. pylori . MATERIAL S AND METHODS Forty-seven patients ( 36 males , 11 females ) with gastric H. pylori infection were enrolled in this study . Gastric H. pylori infection was confirmed by both immunohistological staining with anti-H. pylori antibody and bacterial culture of biopsy specimens . The therapeutic regimen consisted of 30 mg/day lansoprazole , 750 mg/day metronidazole , and 400 mg/day clarithromycin administered for 2 weeks . A fragment of the H. pylori urease gene was amplified by nested PCR for DNA extracted from saliva and dental plaque from the same patients . We examined the correlation between the gastric eradication success rate and the prevalence of H. pylori in the oral cavity as determined by PCR before and after the eradication therapy . RESULTS The eradication success rate was significantly lower in the oral H. pylori-positive cases ( 12/23 , 52.1 % ) than in the negative cases ( 22/24 , 91.6 % ) at 4 weeks after the therapy ( p = . 0028 ) . Two years later , only 16 of the 23 ( 69.5 % ) oral H. pylori-positive cases were disease-free , as compared to 23 of the 24 ( 95.8 % ) oral H. pylori-negative cases ( p = .018 ) . CONCLUSIONS H. pylori in the oral cavity affected the outcome of eradication therapy and was associated with a recurrence of gastric infection . We recommend that oral H. pylori should be examined by nested PCR and , if positive , should be considered a causal factor in refractory or recurrent cases BACKGROUND Helicobacter pylori eradication from the oral cavity is more difficult than from the stomach . Thus , if the bacterium survives the antibacterial therapy in the oral cavity , it would be able to re-infect the stomach within a few weeks . Since oral health status could correspond to oral infection with H. pylori , the aim of the study was to determine whether oral health and oral hygiene practice s affect the efficacy of H. pylori eradication from the stomach . MATERIAL AND METHODS The study was performed in 137 patients with peptic ulcer who had undergone a 7-day course of eradication treatment with one of two sets of drugs : 1 , omeprazole , amoxicillin , and tinidazole or 2 , omeprazole , clarithromycin , and tinidazole . The efficacy of H. pylori eradication from the stomach was evaluated at the second gastroscopy 4 weeks after cessation of eradication therapy by means of two methods : rapid urease test and histology . The examination of natural dentition and prosthetic restorations as well as the assessment of hygienic procedures referring to natural dentition and dentures accompanied the second gastroscopy . RESULTS No association was found between the efficacy of H. pylori eradication from the stomach and the number of natural teeth , decayed teeth , use of dentures , debris index , or periodontal index . However , an association between eradication success and some oral hygiene procedures were noted . Unexpectedly , in patients treated with omeprazole , amoxicillin and tinidazole , the removal of dental prosthesis for the night and brushing the natural teeth twice a day or more reduced the efficacy of H. pylori eradication from the stomach . CONCLUSIONS Oral health and oral hygiene practice s seem unlikely to increase the efficacy of H. pylori eradication from the stomach |
12,207 | 23,626,806 | Pooled data also showed that CWT significantly reduced muscle strength loss at each follow-up time ( < 6 , 24 , 48 , 72 and 96 hours ) in comparison to passive recovery .
Despite comparing CWT to a large number of other recovery interventions , including cold water immersion , warm water immersion , compression , active recovery and stretching , there was little evidence for a superior treatment intervention .
The current evidence base shows that CWT is superior to using passive recovery or rest after exercise ; the magnitudes of these effects may be most relevant to an elite sporting population .
There seems to be little difference in recovery outcome between CWT and other popular recovery interventions | The aim of this systematic review was to examine the effect of Contrast Water Therapy ( CWT ) on recovery following exercise induced muscle damage . | Enhanced recovery following physical activity and exercise-induced muscle damage ( EIMD ) has become a priority for athletes . Consequently , a number of post-exercise recovery strategies are used , often without scientific evidence of their benefits . Within this framework , the purpose of this study was to test the efficacy of whole body cryotherapy ( WBC ) , far infrared ( FIR ) or passive ( PAS ) modalities in hastening muscular recovery within the 48 hours after a simulated trail running race . In 3 non-adjoining weeks , 9 well-trained runners performed 3 repetitions of a simulated trail run on a motorized treadmill , design ed to induce muscle damage . Immediately ( post ) , post 24 h , and post 48 h after exercise , all participants tested three different recovery modalities ( WBC , FIR , PAS ) in a r and om order over the three separate weeks . Markers of muscle damage ( maximal isometric muscle strength , plasma creatine kinase [ CK ] activity and perceived sensations [ i.e. pain , tiredness , well-being ] ) were recorded before , immediately after ( post ) , post 1 h , post 24 h , and post 48 h after exercise . In all testing sessions , the simulated 48 min trail run induced a similar , significant amount of muscle damage . Maximal muscle strength and perceived sensations were recovered after the first WBC session ( post 1 h ) , while recovery took 24 h with FIR , and was not attained through the PAS recovery modality . No differences in plasma CK activity were recorded between conditions . Three WBC sessions performed within the 48 hours after a damaging running exercise accelerate recovery from EIMD to a greater extent than FIR or PAS modalities The aim of this study was to investigate whether post-exercise vitamin C supplementation influences recovery from an unaccustomed bout of exercise . Sixteen male subjects were allocated to either a placebo ( P ; n=8 ) or vitamin C ( VC ) group ( n=8 ) . Subjects performed a prolonged ( 90-min ) intermittent shuttle-running test , and supplementation began after the cessation of exercise . Immediately after exercise the VC group consumed 200 mg of VC dissolved in a 500 ml drink , whereas the subjects in the P group consumed the drink alone . Later on the same day and then in the morning and evening of the following 2 days , subjects consumed additional identical drinks . Plasma VC concentrations in the VC group increased above those in the P group 1 h after exercise and remained above P values for the 3 days after exercise . Nevertheless , post-exercise VC supplementation was not associated with improved recovery . Post-exercise serum creatine kinase activities and myoglobin concentrations were unaffected by supplementation . Muscle soreness and the recovery of muscle function in the leg flexors and extensors were not different in VC and P groups . Furthermore , although plasma concentrations of interleukin-6 and malondialdehyde increased following exercise , there was no difference between VC and P groups . These results suggest that either free radicals are not involved in delaying the recovery process following a bout of unaccustomed exercise , or that the consumption of VC wholly after exercise is unable to deliver this antioxidant to the appropriate sites with sufficient expediency to improve recovery PURPOSE The authors investigated the efficacy of a single exposure to 14 min of cold-water immersion ( COLD ) and contrast water therapy ( CWT ) on posttraining recovery in Australian football ( AF ) . METHOD Fourteen AF players participated in 3 wk of st and ardized training . After week 1 training , all players completed a passive recovery ( PAS ) . During week 2 , COLD or CWT was r and omly assigned . Players undertook the opposing intervention in week 3 . Repeat-sprint ability ( 6 × 20 m ) , countermovement and squat jumps , perceived muscle soreness , and fatigue were measured pretraining and over 48 h posttraining . RESULTS Immediately posttraining , groups exhibited similar performance and psychometric declines . At 24 h , repeat-sprint time had deteriorated by 4.1 % for PAS and 1.0 % for CWT but was fully restored by COLD ( 0.0 % ) . At 24 and 48 h , both COLD and CWT attenuated changes in mean muscle soreness , with COLD ( 0.6 ± 0.6 and 0.0 ± 0.4 ) more effective than CWT ( 1.9 ± 0.7 and 1.0 ± 0.7 ) and PAS having minimal effect ( 5.5 ± 0.6 and 4.0 ± 0.5 ) . Similarly , after 24 and 48 h , COLD and CWT both effectively reduced changes in perceived fatigue , with COLD ( 0.6 ± 0.6 and 0.0 ± 0.6 ) being more successful than CWT ( 0.8 ± 0.6 and 0.7 ± 0.6 ) and PAS having the smallest effect ( 2.2 ± 0.8 and 2.4 ± 0.6 ) . CONCLUSIONS AF training can result in prolonged physical and psychometric deficits persisting for up to 48 h. For restoring physical-performance and psychometric measures , COLD was more effective than CWT , with PAS being the least effective . Based on these results the authors recommend that 14 min of COLD be used after AF training The objectives of the present investigation was to analyze the effect of two different recovery modalities on classical markers of exercise-induced muscle damage ( EIMD ) and inflammation obtained after a simulated trail running race . Endurance trained males ( n = 11 ) completed two experimental trials separated by 1 month in a r and omized crossover design ; one trial involved passive recovery ( PAS ) , the other a specific whole body cryotherapy ( WBC ) for 96 h post-exercise ( repeated each day ) . For each trial , subjects performed a 48 min running treadmill exercise followed by PAS or WBC . The Interleukin ( IL ) -1 ( IL-1 ) , IL-6 , IL-10 , tumor necrosis factor alpha ( TNF-α ) , protein C-reactive ( CRP ) and white blood cells count were measured at rest , immediately post-exercise , and at 24 , 48 , 72 , 96 h in post-exercise recovery . A significant time effect was observed to characterize an inflammatory state ( Pre vs. Post ) following the exercise bout in all conditions ( p<0.05 ) . Indeed , IL-1β ( Post 1 h ) and CRP ( Post 24 h ) levels decreased and IL-1ra ( Post 1 h ) increased following WBC when compared to PAS . In WBC condition ( p<0.05 ) , TNF-α , IL-10 and IL-6 remain unchanged compared to PAS condition . Overall , the results indicated that the WBC was effective in reducing the inflammatory process . These results may be explained by vasoconstriction at muscular level , and both the decrease in cytokines activity pro-inflammatory , and increase in cytokines anti-inflammatory The aim of this investigation was to eluci date the efficacy of repeated cold water immersions ( CWI ) in the recovery of exercise induced muscle damage . A r and omised group consisting of eighteen males , mean ± s age , height and body mass were 24 ± 5 years , 1.82 ± 0.06 m and 85.7 ± 16.6 kg respectively , completed a bout of 100 drop jumps . Following the bout of damaging exercise , participants were r and omly but equally assigned to either a 12 min CWI ( 15 ± 1 ° C ; n = 9 ) group who experienced immersions immediately post-exercise and every 24 h thereafter for the following 3 days , or a control group ( no treatment ; n = 9 ) . Maximal voluntary contraction ( MVC ) of the knee extensors , creatine kinase activity ( CK ) , muscle soreness ( DOMS ) , range of motion ( ROM ) and limb girth were measured pre-exercise and then for the following 96 h at 24 h increments . In addition MVC was also recorded immediately post-exercise . Significant time effects were seen for MVC , CK , DOMS and limb girth ( p < 0.05 ) indicating muscle damage was evident , however there was no group effect or interaction observed showing that CWI did not attenuate any of the dependent variables ( p > 0.05 ) . These results suggest that repeated CWI do not enhance recovery from a bout of damaging eccentric contractions . Key pointsCryotherapy , particularly cold water immersions are one of the most common interventions used in order to enhance recovery post-exercise . There is little empirical evidence demonstrating benefits from cold water immersions . Research evidence is equivocal , probably due to method ological inconsistencies . Our results show that the cryotherapy administered did not attenuate any markers of EIMD or enhance the recovery of function . We conclude that repeated cold water immersions are ineffective in the recovery from heavy plyometric exercise and suggest athletes and coaches should use caution before using this intervention as a recovery strategy OBJECTIVE Contrast therapy has a long history of use in sports medicine . Edema and ecchymosis reduction , vasodilation and vasoconstriction of blood vessels , blood flow changes , and influences on the inflammatory response are physiologic effects attributed to the ability of this modality to evoke tissue temperature fluctuations . Our purpose was to measure the change in human gastrocnemius intramuscular tissue temperature during a typical contrast therapy treatment . DESIGN AND SETTING A r and omized-group design was used to examine differences between 2 groups of subjects following a 31-minute warm whirlpool ( control ) and a 31-minute contrast therapy ( experimental ) treatment . A hydrotherapy room in a small- college sports medicine facility served as the test environment . SUBJECTS Twenty ( 7 females and 13 males ) healthy college students ( age = 20.9 + /- 1.2 years ; ht = 178.5 + /- 11.1 cm ; wt = 79.2 + /- 21.7 kg ) volunteered to participate in this study . Subjects were r and omly assigned to either a control or a treatment group . MEASUREMENTS Intramuscular tissue temperatures in the gastrocnemius were recorded every 30 seconds . RESULTS There was a significant difference in mean overall temperature change between the experimental group ( 0.85 degrees C + /- 0.60 degrees C ) and the control group ( 2.10 degrees C + /- 1.50 degrees C ) . In addition , there were significant differences between the 2 groups at 10 , 15 , 16 , 20 , 21 , 25 , 26 , 30 , and 31 minutes . At each recording point , the control group temperature change was significantly higher than that of the experimental group . There was no difference in absolute temperatures at the 11-minute recording point between the groups . CONCLUSIONS Contrast therapy did not lead to significant fluctuations in muscle tissue temperature at 4 cm below the skin 's surface . Therefore , it seems unlikely that the physiologic effects attributed to these fluctuations occur . A 1-minute exposure to a cold whirlpool during a typical contrast treatment does not appear to be long enough to significantly decrease tissue temperature after exposure to the warm hydrotherapy environment Kinugasa , T and Kilding , AE . A comparison of post-match recovery strategies in youth soccer players . J Strength Cond Res 23(5 ) : 1402 - 1407 , 2009-The aim of this study was to determine the effect of 3 post-match recovery modalities on physical performance , physiological measures , and players ' perceptions of recovery after 90-minute soccer match play . On separate days , 28 young ( age : 14.3 ± 0.7 years ) soccer players played 3 soccer matches each r and omly followed by 1 of 3 recovery modalities : ( a ) CONT-cold ( 12 ° C ) water immersion and hot ( 38 ° C ) shower , ( b ) COMB-cold water immersion and active recovery using a cycle ergometer , and ( c ) PASS-a passive post-match routine ( stretching and leg raise ) . Performance ( vertical jump height ) , physiological ( heart rate and tympanic temperature ) , and perceptual measures ( perceived quality of recovery ) were determined before each match , 10 minutes after each match , after each recovery method , and after 24 hours . There was a 0.6 ± 6.7 % drop in immediately after a match , but there was no difference in vertical jump height after 24 hours ( p = 0.997 ) . Perceived quality of recovery immediately after COMB was substantially higher than CONT and PASS , but the effect did not last more than 24 hours . The players perceived lighter legs after COMB , compared with the PASS , at post-24 hours . In conclusion , a combined recovery modality ( cold water immersion and active recovery ) after a soccer match did not have a substantial effect on vertical jump height performance when compared with contrast water immersion and passive recovery alone . However , the observed positive effects on perceived recovery ( higher quality of recovery and lighter legs ) after the combined modality ( cold water immersion and active recovery ) suggest that this approach may be effective for young players after intense soccer match play Cryotherapy is an effective treatment for acute sports injury to soft tissue , although the effect of cryotherapy on exercise-induced muscle damage is unclear . The aim of this study was to assess the effects of cold water immersion on the symptoms of exercise-induced muscle damage following strenuous eccentric exercise . After performing a bout of damage-inducing eccentric exercise ( eight sets of five maximal reciprocal contractions at 0.58 rad x s(-1 ) ) of the elbow flexors on an isokinetic dynamometer , 15 females aged 22.0+/-2.0 years ( mean + /- s ) were allocated to a control group ( no treatment , n = 7 ) or a cryotherapy group ( n = 8) . Subjects in the cryotherapy group immersed their exercised arm in cold water ( 15 degrees C ) for 15 min immediately after eccentric exercise and then every 12 h for 15 min for a total of seven sessions . Muscle tenderness , plasma creatine kinase activity , relaxed elbow angle , isometric strength and swelling ( upper arm circumference ) were measured immediately before and for 3 days after eccentric exercise . Analysis of variance revealed significant ( P < 0.05 ) main effects for time for all variables , with increases in muscle tenderness , creatine kinase activity and upper arm circumference , and decreases in isometric strength and relaxed elbow angle . There were significant interactions ( P<0.05 ) of group x time for relaxed elbow angle and creatine kinase activity . Relaxed elbow angle was greater and creatine kinase activity lower for the cryotherapy group than the controls on days 2 and 3 following the eccentric exercise . We conclude that although cold water immersion may reduce muscle stiffness and the amount of post-exercise damage after strenuous eccentric activity , there appears to be no effect on the perception of tenderness and strength loss , which is characteristic after this form of activity King , M and Duffield , R. The effects of recovery interventions on consecutive days of intermittent sprint exercise . J Strength Cond Res 23(6 ) : 1795 - 1802 , 2009-The purpose of this study was to compare four recovery interventions following simulated team sport , intermittent-sprint exercise on consecutive days . Ten female netball players performed four r and omized sessions of a simulated netball exercise circuit on consecutive days . Each condition consisted of two identical sessions ( Session 1 and 2 ) , with the recovery intervention implemented at the completion of Session 1 . Participants performed all interventions involving : passive recovery , active recovery ( ACT ) , cold water immersion ( CWI ) and contrast water therapy ( CTWT ) . No significant differences ( p > 0.05 ) were evident between conditions for exercise performance ( vertical jump , 20-m sprint , 10-m sprint , total circuit time ) during Session 2 . Effect size data indicated trends for an ameliorated decline in 5 × 20-m sprints and vertical jump for CTWT and CWI , respectively . CTWT demonstrated a significant reduction ( p = 0.04 ) in lactate post-intervention compared to ACT recovery . Further , ACT recovery result ed in a significantly elevated ( p < 0.01 ) heart rate compared to all other conditions postintervention and demonstrated significantly higher ( p < 0.01 ) rating of perceived exertion postintervention and muscle soreness pre-exercise Session 2 . It is likely that while interventions may be applicable to team sport practice s , the 24-hour recovery period between exercise bouts was sufficient to allow performance to be maintained , regardless of recovery interventions Eccentric activities are an important component of physical conditioning and everyday activities . Delayed onset muscle soreness ( DOMS ) can result from strenuous eccentric tasks and can be a limiting factor in motor performance for several days after exercise . An efficacious method of treatment for DOMS would enhance athletic performance and hasten the return to activities of daily living . The purpose of this study was to identify a treatment method which could assist in the recovery of DOMS . In the selection of treatment methods , emphasis was directed toward treatments that could be rendered independently by an individual , therefore making the treatment valuable to an athletic trainer in team setting . DOMS was induced in 70 untrained volunteers via 15 sets of 15 eccentric contractions of the forearm extensor muscles on a Lido isokinetic dynamometer . All subjects performed a pilot exercise bout for a minimum of 9 weeks before data collection to assure that DOMS would be produced . Data were collected on 15 dependent variables : active and passive wrist flexion and extension , forearm girth , limb volume , visual analogue pain scale , muscle soreness index , isometric strength , concentric and eccentric wrist total work , concentric and eccentric angle of peak torque . Data were collected on six occasions : pre- and post-induced DOMS , 20 minutes after treatment , and 24 , 48 , and 72 hours after treatment . Subjects were r and omly assigned to 1 of 7 groups ( 6 treatment and 1 control ) . Treatments included a nonsteroidal anti-inflammatory drug , high velocity concentric muscle contractions on an upper extremity ergometer , ice massage , 10-minute static stretching , topical Amica montana ointment , and sublingual A. montana pellets . A 7 x 6 ANOVA with repeated measures on time was performed on the delta values of each of the 15 dependent variables . Significant main effects ( p < .05 ) were found for all of the dependent variables on time only . There were no significant differences between treatments . Therefore , we conclude that none of the treatments were effective in abating the signs and symptoms of DOMS . In fact , the NSAID and A. montana treatments appeared to impede recovery of muscle function Objectives : To examine the effectiveness of four interventions on the rate and magnitude of muscle damage recovery , as measured by creatine kinase ( CK ) . Methods : 23 elite male rugby players were monitored transdermally before , immediately after , 36 hours after , and 84 hours after competitive rugby matches . Players were r and omly assigned to complete one of four post-match strategies : contrast water therapy ( CWT ) , compression garment ( GAR ) , low intensity active exercise ( ACT ) , and passive recovery ( PAS ) . Results : Significant increases in CK activity in transdermal exu date were observed as a result of the rugby match ( p<0.01 ) . The magnitude of recovery in the PAS intervention was significantly worse than in the ACT , CWT , and GAR interventions at the 36 and 84 hour time points ( p<0.05 ) . Conclusions : An enhanced rate and magnitude of recovery was observed in the ACT , CWT , and GAR treatment groups when compared with the PAS group . Low impact exercise immediately post-competition , wearing compression garments , or carrying out contrast water therapy enhanced CK clearance more than passive recovery in young male athletes It is generally accepted that our sense of limb position and movement is provided , in part , by signals from muscle spindles , while the sense of muscle force derives from signals in tendon organs . Experiments are described here , using human subjects , in which the effects of eccentric and concentric exercise of elbow flexor muscles are compared on the sense of forearm position and the sense of tension in elbow flexors . Subjects were required to compress a preloaded spring with one arm , carrying out a concentric contraction in elbow flexors , then flexors of the other arm released the spring from compression and thereby carried out an eccentric contraction . The force of the spring was adjusted to be 20 % maximum voluntary contraction ( MVC ) , and each subject carried out a minimum of 120 contractions . Position sense was measured in blindfolded subjects by placing one forearm at a set angle and asking subjects to match it by positioning the other arm . Over 4 days postexercise , subjects placed the eccentrically exercised arms in a more extended position than the concentrically exercised arm suggesting that they thought the muscle was shorter than it actually was . In a force-matching task , subjects systematic ally undershot the target 10 % MVC with their eccentrically exercised arm . Since it is known that eccentric exercise is associated with damage to muscle fibres , it is postulated that this leads to a disturbance of muscle receptors , the muscle spindles and tendon organs The purpose of this investigation was to , firstly , examine the effects of repeated applications of ice massage on the indirect markers associated with muscle damage using a within-subjects cross-over design and secondly , to examine how ice massage affects muscle function in both static and dynamic contractions following unaccustomed eccentric exercise . Twelve males performed damaging exercise on two separate occasions . The protocol consisted of three sets of 10 maximal eccentric repetitions of the elbow flexors using isokinetic dynamometry . Subjects were r and omly assigned to an ice massage group or placebo group and received treatments immediately post-exercise , 24 and 48 h post-exercise . Muscle function ( maximal isometric , slow and fast isokinetic contractions ) , creatine kinase , myoglobin , muscle soreness , limb girth and range of motion were measured pre , immediately post , 24 , 48 , 72 and 96 h post-exercise . Significant time effects were observed for all dependent variables ( P<0.05 ) . There were no significant differences between treatments . Ice massage is ineffective in reducing the indirect markers associated with exercise-induced muscle damage and enhancing recovery of muscle function in male exercisers unaccustomed to eccentric biased exercise The aim of this investigation was to eluci date the effects of cold water immersions ( CWIs ) following damaging exercise on the repeated bout effect ( RBE ) . Sixteen males performed two bouts of drop jump exercise separated by 14–21 days . Participants were equally , but r and omly assigned to either a CWI ( 12-min CWI at 15 ° C ) or control group ( 12-min seated rest ) . Treatments were given immediately after the first exercise bout , 24 , 48 and 72 h post-exercise . No interventions were given following the second bout . Maximum voluntary contraction ( MIVC ) , soreness ( DOMS ) , creatine kinase ( CK ) , thigh girth and range of motion ( ROM ) were recorded before and for 96 h following the initial and repeated bouts of damaging exercise . All variables , except ROM , showed a significant time effect ( P < 0.01 ) indicating the presence of muscle damage following the initial bout ; there were no differences between the CWI and control groups after the initial bout . Following the repeated bout of exercise there was a significant attenuation in the reduction of MIVC ( P = 0.002 ) and a reduction in DOMS ( P < 0.001 ) , which is indicative of the RBE . There were no significant differences between groups following the repeated bout of damaging exercise . These data show that CWI had no effect following damaging exercise and did not inhibit the RBE . Despite CWI being used routinely , its efficacy remains unclear and there is a need to eluci date the benefits of this intervention on recovery and adaptation to provide practitioners with evidence based practice Abstract Higgins , TR , Climstein , M , and Cameron , M. Evaluation of hydrotherapy , using passive tests and power tests , for recovery across a cyclic week of competitive rugby union . J Strength Cond Res 27(4 ) : 954–965 , 2013—In team sports , a cycle of training , competition , and recovery occurs weekly during the competitive season . In this research , we evaluated hydrotherapy for recovery from a simulated game of rugby union tracked over a week of training . Twenty-four experienced male rugby union players ( mean ± SD age 19.46 ± 0.82 years , weight 82.38 ± 11.12 kg , height 178.54 ± 5.75 cm ) were r and omly divided into 3 groups : cold water immersion ( n = 8) , contrast bath therapy ( n = 8) , and a control group ( n = 8) . The 2 forms of hydrotherapy were administered immediately after a simulated rugby game . Testing was conducted 1 hour before the game and at 5 intervals postgame : 1 , 48 , 72 , 96 , and 144 hours . Dependent variables included countermovement jump , 10- and 40-m sprints , sessional rating of perceived exertion ( RPE ) , flexibility , thigh circumference , and self-reported delayed onset muscle soreness ( DOMS ) . Significant differences in DOMS were found between the cold water immersion and contrast bath groups at 48 hours post intervention ( p = 0.02 ) , and between the control and contrast bath groups at 72 ( p = 0.03 ) and 96 ( p = 0.04 ) hours post intervention . Cold water immersion and contrast bath groups reported significantly different RPE at 72 hours ( p = ? ) and 96 hours post ( p = 0.05 ) intervention . Athletes ' perceptions of muscle soreness and sessional RPE scores for training were greater in the contrast bath group ( 20 % ) after the simulated game and throughout the training week . Although results from passive and power tests were inconclusive in determining whether cold water immersion or passive recovery was more effective in attenuating fatigue , results indicated contrast baths had little benefit in enhancing recovery during a cyclic week of rugby union Repeated bouts of eccentric muscle contractions were used to examine indirect indices of exercise-induced muscle damage and adaptation in human skeletal muscle . Twenty-four subjects ( 18 females , 6 males ) aged 20.0 + /- 1.4 years ( mean + /- S.D. ) performed an initial bout of either 10 ( n = 7 ) , 30 ( n = 9 ) or 50 ( n = 8) maximum voluntary eccentric contractions of the knee extensors , followed by a second bout of 50 contractions 3 weeks later using the same leg . Muscle soreness was elevated after all bouts ( P < 0.05 , Wilcoxon test ) , although the initial bout reduced the soreness associated with the second bout . Force loss and a decline in the 20:100 Hz percutaneous electrical myostimulation force ratio were observed after all exercise bouts ( P < 0.01 ) . Serum creatine kinase activity was elevated following the initial bouts of 30 and 50 repetitions ( P < 0.01 ) , but there was no increase following 10 repetitions . No increase in serum creatine kinase activity was observed in any group following the second bout of contractions ( P > 0.05 ) . We conclude that skeletal muscle adaptation can be brought about by a single bout of relatively few eccentric muscle contractions . Increasing the number of eccentric muscle repetitions did not result in an increased prophylactic effect on skeletal muscle The loss of the ability of skeletal muscle to generate force is one of the most appropriate and valid means to quantify muscle damage . Routine measurements of maximal muscle force , however , include many potential sources of error , the most important of which may be a possible lack of central drive to the muscles . The aim of the present study was to determine the reliability of maximal isometric quadriceps muscle force and voluntary activation over a timescale that is typically employed to examine the aetiology of exercise-induced muscle damage . We also attempted to characterise the reliability of several twitch interpolation variables including the size of the interpolated twitch and the state ( i.e. unpotentiated vs potentiated ) and size of the resting twitch . Over a 7-day period , eight healthy active males performed repeated maximal voluntary isometric contractions ( MVC ) of the quadriceps ( baseline and 2 h , 6 h , 24 h , 48 h , 72 h and 7 days post ) . Systematic variations in maximal muscle force , voluntary activation , interpolated twitch , unpotentiated twitch and potentiated twitch were not statistically significant ( P>0.05 ) and 95 % repeatability coefficients of ±76.03 N , ±4.42 % , ± 8.44 N , ±25.92 N and ±43.58 N were observed , respectively . These data indicate that young healthy well-familiarised male subjects can reproduce their perceived maximal efforts both within and between days where activation levels of > 90 % are routinely achieved . Providing activation remains within these limits in the 7 days following an acute bout of exercise , the research er would be 95 % certain that exercise-induced muscle damage is present in individual subjects ( taken from similar subject population s ) if MVC force falls outside these limits Contrast therapy , although having a long history of use in sports medicine and physical therapy , remains insufficiently research ed . We investigated the thermal effects of contrast therapy on intramuscular temperature . We r and omly assigned 28 college students to either a control or a contrast group , eight women and six men per group . We shaved and cleansed a 4- x 4-cm area of skin over the right medial calf and inserted a microprobe to a depth of 1 cm below the skin and subcutaneous fat in the center of the gastrocnemius . Each control subject immersed the treatment leg in a hot whirlpool ( 40.6 degrees C ) for 20 minutes . Each contrast subject first immersed the treatment leg in a hot whirlpool ( 40.6 degrees C ) for 4 minutes then into a cold whirlpool ( 15.6 degrees C ) for 1 minute . Contrast subjects repeated this sequence three additional times . We recorded intramuscular temperatures every 30 seconds over the entire treatment time for both groups . The control group had a temperature increase of 2.83 + /- 1.14 degrees C over the 20-minute treatment . The contrast group temperature increased 0.39 + /- 0.46 degrees C from baseline to the end of the treatment . The largest temperature change from the end of one contrast immersion to the end of the next was only 0.15 + /- 0.10 degrees C. None of the differences between the end of one immersion to the end of the next were significant . Conversely , all differences between the same time periods in the control group had significant temperature increases . Apparently contrast therapy , as studied , is incapable of producing any significant physiological effect on the intramuscular tissue temperature 1 cm below the skin and subcutaneous tissue . We recommend that further research be done to examine the effects of longer periods in both the hot and cold environments on the intramuscular temperature of the human leg . Further investigation of intra-articular or peri-articular temperature change produced by contrast therapy should also be undertaken PURPOSE To examine effects of local tissue cooling on contusion-induced microvascular hemodynamics and leukocytes behavior using real-time intravital microscopy . METHODS Male Wistar rats ( N = 21 , 130 - 150 g ) were r and omly assigned to intensive cooling group ( 3 degrees C , N = 7 ) , a moderate cooling group ( 27 degrees C , N = 7 ) , or control group ( 37 degrees C , N = 7 ) . Contusion was induced by dropping a plastic ball on exposed cremaster muscle . After 5 min , the cremaster muscle was superfused with a saline solution for 10 min at controlled temperature of either 3 degrees C ( cooling ) , 27 degrees C ( moderate cooling ) , or 37 degrees C ( control ) . Microvascular hemodynamics ( vessel internal diameter , blood flow rate and erythrocyte velocity ) and leukocyte behavior ( rolling and adhesion ) were measured from recorded videotapes in the same venules before and after contusion , and after cooling . RESULTS Cooling-induced vasoconstriction was marked at 3 degrees C and moderate at 27 degrees C compared with that at 37 degrees C. Blood flow rate and erythrocyte velocity were markedly lower at 3 degrees C compared to 37 degrees C. At 27 degrees C , erythrocyte velocity was higher than that at 37 degrees C , but blood flow rate was maintained at a level similar to that at 37 degrees C. The number of rolling and adhering leukocytes at 3 degrees C and 27 degrees C were significantly less than at 37 degrees C. CONCLUSION Our results suggest that local tissue cooling , similar to cryotherapy , improves edema and inflammatory reaction , and may be useful for reducing inflammatory response without inhibiting blood flow after contusion Burt , DG and Twist , C. The effects of exercise-induced muscle damage on cycling time-trial performance . J Strength Cond Res 25(8 ) : 2185 - 2192 , 2011—Previous research has advocated that plyometric training improves endurance performance . However , a consequence of such a training is the immediate and prolonged appearance of exercise-induced muscle damage ( EIMD ) . This study examined whether a single bout of plyometric exercise , design ed to elicit muscle damage , affected cycling endurance performance . Seventeen participants were r and omly assigned to either a muscle damage ( n = 7 men , 1 woman ) or nonmuscle damage ( n = 8 men , 1 woman ) group . Before and at 48 hours , participants were measured for perceived muscle soreness , peak isokinetic strength , and physiological , metabolic , and perceptual responses during 5-minute submaximal cycling at ventilatory threshold ( VT ) and a 15-minute time trial . Perceived muscle soreness and isokinetic strength ( p < 0.05 ) were significantly altered in the muscle damage group after EIMD . No changes in heart rate or blood lactate were evident during submaximal exercise ( p > 0.05 ) . However , & OV0312;o2 , & OV0312;E , and rating of perceived exertion ( RPE ) values were increased at VT in the muscle damage group at 48 hours after EIMD ( p < 0.05 ) . During the time trial , mean power output , distance covered , and & OV0312;o2 were lower in the muscle damage group at 48 hours after EIMD ( p < 0.05 ) . However , there was no change in RPE ( p > 0.05 ) , suggesting effort perception was unchanged during time-trial performance after EIMD . In conclusion , individuals using concurrent plyometric and endurance training programs to improve endurance performance should be aware of the acute impact of muscle-damaging exercise on subsequent cycling performance OBJECTIVE To examine arterial blood flow in the lower leg during warm- , cold- , and contrast-water therapy . DESIGN A crossover trial with repeated measurements on the dependent variable . SETTING Hydrotherapy area of a climate-controlled sports medicine clinic . PARTICIPANTS A volunteer sample of 24 healthy men . INTERVENTION Four r and omly assigned treatments were performed on each subject on consecutive days . MAIN OUTCOME MEASURE Arterial blood flow ( mL per 100mL/min ) from baseline measurements were recorded in a 3-minute to 1-minute on-off ratio for 20 minutes by using strain gauge plethysmography . RESULTS Contrast therapy produced fluctuations in blood flow throughout the 20-minute treatment . Warm-water therapy ( 40 degrees C ) result ed in significant ( P < .001 ) changes in blood flow compared with the control and contrast conditions . Cold-water therapy ( 13 degrees C ) did not produce significantly decreased blood flow as compared with the control condition . CONCLUSIONS We suggest that further studies involving contrast therapy to the lower leg in injured population s be carried out to determine whether our initial findings are clinical ly relevant PURPOSE The efficacy of a single exposure to 14 min of contrast water therapy ( CWT ) or cold-water immersion ( COLD ) on recovery postmatch in elite professional footballers was investigated . METHOD Twenty-four elite footballers participated in a match followed by 1 of 3 recovery interventions . Recovery was monitored for 48 h postmatch . Repeat-sprint ability ( 6 × 20-m ) , static and countermovement jump performance , perceived soreness , and fatigue were measured prematch and immediately , 24 h , and 48 h after the match . Soreness and fatigue were also measured 1 h postmatch . Postmatch , players were r and omly assigned to complete passive recovery ( PAS ; n = 8) , COLD ( n = 8) , or CWT ( n = 8) . RESULTS Immediately postmatch , all groups exhibited similar psychometric and performance decrements , which persisted for 48 h only in the PAS group . Repeat-sprinting performance remained slower at 24 and 48 h for PAS ( 3.9 % and 2.0 % ) and CWT ( 1.6 % and 0.9 % ) but was restored by COLD ( 0.2 % and 0.0 % ) . Soreness after 48 h was most effectively attenuated by COLD ( ES 0.59 ± 0.10 ) but remained elevated for CWT ( ES 2.39 ± 0.29 ) and PAS ( ES 4.01 ± 0.97 ) . Similarly , COLD more successfully reduced fatigue after 48 h ( ES 1.02 ± 0.72 ) than did CWT ( ES 1.22 ± 0.38 ) and PAS ( ES 1.91 ± 0.67 ) . Declines in static and countermovement jump were ameliorated best by COLD . CONCLUSIONS An elite professional football match results in prolonged physical and psychometric deficits for 48 h. COLD was more successful at restoring physical performance and psychometric measures than CWT , with PAS being the poorest Higgins , TR , Heazlewood , IT , and Climstein , M. A r and om control trial of contrast baths and ice baths for recovery during competition in U/20 rugby union . J Strength Cond Res 25(4 ) : 1046 - 1051 , 2011-Players in team sports must recover in a relatively short period of time to perform at optimal levels . To enhance recovery , cryotherapy is widely used . To date , there are limited scientific data to support the use of cryotherapy for recovery . Players ( n = 26 ) from a premier rugby club volunteered to participate in a r and om control trial ( RCT ) using contrast baths , ice baths , and no recovery . Statistical analysis , between group and within group , with repeated measures was conducted along with determination of effect sizes in 2 field tests . Pre and postfield tests including a 300-m test and a phosphate decrement test and subjective reports were conducted during the RCT . No significant difference was identified between base tests and retests in the phosphate decrement test or the 300-m tests . Effect size calculations identified a medium to large effect ( d = 0.72 ) for 300-m tests for contrast baths against control . Trivial effects were identified for ice baths ( d = 0.17 ) in the 300-m test against control . Effect size calculations in the phosphate decrement test showed a trivial effect ( d = 0.18 ) contrast baths and a negative effect ( d = −0.62 ) for ice baths . Treatment-treatment analysis identified a large effect for contrast baths ( d = 0.99 ) in the phosphate decrement test and a medium effect for contrast baths ( d = 0.53 ) in the 300-m test . Effect scores across contrast baths , ice baths , and passive recovery along with subjective reports indicate a trend toward contrast baths benefiting recovery in rugby . The continued use of 5-minute ice baths for recovery should be reconsidered based on this research because trends suggest a detrimental effect OBJECTIVE To determine if ice-water immersion after eccentric quadriceps exercise minimises the symptoms of delayed-onset muscle soreness ( DOMS ) . DESIGN A prospect i ve r and omised double-blind controlled trial was undertaken . 40 untrained volunteers performed an eccentric loading protocol with their non-dominant leg . INTERVENTIONS Participants were r and omised to three 1-min immersions in either ice water ( 5+/-1 degrees C ) or tepid water ( 24 degrees C ) . MAIN OUTCOME MEASURES Pain and tenderness ( visual analogue scale ) , swelling ( thigh circumference ) , function ( one-legged hop for distance ) , maximal isometric strength and serum creatine kinase ( CK ) recorded at baseline , 24 , 48 and 72 h after exercise . Changes in outcome measures over time were compared to determine the effect of group allocation using independent t tests or Mann-Whitney U tests . RESULTS No significant differences were observed between groups with regard to changes in most pain parameters , tenderness , isometric strength , swelling , hop-for-distance or serum CK over time . There was a significant difference in pain on sit-to-st and at 24 h , with the intervention group demonstrating a greater increase in pain than the control group ( median change 8.0 vs 2.0 mm , respectively , p = 0.009 ) . CONCLUSIONS The protocol of ice-water immersion used in this study was ineffectual in minimising markers of DOMS in untrained individuals . This study challenges the wide use of this intervention as a recovery strategy by athletes The purpose of this study was to compare the effectiveness of three different recovery modalities -- active ( ACT ) , passive ( PAS ) and contrast temperature water immersion (CTW)--on the performance of repeated treadmill running , lactate concentration and pH. Fourteen males performed two pairs of treadmill runs to exhaustion at 120 % and 90 % of peak running speed ( PRS ) over a 4-hour period . ACT , PAS or CTW was performed for 15-min after the first pair of treadmill runs . ACT consisted of running at 40 % PRS , PAS consisted of st and ing stationary and CTW consisted of alternating between 60-s cold ( 10 degrees C ) and 120-s hot ( 42 degrees C ) water immersion . Run times were converted to time to cover set distance using critical power . Type of recovery modality did not have a significant effect on change in time to cover 400 m ( Mean + /- SD ; ACT 2.7 + /- 3.6 s , PAS 2.9 + /- 4.2 s , CTW 4.2 + /- 6.9 s ) , 1000 m ( ACT 2.2 + /- 4.0 s , PAS 4.8 + /- 8.6 s , CTW 2.1 + /- 7.2 s ) or 5000 m ( ACT 1.4 + /- 29.0 s , PAS 16.7 + /- 58.5 s , CTW 11.7 + /- 33.0 s ) . Post exercise blood lactate concentration was lower in ACT and CTW compared with PAS . Participants reported an increased perception of recovery in the CTW compared with ACT and PAS . Blood pH was not significantly influenced by recovery modality . Data suggest both ACT and CTW reduce lactate accumulation after high intensity running , but high intensity treadmill running performance is returned to baseline 4-hours after the initial exercise bout regardless of the recovery strategy employed This study examined the effect of contrast water therapy ( CWT ) on the physiological and functional symptoms of delayed onset muscle soreness ( DOMS ) following DOMS-inducing leg press exercise . Thirteen recreational athletes performed 2 experimental trials separated by 6 weeks in a r and omized crossover design . On each occasion , subjects performed a DOMS-inducing leg press protocol consisting of 5 X 10 eccentric contractions ( 180 seconds recovery between sets ) at 140 % of 1 repetition maximum ( 1RM ) . This was followed by a 15-minute recovery period incorporating either CWT or no intervention , passive recovery ( PAS ) . Creatine kinase concentration ( CK ) , perceived pain , thigh volume , isometric squat strength , and weighted jump squat performance were measured prior to the eccentric exercise , immediately post recovery , and 24 , 48 , and 72 hours post recovery . Isometric force production was not reduced below baseline measures throughout the 72-hour data collection period following CWT ( ∼4–10 % ) . However , following PAS , isometric force production ( mean ± SD ) was 14.8 ± 11.4 % below baseline immediately post recovery ( p > 0.05 ) , 20.8 ± 15.6 % 24 hours post recovery ( p > 0.05 ) , and 22.5 ± 12.3 % 48 hours post recovery ( p > 0.05 ) . Peak power produced during the jump squat was significantly reduced ( p > 0.05 ) following both PAS ( 20.9 ± 13.4 % ) and CWT ( 12.8 ± 8.0 % ) , with the mean reduction in power for PAS being marginally ( not significantly ) greater than for CWT ( effect size = 0.76 ) . Thigh volume measured immediately following CWT was significantly less than PAS . No significant differences in the changes in CK were found ; in addition , there were no significant ( p > 0.01 ) differences in perceived pain between treatments . Contrast water therapy was associated with a smaller reduction , and faster restoration , of strength and power measured by isometric force and jump squat production following DOMS-inducing leg press exercise when compared to PAS . Therefore , CWT seems to be effective in reducing and improving the recovery of functional deficiencies that result from DOMS , as opposed to passive recovery This study compared the effects of hot/cold water immersion , static stretching , and no recovery ( control ) interventions on leg strength , rowing performance , and indicators of muscle soreness/damage in the 72 hours following strenuous stair-climb running . Club ( n = 14 ) and elite ( Sports Institute ) ( n = 6 ) rowers performed the training run on three separate occasions . After each run , participants completed a r and omly assigned 15-minute recovery treatment , either hot/cold , static stretching , or control , which were repeated at 24 and 48 hours postrun . No significant strength or performance differences existed between the three recovery treatments for either group . Muscle soreness for both groups remained significantly elevated ( p < 0.05 ) above baseline at 72 hours postrun . At 48-hours postrun serum creatine kinase levels had returned to baseline and at 72 hours postrun were below baseline in both groups . In conclusion , neither hot/cold nor static stretching accelerated recovery at 72 hours beyond that achieved by the control condition STUDY DESIGN A between groups design was used to compare recovery following eccentric muscle damage under 2 experimental conditions . OBJECTIVE To determine if a compression sleeve donned immediately after maximal eccentric exercise would enhance recovery of physical function and decrease symptoms of soreness . BACKGROUND Prior investigations using ice , intermittent compression , or exercise have not shown efficacy in relieving symptoms of delayed onset muscle soreness ( DOMS ) . To date , no study has shown the effect of continuous compression on DOMS , yet this would offer a low cost intervention for patients suffering with the symptoms of DOMS . METHODS AND MEASURES Twenty nonimpaired non-strength-trained women participated in the study . Subjects were matched for age , anthropometric data , and one repetition maximum concentric arm curl strength and then r and omly placed into a control group ( n = 10 ) or an experimental compression sleeve group ( n = 10 ) . Subjects were instructed to avoid pain-relieving modalities ( eg , analgesic medications , ice ) throughout the study . The experimental group wore a compressive sleeve garment for 5 days following eccentric exercise . Subjects performed 2 sets of 50 passive arm curls with the dominant arm on an isokinetic dynamometer with a maximal eccentric muscle action superimposed every fourth passive repetition . One repetition maximum elbow flexion , upper arm circumference , relaxed elbow angle , blood serum cortisol , creatine kinase , lactate dehydrogenase , and perception of soreness question naires were collected prior to the exercise bout and daily thereafter for 5 days . RESULTS Creatine kinase was significantly elevated from the baseline value in both groups , although the experimental compression test group showed decreased magnitude of creatine kinase elevation following the eccentric exercise . Compression sleeve use prevented loss of elbow motion , decreased perceived soreness , reduced swelling , and promoted recovery of force production . CONCLUSIONS Results from this study underline the importance of compression in soft tissue injury management BACKGROUND Many strategies are in use with the intention of preventing or minimising delayed onset muscle soreness and fatigue after exercise . Cold-water immersion , in water temperatures of less than 15 ° C , is currently one of the most popular interventional strategies used after exercise . OBJECTIVES To determine the effects of cold-water immersion in the management of muscle soreness after exercise . SEARCH METHODS In February 2010 , we search ed the Cochrane Bone , Joint and Muscle Trauma Group Specialised Register , the Cochrane Central Register of Controlled Trials ( The Cochrane Library ( 2010 , Issue 1 ) , MEDLINE , EMBASE , Cumulative Index to Nursing and Allied Health ( CINAHL ) , British Nursing Index and archive ( BNI ) , and the Physiotherapy Evidence Data base ( PEDro ) . We also search ed the reference lists of articles , h and search ed journals and conference proceedings and contacted experts . In November 2011 , we up date d the search es of CENTRAL ( 2011 , Issue 4 ) , MEDLINE ( up to November Week 3 2011 ) , EMBASE ( to 2011 Week 46 ) and CINAHL ( to 28 November 2011 ) to check for more recent publications . SELECTION CRITERIA R and omised and quasi-r and omised trials comparing the effect of using cold-water immersion after exercise with : passive intervention ( rest/no intervention ) , contrast immersion , warm-water immersion , active recovery , compression , or a different duration /dosage of cold-water immersion . Primary outcomes were pain ( muscle soreness ) or tenderness ( pain on palpation ) , and subjective recovery ( return to previous activities without signs or symptoms ) . DATA COLLECTION AND ANALYSIS Three authors independently evaluated study quality and extracted data . Some of the data were obtained following author correspondence or extracted from graphs in the trial reports . Where possible , data were pooled using the fixed-effect model . MAIN RESULTS Seventeen small trials were included , involving a total of 366 participants . Study quality was low . The temperature , duration and frequency of cold-water immersion varied between the different trials as did the exercises and setting s. The majority of studies failed to report active surveillance of pre-defined adverse events . Fourteen studies compared cold-water immersion with passive intervention . Pooled results for muscle soreness showed statistically significant effects in favour of cold-water immersion after exercise at 24 hour ( st and ardised mean difference ( SMD ) -0.55 , 95 % CI -0.84 to -0.27 ; 10 trials ) , 48 hour ( SMD -0.66 , 95 % CI -0.97 to -0.35 ; 8 trials ) , 72 hour ( SMD -0.93 ; 95 % CI -1.36 to -0.51 ; 4 trials ) and 96 hour ( SMD -0.58 ; 95 % CI -1.00 to -0.16 ; 5 trials ) follow-ups . These results were heterogeneous . Exploratory subgroup analyses showed that studies using cross-over design s or running based exercises showed significantly larger effects in favour of cold-water immersion . Pooled results from two studies found cold-water immersion groups had significantly lower ratings of fatigue ( MD -1.70 ; 95 % CI -2.49 to -0.90 ; 10 units scale , best to worst ) , and potentially improved ratings of physical recovery ( MD 0.97 ; 95 % CI -0.10 to 2.05 ; 10 units scale , worst to best ) immediately after the end of cold-water immersion . Five studies compared cold-water with contrast immersion . Pooled data for pain showed no evidence of differences between the two groups at four follow-up times ( immediately , 24 , 48 and 72 hours after treatment ) . Similar findings for pooled analyses at 24 , 48 and 72 hour follow-ups applied to the four studies comparing cold-water with warm-water immersion . Single trials only compared cold-water immersion with respectively active recovery , compression and a second dose of cold-water immersion at 24 hours . AUTHORS ' CONCLUSIONS There was some evidence that cold-water immersion reduces delayed onset muscle soreness after exercise compared with passive interventions involving rest or no intervention . There was insufficient evidence to conclude on other outcomes or for other comparisons . The majority of trials did not undertake active surveillance of pre-defined adverse events . High quality , well reported research in this area is required |
12,208 | 28,544,858 | Resistance training led to general improvements in muscular strength , running economy , muscle power factors , and direct performance in distances between 1,500 and 10,000 m. Such improvements were not accompanied by a significant increase in body mass or signs of overtraining .
However , improvements did not occur in all cases , suggesting that they might depend on the specific characteristics of the resistance training applied . | ABSTRACT The aim of this work was to identify , synthesize and evaluate the results of r and omized controlled trials examining the effects of resistance training on performance indicators in previously trained endurance runners . | To investigate the effects of simultaneous explosive-strength and endurance training on physical performance characteristics , 10 experimental ( E ) and 8 control ( C ) endurance athletes trained for 9 wk . The total training volume was kept the same in both groups , but 32 % of training in E and 3 % in C was replaced by explosive-type strength training . A 5-km time trial ( 5 K ) , running economy ( RE ) , maximal 20-m speed ( V20 m ) , and 5-jump ( 5J ) tests were measured on a track . Maximal anaerobic ( MART ) and aerobic treadmill running tests were used to determine maximal velocity in the MART ( VMART ) and maximal oxygen uptake ( VO2 max ) . The 5 K time , RE , and VMART improved ( P < 0.05 ) in E , but no changes were observed in C. V20 m and 5J increased in E ( P < 0.01 ) and decreased in C ( P < 0.05 ) . VO2 max increased in C ( P < 0.05 ) , but no changes were observed in E. In the pooled data , the changes in the 5 K velocity during 9 wk of training correlated ( P < 0.05 ) with the changes in RE [ O2 uptake ( r = -0.54 ) ] and VMART ( r = 0.55 ) . In conclusion , the present simultaneous explosive-strength and endurance training improved the 5 K time in well-trained endurance athletes without changes in their VO2 max . This improvement was due to improved neuromuscular characteristics that were transferred into improved VMART and running economy Fifteen highly trained distance runners ( & OV0312;O2max 71.1 ± 6.0 ml·min−1·kg−1 , mean ± SD ) were r and omly assigned to a plyometric training ( PLY ; n = 7 ) or control ( CON ; n = 8) group . In addition to their normal training , the PLY group undertook 3 × 30 minutes PLY sessions per week for 9 weeks . Running economy ( RE ) was assessed during 3 × 4 minute treadmill runs ( 14 , 16 , and 18 km·h−1 ) , followed by an incremental test to measure & OV0312;O2max . Muscle power characteristics were assessed on a portable , unidirectional ground reaction force plate . Compared with CON , PLY improved RE at 18 km·h−1 ( 4.1 % , p = 0.02 ) , but not at 14 or 16 km·h−1 . This was accompanied by trends for increased average power during a 5-jump plyometric test ( 15 % , p = 0.11 ) , a shorter time to reach maximal dynamic strength during a strength quality assessment test ( 14 % , p = 0.09 ) , and a lower & OV0312;O2-speed slope ( 14 % , p = 0.12 ) after 9 weeks of PLY . There were no significant differences in cardiorespiratory measures or & OV0312;O2max as a result of PLY . In a group of highly-trained distance runners , 9 weeks of PLY improved RE , with likely mechanisms residing in the muscle , or alternatively by improving running mechanics The purpose of this study was to determine if changes in triceps-surae tendon stiffness ( TST K ) could affect running economy ( RE ) in highly trained distance runners . The intent was to induce increased TST K in a subgroup of runners by an added isometric training program . If TST K is a primary determinant of RE , then the energy cost of running ( EC ) should decrease in the trained subjects . EC was measured via open-circuit spirometry in 12 highly trained male distance runners , and TST K was measured using ultrasonography and dynamometry . Runners were r and omly assigned to either a training or control group . The training group performed 4 × 20 s isometric contractions at 80 % of maximum voluntary plantarflexion moment three times per week for 8 weeks . All subjects ( mean $ $ \dot{V}{\text{O } } _ { 2 } { \max } $ $ = 67.4 ± 4.6 ml kg−1 min−1 ) continued their usual training for running . TST K was measured every 2 weeks . EC was measured in both training and control groups before and after the 8 weeks at three submaximal velocities , corresponding to 75 , 85 and 95 % of the speed at lactate threshold ( sLT ) . Isometric training did neither result in a mean increase in TST K ( 0.9 ± 25.8 % ) nor a mean improvement in RE ( 0.1 ± 3.6 % ) ; however , there was a significant relationship ( r2 = 0.43 , p = 0.02 ) between the change in TST K and change in EC , regardless of the assigned group . It was concluded that TST K and EC are somewhat labile and change together Berryman , N , Maurel , D , and Bosquet , L. Effect of plyometric vs. dynamic weight training on the energy cost of running . J Strength Cond Res 24(7 ) : 1818 - 1825 , 2010-The purpose of this study is to compare the effects of 2 strength training methods on the energy cost of running ( Cr ) . Thirty-five moderately to well-trained male endurance runners were r and omly assigned to either a control group ( C ) or 2 intervention groups . All groups performed the same endurance-training program during an 8-week period . Intervention groups added a weekly strength training session design ed to improve neuromuscular qualities . Sessions were matched for volume and intensity using either plyometric training ( PT ) or purely concentric contractions with added weight ( dynamic weight training [ DWT ] ) . We found an interaction between time and group ( p < 0.05 ) and an effect of time ( p < 0.01 ) for Cr . Plyometric training induced a larger decrease of Cr ( 218 ± 16 to 203 ± 13 ml·kg−1·km−1 ) than DWT ( 207 ± 15 to 199 ± 12 ml·kg−1·km−1 ) , whereas it remained unchanged in C. Pre-post changes in Cr were correlated with initial Cr ( r = −0.57 , p < 0.05 ) . Peak vertical jump height ( VJHpeak ) increased significantly ( p < 0.01 ) for both experimental groups ( DWT = 33.4 ± 6.2 to 34.9 ± 6.1 cm , PT = 33.3 ± 4.0 to 35.3 ± 3.6 cm ) but not for C. All groups showed improvements ( p < 0.05 ) in Perf3000 ( C = 711 ± 107 to 690 ± 109 seconds , DWT = 755 ± 87 to 724 ± 77 seconds , PT = 748 ± 81 to 712 ± 76 seconds ) . Plyometric training were more effective than DWT in improving Cr in moderately to well-trained male endurance runners showing that athletes and coaches should include explosive strength training in their practice s with a particular attention on plyometric exercises . Future research is needed to establish the origin of this adaptation Abstract .Previous research has reported that plyometric training improves running economy ( RE ) and ultimately distance-running performance , although the exact mechanism by which this occurs remains unclear . This study examined whether changes in running performance result ing from plyometric training were related to alterations in lower leg musculotendinous stiffness ( MTS ) . Seventeen male runners were pre- and post-tested for lower leg MTS , maximum isometric force , rate of force development , 5-bound distance test ( 5BT ) , counter movement jump ( CMJ ) height , RE , V˙O2max , lactate threshold ( Thla ) , and 3-km time . Subjects were r and omly split into an experimental ( E ) group which completed 6 weeks of plyometric training in conjunction with their normal running training , and a control ( C ) group which trained as normal . Following the training period , the E group significantly improved 3-km performance ( 2.7 % ) and RE at each of the tested velocities , while no changes in V˙O2max or Thla were recorded . CMJ height , 5BT , and MTS also increased significantly . No significant changes were observed in any measures for the C group . The results clearly demonstrated that a 6-week plyometric programme led to improvements in 3-km running performance . It is postulated that the increase in MTS result ed in improved RE . We speculate that the improved RE led to changes in 3-km running performance , as there were no corresponding alterations in V˙O2max or Thla Purpose The purpose of the current study was to investigate the effects of adding strength training to normal endurance training on running performance and running economy in well-trained female athletes . We hypothesized that the added strength training would improve performance and running economy through altered stiffness of the muscle-tendon complex of leg extensors . Methods Nineteen female endurance athletes [ maximal oxygen consumption ( VO2max ) : 53±3 ml∙kg-1∙min-1 , 5.8 h weekly endurance training ] were r and omly assigned to either normal endurance training ( E , n = 8) or normal endurance training combined with strength training ( E+S , n = 11 ) . The strength training consisted of four leg exercises [ 3 x 4–10 repetition maximum ( RM ) ] , twice a week for 11 weeks . Muscle strength , 40 min all-out running distance , running performance determinants and patellar tendon stiffness were measured before and after the intervention . Results E+S increased 1RM in leg exercises ( 40 ± 15 % ) and maximal jumping height in counter movement jump ( 6 ± 6 % ) and squat jump ( 9 ± 7 % , p < 0.05 ) . This was accompanied by increased muscle fiber cross sectional area of both fiber type I ( 13 ± 7 % ) and fiber type II ( 31 ± 20 % ) in m. vastus lateralis ( p < 0.05 ) , with no change in capillary density in m. vastus lateralis or the stiffness of the patellar tendon . Neither E+S nor E changed running economy , fractional utilization of VO2max or VO2max . There were also no change in running distance during a 40 min all-out running test in neither of the groups . Conclusion Adding heavy strength training to endurance training did not affect 40 min all-out running performance or running economy compared to endurance training only PURPOSE It has been suggested that endurance training influences the running economy ( CR ) and the oxygen uptake ( .VO(2 ) ) kinetics in heavy exercise by accelerating the primary phase and attenuating the .VO(2 ) slow component . However , the effects of heavy weight training ( HWT ) in combination with endurance training remain unclear . The purpose of this study was to examine the influence of a concurrent HWT+endurance training on CR and the .VO(2 ) kinetics in endurance athletes . METHODS Fifteen triathletes were assigned to endurance+strength ( ES ) or endurance-only ( E ) training for 14 wk . The training program was similar , except ES performed two HWT sessions a week . Before and after the training period , the subjects performed 1 ) an incremental field running test for determination of .VO(2max ) and the velocity associated ( V(.VO2max ) ) , the second ventilatory threshold ( VT(2 ) ) ; 2 ) a 3000-m run at constant velocity , calculated to require 25 % of the difference between .VO(2max ) and VT(2 ) , to determine CR and the characteristics of the VO(2 ) kinetics ; 3 ) maximal hopping tests to determine maximal mechanical power and lower-limb stiffness ; 4 ) maximal concentric lower-limb strength measurements . RESULTS After the training period , maximal strength were increased ( P < 0.01 ) in ES but remained unchanged in E. Hopping power decreased in E ( P < 0.05 ) . After training , economy ( P < 0.05 ) and hopping power ( P < 0.001 ) were greater in ES than in E. .VO(2max ) , leg hopping stiffness and the .VO(2 ) kinetics were not significantly affected by training either in ES or E. CONCLUSION Additional HWT led to improved maximal strength and running economy with no significant effects on the .VO(2 ) kinetics pattern in heavy exercise Abstract Ramírez-Campillo , R , Álvarez , C , Henríquez-Olguín , C , Baez , EB , Martínez , C , And rade , DC , and Izquierdo , M. Effects of plyometric training on endurance and explosive strength performance in competitive middle- and long-distance runners . J Strength Cond Res 28(1 ) : 97–104 , 2014—The purpose of this study was to examine the effect of a short-term plyometric training program on explosive strength and endurance performance in highly competitive middle- and long-distance runners . Athletes were r and omly assigned to a control group ( CG , n = 18 , 12 men ) and an explosive strength training group ( TG , n = 18 , 10 men ) . Drop jump ( DJ ) from 20 ( DJ20 ) and 40 cm ( DJ40 ) , countermovement jump with arms ( CMJA ) , 20-m sprint time , and 2.4-km endurance run time test were carried out before and after 6 weeks of explosive strength training . Also , the combined st and ardized performance ( CSP ) in the endurance and explosive strength test was analyzed . After intervention , the CG did not show any significant change in performance , whereas the TG showed a significant reduction in 2.4-km endurance run time ( −3.9 % ) and 20-m sprint time ( −2.3 % ) and an increase in CMJA ( + 8.9 % ) , DJ20 ( + 12.7 % ) , and DJ40 ( 16.7 % ) explosive performance . Strength training group also exhibited a significant increase in CSP , although the CG showed significant reduction . We conclude that properly programmed concurrent explosive strength and endurance training could be advantageous for middle- and long-distance runners in their competitive performance , especially in events characterized by sprinting actions with small time differences at the end of the race We investigated the effects of strength maintenance training on thigh muscle cross-sectional area ( CSA ) , leg strength , determinants of cycling performance , and cycling performance . Well-trained cyclists completed either ( 1 ) usual endurance training supplemented with heavy strength training twice a week during a 12-week preparatory period followed by strength maintenance training once a week during the first 13 weeks of a competition period ( E + S ; n = 6 [ ♂ = 6 ] ) , or ( 2 ) usual endurance training during the whole intervention period ( E ; n = 6 [ ♂ = 5 , ♀ = 1 ] ) . Following the preparatory period , E + S increased thigh muscle CSA and 1RM ( p < 0.05 ) , while no changes were observed in E. Both groups increased maximal oxygen consumption and mean power output in the 40-min all-out trial ( p < 0.05 ) . At 13 weeks into the competition period , E + S had preserved the increase in CSA and strength from the preparatory period . From the beginning of the preparatory period to 13 weeks into the competition period , E + S increased peak power output in the Wingate test , power output at 2 mmol l−1 [ la− ] , maximal aerobic power output ( Wmax ) , and mean power output in the 40-min all-out trial ( p < 0.05 ) . The relative improvements in the last two measurements were larger than in E ( p < 0.05 ) . For E , Wmax and power output at 2 mmol l−1 [ la− ] remained unchanged . In conclusion , in well-trained cyclists , strength maintenance training in a competition period preserved increases in thigh muscle CSA and leg strength attained in a preceding preparatory period and further improved cycling performance determinants and performance PURPOSE The present study investigated the effect of maximal strength training on running economy ( RE ) at 70 % of maximal oxygen consumption ( V[spacing dot above]O2max ) and time to exhaustion at maximal aerobic speed ( MAS ) . Responses in one repetition maximum ( 1RM ) and rate of force development ( RFD ) in half-squats , maximal oxygen consumption , RE , and time to exhaustion at MAS were examined . METHODS Seventeen well-trained ( nine male and eight female ) runners were r and omly assigned into either an intervention or a control group . The intervention group ( four males and four females ) performed half-squats , four sets of four repetitions maximum , three times per week for 8 wk , as a supplement to their normal endurance training . The control group continued their normal endurance training during the same period . RESULTS The intervention manifested significant improvements in 1RM ( 33.2 % ) , RFD ( 26.0 % ) , RE ( 5.0 % ) , and time to exhaustion at MAS ( 21.3 % ) . No changes were found in V[spacing dot above]O2max or body weight . The control group exhibited no changes from pre to post values in any of the parameters . CONCLUSION Maximal strength training for 8 wk improved RE and increased time to exhaustion at MAS among well-trained , long-distance runners , without change in maximal oxygen uptake or body weight QUESTIONS Does the PEDro scale measure only one construct ie , the method ological quality of clinical trials ? What is the hierarchy of items of the PEDro scale from least to most adhered to ? Is there any effect of year of publication of trials on item adherence ? Are PEDro scale ordinal scores equivalent to interval data ? DESIGN Rasch analysis of two independent sample s of 100 clinical trials from the PEDro data base scored using the PEDro scale . RESULTS Both sample s of PEDro data showed fit to the Rasch model with no item misfit . The PEDro scale item hierarchy was the same in both sample s , ranging from the most adhered to item r and om allocation , to the least adhered to item therapist blinding . There was no differential item functioning by year of publication . Original PEDro ordinal scores were highly correlated with transformed PEDro interval scores ( r = 0.99 ) . CONCLUSION The PEDro scale is a valid measure of the method ological quality of clinical trials . It is valid to sum PEDro scale item scores to obtain a total score that can be treated as interval level measurement and subjected to parametric statistical analysis BACKGROUND Altered neuromotor control during running after cycling has been associated with exercise-related leg pain and may have performance implication s for triathletes . OBJECTIVE To investigate the effectiveness of adding plyometric training to regular endurance training on triathletes ' neuromotor control and running economy in those in which it is aberrant . DESIGN R and omised controlled trial . SETTING Institutional . PARTICIPANTS 15 moderately-trained triathletes . INTERVENTIONS Eight-week endurance only ( control group ) or endurance plus plyometric ( plyometric group ) training program . MAIN OUTCOME MEASURES Neuromotor control and running economy during running after cycling . RESULTS Eight of the fifteen triathletes exhibited aberrant neuromotor control and were r and omised to control or plyometric groups . Combined plyometric and endurance training produced favourable neuromotor adaptations during running after cycling beyond that of endurance training at 8 weeks ( numbers needed to treat 2 ) . There were significant differences between control and plyometric groups at eight weeks for the coefficient of multiple correlation ( p=0.03 ) and root mean square error ( p = 0.01 ) between control and transition runs . Running economy was not different between groups at follow-up . CONCLUSION Our results provide some support for the utility of plyometrics as an intervention to correct altered neuromotor control in those triathletes in which it is aberrant BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . Abstract Piacentini , MF , De Ioannon , G , Comotto , S , Spedicato , A , Vernillo , G , and La Torre , A. Concurrent strength and endurance training effects on running economy in master endurance runners . J Strength Cond Res 27(8 ) : 2295–2303 , 2013—Running economy ( RE ) has been seen to improve with concurrent strength and endurance training in young and elite endurance athletes . The purpose of this study was to evaluate the effects of 2 different strength training protocol s on RE and strength parameters in a group of regularly training master marathon runners . Sixteen participants were r and omly assigned to a maximal strength training program ( MST ; n = 6 ; 44.2 ± 3.9 years ) , a resistance training ( n = 5 ; 44.8 ± 4.4 years ) , and a control group ( n = 5 ; 43.2 ± 7.9 years ) . Before and after the experimental period , resting metabolic rate , body composition , 1 repetition maximum ( 1RM ) , squat jump , countermovement jump , and RE were evaluated . The MST group showed significant increases ( p < 0.05 ) in 1RM ( + 16.34 % ) and RE ( + 6.17 % ) at marathon pace . No differences emerged for the other groups ( p > 0.05 ) . Anthropometric data were unchanged after the training intervention ( p > 0.05 ) . Taken together , the results of this preliminary study indicate that master endurance athletes seem to benefit from concurrent strength and endurance training because the rate of force development may be crucial for RE improvement , one of the major determinants of endurance performance PURPOSE The purpose of this study was to examine the efficacy of 8 wk of resistance training to failure versus not to failure training regimens at both moderate and low volumes for increasing upper-body strength and power as well as cardiovascular parameters into a combined resistance and endurance periodized training scheme . METHODS Forty-three trained male rowers were matched and then r and omly assigned to four groups that performed the same endurance training but differed on their resistance training regimen : four exercises leading to repetition failure ( 4RF ; n = 14 ) , four exercises not leading to failure ( 4NRF ; n = 15 ) , two exercises not to failure ( 2NRF ; n = 6 ) , and control group ( C ; n = 8) . One-repetition maximum strength and maximal muscle power output during prone bench pull ( BP ) , average power during a 20-min all-out row test ( W 20 min ) , average row power output eliciting a blood lactate concentration of 4 mmol x L(-1 ) ( W 4 mmol x L(-1 ) ) , and power output in 10 maximal strokes ( W 10 strokes ) were assessed before and after 8 wk of periodized training . RESULTS 4NRF group experienced larger gains in one- repetition maximum strength and muscle power output ( 4.6 % and 6.4 % , respectively ) in BP compared with both 4RF ( 2.1 % and j1.2 % ) and 2NRF ( 0.6 % and -0.6 % ) . 4NRF and 2NRF groups experienced larger gains in W 10 strokes ( 3.6 % and 5 % ) and in W 20 min ( 7.6 % and 9 % ) compared with those found after 4RF ( -0.1 % and 4.6 % ) , whereas no significant differences between groups were observed in the magnitude of changes in W 4 mmol x L(-1 ) ( 4NRF = 6.2 % , 4RF = 5.3 % , 2NRF = 6.8 % , and C = 4.5 % ) . CONCLUSIONS An 8-wk linear periodized concurrent strength and endurance training program using a moderate number of repetitions not to failure ( 4NRF group ) provides a favorable environment for achieving greater enhancements in strength , muscle power , and rowing performance when compared with higher training volumes of repetitions to failure in experienced highly trained rowers Abstract Sedano , S , Marín , PJ , Cuadrado , G , and Redondo , JC . Concurrent training in elite male runners : The influence of strength versus muscular endurance training on performance outcomes . J Strength Cond Res 27(9 ) : 2433–2443 , 2013—Much recent attention has been given to the compatibility of combined aerobic and anaerobic training modalities . However , few of these studies have reported data related to well-trained runners , which is a potential limitation . Therefore , because of the limited evidence available for this population , the main aim was to determine which mode of concurrent strength-endurance training might be the most effective at improving running performance in highly trained runners . Eighteen well-trained male runners ( age 23.7± 1.2 years ) with a maximal oxygen consumption ( V[Combining Dot Above]O2max ) more than 65 ml·kg−1·min−1 were r and omly assigned into 1 of the 3 groups : Endurance-only Group ( n = 6 ) , who continued their usual training , which included general strength training with Thera-b and latex-free exercise b and s and endurance training ; Strength Group ( SG ; n = 6 ) who performed combined resistance and plyometric exercises and endurance training ; Endurance-SG ( ESG ; n = 6 ) who performed endurance-strength training with loads of 40 % and endurance training . The study comprised 12 weeks of training in which runners trained 8 times a week ( 6 endurance and 2 strength sessions ) and 5 weeks of detraining . The subjects were tested on 3 different occasions ( countermovement jump height , hopping test average height , 1 repetition maximum , running economy ( RE ) , V[Combining Dot Above]O2max , maximal heart rate [ HRmax ] , peak velocity ( PV ) , rating of perceived exertion , and 3-km time trial were measured ) . Findings revealed significant time × group interaction effects for almost all tests ( p < 0.05 ) . We can conclude that concurrent training for both SG and ESG groups led to improved maximal strength , RE , and PV with no significant effects on the V[Combining Dot Above]O2 kinetics pattern . The SG group also seems to show improvements in 3-km time trial tests In a recent study competitive road cyclists experienced substantial gains in sprint and endurance performance when sessions of high-intensity interval training were added to their usual training in the competitive phase of a season . The current study reports the effect of this type of training on performance of 20 distance runners r and omized to an experimental or control group for 5 to 7 weeks of training . The experimental group replaced part of their usual competitive-phase training with 10 x ? 30-minute sessions consisting of 3 sets of explosive single-leg jumps ( 20 for each leg ) alternating with 3 sets of resisted treadmill sprints ( 5 x ? 30-second efforts alternating with 30-second recovery ) . Before and after the training period all runners completed an incremental treadmill test for assessment of lactate threshold and maximum running speed , 2 treadmill runs to exhaustion for prediction of 800- and 1500-m times , and a 5-km outdoor time trial . Relative to the control group , the mean changes ( + /-90 % confidence limits ) in the experimental group were : maximum running speed , 1.8 % ( + /- 1.1 % ) ; lactate-threshold speed , 3.5 % ( + /-3.4 % ) ; predicted 800-m speed , 3.6 % ( + /- 1.8 % ) ; predicted 1500-m speed , 3.7 % ( + /- 3.0 % ) ; and 5-km time-trial speed , 1.2 % ( + /- 1.1 % ) . We conclude that high-intensity resistance training in the competitive phase is likely to produce beneficial gains in performance for most distance runners We compared the effects of two resistance training ( RT ) programs only differing in the repetition velocity loss allowed in each set : 20 % ( VL20 ) vs 40 % ( VL40 ) on muscle structural and functional adaptations . Twenty-two young males were r and omly assigned to a VL20 ( n = 12 ) or VL40 ( n = 10 ) group . Subjects followed an 8-week velocity-based RT program using the squat exercise while monitoring repetition velocity . Pre- and post-training assessment s included : magnetic resonance imaging , vastus lateralis biopsies for muscle cross-sectional area ( CSA ) and fiber type analyses , one-repetition maximum strength and full load-velocity squat profile , countermovement jump ( CMJ ) , and 20-m sprint running . VL20 result ed in similar squat strength gains than VL40 and greater improvements in CMJ ( 9.5 % vs 3.5 % , P < 0.05 ) , despite VL20 performing 40 % fewer repetitions . Although both groups increased mean fiber CSA and whole quadriceps muscle volume , VL40 training elicited a greater hypertrophy of vastus lateralis and intermedius than VL20 . Training result ed in a reduction of myosin heavy chain IIX percentage in VL40 , whereas it was preserved in VL20 . In conclusion , the progressive accumulation of muscle fatigue as indicated by a more pronounced repetition velocity loss appears as an important variable in the configuration of the resistance exercise stimulus as it influences functional and structural neuromuscular adaptations This study aim ed to compare the effect on neuromuscular performance of 2 isoinertial resistance training programs that differed only in actual repetition velocity : maximal intended ( MaxV ) vs. half-maximal ( HalfV ) concentric velocity . 21 resistance-trained young men were r and omly assigned to a MaxV ( n=10 ) or HalfV ( n=11 ) group and trained for 6 weeks using the full squat exercise . A complementary study ( n=8 ) described the acute metabolic and mechanical response to the protocol s used . MaxV training result ed in a likely more beneficial effect than HalfV on squat performance : maximum strength ( ES : 0.94 vs. 0.54 ) , velocity developed against all ( ES : 1.76 vs. 0.88 ) , light ( ES : 1.76 vs. 0.75 ) and heavy ( ES : 2.03 vs. 1.64 ) loads common to pre- and post-tests , and CMJ height ( ES : 0.63 vs. 0.15 ) . The effect on 20-m sprint was unclear , however . Both groups attained the greatest improvements in squat performance at their training velocities . Movement velocity seemed to be of greater importance than time under tension for inducing strength adaptations . Slightly higher metabolic stress ( blood lactate and ammonia ) and CMJ height loss were found for MaxV vs. HalfV , while metabolite levels were low to moderate for both conditions . MaxV may provide a superior stimulus for inducing adaptations directed towards improving athletic performance |
12,209 | 28,384,533 | Maximal pressure injury prevention efforts are particularly important among critical-care patients who are older , have altered mobility , experience poor perfusion , or who are receiving a vasopressor infusion | OBJECTIVE To identify risk factors independently predictive of pressure injury ( also known as pressure ulcer ) development among critical-care patients . | The purpose of this study was to identify pressure ulcer ( PU ) incidence and risk factors that are associated with PU development in patients in two adult intensive care units ( ICU ) in Saudi Arabia . A prospect i ve cohort study design was used . A total of 84 participants were screened second daily basis until discharge or death , over a consecutive 30-day period , out of which 33 participants with new PUs were identified giving a cumulative hospital-acquired PU incidence of 39·3 % ( 33/84 participants ) . The incidence of medical devices-related PUs was 8·3 % ( 7/84 ) . Age , length of stay in the ICU , history of cardiovascular disease and kidney disease , infrequent repositioning , time of operation , emergency admission , mechanical ventilation and lower Braden Scale scores independently predicted the development of a PU . According to binary logistic regression analyses , age , longer stay in ICU and infrequent repositioning were significant predictors of all stages of PUs , while the length of stay in the ICU and infrequent repositioning were associated with the development of stages II-IV PUs . In conclusion , PU incidence rate was higher than that reported in other international studies . This indicates that urgent attention is required for PU prevention strategies in this setting AIM This study identified risk factors for pressure ulcer development early in the admission stage to determine what appropriate interventions might be conducted early in the admission stage to decrease the risk of pressure ulcer development . BACKGROUND Among patients who develop pressure ulcers , 8 - 40 % of them occur in a critical care setting . Therefore , the development of pressure ulcers is a common problem . DESIGN Prospect i ve cohort study . METHODS The study facility was a 606-bed tertiary care hospital . Ninety eight patients admitted to the intensive care unit ( ICU ) or the high care unit ( HCU ) from 16 April 2003 - 15 July 2003 were evaluated in the final analysis . RESULTS The mean patient age was 62.3 ( SD 16.1 ) years , and the incidence of pressure ulcers in this study was 11.2 % during the observation period . Multivariate analysis showed that ' emergency ICU/HCU patients ' and ' infrequent turning ' were related to pressure ulcer development . Patients with pressure ulcers experienced significantly fewer turns and repositionings ( OR = 0.452 , 95 % CI : 0.212 - 0.966 ] , p < 0.05 . Fewer pressure ulcers developed in scheduled ICU/HCU patients than in emergency ICU/HCU patients ( OR = 0.041 [ 95 % CI : 0.004 - 0.470 ] , p < 0.01 ) . CONCLUSION There was no relationship between pressure ulcer development and APACHE II score , or any medication that affected skin integrity . The frequency of turning and repositioning and patients with an emergency admission to the ICU/HCU can be the prognostic indicators for developing scoring system in critical care setting s. RELEVANCE TO CLINICAL PRACTICE These patients admitted directly to ICU or HCU were in a high risk group , further preventive strategies will be required AIMS To determine the incidence of pressure ulcers occurring at least 48 hours after admission and risk factors for pressure ulcers grade 2 - 4 in a long-stay surgical Intensive Care Unit ( ICU ) population . BACKGROUND The incidence of pressure ulcers in intensive care units is larger than in non-intensive environments . DESIGN Prospect i ve descriptive research design . METHODS Using pressure ulcers grade 2 - 4 as an outcome measure , a multivariate logistic regression analysis was used to identify the risk factors . Data were obtained on a daily basis in a surgical intensive care unit of the University Hospital Leuven between November 2003-March 2004 . A total of 520 long-stay ( > or= 24 hours ) intensive care patients were included . RESULTS Cumulative incidence of pressure ulcers grade 2 - 4 was 20.1 % . The following variables were positively associated with pressure ulcers grade 2 - 4 : history of vascular disease , treatment with Dopamine or Dobutamine , intermittent haemodialysis ( IHD ) or continuous veno-venous haemofiltration ( CVVH ) , mechanical ventilation . Also preventive measures were statistically positively associated with pressure ulcers grade 2 - 4 : turning , floating heels , alternating mattresses , adequate prevention . The use of sedatives , body temperature above 38.5 degrees C and sitting in chair where negatively associated with pressure ulcers . Pressure ulcers are statistically associated with different risk factors and preventive measures . CONCLUSION The identified risk factors are eligible to be included in a new risk assessment scale for patients admitted to intensive care units . RELEVANCE TO CLINICAL PRACTICE The novel insights have implication s for risk assessment for patients in intensive care units . Patients admitted to intensive care units have other risk factors for pressure ulcers which are eligible to be included in a new risk assessment scale The analytical effect of the number of events per variable ( EPV ) in a proportional hazards regression analysis was evaluated using Monte Carlo simulation techniques for data from a r and omized trial containing 673 patients and 252 deaths , in which seven predictor variables had an original significance level of p < 0.10 . The 252 deaths and 7 variables correspond to 36 events per variable analyzed in the full data set . Five hundred simulated analyses were conducted for these seven variables at EPVs of 2 , 5 , 10 , 15 , 20 , and 25 . For each simulation , a r and om exponential survival time was generated for each of the 673 patients , and the simulated results were compared with their original counterparts . As EPV decreased , the regression coefficients became more biased relative to the true value ; the 90 % confidence limits about the simulated values did not have a coverage of 90 % for the original value ; large sample properties did not hold for variance estimates from the proportional hazards model , and the Z statistics used to test the significance of the regression coefficients lost validity under the null hypothesis . Although a single boundary level for avoiding problems is not easy to choose , the value of EPV = 10 seems most prudent . Below this value for EPV , the results of proportional hazards regression analyses should be interpreted with caution because the statistical model may not be valid OBJECTIVE To identify the independent effect of pressure ulcers on excess length of stay and control for all observable factors that may also contribute to excess length of stay . Hospitalized patients who develop a pressure ulcer during their hospital stay are at a greater risk for increased length of stay as compared with patients who do not . DESIGN Cross-sectional , observational study . SETTING Tertiary-care referral and teaching hospital in Australia . PATIENTS Two thous and hospitalized patients 18 years and older who had a minimum stay in the hospital of 1 night and admission to selected clinical units . METHODS Two thous and participants were r and omly selected from 4,500 patients enrolled in a prospect i ve survey conducted between October 2002 and January 2003 . Quantile median robust regression was used to assess risk factors for excess length of hospital stay . RESULTS Having a pressure ulcer result ed in a median excess length of stay of 4.31 days . Twenty other variables were statistically significant at the 5 % level in the final model . CONCLUSIONS Pressure ulcers make a significant independent contribution to excess length of hospitalization beyond what might be expected based on admission diagnosis . However , our estimates were substantially lower than those currently used to make predictions of the economic costs of pressure ulcers ; existing estimates may overstate the true economic cost Stage 1 pressure ulcers are difficult to diagnose . Several prevalence studies have shown that almost half of the pressure ulcers identified are stage 1 . The present study investigated the importance of stage 1 . The following research questions were formulated : Is there a difference between the prevalence of stage 1 pressure ulcers identified in the institutions participating in the present study and that found in the other institutions participating in the Dutch National Prevalence Survey ? What percentage of stage 1 pressure ulcers are reversible within a few hours ? What is the clinical course of stage 1 pressure ulcers ? Which patient characteristics and preventive interventions are related to the clinical course of stage 1 ? The study used a prospect i ve , descriptive and comparative design . All patients of six long-term care hospitals and six acute care hospitals in whom stage 1 pressure ulcers were identified during the 1999 National Prevalence Survey in the Netherl and s were followed for 1 week ( acute care hospitals ; n = 68 patients ) or 2 weeks ( long-term care hospitals ; n = 115 patients ) . The patients were reassessed using the question naire developed for the National Prevalence Survey ( patient characteristics , assessment of risk of pressure ulcers , characteristics of the pressure ulcers and use of preventive methods ) on the same day as the national survey itself , and again after 3 days , after 7 days and after 14 days ( only long-term care hospitals ) . The results showed fewer stage 1 pressure ulcers in the institutions participating in the present study than in the National Prevalence Survey , the difference being almost 50 % . The first re assessment found the prevalence of stage 1 to be further reduced by an average of almost 50 % , a reduction which was greater for the long-term care hospitals than for the acute care hospitals . However , some of the ulcers that had disappeared reappeared in subsequent re assessment s. In the long-term care hospitals , 8.7 % of the stage 1 pressure ulcers deteriorated to a higher stage , vs. 22.1 % in acute care hospitals . No significant patient characteristics were found to affect the course of stage 1 , except that women in acute care hospitals more often had a stage 1 pressure ulcer at the first re assessment than men . In general , patients whose stage 1 ulcer deteriorated were undergoing more preventive interventions ; not all differences were significant . We conclude that , although stage 1 is reversible in most cases , it can be interpreted as an important warning sign for nurses and patients to act . If no adequate interventions are applied , the pressure ulcer may deteriorate BACKGROUND Implementation of the ruling on the Inpatient Prospect i ve Payment System by the Centers for Medicare and Medicaid has challenged nurses to focus on the prevention of pressure ulcers . Despite years of research , pressure ulcers are still one of the most common complications experienced by patients in health care facilities . OBJECTIVE To examine the relationship between patients ' characteristics ( age , sex , body mass index , history of diabetes , and Braden Scale score at admission ) and care characteristics ( total operating room time , multiple surgeries , and vasopressor use ) and the development of pressure ulcers . METHODS In a cohort study , data from the electronic medical records of 3225 surgical patients admitted to a Midwest hospital , from November 2008 to August 2009 were analyzed statistically to determine predictors of pressure ulcers . RESULTS A total of 12 % of patients ( n = 383 ) had at least 1 pressure ulcer develop during their hospitalization . According to logistic regression analysis , scores on the Braden Scale at admission ( P < .001 ) , low body mass index ( P < .001 ) , number of vasopressors ( P = .03 ) , multiple surgeries during the admission ( P < .001 ) , total surgery time ( P < .001 ) , and risk for mortality ( P < .001 ) were significant predictors of pressure ulcers . CONCLUSION Scores on the Braden Scale at admission can be used to identify patients at increased risk for pressure ulcers . For other high-risk factors , such as low body mass index and long operative procedures , appropriate clinical interventions to manage these conditions can help prevent pressure ulcers PURPOSE : We sought to describe the occurrence of pressure ulcers in patients managed in a surgical intensive care unit ( ICU ) and report preliminary work toward development of a pressure ulcer risk assessment tool for use in this population that incorporates comorbidities and other factors not addressed in previous instruments . SUBJECTS AND SETTING S : Three hundred sixty-nine patients managed in the surgical ICU at Yale-New Haven Hospital comprised the sample . METHODS : Demographic and clinical data , including Braden Scale scores , were collected in this prospect i ve , 2-phase study . The principal investigator ( G.C.S. ) performed skin assessment s on all patients . We used chi-square analysis and t tests to determine variables to include in a stepwise logistic regression analysis to determine factors independently associated with the development of pressure ulcers . INSTRUMENT : We collected data , using a form we developed that contained demographic and clinical factors found in previous research and in our clinical practice to be associated with pressure ulcers . RESULTS : Eighty-eight out of 369 patients ( 23.9 % ) experienced a hospital-acquired pressure ulcer . Braden Scale scores ranged from 6 to 21 , with a mean score of 11.9 ± 2.2 . A lower Braden Scale score , the presence of diabetes mellitus , and patient age 70 years or older independently predicted the development of a pressure ulcer . These factors have been incorporated into the preliminary Surgical ICU Pressure Ulcer Risk Assessment scale . CONCLUSIONS : Findings from this study suggest that , in addition to a low Braden Scale score , age > 70 years and a diagnosis of diabetes may represent clinical ly relevant pressure ulcer risk factors in the surgical intensive care population and that patients with these factors may benefit from more aggressive preventive care . In addition , the Surgical ICU Pressure Ulcer Risk Assessment scale requires additional psychometric testing before its use can be recommended for the research or practice setting AIMS AND OBJECTIVES The study aim ed to evaluate the predictive validity and accuracy of a new pressure ulcer risk assessment scale in two Indonesia intensive care units ( ICUs ) . BACKGROUND Several risk assessment scales have been design ed to identify patients at risk of developing pressure ulcers in ICU . However , the relative weight of each variable that contributes to pressure ulcer development in these scales is not described to enable design ing of a risk assessment scale . Currently , the risk factors contributing to pressure ulcer development include interface pressure , body temperature and cigarette smoking . DESIGN A prospect i ve cohort study was conducted in two ICUs in Pontianak , Indonesia . METHODS A total of 253 patients were recruited to the study from both hospitals . Data collection included new risk assessment scale [ i.e. the Suriadi and Sanada ( S.S. ) scale ] scoring , demographic , pressure ulcer severity scores ( based on the National Pressure Ulcer Advisory Panel ) and skin condition measures . Using the S.S. scale , trained data collectors scored patients once and assessed the body temperature daily until patients were discharged . Additionally , daily data were also collected in relation to the patient 's skin condition and stage of pressure ulcer . RESULTS Out of the 253 patients , 72 ( 28.4 % ) developed pressure ulcers . In ICU A , the incidence was 27 % ; pressure ulcers developed into stage I ( 41.7 % ) , stage II ( 45.8 % ) , stage III ( 10.4 % ) and stage IV ( 2.1 % ) . In ICU B , the incidence was 31.6 % ; the development of pressure ulcers was 48 % in stage I and 52 % in stage II . Using the predictive validity test , the S.S. scale balanced sensitivity ( 81 % ) and specificity ( 83 % ) at a cut-off score of 4 . The area under the receiver-operating characteristic curve was 0.888 ( confidence interval : 0.84 - 0.93 ) . CONCLUSION The S.S. scale was found to be a valid risk assessment tool to identify the patients at risk of developing pressure ulcers in Indonesia ICU PURPOSE The aim of this study was to determine the incidence of pressure ulcers ( PUs ) in ventilated patients in all intensive care units ( ICUs ) in Granada ( Spain ) and identify risk factors for their development . MATERIAL S AND METHODS A prospect i ve cohort study in 9 medical-surgical ICUs was conducted . Two hundred ninety-nine patients with more than 24 hours on mechanical ventilation ( MV ) were enrolled during 2 periods in a 5-month study . Pressure ulcers of patients were measured according to the European Pressure Ulcer Advisory Panel . RESULTS Of the 299 patients initially enrolled , 47 ( 16 % ) developed PUs of at least grade II severity . The incidence density of PUs was 13.4 cases per 1000 patient-days of ICU stay and 19.6 cases per 1000 patient-days on MV . Logistic regression identified first-day respiratory sequential organ failure assessment ( odds ratio [ OR ] , 1.56 ; 95 % confidence interval [ CI ] , 1.026 - 2.360 ; P = .037 ) , fourth-day cardiovascular sequential organ failure assessment ( OR , 1.33 ; 95 % CI , 1.066 - 1.664 ; P = .012 ) , age ( OR , 1.042 ; 95 % CI , 1.013 - 1.072 ; P = .004 ) , winter period ( OR , 4.60 ; 95 % CI , 1.99 - 10.59 ; P < .001 ) , and length of MV before PUs ( OR , 1.042 ; 95 % CI , 1.005 - 1.080 ; P = .024 ) as significant independent predictors of PU development . CONCLUSIONS Among other factors previously known in ventilated patients , duration of MV and winter period were identified as risk factors for PUs AIMS To determine incidence of pressure ulcers in patients at risk according to the Waterlow scale in intensive care units and to evaluate the effects of risk factors in critically ill patients . BACKGROUND Pressure ulcers continue to be an important health problem that increases the risk of illness and death , extends patients ' length of hospital stay and increases healthcare expenses . DESIGN The study was conducted as a descriptive and prospect i ve study . METHOD The sample consisted of 140 patients . Data were collected using a data collection form , the skin assessment instrument and the Waterlow scale . RESULTS The incidence of pressure ulcers in intensive care unit patients was found to be 14.3 % . The majority of pressure ulcers ( 74 % ) were grade I. The mean length of time for pressure ulcer development was found to be 10.4 ( SD 1.85 ) days . A statistically significant difference was found in the patients for pressure ulcer development according to their level of consciousness , activity , cooperation , length of stay , Waterlow scale score and C-reactive protein level . In the multiple stepwise logistic regression analysis , the most influential factors for pressure ulcer development were determined to be length of stay and activity level . CONCLUSIONS Extra care needs to be taken to prevent pressure ulcer development in intensive care unit patients who have an extended length of stay , are dependent for activities , have high Waterlow scores , are unconscious and are not cooperative . RELEVANCE TO CLINICAL PRACTICE This study determined the incidence of and factors that can affect the development of pressure ulcers in intensive care unit patients who are in a high risk group for the development of pressure ulcers and presented the importance of having Turkish nurses implement interventions directed at these factors OBJECTIVE To evaluate objective parameters and subjective nursing assessment as pressure ulcer risk factors for intensive care unit ( ICU ) patients , and compared them with the performance of a general assessment tool ( Waterlow scale ) . To vali date the newly developed assessment method . METHOD This prospect i ve epidemiological study involved 698 patients admitted to an ICU between April 2001 and December 2004 without pressure ulcers and who stayed in the ICU for more than 72 hours . Objective parameters routinely determined during the first 24 hours in the ICU as well as subjective nursing assessment on admission were analysed for their significance as pressure ulcer risk predictors . RESULTS Of the 698 patients 121 ( 17 % ) developed pressure ulcers in the ICU . With univariate analysis , a variety of objective ly measurable parameters relating to organ dysfunction , circulatory impairment and sepsis showed significant association with the occurrence of pressure ulcers . When multiple logistic regression was performed , subjective nursing skin assessment parameters outweighed these parameters as pressure ulcer risk predictors . A risk function comprised of five skin-related and one other parameter yielded an overall correct pressure ulcer prediction proportion of 84.6 % . With receiver-operator characteristic curve analysis , the area under the curve ( AUC ) was 0.82 . Results were vali date d in 329 patients treated in the same ICU between January 2005 and May 2006 , yielding an AUC of 0.80 . CONCLUSION Nursing skin assessment is an important pressure ulcer risk stratification tool in the ICU despite the availability of a large number of objective ly measureable ICU specific parameters in these patients Aims and objective . To verify association between PU development with nursing workload and illness severity and to verify whether nursing workload and illness severity are related with Braden Scale scores . Background . Critically ill patients are more susceptible to treatment complications because of the severity of their clinical condition . Design . Prospect i ve descriptive study . Methods . Patients consecutively admitted to three intensive care units ( ICUs ) of a public university hospital located in Sao Paulo , Brazil and without pressure ulcer ( PU ) at admission and a minimum stay of 24 hours were included in the sample . Prospect i ve data collection included demographic , clinical and hospitalisation data , Nursing Activities Score ( NAS ) , Simplified Acute Physiology Score ( SAPSII ) and Braden Scale . Multivariate linear regression analysis was applied to verify whether nursing workload and illness severity are related with Braden Scale scores . Multivariate logistic regression analysis was used to verify whether nursing workload and illness severity were risk factors associated with PU development . Results . The study sample included 160 patients . The mean Braden score was 12·0 and PU incidence was 34·4 % . Multivariate linear regression analysis identified as factors related to variation of Braden scores : illness severity ( SAPSII ) , nursing workload ( NAS ) and age . Multivariate logistic regression showed a model with risk factors associated with PU development : sex , length of ICU stay , illness severity and nursing workload . Conclusion . Nursing workload , severity of illness , sex and length of ICU stay were identified as risk factors associated with PU development . However , nursing workload acted as a protective factor . Illness severity , nursing workload and age were related to Braden scores . Relevance to clinical practice . Accurate identification of risk factors and the use of clinical judgment in skin assessment are prerequisites for determining appropriate strategies to prevent pressure ulcers , to improve quality of care for patient safety and to reduce length of ICU and hospital stay and costs OBJECTIVE To determine whether or not the development of a Stage II or greater pressure ulcer in-hospital is associated with increased hospital costs and length of stay after adjusting for admission severity of illness , comorbidities , nosocomial infections , and other hospital complications . DESIGN Prospect i ve , inception cohort study . SETTING Tertiary care , urban , university teaching hospital . PARTICIPANTS 286 patients identified within 3 days of admission to a tertiary care , urban teaching hospital were enrolled in a prospect i ve , inception cohort study . Patients were age 55 or greater ; expected to be confined to bed or chair or with a hip fracture ; and expected to remain in hospital at least 5 days . MEASUREMENTS Baseline data were collected within 3 days of admission . Weekly skin assessment s were performed by study nurses to document the development of pressure ulcers . Medical record review s , patient exams , and physician and nurse interviews were used to obtain baseline demographic , medical , functional , nutritional , and global measures of disease severity . The incidence of nosocomial infections and the number of other hospital complications were monitored by medical record review s. Hospital costs were estimated using category-specific cost-to-charge ratios . Diagnostic-related group ( DRG ) adjusted length of stay was calculated by subtracting the mean length of stay for assigned DRGs from actual stays . RESULTS Incident pressure ulcers were associated with significantly higher mean unadjusted hospital costs ( $ 37,288 vs $ 13,924 , P = 0.0001 ) and length of stay ( 30.4 vs 12.8 days , P = 0.0001 ) . In addition to pressure ulcers , other independent predictors of hospital costs and length of stay after multivariable analyses included : admission to an intensive care unit or surgical service , younger age , nosocomial infection , the physician assessment of disease severity , and the number of other hospital complications . Compared with those who did not develop pressure ulcers , patients who developed pressure ulcers also were more likely to develop nosocomial infections ( 45.9 % [ 17/37 ] vs 20.1 % [ 50/249 ] , P = 0.001 ) and other hospital complications ( 86.5 % [ 32/37 ] vs 43.0 % [ 107/249 ] , P < 0.001 ) . After adjusting for only the admission predictors of costs and length of stay by multivariable analyses , hospital costs , and length of stay for those who developed pressure ulcers remained significantly greater than for those who did not develop pressure ulcers ( $ 14,260 vs $ 12,382 , P = 0.03 , and 16.9 vs 12.9 days , P = 0.02 , respectively ) . The differences in costs and length of stay for those with and without incident pressure ulcers were even greater when adjusted for admission predictors and also the occurrence of nosocomial infections and other complications ( $ 29,048 vs $ 13,819 , P = 0.002 , and 20.9 vs 12.7 days , P = 0.0001 , respectively ) . CONCLUSION Incident pressure ulcers are associated with substantial and significant increases in hospital costs and length of stay . Nosocomial infections and other hospital complications are additional significant independent predictors of health care utilization among patients at risk for pressure ulcers Many risk factors for the development of pressure ulcers ( PUs ) in the general hospital population have been identified , but consensus is lacking on specific PU risk factors for critical care patients . A prospect i ve , descriptive study was conducted to determine the incidence of and risk factors for PU development among high-risk patients ( Braden risk scale score < 12 ) admitted to an intensive care unit ( ICU ) of a university hospital in Turkey . Demographic variables , APACHE II scores , serum albumin , hemoglobin , and glucose levels were obtained , and patients ' skin was assessed daily until discharge . Data were analyzed using percentage distributions , Student 's t-test , chi-square , and logistic regression analysis . Seventy ( 70 ) patients ( 22 women , 48 men ) , average age 56.2 ( SD 19.2 ) years , mean albumin level 2.86 ( median : 2.86 , SD 2.73 ) , and mean APACHE II score 17.2 ( SD 6.48 ) , completed the study . During an average length of stay of 17.2 days ( SD 4.2 ) , PU incidence was 28.6 % . Of the 23 ulcers that developed , 12 ( 52.1 % ) were Stage I , eight ( 8 , 34.8 % ) were Stage II , and three ( 3 , 13.1 % ) were Stage III ; no patient developed a Stage IV ulcer . Multivariate logistic regression analysis showed that being female ( OR = 0.15 , [ 95 % CI:0.03- 0.71 ] P < 0.05 ) and having a lower serum albumin level ( OR=11.6 , [ 95 % CI:1.92- 70.4 ] P < 0.01 ) were independent risk factors for PU development . Patient gender and serum albumin levels should be considered as risk factors for PU development in ICU patients . Larger prospect i ve studies examining these risk factors in ICU patients are warranted |
12,210 | 25,887,049 | The studies review ed suggested that orthodontic treatment alters the original color of enamel , and both adhesive systems and resin-removal methods can contribute to this change .
Conclusion There is no strong evidence from this review that orthodontic treatment with fixed appliances alters the original color of enamel . | Background The purpose s of this systematic review were to identify and review the orthodontic literature with regard to enamel color alterations after orthodontic treatment with fixed appliances .
The effects of clean-up procedures on the surface of enamel were also investigated . | INTRODUCTION Our aim was to prospect ively assess in-vivo color alterations of natural teeth associated with fixed orthodontic treatment . METHODS Twenty-six consecutive patients were treated with fixed appliances bonded with a chemically cured or a light-cured resin with a split-mouth design . The spectrophotometric data of a st and ardized labial circular area of all teeth were recorded , before bracket bonding and after debonding and cleaning procedures . The color parameters of the Commission Internationale de l'Eclairage-L∗ , a∗ , and b∗ ( lightness , red/green , and blue/yellow)-were measured for each adhesive and type of tooth , and the corresponding color differences ( ΔE ) between the interval groups were calculated . The effect of these parameters on color was assessed with 3-way mixed analysis of variance ( ANOVA ) and the Bonferroni comparisons test ( α < 0.05 ) . RESULTS Orthodontic treatment was associated with changes in color parameters . The L∗ values decreased ( P < 0.001 ) , whereas the a∗ and b∗ values increased ( P < 0.001 ) at the end of treatment . All measured types of teeth demonstrated significant color changes ( ΔE ) ; their mean differences ranged from 2.12 to 3.61 ΔE units . Chemically cured resin was associated with greater color changes than light-cured composite . CONCLUSIONS The color of natural teeth is changed in various ways after fixed orthodontic treatment The purpose of this study was to examine the effects of ultrasonic orthodontic bracket removal and cleanup and compare them with conventional debonding and cleaning of the enamel surfaces with burs and polishing disks . The amount of enamel loss and time for bracket removal and clean-up were also addressed . Thirty extracted human premolars were collected . The teeth were r and omly placed in one of the three debonding groups : debonding with orthodontic pliers and enamel clean-up with finishing burs and polishing disks ( group 1 ) , debonding with orthodontic pliers and ultrasonic clean-up of the enamel surface ( group 2 ) , and ultrasonic debonding enamel clean-up ( group 3 ) . The teeth were stored for 48 hours in 100 % humidity before bracket removal . All brackets were then removed . Polyvinyl siloxane impressions were made before and after bracket removal . Direct measurements of the teeth in micrometers were made at all steps . An additional 30 teeth were similarly prepared , and the brackets were debonded and cleaned-up as in the three groups previously described . The total time for bracket removal and enamel clean-up for each group was recorded in seconds . ( ABSTRACT TRUNCATED AT 250 WORDS The purpose of this study was to evaluate enamel colour alteration of five different orthodontic bonding adhesives by means of digital measurements after exposure to photoageing in order to simulate discolouration of adhesives in vivo . Seventy-five non-carious premolars were r and omly divided into five equal groups . The brackets were bonded with five different adhesives ( Transbond XT , Eagle Bond , Light Bond , Blugloo , Unite ) and subjected to artificial accelerated photoageing for 24 hours . The enamel surfaces were colourimetrically evaluated before bonding , following debonding and cleaning with a tungsten carbide bur , after polishing with Stainbuster , and after photoageing of the debonded enamel surface . The Commission Internationale de l'Eclairage(CIE ) colour parameters ( L*a*b * ) were recorded and colour differences ( DeltaE ) were calculated . The results were statistically analyzed using the Kruskall-Wallis test . Further investigation among subgroups was performed using Dunn 's multiple correlation test ( P < 0.05 ) . The clinical detection threshold for DeltaE value was set at 3.7 units . DeltaE values between the first and second measurements showed an increase in the Transbond XT , Eagle Bond , and Light Bond groups . The highest DeltaE value was 1.51 + /- 1.15 in the Transbond XT group . No clinical ly significant DeltaE value was observed . Colour changes of orthodontic bonding systems induced by photoageing can not be clinical ly observed . Polishing with Stainbuster eliminates enamel surface roughness , which may improve light reflection |
12,211 | 16,952,280 | : This analysis demonstrates a positive association between increasing BMI and the presence of GERD within the United States ; this relationship became apparent only after stratification by country and level of BMI . | BACKGROUND : Gastroesophageal reflux disease ( GERD ) is a common cause of morbidity and health-care utilization in many countries . | OBJECTIVES : Gastroesophageal reflux disease can be divided into three categories : nonerosive GERD ( NERD ) , erosive GERD ( ERD ) , and Barrett´s esophagus . A shift among these categories rarely occurs . The aim of the present study was to eluci date potential patient-associated risk factors associated with ERD . METHODS : A total of 6,215 patients with troublesome heartburn were recruited to a large , prospect i ve , multicenter open cohort study comprising an initial treatment phase and a 5-yr follow-up phase . Each center planned to recruit an equal number of patients with NERD and ERD . All patients underwent an interview based on st and ardized question naires , a physical examination , and endoscopy with biopsies . Data were analyzed by multiple logistic regression analysis . RESULTS : Risk factor analysis was performed on 5,289 patients ( NERD : n = 2,834 ; ERD : n = 2,455 ) , which was the intent-to-treat population excluding patients with suspected/proven complicated reflux disease . Stepwise regression analysis identified the following independent predictors of ERD : male gender , overweight , regular use of alcohol , a history of GERD > 1 yr , and smoker or ex-smoker . A higher level of education and a positive Helicobacter pylori ( H. pylori ) status were associated with a lower risk of ERD . CONCLUSIONS : Some patient-associated factors increase the risk of erosive esophagitis as opposed to nonerosive reflux disease . However , no single factor or combination of factors is capable of predicting mucosal damage with clinical ly sufficient certainty . Thus , endoscopy is still required in all GERD patients if valid information on the state of the esophageal mucosa is needed BACKGROUND Limited research has been done to explore differences between ethnic groups , including Hispanic Americans ( HAs ) , in the association between percentage body fat ( PBF ) and body mass index ( BMI ; in kg/m(2 ) ) ; the numbers of HAs are increasing in the US population . OBJECTIVE We investigated whether the relation between PBF and BMI in adult HAs differed from that of African Americans ( AAs ) and European Americans ( EAs ) . DESIGN We used a multiple regression model in which PBF measured with dual energy X-ray absorptiometry was predicted by the reciprocal of BMI ( 1/ BMI ; in m(2)/kg ) in a sample of 487 men ( n(EA ) = 192 , n(AA ) = 148 , and n(HA ) = 147 ) and 933 women ( n(EA ) = 448 , n(AA ) = 304 , and n(HA ) = 181 ) . RESULTS For men , our results showed no significant differences between HAs and EAs , AAs and EAs , or HAs and AAs in the slope of the line relating 1/ BMI to PBF . In women , there were significant differences in PBF as predicted by BMI between HAs and EAs ( P < 0.002 ) and AAs and HAs ( P = 0.020 ) , but not between AAs and EAs . When PBF was estimated on the basis of predicting equations , the trend of the predicted PBF value in women differed according to ethnic group and BMI category . At a BMI < 30 , HAs tended to have more body fat than did EAs and AAs , and at a BMI > 35 , EAs tended to have more body fat than did the other groups . CONCLUSIONS Our results show that the relation between PBF and BMI in HA women differs from that of EA and AA women AIM Gastroesophageal reflux disease ( GERD ) is a common disorder in the Western population , but detailed population -based data in China are limited . The aim of this study was to underst and the epidemiology of symptomatic gastroesophageal reflux ( SGER ) in adults of Xi'an , a northwestern city of China , and to explore the potential risk factors of GERD . METHODS Symptoms suggestive of GERD , functional dyspepsia ( FD ) , irritable bowel syndrome ( IBS ) , upper respiratory diseases and some potential risk factors were investigated in a face-to-face manner in a region-stratified r and om sample s of 2789 residents aged 18 - 70 years in Xi'an by using a st and ardized question naire . METHODS With a response rate of 91.8 % , the prevalence of SGER was 16.98 % ( 95 % CI , 14.2 - 18.92 ) in Xi'an adults , and no gender-related difference was observed ( P<0.05 ) . SGER was more common among subjects aged 30 - 70 years than in those aged 18 - 29 years ( P<0.01 ) . The prevalence of SGER in rural , urban and suburban subjects was 21.07 % , 17.44 % and 12.12 % , respectively , and there was a significant difference between rural , urban and suburban regions ( P<0.05 ) . Compared with subjects without SGER , the prevalence of symptoms suggestive of FD and IBS , pneumonia , asthma , bronchitis , laryngitis , pharyngitis , chronic cough , wheeze , globus sensation , oral ulcer and snore was significantly increased in subjects with SGER ( P<0.01 ) . Heavy smoking ( OR=5.76 ; CI , 3.70 - 6.67 ) , heavy alcohol use ( OR=2.85 ; CI , 1.67 - 4.49 ) , peptic ulcer ( OR=5.76 ; CI , 3.99 - 8.32 ) , cerebral palsy ( OR=3.97 ; CI , 1.97 - 8.00 ) , abdominal operation ( OR=2.69 ; CI , 1.75 - 4.13 ) , obesity ( OR=2.16 ; CI , 1.47 - 3.16 ) , excessive food intake ( OR=1.43 ; CI , 1.17 - 1.15 ) , sweet food ( OR=1.23 ; CI , 0.89 - 1.54 ) , and consumption of coffee ( OR=1.23 ; CI , 0.17 - 2.00 ) were independently associated with SGER . The episodes of GERD were commonly precipitated by dietary factors ( 66.05 % ) , followed by body posture ( 26.54 % ) , ill temper ( 23.72 % ) , fatigue ( 22.32 % ) and stress ( 10.93 % ) . CONCLUSION GERD is common in Xi'an 's adult population with a mild or moderate degree . The etiology and pathogenesis of GERD are probably associated with FD , IBS , and some respiratory , laryngopharyngeal and odontostological diseases or symptoms . Some lifestyles , diseases and dietary factors are the risk factors of GERD BACKGROUND This paper reports the 3-month prevalence rates of gastrointestinal ( GI ) symptoms from the Domestic/International Gastroenterology Surveillance Study ( DIGEST ) , and their relationship with demographic factors ; namely age , gender and body mass index ( BMI ) . METHODS Subjects were recruited from 10 international sites by a total of 5581 face-to-face interviews conducted with r and omly selected members of the general population aged 18 years and over ( 50.6 % female ; mean age 44 years ) . The sample was divided according to whether subjects reported 1 or more of 14 GI symptoms , or no GI symptoms . Those with any of 11 upper GI symptoms were then subdivided according to their most bothersome symptom : gastro-oesophageal reflux (GORD)-like symptoms , ulcer-like symptoms or dysmotility-like symptoms . Symptoms were classified as relevant if they were of at least moderate severity and /or occurred at least once a week . RESULTS A mean of 46.4 % of subjects reported experiencing one or more of the 14 GI symptoms , with 28.1 % experiencing upper GI symptoms classified as relevant . Significant differences between the prevalences of relevant symptoms were evident between sampling sites . The estimated prevalence of GORD-like symptoms for the pooled sample was 7.7 % . For ulcer-like symptoms , prevalence was 4.1 % , and for dysmotility-like symptoms 15.5 % . Significant differences were observed in the prevalence rates of symptom groups between countries . Women were significantly more likely than men to experience relevant symptoms , with gender differences also observed in the rates of GORD-like and dysmotility-like symptoms . The proportion of those with relevant symptoms experiencing GORD-like symptoms increased significantly with age ; ulcer-like symptoms showed no significant relationship with age ; and dysmotility-like symptoms decreased significantly with age . The prevalence of relevant symptoms increased with increasing BMI . CONCLUSIONS In conclusion , the DIGEST has provided valuable data on the cross-country prevalence of upper GI symptoms , and their association with biological factors Abstract A r and omized chemoprevention trial on precancerous lesions of the stomach is being conducted in Tachira State , Venezuela . The aims of the study are to evaluate the efficacy of vitamin supplementation in preventing the progression rate of precancerous lesions . Here we report on the pilot phase of the study in which two antioxidant preparations were evaluated on their ability to raise antioxidant levels in plasma and in gastric juice . The study aim ed also to determine the antibiotic sensitivity profiles of Helicobacter pylori isolates prevalent in the area . Forty-three subjects with precancerous lesions ( chronic gastritis , chronic atrophic gastritis , intestinal metaplasia and dysplasia ) of the stomach were r and omized to one of two antioxidant treatments . Treatment 1 ( 250 mg of st and ard vitamin C , 200 mg of vitamin E and 6 mg of beta-carotene three times a day ) or treatment 2 ( 150 mg of st and ard vitamin C , 500 mg of slow release vitamin C , 75 mg of vitamin E and 15 mg of beta-carotene once a day ) for 7 days . Blood levels of total vitamin C , beta-carotene and alpha-tocopherol and gastric juice levels of ascorbic acid and total vitamin C were measured before and after treatment on day 8 . Both treatments increased the plasma levels of total vitamin C , beta-carotene and alpha-tocopherol/cholesterol but not those of ascorbic acid or total vitamin C in gastric juice . Treatment 1 was the best choice and result ed in a greater increase in the plasma levels of beta-carotene and alpha-tocopherol . H. pylori was cultured from 90 % of the gastric biopsies ; 35 isolates were identified which were highly resistant to metronidazole , a front-line antibiotic recommended against H. pylori in other setting A question naire study was conducted to assess the prevalence and severity of symptoms suggestive of esophageal disorders in a general population . The study included 407 r and omly selected subjects , evenly distributed in terms of sex and age , within the age span of 20 - 79 years . A total of 337 subjects replied ( 85 % ) . Symptoms suggestive of gastroesophageal reflux were found among 25 % of the participants . Cough on swallowing was common ( 27 % ) , as was globus ( 16 % ) and chest pain ( 13 % ) . In addition , dysphagia was reported by 10 % and vomiting by 9 % . The symptoms were usually mild , and moderate to severe symptoms were reported only occasionally ( 1 - 4 % ) . No statistical correlation was found between esophageal symptoms and age , sex , or the reported consumption of tobacco , alcohol , or non-steroidal anti-inflammatory drugs . The frequency of heartburn and /or acid regurgitation was twice as common among those with symptoms of respiratory disease as among those with no respiratory complaints . A stepwise logistic regression analysis showed that a chronic cough and /or breathing difficulties were significantly related to the presence of symptoms suggestive of gastroesophageal reflux We have studied the response of erosive or ulcerative esophagitis to treatment with omeprazole and its subsequent relapse on cessation of therapy in 196 patients . In the first phase of the study omeprazole ( 20 or 40 mg daily ) was compared with placebo in 64 patients . After 4 wk there was endoscopic healing in 81 % ( 25 of 31 ) of omeprazole-treated patients and in only 6 % ( 2 of 32 ) of placebo-treated patients . Endoscopic healing of esophagitis was accompanied by symptom relief and histologic healing of ulceration . In the second ( dose finding ) phase a further 132 patients were r and omized to omeprazole ( 20 or 40 mg daily ) and endoscopic healing was assessed . In patients with the mildest grade of ulcerative esophagitis ( grade 2 ) , healing occurred at 4 wk in 87 % receiving 20 mg and in 97 % receiving 40 mg . In patients with grade 3 esophagitis , 67 % ( 20 mg ) and 88 % ( 40 mg ) were healed . Less than half the patients with grade 4 esophagitis ( Barrett 's ulcers or confluent ulceration ) healed with either 20 mg ( 48 % ) or 40 mg ( 44 % ) . Regression analysis in the 164 omeprazole-treated patients showed no evidence that healing was influenced by factors other than severity of esophagitis at entry and omeprazole dose . In phase 3 of the study the rate of endoscopic relapse was determined in 107 endoscopically healed patients after stopping omeprazole . Erosive or ulcerative esophagitis recurred in 88 of 107 ( 82 % ) by 6 mo . Neither initial dose , grade of esophagitis , nor smoking was shown to influence relapse rate . Omeprazole is a highly effective treatment for peptic esophagitis . The 40-mg/day dosage produces endoscopic healing slightly more quickly than the 20-mg/day dosage , and the initial endoscopic gradings are of prognostic value . Relapse occurs rapidly when treatment is stopped Controlled clinical trials of the treatment of acute myocardial infa rct ion offer a unique opportunity for the study of the potential influence on outcome of bias in treatment assignment . A group of 145 papers was divided into those in which the r and omization process was blinded ( 57 papers ) , those in which it may have been unblinded ( 45 papers ) , and those in which the controls were selected by a nonr and om process ( 43 papers ) . At least one prognostic variable was maldistributed ( P less than 0.05 ) in 14.0 per cent of the blinded-r and omization studies , in 26.7 per cent of the unblinded-r and omization studies , and in 58.1 per cent of the nonr and omized studies . Differences in case-fatality rates between treatment and control groups ( P less than 0.05 ) were found in 8.8 per cent of the blinded-r and omization studies , 24.4 per cent of the unblinded-r and omization studies , and 58.1 per cent of the nonr and omized studies . These data emphasize the importance of keeping those who recruit patients for clinical trials from suspecting which treatment will be assigned to the patient under consideration BACKGROUND There is a widespread notion that obesity leads to gastro-oesophageal reflux but scientific evidence of an association is limited and inconsistent . AIMS To estimate the strength of the association between body mass and reflux symptoms , we performed a population based cross sectional interview study . SUBJECTS Population based , r and omly selected , middle aged or elderly persons in Sweden in 1995 - 1997 . METHODS At face-to-face interviews we asked a stratified sample of Swedes about body measures and occurrence of reflux symptoms . Odds ratios ( OR ) with 95 % confidence intervals ( CI ) , calculated by logistic regression with multivariate adjustments for covariates , were the measures of association . RESULTS Reflux symptoms occurring at least once a week more than five years before the interview were reported by 135 ( 16 % ) of the 820 interviewees . Among those who had ever been overweight during adulthood ( body mass index ( BMI ) > or = 25 kg/m(2 ) ) , the OR of having recurrent reflux symptoms was 0.99 ( 95 % CI 0.66 - 1.47 ) compared with those who were never overweight . There was no association between BMI at age 20 , BMI 20 years before the interview , or maximum adult BMI and occurrence of reflux symptoms : ORs per unit increase in BMI were 1 . 00 ( 95 % CI 0.93 - 1.09 ) , 1.03 ( 95 % CI 0.96 - 1.10 ) , and 1.01 ( 95 % CI=0.95 - 1.07 ) , respectively . There was no association between BMI and severity or duration of reflux symptoms . CONCLUSIONS Gastro-oesophageal reflux symptoms occur independently of body mass index . Weight reduction may not be justifiable as an antireflux therapy Abstract : Compared with findings in Western countries , the prevalence of reflux esophagitis in Oriental countries is estimated to be low . In this prospect i ve study , we aim ed to examine the proportion of reflux esophagitis in Japanese adults , as evaluated by endoscopy . Endoscopists were prospect ively directed to grade esophageal mucosal breaks with esophagitis according to the Los Angeles Classification of Esophagitis in all subjects that underwent endoscopic examination . In total , 6010 subjects underwent endoscopic examination for evaluation of esophagitis grading from December 1996 to February 1998 . The subjects included 4394 out patients who were not receiving medication for gastrointestinal disease and 1616 subjects who visited the hospital for routine physical examinations . The overall proportion of esophagitis was 16.3 % . Most of the subjects with esophagitis were classified as having grade A or B ( proportion of grade s A and B , 9.6 % and 4.6 % , respectively ) . The age-related proportion of esophagitis and of severe esophagitis ( i.e. , grade s C and D ) increased in females aged over 70 and in males aged over 80 . Increased body mass index ( partly due to decreased height caused by osteoporosis ) , and /or hiatal herniation , were related to the proportion of esophagitis in females aged over 70 . These data indicated that reflux esophagitis is a common disease in Japan . However , severe esophagitis ( grade s C and D ) is not common OBJECTIVE To examine the relationship between body mass and gastro-oesophageal reflux in a large population -representative sample from the UK . DESIGN AND SETTING Cross-sectional population -based study , as part of a r and omized controlled trial of eradication of Helicobacter pylori infection , in Southwest Engl and . Subjects In all , 10 537 subjects , aged 20 - 59 years , were recruited from seven general practice s. Subjects provided data on frequency and severity of dyspeptic symptoms and anthropometric measurements were taken . MAIN OUTCOME MEASURE Relationship between overweight ( body mass index [ BMI ] > /=25 kg/m(2 ) and < /=30 kg/m(2 ) ) or obesity ( BMI > 30 kg/m(2 ) ) and frequency and severity of heartburn and acid regurgitation . RESULTS Body mass index was strongly positively related to the frequency of symptoms of gastro-oesophageal reflux . The adjusted odds ratios ( OR ) for frequency of heartburn and acid regurgitation occurring at least once a week in overweight participants compared with those of normal weight were 1.82 ( 95 % CI : 1.33 - 2.50 ) and 1.50 ( 95 % CI : 1.13 - 1.99 ) respectively . Corresponding OR ( 95 % CI ) relating to obese patients were 2.91 ( 95 % CI : 2.07 - 4.08 ) and 2.23 ( 95 % CI : 1.44 - 3.45 ) respectively . The OR for moderate to severe reflux symptoms were raised in overweight and obese subjects but not to the same extent as frequency of symptoms and only the relationship between obesity and severity of heartburn reached conventional statistical significance : OR = 1.19 ; 95 % CI : 1.07 - 1.33 . CONCLUSIONS Being above normal weight substantially increases the likelihood of suffering from heartburn and acid regurgitation and obese people are almost three times as likely to experience these symptoms as those of normal weight In a prospect i ve study in 1224 patients referred for upper alimentary endoscopy , reflux oesophagitis was found in 195 ( 16 % ) of the patients and hiatus hernia in 249 ( 20 % ) . In patients with reflux oesophagitis a coexisting hiatus hernia was found in 68 % . The weight-for-height index ( W/H1.8 ) , which expresses the degree of overweight , was significantly higher both in patients with hiatus hernia and in the patients with reflux oesophagitis , indicating an overweight of approximately 5 % in both groups . The overweight was most pronounced in oesophagitis grade s 1 and 2 , whereas in patients with severe oesophagitis ( grade 3 ) body weight was normal , possibly owing to weight loss caused by dysphagia and excessive regurgitation . The results support the view that adiposity is associated with both sliding hiatus hernia and reflux oesophagitis and that hiatus hernia plays a role in the development of reflux oesophagitis Background : There is widespread belief that obesity is associated with gastro-oesophageal reflux disease , but the scientific evidence is weak and contradictory . Our aim is to evaluate the relation between body mass and reflux oesophagitis . Methods : A population -based case-control study of endoscopically verified case subjects with reflux oesophagitis , and of r and omly selected , control subjects matched for age , sex and area of residence . Subjects were classified within three body mass index ( BMI ) categories : BMI < 25 ( normal in the WHO classification ) , BMI 25 - 30 ( overweight ) and BMI > 30 ( obese ) . Odds ratios ( OR ) with 95 % confidence intervals ( CI ) were the measures of association . Results : Of 179 matched case-control pairs included in the study , 71 pairs were female . In males , no association between overweight and /or obesity and the risk of reflux oesophagitis was found . In females , there was a strong association between increasing BMI and the risk of reflux oesophagitis , with an OR of 2.9 ( 95 % CI : 1.1 - 7.6 ) in the BMI 25 - 30 group and 14.6 ( 95 % CI : 2.6 - 80.9 ) in the BMI > 30 group ( P value for trend = 0.0007 ) . The association between obesity and oesophagitis was further strengthened by the use of oestrogen replacement medication . Conclusions : The study discloses a strong and dose-dependent association between body mass and reflux oesophagitis in women as opposed to no association among men . This association might be caused by increased oestrogen activity in overweight and obese females OBJECTIVE To assess the method ologic quality of approaches used to allocate participants to comparison groups in r and omized controlled trials from one medical specialty . DESIGN Survey of published , parallel group r and omized controlled trials . DATA SOURCES All 206 reports with allocation described as r and omized from the 1990 and 1991 volumes of four journals of obstetrics and gynecology . MAIN OUTCOME MEASURES Direct and indirect measures of the adequacy of r and omization and baseline comparisons . RESULTS Only 32 % of the reports described an adequate method for generating a sequence of r and om numbers , and only 23 % contained information showing that steps had been taken to conceal assignment until the point of treatment allocation . A mere 9 % described both sequence generation and allocation concealment . In reports of trials that had apparently used unrestricted r and omization , the differences in sample sizes between treatment and control groups were much smaller than would be expected due to chance . In reports of trials in which hypothesis tests had been used to compare baseline characteristics , only 2 % of reported test results were statistically significant , lower than the expected rate of 5 % . CONCLUSIONS Proper r and omization is required to generate unbiased comparison groups in controlled trials , yet the reports in these journals usually provided inadequate or unacceptable information on treatment allocation . Additional analyses suggest that nonr and om manipulation of comparison groups and selective reporting of baseline comparisons may have occurred OBJECTIVE We describe the design and report the first results of the Progression of Gastroesophageal Reflux Disease ( ProGERD ) study , to our knowledge the largest prospect i ve study of GERD patients . STUDY DESIGN AND SETTING Patients were recruited at 1,253 centers in Germany , Austria , and Switzerl and . Following an assessment of medical history , all patients were endoscoped and received esomeprazole for 2 to 8 weeks before entering the 5-year observational phase . RESULTS A total of 6,215 patients ( 53 % male , age 54+/-14 ) were included . Of these patients , 46 % reported at least daily symptoms , 15 % were unable to work at least once during the prior year , and 71 % had visited a physician due to reflux symptoms . Barrett 's esophagus ( BE ) was found in 11 % of our GERD patients . In polychotomous regression analysis , the main factors related to the occurrence of the three GERD subgroups ( nonerosive , erosive disease , and BE ) were age , gender , duration of GERD , body mass index ( BMI ) , smoking , and previous PPI use . Factors associated with longer disease duration were increasing age , male gender , BMI , increasing symptom severity , presence of erosive GERD or BE , positive family history , and smoking . CONCLUSION The findings indicate that GERD is a great burden for patients , and has significant socioeconomic implication s. The long-term follow-up period with further endoscopic and histologic evaluations , will help further our underst and ing of the natural course of the disease |
12,212 | 19,640,281 | Results Published data meeting review eligibility criteria were most plentiful for natural history parameters relating to the progression and regression of cervical intraepithelial neoplasia ( CIN ) without HPV typing , and data concerning the natural history of HPV disease due to specific HPV types were often lacking .
Epidemiologic evidence to support age-dependency in the risk of progression and regression of HPV disease was found to be weak , and an alternative hypothesis concerning the time-dependence of transition rates is explored .
No data were found on the duration of immunity following HPV infection .
In the area of clinical management , data were observed to be lacking on the proportion of clinical ly manifest anogenital warts that are treated and the proportion of cervical cancer cases that become symptomatic by stage . | Background Natural history models of human papillomavirus ( HPV ) infection and disease have been used in a number of policy evaluations of technologies to prevent and screen for HPV disease ( e.g. , cervical cancer , anogenital warts ) , sometimes with wide variation in values for epidemiologic and clinical inputs .
The objectives of this study are to : ( 1 ) Provide an up date d critical and systematic review of the evidence base to support epidemiologic and clinical modeling of key HPV disease-related parameters in the context of an HPV multi-type disease transmission model which we have applied within a U.S. population context ; ( 2 ) Identify areas where additional studies are particularly needed . | BACKGROUND Human papillomavirus ( HPV ) has been associated with cervical intraepithelial neoplasia , but the temporal relation between the infection and the neoplasia remains unclear , as does the relative importance of the specific type of HPV , other sexually transmitted diseases , and other risk factors . METHODS We studied prospect ively a cohort of 241 women who presented for evaluation of sexually transmitted disease and had negative cervical cytologic tests . The women were followed every four months with cytologic and colposcopic examinations of the uterine cervix and tests for HPV DNA and other sexually transmitted diseases . RESULTS Cervical intraepithelial neoplasia grade 2 or 3 was confirmed by biopsy in 28 women . On the basis of survival analysis , the cumulative incidence of cervical intraepithelial neoplasia at two years was 28 percent among women with a positive test for HPV and 3 percent among those without detectable HPV DNA : The risk was highest among those with HPV type 16 or 18 infection ( adjusted relative risk as compared with that in women without HPV infection , 11 ; 95 percent confidence interval , 4.6 to 26 ; attributable risk , 52 percent ) . All 24 cases of cervical intraepithelial neoplasia grade 2 or 3 among HPV-positive women were detected within 24 months after the first positive test for HPV . After adjustment for the presence of HPV infection , the development of cervical intraepithelial neoplasia was also associated with younger age at first intercourse , the presence of serum antibodies to Chlamydia trachomatis , the presence of serum antibodies to cytomegalovirus , and cervical infection with Neisseria gonorrhoeae . CONCLUSIONS Cervical intraepithelial neoplasia is a common and apparently early manifestation of cervical infection by HPV , particularly types 16 and 18 Am J Public Health 2000 90:1431–5 A cross-sectional , door-to-door community survey was used to gather self-report data on Pap smear and cholesterol screening from 195 rural Australian individuals r and omly selected from population statistics . Trained interviewers used a st and ard reporting form to collect information on screening results , knowledge of recommended screening frequency , and demographics . The two regional pathology laboratories were queried about consenting patients . Adequate screening was defined as any smear within 2 years . Of 146 women eligible for validation of Pap smears , the sensitivity of a self-report of inadequate screening was 45 % , the specificity was 98 % , the negative predictive value was 72 % , and the positive predictive value was 93 % . For example , 93 % of women who said they had not had a Pap smear in at least 2 years in fact had not , while only 72 % of those who cl aim ed to have had a smear within 2 years actually had . Among 91 women reporting Pap results , more than half of those with abnormalities were missed by self-report . The accuracy of recall was not associated with knowledge or demographic factors . Comment : Although its use of a rural , Australian population limits the ability to generalize the conclusions of the report for the population in the United States , the results of this study are consistent with those of previous ones : women tend to overestimate the frequency of their Pap smears and to minimize their recall of abnormalities . Self-report should not be used in studies of the adequacy of Pap smear screening , and it should not be relied on to determine who is eligible for screening at 3-year intervals by virtue of three prior normal smears . ( LSM Objective : To estimate the incidence and duration of cervical human papillomavirus (HPV)-6 , HPV-11 , HPV-16 , and HPV-18 infections in a population of young American women . Methods : The study population consisted of U.S. women who at baseline were 16 to 23 years of age , reported zero to five lifetime sexual partners , never having been pregnant , and never having had a prior abnormal Papanicolaou test and were enrolled in the placebo arm of a r and omized multicenter clinical trial of a HPV-16 L1 virus-like particle vaccine . Women underwent type-specific endocervical/ectocervical swab HPV DNA testing at ∼6-month intervals for up to 48 months of follow-up . To contribute person-time in the analyses of type-specific HPV incidence , a woman must have had at least three satisfactory swab specimens available and been negative for the relevant HPV type ( HPV-6 , HPV-11 , HPV-16 , or HPV-18 ) on her first two trial swabs . The duration of incident HPV infections was estimated using Kaplan-Meier survival analysis methods . Results : Person-years of exposure ranged by type-specific analysis from 2,645 to 3,188 , with an incidence rate per 100 person-years of 3.6 for HPV-6 , 0.4 for HPV-11 , 5.4 for HPV-16 , and 2.1 for HPV-18 . With censoring at the time of treatment for cervical intraepithelial neoplasia , where done , the mean duration of incident infections was 9.3 , 8.4 , 18.2 , and 16.4 months , respectively , for HPV-6 ( n = 103 ) , HPV-11 ( n = 13 ) , HPV-16 ( n = 142 ) , and HPV-18 ( n = 62 ) . When the duration of HPV infections was truncated at the time of cervical intraepithelial neoplasia detection ( any grade ) , where applicable , mean duration figures were 8.4 , 8.1 , 14.0 , and 15.1 months for HPV-6 , HPV-11 , HPV-16 , and HPV-18 infections , respectively . Conclusions : Previous studies of the mean duration of cervical HPV infection have been based on prevalent infections and /or featured relatively short duration of follow-up . This study tested women for HPV infection over a period of up to 48 months and observed a mean duration of incident HPV-16/HPV-18 infections approximately twice that of HPV-6/HPV-11 . ( Cancer Epidemiol Biomarkers Prev 2007;16(4):709–15 Human papillomavirus ( HPV ) infection causes cervical cancer and genital warts . Young women ( 1106 ) were r and omized to receive one of three formulations of a quadrivalent HPV ( Types 6/11/16/18 ) L1 virus-like particle ( VLP ) vaccine or one of two placebo formulations . The goal was to assess vaccine safety and immunogenicity in baseline HPV 6/11/16 or 18-naïve and previously infected subjects . All three formulations were highly immunogenic . At Month 2 ( postdose 1 ) , among women with vaccine-type antibodies at baseline , vaccine-induced anti-HPV responses were approximately 12- to 26-fold higher than those observed in baseline-naïve women , suggesting an anamnestic response . Following an initial , similar sized decline , anti-HPV responses plateaued and remained stable through end-of- study ( 3.0 years ) . No vaccine-related serious adverse experiences were reported OBJECTIVE : Human papillomavirus ( HPV ) virus-like particle ( VLP ) vaccines have demonstrated effectiveness in preventing persistent HPV infections . Whether protection lasts longer than 18 months and , thus , impacts rates of cervical intraepithelial neoplasia ( CIN ) 2–3 has not yet been established . We present results from an HPV16 L1 VLP vaccine trial through 48 months . METHODS : A total of 2,391 women , aged 16–23 years , participated in a r and omized , double-blind , placebo-controlled trial . Either 40 & mgr;g HPV16 L1 VLP vaccine or placebo was given intramuscularly at day 1 , month 2 , and month 6 . Genital sample s for HPV16 DNA and Pap tests were obtained at day 1 , month 7 , and then 6-monthly through month 48 . Colposcopy and cervical biopsies were performed if clinical ly indicated and at study exit . Serum HPV16 antibody titer was measured by radioimmunoassay . RESULTS : Among 750 placebo recipients in the per protocol population , 12 women developed HPV16-related CIN2–3 ( 6 CIN2 and 6 CIN3 ) . Among 755 vaccine recipients , there were no cases ( vaccine efficacy 100 % , 95 % confidence interval [ CI ] 65–100 % ) . There were 111 cases of persistent HPV16 infection in placebo recipients and 7 cases in vaccine recipients ( vaccine efficacy 94 % , 95 % CI 88–98 % ) . After immunization , HPV16 serum antibody geometric mean titers peaked at month 7 ( 1,519 milli-Merck units [mMU]/mL ) , declined through month 18 ( 202 mMU/mL ) , and remained relatively stable between month 30 and month 48 ( 128–150 mMU/mL ) . CONCLUSION : The vaccine HPV16 L1 VLP provides high-level protection against persistent HPV16 infection and HPV16-related CIN2–3 for at least 3.5 years after immunization . Administration of L1 VLP vaccines targeting HPV16 is likely to reduce risk for cervical cancer . LEVEL OF EVIDENCE : CONTEXT Every year approximately 2 million US women are diagnosed as having a cervical cytological result of atypical squamous cells of undetermined significance ( ASC-US ) . OBJECTIVE To determine the most efficient and cost-effective management strategy for women in the United States diagnosed as having ASC-US . DESIGN AND SETTING Cost-effectiveness analysis of data from clinical trials , prospect i ve studies , and other published literature . A computer-based model was used to compare 4 management strategies for a cytological result of ASC-US : immediate colposcopy ; human papillomavirus ( HPV ) triage , which includes colposcopy if high-risk HPV types are detected ; repeat cytology , which includes follow-up cytology at 6 and 12 months and referral for colposcopy if a repeat abnormal result occurs ; and reclassifying ASC-US as normal in which a cytological result of ASC-US is ignored . Reflex HPV DNA testing uses either residual liquid-based cytological specimens or sample s co-collected at the time of the initial screening for conventional cytology . Another method , referred to as the 2-visit HPV DNA triage , requires a woman with an ASC-US result to return within 1 month to provide another speciman sample . MAIN OUTCOME MEASURES Years of life saved ( YLS ) , quality -adjusted life-years ( QALYs ) , and incremental cost-effectiveness ratios . RESULTS The least costly strategy for biennial screening was to reclassify ASC-US as normal , result ing in a reduction in total cancer incidence of 75 % for conventional cytology and 84 % for liquid-based cytology compared with no screening . The next least costly strategy was HPV DNA testing result ing in a reduction in total cancer incidence of 86 % for conventional cytology and 90 % for liquid-based cytology , followed by immediate colposcopy with a reduction of 87 % and 91 % , respectively . Compared with reflex HPV DNA testing , a strategy of repeat cervical cytology or delayed HPV testing costs more but is less effective . When all strategies were compared simultaneously , varying frequency and type of cytological test , biennial ( vs every 3 years ) liquid-based cytology with reflex HPV testing had a cost of $ 174 200 per YLS . In a similar comparison , liquid-based cytology with reflex HPV testing conducted every 3 years ( vs every 5 years ) had a cost of $ 59 600 per YLS and was more effective and less costly than a strategy of conventional cytology incorporating repeat cytology or immediate colposcopy conducted biennially . CONCLUSION Reflex HPV DNA testing provides the same or greater life expectancy benefits and is more cost-effective than other management strategies for women diagnosed as having ASC-US In a study involving 13 842 women and 113 gynaecologists , liquid-based cytology and HPV testing for detecting cervical cancer were compared . A total of 1334 women were found to be positive for one or both tests and were invited for colposcopy with biopsy . A total of 1031 satisfactory biopsies on 1031 women were thereafter collected using a systematic biopsy protocol , which was r and om in the colposcopically normal-appearing cervix or directed in the abnormal one . In all , 502 women with negative tests were also biopsied . A total of 82 histologic high- grade squamous intraepithelial lesion ( HSIL ) were reported in biopsies , all from the group with one or both tests positive . Sensitivity and specificity to detect histologic HSIL were 59 and 97 % for cytology , and 97 and 92 % for HPV . In total , 14 % of review ed negative cytological preparations associated with histologic HSIL contained no morphologically abnormal cells despite a positive HPV test . This suggested a theoretical limit for cytology sensitivity . HPV viral load analysis of the 1143 HPV-positive sample s showed a direct relationship between abnormal Pap test frequency and HPV viral load . Thus , not only does the HPV testing have a greater sensitivity than cytology but the probability of the latter being positive can also be defined as a function of the associated HPV viral load BACKGROUND More than 2 million U.S. women receive an equivocal cervical cytologic diagnosis ( atypical squamous cells of undetermined significance [ ASCUS ] ) each year . Effective colposcopy triage strategies are needed to identify the minority of women who have clinical ly significant disease while avoiding excessive follow-up evaluation for others . METHODS The ASCUS/LSIL ( i.e. , low- grade squamous intraepithelial lesion ) Triage Study ( ALTS ) is a multicenter , r and omized trial comparing the sensitivity and specificity of the following three management strategies to detect cervical intraepithelial neoplasia grade 3 ( CIN3 ) : 1 ) immediate colposcopy ( considered to be the reference st and ard ) , 2 ) triage to colposcopy based on human papillomavirus ( HPV ) results from Hybrid Capture 2(TM ) ( HC 2 ) and thin-layer cytology results , or 3 ) triage based on cytology results alone . This article summarizes the cross-sectional enrollment results for 3488 women with a referral diagnosis of ASCUS . All statistical tests are two-sided . RESULTS Among participants with ASCUS , the underlying prevalence of histologically confirmed CIN3 was 5.1 % . Sensitivity to detect CIN3 or above by testing for cancer-associated HPV DNA was 96.3 % ( 95 % confidence interval [ CI ] = 91.6 % to 98.8 % ) , with 56.1 % of women referred to colposcopy . Sensitivity of a single repeat cytology specimen with a triage threshold of HSIL or above was 44.1 % ( 95 % CI = 35.6 % to 52.9 % ) , with 6.9 % referred . Sensitivity of a lower cytology triage threshold of ASCUS or above was 85.3 % ( 95 % CI = 78.2 % to 90.8 % ) , with 58.6 % referred . CONCLUSIONS HC 2 testing for cancer-associated HPV DNA is a viable option in the management of women with ASCUS . It has greater sensitivity to detect CIN3 or above and specificity comparable to a single additional cytologic test indicating ASCUS or above CONTEXT Human papillomavirus ( HPV ) DNA testing of women having Papanicolaou ( Pap ) smears showing atypical squamous cells of undetermined significance ( ASCUS ) has clinical usefulness . Whether HPV DNA testing alone is useful in primary screening remains to be determined . OBJECTIVE To determine the accuracy of HPV DNA testing for detecting cervical intraepithelial neoplasia ( CIN ) grade 3 or cancer ( the criterion st and ard ) . DESIGN , SETTING , AND PARTICIPANTS Between December 1997 and October 2000 , 4075 women who attended Planned Parenthood clinics in Washington State were screened simultaneously using thin-layer Pap and HPV DNA testing by a polymerase chain reaction (PCR)-based method and by a liquid-based RNA-DNA hybridization capture with signal amplification assay ( signal amplification ) . Women who were positive for high-risk HPV types , or had Pap results of ASCUS or higher , were considered to have positive screening test results and were referred for colposcopy and biopsy . Additionally , a r and om sample of women with negative screening test results was referred for colposcopy . Based on individual and combined thin-layer Pap , HPV PCR , and HPV signal amplification test results from the screening and the colposcopy visits , 7 colposcopy triage strategies were defined and evaluated . MAIN OUTCOME MEASURE Sensitivity and specificity for detecting cervical lesions grade d CIN 3 or higher for each of the 7 triage strategies . RESULTS The estimated prevalence of CIN 3 or higher was 3.2 % . The sensitivity ( 95 % confidence interval ) of thin-layer Pap ( with a result of > or = ASCUS ) for identifying women with CIN 3 or higher was only 61.3 % ( 48.5%-70.9 % ) compared with 88.2 % ( 78.9%-93.8 % ) for HPV testing by PCR and 90.8 % ( 83.1%-95.8 % ) by signal amplification . Differences in specificities were also observed : 82.4 % ( 81.8%-83.1 % ) for thin-layer Pap ( with a result of > or = ASCUS ) , 78.8 % ( 77.9%-79.7 % ) for PCR , and 72.6 % ( 69.4%-75.0 % ) for signal amplification . Compared with referral for colposcopy of all women with ASCUS or higher , signal amplification testing of women with ASCUS and referral of those with a positive result was about as sensitive ( 61.3 % vs 60.3 % , respectively ) and significantly more specific ( 82.4 % vs 88.9 % , respectively ) . The strategy requiring repeat positive PCR tests on 2 visits had a sensitivity of 84.2 % ( 75.3%-91.0 % ) and a specificity of 86.2 % ( 85.1%-87.3 % ) . All tests were more specific and less sensitive in older ( > or = 30 years ) vs younger women . CONCLUSIONS Testing for HPV has higher sensitivity but lower specificity than thin-layer Pap screening . In some setting s , particularly where screening intervals are long or haphazard , screening for HPV DNA may be a reasonable alternative to cytology-based screening of reproductive-age women A placebo-controlled trial to evaluate the efficacy and the safety of intramuscular injection of interferon-beta has been performed on 37 patients suffering from cervical intraepithelial neoplasia II ( CIN II ) associated with human papillomavirus ( HPV ) infection of the cervix : twenty-two patients were treated with interferon-beta ( 2 x 10(6 ) I.U. daily ) for ten days ; fifteen received placebo ( 2 ml of saline solution daily ) for ten days . Prior to therapy , and at day 70 , 190 , 370 , 550 , 730 after the beginning of treatment , patients were examined by colposcopy and punch biopsies of the cervix . Results showed a progressive amelioration in the interferon-beta treated patients , which was statistically significant at any control station ( 70 , 190 , 370 , 550 , 730 days ) as compared to placebo treatment . Percentages of lesions that regressed , persisted or progressed were 36.4 % , 54.5 % , 9.1 % respectively in the Interferon-beta group , and 0 % , 67.7 % and 33.3 % respectively in the placebo group . Interferon-beta administered intramuscularly has shown to be an efficacious treatment of CIN II ( cervical intraepithelial neoplasia II ) associated with HPV infection , without evident side effects ; it can be used in patients requiring medical treatment with at least one-year monitoring by cervical biopsies or as an adjuvant surgical treatment ( which remains the principal treatment ) in the management of patients suffering from CIN II associated with HPV infection BACKGROUND Underst and ing older adults ' volume and patterns of health service use is fundamental to efforts to improve the quality and efficiency of services . OBJECTIVE To analyze the accuracy of older adults ' self report of health services use and to determine the proportion of care obtained outside a defined urban academic health care system . RESEARCH DESIGN Telephone survey of self-reports vali date d against data routinely archived in an electronic medical record system . SUBJECTS Stratified r and om sample of 422 patients ( > or = 60 years ) who had contact with the health care system at least once in the previous 3 months . MEASURES Self reports of hospitalizations , emergency room visits , physicians visits , extended care visits , and home care visits over the past 12 months , health status , physical activity , and sociodemographics factors . RESULTS The sample population was more likely to report health services use and functional disability than was a community-based sample of older adults ; 67 % of the sample were women , 53.9 % were African American , 71 % were age 65 and over , 38.7 % lived alone , and 24.6 % reported poor financial re sources . Based on data from the electronic medical record , 27.9 % of the sample were hospitalized at least once in the prior 12 months , 54.6 % had at least one emergency room visit , and the mean number of ambulatory visits was 8.1 . Comparing self-report data to the electronic record data , 24.1 % of older adults with a hospitalization in the prior 12 months failed to report the episode ; 28.1 % of those with an emergency room visit failed to report the episode as did 5.2 % of those with an ambulatory care visit . The accuracy of the self reports of volume of these services were also substantially under reported . We were unable to identify any patient characteristics that were highly correlated with inaccuracy . We estimate that approximately 9.5 % of health care costs are accrued outside this urban health care system . CONCLUSIONS These older adults substantially under-report health services use , including hospital episodes over a 12-month period . Reliance on self-reported use data over the prior year to model patterns of health care use among older adults is not supported by these data The aim of our study was to assess the cumulative 5-year diagnoses of CIN2 , CIN3 or invasive cervical cancer ( CIN2 + ) after concurrent screening by high-risk HPV test and Pap smear in a primary screening setting . Four thous and thirty-four women from Eastern Thuringia/Germany were recruited from 1996 to 1998 for baseline screening that included routine cytology , high-risk HPV testing by consensus primer PCR GP5+/6 + and routine colposcopy . After a median of 59 months 3,153 women participated in final screening using identical methods . Women with abnormal cytology or colposcopy or a positive high-risk HPV test at any time during the study period were recalled for expert colposcopy and histologic verification . CIN2 + was detected in 160 women result ing in a cumulative 5-year proportion of 4.4 % ( 95 % CI : 3.7 - 5.0 % ) . Of 3,702 women who were high-risk HPV negative at baseline , 34 ( 1.1 - 95 % CI : 0.7 - 1.4 % ) had either prevalent CIN2 + or developed CIN2 + within the observation period . HPV/cytology double negatives at baseline were at lowest risk for CIN2 + ( 1.0 - 95 % CI : 0.7 - 1.4 % ) compared to screening positives ( 16.8 - 100 % depending on combined test results ) . The 5-year negative predictive value in HPV-/Cyto- women was 99.0 % ( 95 % CI : 98.6 - 99.3 % ) . This suggests that a prolongation of the screening intervals in this group is feasible . However , it should be noted that 1 woman developed a microinvasive carcinoma within the observation period . Moreover , 2 women with prevalent cancer were missed by both tests . The prognostic relevance of concurrent high-risk HPV/cytology screening needs to be verified further by r and omized trials OBJECTIVE The purpose of this study was to determine cervical cancer screening practice s of obstetrician/gynecologists in the US after recent revised guidelines . STUDY DESIGN Question naires were mailed to 355 r and omly selected US obstetrician/gynecologists . Questions were structured as clinical vignettes . RESULTS Question naires were returned by 60 % ( 213/355 ) of recipients ; 185 were eligible . Seventy-four percent would begin screening virginal girls at age 18 . Sixty percent would continue annual screening in a 35-year-old woman with 3 or more normal tests . Frequent screening is common in women after total hysterectomy for symptomatic fibroids and no history of dysplasia , and in 70-year-old women with a 30-year history of previous normal tests . Most ( 82 % ) use liquid-based cytology ; 78 % of female respondents would prefer it for themselves . Most ( 64 % ) would not adopt triennial Pap/HPV DNA screening , although 58 % of women would choose it for themselves . CONCLUSION Most US obstetrician/gynecologists screen low-risk women often and indefinitely , despite national guidelines design ed to minimize screening harms result ing from overtesting The stability over time of serum IgG antibody levels to human papillomavirus type 16 ( HPV-16 ) was determined by comparing the HPV-16 capsid antibody levels in serial serum sample s of an age-stratified r and om sub sample of 1656 primiparous mothers resident in Helsinki who were followed until their second pregnancy , on average 29.5 months later . The correlation between the first and second pregnancy HPV-16 serum antibody levels of the same woman was high , even when > 4 years had elapsed between pregnancies ( r = .822 ) . Between negativity , indeterminate results , or quartiles of positivity , the predictive values for being classified in the same category on both occasions ranged between 42 % and 91 % . Correlation coefficients , predictive values , and kappa coefficients between serial sample s all were comparable with those of repeat analyses of the same sample , indicating that HPV capsid antibody levels are generally stable during several years of follow-up BACKGROUND Self-reported data about the interval since last cancer screening are often used to determine whether individuals are due for periodic screening and to monitor adherence to guidelines for early cancer detection . PURPOSE In a study conducted within the Kaiser Permanente Medical Care Program , we examined the concordance of self-reported information and medical record documentation about recency of and reasons for six procedures for early cancer detection . We also assessed the concordance of population -level estimates of screening rates based on these two sources . METHODS Data were obtained from a mailed question naire or telephone interview completed by 779 men and women . The data from these r and omly selected study participants ( 431 women and 348 men ) , who had been members of the health plan for the previous 5 years , were compared with information obtained from their medical charts . Inter source agreement about whether each procedure was done within the last 2 years was evaluated , with the medical record used as the gold st and ard . To assess the accuracy of patient self-reporting , we also calculated sensitivity , false-positive and false-negative results , and Kappa statistics . RESULTS Concordance between self-reported data and medical record documentation was greater for procedures that generated a test report ( mammogram , Pap smear , fecal occult blood test , and sigmoidoscopy ) than for those generating a physician 's note ( clinical breast examination and digital rectal examination ) . Kappa statistics showed a similar pattern . Sensitivity of self-reported data was more than 90 % for mammogram , clinical breast examination , Pap smear , and fecal occult blood test and nearly 80 % for sigmoidoscopy and digital rectal examination . However , false-positive results were above 40 % , except for fecal occult blood test and sigmoidoscopy . For all six procedures , estimated population -level rates of screening within the past 2 years would have been significantly higher ( P < .0001 ) if self-reported data were used instead of medical record audit data . CONCLUSIONS Self-reported data may overestimate the percentage of the population that has been screened and underestimate the interval since the last cancer detection procedures . IMPLICATION S Such data should be used cautiously for clinical decision making , research , and surveillance activities at both individual and population levels . Also , comparability of data should be considered when population screening rates are evaluated on the basis of different data sources The results of the nationwide , population -based cervical cancer screening programme ( organized by the Finnish Cancer Society since early 1960s ) were analysed to establish the prevalence figures ( and their changes ) for genital human papillomavirus ( HPV ) infections in an unselected Finnish female population ( aged between 20 and 65 years ) screened in Kuopio Province between 1981 and 1989 . During the study period 82,393 women were invited on a regular basis for the mass-screening , and also 4131 women in a risk group . Of these , a total of 63,115 and 3249 women attended , result ing in the attendance rates of 76.6 % and 78.6 % , respectively . As a result of the screening , a total of 509 ( 0.80 % ) of the 63,115 smears were diagnosed as having the cytological changes consistent with HPV infection in the mass screening . The corresponding figures in the risk group screening were 58/3249 ( 1.78 % ) . There was a sharply increasing trend in the prevalence of genital HPV infections from 1981 through 1987 , from 0.04 % to 1.76 % ( ie a 44-fold increase in 7 years ) which , surprisingly , then declined to 1.43 % in 1988 and 1.04 % in 1989 . Based on a r and om sample of 2084 routine ( non-mass-screening ) Pap smears ( out of 28,861 ) collected from the files of our laboratory , the prevalence of HPV infections was stratified by age groups . The highest prevalence ( 6.1 % ) was observed in women aged between 20 and 29 years , followed by 2.2 % in those aged 30–39 years . Using the figures of the relative risk ( RR ) of HPV infections by age , an estimation was made to assess the prevalence of clinical HPV infections in the Finnish female population in general . With the annual number of female births ( approximately 30,000 ) , it was estimated that some 18,000 women aged between 20 and 29 years will harbour a clinical ly manifest genital HPV infection . It is noteworthy that the above established figures do not include any data of the sub clinical and latent HPV infections , not detectable by the Pap smear . Beyond any doubt , genital HPV infections are the most frequent STD in Finl and The purpose of this r and omized , double-blind , placebo-controlled study was to determine the clinical efficacy and tolerability of an analog of imiquimod (2%)in cream to cure genital warts in women . Sixty preselected women , ranging between 18 and 45 years of age ( mean 24.3 ) and having 411 lesions ( mean 6.8 ) with clinical , histopathological and polymerase chain reaction ( PCR ) confirmed diagnosis of human papilloma virus ( HPV ) infection were r and omized to two parallel groups . Each patient received a precoded 40-g tube and instructions on how to apply the trial medication to their lesions at home two times daily for five consecutive days per week . The active treatment period was six weeks . Patients were evaluated on a weekly basis . A clinical ly and PCR established total clearance of target warts was recorded as a cure . By the end of the treatment , 43.3 % of patients and 42.8 % of warts were cured . Code disclosure revealed that imiquimod cream had cured 83.3 % of the treated patients and 84.3 % of the tested warts , while the placebo healed one subject and four warts ( p < 0.0001 ) . Eight patients ( 13.3 % ) in the imiquimod group experienced mild to moderate , non- objective , drug-induced symptoms with no dropouts . Among the 26 cured patients , five had a relapse after 11 months . In conclusion , the data presented demonstrate that 2 % imiquimod in cream with mild to moderate subjective side effects is significantly more effective than placebo in eliminating genital warts in women OBJECTIVE --To determine the efficacy and morbidity of fine loop diathermy excision of the cervical transformation zone as applied to the management of out patients with abnormal cervical smears . DESIGN -- Prospect i ve programme trial with six month follow up . SETTING --Two hospital based colposcopy clinics . PATIENTS --616 Patients aged 16 - 60 with abnormal cervical smears . INTERVENTIONS --After colposcopic and cytological assessment excision of the cervical transformation zone by fine loop diathermy under local anaesthesia in the outpatient department . MAIN OUTCOME MEASURES --Time to complete the treatment , immediate morbidity in terms of discomfort and bleeding , and cytological and colposcopic findings at six months . RESULTS --Treatment was completed in a mean of 3.47 minutes ( SD 1.99 ) . Immediate morbidity was minimal , and histological specimens were adequate in over 90 % of cases . Almost two thirds of patients were treated at their first visit to the clinic . 58 Patients ( 9.4 % ) failed to attend for follow up at six months and one had had a hysterectomy . Of the 557 patients who attended for colposcopic and cytological follow up at six months , 506 ( 91 % ) were normal cytologically and 19 ( 3.4 % ) had histologically confirmed persistence of cervical intraepithelial neoplasia . The overall confirmed failure rate of the technique was 4.4 % . CONCLUSION --Loop diathermy excision is an effective treatment with low morbidity and is an appropriate modality for patients with abnormal cervical smears A total of 532 women with established cervical HPV infection have been prospect ively followed ( without treatment ) since 1981 for a mean of 45 ( SD 21 ) months . The patients were examined by colposcopy , PAP smears and /or punch biopsy every 6 months . The life-table method was applied to analyze the clinical course ( i.e. regression and progression ) of the HPV lesions , stratified by their colposcopic pattern , PAP smear findings and grade of CIN . During the follow-up , 107 ( 41.8 % ) of 256 patients with HPV-NCIN lesion in the first punch biopsy , experienced spontaneous regression . The corresponding proportions for HPV-CIN I , HPV-CIN II and HPV-CIN III lesions were 31.1%,34.2 % , and 20.7 % , respectively . In the overall comparison between these four groups , the heterogeneity in the probability of regression was statistically significant ( p = 0.0005 ) . Clinical progression was also associated significantly with the histological grade of the lesions in the first biopsy . Progression rate was only 5.8 % for HPV-NCIN lesions , as compared to 12.3 % for HPV-CIN I , 20 % for HPV-CIN II , and 55.2 % for HPV-CIN III . The probability of progression varied significantly between the four groups ( p < 0.00001 ) . Cumulative proportion of regression was 46 % for patients with PAP smear class I , 84 % with class II , and 82 % for those with class III , cells , i.e. PAP smear was not of value in predicting the regression . However , PAP smears predicted clinical progression ( p = 0.006 overall ) . Cumulative proportion of progression was low ( 18 % ) for lesions with normal colposcopic pattern on first clinical examination , as contrasted to 45 % and 53 % for those with mosaic and punctation , respectively ( overall , p = 0.101 ) . These data confirm the previous concepts on HPV-CIN as true precancer lesions with a definite potential for clinical progression . The value of histologic grade and , to lesser extent , the PAP smear findings as prognostic factors is emphasized The objective of this study was to assess and compare the relative accuracy of cl aims data and patient self-reported information with medical records for Pap smear rates . A retrospective analysis of information obtainedfrom administrative cl aims files , patient medical records , and a telephone survey was performed of 400 women age 19 through 75years who were r and omly selectedfor participation in the study . The data were obtained from a large multispecialty group practice in Minneapolis , Minnesota for the study years 1991 through 1993 . Information from administrative cl aims regarding Pap smear status corresponded highly with information in the medical record ( sensitivity 95 % or higher ; specificity 95 % or higher ; kappa 0.896 or better ) . Self-reported information from the telephone survey did not correspond well with medical record information nor with results in administrative cl aims BACKGROUND A r and omised double-blind placebo-controlled phase II study was done to assess the efficacy of a prophylactic quadrivalent vaccine targeting the human papillomavirus ( HPV ) types associated with 70 % of cervical cancers ( types 16 and 18 ) and with 90 % of genital warts ( types 6 and 11 ) . METHODS 277 young women ( mean age 20.2 years [ SD 1.7 ] ) were r and omly assigned to quadrivalent HPV ( 20 microg type 6 , 40 microg type 11 , 40 microg type 16 , and 20 microg type 18 ) L1 virus-like-particle ( VLP ) vaccine and 275 ( mean age 20.0 years [ 1.7 ] ) to one of two placebo preparations at day 1 , month 2 , and month 6 . For 36 months , participants underwent regular gynaecological examinations , cervicovaginal sampling for HPV DNA , testing for serum antibodies to HPV , and Pap testing . The primary endpoint was the combined incidence of infection with HPV 6 , 11 , 16 , or 18 , or cervical or external genital disease ( ie , persistent HPV infection , HPV detection at the last recorded visit , cervical intraepithelial neoplasia , cervical cancer , or external genital lesions caused by the HPV types in the vaccine ) . Main analyses were done per protocol . FINDINGS Combined incidence of persistent infection or disease with HPV 6 , 11 , 16 , or 18 fell by 90 % ( 95 % CI 71 - 97 , p<0.0001 ) in those assigned vaccine compared with those assigned placebo . INTERPRETATION A vaccine targeting HPV types 6 , 11 , 16 , 18 could substantially reduce the acquisition of infection and clinical disease caused by common HPV types BACKGROUND Approximately 20 percent of adults become infected with human papillomavirus type 16 ( HPV-16 ) . Although most infections are benign , some progress to anogenital cancer . A vaccine that reduces the incidence of HPV-16 infection may provide important public health benefits . METHODS In this double-blind study , we r and omly assigned 2392 young women ( defined as females 16 to 23 years of age ) to receive three doses of placebo or HPV-16 virus-like-particle vaccine ( 40 microg per dose ) , given at day 0 , month 2 , and month 6 . Genital sample s to test for HPV-16 DNA were obtained at enrollment , one month after the third vaccination , and every six months thereafter . Women were referred for colposcopy according to a protocol . Biopsy tissue was evaluated for cervical intraepithelial neoplasia and analyzed for HPV-16 DNA with use of the polymerase chain reaction . The primary end point was persistent HPV-16 infection , defined as the detection of HPV-16 DNA in sample s obtained at two or more visits . The primary analysis was limited to women who were negative for HPV-16 DNA and HPV-16 antibodies at enrollment and HPV-16 DNA at month 7 . RESULTS The women were followed for a median of 17.4 months after completing the vaccination regimen . The incidence of persistent HPV-16 infection was 3.8 per 100 woman-years at risk in the placebo group and 0 per 100 woman-years at risk in the vaccine group ( 100 percent efficacy ; 95 percent confidence interval , 90 to 100 ; P<0.001 ) . All nine cases of HPV-16-related cervical intraepithelial neoplasia occurred among the placebo recipients . CONCLUSIONS Administration of this HPV-16 vaccine reduced the incidence of both HPV-16 infection and HPV-16-related cervical intraepithelial neoplasia . Immunizing HPV-16-negative women may eventually reduce the incidence of cervical cancer Recently , conflicting results on human papillomavirus ( HPV ) clearance have been reported and the data on the accumulation of incident HPV infections are still fragmentary . Thus , we completed an analysis of the age-specific incidence and clearance rates of high-risk ( HR ) HPV infectionsin 448 women participating in a multi-centre screening study in three New Independent States countries . At baseline , 239 of the 448 women were negative for HR HPV DNA , whereas 209 were HR HPV-positive and cleared HR HPV during the prospect i ve follow-up . The cumulative incidence and clearanceof HR HPV were modelled using life-table techniques . The monthly incidence rates of HR HPV were significantly age-dependent ( P = 0.0001 ) , whereas monthly clearance rates remained constant across the nine age groups ( P = 0.920 ) . The incidence rates ( 3.04 % and 2.65 % ) exceeded theclearance rates in the two youngest age groups only , 15–20- and 21–25-year-old women , and remained lower ( 0–0.84 % ) in all other age groups . The cumulative rate of incident HR HPV infections ( 1.0 % ) was significantly lower than the overall clearance rate ( 1.9 % ) ( P = 0.001 ) . In life-table analysis , incident HR HPV infections between the nine age groups were significantly different ( P = 0.0001 ) , while cumulative HR HPV clearance was identical in all groups ( P = 0.822 ) . The accumulation of incident HR HPV infections is significantly age-related , whereas virus clearance remains constant between 15 and 60 years of age . These distinct age-specific incidence and clearance rates explain the differences in age-specific prevalence of HR HPV infections in the study population OBJECTIVE : The human leukocyte antigen (HLA)-DRB1 * 13 allele frequency is lower in women with cervical carcinoma than in the general population , suggesting that this allele could exert a protective effect against progression of cervical intraepithelial neoplasia ( CIN ) associated with human papillomaviruses ( HPV ) . To test this hypothesis , we design ed a prospect i ve study of low- grade CIN ( CIN1 ) and analyzed the probability of regression of these lesions according to HLA-DR and HPV status . METHODS : The study sample was composed of 86 women with CIN1 who agreed to regular colposcopic follow-up and no immediate treatment . Biopsy specimens were taken under colposcopy for histology and for the determination of HPV and HLA status . Cases were classified into 3 groups : CIN1 regression , persistence for at least 12 months , or progression to CIN2 or 3 . RESULTS : The rate of spontaneous regression ( 95 % confidence interval ) at 24 months was 51.6 % ( 39–61.6 % ) overall compared with 34.7 % ( 13.4–50.8 % ) in HPV16/18 positive cases and 59.9 % ( 43.7–71.4 % ) in HPV16/18-negative cases ( P = .051 ) . The rate of regression was 71.8 % ( 40.8–86.5 % ) in patients with HLA-DRB1 * 13 and 45.9 % ( 31.5–57.2 % ) in patients with other genotypes ( P = .03 ) . Regression reached 90.5 % ( 38.9–98.5 % ) at 18 months in DRB1 * 13 patients with HPV16/18-negative – associated CIN ( 15.1 % of the cases ) . In multivariable analysis , HLA-DRB1 * 13 allele and HPV16/18-negative status were independently associated with an increased probability for regression ( adjusted hazard ratio 2.1 [ 1.0–4.1 ] and 2.5 [ 1.2–5.4 ] , respectively ) . CONCLUSION : A subset of approximately 15 % of CIN1 highly likely to show spontaneous regression can be defined using 2 biologic parameters that characterize the viral causative agent and the host . LEVEL OF EVIDENCE : BACKGROUND Vaccination against the most common oncogenic human papillomavirus ( HPV ) types , HPV-16 and HPV-18 , could prevent development of up to 70 % of cervical cancers worldwide . We did a r and omised , double-blind , controlled trial to assess the efficacy , safety , and immunogenicity of a bivalent HPV-16/18 L1 virus-like particle vaccine for the prevention of incident and persistent infection with these two virus types , associated cervical cytological abnormalities , and precancerous lesions . METHODS We r and omised 1113 women between 15 - 25 years of age to receive three doses of either the vaccine formulated with AS04 adjuvant or placebo on a 0 month , 1 month , and 6 month schedule in North America and Brazil . Women were assessed for HPV infection by cervical cytology and self-obtained cervicovaginal sample s for up to 27 months , and for vaccine safety and immunogenicity . FINDINGS In the according-to- protocol analyses , vaccine efficacy was 91.6 % ( 95 % CI 64.5 - 98.0 ) against incident infection and 100 % against persistent infection ( 47.0 - 100 ) with HPV-16/18 . In the intention-to-treat analyses , vaccine efficacy was 95.1 % ( 63.5 - 99.3 ) against persistent cervical infection with HPV-16/18 and 92.9 % ( 70.0 - 98.3 ) against cytological abnormalities associated with HPV-16/18 infection . The vaccine was generally safe , well tolerated , and highly immunogenic . INTERPRETATION The bivalent HPV vaccine was efficacious in prevention of incident and persistent cervical infections with HPV-16 and HPV-18 , and associated cytological abnormalities and lesions . Vaccination against such infections could substantially reduce incidence of cervical cancer Objective To determine the effect of directed punch biopsy trauma on the natural history of atypical cervical transformation zones |
12,213 | 23,210,006 | In the few r and omized trials that met our inclusion criteria , the use of rt-PA as a locking solution for hemodialysis catheters seems to be associated with fewer adverse events and catheter malfunctioning as compared with heparin . | BACKGROUND AND OBJECTIVES Hemodialysis catheters are commonly used when renal replacement therapy is initiated .
These catheters have significant complications .
Among " locking " solutions used in an attempt to decrease these complications is recombinant tissue plasminogen activator ( rt-PA ) .
This systematic review is to determine the efficacy of rt-PA versus heparin , the st and ard of care . | PURPOSE Alteplase is approved for use in the restoration of function to occluded central venous access devices ( CVADs ) ; however , there are few prospect i ve studies in children . This study was undertaken to evaluate the safety and efficacy of alteplase in the treatment of CVAD occlusions in a pediatric population . MATERIAL S AND METHODS A prospect i ve , multicenter , open-label , single-arm study evaluating a maximum of two doses ( < or = 2 mg per dose ) of alteplase was performed in pediatric patients . Inclusion criteria included patient age less than 17 years with an occluded CVAD ( single- , double- , and triple-lumen catheter or implanted port ) . Patients with hemodialysis catheters , those with known mechanical occlusion , or those considered at high risk for bleeding or embolization were excluded . Assessment of function was made 30 and 120 minutes ( if required ) after each dose . The primary objective of the study was to evaluate the safety of alteplase as measured by the incidence of intracranial hemorrhage ( ICH ) ; secondary objectives included the evaluation of specific targeted serious adverse events and efficacy of alteplase in the restoration of catheter function . RESULTS A total of 310 patients ( 174 male patients , 136 female patients ; mean age , 7.2 years ; range , 0.04 - 18.3 y ) were treated ; 55 of the patients ( 17.7 % ) were younger than 2 years of age . No patients experienced ICH ( 95 % CI , 0%-1.2 % ) . Nine serious adverse events were noted in eight patients ( 2.6 % incidence ) , two of which were attributed by the investigator to study drug administration ( one case of sepsis and one case of a ruptured catheter lumen ) . The cumulative rate of restoration of CVAD function after serial administration of a maximum of two instillations of alteplase , each with a maximum dwell time of 120 minutes , was 82.9 % ( 95 % CI , 78.2%-86.9 % ) . Similar rates of catheter function restoration were seen among all catheter types studied ; there were no clinical ly meaningful differences among age or sex subgroups . CONCLUSION The administration of alteplase is safe and effective for the restoration of function to CVADs in pediatric patients BACKGROUND Sodium citrate has antibacterial and anticoagulant properties that are confined to the catheter when used as a catheter lock . Studies of its use as a catheter lock have suggested its efficacy in preventing infection and bleeding complications compared with sodium heparin . STUDY DESIGN Open-label r and omized controlled trial of 2 catheter locks to examine the hypothesis that sodium citrate catheter locks will reduce catheter-related bacteremia and exit-site infection . SETTING S & PARTICIPANTS 232 consenting long-term hemodialysis patients in 4 satellite dialysis units to a large dialysis program with protocol ized treatment and targets . All patients were using twin-catheter single-lumen Tesio-Caths ( MedComp , Harleysville , PA ) . INTERVENTION 6 months ' use of 46.7 % sodium citrate ( citrate ) or 5 % heparin ( heparin ) locked postdialysis in the dead space of the central venous catheter . OUTCOMES & MEASUREMENTS Primary end point of catheter-related bacteremia and exit-site infection . Secondary end points of catheter thrombosis defined by the use of urokinase lock and infusion , new catheter insertion , catheter-related admission , blood transfusions , parenteral iron , and erythropoietin requirements . RESULTS Catheter-related bacteremia did not differ in the 2 groups , with an incidence of 0.7 events/1,000 catheter-days . There was no significant difference in rates of exit-site infection ( 0.7 versus 0.5 events/1,000 catheter-days ; P = 0.5 ) . The secondary end point of catheter thrombosis defined by the use of a urokinase lock was significantly more common in the citrate group , with an incidence of 8 versus 4.3/1,000 catheter-days ( P < 0.001 ) . Other secondary end points did not differ . Citrate treatment was curtailed compared with heparin because of a greater incidence of adverse events , with a mean treatment duration before withdrawal of 4.8 + /- 2.0 versus 5.7 + /- 1.2 months , respectively ( P < 0.001 ) . LIMITATIONS Low baseline catheter-related bacteremia and exit-site infection event rates may have underpowered this study . High adverse-event rates may have been related to high-concentration citrate that led to increased overspill and reduction in lock volume . This may also explain the increased rates of thrombosis in this group . CONCLUSION Widespread and long-term use of 46.7 % citrate catheter locks with Tesio-Cath access is not justified by this study The most effective and safe method of maintaining peripheral intravenous lock in children is an important clinical question that has been identified by the research ers . The results of recent studies comparing saline versus 10 units/ml of heparin saline flush using a 24-gauge catheter in neonatal and pediatric population s are conflicting and inconclusive . The objectives of this study were to evaluate the effectiveness and safety of three flush solutions : normal saline , 1 unit/ml of heparin saline and 10 units/ml of heparin saline for maintaining peripheral intravenous locks in children , and to establish a research -based practice in the study hospital . In a prospect i ve , r and omized controlled , double-blind trial , one hundred and twenty-three subjects ranging in age from 1 - 10 years with 123 intravenous locks were r and omly chosen to receive 1 unit/ml of heparin saline , 10 units/ml of heparin saline and normal saline to evaluate length of catheter use , survival rate and incidence of intravenous complications . The study found no statistically significant differences in length of catheter use , estimated catheter survival and the incidence of intravenous complications among the three groups . The group that received 1 unit/ml of heparin saline demonstrated the highest rate of survival . The mean length of catheter use of the group that received 1 unit/ml of heparin saline ( 49.8 hours ) was 17 hours longer than the group that received normal saline ( 32.5 hours ) . There are no significant differences among the three types of flushing solution in terms of the catheter longevity and incidence of intravenous complications From January 1986 to December 1990 we studied angiographically the subclavian-brachiocephalic vein of 100 patients dialysed by subclavian catheter for 50 ( first group ) and by internal jugular catheter for the 50 others ( second group ) . These two groups were not statistically different as regards age ( 61.6 + /- 11.3 years in the first and 61 + /- 11.1 in the second ) , sex ( 48 % and 56 % were women ) , duration of catheter insertion ( 31 + /- 21.8 and 31.7 + /- 16 days ) , and the number of dialysis sessions ( 13.5 + /- 9.1 and 13.6 + /- 7.1 ) . The type of catheters , the frequency of removal for poor flow ( 16 % in both groups ) or infections ( 6 % in both groups ) , and the local nursing were similar in the two groups . The only difference was the side of cannulation : the right side in 58 % of cases in group 1 and 78 % in group 2 . The angiographic study revealed a stenosis of the vein in 42 % of the subclavian group and in 10 % of the internal jugular group : a dramatic difference in favour of the internal jugular route , whose superiority over the subclavian route is asserted in respect of venous access of dialysed patients Soft , cuffed , implantable central venous catheters such as the Quinton Permcath ( Quinton Instrument Co , Seattle , WA ) are increasingly used as permanent access in patients with end-stage renal disease . Their major limitations , besides infection , are thrombosis and inadequate blood flow . To prevent those complications , heparin is conventionally used for priming the Quinton Permcath between dialysis sessions . In this study , we compared recombinant tissue plasminogen activator ( rTPA ) with heparin for priming the Quinton Permcath in a prospect i ve , r and omized , crossover design . Twelve patients were r and omly assigned to receive 2,000 IU of heparin or 2 mg of rTPA injected into each catheter lumen at the end of each dialysis session over a period of 4 months , followed by a switch to the other substance . Blood flow rate ( flow ) , venous pressure ( VP ) , and arterial pressure ( AP ) were monitored at each dialysis session hourly . Flow was significantly greater ( P = 0.0001 ) with rTPA ( mean + /- SD , 237.7 + /- 18.1 and 231.6 + /- 12.4 mL/min for the first and second 2 months , respectively ) compared with heparin ( 208.5 + /- 10.1 and 206.9 + /- 14.2 mL/min for the first and second 2 months , respectively ) . VP was significantly less ( P = 0.0001 ) with rTPA ( 135.4 + /- 8.2 and 140 + /- 15.2 mm Hg for the first and second 2 months , respectively ) compared with heparin ( 160.5 + /- 16.1 and 159.2 + /- 20.7 mm Hg for the first and second 2 months , respectively ) . AP was significantly greater ( P = 0.0002 ) with rTPA ( -113.5 + /- 11.8 and -115.9 + /- 12.7 mm Hg for the first and second 2 months , respectively ) compared with heparin ( -136.5 + /- 23.3 and -134.7 + /- 25.8 mm Hg for the first and second 2 months , respectively ) . In addition , fewer complications ( flow problems , clotting , and need for fibrinolysis ) occurred in the rTPA period . These results show that rTPA is superior to heparin for priming the Quinton Permcath between hemodialysis sessions and can be used as a valuable alternative to conventional heparin in selected patients BACKGROUND Microinflammation is linked to cardiovascular disease , and is highly prevalent in dialysis patients . It is logical to postulate that septicemia , a common macroinflammatory occurrence in dialysis patients , contributes to their large burden of cardiovascular disease . METHODS The Dialysis Morbidity and Mortality Wave 2 was a r and omly selected prospect i ve cohort of incident dialysis patients . Admission cl aims data were used to define and calculate rates of septicemia or bacteremia and cardiovascular events in those with Medicare as the primary payer . Utilizing Cox proportional hazard models we determined the association between baseline access and the development of bacteremia or sepsis , and also the association between bacteremia or sepsis episodes and subsequent cardiovascular events . RESULTS The 2358 ( 59 % ) patients with Medicare as primary payer were older and more likely to have heart failure than those with other payers , but had similar comorbidity-adjusted mortality hazards . Rates of first septicemia , bacteremia , or either condition , were 7.0 , 5.9 and 10.4 events per 100-patient years , respectively . Cox regression identified initial dialysis access as the main antecedent of septicemia or bacteremia . Hazards ratios for hemodialysis with permanent catheters , temporary catheters , and grafts were 1.95 ( 95 % CI 1.47 - 2.57 ) , 1.76 ( 95 % CI 1.29 - 2.41 ) , and 1.05 ( 95 % CI 0.82 - 1.35 ) , respectively , while that for peritoneal dialysis was 0.96 ( 95 % CI 0.75 - 1.23 ) ( reference arteriovenous fistula ) . After adjustment for baseline factors , septicemia or bacteremia , as a time-dependent covariate , was associated with subsequent death [ hazards ratio ( HR ) 2.33 , 95 % CI 1.38 - 2.28 ] , myocardial infa rct ion ( HR 1.78 , 95 % CI 1.38 - 2.28 ) , heart failure ( HR 1.64 , 95 % CI 1.39 - 1.95 ) , peripheral vascular disease ( HR 1.64 , 95 % CI 1.34 - 2.0 ) , and stroke ( HR 2.04 , 95 % CI 1.27 - 3.28 ) . CONCLUSION Septicemia appears to be an important , potentially preventable , cardiovascular risk factor in dialysis patients Tinzaparin offers some advantages over unfractionated heparin ( UFH ) for hemodialysis circuit anticoagulation . No study has compared these two molecules as hemodialysis catheter locks . This study aim ed to compare the efficacy of tinzaparin and UFH as locks for hemodialysis tunnelled central venous catheter in patients with end-stage renal disease ( ESRD ) . A r and omized , prospect i ve , single-blinded , controlled study was undertaken . Patients were r and omly assigned to receive UFH and tinzaparin for two 7-week periods in a crossover fashion . The doses used were 5,000 U of UFH and 2,000 U of tinzaparin per catheter line . The primary outcome was the need for thrombolytic catheter lock use defined with the Hemodialysis Unit alteplase protocol . Forty-two patients with ESRD were enrolled , totalling 815 UFH lock sessions and 729 tinzaparin lock sessions . A 47.4 % reduction in the incidence of alteplase lock use was observed with tinzaparin lock ( 3.16 % vs. 6.01 % , chi-square , p = 0.0078 ) . There was no significant difference in the time to first alteplase use between the two locks by Kaplan-Meier survival analysis ( logrank , p = 0.0900 ) . Our results suggest that tinzaparin could be an appropriate alternative for a hemodialysis tunnelled central venous catheter lock , but these results should be confirmed with a larger trial BACKGROUND AND OBJECTIVES Despite widespread use of tunneled hemodialysis ( HD ) catheters , their utility is limited by the development of thrombotic complications . To address this problem , this study investigated whether the thrombolytic agent tenecteplase can restore blood flow rates ( BFRs ) in dysfunctional HD catheters . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS In this r and omized , double-blind study , patients with dysfunctional tunneled HD catheters , defined as a BFR < 300 ml/min at -250 mmHg pressure in the arterial line , received 1-hour intracatheter dwell with tenecteplase ( 2 mg ) or placebo . The primary endpoint was the percentage of patients with BFR > or = 300 ml/min and an increase of > or = 25 ml/min above baseline 30 minutes before and at the end of HD . Safety endpoints included the incidence of hemorrhagic , thrombotic , and infectious complications . RESULTS Eligible patients ( n = 149 ) were treated with tenecteplase ( n = 74 ) or placebo ( n = 75 ) . Mean baseline BFR was similar for the tenecteplase and placebo groups at 151 and 137 ml/min , respectively . After a 1-hour dwell , 22 % of patients in the tenecteplase group had functional catheters compared with 5 % among placebo controls ( P = 0.004 ) . At the end of dialysis , mean change in BFR was 47 ml/min in the tenecteplase group versus 12 ml/min in the placebo group ( P = 0.008 ) . Four catheter-related bloodstream infections ( one tenecteplase , three placebo ) and one thrombosis ( tenecteplase ) were observed . There were no reports of intracranial hemorrhage , major bleeding , embolic events , or catheter-related complications . CONCLUSIONS Tenecteplase improved HD catheter function and had a favorable safety profile compared with placebo BACKGROUND Uncuffed , nontunneled hemodialysis catheters remain the preferred means to gain immediate access to the circulation for hemodialysis . Bacteremia is the primary complication that limits their use . The risk of bacteremia by site of insertion and duration of use has not been well studied . METHODS Two hundred eighteen consecutive patients who required a temporary hemodialysis catheter were prospect ively followed . RESULTS Catheters were placed at 318 new insertion sites and remained in use for a total of 6235 days . The incidence of bacteremia was 5.4 % after three weeks of placement in internal jugular vein and 10.7 % after one week in femoral vein [ relative risk for bacteremia 3.1 ( 95 % CI , 1.8 to 5.2 ) ] . The incidence of bacteremia was 1.9 % one day after the onset of an exit site infection but increased to 13.4 % by the second day if the catheter was not removed . Guidewire exchange for malfunction and patient factors did not significantly affect the risk of bacteremia . CONCLUSIONS Internal jugular catheters may be left in place for up to three weeks without a high risk of bacteremia , but femoral catheters in bed-bound patients should be removed after one week . Catheter exchanges over a guidewire for catheter malfunction do not increase bacteremia rates . Temporary catheters should be removed immediately if an exit site infection occurs Objectives : To determine whether the tissue plasminogen activator , alteplase , is more effective than heparin in preventing blood clots developing in children ’s haemodialysis central lines between dialysis sessions . Design : A prospect i ve double-blind , within-patient multiperiod cross-over controlled trial of instilling a “ lock ” of either heparin 5000 U/ml or alteplase 1 mg/ml into the central lines of two children haemodialysed twice weekly , and seven dialysed thrice weekly , over 10 weeks . Setting : A UK paediatric nephrology unit . Main outcome measures : Weight of blood clot aspirated from the line at the start of the next dialysis session . Results : The odds of a clot forming was 2.4 times greater with heparin than alteplase ( 95 % CI 1.4 to 4.0 ; p = 0.001 ) , and when present they were 1.9 times heavier ( 31 vs 15 mg ; 95 % CI 1.5 to 2.4 ; p<0.0005 ) . There was no effect of inter-dialytic interval . One child required an alteplase infusion to clear a blocked line following a heparin lock . We subsequently changed our routine locks from heparin to alteplase . Comparing the year before and after that change , the incidence of blocked lines requiring an alteplase or urokinase infusion fell from 2.7 to 1.2 per child ( p<0.03 ) , and the need for surgical replacements from 0.7 to nil ( p<0.02 ) . Conclusion : Alteplase is significantly more effective than heparin in preventing clot formation in central haemodialysis lines . This reduces morbidity and improves preservation of central venous access . It is more expensive , though relatively economic if packaged into syringes and stored frozen until needed , but reduces the costs of unblocking or replacing clotted lines |
12,214 | 23,462,705 | Tumour location ( central versus peripheral ) did not impact overall survival .
Grade 3 or 4 toxicities may be more common following SABR for central tumours , but occurred in less than 9 % of patients .
Post-SABR survival for early-stage NSCLC is not affected by tumour location .
SABR achieves high local control with limited toxicity when appropriate fractionation schedules are used for central tumours | BACKGROUND AND PURPOSE Stereotactic ablative radiotherapy ( SABR ) has improved the survival for medically inoperable patients with peripheral early-stage non-small cell lung cancer ( NSCLC ) .
We performed a systematic review of outcomes for central lung tumours . | Background A phase III multi-centre r and omised trial ( ROSEL ) has been initiated to establish the role of stereotactic radiotherapy in patients with operable stage IA lung cancer . Due to rapid changes in radiotherapy technology and evolving techniques for image-guided delivery , guidelines had to be developed in order to ensure uniformity in implementation of stereotactic radiotherapy in this multi-centre study . Methods / Design A Quality Assurance Working Party was formed by radiation oncologists and clinical physicists from both academic as well as non-academic hospitals that had already implemented stereotactic radiotherapy for lung cancer . A literature survey was conducted and consensus meetings were held in which both the knowledge from the literature and clinical experience were pooled . In addition , a planning study was performed in 26 stage I patients , of which 22 were stage 1A , in order to develop and evaluate the planning guidelines . Plans were optimised according to parameters adopted from RTOG trials using both an algorithm with a simple homogeneity correction ( Type A ) and a more advanced algorithm ( Type B ) . Dose conformity requirements were then formulated based on these results . Conclusion Based on current literature and expert experience , guidelines were formulated for this phase III study of stereotactic radiotherapy versus surgery . These guidelines can serve to facilitate the design of future multi-centre clinical trials of stereotactic radiotherapy in other patient groups and aid a more uniform implementation of this technique outside clinical trials PURPOSE To present the results of stereotactic body radiotherapy ( SBRT ) for medically inoperable patients with Stage I non-small-cell lung cancer ( NSCLC ) and contrast outcomes in patients with and without a pathologic diagnosis . METHODS AND MATERIAL S Between December 2004 and October 2008 , 108 patients ( 114 tumors ) underwent treatment according to the prospect i ve research ethics board-approved SBRT protocol s at our cancer center . Of the 108 patients , 88 ( 81.5 % ) had undergone pretreatment whole-body [18F]-fluorodeoxyglucose positron emission tomography/computed tomography . A pathologic diagnosis was unavailable for 33 ( 28.9 % ) of the 114 lesions . The SBRT schedules included 48 Gy in 4 fractions or 54 - 60 Gy in 3 fractions for peripheral lesions and 50 - 60 Gy in 8 - 10 fractions for central lesions . Toxicity and radiologic response were assessed at the 3 - 6-month follow-up visits using conventional criteria . RESULTS The mean tumor diameter was 2.4-cm ( range , 0.9 - 5.7 ) . The median follow-up was 19.1 months ( range , 1 - 55.7 ) . The estimated local control rate at 1 and 4 years was 92 % ( 95 % confidence interval [ CI ] , 86 - 97 % ) and 89 % ( 95 % CI , 81 - 96 % ) . The cause-specific survival rate at 1 and 4 years was 92 % ( 95 % CI , 87 - 98 % ) and 77 % ( 95 % CI , 64 - 89 % ) , respectively . No statistically significant difference was found in the local , regional , and distant control between patients with and without pathologically confirmed NSCLC . The most common acute toxicity was Grade 1 or 2 fatigue ( 53 of 108 patients ) . No toxicities of Grade 4 or greater were identified . CONCLUSIONS Lung SBRT for early-stage NSCLC result ed in excellent local control and cause-specific survival with minimal toxicity . The disease-specific outcomes were comparable for patients with and without a pathologic diagnosis . SBRT can be considered an option for selected patients with proven or presumed early-stage NSCLC PURPOSE To evaluate the efficacy and adverse effects of image-guided stereotactic body radiation therapy ( SBRT ) in central ly/superiorly located non-small-cell lung cancer ( NSCLC ) . MATERIAL S AND METHODS We delivered SBRT to 27 patients , 13 with Stage I and 14 with isolated recurrent NSCLC . A central /superior location was defined as being within 2 cm of the bronchial tree , major vessels , esophagus , heart , trachea , pericardium , brachial plexus , or vertebral body , but 1 cm away from the spinal canal . All patients underwent four-dimensional computed tomography-based planning , and daily computed tomography-on-rail guided SBRT . The prescribed dose of 40 Gy ( n = 7 ) to the planning target volume was escalated to 50 Gy ( n = 20 ) in 4 consecutive days . RESULTS With a median follow-up of 17 months ( range , 6 - 40 months ) , the crude local control at the treated site was 100 % using 50 Gy . However , 3 of 7 patients had local recurrences when treated using 40 Gy . Of the patients with Stage I disease , 1 ( 7.7 % ) and 2 ( 15.4 % ) developed mediastinal lymph node metastasis and distant metastases , respectively . Of the patients with recurrent disease , 3 ( 21.4 % ) and 5 ( 35.7 % ) developed mediastinal lymph node metastasis and distant metastasis , respectively . Four patients ( 28.6 % ) with recurrent disease but none with Stage I disease developed Grade 2 pneumonitis . Three patients ( 11.1 % ) developed Grade 2 - 3 dermatitis and chest wall pain . One patient developed brachial plexus neuropathy . No esophagitis was noted in any patient . CONCLUSIONS Image-guided SBRT using 50 Gy delivered in four fractions is feasible and result ed in excellent local control PURPOSE This study analyzed patients enrolled in two large , prospect ively r and omized trials of systemic chemotherapy ( adjuvant/palliative setting ) for non-small-cell lung Cancer ( NSCLC ) . The main objective was to determine if age and /or the burden of chronic medical conditions ( comorbidity ) are independent predictors of survival , treatment delivery , and toxicity . PATIENTS AND METHODS Baseline comorbid conditions were scored using the Charlson comorbidity index ( CCI ) , a vali date d measure of patient comorbidity that is weighted according to the influence of comorbidity on overall mortality . The CCI score ( CCIS ) was correlated with demographic data , ( ie , age , sex , race ) , performance status ( PS ) , histology , cancer stage , patient weight , hemoglobin , alkaline phosphatase , lactate dehydrogenase , outcomes of chemotherapy delivery ( ie , type , total dose , and dose intensity ) , survival , and response . RESULTS A total of 1,255 patients were included in this analysis . The median age was 61 years ( range , 34 to 89 years ) ; 34 % of patients were elderly ( at least 65 years of age ) ; and 31 % had comorbid conditions at r and omization . Twenty-five percent of patients had a CCIS of 1 , whereas 6 % had a CCIS of 2 or greater . Elderly patients were more likely to have a CCIS equal to or greater than 1 compared with younger patients ( 42 % v 26 % ; P < .0001 ) , as were male patients ( 35 % v 21 % ; P < .0001 ) and patients with squamous histology ( 36 % v 29 % ; P = .001 ) . Although age did not influence overall survival , the CCIS appeared prognostic ( CCIS 1 v 0 ; hazard ratio 1.28 ; 95%CI , 1.09 to 1.5 ; P = .003 ) . CONCLUSION In these large , r and omized trials , the presence of comorbid conditions ( CCIS > or = 1 ) , rather than age more than 65 years , was associated with poorer survival PURPOSE To compare the efficacy of three lung stereotactic body radiotherapy ( SBRT ) regimens in a large institutional cohort . METHODS Between 2004 and 2009 , 130 patients underwent definitive lung cancer SBRT to a single lesion at the Mallinckrodt Institute of Radiology . We delivered 18 Gy × 3 fractions for peripheral tumors ( n = 111 ) and either 9 Gy × 5 fractions ( n = 8) or 10 Gy × 5 fractions ( n = 11 ) for tumors that were central or near critical structures . Univariate and multivariate analysis of prognostic factors was performed using the Cox proportional hazard model . RESULTS Median follow-up was 11 , 16 , and 13 months for the 9 Gy × 5 , 10 Gy × 5 , and 18 Gy × 3 groups , respectively . Local control statistics for Years 1 and 2 were , respectively , 75 % and 50 % for 9 Gy × 5 , 100 % and 100 % for 10 Gy × 5 , and 99 % and 91 % for 18 Gy × 3 . Median overall survival was 14 months , not reached , and 34 months for the 9 Gy × 5 , 10 Gy × 5 , and 18 Gy × 3 treatments , respectively . No difference in local control or overall survival was found between the 10 Gy × 5 and 18 Gy × 3 groups on log-rank test , but both groups had improved local control and overall survival compared with 9 Gy × 5 . Treatment with 9 Gy × 5 was the only independent prognostic factor for reduced local control on multivariate analysis , and increasing age , increasing tumor volume , and poor performance status predicted independently for reduced overall survival . CONCLUSION Treatment regimens of 10 Gy × 5 and 18 Gy × 3 seem to be efficacious for lung cancer SBRT and provide superior local control and overall survival compared with 9 Gy × 5 OBJECTIVE Sublobar resection ( SR ) is commonly used for patients considered high risk for lobectomy . Nonoperative therapies are increasingly being reported for patients with similar risk because of perceived lower morbidity . We report 30- and 90-day adverse events ( AEs ) from American College of Surgeons Oncology Group Z4032 , a multicenter phase III study for high-risk patients with stage I non-small cell lung cancer . METHODS Data from 222 evaluable patients r and omized to SR ( n = 114 ) or SR with brachytherapy ( n = 108 ) are reported . AEs were recorded using the Common Terminology Criteria for Adverse Events , Version 3.0 , at 30 and 90 days after surgery . Risk factors ( age , percent baseline carbon monoxide diffusion in the lung [ DLCO% ] , percent forced expiratory volume in 1 second [ FEV1 % ] , upper lobe vs lower lobe resections , performance status , surgery approach , video-assisted thoracic surgery vs open and extent , and wedge vs segmentectomy ) were analyzed using a multivariable logistic model for their impact on the incidence of grade 3 or higher ( G3 + ) AEs . Respiratory AEs were also specifically analyzed . RESULTS Median age , FEV1 % , and DLCO% were similar in the 2 treatment groups . There was no difference in the location of resection ( upper vs lower lobe ) or the use of segmental or wedge resections . There were no differences between the groups with respect to " respiratory " G3 + AEs ( 30 days : 14.9 % vs 19.4 % , P = .35 ; 0 - 90 days : 19.3 % vs 25 % , P = .31 ) and " any " G3 + AEs ( 30 days : 25.4 % vs 30.6 % , P = .37 ; 0 - 90 days : 29.8 % vs 37 % , P = .25 ) . Further analysis combined the 2 groups . Mortality occurred in 3 patients ( 1.4 % ) by 30 days and in 6 patients ( 2.7 % ) by 90 days . Four of the 6 deaths were thought to be due to surgery . When considered as continuous variables , FEV1 % was associated with " any " G3 + AE at days 0 to 30 ( P = .03 ; odds ratio [ OR ] = 0.98 ) and days 0 to 90 ( P = .05 ; OR = 0.98 ) , and DLCO% was associated with " respiratory " G3 + AE at days 0 to 30 ( P = .03 ; OR = 0.97 ) and days 0 to 90 ( P = .05 ; OR = 0.98 ) . Segmental resection was associated with a higher incidence of any G3 + AE compared with wedge resection at days 0 to 30 ( 40.3 % vs 22.7 % ; OR = 2.56 ; P < .01 ) and days 0 to 90 ( 41.5 % vs 29.7 % ; OR = 1.96 ; P = .04 ) . The median FEV1 % was 50 % , and the median DLCO% was 46 % . By using these median values as potential cutpoints , only a DLCO% of less than 46 % was significantly associated with an increased risk of " respiratory " and " any " G3 + AE for days 0 to 30 and 0 to 90 . CONCLUSIONS In a multicenter setting , SR with brachytherapy was not associated with increased morbidity compared with SR alone . SR/SR with brachytherapy can be performed safely in high-risk patients with non-small cell lung cancer with low 30- and 90-day mortality and acceptable morbidity . Segmental resection was associated with increased " any " G3 + AE , and DLCO% less than 46 % was associated with " any " G3 + AE and " respiratory " G3 + AE at both 30 and 90 days PURPOSE To evaluate the efficacy and toxicity of hypofractionated stereotactic body radiotherapy in patients with Stage I/II non-small-cell lung cancer . METHODS AND MATERIAL S Forty-three patients with inoperable Stage I/II non-small-cell lung cancer underwent treatment prospect ively using the stereotactic gamma-ray whole-body therapeutic system ( body gamma-knife radiosurgery ) with 30 rotary conical-surface Co(60 ) sources focused on the target volume . Low-speed computed tomography simulation was conducted , which was followed by three-dimensional conformal radiotherapy planning . A total dose of 50 Gy was delivered at 5 Gy/fraction to the 50 % isodose line covering the planning target volume , whereas a total dose of 70 Gy was delivered at 7 Gy/fraction to the gross target volume . The median follow-up duration was 27 months . RESULTS Three to 6 months after treatment , the complete response rate for body-gamma knife radiosurgery was 63 % , and the overall response rate was 95 % . The 1-year , 2-year , and 3-year local control rates were all 95 % in all patients . The 1-year , 2-year , and 3-year overall survival rates were 100 % , 91 % , and 91 % , respectively , in patients with Stage I disease and 73 % , 64 % , and 64 % , respectively , in those with Stage II disease . Only 2.3 % ( 1/43 ) of the patients had Grade 3 pneumonitis . CONCLUSION Our highly focused stereotactic body radiotherapy method result ed in promising local control and survival with minimal toxicity PURPOSE The 50-month results of a prospect i ve Phase II trial of stereotactic body radiation therapy ( SBRT ) in medically inoperable patients are reported . METHODS AND MATERIAL S A total of 70 medically inoperable patients had clinical ly staged T1 ( 34 patients ) or T2 ( 36 patients ) ( < or = 7 cm ) , N0 , M0 , biopsy-confirmed non-small-cell lung carcinoma ( NSCLC ) and received SBRT as per our previously published reports . The SBRT treatment dose of 60 - 66 Gy was prescribed to the 80 % isodose volume in three fractions . RESULTS Median follow-up was 50.2 months ( range , 1.4 - 64.8 months ) . Kaplan-Meier local control at 3 years was 88.1 % . Regional ( nodal ) and distant recurrence occurred in 6 ( 8.6 % ) and 9 ( 12.9 % ) patients , respectively . Median survival ( MS ) was 32.4 months and 3-year overall survival ( OS ) was 42.7 % ( 95 % confidence interval [ 95 % CI ] , 31.1 - 54.3 % ) . Cancer-specific survival at 3 years was 81.7 % ( 95 % CI , 70.0 - 93.4 % ) . For patients with T1 tumors , MS was 38.7 months ( 95 % CI , 25.3 - 50.2 ) and for T2 tumors MS was 24.5 months ( 95 % CI , 18.5 - 37.4 ) ( p = 0.194 ) . Tumor volume ( < or = 5 cc , 5 - 10 cc , 10 - 20 cc , > 20 cc ) did not significantly impact survival : MS was 36.9 months ( 95 % CI , 18.1 - 42.9 ) , 34.0 ( 95 % CI , 16.9 - 57.1 ) , 32.8 ( 95 % CI , 21.3 - 57.8 ) , and 21.4 months ( 95 % CI , 17.8 - 41.6 ) , respectively ( p = 0.712 ) . There was no significant survival difference between patients with peripheral vs. central tumors ( MS 33.2 vs. 24.4 months , p = 0.697 ) . Grade 3 to 5 toxicity occurred in 5 of 48 patients with peripheral lung tumors ( 10.4 % ) and in 6 of 22 patients ( 27.3 % ) with central tumors ( Fisher 's exact test , p = 0.088 ) . CONCLUSION Based on our study results , use of SBRT results in high rates of local control in medically inoperable patients with Stage I NSCLC The dose-response for local tumor control after stereotactic radiotherapy of 92 pulmonary tumors ( 36 NSCLC and 56 metastases ) was evaluated . Short course irradiation of 1 - 8 fractions with different fraction doses was used . After a median follow-up of 14 months ( 2 - 85 months ) 11 local recurrences were observed with significant advantage for higher doses . When normalization to a biologically effective dose ( BED ) is used a dose of 94Gy at the isocenter and 50Gy at the PTV-margin are demonstrated to give 50 % probability of tumor control ( TCD50 ) . Multivariate analysis revealed the dose at the PTV-margin as the only significant factor for local control Background The treatment schedules for stereotactic body radiotherapy ( SBRT ) for lung cancer vary from institution to institution . Several reports have indicated that stage IB patients had worse outcomes than stage IA patients when the same dose was used . We evaluated the clinical outcomes of SBRT for stage I non-small cell lung cancer ( NSCLC ) treated with different doses depending on tumor diameter . Methods Between February 2004 and November 2008 , 124 patients with stage I NSCLC underwent SBRT . Total doses of 44 , 48 , and 52 Gy were administered for tumors with a longest diameter of less than 1.5 cm , 1.5 - 3 cm , and larger than 3 cm , respectively . All doses were given in 4 fractions . Results For all 124 patients , overall survival was 71 % , cause-specific survival was 87 % , progression-free survival was 60 % , and local control was 80 % , at 3 years . The 3-year overall survival was 79 % for 85 stage IA patients treated with 48 Gy and 56 % for 37 stage IB patients treated with 52 Gy ( p = 0.05 ) . At 3 years , cause-specific survival was 91 % for the former group and 79 % for the latter ( p = 0.18 ) , and progression-free survival was 62 % versus 54 % ( p = 0.30 ) . The 3-year local control rate was 81 % versus 74 % ( p = 0.35 ) . The cumulative incidence of grade 2 or 3 radiation pneumonitis was 11 % in stage IA patients and 30 % in stage IB patients ( p = 0.02 ) . Conclusions There was no difference in local control between stage IA and IB tumors despite the difference in tumor size . The benefit of increasing the SBRT dose for larger tumors should be investigated further Platinum‐based adjuvant chemotherapy in r and omized trials has failed to provide a survival benefit in patients with resected stage I nonsmall cell lung cancer ( NSCLC ) . Using data from the California Cancer Registry ( CCR ) , we explored factors that had detrimental effects on survival in patients with stage I NSCLC to identify a subset of patients at high risk for disease recurrence and subsequent mortality PURPOSE Adjuvant chemotherapy for resected non-small-cell lung cancer ( NSCLC ) is now accepted on the basis of several r and omized clinical trials ( RCTs ) that demonstrated improved survival . Although there is strong evidence that adjuvant chemotherapy is effective in stages II and IIIA NSCLC , its utility in stage IB disease is unclear . This report provides a mature analysis of Cancer and Leukemia Group B ( CALGB ) 9633 , the only RCT design ed specifically for stage IB NSCLC . PATIENTS AND METHODS Within 4 to 8 weeks of resection , patients were r and omly assigned to adjuvant chemotherapy or observation . Eligible patients had pathologically confirmed T2N0 NSCLC and had undergone lobectomy or pneumonectomy . Chemotherapy consisted of paclitaxel 200 mg/m(2 ) intravenously over 3 hours and carboplatin at an area under the curve dose of 6 mg/mL per minute intravenously over 45 to 60 minutes every 3 weeks for four cycles . The primary end point was overall survival . RESULTS Three hundred-forty-four patients were r and omly assigned . Median follow-up was 74 months . Groups were well-balanced with regard to demographics , histology , and extent of surgery . Grade s 3 to 4 neutropenia were the predominant toxicity ; there were no treatment-related deaths . Survival was not significantly different ( hazard ratio [ HR ] , 0.83 ; CI , 0.64 to 1.08 ; P = .12 ) . However , exploratory analysis demonstrated a significant survival difference in favor of adjuvant chemotherapy for patients who had tumors > or = 4 cm in diameter ( HR , 0.69 ; CI , 0.48 to 0.99 ; P = .043 ) . CONCLUSION Because a significant survival advantage was not observed across the entire cohort , adjuvant chemotherapy should not be considered st and ard care in stage IB NSCLC . Given the magnitude of observed survival differences , CALGB 9633 was underpowered to detect small but clinical ly meaningful improvements . A statistically significant survival advantage for patients who had tumors > or = 4 cm supports consideration of adjuvant paclitaxel/carboplatin for stage IB patients who have large tumors PURPOSE Validation of a prospect i ve , risk-adapted strategy for early-stage non-small-cell lung cancer ( NSCLC ) patients treated with stereotactic body radiotherapy ( SBRT ) . METHODS AND MATERIAL S Patients with a T1 - 3N0M0 ( American Joint Committee on Cancer 6th edition ) NSCLC were accrued . Using the Radiation Therapy Oncology Group definition , patients were treated to a total dose of 60,Gy in three fractions for peripherally located lesions and four fractions for central ly located lesions . The primary endpoint was toxicity , grade d according to the Radiation Therapy Oncology Group acute and late morbidity scoring system , and the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 . Secondary endpoints were local control and survival . RESULTS A total of 40 patients were included , 17 with a central ly located lesion . The lung toxicity-free survival estimate at 2 years was 74 % and was related to the location ( central vs. peripheral ) and the size of the target volume . No dose volumetric parameters could predict the occurrence of lung toxicity . One patient died because of treatment-related toxicity . The 1-year and 2-year local progression-free survival estimates were 97 % and 84 % , respectively , and were related to stage ( T1 vs. T2 ) related ( p = 0.006 ) . Local failure was not more frequent for patients treated in four fractions . The 1-year local progression-free survival estimate dropped below 80 % for lesions with a diameter of more than 4 cm . CONCLUSION The proposed risk-adapted strategy for both central ly and peripherally located lesions showed an acceptable toxicity profile while maintaining excellent local control rates . The correlation between local control and tumor diameter calls for the inclusion of tumor stage as a variable in future study design Background : Deterioration in health-related quality of life ( HRQOL ) is frequently observed after surgery for stage I non – small-cell lung cancer . As stereotactic ablative radiotherapy ( SABR ) can result in local control percentages exceeding 90 % , we studied baseline and post-treatment HRQOL in SABR patients . Methods : HRQOL data were collected prospect ively using the European Organization for Research and Treatment of Cancer ( EORTC ) QLQ-C30 question naire in 382 consecutive patients treated with SABR . Patients were referred from 68 Dutch centers , with 86 % judged unfit for surgery , and 14 % declining surgery . An SABR dose of 60 Gy was delivered in three- , five- , or eight treatment fractions , depending on tumor diameter and location . HRQOL data were available for 382 patients at baseline ( pre-SABR ) , and for 282 , 212 , 144 , 56 , and 43 patients at 3 , 6 , 12 , 18 , and 24 months post-SABR , respectively . Results : Median survival was 40 months , with a 2-year survival of 66 % . Local , regional , and distant failure percentages at 2 years were 6 % , 13 % , and 22 % , respectively . Mean baseline global HRQOL and physical functioning scores were 62.9 ± 1.1 and 61.7 ± 1.1 , respectively . Baseline symptom scores were highest for dyspnea ( 47.1 ± 1.7 ) and fatigue ( 37.4 ± 1.3 ) . Except for a nonsignificant decrease in 2 to 3 points per year in physical functioning , no statistically or clinical ly significant worsening of any of the HRQOL functioning or symptom scores at any follow-up time point was observed . Conclusions : Patients referred for SABR have substantially worse baseline HRQOL scores than those reported in the surgical literature . Clinical ly relevant deteriorations in HRQOL subscale scores were not observed after SABR Purpose : Local hypofractionated stereotactic radiation treatment ( hfSRT ) of early stage non-small cell lung cancer ( NSCLC ) represents a highly effective treatment alternative in medically inoperable patients . Method : Between June 2007 and December 2010 , 65 patients with NSCLC were treated with image-guided hypofractionated radiotherapy . The Union Internationale Contre le Cancer ( UICC ) stage distribution was : IA , n = 19 ; IB , n = 15 ; IIB , n = 5 ; IIIA , n = 10 ; IIIB , n = 6 ; and IV , n = 10 . The fractionation schedule used was 3 × 12.5 Gy ( n = 36 ) prescribed to the encompassing 67 % isodose line for peripheral primary tumours , and 8 × 6 Gy ( n = 26 ) or 8 × 5 Gy ( n = 3 ) prescribed to the encompassing 80 % isodose line for central ly located tumours . Results : Mean follow-up was 13.8 months ( range 1–41 months ) . Until now 6 patients developed a local recurrence , 2 of them in combination with mediastinal lymph node failure . The 1-year actuarial local control rate was 93 % and overall survival 79 % . Pneumonitis was seen in 14 patients ( 21.5 % ) ( Common Terminology Criteria for Adverse Events ( CTCAE ) grade I : n = 12 , and II : n = 2 ) after a median time period of 9.5 months . No patient developed pneumonitis of CTCAE grade III or higher . Conclusion : Image-guided hfSRT is effective and feasible in patients with non-operable NSCLC , even in higher stages , whenever local control is crucial and there are contraindications against systemic therapy |
12,215 | 14,524,398 | Parenteral opioids provide modest pain relief in labor , and little evidence supports the use of one agent over another .
Although epidural analgesia is the most effective form of pain relief , its use is associated with a longer labor , an increased incidence of maternal fever , and increased rates of operative vaginal delivery .
The effect of epidural analgesia on rates of cesarean delivery is controversial .
Nitrous oxide provides a modest analgesic effect , but it is used less often in the United States than in other developed nations .
Paracervical block provides effective analgesia in the first stage of labor , but its use is limited by postblock bradycardia . | Epidural analgesia is used during labor in most large U.S. hospitals , and its use is rapidly increasing in small hospitals . | Background Reports indicate that the administration of epidural analgesia for pain relief during labor interferes with labor and increases cesarean deliveries . However , only a few controlled trials have assessed the effect of epidural analgesia on the incidence of cesarean delivery . The authors ' primary purpose in this r and omized study was to evaluate the effects of epidural analgesia on the rate of cesarean deliveries by providing a suitable alternative : patient-controlled intravenous analgesia . Methods Seven hundred fifteen women of mixed parity in spontaneous labor at full term were r and omly assigned to receive either epidural analgesia or patient-controlled intravenous meperidine analgesia . Epidural analgesia was maintained with a continuous epidural infusion of 0.125 % bupivacaine with 2 micro gram/ml fentanyl . Patient-controlled analgesia was maintained with 10 - 15 mg meperidine given every 10 min as needed using a patient-controlled pump . Procedures recorded in a manual that prescribed the intrapartum management were followed for each woman r and omized in the study . Results A total of 358 women were r and omized to receive epidural analgesia , and 243 ( 68 % ) of these women complied with the epidural analgesia protocol . Similarly , 357 women were r and omized to receive patient-controlled intravenous meperidine analgesia , and 259 ( 73 % ) of these women complied with the patient-controlled intravenous analgesia protocol . Only five women who were r and omized and received patient-controlled intravenous meperidine analgesia according to the protocol crossed over to epidural analgesia due to inadequate pain relief . There was no difference in the rate of cesarean deliveries between the two analgesia groups using intention-to-treat analysis based on the original r and omization ( epidural analgesia , 4 % [ 95 % CI : 1.9 - 6.2 % ] compared with patient-controlled intravenous analgesia , 5 % [ 95 % CI : 2.6 - 7.2 % ] ) . Similar results were observed for the analysis of the protocol -compliant groups ( epidural analgesia , 5 % [ 95 % CI : 2.6 - 8.5 % ] compared with patient-controlled intravenous analgesia , 6 % [ 95 % CI : 3 - 8.9 % ] ) . Women who received epidural analgesia reported lower pain scores during labor and delivery compared with women who received patient-controlled intravenous analgesia . Conclusions Epidural analgesia was not associated with increased numbers of cesarean delivery when compared with a suitable alternative method of analgesia OBJECTIVE This study was undertaken to determine whether a policy of delayed pushing for nulliparous women with continuous-infusion epidural analgesia reduces the risk of difficult delivery ( cesarean delivery , operative delivery from a midpelvic position , low-pelvic procedures with rotation > 45 degrees ) . STUDY DESIGN In this multicenter , r and omized , controlled trial women in the delayed pushing group ( n = 936 ) were advised to wait > or = 2 hours after full dilatation before commencement of pushing . Women in the early pushing group ( n = 926 ) were advised to commence pushing as soon as they had been r and omly assigned . RESULTS Difficult delivery was reduced with delayed pushing ( relative risk , 0.79 ; 95 % confidence interval , 0.66 - 0.95 ) . The greatest effect was on midpelvic procedures ( relative risk , 0.72 ; 95 % confidence interval , 0.55 - 0.93 ) . Although there was little evidence for an effect on low-pelvic procedures , spontaneous delivery was more frequent among women who practice d delayed pushing ( relative risk , 1.09 ; 95 % confidence interval , 1.00 - 1.18 ) . Abnormal umbilical cord blood pH ( < 7.15 venous value or < 7.10 arterial value ) was more frequent in the delayed pushing group ( relative risk , 2.45 , 95 % confidence interval , 1.35 - 4 . 43 ) . However , scores for a summary indicator , the Neonatal Morbidity Index , were similarly distributed in the 2 groups . CONCLUSION Delayed pushing is an effective strategy to reduce difficult deliveries among nulliparous women We compared the incidence of Caesarean delivery in nulliparous women r and omized to receive epidural analgesia with those r and omized to intramuscular ( i.m . ) pethidine . On admission to the delivery suite in established labour , 802 nulliparae had already agreed to be r and omized with respect to their first analgesia . One hundred and eighty-eight women required either no analgesia or 50 % nitrous oxide in oxygen ( Entonox ) only . Of the remaining 614 women , 310 were r and omly allocated to receive i.m . pethidine up to 300 mg and 304 to receive epidural bupivacaine . Labour management was st and ardized according to the criteria for active management of labour . The intention-to-treat analysis showed similar Caesarean section rates in those r and omized to epidural ( 12 % ) or pethidine analgesia ( 13 % ) . The difference in Caesarean rate was -1.1 % with 95 % confidence intervals from -6.3 % to + 4.1 % . The normal vaginal delivery rates were similar ( epidural , 59 % ; pethidine , 61 % ) The aim of this quasi‐experimental study was to examine the effects of maternal pethidine during labour on the developing breast feeding behaviour in infants in the first 2 h after birth compared with infants not exposed to pethidine . Forty‐four healthy infants were observed immediately after birth . They were placed skin‐to‐skin on their mothers ' chests . The development of mouth and sucking movements as well as rooting behaviour and state of sleep/wakefulness were noted . The observer was blind as to the pain relief the mother had received during labour . Of the 44 mothers 18 had received pethidine . The main findings were that infants exposed to pethidine had delayed and depressed sucking and rooting behaviour . In addition , a smaller proportion of infants exposed to pethidine started to suckle the breast . Rooting movements which are expected to be vigorous at 30 min after birth were affected both by administration of pethidine and a longer second stage of labour . It is suggested that the differences found in sucking behaviour may be a central effect of pethidine . Depression of rooting movements in the pethidine group may be caused by exhaustion due to a longer second stage of labour and administration of pethidine . It is recommended that pethidine‐exposed mother‐infant couples stay together after birth long enough to enable the infant to make the choice to attach or not to attach to the nipple without the forceful helping h and of the health staff Background Some studies suggest that epidural analgesia prolongs labor and increases the incidence of cesarean section , especially if it is administered before 5 cm cervical dilation . The purpose of the current study was to determine whether early administration of epidural analgesia affects obstetric outcome in nulliparous women who are receiving intravenous oxytocin . Methods Informed consent was obtained from healthy nulliparous women with a singleton fetus in a vertex presentation , who requested epidural analgesia while receiving intravenous oxytocin at at least 36 weeks ' gestation . Each patient was r and omized to receive either early or late epidural analgesia . R and omization occurred only after the following conditions were met : ( 1 ) the patient requested pain relief at that moment , ( 2 ) a lumbar epidural catheter had been placed , and ( 3 ) the cervix was at least 3 but less than 5 cm dilated . Patients in the early group immediately received epidural bupivacaine analgesia . Patients in the late group received 10 mg nalbuphlne intravenously . Late-group patients did not receive epidural analgesia until they achieved a cervical dilation of at least 5 cm or until at least 1 h had elapsed after a second dose of nalbuphine . Results Early administration of epidural analgesia did not prolong the interval between r and omization and the diagnosis of complete cervical dilation , and it did not increase the incidence of malposition of the vertex at delivery . Also , early administration of epidural analgesia did not result in an increased incidence of cesarean section or instrumental vaginal delivery . Thirteen ( 18 % ) of 74 women In the early group and 14 ( 19 % ) of 75 women in the late group underwent cesarean section ( relative risk for the early group 0.94 ; 95 % confidence interval 0.48–1.84 ) . Patients in the early group had lower pain scores between 30 and 120 min after r and omization , and were more likely to experience transient hypotension . Infants in the late group had lower umbilical arterial and venous blood pH and higher umbilical arterial and venous blood carbon dioxide tension measurements at delivery . Conclusions Early administration of epidural analgesia did not prolong labor or increase the incidence of operative delivery , when compared with intravenous nalbuphine followed by late administration of epidural analgesia , in nulliparous women who were receiving intravenous oxytocin Background : In 1981 , with support from the American Society of Anesthesiologists and the American College of Obstetricians and Gynecologists , anesthesia and obstetric providers were surveyed to identify the personnel and methods used to provide obstetric anesthesia in the United States . The survey was exp and ed and repeated in 1992 with support from the same organizations . Methods : Comments and questions from the American Society of Anesthesiologists Committee on Obstetrical Anesthesia and the American College of Obstetricians and Gynecologists Committee on Obstetric Practice were added to the original survey instrument to include newer issues while allowing comparison with data from 1981 . Using the American Hospital Association registry of hospitals , hospitals were differentiated by number of births per year ( stratum I , > or= to 1,500 births ; stratum II , 500–1,499 births ; stratum III , < 500 births ) and by U.S. census region . A stratified r and om sample of hospitals was selected . Two copies of the survey were sent to the administrator of each hospital , one for the chief of obstetrics and one for the chief of anesthesiology . Results : Compared with 1981 data , there was an overall reduction in the number of hospitals providing obstetric care ( from 4,163 to 3,545 ) , with the decrease occurring in the smallest units ( 56 % of stratum III hospitals in 1981 compared with 45 % in 1992 ) . More women received some type of labor analgesia , and there was a 100 % increase in the use of epidural analgesia . However , regional analgesia was unavailable in 20 % of the smallest hospitals . Spinal analgesia for labor was used in 4 % of parturients . In 1981 , obstetricians provided 30 % of epidural analgesia for labor ; they provided only 2 % in 1992 . Regional anesthesia was used for 78–85 % ( depending on strata ) of patients undergoing cesarean section , result ing in a marked decrease in the use of general anesthesia . Anesthesia for cesarean section was provided by nurse anesthetists without the medical direction of an anesthesiologist in only 4 % of stratum I hospitals but in 59 % of stratum III hospitals . Anesthesia personnel provided neonatal resuscitation in 10 % of cesarean deliveries compared with 23 % in 1981 . Conclusions : Compared with 1981 , analgesia is more often used by parturients during labor , and general anesthesia is used less often in patients having cesarean section deliveries . In the smallest hospitals , regional analgesia for labor is still unavailable to many parturients , and more than one half of anesthetics for cesarean section are provided by nurse anesthetists without medical direction by an anesthesiologist . Obstetricians are less likely to personally provide epidural analgesia for their patients . Anesthesia personnel are less involved in newborn resuscitation OBJECTIVE Intrathecal narcotics ( ITNs ) are being used in some setting s as a sole labor analgesic . However , they have not been directly compared to epidural analgesia . STUDY DESIGN We used a prospect i ve observational design . POPULATION Eighty-two women with uncomplicated full-term pregnancies were enrolled upon analgesia request during spontaneous labor with cervical dilation 3 to 7 cm . Sixty-three chose ITNs ( morphine and fentanyl ) , and 19 chose epidural analgesia ( continuous infusion of bupivacaine and fentanyl ) . OUTCOMES MEASURED Pain scores were documented using a visual analog scale . Satisfaction and side effects were rated with Likert scales during a structured interview on the first postpartum day . Outcomes were analyzed with multivariate regression techniques . RESULTS Intrathecal narcotics were associated with significantly higher pain scores than was epidural analgesia during the first and second stages of labor and on an overall postpartum rating . The median effective duration of action for ITNs was between 60 and 120 minutes ; however , ITNs provided excellent analgesia for a subgroup of women who delivered within 2 to 3 hours of receiving them . Although women in both groups were satisfied with their pain management , women receiving ITNs had statistically lower overall satisfaction scores . CONCLUSIONS Within the limitations of a nonr and omized study , a single intrathecal injection of morphine and fentanyl has a shorter duration of action and provides less effective pain control than a continuous epidural infusion of bupivacaine and fentanyl . However , ITNs may have a role in setting s with limited support from anesthesiologists or for women whose labors are progressing rapidly Background Some studies suggest that epidural analgesia prolongs labor and increases the incidence of cesarean section , especially if it is administered before 5 cm cervical dilation . The purpose of the current study was to determine whether early administration of epidural analgesia affects obstetric outcome in nulliparous women who are in spontaneous labor . Methods Informed consent was obtained from 344 healthy nulliparous women with a singleton fetus in a vertex presentation , who requested epidural analgesia during spontaneous labor at at least 36 weeks ' gestation . Each patient was r and omized to receive either early or late epidural analgesia . R and omization occurred only after the following conditions were met : ( 1 ) the patient requested pain relief at that moment , ( 2 ) a lumbar epidural catheter had been placed , and ( 3 ) the cervix was at least 3 cm but less than 5 cm dilated . Patients in the early group immediately received epidural bupivacaine analgesia . Patients in the late group received 10 mg nalbuphlne intravenously . Late-group patients did not receive epidural analgesia until they achieved a cervical dilation of at least 5 cm or until at least 1 h had elapsed after a second dose of nalbuphine . Ten of the 344 patients were excluded because of a protocol violation or voluntary withdrawal from the study . Results Early administration of epidural analgesia did not increase the incidence of oxytocin augmentation , prolong the interval between r and omization and the diagnosis of complete cervical dilation , or increase the incidence of malposition of the vertex at delivery . Also , early administration of epidural analgesia did not result in an increased incidence of cesarean section or instrumental vaginal delivery . Seventeen ( 10 % ) of 172 women in the early group and 13 ( 8 % ) of 162 women in the late group underwent cesarean section ( relative risk for the early group 1.22 ; 95 % confidence interval 0.62–2.40 ) . Patients in the early group had lower pain scores between 30 and 150 min after r and omization . Infants in the late group had lower umbilical arterial and venous blood pH and higher umbilical venous blood carbon dioxide tension measurements at delivery . Conclusions Early administration of epidural analgesia did not prolong labor , increase the incidence of oxytocin augmentation , or increase the incidence of operative delivery , when compared with intravenous nalbuphlne followed by late administration of epidural analgesia , in nulliparous women who were in spontaneous labor at term Objective To compare the effects of epidural analgesia with intravenous ( IV ) analgesia on the outcome of labor . Methods Thirteen hundred thirty women with uncomplicated term pregnancies and in spontaneous labor were r and omized to be offered epidural bupivacaine-fentanyl or IV meperidine analgesia during labor . Results Comparison of the allocation groups by intent to treat revealed a significant association between epidural allocation and operative delivery for dystocia . However , only 65 % of each r and omization group accepted the allocated treatment . Four hundred thirty-seven women accepted and received meperidine as allocated , and they were compared with 432 women accepting epidural allocation . Significant associations result ed between epidural administration and prolongation of labor , increased rate of oxytocin administration , chorioamnionitis , low forceps , and cesarean delivery . Because of the high rate of noncompliance with treatment allocation , a multifactorial regression analysis was performed on the entire cohort , and a twofold relative risk of cesarean delivery persisted in association with epidural treatment . The impact of epidural treatment on cesarean delivery was significant for both nulliparous and parous women ( risk ratios 2.55 and 3.81 , respectively ) . Epidural analgesia provided significantly better pain relief in labor than did parenteral meperidine . Conclusion Although labor epidural analgesia is superior to meperidine for pain relief , labor is prolonged , uterine infection is increased , and the number of operative deliveries are increased . A two- to fourfold increased risk of cesarean delivery is associated with epidural treatment in both nulliparous and parous women |
12,216 | 12,076,415 | Some of these trials showed evidence of behavioural change following pedestrian safety education but it is difficult to predict what effect this might have on pedestrian injury risk .
REVIEW ER 'S CONCLUSIONS Pedestrian safety education can result in improvement in children 's knowledge and can change observed road crossing behaviour but whether this reduces the risk of pedestrian motor vehicle collision and injury occurrence is unknown . | BACKGROUND Each year about one million people die and about 10 million are seriously injured on the world 's roads .
Educational measures to teach pedestrians how to cope with the traffic environment are considered to be an essential component of any prevention strategy , and pedestrian education has been recommended in many countries .
However , as re sources available for road safety are limited , a key question concerns the relative effectiveness of different prevention strategies .
OBJECTIVES To quantify the effectiveness of pedestrian safety education programmes in preventing pedestrian-motor vehicle collisions . | In a quasi-experimental study , hospital-treated traffic accident injuries were recorded prospect ively for 7 1/2 years in the two Norwegian cities , Harstad and Trondheim . In Harstad the recorded data were used actively in analysis , planning , and implementation of a community-based injury prevention program . Trondheim was the nonequivalent control city . The intervention was divided into three periods , each of 30 months duration . Preventive efforts were implemented to some extent in period 1 , increasingly in period 2 and period 3 . Traffic safety was promoted in an extensive community program based on the Ottawa charter for health promotion . A 26.6 % overall reduction of traffic injury rates was found in Harstad from period 1 to period 3 ( p < 0.01 ) , whereas a corresponding significant increase was found in the comparison city . Analysis of data from other sources were not conclusive in supporting the Trondheim data as showing the national trend . Alternative explanations for the injury rate reduction in Harstad were assessed by means of other available relevant data . The exact mechanisms that brought about the reduction of injury rates were hard to eluci date because so many intervention elements were implemented at the same time . It is concluded that at least some of the reduction was due to behavioural and structural changes brought about by health promotion . Important factors for the effect of and participation in the prevention program were local relevance and continuous feedback of accident injury data Parents of 171 children coming to the Yale-New Haven Hospital Primary Care Center for their 6-month checkup were r and omized into an intervention group ( n = 85 ) and a control group ( n = 86 ) . Parents in the intervention group received a three-part individualized course in child safety that required active parental participation . Parts 1 , 2 , and 3 were given at the 6-month , 9-month , and 12-month well-child visits , respectively . Parents in the control group received routine safety education as provided at well-child visits . The educational phase of the study was completed by 129 families , 65 in the intervention group and 64 in the control group . Safety knowledge , number of hazards in the home , and reported accidents were assessed by a " blinded " community health worker approximately 1 month after the 12-month well-child visit . A total of 109 home visits were made , 55 for the intervention group and 54 for the control group . Parental safety knowledge was assessed based upon pictorial hazard recognition . Of 13 possible hazards , the mean number of hazards recognized by the intervention group parents was 9.4 ( n = 55 ) v 8.4 ( n = 50 ) by the control group parents ( t = 2.1 , P less than .05 , two-tailed ) . A hazard score was determined for each family based on nine possible hazards observed at the home visit . The mean hazard score for the intervention group was 2.4 ( n = 55 v 3.0 ( n = 54 ) for the control group ( t = 2.4 , P less than .02 , two-tailed ) . Parentally reported accidents and accidents reported in hospital records were similar for both groups . Results of this study suggest that age-appropriate safety education that is repetitive and individualized and that requires active parental participation results in an increase in parental knowledge and an improvement in certain safety practice OBJECTIVE To determine the effectiveness of a safety education program , Safety City , that is design ed to teach kindergarten and first grade children how to cross the street , call 911 in an emergency , and avoid strangers . PARTICIPANTS / SETTING Kindergarten students at 10 urban elementary schools . DESIGN Each school was r and omized to either the intervention or control group . An evaluation tool was administered to all participants as a pretest . The Safety City program was then presented to the intervention schools . Afterward , the same evaluation tool was used as a post-test . The posttest was administered to the intervention group 6 months after the Safety City program was presented . The control group took the posttest 6 months after the pretest . MAIN OUTCOME MEASURE Change in individual test scores . RESULTS One hundred eighty-one children completed the pretest and posttest evaluations . There was no statistical difference in the change between pretest and posttest scores of children who participated in the Safety City program and those in the control group ( crossing the street , P = .29 ; calling 911 , P = .41 ; stranger avoidance , P = .57 ) . CONCLUSIONS Exposure to the Safety City program did not achieve the desired changes in safety knowledge among participants . This is most likely owing to the fact that Safety City attempts to convey a large amount of relatively complex information to young children in a brief period . We conclude that programs such as Safety City are not sufficient to teach children these behaviors . This report also emphasizes the importance of building an evaluation component into educational programs Summary . Trends in road casualty figures among children in recent years are evaluated and interpretations suggested . The experiment reported here shows that the educator 's conception of the function of the kerb drill , i.e. , to detect traffic , is not reflected in its function as perceived by many young children , who in the experimental setting behave as though they regarded the performance of the kerb drill as in itself sufficient to ward off the dangers of the road . The experiment also demonstrates that the notions of directionality which the kerb drill presupposes are not those of 5–6-year-old children , who often regard ‘ left ’ and ‘ right ’ as parts of the environment rather than relations to the person . The ‘ static ’ conception of directionality becomes more frequent after exposure to a propag and a film in which the kerb drill exemplars perform facing their audience OBJECTIVE To test the feasibility of a hospital-based injury recording for accident analysis and outcome evaluation of bicyclist and pedestrian injury prevention . DESIGN Prospect i ve injury recording lasting 7 1/2 years , using a quasi-experimental design . SETTING The population of Harstad ( 22,000 ) . INTERVENTION Injury data were evaluated in an injury prevention group and used in planning a community-based intervention . Promotion of bicyclist helmet use and pedestrian safe behaviour was implemented by activating public and voluntary organizations and media . A traffic safety pamphlet containing local traffic injury data was distributed . Changes were made in the physical traffic environment . MAIN OUTCOME MEASURES Injury rates for bicyclists and pedestrians . RESULTS In 275 bicyclists upper extremity and head injuries were predominant 70 % were below 16 years . In 137 pedestrians lower extremity injury was most frequent and children below 10 years had the highest injury rates . Significant injury rate reductions were observed after intervention for child bicyclists and pedestrians . CONCLUSION A hospital-based injury recording is feasible for bicyclists and pedestrian accident analysis , planning injury prevention , and outcome evaluation of the programme . This study indicates that a significant injury rate reduction in children may have been the result of the intervention HYPOTHESIS Young children can learn safety behavior in the public school system . These children will modify family seat belt use . SETTING DESIGN : This is a prospect i ve cohort analytic study conducted in a 50,000 square mile regionalized trauma center referral area . METHODS A school-based injury prevention program targeting kindergarten through second- grade ( K-2 ) students addressed four aspects of traffic safety : seat belt use , pedestrian and bicycle safety , school bus safety , and unsafe rides . After inservice instruction , teachers taught the program over a 10-week period . A simultaneous community traffic safety program was conducted through the media . Family seat belt use was monitored by blinded observation at six study schools and one control school . Income level of schools was characterized as low or high , based on student use of federal lunch subsidies . School program implementation was defined as good or poor , based on adherence to teaching protocol . RESULTS A total of 68,650 K-2 students have completed this traffic safety program during 1990 to 1994 . During the study year ( 1992 to 1993 ) , 25,900 students completed the program taught by 1,400 teachers in 95 schools . A total of 5,936 observations of seat belt use were made in seven schools . Income stratification delineated a subset of these schools in which seat belt use increased by 86 % ( p = 0.01 ) . Half of the schools failed to follow protocol , and no change in seat belt use was observed . CONCLUSIONS ( 1 ) School K-2 safety education improves family seat belt use , ( 2 ) low income schools should be targeted , and ( 3 ) strict adherence to the teaching protocol is essential Using a simulation game design ed to teach children to obey certain traffic safety rules , an experimental study was conducted with 136 five-year-old children in four Quebec schools . Within each classroom , subjects were r and omly divided into four groups : three intervention groups and one control group . Each of the experimental groups was subjected to a different intervention with outcome measured using three instruments related to attitudes , behavior , and transfer of learning of pedestrian traffic safety . Results suggest that simulation games including role-playing/group dynamics and modeling/training can change attitudes and modify behavior in the area of pedestrian traffic safety in children of this age BACKGROUND Programmes design ed to teach children about road safety have often failed to assess their effectiveness in terms of either an increase in children 's knowledge or an improvement in children 's behaviour . AIM The two studies reported here sought to address both issues , by focusing on the abilities of Primary 1 children ( 5 years old ) . SAMPLE A total of 120 Primary 1 children within the age range 4 - 5 years old participated in this study , drawn from three different primary schools within an educational district of Scotl and . METHODS In the first study the effects of three different road safety interventions were tested , all of which employed commercially marketed products : 1 ) a three-dimensional model of the traffic environment ; 2 ) a road safety board game ; and 3 ) illustrated posters and flip-chart material s. In the second study the transfer of knowledge to children 's behaviour in a real-life traffic environment was tested , using a sub sample of 47 children who had taken part in the first study . RESULTS Results from the first study showed , surprisingly , that all three interventions were effective in increasing children 's knowledge about safe and dangerous locations at which to cross the street , and that this knowledge was retained for a period of six months . Study 2 , however , showed that increased knowledge did not result in improved traffic behaviour . Children who had received training performed no better than children in a control group . CONCLUSION These findings highlight the need to distinguish between children 's road safety knowledge and their behaviour , particularly for teachers and parents , who may mistakenly believe that children who know more will be safer on the road Abstract Pedestrian-skills training procedures were compared using 30 mentally retarded institutionalized adults . Ten subjects were r and omly assigned to a no-treatment control group and ten subjects were assigned to each of two modes of pedestrian-skills training . The training methods included a form of individualized classroom training consisting of the practice of correct behavior using movable figures on a scale model of an intersection , vs independence training which emphasized self-evaluation of performance , social reinforcement , sign recognition and the utilization of a mock-up of an intersection on the hospital grounds . Data were taken on sign recognition , verbal and performance based responses to classroom training of pedestrian skills , performance of skills at an intersection on the hospital grounds , and performance of pedestrian skills in the community . Independence training proved to be significantly more effective than no treatment or classroom training . In addition , classroom training proved to be significantly more effective than no treatment at all A r and omized pretest and posttest comparative design was used to evaluate the outcome of implementing Think First for Kids ( TFFK ) , an injury prevention program for children grade s 1 , 2 , and 3 , among intervention and controls schools . The study showed that children often lack basic knowledge regarding safety and do not recognize behaviors considered high risk for injury . By using multivariate analysis , the intervention children had a significantly greater increase in knowledge about the brain and spinal cord and safe behaviors to prevent traumatic injury , and a decrease in self-reported , high-risk behaviors ( p < .001 ) when compared with control subjects , adjusting for the covariates gender , socioeconomic status , and race/ethnicity . African American and Hispanic children , although displaying the lowest test scores at baseline , had the largest absolute improvement in posttest scores . The TFKK prevention program addresses the leading causes of trauma among children including sports , motor vehicle crashes , falls , drowning , and pedestrian injuries Methods of confidence interval construction are provided for summary measures of treatment effect arising from design s r and omizing clusters to one of two treatment groups . Three basic design s are considered for the case of continuous and dichotomous variables : completely r and omized , pair-matched and stratified |
12,217 | 27,621,871 | Our analysis shows that ultrasonography may be an effective and reliable approach to detect cervical lymph node metastasis in esophageal cancer . | BACKGROUND Esophageal cancer is considered a serious malignancy with respect to its prognosis and mortality rate .
Cervical lymph node status is one of the keys to determining prognosis and treatment methods .
However , published data vary regarding the accuracy of ultrasound in the diagnosis of cervical lymph node metastasis .
We performed a meta- analysis to assess the efficacy of ultrasound for detecting cervical lymph node metastasis in patients with esophageal cancer . | Prospect i ve assessment of lymph node status , based on the findings of computed tomography , external ultrasonography and palpation , was compared with clinical results in 179 patients who underwent oesophagectomy with systematic node dissection . Preoperative findings for each node group were classified into four grade s : involvement not suspected ( − ) ; possible involvement ( ± ) ; probable involvement ( + ) ; and definite involvement ( + + ) . When only ( + + ) or ( + ) assessment was categorized as positive , the specificity was more than 94 per cent , although the sensitivity was less than 40 per cent . The preoperative assessment correlated significantly with the incidence of node involvement ( P < 0·02 ) , the degree of lymphatic invasion ( P < 0·0001 ) and outcome after operation . For patients with all nodes assessed as ( − ) , the 5‐year survival rate was 70 per cent , compared with 26 per cent for those with nodes assessed as ( + ) , P = 0·001 . Preoperative assessment provided useful information on nodal status PURPOSE To evaluate the value of external ultrasonography ( US ) of the neck in current dedicated preoperative staging of patients with cancer of the esophagus and gastroesophageal junction ( GEJ ) . MATERIAL S AND METHODS We analyzed 180 consecutive patients ( 154 men , 26 women , and mean age 63 ( 38 - 84 ) years ) without palpable cervical lymphadenopathy , treated between January 2001 and March 2006 . Suspicious lesions were confirmed by cytological examination . All first 125 consecutive patients ( group A ) were staged by st and ard endoscopic ultrasonography ( EUS ) , multidetector computed tomography ( md-CT ) , positron emission tomography with (18)F-fluorodeoxyglucose ( FDG-PET ) and external US . The other 55 patients ( group B ) were prospect ively staged according to a revised protocol consisting of routine EUS and md-CT , while PET was only performed in subjects with T3-T4 and /or N1 disease and external US solely on indication . RESULTS Cervical metastases were found in seven patients from group A ( 6 % ) and in five from group B ( 9 % ) . Twenty percent ( 4/20 ) of the tumors above the carina and 5 % ( 8/160 ) of the distal tumors presented with cervical metastases . All were diagnosed as T3 and T4 tumors on EUS . Eleven of these metastases were detected by external US and nine on md-CT . All nodal metastases were detected by the combination of PET and md-CT . No cervical metastases were missed by the diagnostic algorithm in group B. CONCLUSION In present staging procedures for esophageal cancer , routine external US seems to have no additional value in detecting cervical metastases . It is still indicated to obtain cytological proof of suspected cervical lesions BACKGROUND AND OBJECTIVE A range of fixed-effect and r and om-effects meta-analytic methods are available to obtain summary estimates of measures of diagnostic test accuracy . The hierarchical summary receiver operating characteristic ( HSROC ) model proposed by Rutter and Gatsonis in 2001 represents a general framework for the meta- analysis of diagnostic test studies that allows different parameters to be defined as a fixed effect or r and om effects within the same model . The Bayesian method used for fitting the model is complex , however , and the model is not widely used . The objective of this report is to show how the model may be fitted using the SAS procedure NLMIXED and to compare the results to the fully Bayesian analysis using an example . METHODS The HSROC model , its assumptions , and its interpretation are described . The advantages of this model over the usual summary ROC ( SROC ) regression model are outlined . A complex example is used to compare the estimated SROC curves , expected operating points , and confidence intervals using the alternative approaches to fitting the model . RESULTS The empirical Bayes estimates obtained using NLMIXED agree closely with those obtained using the fully Bayesian analysis . CONCLUSION This alternative and more straightforward method for fitting the HSROC model makes the model more accessible to meta-analysts Objective To determine the prevalence of occult cervical nodal metastases in patients with squamous cell cancer and adenocarcinoma of the esophagus , and to determine the impact of esophagectomy with three-field lymph node dissection on survival and recurrence rates . Summary Background Data Although esophagectomy with three-field lymph node dissection is commonly practice d in Japan , its role in the surgical management of esophageal cancer in the United States , especially in patients with esophageal adenocarcinoma , is essentially unknown . Methods This is a prospect i ve observational study of esophagectomy with three-field lymphadenectomy . Eighty patients underwent resection between August 1994 and April 2001 . Clinicopathological information and follow-up data were collected on all patients until death or June 2001 . Results Hospital mortality and morbidity rates were 5 % and 46 % , respectively . Metastases to the recurrent laryngeal and /or deep cervical nodes occurred in 36 % of patients irrespective of cell type ( adenocarcinoma 37 % , squamous 34 % ) or location within the esophagus ( lower third 32 % , middle third 60 % ) . Overall 5-year and disease-free survival rates were 51 % and 46 % , respectively . Sixty-nine percent presented with nodal metastases . The 5-year survival rate for node-negative patients was 88 % ; that for those with nodal metastases was 33 % . The 5-year survival rate in patients with positive cervical nodes was 25 % ( squamous 40 % , adenocarcinoma 15 % ) . Conclusions Esophagectomy with three-field lymph node dissection can be performed with a low mortality and reasonable morbidity . Unsuspected metastases to the recurrent laryngeal and /or cervical nodes are present in 36 % of patients regardless of cell type or location within the esophagus . Thirty percent of patients were upstaged , mainly from stage III to stage IV . An overall 5-year survival rate of 51 % suggests a true survival benefit beyond that achieved solely on the basis of stage migration BACKGROUND AND OBJECTIVES Both ultrasound ( US ) and computed tomography ( CT ) can be used to detect supraclavicular lymph node metastases . Aim was to compare US , US plus fine-needle aspiration ( US-FNA ) , CT , US + CT , and US-FNA + CT for the detection of these metastases in esophageal or gastric cardia cancer patients . METHODS Between 1994 and 2004 , 567 patients underwent US and CT for esophageal or gastric cardia cancer staging . Gold st and ard was postoperative detection of lymph nodes in the resected specimen , FNA , or a radiological result with follow-up . RESULTS Sensitivities of US ( 75 % ) , US-FNA ( 72 % ) , US + CT ( 80 % ) , and US-FNA + CT ( 79 % ) were higher than sensitivity of CT alone ( 25 % ) ( P < 0.001 ) . Specificities were high for US-FNA ( 100 % ) , CT ( 99 % ) , and US-FNA + CT ( 99 % ) , whereas those of US alone ( 91 % ) and US + CT ( 91 % ) were lower ( P < 0.001 ) . In 4/65 ( 6 % ) patients with true-positive malignant lymph nodes , CT was positive with US and /or US-FNA being negative . However , in 36/65 ( 55 % ) patients , US and /or US-FNA were positive with CT being negative . CONCLUSION US-FNA seems the preferred diagnostic modality for the detection of supraclavicular lymph node metastases in patients with esophageal or gastric cardia cancer . Sensitivity of metastases detection only slightly improves if US-FNA is combined with CT . A prospect i ve , comparative study is however needed BACKGROUND AND OBJECTIVE Publication bias and other sample size effects are issues for meta-analyses of test accuracy , as for r and omized trials . We investigate limitations of st and ard funnel plots and tests when applied to meta-analyses of test accuracy and look for improved methods . METHODS Type I and type II error rates for existing and alternative tests of sample size effects were estimated and compared in simulated meta-analyses of test accuracy . RESULTS Type I error rates for the Begg , Egger , and Macaskill tests are inflated for typical diagnostic odds ratios ( DOR ) , when disease prevalence differs from 50 % and when thresholds favor sensitivity over specificity or vice versa . Regression and correlation tests based on functions of effective sample size are valid , if occasionally conservative , tests for sample size effects . Empirical evidence suggests that they have adequate power to be useful tests . When DORs are heterogeneous , however , all tests of funnel plot asymmetry have low power . CONCLUSION Existing tests that use st and ard errors of odds ratios are likely to be seriously misleading if applied to meta-analyses of test accuracy . The effective sample size funnel plot and associated regression test of asymmetry should be used to detect publication bias and other sample size related effects BACKGROUND Exact clinical staging before treatment of esophageal cancer has become increasingly important in the evaluation and comparison of the results of different treatment modalities , including surgery , chemotherapy , and radiotherapy . METHODS The accuracy of preoperative tumor staging by using an esophagography , esophagoscopy , percutaneous and endoscopic ultrasonography , and computed tomography was assessed in 224 patients with resectable esophageal cancer . The results of tumor staging by these tests were compared prospect ively with the pathologic stage of the esophagectomy specimens with respect to the T and N categories defined by the International Union Against Cancer TNM classification . RESULTS For the T category , the overall accuracy was 80 % . For the N category , overall accuracy was 72 % , with a sensitivity of 78 % , a specificity of 60 % , and a positive predictive value of 78 % . Overall , the accuracy of stage grouping was 56 % . CONCLUSIONS Either the T or N categories can be predicted reliably by clinical staging techniques . However , the preoperative stage grouping might not be valid in resectable , localized esophageal cancer Objective To determine the impact of radical node dissection on the recurrence patterns and survival rates of patients with carcinoma of the esophagus . Summary Background Data The role of esophagectomy with radical lymphadenectomy in the treatment of esophageal cancer is controversial . Most centers favor a limited operation with no attempt at nodal clearance . However , disease recurrence and patient survival rates remain dismal with or without preoperative therapy . The authors postulate that a more radical node dissection would reduce local failure rates and enhance survival . Methods One hundred eleven patients with esophageal cancer underwent en bloc esophagectomy with radical lymph node dissection between 1988 and 1998 . In 90 % of patients the procedure was applied nonselectively and without any preoperative therapy . Patients were prospect ively followed up for recurrence patterns and survival . Results The 5-year survival rate including noncancer deaths was 40 % . The 5-year survival rates for patients with stage 1 , 2A , 2B , 3 , and 4 disease were 78 % , 72 % , 0 % , 39 % , and 27 % , respectively . Forty percent of patients had node-negative disease ( 5-year survival rate , 75 % ) , and 60 % had nodal metastases ( 5-year survival rate , 26 % ) . Recurrence occurred in 39 % of patients and was local in only 8 % . Conclusions Radical esophagectomy results in superior overall and stage-specific 5-year survival rates . Extensive node dissection has a positive impact on survival rates , particularly in patients with nodal metastases AIM This study evaluates the use of neck ultrasound in staging squamous oesophageal carcinoma . MATERIAL S AND METHODS A prospect i ve analysis of the clinical , neck ultrasound ( US ) and thoraco-abdominal computed tomography ( CT ) findings in 121 patients with squamous oesophageal carcinoma at presentation was performed . The relationship between malignant neck nodes , mediastinal and abdominal adenopathy , location and size of the primary tumour was analysed . RESULTS Ten of 121 patients ( 8 % ) had clinical ly palpable neck nodes which were deemed malignant in six ( 5 % ) following US and fine-needle aspiration for cytology . Of those 111 patients with no palpable neck nodes , 31 ( 28 % ) had malignant nodes shown on US . The more cephalad the location of the primary tumour , the higher the frequency of malignant neck nodes which were found in 80 % , 52 % , 29 % and 9 % of cervical , upper thoracic , mid-thoracic and lower thoracic oesophageal tumours , respectively . Eleven ( 29 % ) of the 38 patients with malignant neck nodes shown on US had no CT evidence of additional adenopathy in the mediastinum or upper abdomen . Neck US altered TNM staging in 22/121 ( 18 % ) patients at presentation . CONCLUSION Neck US frequently detects clinical ly impalpable metastatic nodes leading to altered TNM staging in patients with squamous oesophageal carcinoma . We advocate its routine use when staging squamous oesophageal carcinoma Introduction : Lymphatic dissemination of a ( non-cervical ) esophageal tumor to the neck is generally considered as distant metastasis . The aim of this study was to determine the additional value of external ultrasonography ( US ) to detect lymphatic metastasis to the neck after normal CT scan ( CT ) with or without normal PET scan ( PET ) . Methods : Between January 2003 and December 2005 , 306 patients were analyzed for esophageal cancer in our department . A total of 233 patients underwent both CT and external US of the neck . PET was performed in 109 of these patients as part of a prospect i ve cohort study . Fine needle aspiration ( FNA ) was only performed if external US reported suspected lymph nodes . FNA was defined as gold st and ard . Results : In 176 patients ( 76 % ) , CT did not identify any suspected nodes , but external US disagreed in 36 of them . In 9 of these patients , FNA confirmed metastasis , result ing in an additional value of external US after normal CT scanning of 5 % ( 9/176 ) . In 74 patients ( 68 % ) , CT and PET did not identify any suspected nodes , but external US disagreed in 11 of them . In 3 of these patients , FNA confirmed metastasis , result ing in an additional value of external US after normal CT and PET of 4 % ( 3/74 ) . Conclusion : Considering its minimal invasiveness and wide availability in combination with the importance of the potential therapeutic consequences , we conclude that external US of the neck should be part of the routine diagnostic work-up in patients with esophageal cancer , even after normal CT and PET scanning This study was performed to evaluate the use of cervical ultrasonography and ultrasound-guided fine-needle aspiration for pretherapeutic staging of oesophageal cancer . 50 patients with a thoracic-oesophageal cancer ( upper third = 8 , middle = 36 , lower = 6 ) , previously untreated , underwent cervical ultrasonography to detect supraclavicular lymph node metastases ( LN ) . An ultrasound fine-needle aspiration biopsy was attempted in 12 cases of suspected LN . 26 patients were operated on , of which 13 had surgical exploration of the neck . All patients were followed after treatment with special attention to the supraclavicular area . 14 patients ( 28 % ) were ultrasonography positive , 5 of 8 in the upper third , 9 of 42 in the two other thirds . Of the 12 patients where a fine-needle biopsy was attempted , 9 showed neoplastic cells ( 75 % ) . 5 patients had cervical metastatic LN at surgery , and 5 other patients demonstrated supraclavicular LN metastases during the follow-up . There was one false positive and six false negatives from cervical ultrasonography and two false negatives of UGFAB ( ultrasound-guided fine-needle aspiration biopsy ) . The sensitivity and the specificity of the cervical ultrasonography were 68 and 97 % , respectively . The pretherapeutic staging was modified : 7 patients initially stage II-III were re grade d to stage IV . Cervical ultrasonography is a reliable method of assessment of supraclavicular LN in thoracic oesophageal carcinoma BACKGROUND AND OBJECTIVES Although the three-field lymphadenectomy has established as a st and ard operation for esophageal cancer in Japan , criticism remains due to the lack of r and omized controlled trials with a high EBM level . This retrospective study aims to clarify the effectiveness of the three-field lymphadenectomy using the data obtained from 906 consecutive patients with esophageal cancer who underwent R0 esophagectomy with the three-field lymphadenectomy . METHOD Efficacy Index ( EI ) was calculated for each lymph node station and grossly cervical , mediastinal , or abdominal dissection field . The values of EI were compared according to main tumor location . RESULTS Cervical lymph node dissection had high EI in upper and middle thoracic esophageal cancer but it was very small in lower esophageal cancer . Abdominal lymphadenectomy for upper thoracic esophageal cancer had some but limited efficacy only in paracardiac and lesser curvature stations . Cervical lymphadenectomy for lower esophageal cancer showed some but limited efficacy only in cervical paraesophageal stations . CONCLUSION Our investigation clearly shows the effectiveness and importance of wide range lymph node dissection defined as D3 according to the Japanese N-grouping system for thoracic esophageal cancer . The three-field lymphadenectomy is regarded as a st and ard procedure for upper and middle thoracic esophageal cancer |
12,218 | 29,797,177 | Conclusion This systematic review revealed that the highest negative impact on quality of life of individuals su bmi tted to third molar surgery was observed on the first postoperative day , decreasing over the follow-up period | Objective The purpose of this systematic review was to assess the impact of third molar removal on patient ’s quality of life . | Objectives This study describes patients ' perceptions of changes in oral health related quality of life ( OHQOL ) in the early postoperative period following third molar surgery . Methods One hundred patients were enrolled in a prospect i ve cohort study of the surgical removal of lower third molars under local anaesthetic . Two specific oral health related quality of life measures , OHIP-14 and OHQoLUK Results Both oral health related quality of life measures identified a significant deterioration in quality of life on POD1 ( P<0.01 ) and this remained evident on POD2 ( P<0.01 ) , POD3 ( P<0.01 ) , POD4 ( P<0.01 ) and POD5 ( P<0.05 ) . By POD6 and POD7 there was no significant difference in quality of life compared with preoperative status ( P>0.05 ) . Deterioration in life quality over the study period was associated with postoperative clinical findings ( P<0.05 ) : swelling and trismus . Conclusion The study concludes that there is a significant deterioration in oral health related quality of life in the immediate postoperative period following third molar surgery ; particularly during the first five days . This is associated with postoperative clinical findings . This has implication for patients deciding on third molar surgery and informed consent Aim The aim of this study was to evaluate the changes in oral health-related Quality of Life ( QoL ) following third molar surgery with either oral administration or submucosal injection of prednisolone . Patient and methods Subjects were r and omly distributed into three groups of 62 subjects each : Group A consisted of subjects who received 40 mg oral prednisolone ; group B received 40 mg submucosal injection of prednisolone , while group C did not receive prednisolone . Preoperative and postoperative quality of life evaluations of all subjects were done using the 14-item Oral Health Impact Profile ( OHIP-14 ) question naire . Postoperatively , quality of life evaluation was done on postoperative days 1 , 3 , and 7 . Subjects were categorized as either affected ( OHIP score ≤28 ) or not affected ( OHIP score > 28 ) . Mean OHIP scores between preoperative and postoperative periods , as well as between the three groups , were compared . Results A significant increase in the mean total and subscale scores was found in all the groups postoperatively . This was most marked on the first postoperative day , and it gradually improved throughout the immediate postoperative period . Subjects who received prednisolone experienced a statistically significant better quality of life than those who did not . Subjects who received submucosal injection of prednisolone showed statistically significant less deterioration in QoL than those who received oral prednisolone ( P = 0.001 ) . Conclusion Administration of prednisolone was significantly associated with less deterioration in quality of life and earlier recovery when compared with subjects who did not receive prednisolone . Submucosal injection of prednisolone 40 mg ( which offers a simple , safe , painless , and cost-effective therapeutic option ) is an effective therapeutic strategy for improving the quality of life after surgical removal of impacted lower third molars PURPOSE This study was design ed to assess the impact of " pain and swelling " associated with third molars on patients ' quality of life before surgery . PATIENTS AND METHODS The data for these analyses were obtained from a larger ongoing study design ed to examine the surgical and medical management of problems associated with third molars . Data from 480 patients with 4 third molars scheduled for removal were used in the analysis . Question naires administered presurgery assessed patients ' medical and dental history , their reasons for seeking third molar removal , and sociodemographic characteristics . Adverse impacts on oral health-related quality of life were measured using the 14-item Oral Health Impact Profile ( OHIP ) question naire . The primary outcome variable was the percentage of people reporting 1 or more of the 12 non-pain-specific OHIP items " fairly often " or " very often " during the 3 months before enrollment . RESULTS One third ( 178 of 480 ) of patients said they were seeking third molar surgery because of current or previous symptoms of pain/swelling , and 17 % reported 1 or more of the 12 non-pain-specific OHIP items . In the multivariate logistic regression model , the odds of one or more impacts was greater for people who presented because of symptoms ( odds ratio [ OR ] , 2.9 ; 95 % confidence interval [ CI ] , 1.7 to 4.8 ) , who were aged 25 years or more ( OR , 1.9 ; 95 % CI , 1.1 - 3.3 ) , and who had a self-reported history of tooth loss due to pathology or trauma ( OR , 2.9 ; 95 % CI , 1.9 to 5.5 ) . CONCLUSIONS Adverse impacts on quality of life occurred for 1 in 8 patients seeking third molar surgery , and the odds increased 3-fold for patients who had experienced pain/swelling compared with those who were asymptomatic Background This study aim ed to evaluate the patient 's pain and quality of life after suture removal at either 3 or 7 days following the bilateral surgical extraction of impacted lower third molars . Methods This study was a prospect i ve , r and omized controlled clinical trial carried out in 30 patients , who acted as their own control . Each patient required the bilaterally impacted m and ibular third molars to be extracted . The impacted teeth were removed and the wound margins were approximated and sutured with black braided silk . The suture material was removed on day 3 on one side and on day 7 on the other . Each participant was asked to complete a question naire after the removal of the suture material on each design ated day . Results Regarding overall clinical symptoms , the mean VAS scores of male and female participants on day 3 were not significantly different from those on day 7 . A significant difference was found in female participants , in that overall daily activity was better on day 7 . There were significant differences in the ability to smile and laugh in both sexes and the ability to chew in the male participants was better on day 7 . Conclusions There were no significant differences in the patient 's pain and quality of life between suture removal on day 3 or on day 7 following surgery to remove impacted lower third molars PURPOSE The aim of this study was to verify possible associations between oral health-related quality of life ( QoL ) and the position of the lower third molar among patients undergoing lower third molar surgery during the first postoperative week . MATERIAL S AND METHODS We performed an interventional prospect i ve study of 86 patients for whom the preoperative treatment plan included the removal of 2 third molar teeth from the same side in a 1-time procedure . The patients were divided into 2 groups depending on the position of the lower third molar . QoL was evaluated before and after the surgical procedure ( during the first 7 days ) with the Oral Health Impact Profile ( OHIP ) 14 question naire . Data were treated according to Stata 10.0 ( StataCorp , College Station , TX ) . Variables were evaluated by use of split-plot analysis of variance for the repeated- measures analysis to identify the association between QoL and the position of the lower third molar . RESULTS Patients can have deterioration in their QoL immediately after surgery , especially during the first and second postoperative days , and subsequently show rapid improvement . The variation in the total OHIP score during the days after surgery was significant , whereas a decrease in QoL was observed immediately after the procedure ( P = .001 ) , which returned to initial value ( preoperative ) levels after the sixth postoperative day . The OHIP domains with higher scores ( ie , those that had an impact ) were physical pain , psychological discomfort , and physical disability ( domains 2 , 3 , and 4 , respectively ) . CONCLUSIONS Teeth considered to be associated with technical difficulties for extraction based on their position had a higher score on the OHIP-14 question naire and worse health-related QoL score . QoL outcomes may be as important as clinical signs in decisions regarding third molar extraction Cold therapy is a conventional and widely used modality for reducing pain , trismus , and oedema after dentoalveolar surgeries . However , information reported in the literature on its effectiveness is insufficient and controversial . This study was performed to evaluate the effect of local cold application in reducing pain , trismus , and swelling after impacted m and ibular third molar surgery . Thirty patients ( seven males and 23 females ) with bilateral symmetrical m and ibular impacted third molars were enrolled in this r and omized , self-controlled , observer-blind clinical trial . The patients were aged between 18 and 30 years . After surgical removal of the tooth on one side ( intervention ) , ice pack therapy was given for 24h after surgery ; for the other side ( control ) , no cold therapy was given . The time interval between the two surgeries was at least 4 weeks . The amount of pain , trismus , and facial swelling was measured on days 2 and 7 postoperative , and patient satisfaction with the cold therapy vs. no cold therapy was assessed . The amount of pain , trismus , and facial swelling , and the extent of patient satisfaction were not significantly different between the intervention and control sides . Cold therapy had no beneficial effects on postoperative sequelae after impacted m and ibular third molar surgery The aim of this study was to evaluate the efficacy of electro-acupuncture ( EAC ) on postoperative pain control after m and ibular third molar surgery . Twenty four young patients ( 12 male and 12 female ) with symmetrically impacted m and ibular third molars were selected . Each patient was su bmi tted to two separate surgical procedures under local anesthesia . At one side , extraction was carried out employing both prior ( 24h ) and immediately postoperative application of EAC , while on the contralateral side surgery was carried out without any treatment . EAC was applied on 6 bilateral systemic and 2 auricular points with a WQ10Dl appliance using 40 - 60Hz frequency for 20 min and individually adjusted intensity . Postoperative pain intensity was rated on a 100 mm visual analog scale ( VAS ) between 2 and 72 h and recording the amount of analgesics intake after surgery . Statistical analysis was performed using theWilcoxon test . Postoperative pain VAS scores were significantly lower for the EAC group ( p<0.05 ) and analgesic intake decreased ( p<0.05 ) for all evaluated periods ( p<0.05 ) . Under the tested conditions EAC therapy is efficient was proved controlling postoperative pain following m and ibular third molar surgical removal This study aims to evaluate the efficacy of the ozone and laser application in the management of pain , swelling , and trismus after third-molar surgery . Sixty consecutive patients with asymptomatic impacted m and ibular third molars were recruited into the study . Patients were r and omized into three treatment groups of 20 patients each : two study groups ( group 1 = low-level laser therapy ( LLLT ) , group 2 = ozone therapy ) and a control group ( no-LLLT or ozone therapy ) . Twenty teeth extraction s were performed in each group . Evaluations of postoperative pain , the number of analgesics tablets taken , trismus , swelling , and quality of life ( Oral Health Impact Profile-14 question naire ) were made . The sample consisted of 28 female and 32 male patients , whose total mean age was 23.5 ± 3.4 ( range , 18–25 ) years . The pain level and the number of analgesics tablets taken were lower in the ozonated and LLLT applied groups than in the control group . This study showed that ozone and low power laser therapies had a positive effect on the patients ’ quality of life . Trismus in the LLLT group was significantly less than in the ozonated and control groups ( p = 0.033 ) . Ozone application showed no superiority in regards of postoperative swelling ; however , LLLT group had significantly lower postoperative swelling . This study demonstrates that ozone and laser therapies are useful for the reduction of postoperative pain and they increase quality of life after third-molar surgery . Although the ozone therapy had no effect on postoperative swelling and trismus after surgical removal of impacted lower third molars , LLLT had a positive effect BACKGROUND Oral and Maxillofacial operations can be extremely frightening treatment situations . General data on this phenomenon should be acquired through a multi-centre trial . METHOD A 10-page question naire was developed which was answered by 600 oral and maxillofacial patients before individual treatment . Control groups consisted of 800 surgical , dental and general practitioners/internal medicine patients . Twenty six medical practice s and hospital departments in 11 German cities were involved in the trial . RESULTS Both subjective anxiety assessment by patients and objective testing ( State Trait Anxiety Inventory ; STAI ) indicated a high level of treatment anxiety for oral and maxillofacial treatment situations . Oral and Maxillofacial Surgery ( OMFS ) patients ' scores were significantly higher than those of control groups . Especially younger and female patients , patients treated under local anaesthesia and out- patients showed intensive anxiety . Previous treatment experience in OMFS did not modify test results . CONCLUSION Managing perioperative anxiety is still a major challenge in OMFS . Irrespective of technical , pharmacological and surgical advances , developing and establishing stress-reducing and anxiolytic perioperative techniques is of considerable importance for both patients and surgeons Abstract Introduction Third molar surgery ( TMS ) became a routine , safe office procedure with generally predictable outcomes and relative low cost . It affects quality of life ( QOL ) of patients by causing considerable pain , swelling and trismus ; by changing what people eat , their speech in the first few days after surgery . The purpose of the present study was to improve QOL of patient after lower TMS by injecting single dose 8 mg submucosal dexamethasone . Material s and Methods Forty healthy adult subjects of either gender underwent surgical removal of the lower impacted third molar under local anaesthesia and after being r and omly assigned to receive either 8 mg dexamethasone submucosal injection or normal saline injection in proximity to surgical site . Statistical Analysis UsedChi-square test , Mann – Whitney U test ( Z ) , t student and unpaired t test , and Fisher extract test were used for calculation of data . Results Facial swelling , trismus showed significant reduction immediate postoperative day in dexamethasone groups . Patient perception postoperative pain on VAS score was not significant . PoSSe statistics , only three out of seven subscales showed a statistically significant difference between groups viz . , Eating subscale , Appearance subscale , Sickness subscale but over all improvement in QOL was observed . Conclusions Submucosal dexamethasone effectively reduces postoperative sequelae and improves postoperative QOL after TMS PURPOSE The purpose of this study was to identify the risk factors for severe discomfort after m and ibular third molar surgery and to assess the validity of the Postoperative Symptom Severity ( PoSSe ) scale . PATIENTS AND METHODS In a 2-year prospect i ve study , a total of 255 unilateral impacted m and ibular third molar teeth were surgically removed under local anesthesia by 3 surgeons . St and ardized surgical and analgesic protocol s were followed . At the review appointment , 1 week after surgery , all patients returned a completed follow-up question naire ( PoSSe scale ) and were evaluated clinical ly for postoperative pain ( number of painkillers taken ) and trismus ( differences in mouth opening ) . Sixteen predictive variables were evaluated using stepwise logistic regression analysis to identify the risk factors associated with severe discomfort . RESULTS Severe postoperative discomfort was predicted by these independent variables : gender , tobacco use , ramus relationship/space available , and antibiotic prophylaxis . Oral contraceptive use and operation time were not identified as risk factors . The patients ' perceptions of the severity of symptoms ( PoSSe scale score ) was strongly correlated with clinical assessment of trismus ( r = 0.54 ) and pain ( r = 0.42 ) . CONCLUSION The PoSSe scale result ed in a valid and responsive measure of the severity of symptoms after surgical extraction of lower third molars and reflected the clinical severity of the postoperative discomfort . From a patient 's perspective , operative factors had little bearing on the quality of life after removal of m and ibular third molars PURPOSE The purpose of the present study was to compare the effect of submucosal versus intramuscular administration of dexamethasone sodium phosphate on patients ' quality of life after surgical removal of impacted lower third molars . PATIENTS AND METHODS A r and omized , non-blind , clinical trial was planned . The sample was composed of patients requiring extraction under local anesthesia of a single partial bony impacted m and ibular third molar with Class II or III and position B or C , according to the Pell and Gregory classification . The patients were r and omly distributed into 1 of 3 groups : submucosal dexamethasone , intramuscular dexamethasone , and a control group that received no steroid . A modified translated question naire was used to assess the patients ' perception regarding different quality of life dimensions . In addition , the objective measurements of facial pain , swelling , and trismus were performed on days 1 , 3 , and 7 postoperatively . RESULTS A total of 33 subjects requiring surgical removal of a single impacted m and ibular third molar under local anesthesia were included in the present study . Both dexamethasone groups showed a significant reduction in swelling and pain compared with the control group at all intervals ( P < .05 ) . Submucosal dexamethasone provided significant improvement in trismus compared with the control group on day 1 postoperatively ( P = .026 ) . Both dexamethasone groups showed a highly significant difference in the effect on quality of life and the duration of effect in all subscale scores ( P < .01 ) except for the " speech " and " appearance " subscales . The effect was comparable between the 2 treated groups in all parameters . The effect of the 2 routes of dexamethasone was also comparable for all parameters . CONCLUSIONS Submucosal injection of dexamethasone 4 mg is an effective therapeutic strategy for improving the quality of life after surgical removal of impacted lower third molars with a comparable effect on postoperative sequelae to intramuscular injection . It offers a simple , safe , painless , noninvasive , and cost effective therapeutic option for moderate and severe cases The objective of this study was to evaluate the quality of life ( QoL ) and degree of satisfaction among adult out patients after surgical extraction of a lower third molar under local anaesthesia , and to assess the impact of thorough explanation of the anticipated postoperative course on their pain and daily activities . Ninety-two patients filled a question naire assessing social isolation , working isolation , eating ability , speaking ability , sleep impairment , physical appearance , discomfort at suture removal and overall satisfaction on days 4 and 7 after surgery . A 100-mm visual analogue scale ( VAS ) of pain was scored by the patients every day after extraction until day 7 . Before extraction , patients were r and omly allocated to one of two groups : the test group received detailed verbal instructions from a surgeon about the postoperative course after extraction of the third molars , together with a written text containing postoperative instructions . One day after extraction , they were asked by telephone about their status . The control group only received the written text with postoperative instructions , with a few basic oral explanations . Ninety-one patients ( 53 of them female ) completed the question naires . The decrease in pain was linear over time . Men referred significantly less pain than women , but there were no statistically significant differences between the test and control groups . The test group was characterized by a significantly greater inability to work . Lower third molar surgery significantly affects patient quality of life and environment , particularly during the first 3 days after extraction Aim To evaluate the effect of ice pack therapy on oral health-related quality of life ( OHRQoL ) following third molar surgery . Methods All consecutive subjects who required surgical extraction of lower third molars and satisfied the inclusion criteria were r and omly allocated into two groups . Subjects in group A were instructed to apply ice packs directly over the masseteric region on the operated side intermittently after third molar surgery . This first application was supervised in the clinic and was repeated at the 24-h postoperative review . Subjects in group A were further instructed to apply the ice pack when at home every one and a half hours on postoperative days 0 and 1 while he/she was awake as described . Group B subjects did not apply ice pack therapy . Facial swelling , pain , trismus , and quality of life ( using Oral Health Impact Profile-14 ( OHIP-14 ) instrument ) were evaluated both preoperatively and postoperatively . Postoperative scores in both groups were compared . Results A significant increase in the mean total and subscale scores of OHIP-14 was found in both groups postoperatively when compared with preoperative value . Subjects who received ice pack therapy had a better quality of life than those who did not . Subjects whose postoperative QoL were affected were statistically significantly higher in group B than in group A at all postoperative evaluation points ( P < 0.05 ) . Statistically significant differences were also observed between the groups in the various subscales analyzed , with better quality of life seen among subjects in group A. Conclusions Quality of life after third molar surgery was significantly better in subjects who had cryotherapy after third molar than those who did not have cryotherapy . Cryotherapy is a viable alternative or adjunct to other established modes of improving the quality of life of patients following surgical extraction of third molars PURPOSE The purpose of this study was to measure the difficulty of third molar ( M3 ) extraction s and to identify demographic , anatomic , and operative variables associated with extraction difficulty . MATERIAL S AND METHODS To address the research purpose , we implemented a prospect i ve cohort study and enrolled a sample composed of patients presenting for M3 removal . Predictor variables were categorized as demographic , anatomic , and operative . The primary outcome variable was difficulty of extraction , measured as extraction time per tooth . The secondary outcome variable was the surgeons postoperative estimate of M3 extraction difficulty , measured on a 100-mm visual analog scale ( VAS ) . Appropriate univariate , bivariate , and multivariate statistics were computed . RESULTS The sample was composed of 82 subjects , having 250 M3s ( 53.2 % m and ibular ) extracted , with a mean age of 26.2 + /- 10.7 years ; 57.3 % were female , 72.0 % were white . The mean operating time per M3 extraction was 6.9 + /- 7.6 minutes . The mean estimate of difficulty was 39.6 + /- 24.7 mm and was significantly correlated ( r = 0.68 ) with extraction time ( P < .01 ) . Surgical experience , M3 location ( maxillary versus m and ibular ) , procedure type , tooth position , number of teeth extracted , and tooth morphology were statistically associated ( P < or = .05 ) with extraction time in a multivariate model . CONCLUSION Our model indicates that the difficulty of M3 extraction s is governed primarily by anatomic and operative factors with minimal influence from demographic factors PURPOSE The study goal was to assess both clinical and health-related quality of life ( HRQOL ) outcomes after third molar surgery . METHODS Patients who were having 4 third molars removed were enrolled in a prospect i ve clinical trial . Baseline data were recorded that included demographics , the patient 's and surgeon 's assessment of third molar conditions , and details of the surgical procedure . After surgery , clinical data were collected that detailed healing and any treatment that was rendered . Each patient was given an HRQOL instrument to complete on each postsurgery day for 14 days ; the instrument was design ed to assess a patient 's perception of recovery in 4 main categories : pain , lifestyle , oral function , and other symptoms related to the procedure . RESULTS Recovery data were available for 630 of 740 enrolled patients . The median age of the 630 patients was 21 years , and the median operation time was 30 minutes . Recovery for most HRQOL measures occurred within 5 days after surgery . However , recovery from pain to the criterion of " little or none " was delayed relative to other HRQOL measures . Twenty-two percent of patients were treated for delayed healing after surgery . CONCLUSIONS Having both clinical and HRQOL data on recovery after third molar surgery could assist the surgeon when informing prospect i ve patients about what to expect after surgery to remove third molars PURPOSE The aim of this study was to evaluate the effect of two different concentrations ( 4 and 8 mg ) of dexamethasone to decrease the swelling and trismus after the surgical extraction of m and ibular impacted third molars . METHODS This r and omized clinical trial comprised thirty ( 30 ) adult patients of both genders with no local or systemic problems , with bilateral impacted lower third molars in similar position , where surgical extraction had been indicated . They were given 4 mg and 8 mg of dexamethasone 1 hour before the surgical procedure at the first or second surgery . The choice of which side to operate first and the amount of concentration of medication to use was made r and omly and double-blindly . Postoperative pain was evaluated using a visual analog scale ( VAS ) and the degree of swelling was evaluated through facial reference points ' variation . The presence of trismus was analyzed through measurement of the interincisal distance ( IID ) . These assessment s were obtained before the operation and 24h and 48 h after the surgery . RESULTS Based on statistic analysis ( pared t-student and Wilcoxon tests ) , the results showed a significant difference in the measurements of the degree of swelling and trismus of the treated sample . 8 mg of dexamethasone promoted a greater reduction of symptoms than 4 mg of dexamethasone CONCLUSIONS The administration of 8 mg of the dexamethasone was more effective than 4 mg of the dexamethasone to reduce the degree of swelling and trismus . However , it had no effect on pain control The aim of this study was to evaluate the efficacy of therapeutic ozone application in the management of pain , swelling , and trismus associated with the surgical removal of impacted m and ibular third molars . Sixty consecutive patients with asymptomatic bilateral impacted m and ibular third molars were recruited into the study . R and omly , by use of envelops , the molar on one side was extracted and ozone therapy was given ( study side ) ; the molar on the other side was extracted 2 weeks later and sham ozone therapy was given ( negative control side ) . The mean age of the 60 patients was 22.6±2.3 years ( range 18 - 25 years ) . No differences were found between the two sides for mouth opening or swelling . The degree of pain and the number of analgesic tablets taken was significantly lower for the study side . This study showed ozone therapy to have a positive effect on OHIP-14 question naire results PURPOSE To compare recovery for clinical and health-related quality of life ( HRQOL ) outcomes after third molar surgery in patients predicted to be at risk for delayed recovery , treated with or without intravenous ( IV ) corticosteroids at surgery . PATIENTS AND METHODS Patients at least 18 years of age and with all 4 third molars below the occlusal plane were given IV corticosteroids just before third molar surgery . Clinical and HRQOL outcomes of these patients were compared with those of a nonconcurrent control group who did not receive corticosteroids . No antibiotics were administered . The control group was selected using the same criteria and treated under the same surgical protocol as the corticosteroid group . Differences between the groups were assessed with Cochran-Mantel-Haenszel row mean score statistics . RESULTS Sixty patients were in each cohort . The incidence of delayed clinical recovery , a postsurgery visit with treatment , was higher in the control group compared with the corticosteroid group . In the corticosteroid group , 6 patients ( 10 % ) had 1 postsurgery visit with treatment . In the control group without corticosteroids , 17 patients ( 28 % ) had at least 1 postsurgery visit with treatment ( P = .01 ) . Compared with the control group , nausea tended to bother patients less on postsurgery day 1 ( P = .07 ) ; sleep was improved on postsurgery days 1 through 4 ( P < .05 ) . Though not statistically significant , corticosteroids reduced the patients reported recovery by at least 1 day for pain , lifestyle , and oral function . CONCLUSION Administration of IV corticosteroids before third molar surgery without antibiotics does not hamper clinical recovery even when healthy adult patients are predicted to have delayed recovery . Overall , IV corticosteroid administration had a limited , but beneficial effect on HRQOL outcomes OBJECTIVES This study had two objectives : ( i ) to explore and model domains describing the real-time impact of third molars ( TMs ) on quality of life ( QoL ) ; and ( ii ) to assess the percentage coverage , in some generic health-related quality of life ( HRQoL ) and oral health-related quality of life ( OHRQoL ) instruments , of the TM QoL domains identified in this study . METHODOLOGY A global cross-sectional sample of tweets containing ' wisdom tooth ' over a 1-week period retrieved 3,537 tweets . After r and om quota sampling , classification and filtering , only 843 tweets were included in the thematic analysis . A TM QoL model was constructed based on the associations of the identified domains . Domains for the selected generic HRQoL and OHRQoL instruments were plotted against the domains identified in the study to calculate the percentage coverage for each . RESULTS The QoL domains identified were pain ( n = 348 , 41 % ) , mood ( n = 173 , 20 % ) , anxiety and fear ( n = 54 , 7 % ) , enjoying food ( n = 41 , 4 % ) , coping ( n = 37 , 4 % ) , daily activities ( n = 34 , 4 % ) , sleep ( n = 24 , 2 % ) , social life ( n = 19 , 2 % ) , physical health ( n = 17 , 2 % ) , ability to think ( n = 9 , 1 % ) , self-care ( n = 8 , 1 % ) and sporting & recreation ( n = 2 , < 1 % ) . The Assessment Quality of Life instrument ( AQoL-8D ) covers 87 % of the TM QoL domains , while the rest of the HRQoL and OHRQoL instruments cover 33 - 60 % . CONCLUSION This study shows how Twitter can be used to obtain real-time QoL data , which might be used to model how TMs impact on QoL. The TM QoL domains identified in the study were generally under-represented among the generic OHRQoL instruments assessed while , the HRQoL AQoL-8D covered most of the TM QoL domains . The QoL domains identified in the study might be used to develop a new OHRQoL measure for TMs |
12,219 | 31,248,217 | RESULTS The majority of the review ed studies were conducted in the U.S. , but there seems to be an increase in literature on pesticide take-home pathway in developing countries .
Most of the articles provided evidence that farmworkers ' families are exposed to pesticides at higher levels than non-farmworkers ' families .
The levels may depend on several factors such as seasonality , parental occupation , cohabitation with a farmworker , behavior at work/home , age , and gender .
Community-based interventions disrupting the take-home pathway seem to be effective at reducing pesticide exposure . | BACKGROUND Exposure to pesticides via take-home can be an important pathway for farmworkers ' families .
OBJECTIVE The aim of this review was to summarize and analyze the literature published during the last decade of exposure to pesticides via take-home pathway in farmworkers ' families . | Pesticides are a collective term for a wide array of chemicals intended to kill unwanted insects , plants , molds , and rodents . Food , water , and treatment in the home , yard , and school are all potential sources of children ’s exposure . Exposures to pesticides may be overt or subacute , and effects range from acute to chronic toxicity . In 2008 , pesticides were the ninth most common substance reported to poison control centers , and approximately 45 % of all reports of pesticide poisoning were for children . Organophosphate and carbamate poisoning are perhaps the most widely known acute poisoning syndromes , can be diagnosed by depressed red blood cell cholinesterase levels , and have available antidotal therapy . However , numerous other pesticides that may cause acute toxicity , such as pyrethroid and neonicotinoid insecticides , herbicides , fungicides , and rodenticides , also have specific toxic effects ; recognition of these effects may help identify acute exposures . Evidence is increasingly emerging about chronic health implication s from both acute and chronic exposure . A growing body of epidemiological evidence demonstrates associations between parental use of pesticides , particularly insecticides , with acute lymphocytic leukemia and brain tumors . Prenatal , household , and occupational exposures ( maternal and paternal ) appear to be the largest risks . Prospect i ve cohort studies link early-life exposure to organophosphates and organochlorine pesticides ( primarily DDT ) with adverse effects on neurodevelopment and behavior . Among the findings associated with increased pesticide levels are poorer mental development by using the Bayley index and increased scores on measures assessing pervasive developmental disorder , inattention , and attention-deficit/hyperactivity disorder . Related animal toxicology studies provide supportive biological plausibility for these findings . Additional data suggest that there may also be an association between parental pesticide use and adverse birth outcomes including physical birth defects , low birth weight , and fetal death , although the data are less robust than for cancer and neurodevelopmental effects . Children ’s exposures to pesticides should be limited as much as possible The take-home pathway is a significant source of organophosphate pesticide exposure for young children ( 3–5 years old ) living with an adult farmworker . This avoidable exposure pathway is an important target for intervention . We selected 24 agricultural communities in the Yakima Valley of Washington State and r and omly assigned them to receive an educational intervention ( n = 12 ) to reduce children ’s pesticide exposure or usual care ( n = 12 ) . We assessed exposure to pesticides in nearly 200 adults and children during the pre and post-intervention periods by measuring metabolites in urine . We compared pre- and post-intervention exposures by expressing the child ’s pesticide metabolite concentration as a fraction of the adult ’s concentration living in the same household , because the amount of pesticides applied during the collection periods varied . Exposures in our community were consistently higher , sometimes above the 95th percentile of the exposures reported by the National Health and Nutrition Examination Survey ( NHANES ) . While intervention and control communities demonstrated a reduction in the ratio of child to adult exposure , this reduction was more pronounced in intervention communities ( 2.7-fold , p < 0.001 compared to 1.7-fold , p = 0.052 for intervention and control , respectively ) . By examining the child/adult biomarker ratio , we demonstrated that our community-based intervention was effective in reducing pesticide exposure to children in agricultural communities We conducted a r and omized-controlled trial of a home-based intervention to reduce pesticide exposures to farmworkers ’ children in Monterey County , California ( n=116 families ) . The intervention consisted of three home-based educational sessions delivered by community health workers in Spanish . Measurements of organophosphate ( OP ) insecticide metabolites in child urine ( n=106 ) and pesticides in home floor wipes ( n=103 ) were collected before and after the intervention . Median child urinary dialkyl phosphate ( DAP ) metabolite levels were slightly lower among the intervention group children at follow-up compared with baseline , albeit nonsignificantly . DAP metabolite levels in the control group children were markedly higher at follow-up compared with baseline . In adjusted models , intervention participation was associated with a 51 % decrease in total DAP metabolite levels . Carbaryl , chlorpyrifos , cypermethrin , dacthal , diazinon , malathion , and trans-permethrin were commonly detected in the floor wipes . In adjusted models , intervention participation was significantly associated with a 37 % decrease in trans-permethrin floor wipe levels in homes , but not OP or other agricultural pesticides . In summary , intervention group children had slightly reduced pesticide exposures , whereas child exposures were higher among the control group . Additional intervention studies evaluating methods to reduce pesticide exposures to farmworker families and children are needed Background Exposure to organophosphate ( OP ) pesticides is an occupational hazard for farmworkers and affects their children through the take-home pathway . Objectives We examined the effectiveness of a r and omized community intervention to reduce pesticide exposure among farmworkers and their children . Methods We conducted a baseline survey of a cross-sectional sample of farmworkers ( year 1 ) in 24 participating communities . Communities were r and omized to intervention or control . After 2 years of intervention , a new cross-sectional survey of farmworkers was conducted ( year 4 ) . Farmworkers with a child 2–6 years of age were asked to participate in a sub study in which urine was collected from the farmworker and child , and dust was collected from the home and the vehicle driven to work . Results The median concentration of urinary metabolites was higher in year 4 than in year 1 for dimethylthiophosphate ( DMTP ) and dimethyldithiophosphate in adults and for DMTP for children . There were significant increases within both the intervention and control communities between year 1 and year 4 ( p < 0.005 ) ; however , the differences were not significant between study communities after adjusting for year ( p = 0.21 ) . The dust residue data showed azinphos-methyl having the highest percentage of detects in vehicles ( 86 % and 84 % in years 1 and 4 , respectively ) and in house dust ( 85 % and 83 % in years 1 and 4 , respectively ) . There were no significant differences between intervention and control communities after adjusting for year ( p = 0.49 ) . Conclusions We found no significant decreases in urinary pesticide metabolite concentrations or in pesticide residue concentrations in house and vehicle dust from intervention community households compared with control community households after adjusting for baseline . These negative findings may have implication s for future community-wide interventions |
12,220 | 31,332,919 | Testing targeted to population s at higher risk yielded high coverage rates in many setting s. Implementation of novel testing approaches , including dried blood spot ( DBS ) testing , was associated with increased coverage in several setting s including drug services , pharmacies and STI clinics .
Community‐based testing services were effective in reaching population s at higher risk for infection , vulnerable and hard‐to‐reach population s. In conclusion , our review identified several successful testing approaches implemented in healthcare and community setting s , including testing approaches targeting groups at higher risk , community‐based testing services and DBS testing .
Combining a diverse set of testing opportunities within national testing strategies may lead to higher impact both in terms of testing coverage and in terms of reduction , on the undiagnosed fraction | Abstract An estimated 9 million individuals are chronically infected with hepatitis B virus ( HBV ) and hepatitis C virus ( HCV ) across the European Union/European Economic Area ( EU/EEA ) , many of which are yet to be diagnosed .
We performed a systematic review to identify interventions effective at improving testing offer and uptake in the EU/EEA . | Aims The community-based AERLI intervention provided training and education to people who inject drugs ( PWID ) about HIV and HCV transmission risk reduction , with a focus on drug injecting practice s , other injection-related complications , and access to HIV and HCV testing and care . We hypothesized that in such a population where HCV prevalence is very high and where few know their HCV serostatus , AERLI would lead to increased HCV testing . Methods The national multisite intervention study ANRS-AERLI consisted in assessing the impact of an injection-centered face-to-face educational session offered in volunteer harm reduction ( HR ) centers ( “ with intervention ” ) compared with st and ard HR centers ( “ without intervention ” ) . The study included 271 PWID interviewed on three occasions : enrolment , 6 and 12 months . Participants in the intervention group received at least one face-to-face educational session during the first 6 months . Measurements The primary outcome of this analysis was reporting to have been tested for HCV during the previous 6 months . Statistical analyses used a two-step Heckman approach to account for bias arising from the non-r and omized clustering design . This approach identified factors associated with HCV testing during the previous 6 months . Findings Of the 271 participants , 127 and 144 were enrolled in the control and intervention groups , respectively . Of the latter , 113 received at least one educational session . For the present analysis , we selected 114 and 88 participants eligible for HCV testing in the control and intervention groups , respectively . In the intervention group , 44 % of participants reported having being tested for HCV during the previous 6 months at enrolment and 85 % at 6 months or 12 months . In the control group , these percentages were 51 % at enrolment and 78 % at 12 months . Multivariable analyses showed that participants who received at least one educational session during follow-up were more likely to report HCV testing , compared with those who did not receive any intervention ( 95%[CI ] = 4.13[1.03;16.60 ] ) . Conclusion The educational intervention AERLI had already shown efficiency in reducing HCV at-risk practice s and associated cutaneous complications and also seems to have a positive impact in increasing HCV testing in PWID Background Supporting 21st century health care and the practice of evidence -based medicine ( EBM ) requires ubiquitous access to clinical information and to knowledge-based re sources to answer clinical questions . Many questions go unanswered , however , due to lack of skills in formulating questions , crafting effective search strategies , and accessing data bases to identify best levels of evidence . Methods This r and omized trial was design ed as a pilot study to measure the relevancy of search results using three different interfaces for the PubMed search system . Two of the search interfaces utilized a specific framework called PICO , which was design ed to focus clinical questions and to prompt for publication type or type of question asked . The third interface was the st and ard PubMed interface readily available on the Web . Study subjects were recruited from interns and residents on an inpatient general medicine rotation at an academic medical center in the US . Thirty-one subjects were r and omized to one of the three interfaces , given 3 clinical questions , and asked to search PubMed for a set of relevant articles that would provide an answer for each question . The success of the search results was determined by a precision score , which compared the number of relevant or gold st and ard articles retrieved in a result set to the total number of articles retrieved in that set . Results Participants using the PICO templates ( Protocol A or Protocol B ) had higher precision scores for each question than the participants who used Protocol C , the st and ard PubMed Web interface . ( Question 1 : A = 35 % , B = 28 % , C = 20 % ; Question 2 : A = 5 % , B = 6 % , C = 4 % ; Question 3 : A = 1 % , B = 0 % , C = 0 % ) 95 % confidence intervals were calculated for the precision for each question using a lower boundary of zero . However , the 95 % confidence limits were overlapping , suggesting no statistical difference between the groups . Conclusion Due to the small number of search es for each arm , this pilot study could not demonstrate a statistically significant difference between the search protocol s. However there was a trend towards higher precision that needs to be investigated in a larger study to determine if PICO can improve the relevancy of search results Background Rising rates of infectious diseases in international migrants has reignited the debate around screening . There have been calls to strengthen primary -care-based programmes , focusing on latent TB . We did a cross-sectional study of new migrants to test an innovative one-stop blood test approach to detect multiple infections at one appointment ( HIV , latent tuberculosis , and hepatitis B/C ) on registration with a General Practitioner ( GP ) in primary care . Methods The study was done across two GP practice s attached to hospital Accident and Emergency Departments ( A&E ) in a high migrant area of London for 6 months . Inclusion criteria were foreign-born individuals from a high TB prevalence country ( > 40 cases per 100,000 ) who have lived in the UK ≤ 10 years , and were over 18 years of age . All new migrants who attended a New Patient Health Check were screened for eligibility and offered the blood test . We followed routine care pathways for follow-up . Results There were 1235 new registration s in 6 months . 453 attended their New Patient Health Check , of which 47 ( 10.4 % ) were identified as new migrants ( age 32.11 years [ range 18–72 ] ; 22 different nationalities ; time in UK 2.28 years [ 0–10 ] ) . 36 ( 76.6 % ) participated in the study . The intervention only increased the prevalence of diagnosed latent TB ( 18.18 % [ 95 % CI 6.98 - 35.46 ] ; 181.8 cases per 1000 ) . Ultimately 0 ( 0 % ) of 6 patients with latent TB went on to complete treatment ( 3 did not attend referral ) . No cases of HIV or hepatitis B/C were found . Foreign-born patients were under-represented at these practice s in relation to 2011 Census data ( Chi-square test −0.111 [ 95 % CI −0.125 to −0.097 ] ; p < 0.001 ) . Conclusion The one-stop approach was feasible in this context and acceptability was high . However , the number of presenting migrants was surprisingly low , reflecting the barriers to care that this group face on arrival , and none ultimately received treatment . The ongoing UK debate around immigration checks and charging in primary care for new migrants can only have negative implication s for the promotion of screening in this group . Until GP registration is more actively promoted in new migrants , a better place to test this one-stop approach could be in A&E departments where migrants may present in larger numbers Background : The prevalence of hepatitis C ( HCV ) is elevated within prison population s , yet diagnosis in prisons remains low . Dried blood spot testing ( DBST ) is a simple procedure for the detection of HCV antibodies ; its impact on testing in the prison context is unknown . Methods : We carried out a stepped-wedge cluster-r and omized control trial of DBST for HCV among prisoners within five male prisons and one female prison . Each prison was a separate cluster . The order in which the intervention ( training in use of DBST for HCV testing and logistic support ) was introduced was r and omized across clusters . The outcome measure was the HCV testing rate by prison . Imputation analysis was carried out to account for missing data . Planned and actual intervention times differed in some prisons ; data were thus analysed by intention to treat ( ITT ) and by observed step times . Results : There was insufficient evidence of an effect of the intervention on testing rate using either the ITT intervention time ( OR : 0.84 ; 95 % CI : 0.68–1.03 ; P = 0.088 ) or using the actual intervention time ( OR : 0.86 ; 95 % CI : 0.71–1.06 ; P = 0.153 ) . This was confirmed by the pooled results of five imputed data sets . Conclusions : DBST as a st and -alone intervention was insufficient to increase HCV diagnosis within the UK prison setting . Factors such as staff training and allocation of staff time for regular clinics are key to improving service delivery . We demonstrate that prisons can conduct rigorous studies of new interventions , but data collection can be problematic . Trial registration : International St and ard R and omized Controlled Trial Number Register ( IS RCT N number IS RCT N05628482 ) INTRODUCTION Because of its lack of clinical signs , the detection of hepatitis C virus ( HCV ) infection in the Netherl and s remains suboptimal . Therefore , the Dutch Health Council proposed an HCV campaign aim ed to inform the general public and motivate people at risk to seek medical advice . Because knowledge and awareness of HCV infection is low among primary care workers , the implementation of a support programme for primary care complementary to a HCV campaign seems appropriate . OBJECTIVE To evaluate the added value of a support programme for primary care complementary to a public HCV campaign . METHODS We performed a non-r and omized controlled intervention study . In two similar regions , a public HCV campaign was organized . In the intervention region , an additional support for primary care was provided by means of brochures , short courses and informative visits . RESULTS In the intervention region , the proportional increase in anti-HCV tests was 3.02 ( 57 - 172 tests ) . In the control region , this increase was 1.36 ( 86 - 118 tests ) . In the intervention region , the increase in positive anti-HCV tests was 1.7 % ( 95 % confidence interval ( CI ) : -0.2 % to -3.7 % ) . In the control region , this number decreased by 0.9 % ( 95 % CI : -4.1 % to 2.3 % ) . CONCLUSIONS The addition of primary care practice support leads to considerable improvements in medical consciousness regarding HCV infection in primary care . Even though the positive effect on case finding can not be indisputably demonstrated due to low prevalence , our results indicate such a positive effect . Therefore , future campaigns aim ed at hepatitis C should invariably implement additional support for primary care to improve diagnostic uptake and optimize case finding Objectives To assess the impact of computer-assisted interview compared with pen and paper on disclosure of sexual behaviour , diagnostic testing by clinicians , infections diagnosed and referral for counselling . Methods Two-centre parallel three-arm r and omised controlled open trial . Computer-generated r and omisation with allocation concealment using sealed envelopes . Setting Two London teaching hospital sexual health clinics . Participants 2351 clinic attenders over the age of 16 years . Interventions Computer-assisted self-interview ( CASI ) . Computer-assisted personal interview ( CAPI ) . Pen and paper interview ( PAPI ) . Main Outcome Measures Diagnostic tests ordered , sexually transmitted infections ( STI ) . Secondary Outcomes Disclosure of sexual risk , referral for counselling . Results 801 , 763 and 787 patients r and omly allocated to receive CASI , CAPI and PAPI . 795 , 744 and 779 were available for intention-to-treat analysis . Significantly more diagnostic testing for hepatitis B and C and rectal sample s in the CAPI arm ( odds for more testing relative to PAPI 1.32 ; 95 % CI 1.09 to 1.59 ) . This pattern was not seen among CASI patients . HIV testing was significantly lower among CASI patients ( odds for less testing relative to PAPI 0.73 ; 95 % CI 0.59 to 0.90 ) . STI diagnoses were not significantly different by trial arm . A summary measure of seven prespecified sensitive behaviours found greater reporting with CASI ( OR 1.4 ; 95 % CI 1.2 to 1.6 ) and CAPI ( OR 1.4 ; 95 % CI 1.2 to 1.7 ) compared with PAPI . Conclusion CASI and CAPI can generate greater recording of risky behaviour than traditional PAPI . Increased disclosure did not increase STI diagnoses . Safeguards may be needed to ensure that clinicians are prompted to act upon disclosures made during self-interview . Trial registration IS RCT N : 97674664 In this r and omized-control trial , conducted at a free clinic in France for predominately immigrant population s without healthcare , we demonstrate that simultaneous HIV/HBV/HCV point-of-care rapid testing improves screening outcomes . Increased awareness of infection status likely helped link these patients to care BACKGROUND Direct-acting antiviral therapy ( DAAs ) for hepatitis C infection ( HCV ) have a much smaller burden of treatment than interferon-based regimes , require less monitoring and are very effective . New pathways are required to increase access to treatment amongst people prescribed opioid substitution therapy ( OST ) . METHODS An exploratory cluster r and omised controlled trial with mixed methods evaluation was undertaken to compare the uptake of dried blood spot testing ( DBST ) and treatment of people with genotype 1 HCV infection in a conventional service pathway versus a pharmacist-led pathway in a population receiving OST . RESULTS Pharmacies r and omised to the conventional pathway obtained 58 DBST from 244 patients (24%):15 new reactive tests and 33 new negative tests were identified . Within the pharmacist-led pathway , 94 DBST were obtained from 262 patients ( 36 % ) : 26 new reactive tests and 54 new negative tests were identified . Participants in the pharmacist-led pathway were more likely to take a DBST ( p<0.003 ) . Of participants referred for treatment through the conventional pathway , 4 patients from 15 with new reactive tests ( 27 % ) attended clinic for assessment . In the pharmacist-led treatment pathway , 20 patients from 26 with new reactive tests ( 77 % ) attended for assessment blood tests . Participants in the pharmacist-led pathway were more likely to proceed through the assessment for treatment ( p<0.002 ) . One participant completed treatment through the conventional pathway and three patients completed treatment through the pharmacist-led pathway . The process evaluation identified key themes important to service user completers and staff participants . CONCLUSION The study provides evidence that testing and treatment for HCV in a pharmacist led-pathway is a feasible treatment pathway for people who receive supervised OST consumption through community pharmacies . This feasibility trial therefore provides sufficient confirmation to justify proceeding to a full trial BACKGROUND Screening migrants from areas where hepatitis B virus ( HBV ) infection is endemic is important to implement preventive measures in Europe . The aim of our study was to assess ( 1 ) the feasibility of point-of-care screening in a primary care clinic and ( 2 ) hepatitis B surface antigen ( HBsAg ) prevalence , associated risk factors , and its clinical and epidemiological implication s in undocumented migrants in Brescia , northern Italy . METHODS A longitudinal prospect i ve study was conducted from January 2006 to April 2010 to assess HBsAg reactivity and associated risk factors among consenting undocumented migrants who accessed the Service of International Medicine of Brescia 's Local Health Authority . Genotyping assay was also performed in HBV DNA-positive patients . RESULTS Screening was accepted by 3,728/4,078 ( 91.4 % ) subjects consecutively observed during the study period , 224 ( 6 % ) of whom were found to be HBsAg-positive . HBsAg reactivity was independently associated with the prevalence of HBsAg carriers in the geographical area of provenance ( p < 0.001 ) . On the contrary , current or past sexual risk behaviors ( despite being common in our sample ) were not associated with HBV infection . Half of the HBsAg patients ( 111/224 ) had either hepatitis B e-antigen (HBeAg)-positive or -negative chronic HBV infection with a possible indication for treatment . HBV genotypes were identified in 45 of 167 HBV-infected patients as follows : genotype D , 27 subjects ; genotype A , 8 ; genotype B , 5 ; and genotype C , 5 . The geographical distribution of genotypes reflected the geographic provenance . CONCLUSIONS Our results suggest that point-of-care screening is feasible in undocumented migrants and should be targeted according to provenance . Case detection of HBV infection among migrants could potentially reduce HBV incidence in migrants ' contacts and in the general population by prompting vaccination of susceptible individuals and care of eligible infected patients INTRODUCTION AND AIMS This study was design ed to determine whether providing an oral swab test in the community for blood borne virus testing leads to an increase in subsequent attendance for sexually transmitted infection ( STI ) screening at the STI clinic compared with making appointments for young people to attend the clinic for same day HIV testing and STI screening . DESIGN AND METHODS Participants were r and omised into either the oral swab test group or the blood test group of the trial if eligible . RESULTS All the 27 participants in the oral swab test group were tested for HIV and hepatitis C compared with five for HIV and two for hepatitis C in the blood test group ( P < 0.001 ) . Only two of the 27 participants in the blood test group were tested for hepatitis B compared with 25 in the oral swab test group ( P < 0.001 ) . Nine participants in the oral swab test group attended the STI clinic for STI screening compared with three in the blood test group ( P = 0.09 ) . DISCUSSION AND CONCLUSIONS An oral swab test in the community for blood borne virus testing leads to an increase in the number of young high-risk people tested for blood borne infections and is associated with a trend towards higher rates of subsequent attendance for STI screening BACKGROUND We compared the efficacy of two viral hepatitis B and C ( VHBC ) screening strategies , relative to no intervention , among underprivileged people ( UP ) living in shelters in the Lyon area . METHODS Eighteen of 37 shelters were r and omly sample d after stratification based on the accommodation capacity and the screening centres/shelters distance . Through r and omization , the S0 strategy ( no intervention ) , the S1 strategy [ group information ( GI ) and referral for screening ] and the S2 strategy ( GI and in situ screening ) were each applied in six shelters . A st and ardized question naire was offered to each participant . Follow-up of positive cases was organized via the reference centre of VHBC of Lyon . RESULTS The screening completion rate ( SCR ) among 1276 included subjects in S0 , S1 and S2 was 1.5 , 42.8 and 59.7 % , respectively ( P < 10(-6 ) ) . This rate was higher in S2 regardless of the sociodemographic variable considered . Odds ratios ( OR ) of screening completion ( SC ) was significantly higher in S1 versus S0 , OR = 49.8 [ 95 % confidence interval ( CI ) : 26.1 - 102.1 ] , in S2 versus S0 , OR = 98.5 ( 95 % CI : 51.9 - 200.8 ) and in S2 versus S1 , OR = 2.0 ( 95 % CI : 1.3 - 2.9 ) . Age , country of birth and professional inactivity were independently associated with SC . CONCLUSIONS Health authorities must ensure widespread screening of UP , which is more effective when conducted in shelters than in screening centres The objective of this study was to assess whether introducing dried blood spot testing can increase hepatitis C virus ( HCV ) diagnostic testing . A cluster r and omized controlled trial was conducted . Sites were matched into pairs , with one site in each pair r and omly allocated to receive the intervention ( training and use of dried blood spot ) . Data were collected from all sites for 6 months before and 6 months after the start of the intervention . The participants were 22 specialist drug clinics and six prisons in Engl and and Wales . The main outcome measure of this study was percentage point difference in individuals tested for HCV ( the difference between the percentage of patients tested 6 months after and 6 months before the introduction of dried blood spot tests ) . Before the trial , 8 % of patients at control and intervention sites had been tested for HCV , with 16 sites testing less than 5 % of their caseload . The average percentage point difference between intervention and control sites was 14.5 % ( 95 % CI 1.3 - 28 % , paired t-test , P = 0.03 ) ; with 13 of the 14 pairs contributing to the positive effect of the intervention ( Wilcoxon matched-pairs signed-rank-test , P = 0.002 ) . The size of the difference between intervention and control sites varied considerably . The study provides preliminary supporting evidence that dried blood spot testing may increase the uptake of HCV diagnostic testing , by increasing the opportunity for patients to be offered testing . Additional trials with a larger number of sites are justified , ideally in the context of drug and treatment policies that gave clearer priority ( and targets ) to infection control and testing Objective The aim of the study was to evaluate the effectiveness of Dry Blood Spot testing ( DBST ) for hepatitis C within a geographical area . Design This is a prospect i ve cohort study of all individuals living in Tayside who had received a hepatitis C virus ( HCV ) DBST between 2009 and 2011 . Results During the study , 1123 DBSTs were carried out . 946 individuals had one test . 295 ( 31.2 % ) of these individuals were HCV antibody positive on their first test . Overall , 94.3 % ( 902/956 ) individuals returned for the results of their test . During the course of the study 177 individuals were retested and 29 new cases of hepatitis C were detected . 249 individuals attended for further follow-up , and 164 ( 65.5 % ) were PCR positive . All 164 PCR-positive individuals were offered referral into specialist HCV services for further assessment . Data showed 62.5 % were genotype 3 , 65.1 % had a low viral load ( < 600 000 iu/ml ) and 77.5 % had a Fibroscan score below 7 KPa . To date , 40 have commenced treatment and a further 16 are currently in the assessment period . Overall , we have retained in services or treated 63.6 % ( 105/164 ) of patients who were initially referred and with effective support mechanisms in place we have achieved sustained viral response rates of 90 % . Conclusions The study has shown that DBST is a complementary technique to conventional venepuncture for the diagnosis of HCV . The majority of patients have low viral loads and low fibrosis scores , so that while this group of patients may be difficult to reach and may be challenging to maintain in therapy , they are easier to cure BACKGROUND Treatment uptake for hepatitis C virus ( HCV ) infection remains low in persons who inject drugs ( PWID ) , due to lack of knowledge and low perceived need for treatment . Therefore , we conducted a pilot study to assess the influence on knowledge and willingness for HCV screening and treatment among persons who use drugs ( PWUD ) by combining formal and peer education with FibroScan measurement . METHODS Clients of the Center for Alcohol and other Drug problems ( CAD ) in Limburg ( Belgium ) were r and omized into a control group , which received the st and ard of care , and an intervention group , which received an innovative combination of formal and peer education followed by FibroScan . Knowledge of HCV infection and willingness for screening and treatment were evaluated at baseline , after intervention and 1 and 3months after intervention by means of question naires . RESULTS Baseline knowledge was similar for the control ( n=27 ) and the intervention group ( n=25 ) ( 58 vs. 59 % ; p=0.67 ) . Immediately after the information session , knowledge increased to 86 % ( p<0.001 ) in the intervention group . After 3months , knowledge decreased significantly ( 69 % ; p=0.01 ) . No significant changes in knowledge were found in the control group . Baseline willingness for treatment was 81 % in both the control and intervention groups , but after 1 month decreased in the control group ( 44 % ) and remained stable in the intervention group ( 75 % ) . Differences in actual screening uptake between the control and intervention group were not significant ( 7 % vs. 20 % ) . Four percent of the intervention group and no one in the control group started treatment . CONCLUSION The small number of subjects should be considered when interpreting the results of this study . In brief , the single information session significantly improved HCV knowledge among PWUD , but did not result in a higher uptake for screening and treatment . This could signify that there are other important reasons , besides lack of knowledge , not to undergo screening or start treatment . The fact that knowledge decreased after 3months indicates that it would be beneficial to repeat the information session regularly Although hepatitis C virus ( HCV ) infection prevalence is high among drug users , they do not commonly receive regular care in academic centres . The aim of this prospect i ve study was to assess the influence of FibroScan use on HCV screening and management in street-based outreach . From January 2006 to January 2007 , all consecutive drug users were offered noninvasive evaluation of liver fibrosis with FibroScan . After FibroScan , parameters were recorded with a structured , face-to-face question naire by outreach workers . All 298 subjects accepted FibroScan evaluation drug use was -- ever injected heroin ( 69 % ) , ever snorted or injected cocaine ( 89 % ) , current chronic alcohol abuse ( 44 % ) . The median FibroScan score was 5.3 kPa . Before blood sampling , 34 % of subjects reported HCV positivity . HCV positivity was found in 83 cases . All these subjects had positive HCV-RNA . Forty-five subjects agreed to meet a hepatologist . By multivariate analysis , never snorted cocaine , consumed alcohol < 21 drinks per week , duration of injected heroin > 7 years , and FibroScan > 7.1 kPa were significantly associated with HCV positivity . Thus in a street-based outreach service for drug users , the acceptance of FibroScan is excellent . FibroScan with a hospital-based physician may facilitate screening and management of drug users for HCV infection |
12,221 | 25,803,792 | Our review offers encouraging evidence that community-based intervention packages reduce morbidity for women , mortality and morbidity for babies , and improves care-related outcomes particularly in low- and middle-income countries .
It has highlighted the value of integrating maternal and newborn care in community setting s through a range of interventions , which can be packaged effectively for delivery through a range of community health workers and health promotion groups .
While the importance of skilled delivery and facility-based services for maternal and newborn care can not be denied , there is sufficient evidence to scale up community-based care through packages which can be delivered by a range of community-based workers | BACKGROUND While maternal , infant and under-five child mortality rates in developing countries have declined significantly in the past two to three decades , newborn mortality rates have reduced much more slowly .
While it is recognised that almost half of the newborn deaths can be prevented by scaling up evidence -based available interventions ( such as tetanus toxoid immunisation to mothers , clean and skilled care at delivery , newborn resuscitation , exclusive breastfeeding , clean umbilical cord care , and /or management of infections in newborns ) , many require facility-based and outreach services .
It has also been stated that a significant proportion of these mortalities and morbidities could also be potentially addressed by developing community-based packaged interventions which should also be supplemented by developing and strengthening linkages with the local health systems .
Some of the recent community-based studies of interventions targeting women of reproductive age have shown variable impacts on maternal outcomes and hence it is uncertain if these strategies have consistent benefit across the continuum of maternal and newborn care .
OBJECTIVES To assess the effectiveness of community-based intervention packages in reducing maternal and neonatal morbidity and mortality ; and improving neonatal outcomes .
Assessment of risk of bias in these studies suggests concerns regarding insufficient information on sequence generation and regarding failure to adequately address incomplete outcome data , particularly from r and omised controlled trials . | Background Pakistan has high maternal mortality , particularly in the rural areas . The delay in decision making to seek medical care during obstetric emergencies remains a significant factor in maternal mortality . Methods We present results from an experimental study in rural Pakistan . Village clusters were r and omly assigned to intervention and control arms ( 16 clusters each ) . In the intervention clusters , women were provided information on safe motherhood through pictorial booklets and audiocassettes ; traditional birth attendants were trained in clean delivery and recognition of obstetric and newborn complications ; and emergency transportation systems were set up . In eight of the 16 intervention clusters , husb and s also received specially design ed education material s on safe motherhood and family planning . Pre- and post-intervention surveys on selected maternal and neonatal health indicators were conducted in all 32 clusters . A district-wide survey was conducted two years after project completion to measure any residual impact of the interventions . Results Pregnant women in intervention clusters received prenatal care and prophylactic iron therapy more frequently than pregnant women in control clusters . Providing safe motherhood education to husb and s result ed in further improvement of some indicators . There was a small but significant increase in percent of hospital deliveries but no impact on the use of skilled birth attendants . Perinatal mortality reduced significantly in clusters where only wives received information and education in safe motherhood . The survey to assess residual impact showed similar results . Conclusions We conclude that providing safe motherhood education increased the probability of pregnant women having prenatal care and utilization of health services for obstetric complications David Osrin and colleagues report findings from a cluster-r and omized trial conducted in Mumbai slums ; the trial aim ed to evaluate whether facilitator-supported women 's groups could improve perinatal outcomes Abstract Objectives : To establish the relative cost effectiveness of postnatal support in the community in addition to the usual care provided by community midwives . Design : R and omised controlled trial with six month follow up . Setting : Recruitment in a university teaching hospital and care provided in women 's homes . Participants : 623 postnatal women allocated at r and om to intervention ( 311 ) or control ( 312 ) group . Intervention : Up to 10 home visits in the first postnatal month of up to three hours duration by a community postnatal support worker . Main outcome measure : General health status as measured by the SF-36 and risk of postnatal depression . Breast feeding rates , satisfaction with care , use of services , and personal costs . Results : At six weeks there was no significant improvement in health status among the women in the intervention group . At six weeks the mean total NHS costs were £ 635 for the intervention group and £ 456 for the control group ( P=0.001 ) . At six months figures were £ 815 and £ 639 ( P=0.001 ) . There were no differences between the groups in use of social services or personal costs . The women in the intervention group were very satisfied with the support worker visits . Conclusions : There was no health benefit of additional home visits by community postnatal support workers compared with traditional community midwifery visiting as measured by the SF-36 . There were no savings to the NHS over six months after the introduction of the community postnatal support worker service Background Maternal and newborn mortality rates remain unacceptably high , especially where the majority of births occur in home setting s or in facilities with inadequate re sources . The introduction of emergency obstetric and newborn care services has been proposed by several organizations in order to improve pregnancy outcomes . However , the effectiveness of emergency obstetric and neonatal care services has never been proven . Also unproven is the effectiveness of community mobilization and community birth attendant training to improve pregnancy outcomes . Methods / Design We have developed a cluster-r and omized controlled trial to evaluate the impact of a comprehensive intervention of community mobilization , birth attendant training and improvement of quality of care in health facilities on perinatal mortality in low and middle-income countries where the majority of births take place in homes or first level care facilities . This trial will take place in 106 clusters ( 300 - 500 deliveries per year each ) across 7 sites of the Global Network for Women 's and Children 's Health Research in Argentina , Guatemala , India , Kenya , Pakistan and Zambia . The trial intervention has three key elements , community mobilization , home-based life saving skills for communities and birth attendants , and training of providers at obstetric facilities to improve quality of care . The primary outcome of the trial is perinatal mortality . Secondary outcomes include rates of stillbirth , 7-day neonatal mortality , maternal death or severe morbidity ( including obstetric fistula , eclampsia and obstetrical sepsis ) and 28-day neonatal mortality . Discussion In this trial , we are evaluating a combination of interventions including community mobilization and facility training in an attempt to improve pregnancy outcomes . If successful , the results of this trial will provide important information for policy makers and clinicians as they attempt to improve delivery services for pregnant women and newborns in low-income countries . Trial Registration Clinical Trials.gov Background A community-based r and omized control prenatal care trial was performed in a rural county of China during 2000 - 2003 . The purpose of this paper is to describe the trial implementation and the impact of the trial on the utilization of prenatal care and perinatal outcomes . Material s and methods In the study county , 10 townships ( from a total of 55 ) were each paired with a control ( 20 study townships in total ) , with the criteria for pairing being the township 's socioeconomic development , perinatal health , and maternal care utilization and provision . One of each township pair was r and omly allocated to the intervention or control groups . The trial interventions were : 1 ) training township hospital midwives and instructing them in how to provide systematic maternal care , 2 ) informing women in the community of the importance of prenatal care , 3 ) if needed , providing basic medical instruments to the hospitals . A variety of data sources were used to describe the trial implementation ( observations , group discussion s , field notes , survey to women ) . The data on pregnancy and perinatal outcomes were from the original h and -written work-records in the village family planning centers of the study townships . Results Implementation of the intervention was deficient . The factors hindering the trial implementation included poor coordination between midwives and family planning officers , broader policy changes implemented by the provincial government during the trial , the de central ization of county governance , and the lack of government funding for maternal care . There was only little difference in the use of maternal care , in women 's opinions related to maternal care or content of prenatal care , and no difference in the perinatal outcomes between the intervention and control townships . Conclusions A community based r and omized controlled trial could not be fully carried out in rural China as planned due to the changing political l and scape , the complexity of the socio-economic situation and a lengthy planning stage . The study could not answer if perinatal outcomes could be improved by increased use of prenatal care . Trial registration NCT Abstract Background Neonatal mortality remains high in rural Nepal . Previous work suggests that local women 's groups can effect significant improvement through community mobilisation . The possibility of identification and management of newborn infections by community-based workers has also arisen . Methods / Design The objective of this trial is to evaluate the effects on newborn health of two community-based interventions involving Female Community Health Volunteers . MIRA Dhanusha community groups : a participatory intervention with women 's groups . MIRA Dhanusha sepsis management : training of community volunteers in the recognition and management of neonatal sepsis . The study design is a cluster r and omized controlled trial involving 60 village development committee clusters allocated 1:1 to two interventions in a factorial design . MIRA Dhanusha community groups : Female Community Health Volunteers ( FCHVs ) are supported in convening monthly women 's groups . Nine groups per cluster ( 270 in total ) work through two action research cycles in which they ( i ) identify local issues around maternity , newborn health and nutrition , ( ii ) prioritise key problems , ( iii ) develop strategies to address them , ( iv ) implement the strategies , and ( v ) evaluate their success . Cycle 1 focuses on maternal and newborn health and cycle 2 on nutrition in pregnancy and infancy and associated postpartum care practice s. MIRA Dhanusha sepsis management : FCHVs are trained to care for vulnerable newborn infants . They ( i ) identify local births , ( ii ) identify low birth weight infants , ( iii ) identify possible newborn infection , ( iv ) manage the process of treatment with oral antibiotics and referral to a health facility to receive parenteral gentamicin , and ( v ) follow up infants and support families . Primary outcome : neonatal mortality rates . Secondary outcomes : MIRA Dhanusha community group : stillbirth , infant and under-two mortality rates , care practice s and health care seeking behaviour , maternal diet , breastfeeding and complementary feeding practice s , maternal and under-2 anthropometric status . MIRA Dhanusha sepsis management : identification and treatment of neonatal sepsis by community health volunteers , infection-specific neonatal mortality . Trial Registration noIS RCT N : IS RCT Background In Pakistan , only 59 - 73 % of children 12 - 23 months of age are fully immunized . This r and omized , controlled trial was conducted to assess the impact of a low-literacy immunization promotion educational intervention for mothers living in low-income communities of Karachi on infant immunization completion rates . Methods Three hundred and sixty-six mother-infant pairs , with infants aged ≤ 6 weeks , were enrolled and r and omized into either the intervention or control arm between August - November 2008 . The intervention , administered by trained community health workers , consisted of three targeted pictorial messages regarding vaccines . The control group received general health promotion messages based on Pakistan 's Lady Health Worker program curriculum . Assessment of DPT/Hepatitis B vaccine completion ( 3 doses ) was conducted 4-months after enrollment . A Poisson regression model was used to estimate effect of the intervention . The multivariable Poisson regression model included maternal education , paternal occupation , ownership of home , cooking fuel used at home , place of residence , the child 's immunization status at enrollment , and mother 's perception about the impact of immunization on child 's health . Results Baseline characteristics among the two groups were similar . At 4 month assessment , among 179 mother-infant pairs in the intervention group , 129 ( 72.1 % ) had received all 3 doses of DPT/Hepatitis B vaccine , whereas in the control group 92/178 ( 51.7 % ) had received all 3 doses . Multivariable analysis revealed a significant improvement of 39 % ( adjusted RR = 1.39 ; 95 % CI : 1.06 - 1.81 ) in DPT-3/Hepatitis B completion rates in the intervention group . Conclusion A simple educational intervention design ed for low-literate population s , improved DPT-3/Hepatitis B vaccine completion rates by 39 % . These findings have important implication s for improving routine immunization rates in Pakistan OBJECTIVES To determine the effectiveness of birth plans in increasing use of skilled care at delivery and in the postnatal period among antenatal care ( ANC ) attendees in a rural district with low occupancy of health units for delivery but high antenatal care uptake in northern Tanzania . METHODS Cluster r and omised trial in Ngorongoro district , Arusha region , involving 16 health units ( 8 per arm ) . Nine hundred and five pregnant women at 24 weeks of gestation and above ( 404 in the intervention arm ) were recruited and followed up to at least 1 month postpartum . RESULTS Skilled delivery care uptake was 16.8 % higher in the intervention units than in the control [ 95 % CI 2.6 - 31.0 ; P = 0.02 ] . Postnatal care utilisation in the first month of delivery was higher ( difference in proportions : 30.0 % [ 95 % CI 1.3 - 47.7 ; P < 0.01 ] ) and also initiated earlier ( mean duration 6.6 ± 1.7 days vs. 20.9 ± 4.4 days , P < 0.01 ) in the intervention than in the control arm . Women 's and providers ' reports of care satisfaction ( received or provided ) did not differ greatly between the two arms of the study ( difference in proportion : 12.1 % [ 95 % CI -6.3 - 30.5 ] P = 0.17 and 6.9 % [ 95 % CI -3.2 - 17.1 ] P = 0.15 , respectively ) . CONCLUSION Implementation of birth plans during ANC can increase the uptake of skilled delivery and post delivery care in the study district without negatively affecting women 's and providers ' satisfaction with available ANC services . Birth plans should be considered along with the range of other recommended interventions as a strategy to improve the uptake of maternal health services Background Around a quarter of the world 's neonatal and maternal deaths occur in India . Morbidity and mortality are highest in rural areas and among the poorest wealth quintiles . Few interventions to improve maternal and newborn health outcomes with government-m and ated community health workers have been rigorously evaluated at scale in this setting .The study aims to assess the impact of a community mobilisation intervention with women 's groups facilitated by ASHAs to improve maternal and newborn health outcomes among rural tribal communities of Jharkh and and Orissa . Methods / design The study is a cluster-r and omised controlled trial and will be implemented in five districts , three in Jharkh and and two in Orissa . The unit of r and omisation is a rural cluster of approximately 5000 population . We identified villages within rural , tribal areas of five districts , approached them for participation in the study and enrolled them into 30 clusters , with approximately 10 ASHAs per cluster . Within each district , 6 clusters were r and omly allocated to receive the community intervention or to the control group , result ing in 15 intervention and 15 control clusters . R and omisation was carried out in the presence of local stakeholders who selected the cluster numbers and allocated them to intervention or control using a pre-generated r and om number sequence . The intervention is a participatory learning and action cycle where ASHAs support community women 's groups through a four-phase process in which they identify and prioritise local maternal and newborn health problems , implement strategies to address these and evaluate the result . The cycle is design ed to fit with the ASHAs ' m and ate to mobilise communities for health and to complement their other tasks , including increasing institutional delivery rates and providing home visits to mothers and newborns . The trial 's primary endpoint is neonatal mortality during 24 months of intervention . Additional endpoints include home care practice s and health care-seeking in the antenatal , delivery and postnatal period . The impact of the intervention will be measured through a prospect i ve surveillance system implemented by the project team , through which mothers will be interviewed around six weeks after delivery . Cost data and qualitative data are collected for cost-effectiveness and process evaluations . Study registration IS RCT N : IS RCT BACKGROUND Most mothers breastfeed in Bangladesh , but they rarely practise exclusive breastfeeding . Hospital-based strategies for breastfeeding promotion can not reach them because about 95 % have home deliveries . We postulated that with the intervention of trained peer counsellors , mothers could be enabled to breastfeed exclusively for the recommended duration of 5 months . METHODS 40 adjacent zones in Dhaka were r and omised to intervention or control groups . Women were enrolled during the last trimester of pregnancy between February and December , 1996 . In the intervention group , 15 home-based counselling visits were scheduled , with two visits in the last trimester , three early postpartum ( within 48 h , on day 5 , between days 10 and 14 ) , and fortnightly thereafter until the infant was 5 months old . Peer counsellors were local mothers who received 10 days ' training . FINDINGS 363 women were enrolled in each group . Peer counselling significantly improved breastfeeding practice s. For the primary outcome , the prevalence of exclusive breastfeeding at 5 months was 202/228 ( 70 % ) for the intervention group and 17/285 ( 6 % ) for the control group ( difference=64 % ; 95 % CI 57%-71 % , p>0.0001 ) . For the secondary outcomes , mothers in the intervention group initiated breastfeeding earlier than control mothers and were less likely to give prelacteal and postlacteal foods . At day 4 , significantly more mothers in the intervention group breastfed exclusively than controls . INTERPRETATION Peer counsellors can effectively increase the initiation and duration of exclusive breastfeeding . We recommend incorporation of peer counsellors in mother and child health programmes in developing countries Background The disability associated with depression and its impact on maternal and child health has important implication s for public health policy . While the prevalence of postnatal depression is high , there are no prevalence data on antenatal depression in South Africa . The purpose of this study was to determine the prevalence and correlates of depressed mood in pregnancy in Cape Town peri-urban settlements . Methods This study reports on baseline data collected from the Philani Mentor Mothers Project ( PMMP ) , a community-based , cluster-r and omized controlled trial on the outskirts of Cape Town , South Africa . The PMMP aims to evaluate the effectiveness of a home-based intervention for preventing and managing illnesses related to HIV , TB , alcohol use and malnutrition in pregnant mothers and their infants . Participants were 1062 pregnant women from Khayelitsha and Mfuleni , Cape Town . Measures included the Edinburgh Postnatal Depression Scale ( EPDS ) , the Derived AUDIT-C , indices for social support with regards to partner and parents , and questions concerning socio-demographics , intimate partner violence , and the current pregnancy . Data were analysed using bivariate analyses followed by logistic regression . Results Depressed mood in pregnancy was reported by 39 % of mothers . The strongest predictors of depressed mood were lack of partner support , intimate partner violence , having a household income below R2000 per month , and younger age . Conclusions The high prevalence of depressed mood in pregnancy necessitates early screening and intervention in primary health care and antenatal setting s for depression . The effectiveness and scalability of community-based interventions for maternal depression must be developed for pregnant women in peri-urban settlements . Trial registration Clinical Trials.gov : NCT00972699 Study objective : To evaluate the effect of two forms of postnatal social support for disadvantaged inner city mothers on maternal and child health outcomes . Design : R and omised controlled trial with economic and process evaluations and follow up at 12 and 18 months . The two intervention groups received either the offer of a year of monthly supportive listening home visits by a support health visitor ( SHV ) , or a year of support from community groups providing drop in sessions , home visiting and /or telephone support ( CGS ) . Each was compared with a control group that received st and ard health visitor services . Setting : Two disadvantaged boroughs of London , United Kingdom . Participants : 731 women from culturally diverse background s with infants . Main results : At 12 and 18 months , there was little impact for either intervention on the main outcomes : child injury ( SHV : relative risk 0.99 ; 95 % confidence intervals 0.68 to 1.45 , CGS : 0.91 ; 0.61 to1.36 ) , maternal smoking ( SHV : 0.86 ; 0.62 to 1.19 , CGS : 0.97 ; 0.72 to 1.33 ) or maternal depression ( SHV : 0.86 ; 0.62 to1.19 , CGS : 0.93 ; 0.69 to 1.27 ) . SHV women had different patterns of health service use ( with fewer taking their children to the GP ) and had less anxious experiences of motherhood than control women . User satisfaction with the SHV intervention was high . Uptake of the CGS intervention was low : 19 % , compared with 94 % for the SHV intervention . Conclusions : There was no evidence of impact on the primary outcomes of either intervention among this culturally diverse population . The SHV intervention was associated with improvement in some of the secondary outcomes In response to the H1N1 epidemic , we used community health workers to design and implement a r and omized controlled trial to test the efficacy of a new automated call-monitoring system for second and third trimester predominantly Medicaid-eligible pregnant women in an urban free st and ing birth center to promptly detect symptoms of influenza and assure rapid treatment to prevent adverse outcomes from influenza . Daily automated telephone call to second and third trimester pregnant women asking if the woman experienced flu-like symptoms . Calls continued daily until 38 weeks gestation . A community health worker ’s voice was used for the automated call recording . Positive responses triggered an immediate referral to a nurse-midwife for prompt treatment with anti-viral medication . Fifty pregnant participants were r and omized into daily-automated call group ( n = 26 ) or health information group ( n = 24 ) . The automated call group participants ranged in age from 14 to 36 ( mean = 23.5 , SD = 6.3 ) , 84.7 % identified their race/ethnicity as African-American Non-Hispanic , and 80.7 % were Medicaid-Eligible . In the automated call group , 11.5 % chose to be immunized against H1N1 . The mean percent of patients reached daily was 45.1 % ( SD = 3.2 % ) and at least once every 3 days was 65.1 % ( SD = 3.1 % ) . One pregnant woman in the automated call group contracted H1N1 influenza and received prompt anti-viral treatment without any serious outcomes . Participation in daily-automated telephone calls did not differ significantly between patients younger than 18 years old versus patients 18 years or older . There was also no difference in participation between patients with parity of 0 versus patients with parity ≥1 . Participation in daily telephone calls significantly ( alpha ≤0.05 ) increased when a community health worker provided personal follow-up of non-responsive participants . 93.3 % of surveyed pregnant women , who received automated daily calls , recommended to use a similar daily call system in response to a future health crisis . Automated daily phone calls , design ed and produced by community health workers , is a feasible , well received strategy to provide urgent health information to an urban , Medicaid-eligible group of pregnant women , regardless of age or parity Background To evaluate a delivery strategy for newborn interventions in rural Bangladesh . Methods A cluster-r and omized controlled trial was conducted in Mirzapur , Bangladesh . Twelve unions were r and omized to intervention or comparison arm . All women of reproductive age were eligible to participate . In the intervention arm , community health workers identified pregnant women ; made two antenatal home visits to promote birth and newborn care preparedness ; made four postnatal home visits to negotiate preventive care practice s and to assess newborns for illness ; and referred sick neonates to a hospital and facilitated compliance . Primary outcome measures were antenatal and immediate newborn care behaviours , knowledge of danger signs , care seeking for neonatal complications , and neonatal mortality . Findings A total of 4616 and 5241 live births were recorded from 9987 and 11153 participants in the intervention and comparison arm , respectively . High coverage of antenatal ( 91 % visited twice ) and postnatal ( 69 % visited on days 0 or 1 ) home visitations was achieved . Indicators of care practice s and knowledge of maternal and neonatal danger signs improved . Adjusted mortality hazard ratio in the intervention arm , compared to the comparison arm , was 1.02 ( 95 % CI : 0.80–1.30 ) at baseline and 0.87 ( 95 % CI : 0.68–1.12 ) at endline . Primary causes of death were birth asphyxia ( 49 % ) and prematurity ( 26 % ) . No adverse events associated with interventions were reported . Conclusion Lack of evidence for mortality impact despite high program coverage and quality assurance of implementation , and improvements in targeted newborn care practice s suggests the intervention did not adequately address risk factors for mortality . The level and cause-structure of neonatal mortality in the local population must be considered in developing interventions . Programs must ensure skilled care during childbirth , including management of birth asphyxia and prematurity , and curative postnatal care during the first two days of life , in addition to essential newborn care and infection prevention and management . Trial Registration Clinical trials.gov Background Maternal , perinatal and neonatal mortality remains high in low-income countries . We evaluated community and facility-based interventions to reduce deaths in three districts of Malawi . Methods We evaluated a rural participatory women ’s group community intervention ( CI ) and a quality improvement intervention at health centres ( FI ) via a two-by-two factorial cluster r and omized controlled trial . Consenting pregnant women were followed-up to 2 months after birth using key informants . Primary outcomes were maternal , perinatal and neonatal mortality . Clusters were health centre catchment areas assigned using stratified computer-generated r and omization . Following exclusions , including non-birthing facilities , 61 clusters were analysed : control ( 17 clusters , 4912 births ) , FI ( 15 , 5335 ) , CI ( 15 , 5080 ) and FI + CI ( 14 , 5249 ) . This trial was registered as International St and ard R and omised Controlled Trial [ IS RCT N18073903 ] . Outcomes for 14 576 and 20 576 births were recorded during baseline ( June 2007–September 2008 ) and intervention ( October 2008–December 2010 ) periods . Results For control , FI , CI and FI + CI clusters neonatal mortality rates were 34.0 , 28.3 , 29.9 and 27.0 neonatal deaths per 1000 live births and perinatal mortality rates were 56.2 , 55.1 , 48.0 and 48.4 per 1000 births , during the intervention period . Adjusting for clustering and stratification , the neonatal mortality rate was 22 % lower in FI + CI than control clusters ( OR = 0.78 , 95 % CI 0.60–1.01 ) , and the perinatal mortality rate was 16 % lower in CI clusters ( OR = 0.84 , 95 % CI 0.72–0.97 ) . We did not observe any intervention effects on maternal mortality . Conclusions Despite implementation problems , a combined community and facility approach using participatory women ’s groups and quality improvement at health centres reduced newborn mortality in rural Malawi BACKGROUND Women 's groups and health education by peer counsellors can improve the health of mothers and children . We assessed their effects on mortality and breastfeeding rates in rural Malawi . METHODS We did a 2 × 2 factorial , cluster-r and omised trial in 185,888 people in Mchinji district . 48 equal-sized clusters were r and omly allocated to four groups with a computer-generated number sequence . 24 facilitators guided groups through a community action cycle to tackle maternal and child health problems . 72 trained volunteer peer counsellors made home visits at five timepoints during pregnancy and after birth to support breastfeeding and infant care . Primary outcomes for the women 's group intervention were maternal , perinatal , neonatal , and infant mortality rates ( MMR , PMR , NMR , and IMR , respectively ) ; and for the peer counselling were IMR and exclusive breastfeeding ( EBF ) rates . Analysis was by intention to treat . The trial is registered as IS RCT N06477126 . FINDINGS We monitored outcomes of 26,262 births between 2005 and 2009 . In a factorial model adjusted only for clustering and the volunteer peer counselling intervention , in women 's group areas , for years 2 and 3 , we noted non-significant decreases in NMR ( odds ratio 0.93 , 0.64 - 1.35 ) and MMR ( 0.54 , 0.28 - 1.04 ) . After adjustment for parity , socioeconomic quintile , and baseline measures , effects were larger for NMR ( 0.85 , 0.59 - 1.22 ) and MMR ( 0.48 , 0.26 - 0.91 ) . Because of the interaction between the two interventions , a stratified analysis was done . For women 's groups , in adjusted analyses , MMR fell by 74 % ( 0.26 , 0.10 - 0.70 ) , and NMR by 41 % ( 0.59 , 0.40 - 0.86 ) in areas with no peer counsellors , but there was no effect in areas with counsellors ( 1.09 , 0.40 - 2.98 , and 1.38 , 0.75 - 2.54 ) . Factorial analysis for the peer counselling intervention for years 1 - 3 showed a fall in IMR of 18 % ( 0.82 , 0.67 - 1.00 ) and an improvement in EBF rates ( 2.42 , 1.48 - 3.96 ) . The results of the stratified , adjusted analysis showed a 36 % reduction in IMR ( 0.64 , 0.48 - 0.85 ) but no effect on EBF ( 1.18 , 0.63 - 2.25 ) in areas without women 's groups , and in areas with women 's groups there was no effect on IMR ( 1.05 , 0.82 - 1.36 ) and an increase in EBF ( 5.02 , 2.67 - 9.44 ) . The cost of women 's groups was US$ 114 per year of life lost ( YLL ) averted and that of peer counsellors was $ 33 per YLL averted , using stratified data from single intervention comparisons . INTERPRETATION Community mobilisation through women 's groups and volunteer peer counsellor health education are methods to improve maternal and child health outcomes in poor rural population s in Africa . FUNDING Saving Newborn Lives , UK Department for International Development , and Wellcome Trust An intervention program was undertaken to assess dietary habits and the impact of nutrition education among pregnant women in the rural county of Florina , northern Greece . Analysis of dietary habits , nutrient intake , hemoglobin , and serum vitamin concentrations in an intervention and control group indicated that the population was adequately nourished although nutrient intake was below recommended levels for pregnant women . Nutrition counseling was associated with improvements in dietary intake and significantly greater maternal weight gain ( p less than 0.05 ) . Mean birth weight was slightly higher in the intervention group but so was the incidence of low birth weight ( 4.5 % vs 3.9 % ) . The prematurity rate was marginally lower in the intervention group ( p less than 0.04 ) , as was the number of perinatal deaths ( 9 vs 11 ) . The results indicate that nutrition counseling during pregnancy can improve dietary intake and maternal weight gain but the mediating influence on low frequency pregnancy outcomes is indeterminate in a population that is not nutritionally at risk BACKGROUND Neonatal deaths in developing countries make the largest contribution to global mortality in children younger than 5 years . 90 % of deliveries in the poorest quintile of households happen at home . We postulated that a community-based participatory intervention could significantly reduce neonatal mortality rates . METHODS We pair-matched 42 geopolitical clusters in Makwanpur district , Nepal , selected 12 pairs r and omly , and r and omly assigned one of each pair to intervention or control . In each intervention cluster ( average population 7000 ) , a female facilitator convened nine women 's group meetings every month . The facilitator supported groups through an action-learning cycle in which they identified local perinatal problems and formulated strategies to address them . We monitored birth outcomes in a cohort of 28?931 women , of whom 8 % joined the groups . The primary outcome was neonatal mortality rate . Other outcomes included stillbirths and maternal deaths , uptake of antenatal and delivery services , home care practice s , infant morbidity , and health-care seeking . Analysis was by intention to treat . The study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N31137309 . FINDINGS From 2001 to 2003 , the neonatal mortality rate was 26.2 per 1000 ( 76 deaths per 2899 livebirths ) in intervention clusters compared with 36.9 per 1000 ( 119 deaths per 3226 livebirths ) in controls ( adjusted odds ratio 0.70 [ 95 % CI 0.53 - 0.94 ] ) . Stillbirth rates were similar in both groups . The maternal mortality ratio was 69 per 100000 ( two deaths per 2899 livebirths ) in intervention clusters compared with 341 per 100000 ( 11 deaths per 3226 livebirths ) in control clusters ( 0.22 [ 0.05 - 0.90 ] ) . Women in intervention clusters were more likely to have antenatal care , institutional delivery , trained birth attendance , and hygienic care than were controls . INTERPRETATION Birth outcomes in a poor rural population improved greatly through a low cost , potentially sustainable and scalable , participatory intervention with women 's groups To determine whether a Nurse-Community Health Worker ( CHW ) home visiting team , in the context of a Medicaid enhanced prenatal/postnatal services ( EPS ) , would demonstrate greater reduction of depressive symptoms and stress and improvement of psychosocial re sources ( mastery , self-esteem , social support ) when compared with usual Community Care ( CC ) that includes Medicaid EPS delivered by professionals . Greatest program benefits were expected for women who reported low psychosocial re sources , high stress , or both at the time of enrollment . Medicaid eligible pregnant women ( N = 613 ) were r and omly assigned to either usual CC or the Nurse-CHW team . Mixed effects regression was used to analyze up to five prenatal and postnatal psychosocial assessment s. Compared to usual CC , assignment to the Nurse-CHW team result ed in significantly fewer depressive symptoms , and as hypothesized , reductions in depressive symptoms were most pronounced for women with low psychosocial re sources , high stress , or both high stress and low re sources . Outcomes for mastery and stress approached statistical significance , with the women in the Nurse-CHW group reporting less stress and greater mastery . Women in the Nurse-CHW group with low psychosocial re sources reported significantly less perceived stress than women in usual CC . No differences between the groups were found for self-esteem and social support . A Nurse-CHW team approach to EPS demonstrated advantage for alleviating depressive symptoms in Medicaid eligible women compared to CC , especially for women at higher risk Background Progress on neonatal survival has been slow in most countries . While there is evidence on what works to reduce newborn mortality , there is limited knowledge on how to deliver interventions effectively when health systems are weak . Cluster r and omized trials have shown strong reductions in neonatal mortality using community mobilisation with women 's groups in rural Nepal and India . A similar trial in Bangladesh showed no impact . A main hypothesis is that this negative finding is due to the much lower coverage of women 's groups in the intervention population in Bangladesh compared to India and Nepal . For evidence -based policy making it is important to examine if women 's group coverage is a main determinant of their impact . The study aims to test the effect on newborn and maternal health outcomes of a participatory women 's group intervention with a high population coverage of women 's groups . Methods A cluster r and omised trial of a participatory women 's group intervention will be conducted in 3 districts of rural Bangladesh . As we aim to study a women 's group intervention with high population coverage , the same 9 intervention and 9 control unions will be used as in the 2005 - 2007 trial . These had been r and omly allocated using the districts as strata . To increase coverage , 648 new groups were formed in addition to the 162 existing groups that were part of the previous trial . An open cohort of women who are permanent residents in the union in which their delivery or death was identified , is enrolled . Women and their newborns are included after birth , or , if a woman dies during pregnancy , after her death . Excluded are women who are temporary residents in the union in which their birth or death was identified . The primary outcome is neonatal mortality in the last 24 months of the study . A low cost surveillance system will be used to record all birth outcomes and deaths to women of reproductive age in the study population . Data on home care practice s and health care use are collected through interviews . Trial registration IS RCT N : IS RCT Background Reducing neonatal-related deaths is one of the major bottlenecks to achieving Millennium Development Goal 4 . Studies in Asia and South America have shown that neonatal mortality can be reduced through community-based interventions , but these have not been adapted to scalable intervention packages for sub-Saharan Africa where the culture , health system and policy environment is different . In Ug and a , health outcomes are poor for both mothers and newborn babies . Policy opportunities for neonatal health include the new national Health Sector Strategic Plan , which now prioritizes newborn health including use of a community model through Village Health Teams ( VHT ) . The aim of the present study is to adapt , develop and cost an integrated maternal-newborn care package that links community and facility care , and to evaluate its effect on maternal and neonatal practice s in order to inform policy and scale-up in Ug and a. Methods / Design Through formative research around evidence -based practice s , and dialogue with policy and technical advisers , we constructed a home-based neonatal care package implemented by the responsible VHT member , effectively a Community Health Worker ( CHW ) . This CHW was trained to identify pregnant women and make five home visits - two before and three just after birth - so that linkages will be made to facility care and targeted messages for home-care and care-seeking delivered . The project is improving care in health units to provide st and ardized care for the mother and the newborn in both intervention and comparison areas .The study is taking place in a new Demographic Surveillance Site in two rural districts , Iganga and Mayuge , in Ug and a. It is a two-arm cluster r and omized controlled design with 31 intervention and 32 control areas ( villages ) . The comparison parishes receive the st and ard care already being provided by the district , but to the intervention villages are added a system for CHWs to visit the mother five times in her home during pregnancy and the neonatal period . Both areas benefit from a st and ardized strengthening of facility care for mothers and neonates . Discussion UNEST is design ed to directly feed into the operationalization of maternal and newborn care in the national VHT strategy , thereby helping to inform scale-up in rural Ug and a. The study is registered as a r and omized controlled trial , number IS RCT N50321130 Background In sub-Saharan Africa , malaria continues to cause over 10,000 maternal deaths and 75,000 to 200,000 infant deaths . Successful control of malaria in pregnancy could save lives of mothers and babies and is an essential part of antenatal care in endemic areas . The primary objective is to determine the protective efficacy of community-scheduled screening and treatment ( CSST ) using community health workers ( CHW ) against the primary outcome of prevalence of placental malaria . The secondary objectives are to determine the protective efficacy of CSST on maternal anaemia , maternal peripheral infection , low birth weight , selection of sulfadoxine-pyrimethamine ( SP ) resistance markers , and on antenatal clinic ( ANC ) attendance and coverage of intermittent preventive treatment during pregnancy ( IPTp-SP ) . Methods / design This is a multi-centre cluster-r and omised controlled trial involving three countries with varying malaria endemicity ; low ( The Gambia ) versus high transmission ( Burkina Faso and Benin ) , and varying degrees of SP resistance ( high in Benin and moderate in Gambia and Burkina Faso ) . CHW and their related catchment population who are r and omised into the intervention arm will receive specific training on community-based case management of malaria in pregnancy . All women in both study arms will be enrolled at their first ANC visits in their second trimester where they will receive their first dose of IPTp-SP . Thereafter , CHW in the intervention arm will perform scheduled monthly screening and treatment in the womens homes . At time of delivery , a placental biopsy will be collected from all women to determine placental malaria . At each contact point , filter paper and blood slides will be collected for detection of malaria infection and SP resistance markers . Discussion To reach successful global malaria control , there is an urgent need to access those at greatest risk of malaria infection . The project is design ed to develop a low-cost intervention in pregnant women which will have an immediate impact on the malaria burden in re source -limited countries . This will be done by adding to the st and ard IPTp-SP delivered through the health facilities : an “ extension ” strategy to the communities in rural areas thus bringing health services closer to where women live . Trial registration Current Controlled Trials : IS RCT N37259296 ( 5 July 2013 ) , and clinical trials.gov : NCT01941264 ( 10 September 2013 ) Background Antenatal care provides an important opportunity to improve maternal underst and ing of care during and after pregnancy . Yet , studies suggest that communication is often insufficient . This research examined the effect of a job aids-focused intervention on quality of counseling and maternal underst and ing of care for mothers and newborns . Methods Counseling job aids were developed to support provider communication to pregnant women . Fourteen health facilities were r and omized to control or intervention , where providers were trained to use job aids and provided implementation support . Direct observation of antenatal counseling sessions and patient exit interviews were undertaken to assess quality of counseling and maternal knowledge . Providers were also interviewed regarding their perceptions of the tools . Data were collected before and after the job aids intervention and analyzed using a difference-in-differences analysis to quantify relative changes over time . Results Mean percent of recommended messages provided to pregnant women significantly improved in the intervention arm as compared to the control arm in birth preparedness ( difference-in-differences [ ΔI-C ] = + 17.9 , 95%CI : 6.7,29.1 ) , danger sign recognition ( ΔI-C = + 26.0 , 95%CI : 14.6,37.4 ) , clean delivery ( ΔI-C = + 21.7 , 95%CI : 10.9,32.6 ) , and newborn care ( ΔI-C = + 26.2 , 95%CI : 13.5,38.9 ) . Significant gains were also observed in the mean percent of communication techniques applied ( ΔI-C = + 28.8 , 95%CI : 22.5,35.2 ) and duration ( minutes ) of antenatal consultations ( ΔI-C = + 5.9 , 95%CI : 3.0,8.8 ) . No relative increase was found for messages relating to general prenatal care ( ΔI-C = + 8.2 , 95%CI : -2.6,19.1 ) . The proportion of pregnant women with correct knowledge also significantly improved for birth preparedness ( ΔI-C = + 23.6 , 95%CI : 9.8,37.4 ) , danger sign recognition ( ΔI-C = + 28.7 , 95%CI : 14.2,43.2 ) , and clean delivery ( ΔI-C = + 31.1 , 95%CI : 19.4,42.9 ) . There were no significant changes in maternal knowledge of general prenatal ( ΔI-C = -6.4 , 95%CI : -21.3,8.5 ) or newborn care ( ΔI-C = + 12.7 , 95%CI : -6.1,31.5 ) . Job aids were positively perceived by providers and pregnant women , although time constraints remained for health workers with other clinical responsibilities . Conclusions This study demonstrates that a job aids-focused intervention can be integrated into routine antenatal care with positive outcomes on provider communication and maternal knowledge . Efforts are needed to address time constraints and other communication barriers , including introduction of on-going quality assessment for long-term sustainability Background Nepal is on track to achieve MDG 5 but there is a huge sub-national disparity with existing high maternal mortality in western and hilly regions . The national priority is to reduce this disparity to achieve the goal at sub-national level . Evidence s from developing countries show that increasing utilization of skilled attendant at birth is an important indicator for reducing maternal death . Further , there is a very low utilization during childbirth in western and hilly regions of Nepal which clearly depicts the barriers in utilization of skilled birth attendants . So , there is a need to overcome the identified barriers to increase the utilization thereby decreasing the maternal mortality . The hypothesis of this study is that through a package of interventions the utilization of skilled birth attendants will be increased and hence improve maternal health in Nepal . Method / Design This study involves a cluster r and omized controlled trial involving approximately 5000 pregnant women in 36 clusters . The 18 intervention clusters will receive the following interventions : i ) mobilization of family support for pregnant women to reach the health facility , ii ) availability of emergency funds for institutional childbirth , iii ) availability of transport options to reach a health facility for childbirth , iv ) training to health workers on communication skills , v ) security provisions for SBAs to reach services 24/24 through community mobilization ; 18 control clusters will not receive the intervention package . The final evaluation of the intervention is planned to be completed by October 2014 . Primary study output of this study is utilization of SBA services . Secondary study outputs measure the uptake of antenatal care , post natal checkup for mother and baby , availability of transportation for childbirth , operation of emergency fund , improved reception of women at health services , and improved physical security of SBAs . Discussion The intervention package is design ed to increase the utilization of skilled birth attendants by overcoming the barriers related to awareness , finance , transport , security etc . If proven effective , the Ministry of Health has committed to scale up the intervention package throughout the country . Trial registration numberIS RCT N78892490 Background Maternal and perinatal mortality continue to be a high priority problem on the health agendas of less developed countries . Despite the progress made in the last decade to quantify the magnitude of maternal mortality , few interventions have been implemented with the intent to measure impact directly on maternal or perinatal deaths . The success of interventions implemented in less developed countries to reduce mortality has been question ed , in terms of the tendency to maintain a clinical perspective with a focus on purely medical care separate from community-based approaches that take cultural and social aspects of maternal and perinatal deaths into account . Our innovative approach utilizes both the clinical and community perspectives ; moreover , our study will report the weight that each of these components may have had on reducing perinatal mortality and increasing institution-based deliveries . Methods / Design A matched pair cluster-r and omized trial will be conducted in clinics in four rural indigenous districts with the highest maternal mortality ratios in Guatemala . The individual clinic will serve as the unit of r and omization , with 15 matched pairs of control and intervention clinics composing the final sample . Three interventions will be implemented in indigenous , rural and poor population s : a simulation training program for emergency obstetric and perinatal care , increased participation of the professional midwife in strengthening the link between traditional birth attendants ( TBA ) and the formal health care system , and a social marketing campaign to promote institution-based deliveries . No external intervention is planned for control clinics , although enhanced monitoring , surveillance and data collection will occur throughout the study in all clinics throughout the four districts . All obstetric events occurring in any of the participating health facilities and districts during the 18 months implementation period will be included in the analysis , controlling for the cluster design . Our main outcome measures will be the change in perinatal mortality and in the proportion of institution-based deliveries . Discussion A unique feature of this protocol is that we are not proposing an individual intervention , but rather a package of interventions , which is design ed to address the complexities and realities of maternal and perinatal mortality in developing countries . To date , many other countries , has focused its efforts to decrease maternal mortality indirectly by improving infrastructure and data collection systems rather than on implementing specific interventions to directly improve outcomes .Trial registration Clinical Trial.gov , http://NCT01653626 BACKGROUND Effective and scalable community-based strategies are needed for identification and management of serious neonatal illness . METHODS As part of a community-based , cluster-r and omized controlled trial of the impact of a package of maternal-neonatal health care , community health workers ( CHWs ) were trained to conduct household surveillance and to identify and refer sick newborns according to a clinical algorithm . Assessment s of newborns by CHWs at home were linked to hospital-based assessment s by physicians , and factors impacting referral , referral compliance and outcome were evaluated . RESULTS Seventy-three per cent ( 7310/10,006 ) of live-born neonates enrolled in the study were assessed by CHWs at least once ; 54 % were assessed within 2 days of birth , but only 15 % were attended at delivery . Among assessment s for which referral was recommended , compliance was verified in 54 % ( 495/919 ) . Referrals recommended to young neonates 0 - 6 days old were 30 % less likely to be complied with compared to older neonates . Compliance was positively associated with having very severe disease and selected clinical signs , including respiratory rate > or = 70/minute ; weak , abnormal or absent cry ; lethargic or less than normal movement ; and feeding problem . Among 239 neonates who died , only 38 % were assessed by a CHW before death . CONCLUSIONS Despite rigorous programmatic effort , reaching neonates within the first 2 days after birth remained a challenge , and parental compliance with referral recommendation was limited , particularly among young neonates . To optimize potential impact , community postnatal surveillance must be coupled with skilled attendance at delivery , and /or a worker skilled in recognition of neonatal illness must be placed in close proximity to the community to allow for rapid case management to avert early deaths We investigated whether early life chronic exposure to woodsmoke , using personal passive 48-h carbon monoxide ( CO ) as an indicator , is associated with children 's neurodevelopmental and behavioral performance . CO measures were collected every 3 months from 2002 to 2005 among mother-child dyads during the R and omized Exposure Study of Pollution Indoors and Respiratory Effects ( RESPIRE ) stove intervention trial in San Marcos , Guatemala . From March to June , 2010 , study children of age 6 - 7 years , performed a follow-up non-verbal , culturally adapted neurodevelopmental assessment . We found inverse associations between CO exposure of pregnant mothers during their 3rd trimesters ( m=3.8ppm ± 3.0ppm ; range : 0.6 - 12.5 ppm ) and child neuropsychological performance . Scores on 4 out of 11 neuropsychological tests were significantly associated with mothers ' 3rd trimester CO exposures , including visuo-spatial integration ( p<0.05 ) , short-term memory recall ( p<0.05 ) , long-term memory recall ( p<0.05 ) , and fine motor performance ( p<0.01 ) measured using the Bender Gestalt-II 's Copy , Immediate Recall , and an adapted version of a Delayed Recall Figures drawing , and the Reitan-Indiana 's Finger Tapping Tests , respectively . These 4 significant finding persisted with adjustment for child sex , age , visual acuity , and household assets ( socio-economic status ) . Summary performance scores were also significantly associated with maternal 3rd trimester CO when adjusted for these covariates . Other variables accounting for variance but were excluded in our final multiple regression models included the following : HOME environment stimulation score , child examiner , WHO height-for-age percentile , and age that the infant stopped breastfeeding . This seems to be the first study on woodsmoke exposure and neurodevelopment , and the first longitudinal birth cohort study on chronic early life CO exposures , determined by high quality measures of mothers ' and infants ' personal CO exposures , and using well-established , reliable child neuropsychological tests . Further research is needed to replicate our results and inform future interventions and air quality st and ards for woodsmoke and CO Background : A growing body of evidence indicates a relationship between household indoor air pollution from cooking fires and adverse neonatal outcomes , such as low birth weight ( LBW ) , in re source -poor countries . Objective : We examined the effect of reduced wood smoke exposure in pregnancy on LBW of Guatemalan infants in RESPIRE ( R and omized Exposure Study of Pollution Indoors and Respiratory Effects ) . Methods : Pregnant women ( n = 266 ) either received a chimney stove ( intervention ) or continued to cook over an open fire ( control ) . Between October 2002 and December 2004 we weighed 174 eligible infants ( 69 to mothers who used a chimney stove and 105 to mothers who used an open fire during pregnancy ) within 48 hr of birth . Multivariate linear regression and adjusted odds ratios ( ORs ) were used to estimate differences in birth weight and LBW ( < 2,500 g ) associated with chimney-stove versus open-fire use during pregnancy . Results : Pregnant women using chimney stoves had a 39 % reduction in mean exposure to carbon monoxide compared with those using open fires . LBW prevalence was high at 22.4 % . On average , infants born to mothers who used a stove weighed 89 g more [ 95 % confidence interval ( CI ) , –27 to 204 g ] than infants whose mothers used open fires after adjusting for maternal height , diastolic blood pressure , gravidity , and season of birth . The adjusted OR for LBW was 0.74 ( 95 % CI , 0.33–1.66 ) among infants of stove users compared with open-fire users . Average birth weight was 296 g higher ( 95 % CI , 109–482 g ) in infants born during the cold season ( after harvest ) than in other infants ; this unanticipated finding may reflect the role of maternal nutrition on birth weight in an impoverished region . Conclusions : A chimney stove reduced wood smoke exposures and was associated with reduced LBW occurrence . Although not statistically significant , the estimated effect was consistent with previous studies OBJECTIVE To determine if a community-based intervention program focusing on parenting education will have an impact on preventive health care utilization behaviors among low-income , minority mothers in Washington , DC . DESIGN The experimental design was a r and omized , controlled study in which 286 mother-infant dyads were assigned to either the st and ard social services ( control ) group or to the intervention group . Women and their newborn infants were recruited during the immediate postpartum period in 4 Washington , DC , hospital sites from April 1995 to April 1997 . The year-long multicomponent intervention included home visits and hospital-based group sessions in addition to the st and ard social services available at the hospital sites . A total of 286 postpartum women with inadequate prenatal care were assigned r and omly to the control or the intervention group . Women and their infants were followed for 1 full year . Outcome measures included usage of preventive health care services including well care infant visits and adherence to immunization schedules during the first year of the infant 's life . RESULTS Infants in the intervention group initiated well care at an earlier age than controls ( by 6 weeks , 62.5 % vs 50 % had received their first well infant visit ) . Infants in the intervention group had more frequent well visits ( by 12 months of age , 3.5 vs 2.7 visits ) . Multivariate analyses showed infants in the intervention group to be more likely to complete their scheduled immunizations ( by 9 months , odds ratio = 2.2 , 95 % confidence interval : 1.09 - 4.53 ) . Those in the intervention group with more frequent contacts ( 30 + visits ) with study personnel were most likely to have followed age-appropriate immunization schedules when compared with controls ( at 9 months odds ratio = 3.63 , 95 % confidence interval : 1.58 - 8.33 ) . CONCLUSIONS It is possible to influence health care usage patterns of high-risk minority population s through public health interventions that are global in their perspective . Focusing on parental knowledge and beliefs regarding health-related issues and life skills in a self-efficacy model is associated with improved usage of infant health care re sources OBJECTIVE To describe the most acceptable methods for educating women in Medrogongkar County , Tibet , about healthy pregnancy and safe motherhood . DESIGN Focus group discussion s with key informants were used to develop a quantitative , orally administered r and om sample survey . SETTING Thirty-two r and omly selected villages in Medrogongkar County . PARTICIPANTS One hundred and forty-eight multigravida over the age of 18 living in Medrogongkar County . RESULTS Most participants reported receiving pregnancy-related information either from family members ( n=85 , 57.4 % ) or from community health workers ( n=81 , 54.7 % ) , while very few reported group teaching or radio/television/videos as sources . When asked what modalities of health communication are most effective for them , participants preferred discussion s with family members ( n=59 , 39.8 % ) , specifically their mothers ( n=34 , 23.0 % ) . Community health worker teaching ( n=15 , 10.1 % ) or group teaching ( n=7 , 4.7 % ) were reported as less effective . CONCLUSIONS Despite recent efforts in Tibet to use group teaching , television/radio programs , and health professionals visiting patients ' homes as health communication modalities , participants preferred to learn pregnancy-related health messages from their close family , especially their mothers . Future health communication interventions in rural Tibet and similar communities should consider targeting close family members as well as pregnant women to maximize acceptability of advice on healthy pregnancy and delivery Objective To evaluate the Indian Integrated Management of Neonatal and Childhood Illness ( IMNCI ) programme , which integrates improved treatment of illness for children with home visits for newborn care , to inform its scale-up . Design Cluster r and omised trial . Setting 18 clusters ( population 1.1 million ) in Haryana , India . Participants 29 667 births in intervention clusters and 30 813 in control clusters . Intervention Community health workers were trained to conduct postnatal home visits and women ’s group meetings ; physicians , nurses , and community health workers were trained to treat or refer sick newborns and children ; supply of drugs and supervision were strengthened . Main outcome measures Neonatal and infant mortality ; newborn care practice s. Results The infant mortality rate ( adjusted hazard ratio 0.85 , 95 % confidence interval 0.77 to 0.94 ) and the neonatal mortality rate beyond the first 24 hours ( adjusted hazard ratio 0.86 , 0.79 to 0.95 ) were significantly lower in the intervention clusters than in control clusters . The adjusted hazard ratio for neonatal mortality rate was 0.91 ( 0.80 to 1.03 ) . A significant interaction was found between the place of birth and the effect of the intervention for all mortality outcomes except post-neonatal mortality rate . The neonatal mortality rate was significantly lower in the intervention clusters in the subgroup born at home ( adjusted hazard ratio 0.80 , 0.68 to 0.93 ) but not in the subgroup born in a health facility ( 1.06 , 0.91 to1.23 ) ( P value for interaction=0.001 ) . Optimal newborn care practice s were significantly more common in the intervention clusters . Conclusions Implementation of the IMNCI result ed in substantial improvement in infant survival and in neonatal survival in those born at home . The IMNCI should be a part of India ’s strategy to achieve the millennium development goal on child survival . Trial registration Clinical trials NCT00474981 ; ICMR Clinical Trial Registry CTRI/2009/091/000715 Pregnant mothers in South African townships face multiple health risks for themselves and their babies . Existing clinic-based services face barriers to access , utilization , and human re source capacities . Home visiting by community health workers ( CHW ) can mitigate such barriers . The Philani Plus ( + ) Intervention Program builds upon the original Philani CHW home-visiting intervention program for maternal and child nutrition by integrating content and activities to address HIV , alcohol , and mental health . Pregnant Mothers at Risk ( MAR ) for HIV , alcohol , and /or nutrition problems in 24 neighborhoods in townships in Cape Town , South Africa ( n = 1,239 ) were r and omly assigned by neighborhood to an intervention ( Philani Plus ( + ) , N = 12 neighborhoods ; n = 645 MAR ) or a st and ard-care control condition of neighborhood clinic-based services ( N = 12 neighborhoods ; n = 594 MAR ) . Positive peer deviant “ Mentor Mother ” CHWs are recruited from the township neighborhoods and trained to deliver four antenatal and four postnatal home visits that address HIV , alcohol , nutrition , depression , health care regimens for the family , caretaking and bonding , and securing government-provided child grants . The MAR and their babies are being monitored during pregnancy , 1 week post-birth , and 6 and 18 months later . Among the 1,239 MAR recruited : 26 % were HIV-positive ; 27 % used alcohol during pregnancy ; 17 % previously had low-birthweight babies ; 23 % had at least one chronic condition ( 10 % hypertension , 5 % asthma , 2 % diabetes ) ; 93 % had recent sexual partners with 10 % known to be HIV+ ; and 17 % had clinical ly significant prenatal depression and 42 % had borderline depression . This paper presents the intervention protocol and baseline sample characteristics for the “ Philani Plus ( + ) ” CHW home-visiting intervention trial Abstract In this article we present the results of three studies investigating methods for including men in antenatal education in Istanbul , Turkey . Participants were first-time expectant parents living in low and middle-income areas . After a formative study on the roles of various family members in health during the period surrounding a first birth , an antenatal-clinic-based education programme for women and for couples was carried out as a r and omised , controlled study . Based on the results , separate community-based antenatal education programmes for expectant mothers and expectant fathers were tested . There was dem and among many pregnant women and some of their husb and s for including expectant fathers in antenatal education . In the short term , these programmes seemed to have positive effects on women and men 's reproductive health knowledge , attitudes and behaviours . In the clinic-based programme the positive effects of including men were mainly in the area of post-partum family planning , while in the community-based programme positive effects among men were also seen in the areas of infant health , infant feeding and spousal communication and support . Free an tenatal education should be made available to all expectant mothers and when possible , men should be included , either together with their wives or in a culture such as that of Turkey , in separate groups . Résumé Trois etudes ont analysé des méthodes pour associer les hommes á l'éducation prénatale . Les participants , issus de quartiers à revenus faibles et moyens d'Istanbul , Turquie , attendaient leur premier enfant . Après une étude initiale des rôles en matiere de santé des membres de la famille pendant la période entourant une première naissance , un programme d'éducation a donné des soins prénatals en dispensaire aux femmes et aux couples , dans le cadre d'une etude aléatorie et contrôlée . En fonction des résultats , des programmes communautaires d'education prénatale , séparés pour les futurs péres et les futures mères , ont été testes . Beaucoup de femmes enceintes et quelques maris souhaitaient associer les futurs pères à l'éducation prénatale . A court terme , ces programmes semblaient avoir des effets positifs sur les connaissances , les attitudes et les comportements des hommes et des femmes en matière de santé génésique . Darts le programme mené au dispensaire , l'ínclusion des hommes avait des avantages touchant à la planification familiale post-partum , alors que les effets positifs du programme communautaire concernaient la santé infantile , 1'alimentation des nourrissons , la communication et le soutien entre époux . Une éducation prénatale gratuite devrait être proposée à toutes les futures mères et , lorsque c'est possible , les hommes devraient y être associés , soit avec leurs épouses soit , dans une culture comme celle de la Turquie , dans des groupes séparés . Resumen Tres investigaciones analizaron los métodos para incluir a los hombres en la educación prenatal en Estambul , Turquia . Los participantes eran parejas que vivían en Areas de bajos y medianos ingresos , quienes esperaban su primer bebé . Después de un estudio formativo acerca de los roles de los distintos integrantes de la familia en relación a la salud durante el período previo y posterior a un primer nacimiento , se implementó un estudio aleatorio controlado en la forma de un programa educativo para mujeres y para parejas en una clínica prenatal . En base a los result ados , se probaron programas educativos prenatales comunitarios para mujeres embarazadas y sus parejas . Hubo una dem and a entre muchas de las mujeres embarazadas y algunos de sus esposos para incluir a los futures padres en la educación prenatal . A couo plazo , estos programas parecían tener efectos positivos en las actitudes , comportamientos y conocimientos de la salud reproductiva de las mujeres y los hombres . En el programa de la clinica , los efectos positivos de incluir a los hombres se notaban principalmente en el ámbito de la planificación familiar postparto , mientras que en el programa comunitario , se notaban además los efectos positivos en los ámbitos de la salud y la alimentacion infantil , el apoyo de los hombres a sus esposas y la comunicacíon con ellas . Se recomienda ofrecer educacion prenatal gratuita a todas las mujeres embarazadas y cu and o sea posible a los hombres , en conjunto con sus esposas o , en una cultura como la de Turquía , en grupos separados OBJECTIVE : We found a high burden of morbidities in a cohort of neonates observed in rural Gadchiroli , India . We hypothesised that interventions would reduce the incidence of neonatal morbidities , including the seasonal increase observed in many of them . This article reports the effect of home-based neonatal care on neonatal morbidities in the intervention arm of the field trial by comparing the early vs late periods , and the possible explanation for this effect . METHODS : During 3 years ( 1995 to 1998 ) , trained village-health-workers ( VHWs ) in 39 villages prospect ively collected data by making home visits during pregnancy , home-delivery and during neonatal period . We estimated the incidence and burden of neonatal morbidities over the 3 years from these data . In the first year , the VHWs made home visits only to observe . From the second year , they assisted mothers in neonatal care and managed the sick neonates at home . Health education of mothers and family members , individually and in group , was added in the third year . We measured the coverage of interventions over the 3 years and evaluated maternal knowledge and practice s on 21 indicators in the third year . The effect on 17 morbidities was estimated by comparing the incidence in the first year with the third year . RESULTS : The VHWs observed 763 neonates in the first year , 685 in the second and 913 in the third year . The change in the percent incidence of morbidities was ( i ) infections , from 61.6 to 27.5 ( −55 % ; p<0.001 ) , ( ii ) care-related morbidities ( asphyxia , hypothermia , feeding problems ) from 48.2 to 26.3 ( −45 % ; p<0.001 ) ; ( iii ) low birth weight from 41.9 to 35.2 ( −16 % ; p<0.05 ) ; ( iv ) preterm birth and congenital anomalies remained unchanged . The mean number of morbidities/100 neonates in the 3 years was 228 , 170 and 115 ( a reduction of 49.6 % ; p<0.001 ) . These reductions accompanied an increasing percent score of interventions during 3 years : 37.9 , 58.4 and 81.3 , thus showing a dose – response relationship . In the third year , the proportion of correct maternal knowledge was 78.7 % and behaviours was 69.7 % . The significant seasonal increase earlier observed in the incidence of five morbidities reduced in the third year . CONCLUSION : The home-based care and health education reduced the incidence and burden of neonatal morbidities by nearly half . The effect was broad , but was especially pronounced on infections , care-related morbidities and on the seasonal increase in morbidities BACKGROUND Two recent trials have shown that women 's groups can reduce neonatal mortality in poor communities . We assessed the effectiveness of a scaled-up development programme with women 's groups to address maternal and neonatal care in three rural districts of Bangladesh . METHODS 18 clusters ( with a mean population of 27 953 [ SD 5953 ] ) in three districts were r and omly assigned to either intervention or control ( nine clusters each ) by use of stratified r and omisation . For each district , cluster names were written on pieces of paper , which were folded and placed in a bottle . The first three cluster names drawn from the bottle were allocated to the intervention group and the remaining three to control . All clusters received health services strengthening and basic training of traditional birth attendants . In intervention clusters , a facilitator convened 18 groups every month to support participatory action and learning for women , and to develop and implement strategies to address maternal and neonatal health problems . Women were eligible to participate if they were aged 15 - 49 years , residing in the project area , and had given birth during the study period ( Feb 1 , 2005 , to Dec 31 , 2007 ) . Neither study investigators nor participants were masked to treatment assignment . In a population of 229 195 people ( intervention clusters only ) , 162 women 's groups provided coverage of one group per 1414 population . The primary outcome was neonatal mortality rate ( NMR ) . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N54792066 . FINDINGS We monitored outcomes for 36 113 births ( intervention clusters , n=17 514 ; control clusters , n=18 599 ) in a population of 503 163 over 3 years . From 2005 to 2007 , there were 570 neonatal deaths in the intervention clusters and 656 in the control clusters . Cluster-level mean NMR ( adjusted for stratification and clustering ) was 33.9 deaths per 1000 livebirths in the intervention clusters compared with 36.5 per 1000 in the control clusters ( risk ratio 0.93 , 95 % CI 0.80 - 1.09 ) . INTERPRETATION For participatory women 's groups to have a significant effect on neonatal mortality in rural Bangladesh , detailed attention to programme design and context ual factors , enhanced population coverage , and increased enrolment of newly pregnant women might be needed . FUNDING Women and Children First , the UK Big Lottery Fund , Saving Newborn Lives , and the UK Department for International Development Objective To assess the efficacy of an intervention design ed to improve the mother-infant relationship and security of infant attachment in a South African peri-urban settlement with marked adverse socioeconomic circumstances . Design R and omised controlled trial . Setting Khayelitsha , a peri-urban settlement in South Africa . Participants 449 pregnant women . Interventions The intervention was delivered from late pregnancy and for six months postpartum . Women were visited in their homes by previously untrained lay community workers who provided support and guidance in parenting . The purpose of the intervention was to promote sensitive and responsive parenting and secure infant attachment to the mother . Women in the control group received no therapeutic input from the research team . Main outcome measures Primary outcomes : quality of mother-infant interactions at six and 12 months postpartum ; infant attachment security at 18 months . Secondary outcome : maternal depression at six and 12 months . Results The intervention was associated with significant benefit to the mother-infant relationship . At both six and 12 months , compared with control mothers , mothers in the intervention group were significantly more sensitive ( 6 months : mean difference=0.77 ( SD 0.37 ) , t=2.10 , P<0.05 , d=0.24 ; 12 months : mean difference=0.42 ( 0.18 ) , t=−2.04 , P<0.05 , d=0.26 ) and less intrusive ( 6 months : mean difference=0.68 ( 0.36 ) , t=2.28 , P<0.05 , d=0.26 ; 12 months : mean difference=−1.76 ( 0.86 ) , t=2.28 , P<0.05 , d=0.24 ) in their interactions with their infants . The intervention was also associated with a higher rate of secure infant attachments at 18 months ( 116/156 ( 74 % ) v 102/162 ( 63 % ) ; Wald=4.74 , odds ratio=1.70 , P<0.05 ) . Although the prevalence of maternal depressive disorder was not significantly reduced , the intervention had a benefit in terms of maternal depressed mood at six months ( z=2.05 , P=0.04 ) on the Edinburgh postnatal depression scale ) . Conclusions The intervention , delivered by local lay women , had a significant positive impact on the quality of the mother-infant relationship and on security of infant attachment , factors known to predict favourable child development . If these effects persist , and if they are replicated , this intervention holds considerable promise for use in the developing world . Trial registration Current Controlled Trials IS RCT N25664149 BACKGROUND Evidence about the best methods with which to accelerate progress towards achieving the Millennium Development Goals is urgently needed . We assessed the effect of performance-based payment of health-care providers ( payment for performance ; P4P ) on use and quality of child and maternal care services in health-care facilities in Rw and a. METHODS 166 facilities were r and omly assigned at the district level either to begin P4P funding between June , 2006 , and October , 2006 ( intervention group ; n=80 ) , or to continue with the traditional input-based funding until 23 months after study baseline ( control group ; n=86 ) . R and omisation was done by coin toss . We surveyed facilities and 2158 households at baseline and after 23 months . The main outcome measures were prenatal care visits and institutional deliveries , quality of prenatal care , and child preventive care visits and immunisation . We isolated the incentive effect from the re source effect by increasing comparison facilities ' input-based budgets by the average P4P payments made to the treatment facilities . We estimated a multivariate regression specification of the difference-in-difference model in which an individual 's outcome is regressed against a dummy variable , indicating whether the facility received P4P that year , a facility-fixed effect , a year indicator , and a series of individual and household characteristics . FINDINGS Our model estimated that facilities in the intervention group had a 23 % increase in the number of institutional deliveries and increases in the number of preventive care visits by children aged 23 months or younger ( 56 % ) and aged between 24 months and 59 months ( 132 % ) . No improvements were seen in the number of women completing four prenatal care visits or of children receiving full immunisation schedules . We also estimate an increase of 0·157 st and ard deviations ( 95 % CI 0·026 - 0·289 ) in prenatal quality as measured by compliance with Rw and an prenatal care clinical practice guidelines . INTERPRETATION The P4P scheme in Rw and a had the greatest effect on those services that had the highest payment rates and needed the least effort from the service provider . P4P financial performance incentives can improve both the use and quality of maternal and child health services , and could be a useful intervention to accelerate progress towards Millennium Development Goals for maternal and child health . FUNDING World Bank 's Bank-Netherl and s Partnership Program and Spanish Impact Evaluation Fund , the British Economic and Social Research Council , Government of Rw and a , and Global Development Network Background In the year after birth one in six women has a depressive illness , and 30 % are still depressed , or depressed again , when their child is 2 years old , 94 % experience at least one major health problem ( e.g. back pain , perineal pain , mastitis , urinary or faecal incontinence ) , 26 % experience sexual problems and almost 20 % have relationship problems with partners . Women with depression report less practical and emotional support from partners , less social support overall , more negative life events , and poorer physical health . Their perceptions of factors contributing to depression are lack of support , isolation , exhaustion and physical health problems . Fewer than one in three affected women seek help in primary care despite frequent contacts . Methods / Design PRISM aims to reduce depression and physical health problems of recent mothers through primary care strategies to increase practitioners ' response to these issues , and through community-based strategies to develop broader family and community supports for recent mothers . Eligible local governments will be recruited and r and omised to intervention or comparison arms , after stratification ( urban/rural , size , birth numbers , extent of community activity ) , avoiding contiguous boundaries . Maternal depression and physical health will be measured six months after birth , in a one year cohort of mothers , in intervention and comparison communities . The sample size to detect a 20 % relative reduction in depression , adjusting for cluster sampling , and estimating a population response fraction of 67 % is 5740 × 2 . Analysis of the physical and mental health outcomes , by intention to treat , will adjust for the correlated structure of the data OBJECTIVE Demonstrate the effective use of community-based evidence for health promotion by Lady Health Workers ( LHWs ) in Sindh , Pakistan . METHODS A baseline study on mothers and children provided local evidence for risk communication tools design ed and tested by LHWs . The communities were r and omized to intervention and control . LHWs visited women before and after childbirth to discuss safe practice s in pregnancy , in the intervention group LHW using the new tools and in the control group using their st and ard procedures . A household survey and focus groups permitted assessment of the impact of the intervention . RESULTS Women in the intervention communities were more likely to attend prenatal checkups , to stop routine heavy work during pregnancy , to give colostrum to newborn babies , and to maintain exclusive breastfeeding for four months . Community focus groups confirmed a positive reaction to the tools . CONCLUSION Discussion by lay health workers of local evidence underlying safe motherhood messages improved uptake of protective health practice s. PRACTICE IMPLICATION S Door-to-door health promotion based on culturally appropriate interaction around relevant evidence can have a positive impact on health practice s. Engaging health workers from the onset builds capacities , improves dialogue within the health system and performance of frontline health workers Background Few large and rigorous evaluations of participatory interventions systematic ally describe their context and implementation , or attempt to explain the mechanisms behind their impact . This study reports process evaluation data from the Ekjut cluster-r and omised controlled trial of a participatory learning and action cycle with women 's groups to improve maternal and newborn health outcomes in Jharkh and and Orissa , eastern India ( 2005 - 2008 ) . The study demonstrated a 45 % reduction in neonatal mortality in the last two years of the intervention , largely driven by improvements in safe practice s for home deliveries . Methods A participatory learning and action cycle with 244 women 's groups was implemented in 18 intervention clusters covering an estimated population of 114 141 . We describe the context , content , and implementation of this intervention , identify potential mechanisms behind its impact , and report challenges experienced in the field . Methods included a review of intervention documents , qualitative structured discussion s with group members and non-group members , meeting observations , as well as descriptive statistical analysis of data on meeting attendance , activities , and characteristics of group attendees . Results Six broad , interrelated factors influenced the intervention 's impact : ( 1 ) acceptability ; ( 2 ) a participatory approach to the development of knowledge , skills and ' critical consciousness ' ; ( 3 ) community involvement beyond the groups ; ( 4 ) a focus on marginalized communities ; ( 5 ) the active recruitment of newly pregnant women into groups ; ( 6 ) high population coverage . We hypothesize that these factors were responsible for the increase in safe delivery and care practice s that led to the reduction in neonatal mortality demonstrated in the Ekjut trial . Conclusions Participatory interventions with community groups can influence maternal and child health outcomes if key intervention characteristics are preserved and tailored to local context s. Scaling-up such interventions requires ( 1 ) a detailed underst and ing of the way in which context affects the acceptability and delivery of the intervention ; ( 2 ) planned but flexible replication of key content and implementation features ; ( 3 ) strong support for participatory methods from implementing agencies Background Globally , almost 4 million newborns die during the first 4 weeks of life every year . By increased use of evidence -based knowledge in the healthcare system a large proportion of these neonatal deaths could be prevented . But there is a severe lack of knowledge on effective methods for successful implementation of evidence into practice , particularly in low- and middle-income countries . Recent studies have demonstrated promising results with increased survival among both mothers and newborns using community-based approaches . In Vietnam evidence -based guidelines on reproductive health were launched in 2003 and revised in 2009 . The overall objective of the current project is to evaluate if a facilitation intervention on the community level , with a problem-solving approach involving local representatives if the healthcare system and the community , results in improvements of neonatal health and survival . Methods / Design The study , which has been given the acronym NeoKIP ( Neonatal Health - Knowledge Into Practice ) , took place in 8 districts composed by 90 communes in a province in northern Vietnam , where neonatal mortality rate was 24/1000 in 2005 . A cluster r and omised design was used , allocating clusters , as defined as a commune and its correponding Commune Health Center ( CHC ) to either intervention or control arm . The facilitation intervention targeted staff at healthcare centres and key persons in the communes . The facilitator role was performed by lay women ( Women 's Union representatives ) using quality improvement techniques to initiate and sustain improvement processes targeting identified problem areas . The intervention has been running over 3 years and data were collected on the facilitation process , healthcare staff knowledge in neonatal care and their behaviour in clinical practice , and reproductive and perinatal health indicators . Primary outcome is neonatal mortality . Discussion The intervention is participatory and dynamic , focused on developing a learning process and a problem-solving cycle . The study recognises the vital role of the local community as actors in improving their own and their newborns ' health , and applies a bottom-up approach where change will be accomplished by an increasing awareness at and dem and from grass root level . By utilising the existing healthcare structure this intervention may , if proven successful , be well suited for scaling up . Trial registration Current Controlled Trials IS RCT OBJECTIVE To evaluate and compare the cost-effectiveness of two strategies for neonatal care in Sylhet division , Bangladesh . METHODS In a cluster-r and omized controlled trial , two strategies for neonatal care -- known as home care and community care -- were compared with existing services . For each study arm , economic costs were estimated from a societal perspective , inclusive of programme costs , provider costs and household out-of-pocket payments on care-seeking . Neonatal mortality in each study arm was determined through household surveys . The incremental cost-effectiveness of each strategy --compared with that of the pre-existing levels of maternal and neonatal care -- was then estimated . The levels of uncertainty in our estimates were quantified through probabilistic sensitivity analysis . FINDINGS The incremental programme costs of implementing the home-care package were 2939 ( 95 % confidence interval , CI : 1833 - 7616 ) United States dollars ( US$ ) per neonatal death averted and US$ 103.49 ( 95 % CI : 64.72 - 265.93 ) per disability-adjusted life year ( DALY ) averted . The corresponding total societal costs were US$ 2971 ( 95 % CI : 1844 - 7628 ) and US$ 104.62 ( 95 % CI : 65.15 - 266.60 ) , respectively . The home-care package was cost-effective -- with 95 % certainty -- if healthy life years were valued above US$ 214 per DALY averted . In contrast , implementation of the community-care strategy led to no reduction in neonatal mortality and did not appear to be cost-effective . CONCLUSION The home-care package represents a highly cost-effective intervention strategy that should be considered for replication and scale-up in Bangladesh and similar setting s elsewhere Background Globally , 40 % of the 7.6 million deaths of children under five every year occur in the neonatal period ( first 28 days after birth ) . Increased and earlier recognition of illness facilitated by community health workers ( CHWs ) , coupled with effective referral systems can result in better child health outcomes . This model has not been tested in a peri-urban poor setting in Africa , or in a high HIV context . Methods The Good Start Saving Newborn Lives ( SNL ) study ( IS RCT N41046462 ) conducted in Umlazi , KwaZulu-Natal , was a community r and omized trial to assess the effect of an integrated home visit package delivered to mothers by CHWs during pregnancy and post-delivery on uptake of PMTCT interventions and appropriate newborn care practice s. CHWs were trained to refer babies with illnesses or identified danger signs . The aim of this sub- study was to assess the effectiveness of this referral system by describing CHW referral completion rates as well as mothers ’ health-care seeking practice s. Interviews were conducted using a structured question naire with all mothers whose babies had been referred by a CHW since the start of the SNL trial . Descriptive analysis was conducted to describe referral completion and health seeking behaviour of mothers . Results Of the 2423 women enrolled in the SNL study , 148 sick infants were referred between June 2008 and June 2010 . 62 % of referrals occurred during the first 4 weeks of life and 22 % between birth and 2 weeks of age . Almost all mothers ( 95 % ) completed the referral as advised by CHWs . Difficulty breathing , rash and redness/discharge around the cord accounted for the highest number of referrals ( 26 % , 19 % and 17 % respectively ) . Only16 % of health workers gave written feedback on the outcome of the referral to the referring CHW . Conclusions We found high compliance with CHW referral of sick babies in an urban South African township . This suggests that CHWs can play a significant role , within community outreach teams , to improve newborn health and reduce child mortality . This supports the current primary health care re-engineering process being undertaken by the South African National Department of Health which involves the establishment of family health worker teams including CHWs . Trial registration numberIS RCT We did a cost-effectiveness analysis alongside a cluster-r and omised controlled trial of a participatory intervention with women 's groups to improve birth outcomes in rural Nepal . The average provider cost of the women 's group intervention was US0.75 dollars per person per year ( 0.90 dollars with health-service strengthening ) in a population of 86,704 . The incremental cost per life-year saved ( LYS ) was 211 dollars ( 251 dollars ) , and expansion could rationalise on start-up costs and technical assistance , reducing the cost per LYS to 138 dollars ( 179 dollars ) . Sensitivity analysis showed a variation from 83 dollars to 263 dollars per LYS for most variables . This intervention could provide a cost-effective way of reducing neonatal deaths Background Over thirty years have passed since the Alma-Ata Declaration on primary health care in 1978 . Many governments in the first decade following the declaration responded by developing national programmes of community health workers ( CHWs ) , but evaluations of these often demonstrated poor outcomes . As many CHW programmes have responded to the HIV/AIDS p and emic , international interest in them has returned and their role in the response to other diseases should be examined carefully so that lessons can be applied to their new roles . Over half of the deaths in African children under five years of age are due to malaria , diarrhoea and pneumonia - a situation which could be addressed through the use of cheap and effective interventions delivered by CHWs . However , to date there is very little evidence from r and omised controlled trials of the impacts of CHW programmes on child mortality in Africa . Evidence from non-r and omised controlled studies has not previously been review ed systematic ally . Methods We search ed data bases of published and unpublished studies for RCTs and non-r and omised studies evaluating CHW programmes delivering curative treatments , with or without preventive components , for malaria , diarrhoea or pneumonia , in children in sub-Saharan Africa from 1987 to 2007 . The impact of these programmes on morbidity or mortality in children under six years of age was review ed . A descriptive analysis of interventional and context ual factors associated with these impacts was attempted . Results The review identified seven studies evaluating CHWs , delivering a range of interventions . Limited descriptive data on programmes , context s or process outcomes for these CHW programmes were available . CHWs in national programmes achieved large mortality reductions of 63 % and 36 % respectively , when insecticide-treated nets and anti-malarial chemoprophylaxis were delivered , in addition to curative interventions . Conclusions CHW programmes could potentially achieve large gains in child survival in sub-Saharan Africa if these programmes were implemented at scale . Large-scale rigorous studies , including RCTs , are urgently needed to provide policymakers with more evidence on the effects of CHWs delivering these interventions BACKGROUND In rural India , most births take place in the home , where high-risk care practice s are common . We developed an intervention of behaviour change management , with a focus on prevention of hypothermia , aim ed at modifying practice s and reducing neonatal mortality . METHODS We did a cluster-r and omised controlled efficacy trial in Shivgarh , a rural area in Uttar Pradesh . 39 village administrative units ( population 104,123 ) were allocated to one of three groups : a control group , which received the usual services of governmental and non-governmental organisations in the area ; an intervention group , which received a preventive package of interventions for essential newborn care ( birth preparedness , clean delivery and cord care , thermal care [ including skin-to-skin care ] , breastfeeding promotion , and danger sign recognition ) ; or another intervention group , which received the package of essential newborn care plus use of a liquid crystal hypothermia indicator ( ThermoSpot ) . In the intervention clusters , community health workers delivered the packages via collective meetings and two antenatal and two postnatal household visitations . Outcome measures included changes in newborn-care practice s and neonatal mortality rate compared with the control group . Analysis was by intention to treat . This study is registered as International St and ard R and omised Control Trial , number NCT00198653 . FINDINGS Improvements in birth preparedness , hygienic delivery , thermal care ( including skin-to-skin care ) , umbilical cord care , skin care , and breastfeeding were seen in intervention arms . There was little change in care-seeking . Compared with controls , neonatal mortality rate was reduced by 54 % in the essential newborn-care intervention ( rate ratio 0.46 [ 95 % CI 0.35 - 0.60 ] , p<0.0001 ) and by 52 % in the essential newborn care plus ThermoSpot arm ( 0.48 [ 95 % CI 0.35 - 0.66 ] , p<0.0001 ) . INTERPRETATION A socioculturally context ualised , community-based intervention , targeted at high-risk newborn-care practice s , can lead to substantial behavioural modification and reduction in neonatal mortality . This approach can be applied to behaviour change along the continuum of care , harmonise vertical interventions , and build community capacity for sustained development . FUNDING USAID and Save the Children-US through a grant from the Bill & Melinda Gates Foundation OBJECTIVE To determine whether traditional birth attendants ( TBAs ) trained via the " SMART Dai " method were superior to untrained TBAs in knowledge and practice regarding maternal and newborn care . METHODS In a cluster-r and omized trial in the Dera Ghazi Khan District of Punjab , Pakistan , 120 rural communities each with a population of approximately 5000 were r and omly assigned to a community-based intervention ( CBI ) or a health systems intervention ( HSI ) . In the CBI communities , 288 TBAs underwent an innovative 8-day training course on maternal and newborn care , initially evaluated by pre- and post-tests . After an average of 19 months post-training , 277 TBAs , together with 257 comparably chosen untrained TBAs from the HSI communities , were tested and interviewed . Patients from both referred and non-referred deliveries were also interviewed . RESULTS Characteristics of TBAs in the two groups were similar . The TBAs were evaluated according to various measures of knowledge , skill , and practice ( including referral ) , with patient reports on practice compared with TBA reports . By most measures , trained TBAs outperformed untrained ones , often to significant degrees . CONCLUSION SMART Dai training seemed to be an important factor in the significant reduction in perinatal mortality in the CBI areas . Properly trained TBAs can substantially contribute to improved delivery outcomes A study was carried out in Misungwi and Kwimba Districts , Tanzania to determine the effectiveness of clean delivery kits in preventing cord infection and puerperal sepsis and to provide qualitative information on community acceptability , correct use , and appropriateness of the kits . This study involved pregnant women aged 18 - 45 years old . In the delivery kit intervention population , the Maternal and Child Health Aide ( MCHA ) assigned to the health facility provided pregnant mothers with a clean delivery kit on their first antenatal visit . She explained how to use each of the kit components , with the aid of pictorial instructions included in the kit . The pregnant mothers were asked to convey the information to whoever assisted them during delivery . The MCHA also gave them health education based on the principles of the " six cleans " recognized by WHO ( i.e. , clean h and s , clean perineum , clean delivery surface , clean cord cutting and tying instruments , clean cutting surface ) . Women received the clean delivery kit free of charge in accordance with the r and omised stepped-wedge design schedule . During the first week following delivery , the Village Health Workers ( VHWs ) from both the intervention and control groups made two visits to the households of mothers who had delivered . They administered question naire about delivery to mother and birth attendant . During the two scheduled postpartum visits , those who were suspected to have puerperal sepsis or cord infection of the baby were referred to the health facility clinician for confirmation . Results indicated that use of clean delivery kit had a positive effect on reducing both cord infection and puerperal sepsis . The use of a clean home delivery kit coupled with an educational intervention about the " six cleans " had a significant effect on reducing the incidence of cord infection and puerperal sepsis among women enrolled in the study . In low re source setting s where home birth is common and clean delivery supplies are scarce , disposable kits can be made available through health clinics , markets , pharmacies or other channels to help reduce rates of infection Abstract Objectives : To evaluate impact of postnatal health education for mothers on infant care and postnatal family planning practice s in Nepal . Design : R and omised controlled trial with community follow up at 3 and 6 months post partum by interview . Initial household survey of study areas to identify all pregnant women to facilitate follow up . Setting : Main maternity hospital in Kathm and u , Nepal . Follow up in urban Kathm and u and a periurban area southwest of the city . Subjects : 540 mothers r and omly allocated to one of four groups : health education immediately after birth and three months later ( group A ) , at birth only ( group B ) , at three months only ( group C ) , or none ( group D ) . Interventions : Structured baseline household question naire ; 20 minute , one to one health education at birth and three months later . Main outcome measures : Duration of exclusive breast feeding , appropriate immunisation of infant , knowledge of oral rehydration solution and need to continue breast feeding in diarrhoea , knowledge of infant signs suggesting pneumonia , uptake of postnatal family planning . Results : Mothers in groups A and B ( received health education at birth ) were slightly more likely to use contraception at six months after birth compared with mothers in groups C and D ( no health education at birth ) ( odds ratio 1.62 , 95 % confidence interval 1.06 to 2.5 ) . There were no other significant differences between groups with regards to infant feeding , infant care , or immunisation . Conclusions : Our findings suggest that the recommended practice of individual health education for postnatal mothers in poor communities has no impact on infant feeding , care , or immunisation , although uptake of family planning may be slightly enhanced . Key messages Health education is widely promoted in primary care , but there have been few rigorous evaluations of its impact , especially in developing countries A r and omised controlled trial of postnatal individual health education for mothers given by trained female health workers showed no significant impact on maternal knowledge and practice s of child care or on infant health outcomes , but there was a small improvement in uptake of family planning at six months after birth The efficacy of health education interventions that rely solely on giving people information to bring about a change in health behaviour is unproved ; interventions should be evaluated before being implemented on a large scale Alternative strategies for health promotion in developing countries such as interactions within families , peer groups , or communities may be more effective but are costly and difficult to implement on a large PURPOSE To compare effects of an early intervention program ( EIP ) of intense home visitation by public health nurses ( PHNs ) with effects of traditional public health nursing care ( TPHN ) on infant health and selected maternal outcomes of adolescent mothers . METHODS EIP adolescents ( N = 102 ) received preparation-for-motherhood classes and individual home visits ( from pregnancy through 1 year postpartum ) from PHNs employed in a county health department . Participants were predominantly Latina ( 64 % ) and African-American ( 11 % ) and from impoverished background s. Infant health outcomes were determined based on medical record data ; interviews and st and ardized question naires evaluated other program effects ( e.g. , maternal educational achievement and psychological status ) . Data were analyzed using Chi-square and repeated measures ANOVA . RESULTS Infants of EIP mothers experienced significantly fewer total days ( n = 74 ) and actual episodes ( n = 14 ) of hospitalization during the first year of life than those receiving TPHN ( n = 154 , n = 24 , respectively ) . Similarly , positive program effects were found for immunization rates . There were no group differences in emergency room visits or repeat pregnancy rates . Alcohol , tobacco , and marijuana use significantly increased from pregnancy through 1 year postpartum in both groups but remained markedly lower than rates prior to pregnancy ( lifetime rates ) . CONCLUSIONS These findings demonstrate the positive effects of a PHN home visitation program on health outcomes for children of adolescent mothers . Days of infant hospitalization were substantially reduced and immunization rates increased during the first year of life for children of EIP mothers . Greater efforts need to be directed toward preventing repeat pregnancy and return to substance use following childbirth in at-risk adolescent mothers Background The UN Millennium Development Goals call for substantial reductions in maternal and child mortality , to be achieved through reductions in morbidity and mortality during pregnancy , delivery , postpartum and early childhood . The M aiM wana Project aims to test community-based interventions that tackle maternal and child health problems through increasing awareness and local action . Methods / Design This study uses a two-by-two factorial cluster-r and omised controlled trial design to test the impact of two interventions . The impact of a community mobilisation intervention run through women 's groups , on home care , health care-seeking behaviours and maternal and infant mortality , will be tested . The impact of a volunteer-led infant feeding and care support intervention , on rates of exclusive breastfeeding , uptake of HIV-prevention services and infant mortality , will also be tested . The women 's group intervention will employ local female facilitators to guide women 's groups through a four-phase cycle of problem identification and prioritisation , strategy identification , implementation and evaluation . Meetings will be held monthly at village level . The infant feeding intervention will select local volunteers to provide advice and support for breastfeeding , birth preparedness , newborn care and immunisation . They will visit pregnant and new mothers in their homes five times during and after pregnancy . The unit of intervention allocation will be clusters of rural villages of 2500 - 4000 population . 48 clusters have been defined and r and omly allocated to either women 's groups only , infant feeding support only , both interventions , or no intervention . Study villages are surrounded by ' buffer areas ' of non- study villages to reduce contamination between intervention and control areas . Outcome indicators will be measured through a demographic surveillance system . Primary outcomes will be maternal , infant , neonatal and perinatal mortality for the women 's group intervention , and exclusive breastfeeding rates and infant mortality for the infant feeding intervention . Structured interviews will be conducted with mothers one-month and six-months after birth to collect detailed quantitative data on care practice s and health-care-seeking . Further qualitative , quantitative and economic data will be collected for process and economic evaluations . Trial registration IS RCT Background Pregnant women living with HIV ( WLH ) face daily challenges maintaining their own and their babies ' health and mental health . St and ard Prevention of Maternal to Child Transmission ( PMTCT ) programs are not design ed to address these challenges . Methods / Design As part of a cluster r and omized controlled trial , WLH are invited to attend four antenatal and four postnatal small group sessions led by a peer WLH ( a Peer Mentor ) . The WLH and their babies are assessed during pregnancy and at one week , six months , and twelve months post-birth . Mobile phones are used to collect routine information , complete question naires and remain in contact with participants over time . Pregnant WLH ( N = 1200 ) are r and omly assigned by clinic ( N = 8 clinics ) to an intervention program , called Masihambisane ( n = 4 clinics , n = 600 WLH ) or a st and ard care PMTCT control condition ( n = 4 clinics ; n = 600 WLH ) . Discussion Data collection with cellular phones are innovative and effective in low-re source setting s. St and ard PMTCT programs are not design ed to address the daily challenges faced by WLH ; Peer Mentors may be useful in supporting WLH to cope with these challenges . Trial registration Clinical Trials.gov registration # OBJECTIVES We evaluated the efficacy of a primary care intervention targeting pregnant African American women and focusing on psychosocial and behavioral risk factors for poor reproductive outcomes ( cigarette smoking , secondh and smoke exposure , depression , and intimate partner violence ) . METHODS Pregnant African American women ( N = 1044 ) were r and omized to an intervention or usual care group . Clinic-based , individually tailored counseling sessions were adapted from evidence -based interventions . Follow-up data were obtained for 850 women . Multiple imputation methodology was used to estimate missing data . Outcome measures were number of risks at baseline , first follow-up , and second follow-up and within-person changes in risk from baseline to the second follow-up . RESULTS Number of risks did not differ between the intervention and usual care groups at baseline , the second trimester , or the third trimester . Women in the intervention group more frequently resolved some or all of their risks than did women in the usual care group ( odds ratio = 1.61 ; 95 % confidence interval = 1.08 , 2.39 ; P = .021 ) . CONCLUSIONS In comparison with usual care , a clinic-based behavioral intervention significantly reduced psychosocial and behavioral pregnancy risk factors among high-risk African American women receiving prenatal care Background Birth attendance by trained health workers is low in rural Nepal . Local participation in improving health services and increased interaction between health systems and communities may stimulate dem and for health services . Significant increases in birth attendance by trained health workers may be affected through community mobilisation by local women 's groups and health management committee strengthening . We will test the effect of community mobilisation through women 's groups , and health management committee strengthening , on institutional deliveries and home deliveries attended by trained health workers in Makwanpur District . Design Cluster r and omised controlled trial involving 43 village development committee clusters . 21 clusters will receive the intervention and 22 clusters will serve as control areas . In intervention areas , Female Community Health Volunteers are supported in convening monthly women 's groups . The groups work through an action research cycle in which they consider barriers to institutional delivery , plan and implement strategies to address these barriers with their communities , and evaluate their progress . Health management committees participate in three-day workshops that use appreciative inquiry methods to explore and plan ways to improve maternal and newborn health services . Follow-up meetings are conducted every three months to review progress . Primary outcomes are institutional deliveries and home deliveries conducted by trained health workers . Secondary outcome measures include uptake of antenatal and postnatal care , neonatal mortality and stillbirth rates , and maternal morbidity . Trial registration numberIS RCT OBJECTIVE To determine whether a women 's group intervention involving participatory learning and action has a sustainable and replicable effect on neonatal survival in rural , eastern India . METHODS From 2004 to 2011 , births and neonatal deaths in 36 geographical clusters in Jharkh and and Odisha were monitored . Between 2005 and 2008 , these clusters were part of a r and omized controlled trial of how women 's group meetings involving participatory learning and action influence maternal and neonatal health . Between 2008 and 2011 , groups in the original intervention clusters ( zone 1 ) continued to meet to discuss post-neonatal issues and new groups in the original control clusters ( zone 2 ) met to discuss neonatal health . Logistic regression was used to examine neonatal mortality rates after 2008 in the two zones . FINDINGS Data on 41,191 births were analysed . In zone 1 , the intervention 's effect was sustained : the cluster-mean neonatal mortality rate was 34.2 per 1000 live births ( 95 % confidence interval , CI : 28.3 - 40.0 ) between 2008 and 2011 , compared with 41.3 per 1000 live births ( 95 % CI : 35.4 - 47.1 ) between 2005 and 2008 . The effect of the intervention was replicated in zone 2 : the cluster-mean neonatal mortality rate decreased from 61.8 to 40.5 per 1000 live births between two periods : 2006 - 2008 and 2009 - 2011 ( odds ratio : 0.69 , 95 % CI : 0.57 - 0.83 ) . Hygiene during delivery , thermal care of the neonate and exclusive breastfeeding were important factors . CONCLUSION The effect of participatory women 's groups on neonatal survival in rural India , where neonatal mortality is high , was sustainable and replicable IMPORTANCE Community-based interventions can reduce neonatal mortality when health systems are weak . Population coverage of target groups may be an important determinant of their effect on behavior and mortality . A women 's group trial at coverage of 1 group per 1414 population in rural Bangladesh showed no effect on neonatal mortality , despite a similar intervention having a significant effect on neonatal and maternal death in comparable setting s. OBJECTIVE To assess the effect of a participatory women 's group intervention with higher population coverage on neonatal mortality in Bangladesh . DESIGN A cluster r and omized controlled trial in 9 intervention and 9 control clusters . SETTING Rural Bangladesh . PARTICIPANTS Women permanently residing in 18 unions in 3 districts and accounting for 19 301 births during the final 24 months of the intervention . INTERVENTIONS Women 's groups at a coverage of 1 per 309 population that proceed through a participatory learning and action cycle in which they prioritize issues that affected maternal and neonatal health and design and implement strategies to address these issues . MAIN OUTCOMES AND MEASURES Neonatal mortality rate . RESULTS Analysis included 19 301 births during the final 24 months of the intervention . More than one-third of newly pregnant women joined the groups . The neonatal mortality rate was significantly lower in the intervention arm ( 21.3 neonatal deaths per 1000 live births vs 30.1 per 1000 in control areas ) , a reduction in neonatal mortality of 38 % ( risk ratio , 0.62 [ 95 % CI , 0.43 - 0.89 ] ) when adjusted for socioeconomic factors . The cost-effectiveness was US $ 220 to $ 393 per year of life lost averted . Cause-specific mortality rates suggest reduced deaths due to infections and those associated with prematurity/low birth weight . Improvements were seen in hygienic home delivery practice s , newborn thermal care , and breastfeeding practice s. CONCLUSIONS AND RELEVANCE Women 's group community mobilization , delivered at adequate population coverage , is a highly cost-effective approach to improve newborn survival and health behavior indicators in rural Bangladesh . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N01805825 OBJECTIVE --To see whether non-professional volunteer community mothers could deliver a child development programme to disadvantaged first time mothers for children aged up to 1 year . DESIGN --R and omised controlled trial . SETTING --A regional health authority in Dublin . SUBJECTS--262 first time mothers who were delivered during six months in 1989 and who lived in a deprived area of Dublin ; 30 experienced mothers from the same community recruited as community mothers . INTERVENTIONS --All the first time mothers received st and ard support from the public health nurse . In addition , those in the intervention group received the services of a community mother , who was scheduled to visit monthly during the first year of the child 's life . RESULTS --232 ( 89 % ) first time mothers completed the study --127 in the intervention group , 105 controls . At the end of the study children in the intervention group were more likely to have received all of their primary immunisations , to be read to , and to be read to daily , played more cognitive games ; and were exposed to more nursery rhymes . They were less likely to begin cows ' milk before 26 weeks and to receive an inappropriate energy intake and inappropriate amounts of animal protein , non-animal protein , wholefoods , vegetables , fruit , and milk . Mothers in the intervention group also had a better diet than controls . At the end of the study they were less likely to be tired , feel miserable , and want to stay indoors ; had more positive feelings ; and were less likely to display negative feelings . CONCLUSION --Non-professionals can deliver a health promotion programme on child development effectively . Whether they can do so as effectively as professionals requires further study BACKGROUND The aim of the study was to determine whether peer counselling in the antenatal and post-natal period would increase the prevalence and duration of breastfeeding among low-income women in Glasgow . METHODS The study was design ed as a quasi-experimental evaluation of a community-based breastfeeding promotion programme . The intervention comprised peer counselling of pregnant women , support of breastfeeding mothers and local awareness-raising activities . The study subjects were all women attending the antenatal booking clinic resident in either the intervention or control area . Data were collected by means of four self-completion question naires , two administered antenatally and two post-natally . The proportions intending to breastfeed or breastfeeding in the intervention and control groups were compared at each assessment and over time . RESULTS Of the 995 women enrolled in the study , data were available for analysis on 919 ( 92 per cent ) to 6 weeks postnatally . At booking , 18 per cent of the intervention group and 21 per cent of the control group stated an intention to breastfeed . At delivery , the proportions initiating breastfeeding were 23 per cent of the intervention subjects and 20 per cent of the controls , and by 6 weeks post-natally , the proportion providing any breast milk had declined to 10 per cent of the intervention group and 8 per cent of the control group . Using multivariate analysis to adjust for factors ( such as socio-economic status ) known to influence breastfeeding , the breastfeeding prevalence was significantly higher in the intervention group relative to the controls at delivery [ odds ratio ( OR ) 2.0 ; 95 per cent confidence interval ( CI ) 1.2 - 3.1 , p = 0.006 ] . By 6 weeks post-natally the difference between the two groups was not statistically significant ( OR 1.8 ; 95 per cent CI 1.0 - 3.4 , p=0.07 ) . CONCLUSIONS As the impact of the intervention was not sustained even for the modest duration of 6 weeks postnatally , it would be premature to justify widespread use of peer support programmes to increase the prevalence of breastfeeding in socially disadvantaged communities Background Every year an estimated three million neonates die globally and two hundred thous and of these deaths occur in Pakistan . Majority of these neonates die in rural areas of underdeveloped countries from preventable causes ( infections , complications related to low birth weight and prematurity ) . Similarly about three hundred thous and mother died in 2010 and Pakistan is among ten countries where sixty percent burden of these deaths is concentrated . Maternal and neonatal mortality remain to be unacceptably high in Pakistan especially in rural areas where more than half of births occur . Method / Design This community based cluster r and omized controlled trial will evaluate the impact of an Emergency Obstetric and Newborn Care ( EmONC ) package in the intervention arm compared to st and ard of care in control arm . Perinatal and neonatal mortality are primary outcome measure for this trial . The trial will be implemented in 20 clusters ( Union councils ) of District Rahimyar Khan , Pakistan . The EmONC package consists of provision of maternal and neonatal health pack ( clean delivery kit , emollient , chlorhexidine ) for safe motherhood and newborn wellbeing and training of community level and facility based health care providers with emphasis on referral of complicated cases to nearest public health facilities and community mobilization . Discussion Even though there is substantial evidence in support of effectiveness of various health interventions for improving maternal , neonatal and child health . Reduction in perinatal and neonatal mortality remains a big challenge in re source constrained and diverse countries like Pakistan and achieving MDG 4 and 5 appears to be a distant reality . A comprehensive package of community based low cost interventions along the continuum of care tailored according to the socio cultural environment coupled with existing health force capacity building may result in improving the maternal and neonatal outcomes .The findings of this proposed community based trial will provide sufficient evidence on feasibility , acceptability and effectiveness to the policy makers for replicating and scaling up the interventions within the health systemTrial registration Clinical Trial.gov Background Two out of three neonatal deaths occur in just 10 countries and Pakistan st and s third among them . Maternal mortality is also high with most deaths occurring during labor , birth , and first few hours after birth . Enhanced access and utilization of skilled delivery and emergency obstetric care is the demonstrated strategy in reducing maternal and neonatal mortality . This trial aims to compare reduction in neonate mortality and utilization of available safe birthing and Emergency Obstetric and Neonatal Care services among pregnant mothers receiving ‘ structured birth planning ’ , and /or ‘ transport facilitation ’ compared to routine care . Methods A pragmatic cluster r and omized trial , with qualitative and economic studies , will be conducted in Jhang , Chiniot and Khanewal districts of Punjab , Pakistan , from February 2011 to May 2013 . At least 29,295 pregnancies will be registered in the three arms , seven clusters per arm ; 1 ) structured birth planning and travel facilitation , 2 ) structured birth planning , and 3 ) control arm . Trial will be conducted through the Lady Health Worker program . Main outcomes are difference in neonatal mortality and service utilization ; maternal mortality being the secondary outcome . Cluster level analysis will be done according to intention-to-treat . Discussion A nationwide network of about 100,000 lady health workers is already involved in antenatal and postnatal care of pregnant women . They also act as “ gatekeepers ” for the child birthing services . This gate keeping role mainly includes counseling and referral for skill birth attendance and travel arrangements for emergency obstetric care ( if required ) . The review of current arrangements and practice s show that the care delivery process needs enhancement to include adequate information provision as well as informed “ decision ” making and planned “ action ” by the pregnant women . The proposed three-year research is to develop , through national technical working group process , and then test a set of arrangements for achieving the enhanced utilization of safe birthing services . Trial registration Current Controlled Trials IS RCT BACKGROUND Newborn deaths account for 57 % of deaths in children younger than 5 years in Pakistan . Although a large programme of trained lady health workers ( LHWs ) exists , the effectiveness of this training on newborn outcomes has not been studied . We aim ed to evaluate the effectiveness of a community-based intervention package , principally delivered through LHWs working with traditional birth attendants and community health committees , for reduction of perinatal and neonatal mortality in a rural district of Pakistan . METHODS We undertook a cluster r and omised trial between February , 2006 , and March , 2008 , in Hala and Matiari subdistricts , Pakistan . Catchment areas of primary care facilities and all affiliated LHWs were used to define clusters , which were allocated to intervention and control groups by restricted , stratified r and omisation . The intervention package delivered by LHWs through group sessions consisted of promotion of antenatal care and maternal health education , use of clean delivery kits , facility births , immediate newborn care , identification of danger signs , and promotion of careseeking ; control clusters received routine care . Independent data collectors undertook quarterly household surveillance to capture data for births , deaths , and household practice s related to maternal and newborn care . Data collectors were masked to cluster allocation ; those analysing data were not . The primary outcome was perinatal and all-cause neonatal mortality . Analysis was by intention to treat . This trial is registered , IS RCT N16247511 . FINDINGS 16 clusters were assigned to intervention ( 23,353 households , 12,391 total births ) and control groups ( 23,768 households , 11,443 total births ) . LHWs in the intervention clusters were able to undertake 4428 ( 63 % ) of 7084 planned group sessions , but were only able to visit 2943 neonates ( 24 % ) of a total 12,028 livebirths in their catchment villages . Stillbirths were reduced in intervention clusters ( 39·1 stillbirths per 1000 total births ) compared with control ( 48·7 per 1000 ; risk ratio [ RR ] 0·79 , 95 % CI 0·68 - 0·92 ; p=0·006 ) . The neonatal mortality rate was 43·0 deaths per 1000 livebirths in intervention clusters compared with 49·1 per 1000 in control groups ( RR 0·85 , 0·76 - 0·96 ; p=0·02 ) . INTERPRETATION Our results support the scale-up of preventive and promotive maternal and newborn interventions through community health workers and emphasise the need for attention to issues of programme management and coverage for such initiatives to achieve maximum potential . FUNDING WHO ; Saving Newborn Lives Program of Save the Children USA , funded by the Bill & Melinda Gates Foundation Background The United Nations Millennium Development Goals look to substantial improvements in child and maternal survival . Morbidity and mortality during pregnancy , delivery and the postnatal period are prime obstacles to achieving these goals . Given the increasing importance of urban health to global prospect s , Mumbai 's City Initiative for Newborn Health aims to improve maternal and neonatal health in vulnerable urban slum communities , through a combination of health service quality improvement and community participation . The protocol describes a trial of community intervention aim ed at improving prevention , care seeking and outcomes . Objective To test an intervention that supports local women as facilitators in mobilising communities for better health care . Community women 's groups will build an underst and ing of their potential to improve maternal and infant health , and develop and implement strategies to do so . Design Cluster-r and omized controlled trial . Methods The intervention will employ local community-based female facilitators to convene groups and help them to explore maternal and neonatal health issues . Groups will meet fortnightly through a seven-phase process of sharing experiences , discussion of the issues raised , discovery of potential community strengths , building of a vision for action , design and implementation of community strategies , and evaluation . The unit of allocation will be an urban slum cluster of 1000–1500 households . 48 clusters have been r and omly selected after stratification by ward . 24 clusters have been r and omly allocated to receive the community intervention . 24 clusters will act as control groups , but will benefit from health service quality improvement . Indicators of effect will be measured through a surveillance system implemented by the project . Key distal outcome indicators will be neonatal mortality and maternal and neonatal morbidity . Key proximate outcome indicators will be home care practice s , uptake of antenatal , delivery and postnatal care , and care for maternal and neonatal illness . Data will be collected through a vital registration system for births and deaths in the 48 study clusters . Structured interviews with families will be conducted at about 6 weeks after index deliveries . We will also collect both quantitative and qualitative data to support a process evaluation . Trial registration Current controlled trials IS RCT OBJECTIVES In a community r and omized trial , we aim ed to promote exclusive breastfeeding and appropriate complementary feeding practice s in under-twos to ascertain the feasibility of using available channels for nutrition counselling , their relative performance and the relationship between intensity of counselling and behaviour change . We also assessed whether using multiple opportunities to impart nutrition education adversely affected routine activities . METHODS We conducted a community r and omized , controlled effectiveness trial in rural Haryana , India , with four intervention and four control communities . We trained health and nutrition workers in the intervention communities to counsel mothers at multiple contacts on breastfeeding exclusively for 6 months and on appropriate complementary feeding practice s thereafter . The intervention was not just training health and nutrition workers in counselling but included community and health worker mobilization . FINDINGS In the intervention group , about 32 % of caregivers were counselled by traditional birth attendants at birth . The most frequent sources of counselling from birth to 3 months were immunization sessions ( 45.1 % ) and home visits ( 32.1 % ) , followed closely by weighing sessions ( 25.5 % ) ; from 7 to 12 months , home visits ( 42.6 % ) became more important than the other two . An increase in the number of channels through which caregivers were counselled was positively associated with exclusive breastfeeding prevalence at 3 months ( p = 0.002 ) , consumption of milk/cereal gruel or mix use at 9 months ( p = 0.004 ) and 18 months ( p = 0.003 ) , undiluted milk at 9 months ( p<0.0001 ) and 24 hour non-breast-milk energy intakes at 18 months ( p = 0.023 ) , after controlling for potential confounding factors . Intervention areas , compared with the control , had higher coverage for vitamin A ( 45 % vs. 11.5 % ) and iron folic acid ( 45 % vs. 0.4 % ) supplementation . CONCLUSIONS Using multiple available opportunities and workers for counselling caregivers was feasible , result ed in high coverage and impact , and instead of disrupting ongoing services , result ed in their improvement Lars Åke Persson and colleagues conduct a cluster r and omised control in northern Vietnam to analyze the effect of the activity of local community-based maternal- and -newborn stakeholder groups on neonatal mortality . Please see later in the article for the Editors ' Maternal mortality is a global burden , with more than 500,000 women dying each year due to pregnancy and childbirth-related complications . Birth-preparedness and complication readiness is a comprehensive strategy to improve the use of skilled providers at birth , the key intervention to decrease maternal mortality . Birth-preparedness and complication readiness include many elements , including : ( a ) knowledge of danger signs ; ( b ) plan for where to give birth ; ( c ) plan for a birth attendant ; ( d ) plan for transportation ; and ( e ) plan for saving money . The 2003 Burkina Faso Demographic and Health Survey indicated that only 38.5 % of women gave birth with the assistance of a skilled provider . The Maternal and Neonatal Health Program of JHPIEGO implemented a district-based model service-delivery system in Koupéla , Burkina Faso , during 2001–2004 , to increase the use of skilled providers during pregnancy and childbirth . In 2004 , a cross-sectional survey with a r and om sample of respondents was conducted to measure the impact of birth-preparedness and complication readiness on the use of skilled providers at birth . Of the 180 women who had given birth within 12 months of the survey , 46.1 % had a plan for transportation , and 83.3 % had a plan to save money . Women with these plans were more likely to give birth with the assistance of a skilled provider ( p=0.07 and p=0.03 respectively ) . Controlling for education , parity , average distance to health facility , and the number of antenatal care visits , planning to save money was associated with giving birth with the assistance of a skilled provider ( p=0.05 ) . Qualitative interviews with women who had given birth within 12 months of the survey ( n=30 ) support these findings . Most women saved money for delivery , but had less concrete plans for transportation . These findings highlight how birth-preparedness and complication readiness may be useful in increasing the use of skilled providers at birth , especially for women with a plan for saving money during pregnancy BACKGROUND Community mobilisation through participatory women 's groups might improve birth outcomes in poor rural communities . We therefore assessed this approach in a largely tribal and rural population in three districts in eastern India . METHODS From 36 clusters in Jharkh and and Orissa , with an estimated population of 228 186 , we assigned 18 clusters to intervention or control using stratified r and omisation . Women were eligible to participate if they were aged 15 - 49 years , residing in the project area , and had given birth during the study . In intervention clusters , a facilitator convened 13 groups every month to support participatory action and learning for women , and facilitated the development and implementation of strategies to address maternal and newborn health problems . The primary outcomes were reductions in neonatal mortality rate ( NMR ) and maternal depression scores . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N21817853 . FINDINGS After baseline surveillance of 4692 births , we monitored outcomes for 19 030 births during 3 years ( 2005 - 08 ) . NMRs per 1000 were 55.6 , 37.1 , and 36.3 during the first , second , and third years , respectively , in intervention clusters , and 53.4 , 59.6 , and 64.3 , respectively , in control clusters . NMR was 32 % lower in intervention clusters adjusted for clustering , stratification , and baseline differences ( odds ratio 0.68 , 95 % CI 0.59 - 0.78 ) during the 3 years , and 45 % lower in years 2 and 3 ( 0.55 , 0.46 - 0.66 ) . Although we did not note a significant effect on maternal depression overall , reduction in moderate depression was 57 % in year 3 ( 0.43 , 0.23 - 0.80 ) . INTERPRETATION This intervention could be used with or as a potential alternative to health-worker-led interventions , and presents new opportunities for policy makers to improve maternal and newborn health outcomes in poor population s. FUNDING Health Foundation , UK Department for International Development , Wellcome Trust , and the Big Lottery Fund ( UK ) Background Neonatal mortality rates are high in rural Nepal where more than 90 % of deliveries are in the home . Evidence suggests that death rates can be reduced by interventions at community level . We describe an intervention which aim ed to harness the power of community planning and decision making to improve maternal and newborn care in rural Nepal . Methods The development of 111 women 's groups in a population of 86 704 in Makwanpur district , Nepal is described . The groups , facilitated by local women , were the intervention component of a r and omized controlled trial to reduce perinatal and neonatal mortality rates . Through participant observation and analysis of reports , we describe the implementation of this intervention : the community entry process , the facilitation of monthly meetings through a participatory action cycle of problem identification , community planning , and implementation and evaluation of strategies to tackle the identified problems . Results In response to the needs of the group , participatory health education was added to the intervention and the women 's groups developed varied strategies to tackle problems of maternal and newborn care : establishing mother and child health funds , producing clean home delivery kits and operating stretcher schemes . Close linkages with community leaders and community health workers improved strategy implementation . There were also indications of positive effects on group members and health services , and most groups remained active after 30 months . Conclusion A large scale and potentially sustainable participatory intervention with women 's groups , which focused on pregnancy , childbirth and the newborn period , result ed in innovative strategies identified by local communities to tackle perinatal care problems Background Progress towards MDG4 in South Africa will depend largely on scaling up effective prevention against mother to child transmission ( PMTCT ) of HIV and also addressing neonatal mortality . This imperative drives increasing focus on the neonatal period and particularly on the development and testing of appropriate models of sustainable , community-based care in South Africa in order to reach the poor . A number of key implementation gaps affecting progress have been identified . Implementation gaps for HIV prevention in neonates ; implementation gaps for neonatal care especially home postnatal care ; and implementation gaps for maternal mental health support . We have developed and are evaluating and costing an integrated and scaleable home visit package delivered by community health workers targeting pregnant and postnatal women and their newborns to provide essential maternal/newborn care as well as interventions for Prevention of Mother to Child Transmission ( PMTCT ) of HIV . Methods The trial is a cluster r and omized controlled trial that is being implemented in Umlazi which is a peri-urban settlement with a total population of 1 million close to Durban in KwaZulu Natal , South Africa . The trial consists of 30 r and omized clusters ( 15 in each arm ) . A baseline survey established the homogeneity of clusters and neither stratification nor matching was performed . Sample size was based on increasing HIV-free survival from 74 % to 84 % , and calculated to be 120 pregnant women per cluster . Primary outcomes are higher levels of HIV free survival and levels of exclusive and appropriate infant feeding at 12 weeks postnatally . The intervention is home based with community health workers delivering two antenatal visits , a postnatal visit within 48 hours of birth , and a further four visits during the first two months of the infants life . We are undertaking programmatic and cost effectiveness analysis to cost the intervention . Discussion The question is not merely to develop an efficacious package but also to identify and test delivery strategies that enable scaling up , which requires effectiveness studies in a health systems context , adapting and testing Asian community-based studies in various African context s . Trial registration IS RCT N : IS RCT Summary Background The treatment of perinatal depression is a public-health priority because of its high prevalence and association with disability and poor infant development . We integrated a cognitive behaviour therapy-based intervention into the routine work of community-based primary health workers in rural Pakistan and assessed the effect of this intervention on maternal depression and infant outcomes . Methods We r and omly assigned 40 Union Council clusters in rural Rawalpindi , Pakistan , in equal numbers to intervention or control . Married women ( aged 16–45 years ) in their third trimester of pregnancy with perinatal depression were eligible to participate . In the intervention group , primary health workers were trained to deliver the psychological intervention , whereas in the control group untrained health workers made an equal number of visits to the depressed mothers . The primary outcomes were infant weight and height at 6 months and 12 months , and secondary outcome was maternal depression . The interviewers were unaware of what group the participants were assigned to . Analysis was by intention to treat . The study is registered as IS RCT N65316374 . Findings The number of clusters per group was 20 , with 463 mothers in the intervention group and 440 in the control group . At 6 months , 97 ( 23 % ) of 418 and 211 ( 53 % ) of 400 mothers in the intervention and control groups , respectively , met the criteria for major depression ( adjusted odds ratio ( OR ) 0·22 , 95 % CI 0·14 to 0·36 , p<0·0001 ) . These effects were sustained at 12 months ( 111/412 [ 27 % ] vs 226/386 [ 59 % ] , adjusted OR 0·23 , 95 % CI 0·15 to 0·36 , p<0·0001 ) . The differences in weight-for-age and height-for-age Z scores for infants in the two groups were not significant at 6 months ( −0·83 vs −0·86 , p=0·7 and −2·03 vs −2·16 , p=0·3 , respectively ) or 12 months ( −0·64 vs −0·8 , p=0·3 and −1·10 vs −1·36 , p=0·07 , respectively ) . Interpretation This psychological intervention delivered by community-based primary health workers has the potential to be integrated into health systems in re source -poor setting s. Funding Wellcome Trust Background Maternal mortality in much of sub-Saharan Africa is very high whereas there has been a steady decline in over the past 60 years in Europe . Perinatal mortality is 12 times higher than maternal mortality accounting for about 7 million neonatal deaths ; many of these in sub-Saharan countries . Many of these deaths are preventable . Countries , like Malawi , do not have the re sources nor highly trained medical specialists using complex technologies within their healthcare system . Much of the burden falls on healthcare staff other than doctors including non-physician clinicians ( NPCs ) such as clinical officers , midwives and community health-workers . The aim of this trial is to evaluate a project which is training NPCs as advanced leaders by providing them with skills and knowledge in advanced neonatal and obstetric care . Training that will hopefully be cascaded to their colleagues ( other NPCs , midwives , nurses ) . Methods / design This is a cluster r and omised controlled trial with the unit of r and omisation being the 14 districts of central and northern Malawi ( one large district was divided into two giving an overall total of 15 ) . Eight districts will be r and omly allocated the intervention . Within these eight districts 50 NPCs will be selected and will be enrolled on the training programme ( the intervention ) . Primary outcome will be maternal and perinatal ( defined as until discharge from health facility ) mortality . Data will be harvested from all facilities in both intervention and control districts for the lifetime of the project ( 3–4 years ) and comparisons made . In addition a process evaluation using both quantitative and qualitative ( e.g. interviews ) will be undertaken to evaluate the intervention implementation . Discussion Education and training of NPCs is a key to improving healthcare for mothers and babies in countries like Malawi . Some of the challenges faced are discussed as are the potential limitations . It is hoped that the findings from this trial will lead to a sustainable improvement in healthcare and workforce development and training . Trial registration IS RCT Background Poverty may moderate the effect of treatment of depression in low-income countries . Aims To assess poverty and lack of empowerment as moderators of a cognitive – behavioural therapy (CBT)-based intervention for perinatal depression in rural Pakistan . Method Using secondary analysis of data from a r and omised controlled trial ( trial registration : IS RCT N65316374 ) we identified predictors of depression at 1-year follow-up and moderators of the intervention ( n = 791 ) . Results Predictors of follow-up depression included household debt , the participant not being empowered to manage household finance and the interaction terms for these variables with the trial arm . Effect sizes for women with and without household debt were 0.80 and 0.55 respectively . The effect size for women in debt and not empowered financially was 0.94 compared with 0.50 for women with neither of these factors . Conclusions Our findings demonstrate the importance of household debt and lack of financial empowerment of women as important maintaining factors of depression in low-income countries and our locally developed intervention tackled these problems successfully Background Tanzania has been a pioneer in establishing community-level services , yet challenges remain in sustaining these systems and ensuring adequate human re source strategies . In particular , the added value of a cadre of professional community health workers is under debate . While Tanzania has the highest density of primary health care facilities in Africa , equitable access and quality of care remain a challenge . Utilization for many services proven to reduce child and maternal mortality is unacceptably low . Tanzanian policy initiatives have sought to address these problems by proposing expansion of community-based providers , but the Ministry of Health and Social Welfare ( MoHSW ) lacks evidence that this merits national implementation . The Tanzania Connect Project is a r and omized cluster trial located in three rural districts with a population of roughly 360,000 ( Kilombero , Rufiji , and Ulanga).Description of interventionConnect aims to test whether introducing a community health worker into a general program of health systems strengthening and referral improvement will reduce child mortality , improve access to services , exp and utilization , and alter reproductive , maternal , newborn and child health seeking behavior ; thereby accelerating progress towards Millennium Development Goals 4 and 5 . Connect has introduced a new cadre — Community Health Agents ( CHA ) — who were recruited from and work in their communities . To support the CHA , Connect developed supervisory systems , launched information and monitoring operations , and implemented logistics support for integration with existing district and village operations . In addition , Connect ’s district-wide emergency referral strengthening intervention includes clinical and operational improvements . Evaluation design Design ed as a community-based cluster-r and omized trial , CHA were r and omly assigned to 50 of the 101 villages within the Health and Demographic Surveillance System ( HDSS ) in the three study districts . To garner detailed information on household characteristics , behaviors , and service exposure , a r and om sub- sample survey of 3,300 women of reproductive age will be conducted at the baseline and endline . The referral system intervention will use baseline , midline , and endline facility-based data to assess systemic changes . Implementation and impact research of Connect will assess whether and how the presence of the CHA at village level provides added life-saving value to the health system . Discussion Global commitment to launching community-based primary health care has accelerated in recent years , with much of the implementation focused on Africa . Despite extensive investment , no program has been guided by a truly experimental study . Connect will not only address Tanzania ’s need for policy and operational research , it will bridge a critical international knowledge gap concerning the added value of salaried professional community health workers in the context of a high density of fixed facilities . Trial registration : IS RCT Background A r and omised controlled trial of participatory women 's groups in rural Nepal previously showed reductions in maternal and newborn mortality . In addition to the outcome data we also collected previously unreported information from the subgroup of women who had been pregnant prior to study commencement and conceived during the trial period . To determine the mechanisms via which the intervention worked we here examine the changes in perinatal care of these women . In particular we use the information to study factors affecting positive behaviour change in pregnancy , childbirth and newborn care . Methods Women 's groups focusing on perinatal care were introduced into 12 of 24 study clusters ( average cluster population 7000 ) . A total of 5400 women of reproductive age enrolled in the trial had previously been pregnant and conceived during the trial period . For each of four outcomes ( attendance at antenatal care ; use of a boiled blade to cut the cord ; appropriate dressing of the cord ; not discarding colostrum ) each of these women was classified as BETTER , GOOD , BAD or WORSE to describe whether and how she changed her pre-trial practice . Multilevel multinomial models were used to identify women most responsive to intervention . Results Among those not initially following good practice , women in intervention areas were significantly more likely to do so later for all four outcomes ( OR 1.92 to 3.13 ) . Within intervention clusters , women who attended groups were more likely to show a positive change than non-group members with regard to antenatal care utilisation and not discarding colostrum , but non-group members also benefited . Conclusion Women 's groups promoted significant behaviour change for perinatal care amongst women not previously following good practice . Positive changes attributable to intervention were not restricted to specific demographic subgroups Background In the year after birth one in six women has a depressive illness , 94 % experience at least one major health problem ( e.g. back pain , perineal pain , mastitis , urinary or faecal incontinence ) , 26 % experience sexual problems and almost 20 % have relationship problems with partners . Women with depression report less practical and emotional support from partners , less social support , more negative life events , and poorer physical health and see factors contributing to depression as lack of support , isolation , exhaustion and physical health problems . Fewer than one in three seek help in primary care despite frequent health care contacts . Methods Primary care and community-based strategies embedded in existing services were implemented in a cluster-r and omised trial involving 16 rural and metropolitan communities , pair-matched , within the State of Victoria , Australia . Intervention areas were also provided with a community development officer for two years . The primary aim was to reduce the relative risk of depression by 20 % in mothers six months after birth and to improve their physical health . Primary outcomes were obtained by postal question naires . The analysis was by intention-to-treat , unmatched , adjusting for the correlated nature of the data . Results 6,248 of 10,144 women ( 61.6 % ) in the intervention arm and 5057/ 8,411 ( 60.1 % ) in the comparison arm responded at six months , and there was no imbalance in major covariates between the two arms . Women 's mental health scores were not significantly different in the intervention arm and the comparison arm ( MCS mean score 45.98 and 46.30 , mean EPDS score 6.91 and 6.82 , EPDS ≥ 13 ( ' probable depression ' ) 15.7 % vs. 14.9 % , Odds ratioadj 1.06 ( 95%CI 0.91–1.24 ) . Women 's physical health scores were not significantly different in intervention and comparison arms ( PCS mean scores 52.86 and 52.88 ) . Conclusion The combined community and primary care interventions were not effective in reducing depression , or in improving the physical health of mothers six months after birth Background Preterm birth is a major cause of neonatal mortality , responsible for 28 % of neonatal deaths overall . The administration of antenatal corticosteroids to women at high risk of preterm birth is a powerful perinatal intervention to reduce neonatal mortality in re source rich environments . The effect of antenatal steroids to reduce mortality and morbidity among preterm infants in hospital setting s in developed countries with high utilization is well established , yet they are not routinely used in developing countries . The impact of increasing antenatal steroid use in hospital or community setting s with low utilization rates and high infant mortality among premature infants due to lack of specialized services has not been well research ed . There is currently no clear evidence about the safety of antenatal corticosteroid use for community-level births . Methods We hypothesize that a multi country , two-arm , parallel cluster r and omized controlled trial to evaluate whether a multifaceted intervention to increase the use of antenatal corticosteroids , including components to improve the identification of pregnancies at high risk of preterm birth and providing and facilitating the appropriate use of steroids , will reduce neonatal mortality at 28 days of life in preterm newborns , compared with the st and ard delivery of care in selected population s of six countries . 102 clusters in Argentina , Guatemala , Kenya , India , Pakistan , and Zambia will be r and omized , and around 60,000 women and newborns will be enrolled . Kits containing vials of dexamethasone , syringes , gloves , and instructions for administration will be distributed . Improving the identification of women at high risk of preterm birth will be done by ( 1 ) diffusing recommendations for antenatal corticosteroids use to health providers , ( 2 ) training health providers on identification of women at high risk of preterm birth , ( 3 ) providing reminders to health providers on the use of the kits , and ( 4 ) using a color-coded tape to measure uterine height to estimate gestational age in women with unknown gestational age . In both intervention and control clusters , health providers will be trained in essential newborn care for low birth weight babies . The primary outcome is neonatal mortality at 28 days of life in preterm infants . Trial registration Clinical Trials.gov . Identifier : In the context of high neonatal mortality rate ( NMR ) in developing country setting s , a promising strategy for enhancing newborn health is promotion of preventive newborn care practice s. We measured the effect of a behaviour-change intervention on perceived neonatal illnesses in rural Uttar Pradesh , India . The study was nested in a cluster-r and omized controlled trial of the impact of a package of essential newborn care on NMR . We prospect ively enrolled 802 mothers and administered a question naire on perceived neonatal morbidities . Regression analysis showed that newborns in the intervention clusters had significantly lower risk of perceived diarrhoea [ adjusted relative risk ( aRR ) 0.67 , 95 % confidence interval ( CI ) 0.49 - 0.90 ] and skin-related complications [ aRR 0.67 , 95 % CI 0.45 - 1.00 ] compared to newborns in the comparison area . Assuming incidence of perceived illnesses is a proxy for actual morbidity rates , we conclude that promotion of preventive care practice s through behaviour-change interventions was effective in reducing neonatal morbidities Observational studies suggest that including men in reproductive health interventions can enhance positive health outcomes . A r and omized controlled trial was design ed to test the impact of involving male partners in antenatal health education on maternal health care utilization and birth preparedness in urban Nepal . In total , 442 women seeking antenatal services during second trimester of pregnancy were r and omized into three groups : women who received education with their husb and s , women who received education alone and women who received no education . The education intervention consisted of two 35-min health education sessions . Women were followed until after delivery . Women who received education with husb and s were more likely to attend a post-partum visit than women who received education alone [ RR = 1.25 , 95 % CI = ( 1.01 , 1.54 ) ] or no education [ RR = 1.29 , 95 % CI = ( 1.04 , 1.60 ) ] . Women who received education with their husb and s were also nearly twice as likely as control group women to report making > 3 birth preparations [ RR = 1.99 , 95 % CI = ( 1.10 , 3.59 ) ] . Study groups were similar with respect to attending the recommended number of antenatal care checkups , delivering in a health institution or having a skilled provider at birth . These data provide evidence that educating pregnant women and their male partners yields a greater net impact on maternal health behaviors compared with educating women alone Background In many developing countries , the majority of births are attended by traditional birth attendants , who lack formal training in neonatal resuscitation and other essential care required by the newly born infant . In these countries , the major causes of neonatal mortality are birth asphyxia , infection , and low-birth-weight/prematurity . Death from these causes is potentially modifiable using low-cost interventions , including neonatal resuscitation training . The purpose of this study was to evaluate the effect on perinatal mortality of training birth attendants in a rural area of the Democratic Republic of Congo ( DRC ) using two established programs . Methods This study , a secondary analysis of DRC-specific data collected during a multi-country study , was conducted in two phases . The effect of training using the WHO Essential Newborn Care ( ENC ) program was evaluated using an active baseline design , followed by a cluster r and omized trial of training using an adaptation of a neonatal resuscitation program ( NRP ) . The perinatal mortality rates before ENC , after ENC training , and after r and omization to additional NRP training or continued care were compared . In addition , the influence of time following resuscitation training was investigated by examining change in perinatal mortality during sequential three-month increments following ENC training . Results More than two-thirds of deliveries were attended by traditional birth attendants and occurred in homes ; these proportions decreased after ENC training . There was no apparent decline in perinatal mortality when the outcome of all deliveries prior to ENC training was compared to those after ENC but before NRP training . However , there was a gradual but significant decline in perinatal mortality during the year following ENC training ( RR 0.73 ; 95 % CI : 0.56 - 0.96 ) , which was independently associated with time following training . The decline was attributable to a decline in early neonatal mortality . NRP training had no demonstrable effect on early neonatal mortality . Conclusion Training DRC birth attendants using the ENC program reduces perinatal mortality . However , a period of utilization and re-enforcement of training may be necessary before a decline in mortality occurs . ENC training has the potential to be a low cost , high impact intervention in developing countries . Trial registration This trial has been registered at http://www . clinical trials.gov ( identifier NCT00136708 ) Objective To determine whether training traditional birth attendants to manage several common perinatal conditions could reduce neonatal mortality in the setting of a re source poor country with limited access to healthcare . Design Prospect i ve , cluster r and omised and controlled effectiveness study . Setting Lufwanyama , an agrarian , poorly developed district located in the Copperbelt province , Zambia . All births carried out by study birth attendants occurred at mothers ’ homes , in rural village setting s. Participants 127 traditional birth attendants and mothers and their newborns ( 3559 infants delivered regardless of vital status ) from Lufwanyama district . Interventions Using an unblinded design , birth attendants were cluster r and omised to intervention or control groups . The intervention had two components : training in a modified version of the neonatal resuscitation protocol , and single dose amoxicillin coupled with facilitated referral of infants to a health centre . Control birth attendants continued their existing st and ard of care ( basic obstetric skills and use of clean delivery kits ) . Main outcome measures The primary outcome was the proportion of liveborn infants who died by day 28 after birth , with rate ratios statistically adjusted for clustering . Secondary outcomes were mortality at different time points ; and comparison of causes of death based on verbal autopsy data . Results Among 3497 deliveries with reliable information , mortality at day 28 after birth was 45 % lower among liveborn infants delivered by intervention birth attendants than control birth attendants ( rate ratio 0.55 , 95 % confidence interval 0.33 to 0.90 ) . The greatest reductions in mortality were in the first 24 hours after birth : 7.8 deaths per 1000 live births for infants delivered by intervention birth attendants compared with 19.9 per 1000 for infants delivered by control birth attendants ( 0.40 , 0.19 to 0.83 ) . Deaths due to birth asphyxia were reduced by 63 % among infants delivered by intervention birth attendants ( 0.37 , 0.17 to 0.81 ) and by 81 % within the first two days after birth ( 0.19 , 0.07 to 0.52 ) . Stillbirths and deaths from serious infection occurred at similar rates in both groups . Conclusions Training traditional birth attendants to manage common perinatal conditions significantly reduced neonatal mortality in a rural African setting . This approach has high potential to be applied to similar setting s with dispersed rural population s. Trial registration Clinical trials.gov NCT00518856 OBJECTIVES This study aim ed to measure the effect and the total cost per woman of providing postnatal support at home , based on a Dutch model . The research hypothesis was furnished by some existing evidence that postnatal support could reduce the risk of postnatal depression and encourage breastfeeding . DESIGN The r and omised controlled trial aim ed to measure differences in health status in a group of women who were offered postnatal support from a community midwifery support worker ( SW ) compared with a control group of women who were not offered this support . Women were followed-up by postal question naire at 6 weeks and 6 months postnatally . SETTING AND SUBJECTS All women who delivered a baby at the recruiting hospital were eligible to take part in the trial if they lived within the study area , were aged 17 years or over , and could underst and English . INTERVENTION The intervention consisted of the SW offering practical and emotional support and to help women rest and recover after childbirth . The SW offered ten visits in the first 28 days postnatally , for up to 3 hours per day . The SW 's activities included housework , talking with the mother , and care for the baby or other siblings . The service was provided in addition to routine visits by the community midwife . MAIN OUTCOME MEASURES The primary outcome was the general health perception domain of the Short Form-36 at 6 weeks . Secondary outcomes were mean Edinburgh Postnatal Depression Scale ( EPDS ) , Duke Functional Social Support ( DUFSS ) scores and breastfeeding rates . RESULTS The 623 r and omised women were well-matched by group with a good response to follow-up . At 6 weeks there was no evidence of a significant difference between the two groups for the primary outcome . There was a non-significant trend for the control group to have better mean DUFSS and EPDS scores at 6 weeks . Breastfeeding rates were not significantly different at follow-up . At 6 months , both groups had similar health status . Satisfaction with the service was higher than for all other services received . The incremental cost of introducing the service comprised setting up and running the service . There were no differences between the groups in other re source use ( general practitioner contacts , hospital services , prescriptions or medicines bought for mothers and babies ) to 6-month follow-up . The total mean NHS cost to 6-month follow-up for the intervention group was pound180 per woman greater than for the control group ( confidence interval , pound79.60 , pound272.40 ) . CONCLUSIONS Although women valued the service , there was no evidence of any health benefit at the 6-week or 6-month follow-up , no difference in use of NHS services , and the additional cost of the service provision would be around pound 180 per woman Women with inadequate prenatal care were recruited to a multi-component parenting intervention study . Because it was anticipated that this high-risk population might present challenges to retention , a variety of strategies were employed to maintain their participation in the study . This report review s the results of these retention efforts and compares the population that completed the study versus those that terminated prior to study completion . Two hundred and eighty-six women were r and omized to an intervention or control group . Careful tracking of the mothers , offering incentives for completing various study activities and providing a culturally competent staff were among the strategies employed to maintain participation . Comparison was made of those mothers terminating before study completion versus those retained , and of those terminating early in the study period versus later . Despite retention efforts , attrition at a level of 41 % occurred . A few characteristics of mothers terminating early from the study were significant including older maternal age , a larger number of children , and incidence of no prenatal care . Despite comprehensive tracking procedures , some mothers were lost to follow up after change of residence . Other reasons for attrition included child outplacement and refusal of services or data collection procedures Background Children of adolescent mothers have higher rates of morbidity and unintentional injuries and hospitalizations during the first 5 years of life than do children of adult mothers . Objective The purpose of this study was to evaluate the 2-year postbirth infant health and maternal outcomes of an early intervention program ( EIP ) of home visitation by public health nurses ( PHNs ) . Methods In a r and omized controlled trial , a sample of predominantly Latina and African American adolescent mothers was followed from pregnancy through 2 years postpartum . The experimental group ( EIP , n = 56 ) received preparation-for-motherhood classes plus intense home visitation by PHNs from pregnancy through 1 year postbirth ; the control group ( TPHNC , n = 45 ) received traditional public health nursing care ( TPHNC ) . Health outcomes were determined based on medical record data ; other measures evaluated selected maternal behaviors , social competence , and mother-child interactions . Results The total days of non-birth-related infant hospitalizations during the first 24 months was significantly lower in the EIP ( 143 days ) than the TPHNC group ( 211 days ) and episodes of hospitalization were fewer ; more EIP than THHNC infants were never seen in the emergency room . The EIP mothers had 15 % fewer repeat pregnancies in the first 2 years postbirth than TPHNC mothers . The TPHNC mothers significantly increased marijuana use over time , whereas EIP mothers did not . Conclusions The EIP improved in selected areas of infant and maternal health , and these improvements were sustained for a period of 1 year following program termination . These findings have important implication s for healthcare services OBJECTIVE : To evaluate the efficacy of an integrated multiple risk intervention , delivered mainly during pregnancy , in reducing such risks ( cigarette smoking , environmental tobacco smoke exposure , depression , and intimate partner violence ) postpartum . METHODS : Data from this r and omized controlled trial were collected prenatally and on average 10 weeks postpartum in six prenatal care sites in the District of Columbia . African Americans were screened , recruited , and r and omly assigned to the behavioral intervention or usual care . Clinic-based , individually tailored counseling was delivered to intervention women . The outcome measures were number of risks reported postpartum and reduction of these risks between baseline and postpartum . RESULTS : The intervention was effective in significantly reducing the number of risks reported in the postpartum period . In bivariate analyses , the intervention group was more successful in resolving all risks ( 47 % compared with 35 % , P=.007 , number needed to treat=9 , 95 % confidence interval [ CI ] 5–31 ) and in resolving some risks ( 63 % compared with 54 % , P=.009 , number needed to treat=11 , 95 % CI 7–43 ) as compared with the usual care group . In logistic regression analyses , women in the intervention group were more likely to resolve all risks ( odds ratio 1.86 , 95 % CI 1.25–2.75 , number needed to treat=7 , 95 % CI 4–19 ) and resolve at least one risk ( odds ratio 1.60 , 95 % CI 1.15–2.22 , number needed to treat=9 , 95 % CI 6–29 ) . CONCLUSION : An integrated multiple risk factor intervention addressing psychosocial and behavioral risks delivered mainly during pregnancy can have beneficial effects in risk reduction postpartum . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00381823 LEVEL OF EVIDENCE : BACKGROUND Exclusive breastfeeding is recommended until age 6 months . We assessed the feasibility , effectiveness , and safety of an educational intervention to promote exclusive breastfeeding for this length of time in India . METHODS We developed the intervention through formative research , pair-matched eight communities on their baseline characteristics , and r and omised one of each pair to receive the intervention and the other to no specific intervention . We trained health and nutrition workers in the intervention communities to counsel mothers for exclusive breastfeeding at multiple opportunities . We enrolled 1115 infants born in the 9 months after training-552 in the intervention and 473 in the control communities . Feeding at age 3 months , and anthropometry and of diarrhoea prevalence at age 3 months and 6 months were assessed . All analyses were by intention to treat . FINDINGS We assessed 483 and 412 individuals at 3 months in the intervention and control groups , respectively , and 468 and 412 at 6 months . At 3 months , exclusive breastfeeding rates were 79 % ( 381 ) in the intervention and 48 % ( 197 ) in the control communities ( odds ratio 4.02 , 95 % CI 3.01 - 5.38 , p<0.0001 ) . The 7-day diarrhoea prevalence was lower in the intervention than in the control communities at 3 months ( 0.64 , 0.44 - 0.95 , p=0.028 ) and 6 months ( 0.85 , 0.72 - 0.99 , p=0.04 ) . The mean weights and lengths , and the proportion with weight-for-height or height-for-age Z scores of 2 or less , at age 3 months and 6 months did not differ much between groups . Intervention effect on exclusive breastfeeding , diarrhoeal morbidity , and anthropometry at age 6 months in the low-birthweight subgroup was similar to that for all births . INTERPRETATION Promotion of exclusive breastfeeding until age 6 months in a developing country through existing primary health-care services is feasible , reduces the risk of diarrhoea , and does not lead to growth faltering OBJECTIVE To evaluate a community-based intervention aim ed to improve women 's knowledge on alarm signs for preeclampsia-eclampsia , obstetrical hemorrhage , and puerperal sepsis , in Mayan pregnant women in the state of Yucatan , Mexico , in 2008 , using participatory methodology . MATERIAL AND METHODS Community-based r and omized controlled trial , with experimental ( n = 28 ) and control ( n = 28 ) groups . Participatory strategies with translators of Mayan language were used . Analysis of differences in differences was carried out to evaluate the effect of intervention . RESULTS The intervention increased knowledge on alarm signs for preeclampsia-eclampsia in 42.9 % ( p = 0.012 ) , obstetrical hemorrhage in 32.1 % ( p = 0.071 ) and puerperal sepsis in 25.0 % ( p = 0.659 ) . Control group increased 32.1 % ( p = 0.033 ) knowledge on alarm signs for puerperal sepsis . Overall effect of intervention was 33.3 % ( p = 0.007 ) . CONCLUSIONS The community-based intervention improved overall knowledge of women on alarm signs and specific knowledge on alarm signs for preeclampsia-eclampsia . It is necessary to spread this methodology , so that a greater number of women of the community will also be benefitted with the intervention BACKGROUND Adolescent pregnancy and parenting remain a major public concern because of their impact on maternal-child health and on the social and economic well-being of the nation . Federal welfare reform legislation has created an urgent need for community-based nursing intervention programs to improve health and social outcomes for disadvantaged adolescent mothers and to promote their self-sufficiency . OBJECTIVE To evaluate the effects of an early intervention program ( EIP ) that uses a public health nursing model on health and social outcomes of adolescent mothers and their children and on the quality of mother-child interaction . METHODS Pregnant adolescents referred to a county health department were r and omly assigned to an experimental ( EIP ) or control ( traditional public health nursing [ TPHN ] ) group . The sample included 121 adolescents from predominantly minority and impoverished background s who were followed from pregnancy through 6 weeks postpartum . Intense and comprehensive home visitation by public health nurses and preparation-for-motherhood classes were provided to adolescents in the EIP . Health outcomes were determined on the basis of medical record data . Other measures included maternal self-report on selected behaviors , nurse interviews , and the Nursing Child Assessment Teaching Scale ( NCATS ) . RESULTS Early findings indicate reduced premature birth and low-birth-weight ( LBW ) rates for young mothers receiving both forms of public health nursing care . No significant differences between groups were found for infant birth weight or type of delivery . Infants in the EIP had significantly fewer total days of birth-related hospitalization and rehospitalization than those in the TPHN group during the first 6 weeks of life ( chi2(1 ) = 6.41 ; p = 0.01 ) . Adolescents in the EIP demonstrated significantly more positive educational outcomes ( e.g. , lower school dropout rates ) than those in the TPHN group ( chi2(1 ) = 6.76 ; p < 0.009 ) . CONCLUSIONS The early findings of this study demonstrate that pregnant adolescents benefit from both traditional and more intense public health nursing care in terms of prenatal and perinatal outcomes . The EIP was associated with decreased infant morbidity during the first 6 weeks of life and decreased maternal school dropout . Long-term outcomes for the EIP are being evaluated The persistence of high perinatal and neonatal mortality rates in many developing countries make efforts to improve perinatal care in the home and at local health facilities important public health concerns . We describe a study which aims to evaluate a community-level participatory intervention in rural Nepal . The effectiveness of community-based action research interventions with mothers and other key members of the community in improving perinatal health outcomes is being examined using a cluster r and omized , controlled trial covering a population of 28,000 married women of reproductive age . The unit of r and omization was the village development committee ( VDC ) : 12 VDCs receive the intervention while 12 serve as controls . The key elements of the intervention are the activities of female facilitators , each of whom works in one VDC facilitating the activities of women 's groups in addressing problems in pregnancy , childbirth and the newborn period . Each group moves through a participatory planning cycle of assessment , sharing experiences , planning , action and re assessment , with the aim of improving essential maternal and newborn care . Outcomes assessed are neonatal and perinatal mortality rates , changes in patterns of home care , health care seeking and referral . The study also aims to generate programmatic information on the process of implementation in communities BACKGROUND Of the 3.7 million neonatal deaths and 3.3 million stillbirths each year , 98 % occur in developing countries . An evaluation of community-based interventions design ed to reduce the number of these deaths is needed . METHODS With the use of a train-the-trainer model , local instructors trained birth attendants from rural communities in six countries ( Argentina , Democratic Republic of Congo , Guatemala , India , Pakistan , and Zambia ) in the World Health Organization Essential Newborn Care course ( which focuses on routine neonatal care , resuscitation , thermoregulation , breast-feeding , " kangaroo " [ skin-to-skin ] care , care of the small baby , and common illnesses ) and ( except in Argentina ) in a modified version of the American Academy of Pediatrics Neonatal Resuscitation Program ( which teaches basic resuscitation in depth ) . The Essential Newborn Care intervention was assessed among 57,643 infants with the use of a before- and -after design . The Neonatal Resuscitation Program intervention was assessed as a cluster-r and omized , controlled trial involving 62,366 infants . The primary outcome was neonatal death in the first 7 days after birth . RESULTS The 7-day follow-up rate was 99.2 % . After birth attendants were trained in the Essential Newborn Care course , there was no significant reduction from baseline in the rate of neonatal death from all causes in the 7 days after birth ( relative risk with training , 0.99 ; 95 % confidence interval [ CI ] , 0.81 to 1.22 ) or in the rate of perinatal death ; there was a significant reduction in the rate of stillbirth ( relative risk with training , 0.69 ; 95 % CI , 0.54 to 0.88 ; P=0.003 ) . In clusters of births in which attendants had been r and omly assigned to receive training in the Neonatal Resuscitation Program , as compared with control clusters , there was no reduction in the rates of neonatal death in the 7 days after birth , stillbirth , or perinatal death . CONCLUSIONS The rate of neonatal death in the 7 days after birth did not decrease after the introduction of Essential Newborn Care training of community-based birth attendants , although the rate of stillbirths was reduced . Subsequent training in the Neonatal Resuscitation Program did not significantly reduce the mortality rates . ( Clinical Trials.gov number , NCT00136708 . OBJECTIVES To compare the clinical and cost-effectiveness of two different compression b and ages for the healing of venous leg ulcers . DESIGN A pragmatic , r and omised controlled trial with an economic evaluation . SETTING Community , district nurse-led services ; community leg ulcer clinics ; hospital leg ulcer clinics with community outreach . A range of urban and rural setting s in Engl and and Scotl and . PARTICIPANTS Patients with a venous leg ulcer of at least 1-week 's duration , at least 1 cm in length or width and an ankle : brachial pressure index of at least 0.8 . INTERVENTIONS The four-layer b and age ( 4LB ) ( which is multilayer elastic compression ) compared with the short-stretch b and age ( SSB ) ( multilayer , inelastic compression ) . MAIN OUTCOME MEASURES The primary end-point was complete healing of all the ulcers on the trial leg . Secondary outcomes were the proportion of patients healed at 12 and 24 weeks , rate of recurrence , costs of leg ulcer treatment and quality of life . RESULTS Between April 1999 and December 2000 the trial recruited 387 people aged from 23 to 97 years at trial entry . The majority of patients in this trial ( 82 % ; 316/387 ) had a reference ulcer of area < /=10 cm(2 ) . To test the difference over time of Kaplan -- Meier curves for the two b and age groups , the distribution of the cumulative times to healing of individuals in the two trial groups was compared using the log-rank test . The difference in the distribution of cumulative healing times between the individuals in the two groups was not statistically significant at the 5 % level . Adjusting for the effects of variables which may influence healing ( centre , baseline ulcer area , duration , episodes , ankle mobility , weight ) in a Cox proportional hazards model , a statistically significant treatment effect in favour of the 4LB was identified . At any point in time , the probability of healing for individuals in the SSB treatment arm is significantly lower than that for people treated with the 4LB . Our base case economic analysis showed that the 4LB is the dominant strategy , that is , it is associated with a greater health benefit and lower costs than the SSB , although the differences are not statistically significant . This result is explained largely by the greater number of community nurse visits required by participants in the short-stretch arm . CONCLUSIONS The 4LB , which is currently the UK st and ard compression b and age for people with venous leg ulcers , was more clinical ly and cost-effective than the SSB . The b and age costs were less important than the costs of treatment visits , and patients in SSBs required more treatment overall . Generally , this trial supports the use of the 4LB in preference to the SSB . Recommendations for future research include : exploration of the relationship between b and ager skill , application technique and ulcer healing ; the relative cost-effectiveness of community leg ulcer clinics ; and the study of nurse decision-making in venous ulcer management OBJECTIVES To determine whether increased postnatal support could influence maternal and child health outcomes . DESIGN This was a r and omised controlled trial comparing maternal and child health outcomes for women offered either of the support interventions with those for control women receiving st and ard services only . Outcome data were collected through question naires distributed 12 and 18 months postr and omisation . Process data were also collected . There was also an integral economic evaluation . SETTING AND PARTICIPANTS Women living in deprived enumeration districts in selected London boroughs were eligible for the trial if they gave birth between 1 January and 30 September 1999 . RESULTS The 731 participants were found to be well matched in terms of socio-economic characteristics and health and support variables ( 14 % of the participants were non-English speaking ) . Response rates at the two follow-up points were 90 % and 82 % . At both points there were no differences that could not be attributed to chance on the primary outcomes of maternal depression , child injury or maternal smoking . At the first follow-up , there was reduced use of general practitioners by support health visitor ( SHV ) children , but increased use of NHS health visitors and social workers by mothers . At the second follow-up , both community group support ( CGS ) and SHV mothers had less use of midwifery services ( fewer were pregnant ) , and SHV mothers were less worried about their child 's health and development . Uptake of the CGS intervention was low : 19 % , compared with 94 % for the SHV intervention . Satisfaction with the intervention among women in the SHV group was high . Based on the assumptions and conditions of the costing methods , the economic evaluation found no net economic cost or benefit of choosing either of the two interventions . CONCLUSIONS There was no evidence of impact on the primary outcomes of either intervention . The SHV intervention was popular with women , and was associated with improvement in some of the secondary outcomes . This suggests that greater emphasis on the social support role of health visitors could improve some measures of family well-being . Possible areas for future research include a systematic review of social support and its effect on health ; developing and testing other postnatal models of support that match more closely the age of the baby and the changing patterns of mothers ' needs ; evaluating other strategies for mobilising ' non-professional ' support ; developing and testing more culturally specific support interventions ; developing more culturally appropriate st and ardised measures of health outcomes ; providing longer term follow-up of social support interventions ; and exploring the role of social support on the delay in subsequent pregnancy A r and omised community intervention trial was undertaken in 12 subcentres in Karur health unit district , Tamil Nadu , to compare the efficacy of two antenatal care packages . A newly recommended ' high-risk ' strategy package and a uniform package recommended by the Tamil Nadu Government were each implemented in 4 r and omly selected subcentres by the study team , and the latter was also delivered by routine health services in the 4 remaining subcentres . Analyses were based on 294 pregnant women on the high-risk package ( HR ) , 242 on the Tamil Nadu Government ( TNG ) package and 335 women in the control series . The HR package reduced the differences between the high-risk women and the others in mean haemoglobin and the percentages with preventable neonatal morbidity and low birth weight , and consequently the overall outcome was better in the HR series than in the TNG series . Finally , the results with the TNG package were better when it was implemented by the study team than by the routine health services , in terms of preventable maternal morbidity and preventable perinatal morbidity , but there was no impact on birth weight BACKGROUND Much postpartum physical and psychological morbidity is not addressed by present care , which tends to focus on routine examinations . We undertook a cluster r and omised controlled trial to assess community postnatal care that has been re design ed to identify and manage individual needs . METHODS We r and omly allocated 36 general practice clusters from the West Midl and s health region of the UK to intervention ( n=17 ) or control ( 19 ) care . Midwives from the practice s recruited women and provided care . 1087 ( 53 % ) of 2064 women were in practice s r and omly assigned to the intervention group , with 977 ( 47 % ) women in practice s assigned to the control group . Care was led by midwives , with no routine contact with general practitioners , and was extended to 3 months . Midwives used symptom checklists and the Edinburgh postnatal depression scale ( EPDS ) to identify health needs and guidelines for the management of these needs . Primary outcomes at 4 months were obtained by postal question naire and included the women 's short form 36 physical ( PCS ) and mental ( MCS ) component summary scores and the EPDS . Secondary outcomes were women 's views about care . Multilevel analysis accounted for possible cluster effects . FINDINGS 801 ( 77 % ) of 1087 women in the intervention group and 702 ( 76 % ) of 977 controls responded at 4 months . Women 's mental health measures were significantly better in the intervention group ( MCS , 3.03 [ 95 % CI 1.53 - 4.52 ] ; EPDS -1.92 [ -2.55 to -1.29 ] ; EPDS 13 + odds ratio 0.57 [ 0.43 - 0.76 ] ) than in controls , but the physical health score did not differ . INTERPRETATION Re design of care so that it is midwife-led , flexible , and tailored to needs , could help to improve women 's mental health and reduce probable depression at 4 months ' postpartum BACKGROUND In 2009 , on the basis of promising evidence from trials in south Asia , WHO and UNICEF issued a joint statement about home visits as a strategy to improve newborn survival . In the Newhints trial , we aim ed to test this home-visits strategy in sub-Saharan Africa by assessing the effect on all-cause neonatal mortality rate ( NMR ) and essential newborn-care practice s. METHODS The Newhints cluster r and omised trial was undertaken in 98 zones in seven districts in the Brong Ahafo Region , Ghana . 49 zones were r and omly assigned to the Newhints intervention and 49 to the control intervention by use of restricted r and omisation with stratification to ensure comparability between interventions . Community-based surveillance volunteers ( CBSVs ) in Newhints zones were trained to identify pregnant women in their community and to make two home visits during pregnancy and three in the first week of life to promote essential newborn-care practice s , weigh and assess babies for danger signs , and refer as necessary . Primary outcomes were NMR and coverage of key essential newborn-care practice s. Analyses were by intention to treat . This study is registered with Clinical Trials.gov , number NCT00623337 . FINDINGS 16,168 ( 99 % ) of 16,329 deliveries between November , 2008 , and December , 2009 , were livebirths ; the status at 1 month was known for 15,619 ( 97 % ) livebirths . 482 neonatal deaths were recorded . Coverage data were available from 6029 women in Newhints zones ; of these 4358 ( 72 % ) reported having CBSV visits during pregnancy and 3815 ( 63 % ) reported having postnatal visits . This coverage increased substantially from June , 2009 , after the introduction of new implementation strategies and reached almost 90 % for pregnancy visits by the end of the trial and 75 % for postnatal visits . The Newhints intervention significantly increased coverage of key essential newborn-care behaviours , except for four or more antenatal-care visits ( 5975 [ 76 % ] of 7859 vs 5988 [ 74 % ] of 8121 , respectively ; relative risk 1·02 , 95 % CI 0·96 - 1·09 ; p=0·52 ) and baby delivered in a facility ( 5373 [ 68 % ] vs 5539 [ 68 % ] , respectively ; 0·97 , 0·81 - 1·14 ; p=0·69 ) . The largest increase was for care-seeking , with 102 ( 77 % ) of 132 sick babies in Newhints zones taken to a hospital or clinic compared with 77 ( 55 % ) of 139 in control zones ( 1·43 , 1·17 - 1·76 ; p=0·001 ) . Increases were also noted in bednet use during pregnancy ( 5398 [ 69 % ] of 7859 vs 5135 [ 63 % ] of 8121 , respectively ; 1·12 , 1·03 - 1·21 ; p=0·005 ) , money saved for delivery or emergency ( 5730 [ 86 % ] of 6681 vs 5525 [ 80 % ] of 6941 , respectively ; 1·09 , 1·05 - 1·12 ; p<0·0001 ) , transport arranged in advance for facility ( 2496 [ 37 % ] vs 2061 [ 30 % ] , respectively ; 1·30 , 1·12 - 1·49 ; p=0·0004 ) , birth assistant for home delivery washed h and s with soap ( 1853 [ 93 % ] of 1992 vs 1817 [ 87 % ] of 2091 , respectively ; 1·05 , 1·02 - 1·09 ; p=0·001 ) , initiation of breastfeeding in less than 1 h of birth ( 3743 [ 49 % ] of 7673 vs 3280 [ 41 % ] of 7921 , respectively ; 1·22 , 1·07 - 1·40 ; p=0·004 ) , skin to skin contact ( 3355 [ 44 % ] vs 1931 [ 24 % ] , respectively ; 2·30 , 1·85 - 2·87 ; p=0·0002 ) , first bath delayed for longer than 6 h ( 3131 [ 41 % ] vs 2269 [ 29 % ] , respectively ; 1·65 , 1·27 - 2·13 ; p<0·0001 ) , exclusive breastfeeding for 26 - 32 days ( 1217 [ 86 % ] of 1414 vs 1091 [ 80 % ] of 1371 ; 1·10 , 1·04 - 1·16 ; p=0·001 ) , and baby sleeping under bednet for 8 - 56 days ( 4548 [ 79 % ] of 5756 vs 4291 [ 73 % ] of 5846 ; 1·09 , 1·03 - 1·15 ; p=0·002 ) . There were 230 neonatal deaths in the Newhints zones compared with 252 in the control zones . The overall NMRs per 1000 livebirths were 29·8 and 31·9 , respectively ( 0·92 , 0·75 - 1·12 ; p=0·405 ) . INTERPRETATION The reduction in NMR with Newhints is consistent with the reductions achieved in three trials undertaken in programme setting s in south Asia . Because there is no suggestion of any heterogeneity ( p=0·850 ) between these trials and Newhints , the meta- analysis summary estimate of a reduction of 12 % ( 95 % CI 5 - 18 ) provides the best evidence for the likely effect of the home-visits strategy delivered within programmes in sub-Saharan Africa and in south Asia . Improvements in the quality of delivery and neonatal care in health facilities and development of innovative , effective strategies to increase coverage of home visits on the day of birth could lead to the achievement of more substantial reductions . FUNDING WHO , Bill & Melinda Gates Foundation , and UK Department for International Development BACKGROUND A study in Matlab , Bangladesh , has provided evidence favouring a community-based maternity-care delivery system . 3 years of this programme coincided with a significant reduction in direct obstetric mortality compared with the 3 years before the programme . We have examined whether the effects of the programme are sustained over time . METHODS Using data from the continuing demographic survelliance system and from special investigations into the rates and causes of maternal mortality during 1976 - 93 , we compared the trends in direct obstetric maternal mortality ratios in the Maternal and Child Health and Family Planning ( MCH-FP ) area ( which has received extensive services in health and family planning since 1977 ) with those in the comparison area ( with no such intensive health inputs ) . We divided the areas and time periods into discrete groups that best represented the effects of the introduction of the maternity-care programme . FINDINGS Direct obstetric mortality declined by 3 % per year ( rate ratio 0.97 per year [ 95 % CI 0.95 - 0.99 ] ) ; there was no difference between the MCH-FP and comparison areas ( 1.00 [ 0.96 - 1.05 ] ) . Direct obstetric mortality halved between 1976 - 86 and 1987 - 89 in the northern MCH-FP area , where the maternity-care programme was initiated in 1987 ( 0.50 [ 0.22 - 0.99 ] ) , but showed no change in the southern MCH-FP area , which had no such intervention at that time ( 1.07 [ 0.64 - 1.72 ] ) . After 1990 , when the programme was exp and ed throughout the MCH-FP area , the southern part showed a downward ( non-significant ) trend in direct obstetric mortality ( 0.68 [ 0.35 - 1.32 ] ) . However , direct obstetric mortality also declined between 1987 and 1989 in the southern comparison area ( 0.48 [ 0.26 - 0.83 ] ) in the absence of an intense maternity-care programme , and remained stable thereafter . In the northern comparison area , there was no such decline in direct obstetric mortality ( 0.78 [ 0.40 - 1.40 ] ) . INTERPRETATION Although the introduction of the maternity-care programme coincided with declining trends in direct obstetric mortality in the areas covered by the programme , a decline also occurred in one of the areas not receiving any such interventions . Caution is required in the interpretation of short-term trends in one indicator in studies design ed without r and om allocation of interventions into treatment and control groups OBJECTIVE To assess the effect on maternal health outcomes of a community-based behavior change management intervention for essential newborn care leading to a reduction in neonatal mortality . METHODS A cluster-r and omized controlled trial involving 1 control and 2 intervention arms was conducted in Shivgarh , India , between January 2004 and May 2005 . Risk-enhancing domiciliary newborn care behaviors , including those posing a concomitant risk to maternal health , were targeted through home visits and community meetings . Secondary outcomes included knowledge of maternal danger signs , self-reported complications , maternal care practice s , care-seeking from trained providers , and maternal mortality ratio ( MMR ) . The intervention arms were combined for analysis , which was done by intention to treat . RESULTS Significant improvements were observed in maternal health equity and outcomes including knowledge of danger signs , care practice s , self-reported complications , and timely care-seeking from trained providers . The difference in adjusted MMR was not significant ( relative risk 0.44 ; 95 % confidence interval , 0.14 - 1.43 ; P=0.11 ) owing to the inadequate sample size for this outcome , but may suggest a decline in MMR given improvements in other outcomes in the causal pathway to mortality . CONCLUSION Community-based strategies focused on prevention and care-seeking effectively complemented facility-based strategies toward improving maternal health , while synergizing with newborn care interventions BACKGROUND Progress towards MDG4 for child survival in South Africa requires effective prevention of mother-to-child transmission ( PMTCT ) of HIV including increasing exclusive breastfeeding , as well as a new focus on reducing neonatal deaths . This necessitates increased focus on the pregnancy and early post-natal periods , developing and scaling up appropriate models of community-based care , especially to reach the peri-urban poor . METHODS We used a r and omised controlled trial with 30 clusters ( 15 in each arm ) to evaluate an integrated , scalable package providing two pregnancy visits and five post-natal home visits delivered by community health workers in Umlazi , Durban , South Africa . Primary outcomes were exclusive and appropriate infant feeding at 12 weeks post-natally and HIV-free infant survival . RESULTS At 12 weeks of infant age , the intervention was effective in almost doubling the rate of exclusive breastfeeding ( risk ratio 1.92 ; 95 % CI : 1.59 - 2.33 ) and increasing infant weight and length-for-age z-scores ( weight difference 0.09 ; 95 % CI : 0.00 - 0.18 , length difference 0.11 ; 95 % CI : 0.03 - 0.19 ) . No difference was seen between study arms in HIV-free survival . Women in the intervention arm were also more likely to take their infant to the clinic within the first week of life ( risk ratio 1.10 ; 95 % CI : 1.04 - 1.18 ) . CONCLUSIONS The trial coincided with national scale up of ARVs for PMTCT , and this could have diluted the effect of the intervention on HIV-free survival . We have demonstrated that implementation of a pro-poor integrated PMTCT and maternal , neonatal and child health home visiting model is feasible and effective . This trial could inform national primary healthcare reengineering strategies in favour of home visits . The dose effect on exclusive breastfeeding is notable as improving exclusive breastfeeding has been resistant to change in other studies targeting urban poor families BACKGROUND Neonatal mortality accounts for a high proportion of deaths in children under the age of 5 years in Bangladesh . Therefore the project for advancing the health of newborns and mothers ( Projahnmo ) implemented a community-based intervention package through government and non-government organisation infrastructures to reduce neonatal mortality . METHODS In Sylhet district , 24 clusters ( with a population of about 20 000 each ) were r and omly assigned in equal numbers to one of two intervention arms or to the comparison arm . Because of the study design , masking was not feasible . All married women of reproductive age ( 15 - 49 years ) were eligible to participate . In the home-care arm , female community health workers ( one per 4000 population ) identified pregnant women , made two antenatal home visits to promote birth and newborn-care preparedness , made postnatal home visits to assess newborns on the first , third , and seventh days of birth , and referred or treated sick neonates . In the community-care arm , birth and newborn-care preparedness and careseeking from qualified providers were promoted solely through group sessions held by female and male community mobilisers . The primary outcome was reduction in neonatal mortality . Analysis was by intention to treat . The study is registered with Clinical Trials.gov , number 00198705 . FINDINGS The number of clusters per arm was eight . The number of participants was 36059 , 40159 , and 37598 in the home-care , community-care , and comparison arms , respectively , with 14 769 , 16 325 , and 15 350 livebirths , respectively . In the last 6 months of the 30-month intervention , neonatal mortality rates were 29.2 per 1000 , 45.2 per 1000 , and 43.5 per 1000 in the home-care , community-care , and comparison arms , respectively . Neonatal mortality was reduced in the home-care arm by 34 % ( adjusted relative risk 0.66 ; 95 % CI 0.47 - 0.93 ) during the last 6 months versus that in the comparison arm . No mortality reduction was noted in the community-care arm ( 0.95 ; 0.69 - 1.31 ) . INTERPRETATION A home-care strategy to promote an integrated package of preventive and curative newborn care is effective in reducing neonatal mortality in communities with a weak health system , low health-care use , and high neonatal mortality The purpose of this study was to evaluate the effects of a nursing intervention program on affective and behavioral dimensions of maternal role attainment . The sample comprised 20 primiparous adolescents , ages 12 - 19 years , from predominantly black and Hispanic background s. Adolescents were r and omly assigned to either an experimental or a control group . Participants in the experimental group received an intervention that included four 1 1/2 hour classes held at weekly intervals , selected maternal-fetal interactive activities , recording of fetal movements , and maintaining of maternal diaries . Five instruments were used in the study : Cranley 's Maternal-Fetal Attachment Scale ( MFAS ) ; the two Semantic Differentials , Myself as Mother and My Baby ; the Pharis Self-Confidence Scale ; and the Nursing Child Assessment Feeding Scale ( NCAFS ) . Adolescents receiving intervention demonstrated a significant increase in prenatal attachment ( MFAS scores ) but showed no differences in actual mothering behaviors ( NCAFS scores ) as compared with adolescents in the comparison group . Although significant correlations existed among the affective measures , they were not significantly related to the measures of mothering behaviors . These results suggest that the intervention program was primarily beneficial to adolescents ' achievement of the maternal role through enhancement of maternal-fetal attachment . The data also raise questions about theoretical assumptions concerning the relationship between affective and behavioral components of mothering Educational intervention programs in Florin , Greece , a mountainous rural area with a low ( 15 - 20 % ) attendance at prenatal clinics , were conducted to reduce perinatal and infant morbidity and mortality and to promote physical and psychomotor development . Prior community diagnostic surveys had identified low income , poor living conditions , and illiteracy as very closely linked with poor hygiene , poor nutrition , nonutilization of services , frequent infections and high perinatal and infant mortality . The objectives of the intervention were to assess the effects of health education on breast feeding practice s and use of available medical services . 300 pregnant women participants were r and omly identified by the clinic as the intervention group and 200 as controls . Both groups were similar with predominantly low socioeconomic status ( 69 - 73 % ) and peasant farmers . There were few basic housing amenities ( 13.1 with interventions and 12.7 for controls ) . 70 % of the women lived in extended families . The intervention involved home visits on nutrition , general hygiene , breast feeding , and newborn care . Visits were scheduled every 2 weeks in the 1st 2 months of pregnancy and every month until the infant was 12 months old . It was found that nutrition counseling was positively associated with maternal weight between interventions and controls ( 11.33 vs. 10.30 p.05 ) but not on low birth weight . Prematurity was reduced ( 3.7 % intervention vs. 8.3 % controls , p.04 ) . The perinatal mortality was 31 % for interventions vs. 41 % for controls , but there were a significantly higher number of fetal deaths ( 28 weeks ) for interventions . There was no discernible impact on breast feeding practice s except for dem and feeding ( 61 % interventions vs. 38 % controls ) perhaps because both groups considered breast milk the best . Overfeeding was affected by health counseling , but was reflected only after the 1st year ( 12.1 % control vs. 6.7 % intervention in the 90th percentile ) . The presence of anemia followed a similar pattern with intervention impact after the 1st year . There was no measurable impact in psychomotor development . Reported illness days had a significant lower mean 1 year for interventions . Illness reports checked against clinic visits showed underreporting for both groups . Colds , otitis , and gastroenteritis were the most common ailments . Both showed greater illness between 8 and 12 months with a slightly higher incidence of feverish episodes , gastroenteritis and otitis among controls . Hospitalizations were not significantly different . Both groups used the clinic for infant illness ; home visits depressed the use of free routine checkups for interventions from 0 to 4 months . 5 neonatal deaths occurred among controls and interventions . It was anticipated that mortality is also affected by linkages to the community and improvement in medical services . The results were mixed but the program was partly successful OBJECTIVE Early postpartum home visiting is universal in many Western countries . Studies from developing countries on the effects of home visits are rare . In Syria , where the postpartum period is rather ignored , this study aim ed to assess whether a community-based intervention of postnatal home visits has an effect on maternal postpartum morbidities ; infant morbidity ; uptake of postpartum care ; use of contraceptive methods ; and on selected neonatal health practice s. DESIGN A r and omized controlled trial was carried out in Damascus . Three groups of new mothers were r and omly allocated to receive either 4 postnatal home visits ( A ) , one visit ( B ) , or no visit ( C ) . SAMPLE A total of 876 women were allocated and followed up . INTERVENTION Registered midwives with special training made a one or a series of home visits providing information , educating , and supporting women . RESULTS A significantly higher proportion of mothers in Groups A and B reported exclusively breastfeeding their infants ( 28.5 % and 30 % , respectively ) as compared with Group C ( 20 % ) , who received no visits . There were no reported differences between groups in other outcomes . CONCLUSIONS While postpartum home visits significantly increased exclusive breastfeeding , other outcomes did not change . Further studies framed in a nonbiomedical context are needed . Other innovative approaches to improve postnatal care in Syria are needed BACKGROUND The Community Mothers Programme aims at using experienced volunteer mothers in disadvantaged areas to give support to first-time parents in rearing their children up to 1 year of age . The programme was evaluated by r and omized controlled trial in 1990 . METHODS Seven years later , trial participants were interviewed about child health , nutrition , cognitive stimulation , parenting skills , and maternal self-esteem . The aim of this study was to see whether the demonstrated benefits at 1 year of age of this programme could be sustained at age 8 . RESULTS One-third of the original group ( 38 intervention , 38 control ) , were contacted and interviewed . The risk for having an accident requiring a hospital visit was lower in the intervention group : relative risk ( RR ) 0.59 , 95 per cent confidence interval ( CI ) 0.31 - 1.11 . Intervention children were more likely to visit the library weekly : RR 1.58 , 95 per cent CI 1.10 - 2.26 . Intervention mothers were more likely to check homework every night : RR 1.23 , 95 per cent CI 1.05 - 1.43 ( p=0.006 ) ; and to disagree with the statement ' children should be smacked for persistently bad behaviour ' : RR 2.11 , 95 per cent CI 1.10 - 4.06 . They were more likely to disagree with the statement ' I do not have much to be proud of ' : RR 1.24 , 95 per cent CI 1.04 - 1.40 ; and to make a positive statement about motherhood than controls : RR 1.53 , 95 per cent CI 1.06 - 2.20 . Subsequent children of intervention mothers were more likely to have completed Haemophilus influenzae b : RR 1.26 , 95 per cent CI 1.06 - 1.51 ; and polio immunization : RR 1.19 , 95 per cent CI 1.02 - 1.40 . CONCLUSIONS The Community Mothers programme had sustained beneficial effects on parenting skills and maternal self-esteem 7 years later with benefit extending to subsequent children This study was design ed to assess the utility and impact on perinatal mortality of a model traditional birth attendant ( TBA ) training program in rural Mozambique by comparing birth attendance and outcomes in similar communities with and without trained TBAs . Birth attendants and pregnancy outcomes were compared in 1 ) communities with good access to trained TBAs , 2 ) r and omly selected , comparable communities with no access to trained TBAs , and 3 ) communities with good access to functioning maternities . Information was collected by interviews with women in r and omly selected households . A total of 4,169 women were interviewed who reported on 3,616 completed pregnancies , which result ed in a birth or fetal death . Among women with good access to trained TBAs , 33 % reported giving birth attended by a trained TBA , 43 % reported giving birth at a health facility , and 24 % reported giving birth attended by an untrained person . Among women without access to trained TBAs , 58 % reported giving birth at health facilities , and 42 % reported attendance by untrained persons . Among women with access to functioning maternity centers , 77 % reported giving birth at a health facility and 22 % said their birth was attended by an untrained person . There was no significant difference in perinatal or infant mortality among the groups . This study demonstrated a preference for health facility deliveries among rural Mozambican women with good access to trained TBAs . It also failed to demonstrate a reduction in perinatal or infant mortality associated with TBA training . Women said they preferred to deliver in health facilities because conditions were considered better and interventions could be performed if needed . The preference for health facility birth over home birth with a TBA may have been related to difficulties with TBA neighbors and their families or fear of potential witchcraft . Efforts to promote TBA training should be balanced with support for birthing services based in health facilities BACKGROUND A high rate of maternal depression and associated disturbance in the mother-infant relationship has been found in an indigent peri-urban South African community , Khayelitsha . The question arises whether a community-based intervention could be beneficial . AIMS To train community workers to deliver an intervention to mothers and infants in Khayelitsha , and to compare mothers and infants receiving this intervention with a sample receiving no such intervention . METHOD Four Khayelitsha women were trained in a mother-infant intervention , which they delivered to 32 women recruited in late pregnancy . At 6 months post-partum , maternal mood , the mother-infant relationship and infant growth were assessed . The findings were compared with a matched group of 32 mothers and infants . RESULTS There was no reliable impact of the intervention on maternal mood . However , compared with the comparison sample , the quality of mother-infant engagement was significantly more positive for those who had received the intervention . CONCLUSIONS The pilot study produced preliminary evidence of a benefit of a community-based mother-infant intervention delivered by trained , but otherwise unqualified , community workers , sufficient to warrant a formal controlled evaluation of this treatment Objective : To evaluate the effect of World Health Organization Essential Newborn Care course and the American Academy of Pediatrics Neonatal Resuscitation Program training on perinatal mortality in rural India . Methods : This study was part of a multi-country prospect i ve , community-based cluster r and omized controlled trial . Birth , 7-day and 28-day neonatal outcomes for all women with pregnancies greater than 28 weeks in the 26 study communities in Karnataka , India were included . Mortality rates pre- and post-Essential Newborn Care training were collected prospect ively and then communities r and omized to either receive neonatal resuscitation or refresher newborn care training in the control clusters . Results : Consent was obtained on 99 % of the 25,096 births . Perinatal mortality for infants ≥500 g decreased from 52 to 36/1000 after newborn care training ( RR 0.7 ; 95 % CI 0.5 , 0.9 ) ; stillbirth decreased from 23 to 14/1000 ( RR 0.62 ; 95 % CI 0.46 , 0.83 ) and early neonatal mortality decreased from 29 to 22/1000 ( RR 0.74 ; 95 % CI 0.53 , 1.03 ) . Mortality was not reduced further with resuscitation training . Conclusions : Using a pre – post design , World Health Organization Essential Newborn Care community birth attendant training result ed in a significant reduction in perinatal mortality . In low-re source setting s , the newborn care training package appears to be an effective intervention to decrease perinatal mortality |
12,222 | 25,866,139 | Evidence was unclear regarding the effects of fluid warming on bleeding .
Warmed intravenous fluids also further reduced the risk of shivering compared with room temperature intravenous fluidsInvestigators reported no statistically significant differences in core body temperature or shivering between individuals given warmed and room temperature irrigation fluids .
AUTHORS ' CONCLUSIONS Warm intravenous fluids appear to keep patients warmer during surgery than room temperature fluids .
It is unclear whether the actual differences in temperature are clinical ly meaningful , or if other benefits or harms are associated with the use of warmed fluids .
It is also unclear if using fluid warming in addition to other warming methods confers any benefit , as a ceiling effect is likely when multiple methods of warming are used | BACKGROUND Inadvertent perioperative hypothermia ( a drop in core temperature to below 36 ° C ) occurs because of interference with normal temperature regulation by anaesthetic drugs , exposure of skin for prolonged periods and receipt of large volumes of intravenous and irrigation fluids .
If the temperature of these fluids is below core body temperature , they can cause significant heat loss .
Warming intravenous and irrigation fluids to core body temperature or above might prevent some of this heat loss and subsequent hypothermia .
OBJECTIVES To estimate the effectiveness of preoperative or intraoperative warming , or both , of intravenous and irrigation fluids in preventing perioperative hypothermia and its complications during surgery in adults . | Background Keeping abdominal surgery patients warm is common and warming methods are needed in power outages during natural disasters . We aim ed to evaluate the efficacy of low-cost , low-power warming methods for maintaining normothermia in abdominal surgery patients . Methods Patients ( n = 160 ) scheduled for elective abdominal surgery were included in this prospect i ve clinical study . Five warming methods were applied : heated blood transfusion/fluid infusion vs. unheated ; wrapping patients vs. not wrapping ; applying moist dressings , heated or not ; surgical field rinse heated or not ; and applying heating blankets or not . Patients ’ nasopharyngeal and rectal temperatures were recorded to evaluate warming efficacy . Significant differences were found in mean temperatures of warmed patients compared to those not warmed . Results When we compared temperatures of abdominal surgery patient groups receiving three specific warming methods with temperatures of control groups not receiving these methods , significant differences were revealed in temperatures maintained during the surgeries between the warmed groups and controls . Discussion The value of maintaining normothermia in patients undergoing abdominal surgery under general anesthesia is accepted . Three effective economical and practically applicable warming methods are combined body wrapping and heating blanket ; combined body wrapping , heated moist dressings , and heating blanket ; combined body wrapping , heated moist dressings , and warmed surgical rinse fluid , with or without heating blanket . These methods are practically applicable when low-cost method is indeed needed BACKGROUND Mild perioperative hypothermia , which is common during major surgery , may promote surgical-wound infection by triggering thermoregulatory vasoconstriction , which decreases subcutaneous oxygen tension . Reduced levels of oxygen in tissue impair oxidative killing by neutrophils and decrease the strength of the healing wound by reducing the deposition of collagen . Hypothermia also directly impairs immune function . We tested the hypothesis that hypothermia both increases susceptibility to surgical-wound infection and lengthens hospitalization . METHODS Two hundred patients undergoing colorectal surgery were r and omly assigned to routine intraoperative thermal care ( the hypothermia group ) or additional warming ( the normothermia group ) . The patient 's anesthetic care was st and ardized , and they were all given cefam and ole and metronidazole . In a double-blind protocol , their wounds were evaluated daily until discharge from the hospital and in the clinic after two weeks ; wounds containing culture-positive pus were considered infected . The patients ' surgeons remained unaware of the patients ' group assignments . RESULTS The mean ( + /- SD ) final intraoperative core temperature was 34.7 + /- 0.6 degrees C in the hypothermia group and 36.6 + /- 0.5 degrees C in the normothermia group ( P < 0.001 ) Surgical-wound infections were found in 18 of 96 patients assigned to hypothermia ( 19 percent ) but in only 6 of 104 patients assigned to normothermia ( 6 percent , P = 0.009 ) . The sutures were removed one day later in the patients assigned to hypothermia than in those assigned to normothermia ( P = 0.002 ) , and the duration of hospitalization was prolonged by 2.6 days ( approximately 20 percent ) in hypothermia group ( P = 0.01 ) . CONCLUSIONS Hypothermia itself may delay healing and predispose patients to wound infections . Maintaining normothermia intraoperatively is likely to decrease the incidence of infectious complications in patients undergoing colorectal resection and to shorten their hospitalizations In this prospect i ve trial a study was made of the effect of warm irrigation on blood loss during transurethral prostatectomy ( TURP ) . A control group of 21 patients in whom irrigating fluid at operating room temperature ( mean 21.5 degrees C ) had been used was compared with a statistically comparable group of 19 patients in whom warm irrigating fluid ( mean 33.1 degrees C ) had been used . Blood loss in ml , in ml/g of tissue resected and in ml/min of resection time was not increased by the use of warm rather than room temperature irrigation . It was found that warm irrigation decreased heat loss and shivering in the patient during TURP and led to improved comfort both for patient and operator . The method of heating the irrigation bags was safe and economical Changes in mean body temperature and muscle protein metabolism were studied in elderly patients undergoing large bowel surgery . Two groups were studied : in one , efforts were made to maintain the patients normothermic during and after surgery by warming the fresh gases , the i.v . fluids , by placing warmed cotton padding around the exposed parts of the body and by covering the patients with a metallized plastic sheet in the recovery period . The other group received routine management . Otherwise the anaesthetic technique was comparable . The excretion of the amino acid 3-methylhistidine ( 3-MeH ) , an indicator of muscle protein breakdown , and urea nitrogen loss were measured in the urine collected the day before , and on the 2nd and 4th postoperative days . Prevention of heat loss during and after surgery caused a significant decrease in muscle protein degradation and nitrogen loss OBJECTIVE to verify the effectiveness of warmed intravenous infusion for hypothermia prevention in patients during the intraoperative period . METHOD experimental , comparative , field , prospect i ve and quantitative study undertaken at a federal public hospital . The sample was composed of 60 adults , included based on the criteria of axillary temperature between 36ºC and 37.1ºC and surgical abdominal access , divided into control and experimental groups , using the systematic probability sampling technique . RESULTS 22 patients ( 73.4 % ) from both groups left the operating room with hypothermia , that is , with temperatures below 36ºC ( p=1.0000 ) . The operating room temperature when patients arrived and patients ' temperature when they arrived at the operating room were statistically significant to affect the occurrence of hypothermia . CONCLUSION the planning and implementation of nursing interventions carried out by baccalaureate nurses are essential for preventing hypothermia and maintaining perioperative normothermia Mild intraoperative hypothermia is common . We therefore studied the effects of mild hypothermia on propofol pharmacokinetics , hepatic blood flow , and atracurium duration of action in healthy volunteers . Six young volunteers were studied on two r and omly assigned days , at either 34 degrees C or 37 degrees C. Anesthesia was induced with thiopental , 3 mg/kg , and maintained with 70 % N2 O and 0.6 % isoflurane . Core hypothermia was induced by conductive and convective cooling . On the other study day , normothermia was maintained by a Bair Hugger Registered Trademark ( Augustine Medical , Inc. , Eden Prairie , MN ) forced-air warmer . Propofol , 1 mg/kg lean body mass ( LBM ) , then was given , followed by a 4-h infusion at 5 mg centered dot kg-1 centered dot h-1 . After 2 h , atracurium 0.5 mg/kg was administered as an intravenous bolus . Indocyanine green was administered for estimation of hepatic blood flow . Arterial blood was assayed for propofol and indocyanine green concentration . Pharmacokinetic analysis was performed using NONMEM . Results are reported as means + /- SEM . Propofol blood concentrations averaged approximate equals 28 % more at 34 degrees C than at 37 degrees C ( P < 0.05 ) . Hepatic blood flow decreased 23 % + /- 11 % in normothermic volunteers during the propofol infusion , and 33 % + /- 11 % in hypothermic volunteers ( P = not significant ) . A three-compartment mamillary model fitted the data best . Inclusion of hepatic blood flow change from the prepropofol baseline as a covariate for total body clearance significantly improved the fit . The intercompartmental clearances were decreased in the presence of hypothermia . Core hypothermia prolonged the time to recovery of the first twitch in the train-of-four to 10 % of its control value ( T1 = 10 % ) after atracurium administration by approximate equals 60 % ( P < 0.05 ) , from 44 + /- 4 min to 68 + /- 7 min . In contrast , T1 = 25%-75 % remained unchanged . We conclude that 3 degrees C of core hypothermia increased propofol blood concentrations and prolonged atracurium duration of action . Hepatic blood flow was decreased during propofol administration , and this change was a significant predictor of propofol clearance , indicating that the effect of propofol on hepatic blood flow impairs the clearance of propofol itself . ( Anesth Analg 1995;80:1007 - 14 Twenty-four unpremedicated patients of ASA class II or III undergoing TURP were given esia with 10 mg of tetracaine at level L3 - 4 or L4 - 5 . These patients were r and omly given " warm " or " ambient temperature " irrigating fluids . Those with irrigating fluids of temperature between 25.5 degrees C and 33 degrees C were arranged as Group 1 and those of temperature between 21.5 and 23 degrees C as Group 2 . The results failed to show that the incidence of shivering could be decreased by the use of warm irrigating fluids Background Postoperative hypothermia and shivering is a frequent event in patients during cesarean section under spinal anesthesia . We assessed the effect of preoperative warming during cesarean delivery under spinal anesthesia for prevention of hypothermia and shivering . Methods Forty five patients undergoing elective cesarean section were r and omly assigned to three groups . Group F received warmed intravenous fluid ( 40 ℃ ) . Group A patients were actively warmed by forced air-warming . Group C was the control group . Forced air-warming and warmed fluid was maintained for the 15 min preceding spinal anesthesia . Core temperature ( tympanic membrane ) and the skin temperature of arm and thigh were measured and shivering was grade d simultaneously . Results The core temperature at 45 min decreased less in Groups F and A than Group C ( -0.5 ℃ ± 0.3 ℃ vs -0.6 ℃ ± 0.4 ℃ vs -0.9 ℃ ± 0.4 ℃ , respectively ; P = 0.004 ) . The arm temperature at 15 min and 30 min exhibited a greater increase in Group A than Group F and Group C ( P = 0.001 and P = 0.012 , respectively ) . Leg temperature increased similarly among the three groups . The incidence of shivering was significantly less in Group A and Group F than Group C ( 20 % , 13.3 % , and 53.3 % , respectively ; P = 0.035 ) . Conclusions Preoperative forced air-warming and warmed fluid prevents hypothermia and shivering in patients undergoing elective cesarean delivery with spinal anesthesia OBJECTIVES To investigate the effect using irrigation fluid at body temperature ( isothermic ) on patients ' ( core ) temperature during a transurethral resection of the prostate ( TURP ) and on the amount of peri-operative blood loss , the resection time and the subjective assessment of comfort by the patients . PATIENT AND METHODS In a r and omized study , patients undergoing TURP under spinal anaesthesia were divided into those receiving either isothermic irrigation fluid ( Group 1.28 patients ) or fluid at room temperature ( Group 2.31 patients ) . In Group 1 , a fluid heater maintained the irrigation fluid at body temperature until it reached the bladder . The body temperature of the patients was recorded rectally and orally during and after TURP and the peri-operative blood loss was also measured . The patients were interviewed on the first day after TURP to determine their assessment of comfort during the procedure . RESULTS The decrease in body temperature was 0.74 degree C in Group 1 and 1.71 degrees C in Group 2 , which was significantly different ( P < 0.001 ) . There was no significant difference in blood loss or resection-time . In Group 1 , only four ( 14 % ) of the patients were aware that their body was cooler , compared to 15 ( 50 % ) in Group 2 ( P = 0.038 ) . CONCLUSION Isothermic irrigation during TURP prevents excessive cooling and reduces the level of hypothermia . The reported increased mortality after TURP is probably related to peri-operative cardiac stress , an important factor which could be caused by the rapid decrease in body temperature which accompanies normal irrigation . Because the heating equipment presently available does not interfere with TURP , there are strong arguments for performing every TURP with irrigation fluid at body temperature Purpose To determine the relative efficacy of heat conservation and convective warming in maintaining penoperative normothermia . ( central temperature ≥36 ° C ) . Methods Thirty-seven patients undergoing elective gynaecological , orthopaedic , or general surgery scheduled to last two hours were prospect jvely studied . Patients were r and omized to one of two groups . Group I patients received heat conservation with reflective blankets ( Thermadrape ™ , Vital Signs , Inc. , Totowa , NJ ) applied preoperatively and warmed iv fluids ( Hotline ™ SIMS Level I Technologies , Inc , Rockl and , MA ) . Group 2 patients received convective warming ( BairHugger , Augustine Medical , Inc. , Eden Prairie , MN ) after induction of anaesthesia and iv fluids at room temperature . All patients received general anaesthesia with isoflurane . Tympanic membrane and forearm-fingertip skin temperature gradients were measured penoperatively at 15 min intervals . Results Central temperature decreased after induction to a minimum level of 35.9 ± 0.1 ° C in group I and 36.0 ± 0.1 ° C in group 2 and then increased towards pre-induction values in group 2 , and were higher ( P < 0.05 ) than in group 1 : 95 % group 2 patients had central temperature ≥ 36.0 ° C at the end of surgery ( vs 69 % of group l . P < 0.05 ) . During the first 30 mm in PACU , central temperatures were higher in group 1 than in group 2 ( 36.8 ± 0.1 ° C vs 36.2 ± 0.2 ° C . P < 0.05 ) . After 60 mm , central temperatures were similar ( 36.8 ° C ) . The incidence of shivering and degree of penpheral cutaneous vasoconstnction were also similar . Conclusion Patients receiving convective warming were more likely to leave the operating room normothermic . and had higher central temperatures dunng the first 30 mm in the recovery room . The intergroup temperature differences were small , and by 60 min , had disappeared . RésuméObjectifDéterminer l’efficacité relative de la conservation de la chaleur et du réchauffement par convection pour le maintien de la normothermie pénopératoire ( température central e > 36 ° C).MéthodesTrente-sept patient(e)s soumis(es ) à une chirurgie gynécologique , orthopédique ou viscérale élective et programmée pour une durée approximative de deux heures ou plus ont participé à cette étude . Les patients ont été répartis aléatoirement entre deux groupes . Les patients du groupe I ont été réchauffées par réflexion avec des couvertures appropriées ( Thermadrape ™ , Vital Signs Inc. , Totowa , NJ ) et des perfusion réchauffés en préopératoire ( Hotline ™ SIMS Level I Technologies Inc. Rockl and , MA ) . Le réchauffeur par convesión ( BairHugger , Augustine Medical Inc. Eden Piaine . MN ) a été appliqué après l’induction de l’anesthésie au groupe 2 et des liquides iv maintenus à la température de la pièce ont été perfusés . Tous les patients ont reçu une anesthésie générale à l’isoflurane . Les gradients de température tympanique et de la peau du bout des doigts et de l’avant-bras ont été mesures aux 15 min pendant l’intervention . RésultatsLa température central e a diminué après l’induction à un niveau minimum de 35.9 ± 0.1 ° C dans le groupe I et de 36 ± 0,1 ° C dans le groupe 2 et a par la suite augmenté vers les valeurs préinduction dans le groupe 2 et de façon plus marquée que dans le groupe 1 : 95 % des patients du groupe 2 avaient des températures central es ≥ 36 ° C à la fin de la chirurgie ( vs 69 % du groupe 1.P < 0,05 ) . Pendant les premières 30 min du séjour en salle de réveil , les températures central es étaient plus élevées dans le groupe I que dans le groupe 2 ( 36.8 ± 0.1Cvs 36.2± 0.2C , P < 0.05 ) . Après 60 min , les températures central es étaient identiques ( 36,8 ° C ) . Lincidence des frissons et le degré de vasoconstriction étaient aussi les mêmes . Conclusion Les patients réchauffés par convexion avaient pulus de chance de quitter la salle d’opération en nor mothemnie et avaient des températures central es plus élevées pendant les premières 30 min de leur sejouren salle de réveil . Les différences entre les groupes étaient faibles et sont disparues après 60 min Background Transurethral resection of the prostate gl and with irrigation fluid at room temperature leads to perioperative hypothermia which could give rise to adverse cardiovascular events in the perioperative period . The use of isothermic irrigation fluid reduces but does not eliminate this risk . Routine use of warm intravenous fluids along with isothermic irrigation had not been documented . This study set out to investigate the effect of the use of warm intravenous fluid together with isothermic irrigation fluid on the body temperature in patients undergoing transurethral resection of the prostate gl and . Methods One hundred and twenty consented patients with obstructing benign prostatic hyperplasia were r and omly assigned to one of 3 groups . Group 1 received irrigation and intravenous fluids at room temperature , group 2 received warmed irrigation fluid at 38 ° C along with intravenous fluid at room temperature while group 3 patients received warmed irrigation fluid and warmed intravenous fluids at 38 ° C . Their perioperative body temperature changes were monitored , analyzed and compared . Results The mean decrease in body temperature at the end of the procedure was significantly greater in group 1 ( 0.98 ± 0.56 ° C ) than in group 2 ( 0.42 ± .21 ° C ) ( p < 0.001 ) . Significantly more patients in group 1 also experienced shivering . However , in group 3 , there was no significant change in the mean body temperature ( p > 0.05 ) and none of them felt cold or shivered . Conclusion It is concluded that the use of isothermic irrigation fluid together with warm intravenous fluids during TURP prevents the occurrence of perioperative hypothermia . Trial registration BACKGROUND We assessed the effect of warming intravenous fluids during elective caesarean section under combined spinal-epidural anaesthesia in a blinded , r and omised controlled trial . METHOD Seventy-five women having elective caesarean section were r and omly assigned to receive all intravenous fluids at room temperature , or heated in a cabinet set at 45 degrees C or via a Hotline fluid warmer ( Smiths Medical International Ltd , Watford , Herts , UK ) . After 10 mL/kg crystalloid preload , combined spinal-epidural anaesthesia was performed . Core and ambient temperatures , thermal comfort and shivering were measured every 15 min thereafter . The primary outcome was the temperature at 60 min . RESULTS Temperature decreased in all groups . Although the temperature decrease at 60 min was similar in the heated cabinet and Hotline groups , the room temperature group exhibited a greater decrease [ difference 0.4 degrees C ( 95 % CI 0.2 - 0.6 degrees C ) ; P=0.015 ] . More women felt cold in the room temperature group ( 8 : 32 % ) than in the heated cabinet set ( 3 : 12 % ) and Hotline ( 1 : 4 % ) groups ( P=0.02 ) , but the incidence of shivering was similar : 11 ( 44 % ) , 9 ( 36 % ) and 7 ( 28 % ) respectively . Apgar scores and neonatal cord gases were similar . CONCLUSION Warming intravenous fluids mitigates the decrease in maternal temperature during elective caesarean section under combined spinal-epidural anaesthesia and improves thermal comfort , but does not affect shivering . Intravenous fluids should be warmed routinely in elective caesarean section , especially for cases of expected long duration , but the use of pre-warmed fluids is as efficient and cheaper than using a Hotline fluid warmer OBJECTIVE To investigate the influence of using fluid warming and forced-air warming system on patient core temperature , blood loss , blood transfusion , extubation time , and postoperative shivering . METHODS Forty ASA ( American Society of Anesthesiologists ' Physical Status ) I-II patients , aged 21 - 69 years , scheduled for elective abdominal surgery under general anesthesia , were enrolled in the study . The patients were premedicated with intramuscular dolantin 50 mg and atropine 0.5 mg . Anesthesia was induced with midazolam 1 mg , fentanyl 50 - 100 microg and propofol 1.5 - 2.0 mg/kg . Tracheal intubation was facilitated with vecuronium 1 mg and succinylcholine 1.5 - 2.0 mg/kg . The patients were mechanically ventilated and anesthesia was maintained with isoflurane 1.5 - 2.0 % , 50 % N2O in oxygen and intermittent iv boluses of fentanyl ( total dose 5 - 6 microg/kg ) . Vecuronium was used for muscle relaxation during maintenance of anesthesia . The patients were r and omly divided into 2 groups : control group ( n = 20 ) and warming group ( n = 20 ) . In both groups , the patients were covered with surgery blanket . In the warming group , patients were additionally warmed with fluid warming device and forced-air warming system during the operation . The core temperature was recorded every 20 minutes during the operation , as well as the blood loss , blood transfusion , extubation time and postoperative shivering . RESULTS The core temperature at the end of the surgery was ( 36.4 + /- 0.4 ) degrees C in the warming group and ( 35.3 + /- 0.5 ) degrees C in the control group . The difference was statistically significant ( t = 7.547 , P < 0.001 ) . There was no significant difference of blood loss and blood transfusion between two groups . The extubation time was significantly shorter in the warming group [ ( 18 + /- 6 ) vs ( 26 + /- 10 ) min , t = -3.364 , P = 0.002 ] . 6 patients shivered postoperatively in the control group and none in the warming group ( chi2 = 7.059 , P = 0.008 ) . CONCLUSION Fluid warming system and forced-air warming system can effectively maintain normothermia during the surgery and then help to reduce the extubation time and postoperative shivering Purpose We investigated , first , the safety of use and stability of a plasma substitute — hydroxyethyl starch (HES)—kept in a warming cabinet for a long period , and then the effect on body core temperature of the prewarmed HES in patients during urological surgery . Methods In the first part of the study , HES colloid solutions ( 500 ml per pack ; Hesp and er ) were kept in a warming cabinet ( 40 ° C ) for 3 months and were tested for biological and chemical safety and stability . In the second part of the study , 1000 ml of HES at room temperature ( control group ; n = 10 ) or kept in a warming cabinet for a few days ( warmed group ; n = 10 ) was infused via a central venous catheter for 30 min in patients undergoing urological surgery under general anesthesia with lumbar epidural anesthesia . Esophageal temperature was monitored as the core temperature . HES fluid temperatures in the pack and at the end of a 1-m intravenous tube connected to the central venous catheter were also measured . Results The test of HES products warmed for 3 months passed all inspections performed during the study period . In the warmed group , the pack and intravenous tube temperatures of HES were still high at 15 min after infusion ( 37.1 ° ± 1.5 ° C [ mean ± SD ] and 34.8 ° ± 2.2 ° C , respectively ) . Core temperature in the warmed group decreased significantly , by 0.34 ° ± 0.06 ° C , but was significantly higher than that in the control group ( by 0.84 ° ± 0.13 ° C ) after 30 min of the infusion . Conclusions The use of HES products kept in a warming cabinet prior to surgery can maintain warm body temperature , easily , safely , and effectively The use of room temperature solutions for body cavity irrigation during surgical procedures can lead to the development of perioperative hypothermia . Hypothermia during this period causes patient discomfort , increases oxygen consumption , interferes with the clotting cascade , and increases the length of hospital stay . Perioperative hypothermia in anesthetized patients also contributes to extended sedation , delayed emergence , and prolonged recovery from neuromuscular blockade . Twenty-four adult American Society of Anesthesiologists ( ASA ) class I and II patients were r and omly assigned to receive warmed arthroscopic irrigation solution or room-temperature irrigation solution in this r and omized , prospect i ve study . Tympanic temperatures were monitored every 15 minutes throughout the surgical and postanesthesia recovery periods . P < .05 was considered significant . Statistical comparison of the mean percent temperature decrease from preoperative baseline between the 2 groups did not support the hypothesis that patients receiving warmed irrigation solution would maintain a higher core body temperature than those receiving room temperature solution STUDY OBJECTIVE To compare the fluid warming capabilities of the Hotline and Flotem IIe devices in surgical patients , and whether warming intravenous ( i.v . ) fluids with the Hotline device result ed in less hypothermia and less need for other warming methods compared with the Flotem IIe device . STUDY DESIGN Part 1 . Prospect i ve , nonr and omized . Part 2 . Prospect i ve , r and omized . SETTING Teaching hospital , tertiary care center . PATIENTS Part 1 . 24 adult patients undergoing elective surgery . Part 2 . 49 adult patients scheduled for major elective orthopedic or gynecologic surgery of greater than 2 hours ' duration with general anesthesia . INTERVENTIONS Part 1 . Insertion of sterile in-line thermistors along the path of fluids delivered using the Hotline or Flotem device . Part 2 . Patients were r and omly assigned to receive i.v . fluids via the Hotline ( n = 21 ) or Flotem IIe ( n = 18 ) warmers . Intervention for core hypothermia [ lower esophageal temperature ( Teso ) less than 35.5 degrees C ] , was with forced air warming . Intervention for postoperative shivering was with meperidine by a nurse who was blinded to the treatment group . MEASUREMENTS Part 1 . Temperature of infused fluids before and after the warmer ( T in and T out ) and before the fluid entered the patient after insertion of a st and ard 84 cm extension set having a stopcock for injection of medications ( T distal ) . Part 2 . Tympanic ( Ttym ) was recorded before induction of anesthesia ( baseline ) and at 15-minute intervals after induction . Teso was recorded at 15-minute intervals after induction . The maximum intraoperative Ttym decline from baseline ( delta Ttym max ) was calculated . MAIN RESULTS Part 1 . Flow rates were between 1 and 33 ml/min . T out and T distal ( mean + /- SEM ) of fluids infused through the Hotline device were warmer compared with those infused via the Flotem IIe device ( Hotline T out : 35.7 + /- 0.1 degrees C and Hotline T distal : 33.4 + /- 0.2 degrees C vs. Flotem IIe T out : 28.9 + /- 0.2 degrees C and Flotem IIe T distal : 28.3 + /- 0.2 degrees C ; p < 0.001 between warmers ) . Part 2 . Maximal decrease in Ttym from preoperative baseline ( before intervention ) was greater in the Flotem IIe compared with the Hotline group ( delta Ttym max = -1.4 + /- 0.1 vs. -0.9 + /- 0.1 degree C , p = 0.01 ) . Five patients in the Flotem IIe group required forced air warming for treatment of hypothermia versus none in the Hotline group ( p < 0.01 ) . Postoperatively , five patients in the Flotem IIe group required treatment with meperidine for severe shivering versus one patient in the Hotline group ( p < 0.05 ) . CONCLUSIONS The Hotline device delivered fluids to the patient at consistently warmer temperatures compared with the Flotem IIe device during actual clinical conditions . This was associated with maintenance of near normal core temperatures throughout the procedure in the Hotline group , and a decreased need for interventions such as forced-air warming and treatment for severe shivering PURPOSE The purpose of this study was to compare the effects of intravenous fluid warming and skin surface warming on peri-operative body temperature and acid base balance of abdominal surgical patients under general anesthesia . METHOD Data collection was performed from January 4th , to May 31 , 2004 . The intravenous fluid warming(IFW ) group ( 30 elderly patients ) was warmed through an IV line by an Animec set to 37 degrees C. The skin surface warming ( SSW ) group ( 30 elderly patients ) was warmed by a circulating-water blanket set to 38 degrees C under the back and a 60W heating lamp 40 cm above the chest . The warming continued from induction of general anesthesia to two hours after completion of surgery . Collected data was analyzed using Repeated Measures ANOVA , and Bonferroni methods . RESULTS SSW was more effective than IFW in preventing hypothermia(p= .043 ) , preventing a decrease of HCO(3)(-)(p= .000 ) and preventing base excess ( p= .000 ) respectively . However , there was no difference in pH between the SSW and IFW ( p= .401 ) groups . CONCLUSION We conclude that skin surface warming is more effective in preventing hypothermia , and HCO(3)(- ) and base excess during general anesthesia , and returning to normal body temperature after surgery than intravenous fluid warming ; however , skin surface warming was n't able to sustain a normal body temperature in elderly patients undergoing abdominal surgery under general anesthesia Background : The infusion of several liters of crystalloid solution at room temperature may significantly contribute to intraoperative hypothermia because warming fluid to core temperature requires body heat . The aim of this study was to evaluate the effect of delivering warmed intravenous ( IV ) fluid to the patient on preventing intraoperative hypothermia PURPOSE The purpose of this study was to evaluate the effect of irrigation fluid temperature on body temperature and other variables , and to determine their correlations . METHODS A prospect i ve r and omized study was performed of 50 patients undergoing arthroscopic shoulder surgery who received irrigation fluid either with room temperature or warmed to 37 degrees C to 39 degrees C. Core body temperature was checked at regular intervals , and additional variables , such as length of anesthesia and surgery , amount of irrigation fluid and intravenous fluid used , amount of bleeding , weight gain , and postoperative pain were collected during surgery and postoperatively . RESULTS The final core body temperature was 35.5 + /- 0.3 degrees C in the room-temperature fluid group and 36.2 + /- 0.3 degrees C in the warmed fluid group ( P < .001 ) . The temperature drop was 0.86 + /- 0.2 degrees C in the room-temperature fluid group and 0.28 + /- 0.2 degrees C in the warmed fluid group ( P < .001 ) . Hypothermia occurred in 91.3 % of patients in the room-temperature fluid group ; the incidence of hypothermia was much lower in the warmed fluid group ( 17.4 % ; P < .001 ) . Of the variables measured , the patient 's age and amount of irrigation fluid used correlated with core body temperature in the room-temperature fluid group . No variables correlated with core body temperature in the warmed fluid group . CONCLUSIONS Hypothermia occurred more often in shoulder arthroscopic surgery with room-temperature fluid irrigation than with warmed fluid irrigation . The patient 's age and amount of irrigation fluid used correlate with core body temperature when using room-temperature irrigation fluid . The use of warm irrigation fluid during arthroscopic shoulder surgery decreases perioperative hypothermia , especially in elderly patients . LEVEL OF EVIDENCE Level I , therapeutic r and omized controlled trial Background : Hypothermia is one of the problems occurring during surgery , which can happen due to thermoregulation mechanism disorders and intake of low temperature IV fluids , and may cause increase in blood pressure , heart rate , intracranial pressure , oxygen consumption , pain , and discomfort to the patient . The rate of cesarean section in our country is three times more than the global st and ard . As one of the responsibilities of the nurse is patient 's advocacy , s/he should support them . This study aim ed to investigate the effect of pre-warmed intravenous fluids on prevention of hypothermia during general anesthesia in cesarean section . Material s and Methods : Sixty-two women undergoing elective cesarean section by general anesthesia were r and omly allocated in two groups of intervention and control . Women in the intervention group received pre-warmed serum ( 37 ° C ) while those in the control group received serum at room temperature ( 25.5 ° C ) . The core body temperature and some hemodynamic parameters of the participants were assessed during the operation . Results : The mean of pulse rate , systolic blood pressure , diastolic blood pressure , and arterial O2 saturation in the two groups were not statistically significant ( P > 0.05 ) . But the mean of mothers ’ core body temperature at the end of anesthesia in the intervention and control groups were 36 ± 0.5 ° C and 35.34 ± 0.6 ° C , respectively ( P < 0.05 ) . Conclusion : Infusion of pre-warmed serum ( 37 ° C ) would prevent intraoperative hypothermia and improve the nursing care for women who undergo cesarean section by general anesthesia STUDY OBJECTIVE To test the hypothesis that warming intravenous ( i.v . ) fluids in conjunction with convective warming results in less intraoperative hypothermia ( core temperature < 36.0 degrees C ) than that seen with convective warming alone . DESIGN Prospect i ve , r and omized study . SETTING University affiliated tertiary care teaching hospital . PATIENTS 61 ASA physical status , I , II , and III adults undergoing major surgery and general anesthesia with isoflurane . INTERVENTIONS All patients received convective warming . Group 1 patients received warmed fluids ( setpoint 42 degrees C ) . Group 2 patients received room temperature fluids ( approximately 21 degrees C ) . MEASUREMENTS AND MAIN RESULTS Lowest and final intraoperative distal esophageal temperatures were higher ( p < 0.05 ) in Group 1 ( mean + /- SEM : 35.8 + /- 0.1 degrees C and 36.6 + /- 0.1 degrees C ) versus Group 2 ( 35.4 + /- 0.1 degrees C and 36.1 + /- 0.1 degrees C , respectively ) . Compared with Group 1 , more Group 2 patients were hypothermic at the end of anesthesia ( 10 of 26 patients , or 38.5 % vs. 4 of 30 patients , or 13 % ; p < 0.05 ) . After 30 minutes in the recovery room , there were no differences in temperature between groups ( 36.7 + /- 0.1 degrees C and 36.5 + /- 0.1 degrees C in Groups 1 and 2 , respectively ) . Intraoperative cessation of convective warming because of core temperature greater than 37 degrees C was required in 33 % of Group 1 patients ( vs. 11.5 % in Group 2 ; p = 0.052 ) . CONCLUSIONS The combination of convective and fluid warming was associated with a decreased likelihood of patients leaving the operating room hypothermic . However , average final temperatures were greater than 36 degrees C in both groups , and intergroup differences were small . Care must be taken to avoid overheating the patient when both warming modalities are employed together OBJECTIVES Our purpose was to determine the incidence and etiology of hypothermia during laparoscopic surgery and to evaluate the role of irrigation fluid temperature . STUDY DESIGN A prospect i ve r and omized study was performed of 35 women undergoing operative laparoscopy under general anesthesia who received surgical irrigation fluid either at ambient temperature or warmed to 39 degrees C. The core body temperature was determined with use of both an esophageal sensor and a tympanic membrane sensor and was expressed as the change from baseline . Additional data collected included age , height , weight , amount of irrigation fluid and intravenous fluid used , room temperature , length of anesthesia , and amount of carbon dioxide used for pneumoperitoneum . RESULTS Hypothermia occurred in 94 % of all patients , with no difference in incidence between the groups . The minimal core temperature was lower in the ambient temperature group ( -1.7 degrees + /- 0.2 degrees C ) than in the warmed fluid group ( -1.0 degrees + /- 0.2 degrees C ) . Of the variables measured , length of anesthesia and the amount of ambient temperature fluid alone explained the drop in core temperature . CONCLUSION Hypothermia is extremely common in laparoscopic surgery and is related to the length of anesthesia and the use of ambient temperature irrigation fluid . The use of warmed irrigation fluid can decrease , but not eliminate , this drop in core temperature Background : The aim of this prospect i ve , controlled study was to evaluate the effects on coagulation function of active patient warming during elective plastic surgery . Methods : Seventy-six patients undergoing elective plastic surgery ( additive and reductive mastoplasty , rhinoplasty , and liposuction ) were either covered with st and ard sterile drapes ( control group , n = 38 ) or actively warmed during surgery with countercurrent fluid warming and forced-air skin warming ( treatment group , n = 38 ) . Complete evaluation of the coagulation activity was performed 1 hour before general anesthesia was induced and then at the end of surgery . Results : Although no differences in preoperative core temperature were observed ( 36.0 ± 0.5 ° C in the control group and 36.1 ± 0.4 ° C in the treatment group ; p = 0.12 ) , core temperature was lower at the end of surgery in the control group ( 34 ± 1.0 ° C ) than in the treatment group ( 36 ± 0.6 ° C ) ( p = 0.0005 ) . No differences in prothrombin time and fibrinogen plasma concentrations were observed between the two groups . At the end of surgery , control group patients showed significantly larger activated partial thromboplastin times ( 36.8 ± 3.5 seconds ) and bleeding times ( 8.1 ± 1.6 minutes ) as compared with patients maintained normothermic during surgery ( 34.0 ± 2.9 seconds and 4.3 ± 1.1 minutes ; p = 0.0005 and p = 0.0005 , respectively ) . Conclusion : Actively maintaining intraoperative normothermia allows patients to maintain normal coagulation function during elective plastic surgery lasting longer than 2 hours , potentially reducing the occurrence of bleeding-related complications after plastic surgery OBJECTIVES To determine the effect irrigation fluid temperature has on core body temperature changes in patients undergoing transurethral resection of the prostate ( TURP ) . METHODS Fifty-six male patients ( mean age 71.2 + /- 8.2 years ) scheduled for TURP were enrolled in the study . Patients were r and omized to one of two groups . Group 1 consisted of 27 patients who received room temperature irrigation fluid ( 70 degrees F ) throughout TURP ; group 2 consisted of 29 patients whose procedure was performed with warmed irrigation fluid ( 91.5 degrees F ) . The irrigation fluid used for both groups was glycine . The baseline temperature , final temperature , total time in the operating room , and amount of irrigation fluid used during the procedure were recorded for each patient . RESULTS No significant difference in the average time spent in the operating room or in the total irrigation fluid used between the two groups was observed . Of the 27 patients who received room temperature irrigation fluid , 15 ( 55.6 % ) had a decrease in body temperature . A decrease in temperature was observed in 21 ( 72.4 % ) of the 29 patients who received warm irrigation fluid . Groups 1 and 2 had 12 ( 44.4 % ) of 27 and 8 ( 27.6 % ) of 29 patients , respectively , who demonstrated an elevation in their core body temperature . CONCLUSIONS The results of our study suggest that irrigation fluid temperature is not a factor responsible for altering the core body temperature in patients undergoing TURP OBJECTIVE Even mild perioperative hypothermia ( 34 degrees -36 degrees C ) can cause numerous adverse outcomes , including morbid cardiac events , coagulopathy with increased blood loss , and a decreased resistance to surgical wound infection . The purpose of this study was to evaluate the effect of fluid warming on preventing hypothermia during off-pump coronary artery bypass ( OPCAB ) surgery . DESIGN A prospect i ve r and omized clinical study . SETTING A tertiary care university hospital . PARTICIPANTS Forty patients undergoing OPCAB procedures . INTERVENTIONS Patients were r and omized into control ( n = 20 ) and Hotline ( n = 20 ) groups . In the Hotline group , all intravenous fluids were warmed to 41 degrees C by using 2 Hotline ( SIMS Inc , Rockl and , MD ) systems . All patients ( control and Hotline groups ) were managed with st and ardized institutional practice by using a combination of increased ambient operating room temperature ( to 25 degrees C ) and the use of a warmed water mattress ( 38 degrees C ) . MEASUREMENTS AND MAIN RESULTS Temperatures were recorded every hour after the induction of anesthesia at the pulmonary artery , nasopharynx , rectum , and bladder . In the Hotline group , temperatures were maintained or increased . In the control group , temperatures gradually decreased . There were no significant differences between the 2 groups in hemodynamic parameters , serum catecholamine concentrations , duration of intensive care unit stay , or duration of ward stay . CONCLUSIONS The results show that the warming of intravenous fluids by using the Hotline system prevents decreases in systemic temperatures during OPCAB surgery PURPOSE Adverse outcomes apparently associated with hypothermia led us to examine patients undergoing elective abdominal aortic aneurysm ( AAA ) repairs to test the hypothesis that hypothermia ( temperature less than 34.5 degrees C ) is associated with increased morbidity and excess mortality rates . METHODS Two hundred sixty-two elective AAA repairs were retrospectively review ed for preoperative and intraoperative risk factors . Core temperature , age , Acute Physiology and Chronic Health Evaluation ( APACHE ) II and APACHE III scores ( raw and temperature-adjusted ) , fluid resuscitation , and perioperative organ dysfunction were recorded prospect ively . Outcome measures included lengths of stay in the intensive care unit and in the hospital , and hospital mortality rates . RESULTS Except for a higher risk of hypothermia in women ( p < 0.05 ) , by univariate analysis , preoperative risk factors were similar in patients in the hypothermic and normothermic groups . After operation , patients with hypothermia had significantly greater APACHE scores ( p < 0.0001 ) , and patients in the hypothermic nonsurvivor group took significantly longer to rewarm ( p < 0.05 ) , suggesting marked hypoperfusion . Patients with hypothermia had significantly greater fluid ( p < 0.05 ) , transfusion ( p < 0.01 ) , vasopressor ( p < 0.05 ) , and inotrope ( p < 0.05 ) requirements , result ing in significantly higher incidences of organ dysfunction ( 53.0 % vs 28.7 % , p < 0.01 ) and death ( 12.1 % vs 1.5 % , p < 0.01 ) and markedly prolonged lengths of stay in the unit ( 9.2 + /- 2.0 vs 5.3 + /- 0.6 , p < 0.05 ) and in the hospital ( 24.3 + /- 2.9 vs 15.0 + /- 0.08 , p < 0.01 ) . By multivariate analysis , female gender ( p = 0.004 ) was the only predictor of intraoperative hypothermia , whereas initial hypothermia was significantly predictive of both prolonged hypothermia and development of organ failure ( p < 0.05 ) . Organ failure ( p < 0.05 ) and acute myocardial infa rct ion ( p < 0.01 ) were independent predictors of death . CONCLUSIONS After AAA repair , patients with hypothermia have multiple physiologic derangements associated with adverse outcomes . Although multiple etiologic factors are interacting , body temperature is one variable that should be controlled during aortic surgery STUDY OBJECTIVE To determine whether administration of pre-warmed colloid followed by pre-warmed crystalloid solution prevents the development of hypothermia in patients undergoing Cesarean delivery . DESIGN R and omized , double-blind , placebo-controlled study . PATIENTS 30 parturients scheduled to undergo elective Cesarean delivery during spinal anesthesia . INTERVENTIONS Patients assigned to the warmed fluid group ( n=15 ) received pre-warmed colloid with average molecular weight of 70,000 daltons and substitution ratio of 0.55 , followed by pre-warmed crystalloid ( kept in warmed storage maintained at 41 degrees C ) during surgery . Patients assigned to the unwarmed fluid group ( n=15 ) received non-warmed infusion . All patients received 400 mL before spinal anesthesia followed by another 300 mL before delivery of the newborn . After completion of a 1,000 mL infusion of colloid fluid , acetate Ringer 's solution was infused . MEASUREMENTS Core temperature measured at the tympanic membrane , and forearm and fingertip skin temperatures were recorded just after arrival at the operating room ( baseline ) , after administration of spinal anesthesia ( spinal ) , at incision ( incision ) , at delivery of the newborn ( delivery ) , and at 15 , 30 , and 45 minutes after delivery . Rectal temperature of the baby , Apgar scores at one and 5 minutes after delivery , and umbilical artery pH were evaluated . MAIN RESULTS Core temperature was significantly higher in the warmed fluid group from the time of delivery to 45 minutes after delivery . Apgar scores at one minute after delivery and umbilical arterial pH were significantly higher in the warmed fluid group . CONCLUSION Administration of pre-warmed intravenous colloid followed by crystalloids maintained core temperature during Cesarean delivery and induced higher Apgar scores and umbilical arterial Hypothermia in the immediate postoperative period is associated with postoperative instability , prolonged recovery and increased risk of myocardial ischemia in the subsequent 24 h. This study examined the effect of irrigating-fluid temperature during transurethral resection of the prostate on perioperative temperature regulation . A r and omized prospect i ve study was conducted on twenty-eight consecutive patients undergoing transurethral resections of the prostate . The control group received room-temperature irrigant . The study group received irrigant warmed through the Abbott level-one fluid warmer or in the Ohio Servocare incubator . Fluid temperatures were 17 degrees C for unwarmed fluid , 37 degrees C for level-one fluid , and 35 degrees C for incubator fluid . The incidence of hypothermia ( < or = 36 degrees C ) in the immediate postoperative period was 95 % in the cold-irrigant group and 38 % in the warm-irrigant group ( p = 0.001 ) . The decrease from pre- to postoperative temperature was greater with cold ( 0.95 + /- 0.47 degrees C ) than with warm ( 0.42 + /- 0.64 degrees C ) irrigant ( p = 0.01 ) . The type of anesthesia ( spinal versus general ) and method of fluid warming ( incubator versus level-one ) did not have a significant effect on the perioperative temperature drop . Regression analysis demonstrated that the time of resection , amount of prostate resected , volume of irrigant fluid , and volume of intravenous fluid administered were not independent predictors of intraoperative temperature change BACKGROUND Wound infection after clean surgery is an expensive and often underestimated cause of patient morbidity , and the benefits of using prophylactic antibiotics have not been proven . Warming patients during colorectal surgery has been shown to reduce infection rates . We aim ed to assess whether warming patients before short duration , clean surgery would have the same effect . METHODS 421 patients having clean ( breast , varicose vein , or hernia ) surgery were r and omly assigned to either a non-warmed ( st and ard ) group or one of two warmed groups ( local and systemic ) . We applied warming for at least 30 min before surgery . Patients were followed up and masked outcome assessment s made at 2 and 6 weeks . FINDINGS Analysis was done on an intention-to-treat basis . We identified 19 wound infections in 139 non-warmed patients ( 14 % ) but only 13 in 277 who received warming ( 5 % ; p=0.001 ) . Wound scores were also significantly lower ( p=0.007 ) in warmed patients . There was no significant difference in the development of haematomas or seromas after surgery but the non-warmed group were prescribed significantly more postoperative antibiotics ( p=0.002 ) . INTERPRETATION Warming patients before clean surgery seems to aid the prevention of postoperative wound infection . If applied according to the manufacturers guidelines these therapies have no known side-effects and might , with the support of further studies , provide an alternative to prophylactic antibiotics in this type of surgery Background : Perioperative hypothermia is common and likely contributes to morbidity , but the efficacy of prophylactic fluid warming has hardly been analyzed systematic ally . We tested the hypothesis that the use of an infusion/blood warmer , based on the principle of countercurrent heat exchange , reduces incidence and degree of severe hypothermia following aortic surgery Hemodynamic performance and core temperature were recorded during transurethral prostatectomy in 52 patients who were stratified according to cardiac symptom score and then r and omized to undergo st and ard ( 31 ) or isothermic ( 21 ) transurethral prostatectomy . During the st and ard procedure ambient temperature ( 21C ) irrigant was used , while during isothermic prostatectomy warmed irrigant at 38C was used to prevent heat loss from the bladder , and a warming blanket and humidifying filter were used to decrease cutaneous and respiratory heat loss . Core temperature decreased by a mean of 0.8C ( 95 % confidence interval -0.9 to -0.7 ) during st and ard transurethral prostatectomy and by 0.27C ( -0.4 to -0.15 ) during the isothermic procedure . The st and ard prostatectomy group showed a significant hemodynamic response consisting of increased mean arterial pressure ( p < 0.0002 ) , increased index of systemic vascular resistance ( p < 0.0001 ) , bradycardia ( p < 0.02 ) , and decreased Doppler indexes of stroke volume ( p < 0.005 ) and cardiac output ( p < 0.001 ) . The isothermic transurethral prostatectomy group was hemodynamically stable . These differences between the groups suggest that rapid central cooling exerted a significant effect on perioperative hemodynamic performance during transurethral prostatectomy BACKGROUND We evaluated the performance of a new temperature management system ( Allon Thermowrap , MTRE , Israel ) in maintaining normothermia during OPCAB ( Off-Pump Coronary Artery Bypass ) procedures and Zeus-robotic IMA ( internal mammary artery ) takedowns . MATERIAL / METHODS One hundred patients were prospect ively r and omized to either a conventional temperature management method ( thick blanket , warm intravenous fluids , operating room temperature 25 degrees C ) , or the new Allon Thermowrap system ( pads with temperature-controlled water circulation placed on the patient 's back , legs , and arms ) . The mean age , body surface area , total operating time , and OR air temperature were similar in both groups . RESULTS The Allon Thermowrap system maintained a higher bladder and nasopharyngeal temperature ( p<0.05 ) . The SVR decreased ( p<0.05 ) and the cardiac index increased ( p<0.05 ) in patients with a body temperature>35.80 degrees C. Without reaching a significant level , the postoperative blood loss was lower in the Allon Thermowrap group . CONCLUSIONS The Allon Thermowrap system significantly out-performed conventional techniques in achieving and maintaining normothermia during off-pump and robotic procedures The investigators examined the effect of infusing continuously warmed ( ie , 37.0 degrees C [ 98.6 degrees F ] ) i.v . fluids in two groups of middle-aged female patients undergoing laparoscopic cholecystectomy procedures . They hypothesized that increasing i.v . fluid temperature during surgery would decrease patients ' risk for hypothermia . One group of patients received prewarmed i.v . fluids that cooled to room temperature during surgery . The second group received i.v . fluids that were warmed continuously by a fluid warmer during the surgical procedures . Analyses of covariance , with the first intraoperative temperature measurement treated as the covariate , revealed nonsignificant results at the P < .05 level . The results suggest that administering continuously warmed i.v . fluids intraoperatively has no significant effect on maintaining patients ' body temperatures during short laparoscopic surgical procedures We evaluated whether warming IV fluids result ed in less hypothermia ( core temperature < 35.5[degree sign]C ) compared with room-temperature fluids . Thirty-eight adult out patients undergoing elective gynecological surgery of > 30 min were r and omized to two groups : fluid warming at 42[degree sign]C or control ( room temperature fluids at approximately 21[degree sign]C ) . All patients received general anesthesia with isoflurane , tracheal intubation , st and ard operating room blankets and surgical drapes , and passive humidification of inspired gases . Tympanic membrane ( core ) temperatures were measured at baseline and at 15-min intervals after induction . The incidence of shivering and postoperative requirement for meperidine and /or radiant heat were evaluated . Core temperatures were lower in the control compared with the warm fluid group at the end of surgery ( 35.6 + /- 0.1[degree sign]C vs 36.2 + /- 0.1[degree sign]C ; P < 0.05 ) . More patients had final core temperature < 35.5[degree sign]C in the control compared with the warm fluid group ( 35 % vs 0 % ; P < 0.05 ) . There were no differences in time to discharge from the postanesthesia care unit or the incidence of shivering between the groups . We conclude that fluid warming , in conjunction with st and ard heat conservation measures , was effective in maintaining normothermia during outpatient gynecological surgery ; however , there was no improvement in patient outcome . Implication s : Women who received IV fluid at body temperature had significantly higher core temperatures during and after outpatient gynecological surgery compared with women who received IV fluids at the temperature of the operating room . ( Anesth Analg 1998;87:37 - 41 The changes in body temperature induced by rapid intravenous infusion of lactated Ringer solution and the effect of a fluid warmer system ( HOT LINE , Level 1 Technologies , Inc. , Rockl and , MD ) were investigated in 35 patients undergoing cardiovascular surgery . The patients were divided into 5 groups by categories of the fluid temperature ( -19 or -38 degrees C ) , infusion route ( radial or right subclavian vein ) , and infusion rate of lactated Ringer solution ( 1000 or 250 ml for 30 min ) . Pulmonary arterial , esophageal , bladder , and forehead deep temperatures , which reflect core temperature , were significantly decreased by the rapid infusion of unwarmed solution ( 0.8 - 1.0 degree C , P < 0.05 ) . In contrast , these temperatures were maintained in the warmed solution groups as well as in the group of slow infusion rate . With regard to the infusion route , there was no significant difference in the temperature between the radial vein and subclavian vein groups . Plantar deep temperature showed no significant change during this study . In conclusion , infusion of warmed solution using HOT LINE could prevent hypothermia induced by rapid intravenous infusion , and this effect is not greatly influenced by route of venous infusion |
12,223 | 28,394,084 | AUTHORS ' CONCLUSIONS Analysis of available studies was limited by variable reporting of primary and secondary outcomes ; therefore , it is difficult to draw firm conclusions related to the effectiveness of PAAPs in the management of adult asthma .
In the context of this caveat , we found no observable effect on the primary outcomes of hospital attendance with an asthma exacerbation , asthma symptom scores or adverse events . | BACKGROUND A key aim of asthma care is to empower each person to take control of his or her own condition .
A personalised asthma action plan ( PAAP ) , also known as a written action plan , an individualised action plan , or a self-management action plan , contributes to this endeavour .
A PAAP includes individualised self-management instructions devised collaboratively with the patient to help maintain asthma control and regain control in the event of an exacerbation .
A PAAP includes baseline characteristics ( such as lung function ) , maintenance medication and instructions on how to respond to increasing symptoms and when to seek medical help .
OBJECTIVES To evaluate the effectiveness of PAAPs used alone or in combination with education , for patient-reported outcomes , re source use and safety among adults with asthma . | Background Asthma patients may experience acute episodic exacerbation . The guidelines recommend that written action plan should be given to asthma patients . However , no one can predict when and where acute exacerbation will happen . As people carry smart phone almost anytime and anywhere , smartphone application could be a useful tool in asthma care . We evaluated the feasibility of the ubiquitous healthcare system of asthma care using a smartphone application ( snuCare ) based on the self-management guideline or action plan . Methods Forty-four patients including fragile asthmatics were enrolled from Seoul National University Bundang Hospital between December 2011 and February 2012 . They were r and omly assigned into application user ( n = 22 ) or application nonuser group ( n = 22 ) . We evaluated user-satisfaction , and clinical parameters such as asthma control , Quality of Life Question naire for Adult Korean Asthmatics , and the adherence of patients . Results The characteristics were similar at baseline between the 2 groups except those who treated with short-term systemic steroid or increased dose of systemic steroid during previous 8 weeks ( user vs. nonuser : 31.8 % vs. 4.5 % , p = 0.020 ) . Total of 2,226 signals was generated during 8 weeks including 5 risky states . After eight weeks , the users answered that it was very easy to use the application , which was shown in highest scores in terms of satisfaction ( mean ± st and ard deviation , 4.3 ± 0.56 ) . Seventy-three percent of patients answered that the application was very useful for asthma care . User group showed improved the adherence scores ( p = 0.017 ) . One patient in application user group could avoid Emergency Department visit owing to the application while a patient in nonuser group visited Emergency Department . Conclusion The ubiquitous healthcare system using a smartphone application ( snuCare ) based on the self-management guideline or action plan could be helpful in the monitoring and the management of asthma Background : There is still debate over the benefit of self-management programmes for adults with asthma . A brief self-management programme given during a hospital admission for acute asthma was tested to determine whether it would reduce readmission . Method : A r and omised controlled trial was performed in 280 adult patients with acute asthma admitted over 29 months . Patients on the self-management programme ( SMP ) received 40–60 minutes of education supporting a written self-management plan . Control patients received st and ard care ( SC ) . Results : One month after discharge SMP patients were more likely than SC patients to report no daytime wheeze ( OR 2.6 , 95 % CI 1.5 to 5.3 ) , no night disturbance ( OR 2.0 , 95 % CI 1.2 to 3.5 ) , and no activity limitation ( OR 1.5 , 95 % CI 0.9 to 2.7 ) . Over 12 months 17 % of SMP patients were re-admitted compared with 27 % of SC patients ( OR 0.5 , 95 % CI 0.3 to 1.0 ) . Among first admission patients , OR readmission ( SMP v SC ) was 0.2 ( 95 % CI 0.1 to 0.7 ) , p<0.01 . For patients with a previous admission , OR readmission was 0.8 ( 95 % CI 0.4 to 1.6 ) , p=0.6 . SMP patients were more likely than SC patients to be prescribed inhaled steroids at discharge ( 99 % v 92 % , p=0.03 ) , oral steroids ( 98 % v 90 % , p=0.06 ) , and to have hospital follow up ( 98 % v 84 % , p<0.01 ) but adjustment for these differences did not diminish the effect of the self-management programme . Conclusions : A brief self-management programme during hospital admission reduced post discharge morbidity and readmission for adult asthma patients . The benefit of the programme may have been greater for patients admitted for the first time . The programme also had a small but significant effect on medical management at discharge BACKGROUND The " credit card " asthma self-management plan provides the adult asthmatic patient with simple guidelines for the self-management of asthma , which are based on the self- assessment of peak expiratory flow rate recordings and symptoms . OBJECTIVE The study was a trial of the clinical efficacy of the credit card plan in a high-risk group of asthmatic patients . METHODS In this " before- and -after " trial , patients discharged from the emergency department of Wellington Hospital , after treatment for severe asthma were invited to attend a series of hospital outpatient clinics at which the credit card plan was introduced . Question naires were used to compare markers of asthma morbidity , requirement for emergency medical care , and medication use during the 6-month period before and after intervention with the credit card plan . RESULTS Of the 30 patients with asthma who attended the first outpatient clinic , 26 ( 17 women and 9 men ) completed the program . In these 26 participants , there was a reduction in both morbidity and requirement for acute medical services : specifically , the proportion waking with asthma more than once a week decreased from 65 % to 23 % ( p = 0.005 ) and the proportion visiting the emergency department for treatment of severe asthma decreased from 58 % to 15 % ( p = 0.004 ) . The patients attending the clinics commented favorably on the plan , in particular on its usefulness as an educational tool for monitoring and treating their asthma . CONCLUSIONS Although the interpretation of this study is limited by the lack of a r and omized control group , the findings are consistent with other evidence that the credit card asthma self-management plan can be an effective and acceptable system for improving asthma care in a high-risk group of adult patients with asthma Background : In clinical trials of asthma , the outcomes are often good , but when the same treatment regimens are implemented in primary care , equally good results are not obtained . Objective : To investigate if addition of structured patient information and monitoring by an asthma diary in primary care improves asthma control . Methods : 141 patients from 19 primary care centres were studied . The centres were r and omised to a st and ard care group or to an intervention group . The intervention group received structured written and oral information about asthma and asthma medication , and were instructed to keep an asthma diary . The primary outcome was asthma control as assessed by the Asthma Control Question naire . Secondary outcomes were costs of asthma medication , the Mini Asthma Quality of Life Question naire score and lung function . Results : Asthma Control Question naire score changes differed between the study groups ( p < 0.05 ) . In the intervention group , these changes ( M = –0.45 ) in asthma control were close to clinical significance ( minimal important difference ≈0.5 ) . Both groups improved in disease-specific quality of life scores . For the intervention group , which changed the most ( p < 0.05 ) , the change exceeded the threshold for the minimal important difference ( 0.5 ) . The costs of medications increased significantly in the intervention group , where adjustments of medication were made more often than in controls . Conclusion : Disease-specific quality of life of asthma patients could be improved by adding structured information and monitoring by diary to st and ard care The effects on self management of asthma of a specially prepared book and audiocassette tape with similar contents were observed in a controlled study of 177 patients with asthma in general practice . After a run in period of six months patients were r and omly given the book , the tape , both the book and tape , or neither . Patients ' knowledge of the use of drugs , perceptions of their disability , skill in using an inhaler , consumption of drugs , consultations with their general practitioners , morbidity ( from patients ' entries on diary cards ) , and use of the educational material were measured . Knowledge about the use of drugs was significantly increased in the groups who received the material after three months and persisted after 12 months . Patients who had been given the tape or the book and tape increased their scores of knowledge of drugs more than patients given the book alone . Patients in all groups given the material considered that their disability was reduced . There were no other significant changes . Patients given both the book and the tape preferred the book . Patients with asthma can obtain useful information from such material . The paradoxical result whereby patients learnt more from the tape but preferred the book suggests that a distinction can be made between information that patients need , which may be acquired better from an audiocassette , and information that they want , which may be acquired better from a book OBJECTIVES To improve the asthma control and adherence to asthma preventer medication of older people using the Patient Asthma Concerns Tool ( PACT ) to identify and address unmet needs and patient concerns . METHODS Community dwelling adults over 55 years , living in Victoria or New South Wales were recruited into a single-blind , parallel design , r and omised-controlled trial comparing person-centred education including device technique , versus written information-only education . Fifty-eight participants r and omised to the intervention group and 56 to the control completed participation . OUTCOME MEASURES asthma control , adherence to preventer medication , asthma related quality of life , asthma exacerbations and written action plan ownership were assessed at baseline , and 3 and 12 months post intervention . RESULTS Intervention participants experienced improvements in asthma control , adherence to asthma preventer medication , reduced exacerbations , improved quality of life and an increase in asthma action plan ownership at 3 and 12 months . CONCLUSION Asthma outcomes in older people can be significantly improved by delivering tailored education that identifies specific patient concerns and unmet needs . PRACTICAL IMPLICATION S Use of the PACT to identify patient concerns and unmet needs will assist health professionals to improve the health literacy of patients by addressing gaps in their knowledge and perceptions of asthma control Background Many studies have shown the effectiveness of self-management for patients with asthma . In particular , possession and use of a written asthma action plan provided by a doctor has shown to significantly improve patients ’ asthma control . Yet , uptake of a written asthma action plan and preventative asthma management is low in the community , especially amongst adults . Objective A Web-based personally controlled health management system ( PCHMS ) called Healthy.me will be evaluated in a 2010 CONSORT-compliant 2-group ( static websites verse PCHMS ) parallel r and omized controlled trial ( RCT ) ( allocation ratio 1:1 ) . Methods The PCHMS integrates an untethered personal health record with consumer care pathways and social forums . After eligibility assessment , a sample of 300 adult patients with moderate persistent asthma will be r and omly assigned to one of these arms . After 12 months of using either Healthy.me or information websites ( usual care arm ) , a post- study assessment will be conducted . Results The primary outcome measure is possession of or revision of an asthma action plan during the study . Secondary outcome measures include : ( 1 ) adherence to the asthma action plan , ( 2 ) rate of planned and unplanned visits to healthcare providers for asthma issues , ( 3 ) usage patterns of Healthy.me and attrition rates , ( 4 ) asthma control and asthma exacerbation scores , and ( 5 ) impact of asthma on life and competing dem and s , and days lost from work . Conclusions This RCT will provide insights into whether access to an online PCHMS will improve uptake of a written asthma action plan and preventative asthma actions . Trial Registration Trial Registration : Australian New Zeal and Clinical Trials Registry ACTRN12612000716864 ; https://www.anzctr.org.au/Trial/ Registration /Trial Review .aspx?id=362714 ( Archived by WebCite at http://www.webcitation.org/6IYBJGRnW ) A prospect i ve controlled trial of home monitoring of peak expiratory flow rate ( PEFR ) was conducted to determine the usefulness of an objective measure of lung function in association with an education program and a medication self-management plan in reducing morbidity in adult patients with asthma . Thirty-five patients managed themselves , using peak flow readings as the basis for the therapeutic plan coupled with educational intervention , whereas 35 control patients used symptoms and spirometric data for following physicians ' treatment plans . After a 6-mo study period , patients in the experimental group showed statistically significant improvements in morbidity parameters ( days lost from work , acute asthma attacks , days on antibiotic therapy , physician consultations , and emergency room admissions for asthma ) , increases in FVC , FEV1 , and FEV1/FVC , mean PEFR and mean morning PEFR , decrease in percentage of the mean PEFR amplitude , and a reduction in the use of inhaled beta-agonists , oral theophylline , and oral prednisone . Although improvements in some of these parameters were also found in the control group , they did not reach the levels of significance obtained in the experimental group . The personal use of an objective measure of lung function in association with a medication self-management plan leads to improvement in the patient 's condition OBJECTIVES Despite advances in recent years , asthma morbidity and mortality have been noted to be on the increase in the past decade . The present study examined the failures and recommendations of past studies and introduced a new milieu for asthma care -- the community pharmacy . The study incorporated a care protocol with the important ingredients of asthma education on medications , triggers , self-monitoring and an asthma plan , with pharmacists taking responsibility for outcomes , assessment of a patient 's readiness to change and tailoring education to that readiness , compliance monitoring and physician consultation to achieve asthma prescribing guidelines . METHODS Thirty-three pharmacists in British Columbia , specially trained and certified in asthma care , agreed to participate in a study in which experienced pharmacists would have asthma patients allocated to enhanced ( pharmaceutical ) care ( EC ) or usual care ( UC ) . Pharmacists less experienced were clustered by geography and had their pharmacies r and omized to two levels of care ; each pharmacy then had patients r and omized to EC versus control , UC versus control or EC versus UC depending on their pharmacy r and omization . Six hundred thirty-one patients provided consent , of which 225 in EC or UC were analyzed for all outcomes . Patients were followed for one year . RESULTS Compared with patients in the UC group , the results of those in the EC group were as follows : symptom scores decreased by 50 % ; peak flow readings increased by 11 % ; days off work or school were reduced by approximately 0.6 days/month ; use of inhaled beta-agonists was reduced by 50 % ; overall quality of life improved by 19 % , and the specific domains of activity limitations , symptoms and emotional function also improved ; initial knowledge scores doubled ; emergency room visits decreased by 75 % ; and medical visits decreased by 75 % . A patient satisfaction survey revealed that the population was extremely pleased with their pharmacy services . Cost analysis reinforces the EC model , which is more cost effective than UC in terms of most direct and indirect costs in asthma patients . CONCLUSION Specially trained community pharmacists in Canada , using a pharmaceutical care-based protocol , can produce impressive improvements in clinical , economic and humanistic outcome measures in asthma patients . The health care system needs to produce incentives for such care Background : A study was undertaken to determine the effectiveness of asthma self-management in general practice . Methods : Nineteen general practice s were r and omly allocated to usual care ( UC ) or self-management ( SM ) . Asthma patients were included after confirmation of the GP diagnosis . Follow up was 2 years . Patients kept diary cards and visited the lung function laboratory every 6 months . Outcomes were number of successfully treated weeks , limited activity days , asthma specific quality of life , forced expiratory volume in 1 second ( FEV1 ) , FEV1 reversibility , concentration of histamine provoking a fall in FEV1 of 20 % or more ( PC20 histamine ) , and amount of inhaled steroids . Results : A total of 214 patients were included in the study ( 104 UC/110 SM ; one third of the total asthma population in general practice ) ; 62 % were female . The mean percentage of successfully treated weeks per patient in the UC group was 72 % ( 74/103 weeks ) compared with 78 % ( 81/105 weeks ) in the SM group ( p=0.003 ) . The mean number of limited activity days was 1.2 ( 95 % CI 0.5 to 1.9 ) in the SM group and 3.9 ( 95 % CI 2.5 to 5.4 ) in the UC group . The estimated increase in asthma quality of life score was 0.10 points per visit in the UC group and 0.21 points per visit in the SM group ( p=0.055 ) . FEV1 , FEV1 reversibility , and PC20 histamine did not change . There was a saving of 217 puffs of inhaled steroid per patient in favour of the SM group ( p<0.05 ) . Conclusion : Self-management lowers the burden of illness as perceived by patients with asthma and is at least as effective as the treatment usually provided in Dutch primary care . Self-management is a safe basis for intermittent treatment with inhaled corticosteroids To assess the efficacy of self-management programs it is important to know what behavioural changes take place . This paper assesses whether including self-treatment guidelines ( action plans ) in a self-management program for adult asthmatics , leads to greater behavioural changes than a program without these guidelines . Patients were r and omised into a self-treatment group ( n=123 ) or an active control group ( n=122 ) . All subjects received self-management training . Discussed topics included the pathophysiology of asthma , medication and side-effects , triggers , symptoms , smoking , physical exercise , and compliance . The only difference was that the self-treatment group received instructions about self-treatment of exacerbations and the control group did not . At 1 year of follow-up asthma-specific self-efficacy expectancies , outcome expectancies , and asthma-specific knowledge improved significantly in all patients . Only self-treatment group patients demonstrated favourable changes in generalised self-efficacy , social support , and self-treatment and self-management behaviour , in case of a hypothetical scenario of a slow-onset exacerbation . We conclude that our self-management program is effective in changing the behavioural variables , and including self-treatment guidelines ( action plans ) has added benefit Great emphasis is placed on educating asthmatics to use action plans to achieve better control of symptoms . The use of peak flow meters ( PFM ) has been recommended as an important part of self-management plans . We studied 92 ( 47 F ) adult patients with asthma in a primary care setting to compare the effectiveness of action plans using either peak flow monitoring or symptoms to guide self-management . Each patient was instructed in the use of the action plan in the context of a 6-mo asthma education program taught by a nurse . Patients were already using inhaled corticosteroids or were newly prescribed corticosteroids by their family physician . Forty-four patients were r and omized to the PFM group and 48 to the symptoms group . Spirometry , symptom scores , quality of life , medication use , and measures of health care utilization and morbidity ( emergency department visits , hospitalizations , unscheduled doctor visits , and days lost from work or school ) were recorded at baseline and throughout the study period . PC20 methacholine was measured at the first and at the final visits . There were significant improvements within groups for FEV1 , symptoms score , PC20 methacholine , and quality of life , but no between-group differences . A significant shift from higher to lower daily use of beta-agonists ( p < 0.008 for both groups ) and significant shifts to higher daily doses of inhaled steroids ( p < 0.001 ) occurred in each group . Adherence to the self-management plans was only 65 % in the PFM group and 52 % in the symptoms group . Outcomes for health care utilization were similar except for fewer patients making unscheduled doctor visits within the PFM group . Our findings show that education , regular follow-up , and an action plan are effective in improving asthma control and quality of life , but the routine use of PFM to guide interventions is not the only way to accomplish these objectives METHODS The prevalence of asthma in adults in the United States is approximately 7 % , and 9 % of asthma patients will require hospitalization each year . Many patients do not seek care , as they do not recognize overuse of beta-agonists as a risk factor for poorly controlled asthma . However , pharmacists are able to identify these patients through refill information on reliever medication prescriptions and potentially initiate community-management opportunities for these patients . DESIGN The study is a r and omized , controlled trial . Patients are r and omized to intervention or usual care . STUDY POPULATION Patients are high-risk asthma patients ( defined as having an ER visit or hospitalization in the previous year , or using > 2 canisters of short-acting beta-agonist in the previous 6 months ) . They are identified through community pharmacies . OBJECTIVES The primary objective is to determine the effect of an education and referral intervention program initiated by community pharmacists , working with high-risk asthma patients , family physicians and respiratory therapists , on asthma control , as measured by the Asthma Control Question naire ( ACQ ) . Secondary objectives include determining the effect of this program on ER visits/hospitalizations , inhaled corticosteroid use , courses of oral steroids and FEV(1 ) . INTERVENTION The intervention includes patient education , assessment and optimization of drug therapy , and physician referral as needed . Patients are referred to a respiratory therapist within 1 week of r and omization for measurement of FEV(1 ) and reinforcement of education . Patients assigned to usual care receive written asthma information , referral to a respiratory therapist and usual pharmacy and physician care . UNIQUE ASPECTS : The design of the Better Respiratory Education and Asthma Treatment in Hinton and Edson ( BREATHE ) study is unique , given the multidisciplinary involvement , rural and community based , pharmacist initiated and targets specifically high risk patients . We believe that this study will show that management of asthma patients , involving the major role-players in their asthma care , will improve their asthma control The purpose of the AIR/Kaiser-Permanente asthma project is to evaluate various approaches to the education of adults with asthma , identifying those types of patients for whom particular approaches are most cost effective . Critical self-management prac tices for adults with asthma were identified using the critical incident technique . An individualized and a group administered educational program are being developed to teach the identified critical skills , using the instructional models previously employed in AIR WISE and AIR POWER programs for children with asthma . Three hundred patients with moderate to severe asthma from Northern California Kaiser-Permanente Medical Group clinics will participate in a trial of these programs . Patients will be r and omly assigned to one of four conditions : One of two educational programs , an information/attention control , or a data -only control condition . Data will be collected on all patients for 15 months ; health care utilization data covering a two-year period will be available from medical records . Program effectiveness will be evaluated in terms of pre-post changes in the patients ' knowledge , attitudes , self-man agement practice s , medical condition , daily functioning , and utilization of services . Cost effectiveness will be evaluated , paying specific attention to the cost effectiveness of different educational approaches for different types of patients The purpose of this study was to evaluate the impact of a self-management program for adults with moderate to severe asthma on compliance with inhaled , prescribed , nonemergency medications ; asthma symptoms ; and airway obstruction . In this controlled experimental study , 55 subjects from a rural community were r and omized to one of two groups . Self-efficacy theory served as the framework for this study . Primary measures included the Metered Dose Inhaler ( MDI ) Chronolog , a journal of daily asthma concerns , and a peak-flow meter to appraise airway obstruction . Secondary measures included the Asthma Self-Management Assessment Tool ( ASMAT ) and the Self-Efficacy for Asthma Management Scale ( SEAMS ) . These measures were completed pre- and post-intervention . Data analysis using descriptive and inferential statistics revealed that subjects receiving the self-management program increased compliance with inhaled medications ( U = 271 , p = .043 ) OBJECTIVE Peak flow meters ( PFM ) continue to be recommended as an important part of asthma self-management plans . It remains unclear if there is an advantage in using PFM in people with moderate-to severe asthma who are not poor perceivers of bronchoconstriction . METHODOLOGY Prospect i ve , r and omized controlled trial of 134 adults with moderate-to-severe asthma who did not have evidence of poor perception of bronchoconstriction on histamine challenge testing , who were recruited from in patients and out patients of a university teaching hospital . Comparison was made over 12 months of the effectiveness of written action plans using either peak flow monitoring or symptoms to guide management . Subjects were contacted at monthly intervals by telephone for reinforcement and evaluation of use of the action plans , and to provide ongoing education . Spirometry and PD20 histamine were measured at 3-monthly intervals . Measures of health care utilization and morbidity ( asthma exacerbations ; hospitalizations ; emergency department ( ED ) visits ; days absent from work or school due to asthma ; medication use and a self-rating of asthma severity ) were made monthly . A psychosocial question naire ( attitudes and beliefs , state-trait anxiety , denial ) was given at entry and at 12-months or at withdrawal from the study . RESULTS There were significant improvements for both groups for hospitalizations , ED visits , days off from school or work , and PD20 histamine , but no between-group differences . Appropriate use of action plans was 85 % in the symptoms group and 86 % in the PFM group . For all subjects , those who subsequently had an ED visit had significantly higher levels of denial ( P=0.04 ) and lower scores for self-confidence ( P=0.04 ) , compared to those who did not have an ED visit . CONCLUSIONS Use of written action plans , combined with regular contact to reinforce self-management , improved airway reactivity and reduced health care utilization . However , use of PFM was not superior to symptom-based plans Our aim was to assess the efficacy of budesonide ( Pulmicort Turbohaler Astra ) used as part of a self-management plan in a group of patients with chronic asthma . One hundred and twenty five patients with nocturnal asthma symptoms , despite the use of inhaled prophylactic and beta 2-agonist therapy , were r and omized to inhaled budesonide 200 , 400 or 800 micrograms b.i.d . either with dose adjustments made by the physician , i.e. doctor-managed ( DM ; n = 64 ) , or as part of a self-management plan ( SM ; n = 61 ) . The SM group were allowed to adjust their dose according to written guidelines based on morning peak flow . At the end of the 6 month treatment period , there were no significant differences detected between the DM and the SM groups either from the clinic or diary card data . Both groups demonstrated a significant reduction in the number of sleep-disturbed nights , by 75 % in the DM group and 77 % in the SM group , at the end of the study . In conclusion , for patients with mild-to-moderate asthma , either a doctor-adjusted dose regimen or a peak flow based self-management plan involving budesonide is equally efficacious . For some patients , a simple regimen , adjusted by the physician at clinic visits , may be easier to follow BACKGROUND During the past 15 years , programs to improve self-management practice s in adults with asthma have reported improvement in functional status and reduction of inappropriate use of health care services . However , these programs usually represent an ideal approach , applying multiple patient education methods . Consequently , when these programs are found to be efficacious , it is important to replicate the programs as well as to evaluate less complex methods that may be more appropriate for nonacademic health care setting s. METHODS We compared the following 3 st and ardized self-management treatments in a r and omized , controlled trial : ( 1 ) a replication of the self-management program developed at a university medical center that was previously shown to be efficacious ; ( 2 ) a modified version of this program including only the core elements ; and ( 3 ) a usual-care program . Outcome measures included medication and inhaler regimen adherence , asthma symptoms , respiratory illness , functional status , and use of health care re sources . RESULTS All 3 groups improved on measures of respiratory illnesses , use of health care services , and functional status . Patients in both education groups did no better than the usual-care group . CONCLUSIONS The results are inconsistent with the results of the first asthma self-management study at this institution and with those of efficacy studies of similar programs . Two factors , selection of the patient population and historical changes in asthma treatment , most likely contributed to the lack of impact of the self-management programs . As a result of the improved st and ards for usual care due to both factors , the opportunity to effect patient outcomes was substantially reduced STUDY OBJECTIVE To determine the effect of a symptom-based and a peak flow-based action plan in preventing acute exacerbations in subjects with poorly controlled asthma . DESIGN A r and omized controlled trial in which subjects who had required urgent treatment for their asthma were allocated to receive no action plan , a symptom-based plan , or a peak flow-based action plan . SETTING A university hospital asthma clinic . POPULATION One hundred fifty subjects were recruited after attending an emergency department or a clinic for urgent treatment of asthma . INTERVENTIONS All subjects received evaluation and education for asthma before being r and omly allocated to receive no action plan , a symptom-based action plan , or a peak flowmeter and a peak flow-based action plan . MEASUREMENTS Subjects were assessed by question naire at 3 and 6 months after enrollment with questions relating to their asthma control and their need for urgent treatment or hospital admission for asthma . RESULTS At 6 months after enrollment , although all three intervention groups experienced improvement in their asthma control , there was a striking reduction in emergency department visits for asthma only in the peak flow-based action plan group ( p=0.006 ) . No significant difference in emergency visits was apparent between the symptom-based action plan and no action plan groups . CONCLUSIONS We conclude that a peak flow-based action plan is effective , at least in the short term , in protecting patients with asthma against severe exacerbations of their disease Background Telehealth has the potential to improve asthma management through regular monitoring of lung function and /or asthma symptoms by health professionals in conjunction with feedback to patients . Although the benefits of telehealth for improving asthma management have been extensively studied , the feasibility of telehealth for supporting asthma management in pregnant women has not been investigated . This study aims to evaluate the use of telehealth for remotely monitoring lung function and optimising asthma control during pregnancy . Methods A r and omised controlled trial comparing usual care with a telehealth program ( MASTERY © ) has been conducted . The intervention comprised a mobile application – Breathe-easy © supported by a Bluetooth-enabled h and held device ( COPD -6 ® ) , which was used for self-monitoring of lung function ( FEV1 , FEV6 ) twice daily , and recording asthma symptoms and medication usage weekly ; and a written asthma action plan ( WAAP ) . The primary outcome measure is change in asthma control measured using the Asthma Control Question naire ( ACQ ) . Secondary outcomes include changes in mini-Asthma Quality of Life Question naire ( mAQLQ ) score , lung function , asthma-related health visits , days off work/ study , and oral corticosteroid use . Outcome data were collected at baseline , 3 months and 6 months by a research assistant masked to group allocation . Maternal and neonatal outcomes were also collected post-partum . Discussion This is the first study to evaluate the application of telehealth to optimize asthma management in pregnant women . If effective , this telehealth program could improve asthma self-management by pregnant women which may reduce the maternal and fetal risks of poorly controlled asthma during pregnancy . Trial registration Australian New Zeal and Clinical Trials Registry ( ACTRN 12613000800729 ) 17 July BACKGROUND --Peak flow based asthma self-management plans have been strongly advocated in consensus statements , but convincing evidence for the effectiveness of this approach has been largely lacking . METHODS --A r and omised controlled trial was conducted in 25 general practice s comparing an asthma self-management programme based on home peak flow monitoring and surgery review by a general practitioner or practice nurse with a programme of planned visits for surgery review only over a six month period . RESULTS --Seventy two subjects ( 33 in the self-management group and 39 in the planned visit group ) completed the study protocol , but diary card data for at least three months were available on a total of 84 ( 39 in the self-management group and 45 in the planned visit group ) . Teaching self-management took longer than the planned visit review . In the self-management group home peak flow monitoring was felt to be useful by doctors and patients in 28 ( 85 % ) and 27 ( 82 % ) cases , respectively . There were no between group differences during the study period in terms of lung function , symptoms , quality of life , and prescribing costs . Only within the self-management group were improvements noted in disturbance of daily activities and quality of life . Possible explanations for these negative results include small numbers of subjects , the mild nature of their asthma , and inappropriate self-management strategies for such patients . CONCLUSIONS -- Rigid adherence to long term daily peak flow measurement in the management of mild asthma in general practice does not appear to produce large changes in outcomes . Self-management and the use of prescribed peak flow meters need to be tailored to individual circumstances This study assessed the long-term efficacy of adding self-treatment guidelines to a self-management programme for adults with asthma . In this prospect i ve r and omized controlled trial , 245 patients with stable , moderate to severe asthma were included . They were r and omized into a self-treatment group ( group S ) and a control group ( group C ) . Both groups received self-management education . Additionally , group S received self-treatment guidelines based on peak expiratory flow ( PEF ) and symptoms . Outcome parameters included : asthma symptoms , quality of life , pulmonary function , and exacerbation rate . The 2-yr study was completed by 174 patients . Both groups showed an improvement in the quality of life of 7 % . PEF variability decreased by 32 % and 29 % , and the number of outpatient visits by 25 % and 18 % in groups S and C , respectively . No significant differences in these parameters were found between the two groups . After 1 yr , patients in both groups perceived better control of asthma and had more self-confidence regarding their asthma . The latter improvements were significantly greater in group S as compared to group C. There were no other differences in outcome parameters between the groups . Individual self-treatment guidelines for exacerbations on top of a general self-management programme does not seem to be of additional benefit in terms of improvements in the clinical outcome of asthma . However , patients in the self-treatment group had better scores in subjective outcome measures such as perceived control of asthma and self-confidence than patients in the control group Objective : to assess the effects of an educational program in asthmatic patients , following treatment readjustment . Methods : moderate to severe asthmatic adults underwent a run-in period ( up to 45 days ) in order to optimize their treatment . Patients were then r and omized to an educational or control group over a one-year period . Education consisted of five individual sessions covering : pathophysiology of asthma , role of medication and side-effects , asthma triggers and their avoidance , detection of an asthma flare-up , and self-management plan based on symptoms and peak-flow monitoring . Main outcome criterion : symptom-free days over the study period ( SFD ) . Results : a total of 72 patients were enrolled ( 36 in the “ education group ” and 36 in the “ control group ” ) , 54 of whom completed the study . Mean SFD was comparable in the two groups ( 88 % in the education group and 89 % in the control group , respectively ) . When the analysis was restricted to the education group , those patients who complied perfectly with the action plan ( n = 5 ) exhibited a higher SFD , compared to the others ( 97 % vs. 87 % , p = 0.009 ) . Conclusion : both education and control groups showed high and comparable percentages of SFD . Compliance with self-management plans appears to be an important determining factor in educational programs Asthma education decreases the number of emergency visits in specific subgroups of patients with asthma . However , it remains unknown whether this improvement is related only to the use of an action plan alone or to other components of the educational intervention . A total of 126 patients consulting urgently for an acute asthma exacerbation were recruited ; 98 completed the study . The first 45 patients were assigned to Group C ( control ; usual treatment ) . Thereafter , patients were r and omized to either Group LE ( limited education ; teaching of the inhaler technique plus self- action plan given by the on call physician ) or Group SE ( same as group LE plus a structured educational program emphasizing self-capacity to manage asthma exacerbations ) . At baseline , there was no difference between groups in asthma morbidity , medication needs , or pulmonary function . After 12 mo , only Group SE showed a significant improvement in knowledge , willingness to adjust medications , quality of life scores , and peak expiratory flows . In the last 6 mo , the number of unscheduled medical visits for asthma was significantly lower in Group SE in comparison with groups C and LE ( p = 0.03 ) . The number ( % ) of patients with unscheduled medical visits also decreased significantly in Group SE compared with Groups C and LE ( p = 0.02 ) . We conclude that a structured educational intervention emphasizing self-management improves patient outcomes significantly more than a limited intervention or conventional treatment BACKGROUND A small proportion of patients with asthma account for a disproportionate number of acute health service events . To identify whether factors other than severity and low socioeconomic status were associated with this disproportionate use , a prospect i ve study was undertaken to examine management and psychosocial factors associated with increased risk for admission to hospital with asthma and repeat visits to the emergency department over a 12 month period . METHODS A total of 293 patients with moderate or severe asthma managed at least in part at two teaching hospitals completed surveys of clinical status , acute events , sociodemographic , and psychological variables . RESULTS Twenty three percent had a single admission to hospital and 16 % had two or more hospital admissions . Twenty six percent had one emergency department visit and 32 % had two or more visits to the emergency department . In a multiple logistic regression model , adjusted for age , sex , education and income , odds ratios ( 95 % CI ) for baseline factors associated with hospital admissions over the next 12 months were : moderate severity compared with severe asthma 0.6 ( 0.2 to 0.9 ) ; no hospital admissions in the past 12 months 0.1 ( 0.01 to 0.2 ) ; not possessing a written asthma action plan 4.0 ( 1.5 to 10.7 ) ; less use of an avoidance coping style 0.4 ( 0.3 to 0.7 ) ; lower preferences for autonomy in asthma management decisions 1.4 ( 0.96 to 2.0 ) . Adjusted odds ratios ( 95 % CI ) for repeat emergency department visits were : moderate asthma severity 0.3 ( 0.1 to 0.8 ) ; current regular use of oral corticosteroids 10.0 ( 3.1 to 32.4 ) ; a hospital admission in the past 12 months 2.9 ( 1.8 to 4.8 ) ; not possessing a written asthma action plan 2.2 ( 1.1 to 5.6 ) ; less dislike of asthma medications 0.7 ( 0.5 to 0.9 ) . CONCLUSIONS In addition to factors relating to severity , not possessing a written asthma action plan , avoidance coping , and attitudes to self-management were related to acute use of health services in this at risk group . Interventions need to address or take these factors into account to reduce asthma morbidity The aim of this study was to evaluate the impact of a new patient education programme on adults with asthma . This self-management programme included an individual assessment of patient 's needs and two educational group sessions . Teaching methods and session content are described as well as caregivers training programme . The training sessions included a written asthma action plan based on symptoms and personal peak expiratory flow . Patients ( n = 238 ) aged from 18 to 60 years were allocated to the intervention ( group A ) or control group ( group B ) . Patients filled during 1 year a daily diary and question naire and they were administered telephone interviews . 127 patients were included in the treatment program and 111 in the control group . There was a significant improvement in the educated group with regard to symptoms free days ( P = 0.03 ) , number of awakenings ( P = 0.04 ) , consumption of corticosteroids ( P = 0.03 ) , consumption of beta2-agonists ( P = 0.03 ) , and quality of life score ( P = 0.01 ) . In conclusion , this study vali date s a specific educational approach named " un souffle nouveau " We compared the effectiveness of personalized asthma self-management recommendations with that of a group self-management program . We assigned each of 34 asthma patients r and omly to one of three conditions : individualized asthma self-management , group asthma self-management , and control . We derived individualized self-management recommendations from patient recordings of asthma occurrence , asthma precipitants , and peak expiratory flow rate made during a 3-month period . The group program we used was the Wheezers Anonymous program . As compared to a control group of patients who received no self-management training , the patients in both the individualized and group condition evidence d improvement of pulmonary function , as measured daily with a home peak flow meter . The improvement was equivalent for patients in the two conditions . Patients in the individualized condition also exhibited a drop in frequency of asthma attacks , but patients in the group condition did not . We concluded that individualized asthma self-management is effective in reducing symptoms of asthma BACKGROUND Self-management plans may help patients with asthma intervene when symptoms deteriorate , thus preventing asthma attacks . AIM A study set out to test whether a self-management plan tailored to the circumstances of the individual reduces morbidity from asthma . METHOD General practitioners who had participated in a national audit of asthma attacks were r and omized into intervention and control groups . Six months after the intervention group had issued self-management plans to patients with asthma , both groups of practitioners completed morbidity question naires on patients . Morbidity outcomes were compared for the 6-month periods before and after the issue of the plans . RESULTS In the 6 months before the study , the 376 patients enrolled by the intervention group experienced higher levels of morbidity than the 530 patients for whom details were recorded by the control group . In the 6 months after the issue of the plans , control group patients showed little change in levels of morbidity , but intervention group patients showed significant reductions in hospital admissions , consultations for asthma symptoms , asthma review consultations , courses of oral steroids and use of emergency nebulized bronchodilators . CONCLUSION General practitioners appeared to operate enthusiast bias ' and issued more self-management plans to patients with uncontrolled asthma . The reduction in morbidity in this group is probably a result of the use of the plans , but the verdict on whether plans reduce morbidity must be deemed ' not proven ' OBJECTIVE --To compare a peak flow self management plan for asthma with a symptoms only plan . DESIGN --R and omisation to one of the self management plans and follow up for a year . SETTING --Four partner , rural training practice in Norfolk . SUBJECTS--115 Patients ( 46 children and 69 adults ) with asthma who were having prophylactic treatment for asthma and attending a nurse run asthma clinic . MAIN OUTCOME MEASURES --The number of doctor consultations , courses of oral steroids , and short term nebulised salbutamol treatments and the number of patients who required doctor consultations , courses of oral steroids , and short term nebulised salbutamol . RESULTS --Both self management plans produced significant reductions in the outcome measures but there were no significant differences in the degree of improvement between the groups . The results were similar for children and adults . The proportions of patients requiring a doctor consultation fell from 98 % ( 50/51 ) to 66 % ( 34/51 ) in the peak flow group and from 97 % ( 62/64 ) to 53 % ( 34/64 ) in the symptoms only group and the proportions requiring oral steroids from 73 % ( 34/46 ) to 47 % ( 21/46 ) and 52 % ( 31/60 ) to 12 % ( 7/60 ) . The median number of doctor consultations was reduced from 8.0 to 2.0 in the peak flow group and from 4.5 to 1.0 in the symptoms only group . CONCLUSIONS --The peak flow meter was not the crucial ingredient in the improved illness of the two groups . Teaching patients the importance of their symptoms and the appropriate action to take when their asthma deteriorates is the key to effective management of asthma . Simply prescribing peak flow meters without a system of self management and regular review will be unlikely to improve patient care Objective To determine whether asthma specialist nurses , using a liaison model of care , reduce unscheduled care in a deprived multiethnic area . Design Cluster r and omised controlled trial . Setting 44 general practice s in two boroughs in east London . Participants 324 people aged 4 - 60 years admitted to or attending hospital or the general practitioner out of hours service with acute asthma ; 164 ( 50 % ) were South Asian patients , 108 ( 34 % ) were white patients , and 52 ( 16 % ) were from other , largely African and Afro-Caribbean , ethnicities . Intervention Patient review in a nurse led clinic and liaison with general practitioners and practice nurses comprising educational outreach , promotion of guidelines for high risk asthma , and ongoing clinical support . Control practice s received a visit promoting st and ard asthma guidelines ; control patients were checked for inhaler technique . Main outcome measures Percentage of participants receiving unscheduled care for acute asthma over one year and time to first unscheduled attendance . Results Primary outcome data were available for 319 of 324 ( 98 % ) participants . Intervention delayed time to first attendance with acute asthma ( hazard ratio 0.73 , 95 % confidence interval 0.54 to 1.00 ; median 194 days for intervention and 126 days for control ) and reduced the percentage of participants attending with acute asthma ( 58 % ( 101/174 ) v 68 % ( 99/145 ) ; odds ratio 0.62 , 0.38 to 1.01 ) . In analyses of prespecified subgroups the difference in effect on ethnic groups was not significant , but results were consistent with greater benefit for white patients than for South Asian patients or those from other ethnic groups . Conclusion Asthma specialist nurses using a liaison model of care reduced unscheduled care for asthma in a deprived multiethnic health district . Ethnic groups may not benefit equally from specialist nurse intervention INTRODUCTION Recently published national and international guidelines stress the importance of self-management in asthma . They have recommended that self-management plans should be an essential part of the long-term management of asthmatic patients . These plans essentially focus on the early recognition of unstable or deteoriorating asthma , by monitoring peak flow or symptoms . OBJECTIVE The aim of our one-year study was to compare the efficacy of peak-flow based self-management of asthma with traditional treatment . METHOD Sixty clinical ly stable adult patients with mild and moderate persistent asthma were r and omly allocated to peak-flow based self-management ( Group A , n=30 ) or to conventional treatment ( Group B , n=30 ) , with no significant difference between groups in terms of age , sex distribution and initial lung function . The recorded measurements were : lung function , asthma exacerbations , unscheduled ambulatory care facilities ( hospital-based emergency department , consultations with general practitioner or pulmonologist ) , courses of oral prednisolone , courses of antibiotics , days off work . RESULTS There was a significant difference between groups in number of asthma exacerbations ( p < 0.05 ) , unscheduled visits to ambulatory care facilities ( p < 0.005 ) , days off work ( p < 0.0001 ) , courses of oral prednisolone ( p < 0.001 ) and antibiotics ( p < 0.05 ) . At the final visit , there was a significant improvement in some measurements of asthma severity in group A ( reduced unscheduled visits for ambulatory care , reduced treatment requirements for oral corticosteroids and antibiotics , reduced days off work ) , but a lack of statistical difference in lung function and the maintenance-inhaled corticosteroid dose . There was no significant change in group B. CONCLUSION These results suggest that peak-flow based self-management is more effective than traditonal treatment in mild and moderate persistent asthma OBJECTIVES Re- analysis of a r and omized trial of an asthma education program design ed to assess the effects of the intervention on emergency department visits , limited days of activity and asthma knowledge and beliefs separately for African American and Caucasian adults with asthma . DESIGN Two hundred and forty-one respondents between the ages of 18 and 70 were evaluated in two emergency departments ( one inner city and one suburban location ) of a large , midwestern health care system and were r and omized to an intervention or control group . RESULTS Regardless of race , members of the intervention group showed a decrease in the number of post-intervention emergency department visits ( ANOVA interaction between race and group effect p value = 0.93 ) . The greatest decrease occurred during the first four post-intervention months . No differential effect of the asthma education intervention by race was found on the change in asthma knowledge and beliefs over the study period ( ANCOVA interaction between race and group effect p value = 0.60 ) . CONCLUSION This study demonstrates that post-intervention , both African American and Caucasian study participants showed a decrease in emergency department visits and an increase in asthma self-management . This finding is especially important for African Americans , who face increasing asthma mortality and morbidity BACKGROUND Guided self-management is an important component of asthma care . Most trials have evaluated paper-based strategies . The effectiveness of new communication technologies remains uncertain . OBJECTIVES To compare the feasibility and clinical outcomes of a st and ard paper-based asthma self-management strategy with web-based strategies . METHODS In a crossover trial , 21 patients using inhaled corticosteroids and long-acting B2-agonists ( mean [ SD ] age 29 [ 10 ] years ) were r and omly assigned to use a sequence of web-based and paper-based diary and action plan . Quality of life , asthma control , lung function , and airway inflammation were assessed using the Asthma Life Quality Question naire ( ALQ ) , Asthma Control Question naire ( ACQ-5 ) , Mini Asthma Quality of Life Question naire ( Mini AQLQ ) , and office spirometry . The ratio of forced expiratory volume in the first second of expiration ( FEV1 ) to peak expiratory flow ( PEF ) rate ( PiKo-1 ) and fraction of exhaled nitric oxide ( FE(NO ) ) were monitored . The main clinical outcomes were asthma control and FE(NO ) . Quality of data and adherence to monitoring tools were the main process outcomes . RESULTS Significant improvements were observed in the AQL and ACQ scores , although lung function did not change . FE(NO ) was significantly reduced only after a web-based strategy but a significant period effect occurred ( P = .006 ) . There were no differences in clinical outcomes between web-based and paper-based management . No intervention-related adverse effects were observed . Adherence seemed higher with the paper-based strategy ( P < .001 ) . However , paper data were unreliable when compared to automatic daily electronic FEV1/PEF records . Twelve patients were very interested in continuing self-management with the web-based approach compared with 2 in using paper tools ( P = .002 ) . CONCLUSIONS Web-based management was feasible , safe , and preferred by patients . Short-term outcomes were at least as good , and data quality was improved We investigated whether hospital-based specialist asthma nurses improved recognition and self-treatment of asthma episodes by patients followed up after attending accident and emergency departments ( A&E ) for asthma exacerbations . We carried out a r and omized prospect i ve controlled trial of adult asthma self-management , following a hospital outpatient nurse consultation in two outer-London District General Hospitals ( secondary care centres ) . The study included 211 adults , over 18 years old ( mean age 40 years ) who attended for asthma in two accident and emergency departments over 13 months . One hundred and eight evaluable patients were r and omized into the control group who continued with their usual medical treatment and were not offered any intervention during the study period . One hundred and three evaluable patients were r and omized into the intervention group . They were offered three 6-weekly outpatient appointments with one of two specialist asthma nurses for a structured asthma consultation , after attendance at the accident and emergency department . Following assessment of their asthma treatment and control , the nurses advised patients , through the use of self-management-plans , how to recognize and manage uncontrolled asthma and when to seek medical assistance . Medication and inhaler device type were altered if necessary The primary outcome was patient reported self-management of asthma exacerbations for 6 months . Secondary outcomes were assessed at baseline , 3 months and 6 months . These included home peak flow and symptom diaries , structured telephone question naires and audit of general practitioner records to determine utilization of services ( 6 months before and after A&E ) . Data were analysed on an intention to treat basis by multiple and logistic regression . The intervention group increased their use of inhaled topical steroids in 31/61 ( 51 % ) vs. 15/70 ( 21 % ) attacks in controls ( OR 3.91 CI 1.8 - 8.4 , P<0.001 ) and their use of rescue medication in 54/61 ( 89 % ) severe attacks vs. 53/70 ( 76 % ) controls ( OR 2.88 CI 1.1 - 7.9 , P<0.05 ) . Intervention patients had significantly higher ( mean 20.1 l min(-1 ) ; CI 0.4 - 39.7 ; P<0.05 ) and less variable PEF and significantly lower and less variable symptom scores 6 months after entry . Thirty-four percent of intervention patients vs. 42 % controls had severe attacks ( 61 and 70 respectively , OR 0.96 CI 0.7 - 1.4 ) during the 6 months . Intervention patients had fewer days off work than controls in the first 3 months ( NS ) but similar days off during the 6-month period . Intervention patients had fewer episodes away from work in the first ( 0.34 vs. 0.54 , P = 0.08 ) and the second 3 months ( 0.25 vs. 0.30 , NS ) than the controls . Over 80 % of the patients records were audited by their general practitioners ; the active group had less routine consultations with the doctor ( P = 0.03 ) and practice nurse ( P = 0.03 ) , less consultations for uncontrolled episodes ( P = 0.06 ) and less hospital visits ( NS ) than the controls . Hospital-based specialist nurses reduced asthma morbidity by improving patient self-management behaviour in acute attacks leading to reduced symptoms , improved lung function , less time off work and fewer consultations with health professionals The prevalence and impact of adult asthma are substantial , and poor self-management practice s , especially failures to adhere to treatment regimens , appear to be a significant problem . Desirable characteristics of an intervention program to improve self-management were identified through needs assessment and review of existing patient education re sources . A comprehensive program was developed that integrated a workbook with one-to-one counseling and adherence-enhancing strategies . A longitudinal 1-year study compared patients receiving this self-management program with " usual care " patients receiving st and ard asthma pamphlets . Patients were r and omly assigned to conditions . Baseline score and asthma severity were statistically controlled . Self-management patients had substantially better adherence than usual care patients , as well as improved functional status , at follow-up . Hospital and emergency department visits decreased in both groups but did not differ between groups Objective . We examined the impact of a combination of home environmental interventions and nurse case management services on total settled dust loadings and on allergen concentrations in the homes of asthmatic children . Methods . Using a r and omized longitudinal controlled trial study design , we r and omly assigned homes of asthmatic children in Milwaukee to either a control ( n=64 ) or an intervention ( n=57 ) group . Control group homes received a visual assessment , education , bed/pillow dust mite encasings , and treatment of lead-based paint hazards . The intervention group received these same services plus nurse case management that included tailored , individual asthma action plans , provision of minor home repairs , home cleaning using special vacuuming and wet washing , and integrated pest management . Dust vacuum sample s were collected from measured surface areas of floors in the TV room , kitchen , and child 's bedroom at baseline and at three- , six- , and 12-month follow-up visits . Dust loading ( mass per surface area ) is a means of measuring total dust and the total amount of allergen present . Results . For the intervention group , geometric mean dust loadings declined significantly from baseline ( 39 milligrams per square foot [ mg/ft2 ] ) to post-intervention ( 11 mg/ft2 ) ( p<0.001 ) . Baseline dust loading , treatment group , visit , and season were significant predictors of follow-up dust loadings . Mean post-intervention dust loadings were 72 % higher in the control group . The total amount of allergen in settled house dust declined significantly following the intervention because total dust loading declined ; the concentration of allergens in settled dust did not change significantly . Conclusion . The combination of nurse case management and home environmental interventions promotes collaboration between health and housing professionals and is effective in reducing exposures to allergens in settled dust In this r and omized controlled economic evaluation we compared guided asthma self-management with usual asthma care according to guidelines for Dutch family physicians . Nineteen family practice s were r and omized , and 193 adults with stable asthma ( 98 self-management , 95 usual care ) were included and monitored for 2 years . We hypothesized that introducing self-management would not compromise asthma control and cost would be equal to or lower than in usual care . Patient-specific cost data were collected , preference-based utilities were assessed , and incremental cost per quality -adjusted life year ( QALY ) and successfully treated week gained was calculated . Self-management patients gained 0.039 QALY ( 95 % confidence interval [ CI ] , 0.003 to 0.075 ) and experienced 81 ( 95 % CI , 78 to 84 ) successfully treated weeks in 2 years ' time ; the corresponding figures for usual care were 0.024 ( 95 % CI , -0.022 to 0.071 ) and 75 ( 95 % CI , 72 to 78 ) . Total costs were 1,084 euros(95 % CI , 938 to 1,228 ) for self-management and 1,097 euros ( 95 % CI , 933 to 1,260 ) for usual care . Self-management patients consumed 1,680 ( 95 % CI , 1,538 to 1,822 ) puffs of budesonide , usual care patients 1,897 ( 95 % CI , 1,679 to 2,115 ) . Mean productivity cost due to limited activity days was 213 euros lower among self-management patients . When all costs were included , self-management was cost-effective on all outcomes . The probability that self-management was cost-effective relative to usual care in terms of QALYs was 52 % . We conclude that guided self-management is a safe and efficient alternative approach compared with asthma treatment usually provided in Dutch primary care Abstract Objective : To compare the efficacy of self management of asthma with traditional treatment . Design : 12 month prospect i ve r and omised trial . Setting : Outpatient clinics in Finl and . Subjects : 115 patients with mild to moderately severe asthma . Interventions : Patient education and adjustment of anti-inflammatory therapy guided by peak flow measurements . Main outcome measures : Unscheduled admissions to hospital and outpatient visits , days off work , courses of antibiotics and prednisolone , lung function , and quality of life . Results : The mean number of unscheduled visits to ambulatory care facilities ( 0.5 v 1.0 ) , days off work ( 2.8 v 4.8 ) , and courses of antibiotics ( 0.4 v 0.9 ) and prednisolone ( 0.4 v 1.0 ) per patient were lower and the quality of life score ( 16.6 v 8.4 at 12 months ) higher in the self management group than in the traditionally treated group . In both groups admissions for asthma were rare . Conclusions : Self management reduces incidents caused by asthma and improves quality of life . Key messages Key messages This trial of 115 patients with mild to moderately severe disease r and omised half to a traditional care and half to a self management programme consisting of education about asthma and daily peak flow readings Intervention thresholds of < 85 % of the optimal peak flow for doubling the dose of inhaled steroid for two weeks and of < 70 % of the optimal peak flow for starting a course of oral steroids worked well The self management group had fewer incidents ( consultations , days off work , courses of prednisolone or antibiotics ) than the traditionally treated group and better quality of life scores Adherence of patients to the self management instructions was better than To determine if a comprehensive long-term management program , emphasizing inhaled corticosteroids and patient education , would improve outcomes in adult African-American asthmatics a nonr and omized control trial with a 2-year intervention was performed in a university-based clinic . Inclusion criteria consisted of ( > or = 5 ) emergency department ( ED ) visits or hospitalizations ( > or = 2 ) during the previous 2 years . Intervention patients were volunteers ; a comparable control group was identified via chart review at hospitals within the same area and time period as the intervention patients . Individualized doses of beclomethasone with a spacer , inhaled albuterol " as needed , " and crisis prednisone were the primary therapies . Environmental control , peak flow monitoring , and a partnership with the patient were emphasized . Detailed patient education was an integral part of management . Control patients received usual care from local physicians . ED visits and hospitalizations for 2 years before and 2 years during the intervention period were compared . Quality of life ( QOL ) measurements were made at baseline and every 6 months in the intervention group . Study group ( n = 21 ) had a significant reduction in ED visits ( 2.3 + /- 0.2 pre-intervention versus 0.6 + /- 0.2 post-intervention ; P = 0.0001 ) . Control group ( n = 18 ) did not have a significant change in ED visits during the 2-year post-intervention period ( 2.6 + /- 0.2 pre-intervention versus 2.0 + /- 0.2 post-intervention ; P = 0.11 ) . Both groups had significant reductions in hospitalizations , but the study group had a greater reduction . Sixty-two percent of study patients had complete elimination of ED visits and hospitalizations , whereas no control patients had total elimination of the need for institutional acute care . QOL in the study patients revealed significant improvements for most parameters . A comprehensive long-term management program emphasizing inhaled corticosteroids combined with other state-of-the-art management , including intensive patient education , improves outcomes in adult African-American asthmatics 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 We examined an effectiveness of a new asthma telemedicine system in reducing hospitalizations using a multi-site r and omized control study . In this program , a nurse under physician supervision monitors the patient 's airway status at home and provides instructions to individuals via the telephone , helping them manage exacerbations as well as reinforcing proper use of a zone-controlled management plan . Patients with a high risk for hospitalization were screened based on the numbers of emergency room visits and hospitalizations found in a previous study and r and omly assigned to either the telemedicine or control group . After a six-month study period , an 83 % reduction in hospitalization was demonstrated in the telemedicine group versus the control group , with a P value of 0.01 . Improvement of peak expiratory flow and symptoms were also shown in the study group . We conclude that the key success factors in home asthma management for poorly controlled asthma patients are early detection of exacerbations through daily peak flow monitoring , compliance with prescribed daily prophylactic anti-inflammatory steroid medications , and immediate action as specified by a zone-controlled action plan upon the first signs of deterioration BACKGROUND Adherence to inhaled anti-inflammatory therapy and self-management skills are essential parts of the asthma treatment plan to improve asthma control and prevent exacerbations . Whether self-management education improves long-term medication adherence is less clear . OBJECTIVE A 24-week prospect i ve , r and omized controlled trial was performed to study the effect of self-management education on long-term adherence to inhaled corticosteroid ( ICS ) therapy and markers of asthma control . METHODS After stabilization on ICS medication during a run-in phase , 95 adults with moderate-to-severe asthma were recruited from a large metropolitan community , and 84 were r and omized to individualized self-management education , including self-monitoring of symptoms and peak flow or usual care with self-monitoring alone . The key components of the 30-minute intervention were asthma information , assessment , and correction of inhaler technique ; an individualized action plan based on self-monitoring data ; and environmental control strategies for relevant allergen and irritant exposures . The intervention was personalized based on pulmonary function , allergen skin test reactivity , and inhaler technique and reinforced at 2-week intervals . RESULTS Participants r and omized to the self-management intervention maintained consistently higher ICS adherence levels and showed a 9-fold greater odds of more than 60 % adherence to the prescribed dose compared with control subjects at the end of the intervention ( P = .02 ) and maintained a 3-fold greater odds of higher than 60 % adherence at the end of the study . Perceived control of asthma improved ( P = .006 ) , nighttime awakenings decreased ( P = .03 ) , and inhaled beta-agonist use decreased ( P = .01 ) in intervention participants compared with control subjects . CONCLUSION Our results show that individualized asthma self-management education attenuates the usual decrease in medication adherence and improves clinical markers of asthma control Asthma , a chronic inflammatory condition of the airways , is a major health problem in the United States , affecting about 12 million people ( Bailey et al. , 1992 ; British Thoracic Society , 1990 ; Huss et al. , 1992 ) . People with asthma experience on average more than 100 days of restricted activity annually ( Bailey et al. , 1992 ) . Mortality and morbidity due to asthma are increasing , particularly among African Americans ( Buist & Vollmer , 1990 ; Wilson , 1993 ) . The costs for treating asthma in African Americans are exceptionally high because members of this population tend to use the emergency department as a primary source of care ( Baker , Stevens , & Brooks , 1994 ; Kellerman , 1994 ) . It is important that African Americans learn , through asthma self-management programs , what they need to manage their asthma and how to meet these needs through the health care system and increase their access to health services . As African Americans with asthma increase their access to and use of primary care and their use of inhaled corticosteroids as appropriate , they will better manage their asthma , thus maintaining their activity levels and reducing asthma-related mortality and morbidity and emergency department use ( Bauman et al. , 1989 ; Clark & Starr-Schneidkraut , 1994 ; Sly , Cahill , Willet , & Burton , 1994 ) . ASTHMA SELF-MANAGEMENT Two central components of most asthma education programs are asthma attack prevention and attack management ( Clark & Starr-Schneidkraut , 1994 ) . Asthma education and skills training in self-management help individuals draw from a base of asthma knowledge and make appropriate decisions and take corrective actions ( Bauman et al. , 1989 ; Clark & Starr-Schneidkraut , 1994 ) . The knowledge gained by participants in educational programs , such as accurate use of peak flow meters and asthma inhalers , may positively affect their perceptions of asthma ; these perceptions have been found to play a major role in how well patients adhere to medical treatment regimens ( Acker , 1992 ; Taytard , 1992 ) . As individuals become more proficient at managing their asthma and are able to function better in their daily lives , their asthma-related quality of life should improve ( Juniper , Guyatt , Ferrie , & Griffith , 1993 ; Rowe & Oxman , 1993 ) . Research ers agree that for behavioral changes to be long lasting , they must become sufficiently integrated into aspects of individuals ' daily lives ( Bauman et al. , 1989 ; Bolton , Tilley , Kuder , Reeves , & Schultz , 1991 ) . Empowerment Principles To help individuals integrate asthma management into their daily lives , asthma self-management courses must teach principles of empowerment . Empowerment refers to the development of the personal re sources ( social , psychological , intellectual , and spiritual ) individuals need to give them control and mastery over their lives ( Feste , 1992 ; Kalyanpur & Rao , 1991 ) . Developing these personal re sources is especially critical for African Americans with asthma , a disease in which much of the burden of day-to-day management and recognition of symptoms rests with the individual . In addition , African Americans have traditionally held a disempowered political , economic , and social position in U.S. society and have thus been prevented from exercising control and mastery over their environments ( McKinney , Harel , & Williams , 1990 ; Thomas & Quinn , 1991 ) . Empowerment-centered asthma education can help African Americans with asthma better manage this chronic condition . Church Setting Asthma education programs can be offered in the local church , a context central to many African Americans . Taylor and Chatters ( 1986 ) described the African American church as functioning as an " omnipresent and important institution " ( p. 637 ) for African Americans of all ages . Historically , churches have provided for the educational , nutritional , psychological , and employment needs of African Americans and been focal points for community activities ( Taylor , Thornton , & Chatters , 1987 ; Walls & Zarit , 1991 ) . This study investigated the effectiveness of different educational programs in obtaining better asthma control and asthma-related quality of life ( QoL ) . In 60 adult patients with moderate persistent asthma we tested the benefit of individual verbal instructions ( IVI ) , written information ( " asthma booklet " , B ) , and integrated asthma classes ( " asthma school " , AS ) . At the enrollment and at the end of the study , all participants completed the question naires regarding their asthma-related knowledge ( ArK ) and QoL. During the 12-week period all patients recorded their asthma symptoms , morning and evening peek expiratory flow rates ( PEFR ) , and the use of rescue medication . AS and IVI groups showed a significantly greater improvement in QoL than the B group . AS group obtained the highest ArK but no difference in the level of improvement among the groups has been documented . The improved average asthma symptom score and decreased utilization of the rescue medication were documented in all groups without significant differences among them . We also found significant improvements in both morning and evening PEFR in IVI group as well as in the morning PEFR in AS group . We conclude that among tested educational interventions the AS caused the best improvement in QoL while IVI produced the best overall response in both parameters of the asthma control and An individualised asthma programme directed at behavioural change was evaluated in asthmatic subjects who reported complaints and impairment , despite adequate medical treatment . Mild-to-moderate asthma patients ( n=23 ) were r and omly assigned to a programme or waiting list condition . Outcome measures were : McMaster Asthma Quality of Life Question naire , Asthma Symptom Checklist , Negative Emotionality Scale , Knowledge , Attitude and Self-Efficacy Asthma Question naire , Adherence Scale , and peak flow measurements . Both groups were evaluated at three consecutive moments , each separated by 3 months ; the programme was delivered between the first two evaluations . At onset the patient received a workbook containing information , exercises and homework assignments . Psycho-education , behavioural and cognitive techniques were introduced during six 1‐h individual sessions . Compared with controls the programme group reported less symptoms ( obstruction , fatigue ) , better quality of life ( activity , symptoms , emotions ) , decreased negative affectivity , and increased adherence , immediately after finishing the programme and at 3 months follow-up . All three cognitive variables ( knowledge , attitude towards asthma , self-efficacy ) and day and night peak flow ratings improved in the programme group but not in the waiting list group . Participation in an individualised programme result ed in improvement of asthma morbidity , and asthma-related behaviour and cognitions , in subjects reporting symptoms and impairment despite adequate medical therapy RATIONALE Asthma clinical guidelines suggest written asthma action plans are essential for improving self-management and outcomes . OBJECTIVES To assess the efficacy of written instructions in the form of a written asthma action plan provided by subspecialist physicians as part of usual asthma care during office visits . METHODS A total of 407 children and adults with persistent asthma receiving first-time care in pulmonary and allergy practice s at 4 urban medical centers were r and omized to receive either written instructions ( n = 204 ) or no written instructions other than prescriptions ( n = 203 ) from physicians . MEASUREMENTS AND MAIN RESULTS Using written asthma action plan forms as a vehicle for providing self-management instructions did not have a significant effect on any of the primary outcomes : ( 1 ) asthma symptom frequency , ( 2 ) emergency visits , or ( 3 ) asthma quality of life from baseline to 12-month follow-up . Both groups showed similar and significant reductions in asthma symptom frequency ( daytime symptoms [ P < 0.0001 ] , nocturnal symptoms [ P < 0.0001 ] , β-agonist use [ P < 0.0001 ] ) . There was also a significant reduction in emergency visits for the intervention ( P < 0.0001 ) and control ( P < 0.0006 ) groups . There was significant improvement in asthma quality -of-life scores for adults ( P < 0.0001 ) and pediatric caregivers ( P < 0.0001 ) . CONCLUSIONS Our results suggest that using a written asthma action plan form as a vehicle for providing asthma management instructions to patients with persistent asthma who are receiving subspecialty care for the first time confers no added benefit beyond subspecialty-based medical care and education for asthma . Clinical trial registered with www . clinical trials.gov ( NCT 00149461 ) Aims To evaluate postal prompts to increase patients ' underst and ing and use of self-management plans ( SMP ) . Methods A single-blinded r and omised controlled trial in 545 adults with asthma prescribed an inhaled corticosteroid . The control group were mailed an invitation for a medical review . The second and third groups were mailed invitations with a blank or a personalised written action plan respectively . Outcomes were whether patients had a review , felt they knew how to use SMP , and the self reported ' Royal College of Physicians three questions ' score of current morbidity ( ' RCP score ' ) . Results Compared to the control group , prompts with a personalised written action plan result ed in more patients having a review of their care ( odds ratio 2.33 , 95 % CI 1.37 to 3.93 ) and underst and ing how to use their SMP ( odds ratio 2.20 , 95 % CI 1.13 to 4.30 ) . Prompts with a blank written action plan result ed in more review s ( odds ratio 1.92 , 95 % CI 1.18 to 3.11 ) but no difference in underst and ing how to use their SMP ( odds ratio 1.28 95 % CI 0.66 to 2.45 ) . Review s carried out : 70 % vs 82 % vs 84 % for groups 1 , 2 and 3 respectively ; underst and ing how to use a SMP : 40 % vs 46 % vs 59 % for groups 1 , 2 and 3 respectively . There was no difference in reported ' RCP scores ' between the three groups . Conclusions Personalised prompts increased frequency of review and patients underst and ing of SMPs but SMPs remain underused CONTEXT No consensus exists for adjusting inhaled corticosteroid therapy in patients with asthma . Approaches include adjustment at outpatient visits guided by physician assessment of asthma control ( symptoms , rescue therapy , pulmonary function ) , based on exhaled nitric oxide , or on a day-to-day basis guided by symptoms . OBJECTIVE To determine if adjustment of inhaled corticosteroid therapy based on exhaled nitric oxide or day-to-day symptoms is superior to guideline -informed , physician assessment -based adjustment in preventing treatment failure in adults with mild to moderate asthma . DESIGN , SETTING , AND PARTICIPANTS A r and omized , parallel , 3-group , placebo-controlled , multiply-blinded trial of 342 adults with mild to moderate asthma controlled by low-dose inhaled corticosteroid therapy ( n = 114 assigned to physician assessment -based adjustment [ 101 completed ] , n = 115 to biomarker-based [ exhaled nitric oxide ] adjustment [ 92 completed ] , and n = 113 to symptom-based adjustment [ 97 completed ] ) , the Best Adjustment Strategy for Asthma in the Long Term ( BASALT ) trial was conducted by the Asthma Clinical Research Network at 10 academic medical centers in the United States for 9 months between June 2007 and July 2010 . INTERVENTIONS For physician assessment -based adjustment and biomarker-based ( exhaled nitric oxide ) adjustment , the dose of inhaled corticosteroids was adjusted every 6 weeks ; for symptom-based adjustment , inhaled corticosteroids were taken with each albuterol rescue use . MAIN OUTCOME MEASURE The primary outcome was time to treatment failure . RESULTS There were no significant differences in time to treatment failure . The 9-month Kaplan-Meier failure rates were 22 % ( 97.5 % CI , 14%-33 % ; 24 events ) for physician assessment -based adjustment , 20 % ( 97.5 % CI , 13%-30 % ; 21 events ) for biomarker-based adjustment , and 15 % ( 97.5 % CI , 9%-25 % ; 16 events ) for symptom-based adjustment . The hazard ratio for physician assessment -based adjustment vs biomarker-based adjustment was 1.2 ( 97.5 % CI , 0.6 - 2.3 ) . The hazard ratio for physician assessment -based adjustment vs symptom-based adjustment was 1.6 ( 97.5 % CI , 0.8 - 3.3 ) . CONCLUSION Among adults with mild to moderate persistent asthma controlled with low-dose inhaled corticosteroid therapy , the use of either biomarker-based or symptom-based adjustment of inhaled corticosteroids was not superior to physician assessment -based adjustment of inhaled corticosteroids in time to treatment failure . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00495157 Information for patients provided by the pharmacist is reflected in adhesion to treatment , clinical results and patient quality of life . The objective of this study was to assess an asthma self-management model for rational medicine use . This was a r and omized controlled trial with 60 asthmatic patients assigned to attend five modules presented by a pharmacist ( intervention group ) and 59 patients in the control group . Data collection was performed before and after this 4-month intervention and included an evaluation of asthma knowledge , lifestyle , inhaler techniques , adhesion to treatment , pulmonary function and quality of life . An economic viability analysis was also performed . The intervention group obtained an increase in asthma knowledge scores of 58.3 - 79.5 % ( P < 0.001 ) . In this group , there was also an increase in the number of individuals who practice d physical exercise ( 36 - 43 % ) , in the number of correct replies regarding the use of inhalers , in the percentage of adherent patients , and in quality of life scores for all domains . We concluded that this asthma self-management model was effective in improving the quality of life of asthma patients BACKGROUND The provision of written asthma action plans ( WAAPs ) is regarded by regional and international guidelines as an essential component of patient education and self-management . However , the evidence for this practice in children is deficient . AIM To evaluate the effectiveness of adding a personalized WAAP in the treatment of children with partly controlled asthma . METHODS Children with partly controlled asthma were r and omized to receive a personalized WAAP or no plan , in addition to st and ard care including education . They were followed up with serial measurement of outcome variables . The primary outcome measured was the number of emergency room ( ER ) revisits . RESULTS Ninety-one children participated , 45 in the intervention group and 46 in the control group . Comparison with pretrial data revealed significantly improved outcomes with respect to the numbers of ER visits ( p = 0.005 and 0.0002 ) and acute asthmatic attacks ( p = 0.0064 and 0.0006 ) in both arms of the study . Children in receipt of a personalized WAAP had fewer ER visits ( p = 0.78 ) , asthma attacks ( p = 0.84 ) , missed school days ( p = 0.28 ) , night-time awakenings ( p = 0.48 ) and unscheduled doctor visits ( p = 0.69 ) than those who did not receive a plan . CONCLUSION The results of this study suggest that the provision of personalized WAAPs may play a useful role in the management of children with partly controlled asthma but is no better than st and ard care . Asthma education is a critical component in the prevention of exacerbations in children with partly controlled asthma Background Supporting self-management is a core response of health care systems globally to the increasing prevalence of long-term conditions . Lack of a comprehensive taxonomy ( or classification ) of self-management support components hinders characterization and , ultimately , underst and ing of these frequently complex , multi-component interventions . Objective To develop a comprehensive , descriptive taxonomy of self-management support components . Methods Components were derived from the 969 unique r and omized controlled trials described in the 102 systematic review s and 61 implementation trials , examining 14 diverse long-term conditions included in the Practical Review s in Self-Management Support ( PRISMS ) project followed by discussion at an expert stakeholder workshop . The utility of the taxonomy was then tested using a self-management support intervention for cancer survivors . Results The PRISMS taxonomy comprises 14 components that might be used to support self-management ( e.g. information about condition/management , provision of equipment , social support ) , when delivered to someone with a long-term condition or their carer . Overarching dimensions are delivery mode ; personnel delivering the support ; intervention targeting ; and intensity , frequency and duration of the intervention . The taxonomy does not consider the effectiveness or otherwise of the different components or the overarching dimensions . Conclusions The PRISMS taxonomy offers a framework to research ers describing self-management support interventions , to review ers synthesizing evidence and to developers of health services for people with long-term conditions |
12,224 | 22,020,617 | Such pain vulnerability because of stress system function may interact with the effects of biomechanical injury and psychobehavioral responses to influence the development of WAD . | OBJECTIVE To present several lines of evidence supporting the hypothesis that physiologic stress systems contribute to WAD pathogenesis .
SUMMARY OF BACKGROUND DATA In addition to subjecting soft tissue to biomechanical strain , a motor vehicle collision ( MVC ) event is also an acute stressor which activates physiologic stress systems .
Increasing data from animal and human studies suggest that the activation of these stress systems may contribute to long-lasting changes in pain sensitivity after tissue injury . | Hypersensitivity to a variety of sensory stimuli is a feature of persistent whiplash associated disorders ( WAD ) . However , little is known about sensory disturbances from the time of injury until transition to either recovery or symptom persistence . Quantitative sensory testing ( pressure and thermal pain thresholds , the brachial plexus provocation test ) , the sympathetic vasoconstrictor reflex and psychological distress ( GHQ‐28 ) were prospect ively measured in 76 whiplash subjects within 1 month of injury and then 2 , 3 and 6 months post‐injury . Subjects were classified at 6 months post‐injury using scores on the Neck Disability Index : recovered ( < 8 ) , mild pain and disability ( 10–28 ) or moderate/severe pain and disability ( > 30 ) . Sensory and sympathetic nervous system tests were also measured in 20 control subjects . All whiplash groups demonstrated local mechanical hyperalgesia in the cervical spine at 1 month post‐injury . This hyperalgesia persisted in those with moderate/severe symptoms at 6 months but resolved by 2 months in those who had recovered or reported persistent mild symptoms . Only those with persistent moderate/severe symptoms at 6 months demonstrated generalised hypersensitivity to all sensory tests . These changes occurred within 1 month of injury and remained unchanged throughout the study period . Whilst no significant group differences were evident for the sympathetic vasoconstrictor response , the moderate/severe group showed a tendency for diminished sympathetic reactivity . GHQ‐28 scores of the moderate/severe group were higher than those of the other two groups . The differences in GHQ‐28 did not impact on any of the sensory measures . These findings suggest that those with persistent moderate/severe symptoms at 6 months display , soon after injury , generalised hypersensitivity suggestive of changes in central pain processing mechanisms . This phenomenon did not occur in those who recover or those with persistent mild symptoms A novel therapy for rheumatoid arthritis , regional sympathetic blockade using guanethidine , was investigated in 24 patients with active disease . In a r and omized double blind short-term ( 14 days ) study , we evaluated the effect of therapy on subjective responses , change in pain , stiffness , and morning stiffness and no objective responses , change in pinch strength , grip strength , and joint tenderness . Compared to placebo , guanethidine produced a decrease in pain ( p less than 0.025 ) and an increase in pinch strength ( less than 0.025 ) over the 2-week duration of the study . The therapeutic effect of guanethidine may be mediated by an interruption of the proinflammatory effects of the sympathetic nervous system OBJECTIVE An earlier pilot study suggested that the late whiplash syndrome is uncommon in Greece . The purpose of the present study is to extend the evaluation to a larger sample , and include the prevalence of specific symptoms in the evaluation . METHODS In a prospect i ve , cohort study , a total of 180 accident victims were consecutively recruited following Emergency ward presentation . A st and ard question naire asked about neck pain , headache , shoulder pain , limb numbness or pain , and dizziness . Accident victims were followed for 6 months . RESULTS In the initial 4 weeks after the accident , accident victims reported neck pain , headache , shoulder pain , arm numbness or pain , and dizziness , but at 4 weeks more than 90 % had recovered from these , the remainder of the subjects having minor symptoms ( not requiring therapy ) , and returning to their pre-accident state of health ( which included minor symptoms ) . There were no cases of chronic disability . CONCLUSION In Greece , symptoms after an acute whiplash injury are self-limiting , brief , and do not appear to evolve into the so-called late whiplash syndrome Objectives To determine if genetic variation in genes in the hypothalamic – pituitary – adrenal ( HPA ) axis , the primary stress response system , influences susceptibility to developing musculoskeletal pain . Methods Pain and comorbidity data was collected at three time points in a prospect i ve population -based cohort study . Pairwise tagging single nucleotide polymorphisms ( SNPs ) were selected and genotyped for seven genes . Genetic association analysis was carried out using zero-inflated negative binomial regression to test for association between SNPs and the maximum number of pain sites across the three time points in participants reporting pain , reported as proportional changes with 95 % CIs . SNPs were also tested for association with chronic widespread pain ( CWP ) using logistic regression reporting odds ratios and 95 % CI . Results A total of 75 SNPs were successfully genotyped in 994 participants including 164 cases with persistent CWP and 172 pain-free controls . Multiple SNPs in SERPINA6 were associated with the maximum number of pain sites ; for example , each copy of the T allele of rs941601 was associated with having 16 % ( proportional change=1.16 , 95 % CI 1.04 to 1.28 , p=0.006 ) more pain sites compared to participants with the CC genotype . SERPINA6 gene SNPs were also associated with CWP . Significant associations between the maximum number of pain sites and SNPs in the CRHBP and POMC genes were also observed and a SNP in MC2R was also associated with CWP . Associations between SNPs and comorbidity of poor sleep quality and depression explained some of the associations observed . Conclusions Genetic variation in HPA axis genes was associated with musculoskeletal pain ; however , some of the associations were explained by comorbidities . Replication of these findings is required in independent cohorts & NA ; Patients with postoperative ongoing sciatic pain have been shown to exhibit reduced cortisol levels along with enhanced IL‐6 levels . The aim of the present study was to clarify the relationship between a reduced cortisol secretion and enhanced cytokine levels by performing a prospect i ve study on patients with disc herniation . Twenty‐two patients were examined before and after their disc surgery . Twelve healthy , pain‐free subjects matched for age , education and gender constituted the control group . The preoperative examinations included the assessment of the diurnal pattern of cortisol secretion and the feedback sensitivity of the hypothalamus – pituitary – adrenal ( HPA ) axis . Patients ' subjective stress levels also were assessed during the preoperative examination . The diurnal pattern of cortisol secretion was again assessed during the postoperative examination . Furthermore , blood sample s were collected to measure catecholamine , adrenocorticotropic hormone (ACTH)‐ and interleukin‐6 ( IL‐6 ) levels before and after measuring the pressure pain thresholds ( PPTs ) . An assessment of the sensitivity of circulating monocytes to the immunosuppressive effects of glucocorticoids was further included in the postoperative examinations . Failed back syndrome ( FBS ) patients ( n=12 ) showed a reduced cortisol secretion in the morning hours and enhanced feedback sensitivity of the HPA axis . Furthermore , FBS patients displayed an increased in‐vitro production of proinflammatory cytokines and a relative glucocorticoid resistance of pro‐inflammatory cytokine producing monocytes as compared to non‐FBS patients ( n=10 ) and controls . After PPT measurement FBS patients exhibited an increased norepinephrine but decreased epinephrine response , together with lower ACTH levels and a four times higher plasma IL‐6 response . These findings suggest that chronically stressed patients are at a higher risk for a poor surgical outcome as their reduced cortisol secretion promotes the postoperative ongoing synthesis of proinflammatory cytokines Study Design . An experimental study of motor and sensory function and psychological distress in subjects with acute whiplash injury . Objectives . To characterize acute whiplash injury in terms of motor and sensory systems dysfunction and psychological distress and to compare subjects with higher and lesser levels of pain and disability . Summary of Background Data . Motor system dysfunction , sensory hypersensitivity , and psychological distress are present in chronic whiplash associated disorders ( WAD ) , but little is known of such factors in the acute stage of injury . As higher levels of pain and disability in acute WAD are accepted as signs of poor outcome , further characterization of this group from those with lesser symptoms is important . Material s and Methods . Motor function ( cervical range of movement [ ROM ] , joint position error [ JPE ] ; activity of the superficial neck flexors [ EMG ] during a test of cranio-cervical flexion ) , quantitative sensory testing ( pressure , thermal pain thresholds , and responses to the brachial plexus provocation test ) , and psychological distress ( GHQ-28 , TAMPA , IES ) were measured in 80 whiplash subjects ( WAD II or III ) within 1 month of injury , as were 20 control subjects . Results . Three subgroups were identified in the cohort using cluster analysis based on the Neck Disability Index : those with mild , moderate , or severe pain and disability . All whiplash groups demonstrated decreased ROM and increased EMG compared with the controls ( all P < 0.01 ) . Only the moderate and severe groups demonstrated greater JPE and generalized hypersensitivity to all sensory tests ( all P < 0.01 ) . The three whiplash subgroups demonstrated evidence of psychological distress , although this was greater in the moderate and severe groups . Measures of psychological distress did not impact on between group differences in motor or sensory tests . Conclusions . Acute whiplash subjects with higher levels of pain and disability were distinguished by sensory hypersensitivity to a variety of stimuli , suggestive of central nervous system sensitization occurring soon after injury . These responses occurred independently of psychological distress . These findings may be important for the differential diagnosis of acute whiplash injury and could be one reason why those with higher initial pain and disability demonstrate a poorer outcome BACKGROUND Perioperative myocardial ischemia is the single most important potentially reversible risk factor for mortality and cardiovascular complications after noncardiac surgery . Although more than 1 million patients have such complications annually , there is no effective preventive therapy . METHODS We performed a r and omized , double-blind , placebo-controlled trial to compare the effect of atenolol with that of a placebo on overall survival and cardiovascular morbidity in patients with or at risk for coronary artery disease who were undergoing noncardiac surgery . Atenolol was given intravenously before and immediately after surgery and orally thereafter for the duration of hospitalization . Patients were followed over the subsequent two years . RESULTS A total of 200 patients were enrolled . Ninety-nine were assigned to the atenolol group , and 101 to the placebo group . One hundred ninety-four patients survived to be discharged from the hospital , and 192 of these were followed for two years . Overall mortality after discharge from the hospital was significantly lower among the atenolol-treated patients than among those who were given placebo over the six months following hospital discharge ( 0 vs. 8 percent , P<0.001 ) , over the first year ( 3 percent vs. 14 percent , P=0.005 ) , and over two years ( 10 percent vs. 21 percent , P=0.019 ) . The principal effect was a reduction in deaths from cardiac causes during the first six to eight months . Combined cardiovascular outcomes were similarly reduced among the atenolol-treated patients ; event-free survival throughout the two-year study period was 68 percent in the placebo group and 83 percent in the atenolol group ( P=0.008 ) . CONCLUSIONS In patients who have or are at risk for coronary artery disease who must undergo noncardiac surgery , treatment with atenolol during hospitalization can reduce mortality and the incidence of cardiovascular complications for as long as two years after surgery OBJECTIVE Abnormalities of the biological stress response ( hypothalamic-pituitary-adrenal axis and the autonomic nervous system ) have been identified in both fibromyalgia ( FM ) and chronic fatigue syndrome ( CFS ) . Although these changes have been considered to be partly responsible for symptom expression , we examine an alternative hypothesis that these HPA and autonomic changes can be found in subsets of healthy individuals in the general population who may be at risk of developing these conditions . Exposure to " stressors " ( e.g. , infections , trauma , etc . ) may lead to symptom expression ( pain , fatigue , and other somatic symptoms ) in part by precipitating lifestyle changes . In particular , we focus on the effect of deprivation of routine aerobic exercise on the development of somatic symptoms . METHODS Eighteen regularly exercising ( > /=4 h/week ) asymptomatic , healthy adults refrained from physical activity for 1 week . We predicted that a subset of these individuals would develop symptoms of FM/CFS with exercise deprivation , and this manuscript focuses on the baseline HPA axis , immune , and autonomic function measures that may predict the development of symptoms . RESULTS Eight of the subjects reported a 10 % increase in one or more symptoms ( pain , fatigue , mood ) after 1 week of exercise deprivation . These symptomatic subjects had lower HPA axis ( baseline cortisol prior to VO2max testing ) , immune ( NK cell responsiveness to venipuncture ) , and autonomic function ( measured by heart rate variability ) at baseline ( prior to cessation of exercise ) when compared to the subjects who did not develop symptoms . CONCLUSIONS A subset of subjects developed symptoms of pain , fatigue , or mood changes after exercise deprivation . This cohort was different from the individuals who did not develop symptoms in baseline measures of HPA axis , immune , and autonomic function . We speculate that a subset of healthy individuals who have hypoactive function of the biological stress response systems unknowingly exercise regularly to augment the function of these systems and thus suppress symptoms . These individuals may be at risk for developing chronic multisymptom illnesses ( CMIs ) ( e.g. , FM or CFS among others ) when a " stressor " leads to lifestyle changes that disrupt regular exercise OBJECTIVE To test the hypothesis that abnormalities in the hypothalamic-pituitary-adrenal ( HPA ) stress-response system would act as an effect moderator between HPA function and the onset of chronic widespread pain ( CWP ) . METHODS We conducted a population -based prospect i ve cohort study . Current pain and psychosocial status were ascertained in 11,000 subjects . Of the 768 eligible subjects free of CWP but at future risk based on their psychosocial profile , 463 were r and omly selected , and 267 ( 57.7 % ) consented to assessment of their HPA axis function . Diurnal function was measured by assessing levels of salivary cortisol in the morning ( 9:00 AM ) and evening ( 10:00 PM ) . Serum cortisol levels were measured after an overnight low-dose ( 0.25 mg ) dexamethasone suppression test and a potentially stressful clinical examination . All subjects were followed up 15 months later to identify cases of new-onset CWP . RESULTS A total of 241 subjects ( 94.9 % ) completed the followup study , and 28 ( 11.6 % ) reported the new onset of CWP . High levels of cortisol post-dexamethasone ( odds ratio [ OR ] 3.53 , 95 % confidence interval [ 95 % CI ] 1.17 - 10.65 ) , low levels in morning saliva ( OR 1.43 , 95 % CI 0.52 - 3.94 ) , and high levels in evening saliva ( OR 2.32 , 95 % CI 0.64 - 8.42 ) were all associated with CWP . These 3 factors were found to be independent and additive predictors of CWP ( OR for all 3 factors 8.5 , 95 % CI 1.5 - 47.9 ) in analyses controlling for age , sex , depression , sleep disturbance , recent traumatic life events , and pain status . One or more of these 3 HPA factors identified 26 ( 92.9 % ) cases of new-onset CWP . CONCLUSION Among a group of psychologically at-risk subjects , dysfunction of the HPA axis helps to distinguish those who will and will not develop new-onset CWP |
12,225 | 24,853,692 | For disadvantaged new and expectant mothers , peer or collaborative delivery models could be used in interventions . | AIMS To explore which conditions of community engagement are implicated in effective interventions targeting disadvantaged pregnant women and new mothers .
BACKGROUND Adaptive experiences during pregnancy and the early years are key to reducing health inequalities in women and children worldwide .
Public health nurses , health visitors and community midwives are well placed to address such disadvantage , often using community engagement strategies .
Such interventions are complex ; however , and we need to better underst and which aspects of community engagement are aligned with effectiveness . | Breastfeeding rates among low-income women in the east-south- central United States are among the lowest in the country . This study examined the effect of a peer counseling program on breastfeeding initiation and duration in a low-income rural population in West Tennessee . A postpartum survey and chart review were conducted with WIC clients at nine health departments . Response rate was 99 % ( 291/293 ) . Breastfeeding initiation and duration at 6 weeks were increased in the peer counselor group ( n= 156 ) compared with women in the no-peer counselor group ( n= 135 ) ( 53 % vs. 33%,p<0.001 , and 26 % vs. 13%,p=0.006 , respectively ) . Multivariate analysis revealed that women in the peer counselor group were significantly more likely to initiate breastfeeding ( OR=2.43 , 95 % CI=1.23 - 4.67 ) and to be breastfeeding at 6 weeks ( OR=2.78 , 95 % CI=2.08 - 9.5 1 ) , than those in the no-peer counselor group We evaluated the single and combined effects of introducing a motivational video and peer counseling into four matched WIC clinics on breastfeeding initiation and continuation at 7 - 10 days among African-American WIC participants . Of the 242 women with complete data , 48 % initiated breastfeeding , but only 31 % were still breastfeeding at 7 - 10 days . Initiation was associated with cesarean delivery , infant feeding instruction , no artificial milk discharge pack , attending the peer counselor only-intervention site , and intention to breastfeed . Continuation was influenced by infant feeding instruction , no artificial milk discharge pack , and intention to breastfeed . Overall , trends toward a positive impact of the breastfeeding promotion activities were evident but weak , and largely gone by 7 - 10 days postpartum Objective : To evaluate the effectiveness of a lay delivered intervention to reduce Latino children ’s exposure to environmental tobacco smoke ( ETS ) . The a priori hypothesis was that children living in households that were in the intervention group would have lower exposure over time than measurement only controls . Design : A two group , r and omised control trial was conducted . Setting : Areas of San Diego county with a large Latino population . Participants : 143 Latino parent – child pairs . Intervention : Trained bicultural and bilingual Latina lay community health advisors , or promotoras , conducted problem solving aim ed at lowering the target child ’s exposure to ETS in the household . Six home and telephone sessions were delivered by the promotoras over a four month period . Main outcome measures : Outcome measures were collected at baseline , immediately post-intervention , three months post-intervention , and 12 months post-intervention . Four outcomes were considered : ( 1 ) parent ’s paper- and -pencil reports of the child ’s past month exposure ; ( 2 ) hair sample s from the child analysed for past month nicotine ; ( 3 ) hair sample s from the child analysed for past month cotinine ; and ( 4 ) per cent confirmed reducers . Results : There were no significant condition-by-time interactions , the term indicative of a differential intervention effect . Significant or near significant time main effects were seen for children ’s hair cotinine , per cent confirmed reducers , and , in particular , parent reports of exposure . Conclusions : Applying a lay promotora model to deliver the behavioural problem solving intervention unfortunately was not effective . A likely explanation relates to the difficulty of delivering a relatively complex intervention by lay women untrained in behaviour change theory and research methods OBJECTIVE To assess the effectiveness of a volunteer-driven outreach program on immunization rates in children younger than 2 years . DESIGN R and omized controlled trial . SETTING Pediatric ambulatory clinics in New York , NY . PATIENTS A total of 163 children were r and omly assigned to receive services from the volunteer-driven outreach program or to serve as control subjects . All children were ( 1 ) younger than 2 years , ( 2 ) no-shows for a scheduled appointment in the pediatric clinic , and ( 3 ) due or overdue for a vaccine . INTERVENTION Immunization outreach , tracking , and follow-up were provided by community volunteers throughout follow-up ( mean , 6.5 months ) . Control children were notified of immunization status at enrollment but received no further contact until the conclusion of follow-up ( mean , 6.4 months ) . MAIN OUTCOME MEASURE Immunization status 6 months after enrollment . RESULTS Significantly more intervention children were up-to- date with their vaccination series than controls ( 75 % vs. 54 % ; P = .03 ) . Children in the control group were 2.8 times more likely to be late for a vaccine than intervention children ( odds ratio = 2.8 ; P = .02 ) . In addition , an immunization delay of longer than 30 days at enrollment was a significant predictor of final immunization delay ( odds ratio = 2.6 ; P = .02 ) . CONCLUSIONS This volunteer-driven program significantly improved immunization rates among intervention children compared with controls . Results confirm previous findings that indicate an increased risk of an incomplete immunization series by 2 years of age among children who fall behind early in their primary vaccination series . However , control children were almost 3 times more likely to be late ( for > or = 1 vaccines ) than intervention children , regardless of whether an earlier immunization delay was present BACKGROUND The purpose of this demonstration project was to test the effectiveness of a volunteer peer counseling program for promoting breastfeeding in a community . METHODS The two-year project was conducted in Iowa from September 1994 to September 1996 . Both intervention and control groups were rural low-income pregnant and postpartum women who qualified for the Women , Infants and Children 's ( WIC ) nutritional program . The intervention was initiated in two counties with 143 clients , of whom 72 completed the project . The control group was drawn from six counties that had received no significant breastfeeding promotion programs during the previous three years . The intervention was the assignment of trained volunteers with previous successful personal experience with breastfeeding as peer counselors to low-income pregnant women . Both before and after the baby was born , the volunteers taught a series of in-home , one-to-one lessons about healthy diet and breastfeeding , and maintained informal contact to answer questions or help with concerns . RESULTS Women in the intervention group improved dietary intake when compared with the control group . Knowledge of breastfeeding and good nutrition improved slightly . Eighty-two percent of intervention compared with 31 percent of control group women initiated breastfeeding . Mean duration of breastfeeding for intervention and control group women was 5.7 and 2.5 weeks , respectively . At 4 weeks , 56 percent of intervention and 10 percent of control group women were still breastfeeding . CONCLUSION A volunteer peer counseling program that provides low-income women with role models , accurate information , support , and encouragement can increase the duration of breastfeeding , and thus contribute to healthier infants BACKGROUND Breastfeeding can ameliorate some of the complex health issues faced by low-income families . Women who breastfeed and their infants have lower health care costs compared with those who formula feed . Increasing the duration of breastfeeding is recognized as a national priority , particularly for low-income women . This community-based r and omized clinical trial involving low-income mothers compared usual care with an intervention comprising hospital and home visits , and telephone support by a community health nurse/peer counselor team for 6 months after delivery . METHODS Forty-one women were recruited after delivery of a full-term singleton infant and r and omly assigned to intervention or usual care groups . RESULTS Women receiving the community health intervention breastfed longer than the women receiving usual care . The infants in the intervention group had fewer sick visits and reported use of fewer medications than infants in the usual care group . The intervention cost ( $ 301/mother ) was partially offset by cost savings on formula and health care . CONCLUSIONS Community health nurse and peer counselor support can increase breastfeeding duration in low-income women , and has the potential to reduce total costs including the cost of support OBJECTIVE To assess the efficacy of peer counseling to promote exclusive breastfeeding ( EBF ) among low-income inner-city women in Hartford , Conn. DESIGN Participants recruited prenatally were r and omly assigned to either receive support for EBF from a peer counselor plus conventional breastfeeding support ( peer counseling group [ PC ] ) or only conventional breastfeeding support ( control group [ CG ] ) and followed through 3 months post partum . SETTING Low-income predominantly Latina community . PARTICIPANTS Expectant mothers , less than 32 weeks gestation and considering breastfeeding ( N = 162 ) . Intervention Exclusive breastfeeding peer counseling support offering 3 prenatal home visits , daily perinatal visits , 9 postpartum home visits , and telephone counseling as needed . MAIN OUTCOME MEASURES Exclusive breastfeeding rates at hospital discharge , 1 , 2 , and 3 months post partum ( n = 135 ) . RESULTS At hospital discharge , 24 % in the CG compared with 9 % in the PC had not initiated breastfeeding , with 56 % and 41 % , respectively , nonexclusively breastfeeding . At 3 months , 97 % in the CG and 73 % in the PC had not exclusively breastfed ( relative risk [ RR ] = 1.33 ; 95 % CI , 1.14 - 1.56 ) during the previous 24 hours . The likelihood of nonexclusive breastfeeding throughout the first 3 months was significantly higher for the CG than the PC ( 99 % vs 79 % ; RR = 1.24 ; 95 % CI , 1.09 - 1.41 ) . Mothers in the CG were less likely than their PC counterparts to remain amenorrheic at 3 months ( 33 % vs 52 % ; RR = 0.64 ; 95 % CI , 0.43 - 0.95 ) . The likelihood of having 1 or more diarrheal episode in infants was cut in half in the PC ( 18 % vs 38 % ; RR = 2.15 ; 95 % CI , 1.16 - 3.97 ) . CONCLUSION Well-structured , intensive breastfeeding support provided by hospital and community-based peer counselors is effective in improving exclusive breastfeeding rates among low-income , inner-city women in the United States BACKGROUND Breastfeeding peer counseling has improved breastfeeding rates in developing countries ; however , its impact in this country has not been adequately evaluated . OBJECTIVE To evaluate the effectiveness of an existing , breastfeeding peer counseling program within the United States . DESIGN R and omized , prospect i ve , controlled trial in which participants were recruited prenatally and r and omly assigned to receive either routine breastfeeding education or routine breastfeeding education plus peer counseling . SETTING An urban hospital serving a large population of low-income Latinas . PARTICIPANTS Pregnant women ( < or = 26 weeks ' gestation ) were recruited from the hospital 's prenatal clinic . Inclusion criteria specified that participants be low income , be considering breastfeeding , have delivered a healthy , full-term singleton , and have access to a telephone . Intervention Breastfeeding peer counseling services included 1 prenatal home visit , daily perinatal visits , 3 postpartum home visits , and telephone contact as needed . MAIN OUTCOME MEASURES Breastfeeding rates at birth and 1 , 3 , and 6 months postpartum . RESULTS The proportion not initiating breastfeeding was significantly lower in the intervention group than among controls ( 8/90 [ 9 % ] vs 17/75 [ 23 % ] ; relative risk , 0.39 ; 95 % confidence interval , 0.18 - 0.86 ) . The probability of stopping breastfeeding also tended to be lower in the intervention group at both 1 month ( 36 % vs 49 % ; relative risk , 0.72 ; 95 % confidence interval , 0.50 - 1.05 ) and 3 months ( 56 % vs 71 % ; relative risk , 0.78 ; 95 % confidence interval , 0.61 - 1.00 ) . CONCLUSION These findings demonstrate that , in the United States , peer counselors can significantly improve breastfeeding initiation rates and have an impact on breastfeeding rates at 1 and 3 months post partum This research examined the effect of peer support on breastfeeding duration and exclusivity ( breastfeeding without supplements ) in a population of low-income women during the first 3 months postpartum . Participants in the peer counselor group ( n = 18 ) exhibited higher rates of exclusive breastfeeding across time than those without a counselor ( n = 18 ) , and more exclusive breastfeeding was associated with long duration overall . Mother 's career plans had the greatest effect on duration of breastfeeding . Women who intended to return to work , attend school , or both breastfed 6 to 9 weeks less than participants who intended to stay home . Attendance at a breastfeeding class and knowing someone who had breastfed was significantly correlated with a longer duration of breastfeeding . Nutritionists from the Women , Infants and Children ( WIC ) Program were the primary source of breastfeeding information . Two main factors discouraged women from breastfeeding : returning to work , school , or both and the perception of a diminished milk supply . Greater emphasis should be placed on prenatal breastfeeding education for low-income women , and their mothers and gr and mothers should be included . Peer support is one important component of social support in the area of breastfeeding that community health nurses ( CHNs ) can utilize . CHNs are in a unique position to assist working mothers , provide support , and develop educational programs to enhance breastfeeding success in this population Excess weight gain in American Indian/Alaskan native ( AI/AN ) children is a public health concern . This study tested ( 1 ) the feasibility of delivering community-wide interventions , alone or in combination with family-based interventions , to promote breastfeeding and reduce the consumption of sugar-sweetened beverages ; and ( 2 ) whether these interventions decrease Body Mass Index ( BMI ) -Z scores in children 18–24 months of age . Three AI/AN tribes were r and omly assigned to two active interventions ; a community-wide intervention alone ( tribe A ; n = 63 families ) or community-wide intervention containing a family component ( tribes B and C ; n = 142 families ) . Tribal staff and the research team design ed community-tailored interventions and trained community health workers to deliver the family intervention through home visits . Feasibility and acceptability of the intervention and BMI -Z scores at 18–24 months were compared between tribe A and tribes B & C combined using a separate sample pretest , posttest design . Eighty-six percent of enrolled families completed the study . Breastfeeding initiation and 6-month duration increased 14 and 15 % , respectively , in all tribes compared to national rates for American Indians . Breastfeeding at 12 months was comparable to national data . Parents expressed confidence in their ability to curtail family consumption of sugar-sweetened beverages . Compared to a pretest sample of children of a similar age 2 years before the study begun , BMI -Z scores increased in all tribes . However , the increase was less in tribes B & C compared to tribe A ( −0.75 , P = 0.016 ) . Family , plus community-wide interventions to increase breastfeeding and curtail sugar-sweetened beverages attenuate BMI rise in AI/AN toddlers more than community-wide interventions alone Objective . To compare and measure the effects and cost-effectiveness of two interventions design ed to raise immunization rates . Setting s. Nine primary care sites serving impoverished and middle-class children . Subjects . Complete birth cohorts ( ages 0 to 12 months ; n = 3015 ) from these sites . Interventions . Two 18-month duration interventions : 1 ) tracking with outreach [ tracking/outreach ] to bring underimmunized children to their primary care provider office , and 2 ) a primary care provider office policy change to identify and reduce missed immunization opportunities ( prompting ) . Design . R and omized , controlled trial , r and omizing within sites using a two-by-two factorial design . Subjects were allocated to one of four study groups : control , prompting only , tracking/outreach only , and combined prompting with tracking/outreach . Outcomes were obtained by blinded chart abstract ion . Measures . Immunization status for age ; number of days of delay in immunization ; primary care utilization ; and rates of screening for occult disease . Results . Out of 3015 subjects , 274 subjects ( 9 % ) transferred out of the participating sites or had incomplete charts and were excluded . The 2741 ( 91 % ) remaining subjects were assessed . At baseline , study groups did not differ in age , gender , insurance type , or immunization status . Of the remaining subjects , 63 % received Medicaid . Final series-complete immunization coverage levels were : control , 74 % ; prompting-only , 76 % ; tracking/outreach-only 95 % ; and combined tracking/outreach with prompting , 95 % . Analysis of variance showed that : 1 ) tracking/outreach increased immunization rates 20 percentage points ; 2 ) tracking/outreach decreased mean immunization delay 63 days ; 3 ) tracking/outreach increased mean health supervision visits 0.44 visits per child ; 4 ) tracking/outreach increased mean anemia screening 0.17 screenings per child and mean lead screenings 0.12 screenings per child ; 5 ) impact of tracking/outreach was greatest for uninsured and impoverished patients ; and 6 ) the prompting intervention had no impact on the studied outcomes , and its failure was caused by inconsistent use of prompts and failure to vaccinate ill children when prompted . Using tracking/outreach , the cost per additional child fully immunized was $ 474 . Each $ 1000 spent on the tracking/outreach intervention result ed in : 2.1 additional fully vaccinated children and 668 fewer child-days of delayed immunization ; 4.6 additional health supervision visits and 5.9 additional other visits to the primary care provider ; and 1.8 additional anemia screenings and 1.3 additional lead screenings . Conclusions . Outreach directed toward children not up-to- date on immunizations improves not only immunization status , but also health supervision visit attendance and screening rates . The cost per additional child immunized was high , but should be interpreted in view of the spillover benefits that accompanied improved immunization . Effective means to improve coverage by reducing missed immunization opportunities still need to be identified . immunization , primary care , r and omized , controlled trial , missed immunization opportunities , outreach Recent reports have stressed the importance of social support services to the health and well being of pregnant women and their newborns . The impact of paraprofessional support services on the amount of prenatal care received and birthweight was studied in a sample of 111 low-income women . Paraprofessionals were women who had been on public assistance and successfully attained health and human services for themselves and their infants . They were similar to the patients they served in educational background and ethnicity . A six-week training program prepared them to counsel and assist pregnant women with health and social services , housing , food , transportation and other basic necessities . Women attending a publically-funded prenatal clinic were r and omly assigned to a paraprofessional . A comparison group matched for ethnicity , parity and trimester entering prenatal care was also selected . Women followed by a paraprofessional had significantly more prenatal appointments ( 8.0 vs 6.5 visits ) and infants with average higher birthweight ( 3125 grams ) over the matched comparison group ( 3273 grams ) . While intensity of contact with a paraprofessional contributed significantly to the amount of prenatal care received by patients of paraprofessionals , the mechanism for improvement in birthweight is unknown |
12,226 | 27,197,277 | The decision to participate in colorectal cancer screening depended on an individual 's awareness of colorectal cancer screening .
Awareness affected views of cancer , attitudes towards colorectal cancer screening modalities , and motivation for screening .
Factors mediating awareness included public education to address misconceptions , primary care physician efforts to recommend screening , and the influence of friends and family .
Specific barriers to participation in population s with lower participation rates included language barriers , logistical challenges to attending screening tests , and cultural beliefs . | Screening reduces the incidence , morbidity , and mortality of colorectal cancer , yet participation tends to be low .
We undertook a systematic review and meta- study synthesis of qualitative studies to identify facilitators and barriers to colorectal cancer screening participation . | BACKGROUND Despite the availability of multiple effective screening tests for colorectal cancer , screening rates remain suboptimal . The literature documents patient preferences for different test types and recommends a shared decision-making approach for physician-patient colorectal cancer screening ( CRCS ) discussion s , but it is unknown whether such communication about CRCS preferences and options actually occurs in busy primary -care setting s. OBJECTIVE Describe physician-patient CRCS discussion s during a wellness visit . DESIGN Cross-sectional ; patients audio-recorded with physicians . PARTICIPANTS A subset of patients ( N = 64 ) participating in a behavioral intervention trial design ed to increase CRCS who completed a wellness visit during the trial with a participating physician ( N = 8).APPROACHTranscripts were analyzed using qualitative methods . RESULTS Physicians in this sample consistently recommended CRCS , but focused on colonoscopy . Physicians did not offer a fecal occult blood test alone as a screening choice , which may have created missed opportunities for some patients to get screened . In this single visit , physicians ’ communication processes generally precluded discussion of patients ’ test preferences and did not facilitate shared decision-making . Patients ’ questions indicated their interest in different CRCS test types and appeared to elicit more information from physicians . Some patients remained resistant to CRCS after discussing it with a physician . CONCLUSION If a preference for colonoscopy is widespread among primary -care physicians , the implication s for intervention are either to prepare patients for this preference or to train physicians to offer options when recommending screening to patients Two methods of mass population screening for colorectal cancer - faecal occult blood testing and sigmoidoscopy - have been the subject of r and omized controlled trials in the UK . A national screening programme is currently under consideration and the choice of screening method remains open . To be successful , a programme will require high levels of uptake , and uptake is likely to depend upon subjects ' attitudes towards the screening method introduced . Although a preferred screening method has already been identified from a question naire survey , we undertook a further interview study ( n = 106 ) , with a view to comparing the results of two different approaches to eliciting public preferences . In comparison with the question naire study , a higher proportion of interview subjects stated a preference . Interview subjects were generally more favourably disposed towards sigmoidoscopy , excepting those with previous experience . Compared with the question naire survey , the interviews provided richer information on the reasons for preferences offered . Individual preferences were evidently subjective and dependant on attitudes towards a variety of method characteristics , such as discomfort , convenience and perceived sophistication . Characteristics such as age and low income , which had predicted preferences in the question naire study , predicted preferences in the interview study also . The difference between the results obtained by the different elicitation techniques can be explained in terms of the differential provision of information and sample selection . Conclusions made about public preferences are likely to depend on the technique employed in eliciting them Colorectal cancer is the second leading cause of cancer death in the United States.1 Appropriate screening can reduce incidence of and mortality from colorectal cancer.2–5 The US Preventive Services Task Force recommends that all average-risk individuals aged 50 years and older receive colorectal cancer screening.6 The American Cancer Society recommends several acceptable approaches to screening , including an annual 3-card home fecal occult blood test.7 The Healthy People 2010 objective is to increase the proportion of people aged 50 and older who have received a fecal occult blood test within the preceding 2 years to at least 50%.8 Lack of knowledge , confidence , and skills ; negative attitudes toward the tests themselves ; fear of the consequences of screening ; and inadequate social support all have been suggested as possible barriers to colorectal cancer screening,9 whereas positive attitudes toward colorectal cancer screening and physician encouragement have been associated with receipt of a fecal occult blood test with a home stool kit.10 Despite these studies , gaps remain in what is known about barriers to successful interventions to increase colorectal cancer screening , particularly in minority population s.11,12 This study is based on the assumption that identification and definition of barriers to colorectal cancer screening in low-income , underserved minority population s can help guide the development of effective interventions Background Colorectal cancer screening ( CRCS ) is the only type of cancer screening where both genders reduce risks by similar proportions with identical procedures . It is an important context for examining gender differences in disease-prevention , as CRCS significantly reduces mortality via early detection and prevention . In efforts to increase screening adherence , there is increasing acknowledgment that obstructive attitudes prevent CRCS uptake . Precise identification of the gender differences in obstructive attitudes is necessary to improve uptake promotion . This study r and omly sample d unscreened , screening - eligible individuals in Ontario , employing semi-structured interviews to elicit key differences in attitudinal obstructions towards colorectal cancer screening with the aim of deriving informative differences useful in planning promotions of screening uptake . Methods N = 81 participants ( 49 females , 32 males ) , 50 years and above , with no prior CRCS , were contacted via r and om-digit telephone dialing , and consented via phone-mail contact . Altogether , N = 4,459 calls were made to yield N = 85 participants ( 1.9 % response rate ) of which N = 4 participants did not complete interviews . All subjects were eligible for free-of-charge CRCS in Ontario , and each was classified , via st and ard interview by CRCS screening decision-stage . Telephone-based , semi-structured interviews ( SSIs ) were employed to investigate gender differences in CRCS attitudes , using questions focused on 5 attitudinal domains : 1 ) Screening experience at the time of interview ; 2 ) Barriers to adherence ; 3 ) Predictors of Adherence ; 4 ) Pain-anxiety experiences related to CRCS ; 5 ) Gender-specific experiences re : CRCS , addressing all three modalities accessible through Ontario ’s program : a ) fecal occult blood testing ; b ) flexible sigmoidoscopy ; c ) colonoscopy . Results Interview transcript analyses indicated divergent themes related to CRCS for each gender : 1 ) bodily intrusion , 2 ) perforation anxiety , and 3 ) embarrassment for females and ; 1 ) avoidant procrastination with underlying fatalism , 2 ) unnecessary health care and 3 ) uncomfortable vulnerability for males . Respondents adopted similar attitudes towards fecal occult blood testing , flexible sigmoidoscopy and colonoscopy , and were comparable in decision stage across tests . Gender differences were neither closely tied to screening stage nor modality . Women had more consistent physician relationships , were more screening-knowledgeable and better able to articulate views on screening . Men reported less consistent physician relationships , were less knowledgeable and kept decision-making processes vague and emotionally distanced ( i.e. at ‘ arm ’s length ’ ) . Conclusions Marked differences were observed in obstructive CRCS attitudes per gender . Females articulated reservations about CRCS-associated distress and males suppressed negative views while ambiguously procrastinating about the task of completing screening . Future interventions could seek to reduce CRCS-related stress ( females ) and address the need to overcome procrastination ( males ) INTRODUCTION Uptake is an important determinant of the effectiveness of population -based screening . Uptake of colorectal cancer ( CRC ) screening generally remains sub-optimal . AIM To determine factors influencing the decision whether to participate or not among individuals invited for faecal occult blood test ( FOBT ) or flexible sigmoidoscopy ( FS ) screening . METHODS A question naire was sent to a stratified r and om sample of individuals aged 50 - 74 , previously invited for a r and omised CRC screening trial offering FOBT or FS , and a reference group from the same population not previously invited ( screening naïve group ) . The question naire assessed reasons for (non)-participation , individuals ' characteristics associated with participation , knowledge , attitudes and level of informed choice . RESULTS The response rate was 75 % ( n=341/452 ) for CRC screening participants , 21 % ( n=676/3212 ) for non- participants and 38 % ( n=192/500 ) for screening-naïve individuals . The main reasons for FOBT and FS participation were acquiring certainty about CRC presence and possible early CRC detection . Anticipated regret and positive attitudes towards CRC screening were strong predictors of actual participation and intention to participate in a next round . The main reason for non-participation in FOBT screening was lack of abdominal complaints . Non-participation in FS screening was additionally influenced by worries about burden . Eighty-one percent of participants and 12 % of non- participants made an informed choice on participation . CONCLUSION Only 12 % of non- participants made an informed choice not to participate . These results imply that governments and /or organizations offering screening should focus on adequately informing and educating target population s about the harms and benefits of CRC screening . This may impact uptake of CRC screening While a wide range of behavioral and psychosocial literature explores attitudes and beliefs towards cancer screenings , fewer studies examine attitudes across cancer screening types . We draw on quantitative and qualitative findings from a 4-year prospect i ve study based at a community health center serving diverse , low-income patients . Methods included self-report surveys ( n = 297 ) , medical chart abstract ion , and several qualitative methods with a sub sample of participants . Participants included white , African – American , Vietnamese , and Latino patients who were diagnosed with diabetes , hypertension , or both . Patients ’ attitudes ( both positive and negative ) towards cancer screening types were remarkably consistent across cancer screening types . These effects were stronger among men than women . Never having had a cancer screening was generally associated with more unfavorable attitudes towards all screenings . Qualitative interviews indicate the importance of information circulated through social networks in shaping attitudes towards cancer screenings . Condensed abstract : In a multi- method study of attitudes towards cancer screening among medically underserved patients in a primary care setting , we found that attitudes ( both positive and negative ) were remarkably consistent across cancer screening types OBJECTIVE To identify barriers and facilitators associated with participation in the first round of a population -based program for colorectal cancer ( CRC ) in Catalonia , Spain and to identify strategies for motivating and supporting behavioral change . MATERIAL AND METHODS A two-part , mixed- methods design was used . In first place , a prospect i ve study of individuals aged 50 - 69 years ( n=1961 ) was conducted in 2006 - 2007 . Secondly , focus groups were undertaken with participants and non- participants of the CRC screening , in 2008 . RESULTS Intention to participate was an important determinant of participation ( 82.9 % vs 65.9 % , OR=2.56 , 95%CI:1.95 - 3.36 ) in addition to knowledge about CRC and its early detection . Respondents who reported that CRC may be asymptomatic in early stages enrolled in the screening program more frequently than those who thought CRC is always symptomatic ( 49.4 % vs 44.8 % , OR:1.82 ; 95%CI:1.3 - 2.6 ) . Barriers for participation mentioned in focus groups were competing perceived for other health problems and other dem and s as well as misunderst and ing about personal relevance of the screening . CONCLUSION Individuals ' perceptions of CRC are amenable to change through education-based interventions . Increasing public knowledge related to the burden of CRC and its preventive potential may be an effective way for improving participation in a population -based screening program Objectives To assess the acceptability of bowel cancer screening using flexible sigmoidoscopy ( FS ) . Setting Adults aged 55 to 64 recruited from general practice s in Welwyn Garden City and Leicester , which were the pilot and start up centres of a multicentred r and omised controlled trial of FS screening ( the ICRF/MRC Flexible Sigmoidoscopy Screening Trial ) . Methods Screenees ( n=4422 ) were sent a three month follow up question naire that included measures of satisfaction with information given before the test , facilities at the test unit , attitudes of the staff , and explanation of the results . Measures of pain , embarrassment , feelings of being “ in control ” during the test , willingness to encourage others to have the test , and gladness to have participated were also included . In addition , semistructured telephone interviews were conducted with 60 screenees , stratified by screening outcome and gender . Results The follow up question naire was completed by 94 % of screenees . Responses indicated a high level of satisfaction with the procedure : 99 % were satisfied with the information given before the test , the facilities , the attitudes of the staff , and the explanation of their results ; 91 % reported only mild or no pain ; 97 % reported little or no embarrassment ; and 99 % were glad they had the test . Satisfaction ratings varied little by gender or outcome group . The quantitative results were reinforced by the qualitative data , which also revealed high acceptability . Conclusion In the context of a clinical trial with dedicated trial staff , FS is a well tolerated procedure . There are high levels of satisfaction with service provision and positive attitudes towards the programme |
12,227 | 25,107,290 | Nonbiophysical outcomes , including economic outcomes , were reported too infrequently to meta-analyze , or to draw conclusions from .
MA interventions improve biophysical outcomes among patients with diabetes .
There was inadequate literature to determine SMA effects on patient experience , utilization , and costs | ABSTRACT OBJECTIVES Shared medical appointments ( SMAs ) are an increasingly used system-re design strategy for improving access to and quality of chronic illness care .
We conducted a systematic review of the existing literature on SMA interventions for patients with diabetes in order to underst and their impact on outcomes . | Purpose To assess whether VA MEDIC-E ( Veterans Affairs Multi-disciplinary Education and Diabetes Intervention for Cardiac risk reduction[EM DASH ] Extended for 6 months ) , a pharmacist-led shared medical appointments program , could improve attainment of target goals for hypertension , hyperglycemia , hyperlipidemia , and tobacco use in patients with type 2 diabetes compared to st and ard primary care after 6 months of intervention . Methods A r and omized , controlled trial of VA MEDIC-E ( n = 50 ) versus st and ard primary care ( n = 49 ) in veterans with type 2 diabetes , hemoglobin A1c ( A1C ) > 7 % , blood pressure ( BP ) > 130/80 mmHg , and low density lipoprotein cholesterol ( LDL-C ) > 100mg/dl ( 2.59 mmol/l ) in the previous 6 months was conducted . The VA MEDIC-E intervention consisted of 4 weekly group sessions followed by 5 monthly booster group sessions . Each 2-hour session included 1 hour of multidisciplinary diabetes specific healthy lifestyle education and 1 hour of pharmacotherapeutic interventions performed by a clinical pharmacist . Evaluation measures included lab values of A1C , LDL cholesterol , BP , and goal attainment of these values , and diabetes self-care behavior question naires at 6 months . Results The r and omization groups were similar at baseline in all cardiovascular risk factors except for LDL , which was significantly lower in the MEDIC-E arm . At 6 months , significant improvements from baseline were found in the intervention arm for exercise , foot care , and goal attainment of A1C , LDL-C , and BP but not in the control arm . Conclusions The results of this study demonstrate that the pharmacist-led group intervention program for 6 months was an efficacious and sustainable collaborative care approach to managing diabetes and reducing associated cardiovascular risk Purpose The purpose of this study was to assess whether the VA-MEDIC ( Veterans Affairs Multi-disciplinary Education and Diabetes Intervention for Cardiac risk reduction ) , a pharmacist-led group medical visit program , could improve achievement of target goals in hypertension , hyperglycemia , hyperlipidemia , and tobacco use in patients with type 2 diabetes compared to usual care . Methods This was a r and omized controlled trial of VA-MEDIC intervention in addition to usual care versus usual care alone in diabetic patients to reduce cardiac risk factors . VA-MEDIC consisted of a 40- to 60-minute educational component by nurse , nutritionist , physical therapist , or pharmacist followed by pharmacist-led behavioral and pharmacological interventions over 4 weekly sessions . Measures The attainment of target goals in hemoglobin A1C ( A1C ) , blood pressure , fasting lipids , and tobacco use recommended by the American Diabetes Association . Results Of 118 participants , 109 completed the study . VA-MEDIC ( n = 58 ) participants were younger and had greater tobacco use at baseline than usual care but were similar in other cardiovascular risk factors . After 4 months , a greater proportion of VA-MEDIC participants versus controls achieved an A1C of less than 7 % and a systolic blood pressure less than 130 mm Hg . No significant change was found in lipid control or tobacco use between the 2 study arms . Conclusion Pharmacist-led group medical visits are feasible and efficacious for improving cardiac risk factors Purpose : To study the effectiveness of multidisciplinary nurse practitioner coordinated team ( NPCT ) group visits in medically underserved Appalachia on the health , knowledge , and self‐efficacy of patients with type 2 diabetes ( DM ) . The study also identified perceived barriers to participating in the diabetes programs . Data sources : A research er‐developed tool was used to assess demographic data , clinical data , and barriers to care . The participants completed the Diabetes Knowledge Tests and the Diabetes Empowerment Scales . Two groups were assessed . One group participated in the diabetes intervention , and the other received usual care . Both groups completed the instruments prior to the intervention and after the intervention was completed . Conclusions : The group that participated in the intervention had better clinical outcomes ( blood glucose and A1Cs ) , greater knowledge , and better self‐efficacy following the intervention than the usual care groups . This suggests that the intervention was important in improving outcomes of patients with type 2 DM . Barriers to care included fuel , time , family , work , and transportation . Barriers need to be addressed in order to have more patients participate in such programs . Implication s for practice : NPCT group visits may represent an effective means of integrating diabetes self‐management education and medical management in a family practice clinic in medically underserved areas CONTEXT Emergency department utilization by chronically ill older adults may be an important sentinel event signifying a breakdown in care coordination . A primary care group visit ( i.e. , several patients meeting together with the provider at the same time ) may reduce fragmentation of care and subsequent emergency department utilization . OBJECTIVE To determine whether primary care group visits reduce emergency department utilization in chronically ill older adults . DESIGN R and omized trial conducted over a 2-year period . SETTING Group-model HMO in Denver , Colorado . PATIENTS 295 older adults ( > or = 60 years of age ) with frequent utilization of outpatient services and one or more chronic illnesses . INTERVENTION Monthly group visits ( generally 8 to 12 patients ) with a primary care physician , nurse , and pharmacist held in 19 physician practice s. Visits emphasized self-management of chronic illness , peer support , and regular contact with the primary care team . MEASURES Emergency department visits , hospitalizations , and primary care visits . RESULTS On average , patients in the intervention group attended 10.6 group visits during the 2-year study period . These patients averaged fewer emergency department visits ( 0.65 vs. 1.08 visits ; P = 0.005 ) and were less likely to have any emergency department visits ( 34.9 % vs. 52.4 % ; P = 0.003 ) than controls . These differences remained statistically significant after controlling for demographic factors , comorbid conditions , functional status , and prior utilization . Adjusted mean difference in visits was -0.42 visits ( 95 % CI , -0.13 to -0.72 ) , and adjusted RR for any emergency department visit was 0.64 ( CI , 0.44 to 0.86 ) . CONCLUSION Monthly group visits reduce emergency department utilization for chronically ill older adults OBJECTIVES To compare the effectiveness of Cooperative Health Care Clinic ( ( CHCC ) group outpatient model for chronically ill , older health maintenance organization ( HMO ) patients ) with usual care . DESIGN Two-year , r and omized , controlled trial conducted with recruitment from February 1995 through July of 1996 . SETTING Nonprofit group model HMO . PARTICIPANTS Two hundred ninety-four adults ( 145 intervention and 149 usual care ) , aged 60 and older ( mean age 74.1 ) with 11 or more outpatient visits in the prior 18 months , one or more self-reported chronic conditions , and expressed interest in participating in a group clinic . INTERVENTION Monthly group meetings held by patients ' primary care physicians . MEASUREMENT Differences in clinic visits , inpatient admissions , emergency room visits , hospital outpatient services , professional services , home health , and skilled nursing facility admissions ; measures of patient satisfaction , quality of life , self-efficacy , and activities of daily living ( ADLs ) . RESULTS Outpatient , pharmacy services , home health , and skilled nursing facility use did not differ between groups , but CHCC patients had fewer hospital admissions ( P=.012 ) , emergency visits ( P=.008 ) , and professional services ( P=.005 ) . CHCC patients ' costs were $ 41.80 per member per month less than those of control patients . CHCC patients reported higher satisfaction with their primary care physician ( P=.022 ) , better quality of life ( P=.002 ) , and greater self-efficacy ( P=.03 ) . Health status and ADLs did not differ between groups . CONCLUSION The CHCC model result ed in fewer hospitalizations and emergency visits , increased patient satisfaction , and self-efficacy , but no effect on outpatient use , health , or functional status OBJECTIVE To evaluate the effectiveness of a managed care approach to health care delivery , group visits , in the management of uninsured or inadequately insured patients with type 2 diabetes . RESEARCH DESIGN AND METHODS A total of 120 patients with uncontrolled type 2 diabetes were r and omly assigned to receive their care in group visits or usual care for 6 months . After 6 months , concordance with 10 process-of-care indicators recommended by the American Diabetes Association ( ADA ) st and ards of care was evaluated through chart abstract ion . The 10 items evaluated were up-to- date HbA(1c ) levels and lipid profiles , urine for microalbumin , appropriate use of ACE inhibitor or angiotensin receptor blockers , use of lipid-lowering agents where indicated , daily aspirin use , annual foot examinations , annual referrals for retinal examinations , and immunizations against streptococcal pneumonia and influenza . RESULTS Patients who received care in group visits showed statistically significant improvement in concordance with these 10 process-of-care indicators ( P < 0.001 ) . Of the patients , 76 % who received care in group visits had at least 9 of these 10 items up to date , as compared with 23 % of control patients ; 86 % of patients in group visits had at least 8 of the 10 indicators compared with 47 % of control patients . CONCLUSIONS Group visits proved more effective in promoting concordance with ADA st and ards of care than usual care in the treatment of uninsured or inadequately insured patients with type 2 diabetes OBJECTIVE To evaluate the impact of primary care group visits ( chronic care clinics ) on the process and outcome of care for diabetic patients . RESEARCH DESIGN AND METHODS We evaluated the intervention in primary care practice s r and omized to intervention and control groups in a large-staff model health maintenance organization ( HMO ) . Patients included diabetic patients > or = 30 years of age in each participating primary care practice , selected at r and om from an automated diabetes registry . Primary care practice s were r and omized within clinics to either a chronic care clinic ( intervention ) group or a usual care ( control ) group . The intervention group conducted periodic one-half day chronic care clinics for groups of approximately 8 diabetic patients in their respective doctor 's practice . Chronic care clinics consisted of st and ardized assessment s ; visits with the primary care physician , nurse , and clinical pharmacist ; and a group education/peer support meeting . We collected self-report question naires from patients and data from administrative systems . The question naires were mailed , and telephoned interviews were conducted for nonrespondents , at baseline and at 12 and 24 months ; we queried the process of care received , the satisfaction with care , and the health status of each patient . Serum cholesterol and HbA1c levels and health care use and cost data was collected from HMO administrative systems . RESULTS In an intention-to-treat analysis at 24 months , the intervention group had received significantly more recommended preventive procedures and helpful patient education . Of five primary health status indicators examined , two ( SF-36 general health and bed disability days ) were significantly better in the intervention group . Compared with control patients , intervention patients had slightly more primary care visits , but significantly fewer specialty and emergency room visits . Among intervention participants , we found consistently positive associations between the number of chronic care clinics attended and a number of outcomes , including patient satisfaction and HbA1c levels . CONCLUSIONS Periodic primary care sessions organized to meet the complex needs of diabetic patients imrproved the process of diabetes care and were associated with better outcomes BACKGROUND Current diabetes management guidelines offer blueprints for providers , yet type 2 diabetes control is often poor in disadvantaged population s. The group visit is a new treatment modality originating in managed care for efficient service delivery to patients with chronic health problems . Group visits offer promise for delivering care to diabetic patients , as visits are lengthier and can be more frequent , more organized , and more educational . OBJECTIVE To evaluate the effect of group visits on clinical outcomes , concordance with 10 American Diabetes Association ( ADA ) guidelines [ American Diabetes Association , Diabetes Care , 28:S4–36 , 2004 ] and 3 United States Preventive Services Task Force ( USPSTF ) cancer screens [ U.S. Preventive Services Task Force , http://www.ahrq.gov/clinic/uspstf/re source .htm , 2003 ] . RESEARCH DESIGN AND METHODS A 12-month r and omized controlled trial of 186 diabetic patients comparing care in group visits with care in the traditional patient – physician dyad . Clinical outcomes ( HbA1c , blood pressure [ BP ] , lipid profiles ) were assessed at 6 and 12 months and quality of care measures ( adherence to 10 ADA guidelines and 3 USPSTF cancer screens ) at 12 months . RESULTS At both measurement points , HbA1c , BP , and lipid levels did not differ significantly for patients attending group visits versus those in usual care . At 12 months , however , patients receiving care in group visits exhibited greater concordance with ADA process-of-care indicators ( p < .0001 ) and higher screening rates for cancers of the breast ( 80 vs. 68 % , p = .006 ) and cervix ( 80 vs 68 % , p = .019 ) . CONCLUSIONS Group visits can improve the quality of care for diabetic patients , but modifications to the content and style of group visits may be necessary to achieve improved clinical outcomes OBJECTIVE To evaluate the effectiveness of a cluster visit model led by a diabetes nurse educator for delivering outpatient care management to adult patients with poorly controlled diabetes . RESEARCH DESIGN AND METHODS This study involved a r and omized controlled trial among patients of Kaiser Permanente 's Pleasanton , CA , center who were aged 16 - 75 years and had either poor glycemic control ( HbA1c > 8.5 % ) or no HbA1c test performed during the previous year . Intervention subjects received multidisciplinary outpatient diabetes care management delivered by a diabetes nurse educator , a psychologist , a nutritionist , and a pharmacist in cluster visit setting s of 10 - 18 patients /month for 6 months . Outcomes included change ( from baseline ) in HbA1c levels ; self-reported changes in self-care practice s , self-efficacy , and satisfaction ; and utilization of inpatient and outpatient health care . RESULTS After the intervention , HbA1c levels declined by 1.3 % in the intervention subjects versus 0.2 % in the control subjects ( P < 0.0001 ) . Several self-care practice s and several measures of self-efficacy improved significantly in the intervention group . Satisfaction with the program was high . Both hospital ( P = 0.04 ) and outpatient ( P < 0.01 ) utilization were significantly lower for intervention subjects after the program . CONCLUSIONS A 6-month cluster visit group model of care for adults with diabetes improved glycemic control , self-efficacy , and patient satisfaction and result ed in a reduction in health care utilization after the program BACKGROUND AND AIMS We showed that continuing education can be embedded into routine diabetes care by seeing patients in small groups rather than individually . Group care was cost-effective in improving quality of life , knowledge of diabetes , health behaviours and clinical outcomes in people with type 2 diabetes . The aim of this study was to verify if group care can also be applied to type 1 diabetes . METHODS AND RESULTS R and omized , controlled clinical trial comparing 31 patients managed by group care with 31 managed by traditional one-to-one care . A syllabus was built and later remodulated with the patients in a series of focus-group meetings . The primary end-point was changes in quality of life . Secondary end-points were : knowledge of diabetes , health behaviours , HbA1c and circulating lipids . Differential costs to the Italian National Health System and to the patients were also calculated . After 3 years , quality of life improved among patients on group care , along with knowledge and health behaviours ( p<0.001 , all ) . Knowledge added its effects to those of group care by independently influencing behaviours ( p=0.004 ) while quality of life changed independently of either ( p<0.001 ) . Among controls , quality of life worsened ( p<0.001 ) whereas knowledge and behaviours remained unchanged . HDL cholesterol increased among patients on group care ( p=0.027 ) and total cholesterol decreased in the controls ( p<0.05 ) . HbA1c decreased , though not significantly , in both . Direct costs for group and one-to-one care were Euros 933.19 and Euros 697.10 per patient , respectively , giving a cost-effectiveness ratio of Euros 19.42 spent per point gained in the quality of life scale . CONCLUSIONS Group care is applicable and also cost-effective in type 1 diabetes . It improves quality of life , knowledge and behaviours . Future programme adjustments should strive to impact more on metabolic control It remains unknown whether diabetes and high blood pressure ( BP ) are simply additive risk factors for cardiovascular outcome or whether they act synergistically and potentiate one another . We performed 24-h ambulatory BP monitoring in 8494 subjects ( mean age , 54.6 years ; 47.0 % women ; 6.9 % diabetic patients ) enrolled in prospect i ve population studies in 10 countries . In multivariable-adjusted Cox regression , we assessed the additive as opposed to the synergistic effects of BP and diabetes in relation to a composite cardiovascular endpoint by testing the significance of appropriate interaction terms . During 10.6 years ( median follow-up ) , 1066 participants had a cardiovascular complication . Diabetes mellitus as well as the 24-h ambulatory BP were independent and powerful predictors of the composite cardiovascular endpoint . However , there was no synergistic interaction between diabetes and 24-h , daytime , or nighttime , systolic or diastolic ambulatory BP ( P for interaction , 0.07⩽P⩽0.97 ) . The only exception was a borderline synergistic effect between diabetes and daytime diastolic BP in relation to the composite cardiovascular endpoint ( P=0.04 ) . In diabetic patients , with normotension as the reference group , the adjusted hazard ratios for the cardiovascular endpoint were 1.35 ( 95 % confidence interval ( CI ) , 0.87–2.11 ) for white-coat hypertension , 1.78 ( 95 % CI , 1.22–2.60 ) for masked hypertension and 2.44 ( 95 % CI , 1.92–3.11 ) for sustained hypertension . The hazard ratios for non-diabetic subjects were not different from those of diabetic patients ( P-values for interaction , 0.09⩽P⩽0.72 ) . In conclusion , in a large international population -based data base , both diabetes mellitus and BP contributed equally to the risk of cardiovascular complications without evidence for a synergistic effect BACKGROUND Group medical clinics ( GMCs ) are widely used in the management of diabetes and hypertension , but data on their effectiveness are limited . OBJECTIVE To test the effectiveness of GMCs in the management of comorbid diabetes and hypertension . DESIGN R and omized , controlled trial . ( Clinical Trials.gov registration number : NCT00286741 ) SETTING 2 Veterans Affairs Medical Centers in North Carolina and Virginia . PATIENTS 239 patients with poorly controlled diabetes ( hemoglobin A(1c ) [ HbA(1c ) ] level > or = 7.5 % ) and hypertension ( systolic blood pressure > 140 mm Hg or diastolic blood pressure > 90 mm Hg ) . INTERVENTION Patients were r and omly assigned within each center to either attend a GMC or receive usual care . Clinics comprised 7 to 8 patients and a care team that consisted of a primary care general internist , a pharmacist , and a nurse or other certified diabetes educator . Each session included structured group interactions moderated by the educator . The pharmacist and physician adjusted medication to manage each patient 's HbA(1c ) level and blood pressure . MEASUREMENTS Hemoglobin A(1c ) level and systolic blood pressure , measured by blinded research personnel at baseline , study midpoint ( median , 6.8 months ) , and study completion ( median follow-up , 12.8 months ) . Linear mixed models , adjusted for clustering within GMCs , were used to compare HbA(1c ) levels and systolic blood pressure between the intervention and control groups . RESULTS Mean baseline systolic blood pressure and HbA(1c ) level were 152.9 mm Hg ( SD , 14.2 ) and 9.2 % ( SD , 1.4 ) , respectively . At the end of the study , mean systolic blood pressure improved by 13.7 mm Hg in the GMC group and 6.4 mm Hg in the usual care group ( P = 0.011 by linear mixed model ) , whereas mean HbA(1c ) level improved by 0.8 % in the GMC group and 0.5 % in the usual care group ( P = 0.159 ) . LIMITATION Measurements of effectiveness may have been limited by concomitant improvements in the usual care group that were due to co-intervention . CONCLUSION Group medical clinics are a potent strategy for improving blood pressure but not HbA(1c ) level in diabetic patients . PRIMARY FUNDING SOURCE U.S. Department of Veterans Affairs Health Services Research and Development Service OBJECTIVE To evaluate whether attending diabetes group visits ( GVs ) leads to lower medical care charges for inadequately insured patients with type 2 diabetes mellitus ( DM ) . STUDY DESIGN R and omized controlled clinical trial . METHODS Data were abstract ed from financial records for 186 patients with uncontrolled type 2 DM r and omized to receive care in GVs or usual care for 12 months . Mann-Whitney tests for differences of means for outpatient visits ( primary and specialty care ) , emergency department ( ED ) visits , and inpatient stays were performed . Separate charge models were developed for primary and specialty outpatient visits . Because GV adherence is potentially dependent on unobserved patient characteristics , treatment effect models of outpatient charges and specialty care visits were estimated using maximum likelihood methods . RESULTS Mann-Whitney test results indicated that GV patients had reduced ED and total charges but more outpatient charges than usual care patients . Ordinary least squares estimations confirmed that GVs increased outpatient visit charges ; however , controlling for endogeneity by estimating a treatment effect model of outpatient visit charges showed that GVs statistically significantly reduced outpatient charges ( P < .001 ) . Estimation of a separate treatment effect model of specialty care visits confirmed that GV effects on outpatient visit charges occurred via a reduction in specialty care visits . CONCLUSIONS After controlling for endogeneity via estimation of a treatment effect model , GVs statistically significantly reduced outpatient visit charges . Estimation of a separate treatment effect model of specialty care visits indicated that GVs likely substitute for more expensive specialty care visits OBJECTIVE To assess the feasibility and effectiveness of shared medical appointments ( SMAs ) among Hispanic patients with diabetes mellitus attending a family medicine residency clinic . STUDY DESIGN Exploratory and descriptive study . METHODS Hispanic patients having diabetes with poor glycemic control ( glycated hemoglobin level , > 7 % ) attending a family medicine residency clinic were r and omized to an SMA group ( n = 50 ) or a control group ( n = 53).The main outcome was glycated hemoglobin level . Secondary outcomes were quality of life and diabetes knowledge . RESULTS When comparing pre-post measures , there were mean decreases in glycated hemoglobin level of 1.19 % for the SMA group ( P < .01 ) and 0.67 % for the control group ( P = .02).In the SMA group , quality -of-life and diabetes knowledge scores increased by 5 and 1.5 points , respectively ( P < .01 ) . CONCLUSIONS Implementing SMAs is feasible and effective among Hispanic patients with diabetes attending a family medicine residency clinic . Health plan managers and policy makers can work with family medicine residents to encourage the use of this model as an alternative approach or in addition to conventional one-on-one interactions with patients Background : : Depression is associated with poor glycemic control , increased number of microvascular and macrovascular complications , functional impairment , mortality , and 4.5 times higher total health care costs in patients with diabetes . Shared medical appointments ( SMAs ) may be an effective method to attain national guideline recommendations for glycemic control in diabetes for patients with depression through peer support , counseling , problem solving , and improved access to care . Objective : To test the efficacy as assessed by attainment of a hemoglobin A1c ( A1C ) < 7 % of pharmacistted group SMA visits , Veterans Affairs Multidisciplinary Education in Diabetes and Intervention for Cardiac Risk Reduction in Depression ( VA-MEDIC-D ) , in patients with type 2 diabetes mellitus . Methods : This was a r and omized controlled trial of VA-MEDIC-D added to st and ard care versus st and ard care alone in depressed patients with diabetes with A1C > 6.5 % . VA-MEDIC-D consisted of 4 once-weekly , 2-hour sessions followed by 5 monthly 90-minute group sessions . Each SMA session consisted of multidisciplinary education and pharmacist-led behavioral and pharmacologic interventions for diabetes , lipids , smoking , and blood pressure . No pharmacologic interventions for depression were provided . The change in the proportion of participants who achieved an A1C < 7 % at 6 months was compared . Results : Compared to st and ard care ( n = 44 ) , a lower proportion of patients in VA-MEDIC-D ( n = 44 ) had systolic blood pressure ( SBP ) < 130 mm Hg at baseline , but were similar in other cardiovascular risk factors and psychiatric comorbidity . The change in the proportion of participants achieving an A1C < 7 % was greater in the VA-MEDIC-D arm than in the st and ard care arm ( 29.6 % vs 11.9 % ) , with odds ratio 3.6 ( 95 % CI 1.1 to 12.3 ) . VA-MEDIC-D participants also achieved significant reductions in SBP , low-density lipoprotein cholesterol , and non – high-density lipoprotein ( HDL ) cholesterol from baseline , whereas significant reductions were attained only in non – HDL cholesterol with st and ard care . There was no significant change in depressive symptoms for either arm . Conclusions : Pharmacist-led group SMA visits are efficacious in attainment of glycemic control in patients with diabetes and depression without change in depression symptoms Objective : The epidemic proportions and management complexity of diabetes have prompted efforts to improve clinic throughput and efficiency . One method of system re design based on the chronic care model is the Shared Medical Appointment ( SMA ) in which groups of patients ( 8–20 ) are seen by a multi-disciplinary team in a 1–2 h appointment . Evaluation of the impact of SMAs on quality of care has been limited . The purpose of this quality improvement project was to improve intermediate outcome measures for diabetes ( A1c , SBP , LDL-cholesterol ) focusing on those patients at highest cardiovascular risk . Setting : Primary care clinic at a tertiary care academic medical center . Subjects : Patients with diabetes with one or more of the following : A1c > 9 % , SBP blood pressure > 160 mm Hg and LDL-c > 130 mg/dl were targeted for potential participation ; other patients were referred by their primary care providers . Patients participated in at least one SMA from 4/05 to 9/05 . Study design : Quasi-experimental with concurrent , but non-r and omised controls ( patients who participated in SMAs from 5/06 through 8/06 ; a retrospective period of observation prior to their SMA participation was used ) . Intervention : SMA system re design Analytical methods : Paired and independent t tests , χ2 tests and Fisher Exact tests . Results : Each group had up to 8 patients . Patients participated in 1–7 visits . At the initial visit , 83.3 % had A1c levels > 9 % , 30.6 % had LDL-cholesterol levels > 130 mg/dl , and 34.1 % had SBP ⩾160 mm Hg . Levels of A1c , LDL-c and SBP all fell significantly postintervention with a mean ( 95 % CI ) decrease of A1c 1.4 ( 0.8 , 2.1 ) ( p<0.001 ) , LDL-c 14.8 ( 2.3 , 27.4 ) ( p = 0.022 ) and SBP 16.0 ( 9.7 , 22.3 ) ( p<0.001 ) . There were no significant differences at baseline between control and intervention groups in terms of age , baseline intermediate outcomes , or medication use . The reductions in A1c in % and SBP were greater in the intervention group relative to the control group : 1.44 vs –0.30 ( p = 0.002 ) for A1c and 14.83 vs 2.54 mm Hg ( p = 0.04 ) for SBP . LDL-c reduction was also greater in the intervention group , 16.0 vs 5.37 mg/dl , but the difference was not statistically significant ( p = 0.29 ) . Conclusions : We were able to initiate a programme of group visits in which participants achieved benefits in terms of cardiovascular risk reduction . Some barriers needed to be addressed , and the operations of SMAs evolved over time . Shared medical appointments for diabetes constitute a practical system re design that may help to improve quality of care BACKGROUND Diabetes mellitus ( DM ) group clinics can effectively control hypertension , but data to support glycemic control are equivocal . This study evaluated the comparative effectiveness of 2 DM group clinic interventions on glycosylated hemoglobin ( HbA(1c ) ) levels in primary care . METHODS Eighty-seven participants were recruited from a DM registry of a single regional Veterans Affairs medical center to participate in an open , r and omized comparative effectiveness study . Two primary care-based DM group interventions of 3 months ' duration were compared . Empowering Patients in Care ( EPIC ) was a clinician-led , patient-centered group clinic consisting of 4 sessions on setting self-management action plans ( diet , exercise , home monitoring , medications , etc ) and communicating about progress with action plans . The comparison intervention consisted of group education sessions with a DM educator and dietician followed by an additional visit with one 's primary care provider . Hemoglobin A(1c ) levels were compared after intervention and at the 1-year follow-up . RESULTS Participants in the EPIC intervention had significantly greater improvements in HbA(1c ) levels immediately following the active intervention ( 8.86%-8.04 % vs 8.74%-8.70 % of total hemoglobin ; mean [ SD ] between-group difference 0.67 % [ 1.3 % ] ; P=.03 ) , and these differences persisted at the 1 year follow-up ( 0.59 % [ 1.4 % ] , P=.05 ) . A repeated- measures analysis using all study time points found a significant time-by-treatment interaction effect on HbA(1c ) levels favoring the EPIC intervention ( F(2,85)=3.55 ; P=.03 ) . The effect of the time-by-treatment interaction seems to be partially mediated by DM self-efficacy ( F(1,85)=10.39 ; P=.002 ) . CONCLUSION Primary care-based DM group clinics that include structured goal - setting approaches to self-management can significantly improve HbA(1c ) levels after intervention and maintain improvements for 1 year . Trial Registration clinical trials.gov Identifier : NCT00481286 Hmong refugees with type 2 diabetes mellitus ( DM2 ) have poor glycemic control . For Hmong adults with DM2 , group visits were instituted at a community health center and evaluated for their influence on diabetes management . Pre- and postintervention measures of physical health , mental health , and behavior were collected on 39 participants ( 64 % participation rate ) . Baseline characteristics and clinical outcomes of 39 group visit participants were compared with 22 Hmong DM2 adults who refused to participate and 216 nonparticipating Hmong DM2 adults from a local diabetes registry . Baseline characteristics were similar among the three groups . Although participants received good medical services and their mental health improved ( p < 0.05 ) , clinical outcomes did not significantly improve . Although group visits are feasible for providing medical services for Hmong adults with DM2 , clinical outcomes remain outside of recommended targets . Addressing mental health in this population may be necessary before people can institute behavioral changes that improve diabetes management OBJECTIVE To compare the impact of group outpatient visits to traditional " physician-patient dyad " care among older chronically ill HMO members on health services utilization and cost , self-reported health status , and patient and physician satisfaction . DESIGN A 1-year r and omized trial . SETTING A group model HMO in the Denver Metropolitan area . PARTICIPANTS Three hundred twenty-one members aged 65 and older , r and omized to a group visit intervention ( n = 160 ) or to usual care ( n = 161 ) . INTERVENTION Patients with high health services utilization and one or more chronic conditions had monthly group visits with their primary care physician and nurse . Visits included health education , prevention measures , opportunities for socialization , mutual support , and for one-to-one consultations with their physician , where necessary . MEASUREMENTS Health services utilization and associated cost , health status , and patient and physician satisfaction . RESULTS Outcome measures obtained after a 1-year follow-up period showed that group participants had fewer emergency room visits ( P = .009 ) , visits to subspecialists ( P = .028 ) , and repeat hospital admissions per patient ( P = .051 ) . Group participants made more visits ( P = .021 ) and calls ( P = .038 ) to nurses than control group patients and fewer calls to physicians ( P = .019 ) . In addition , a greater percentage of group participants received influenza and pneumonia vaccinations ( P < .001 ) . Group participants had greater overall satisfaction with care ( P = .019 ) , and participating physicians reported higher levels of satisfaction with the groups than with individual care . No differences were observed between groups on self-reported health and functional status . Cost of care per member per month was $ 14.79 less for the group participants . CONCLUSIONS Group visits for chronically ill patients reduce repeat hospital admissions and emergency care use , reduce cost of care , deliver certain preventive services more effectively , and increase patient and physician satisfaction OBJECTIVE A trial was performed to establish whether our group care model for lifestyle intervention in type 2 diabetes can be exported to other clinics . RESEARCH DESIGN AND METHODS This study was a 4-year , two-armed , multicenter controlled trial in 13 hospital-based diabetes clinics in Italy ( current controlled trials no. IS RCT N19509463 ) . A total of 815 non – insulin-treated patients aged < 80 years with ≥1 year known diabetes duration were r and omized to either group or individual care . RESULTS After 4 years , patients in group care had lower A1C , total cholesterol , LDL cholesterol , triglycerides , systolic and diastolic blood pressure , BMI , and serum creatinine and higher HDL cholesterol ( P < 0.001 , for all ) than control subjects receiving individual care , despite similar pharmacological prescriptions . Health behaviors , quality of life , and knowledge of diabetes had become better in group care patients than in control subjects ( P < 0.001 , for all ) . CONCLUSIONS The favorable clinical , cognitive , and psychological outcomes of group care can be reproduced in different clinical setting In a pair of r and omized controlled trials in the Kaiser Permanente delivery system in Colorado in the 1990s , group visits for older adults ( monthly non-disease-specific group medical appointments for a cohort of patients led by primary care teams ) were proven to reduce costs , decrease hospitalizations , and improve patient and provider satisfaction . As part of a translational effort , this group visit intervention was replicated in a delivery system in Seattle , Washington , and the log of total healthcare costs was measured in the first year of the intervention . Utilization and patient and physician satisfaction were secondary outcomes . For the cost and utilization analysis , a retrospective case-control design compared 221 case patients aged 65 and older with high outpatient usage in the previous 18 months with 1,015 control patients selected r and omly from clinics not participating in the intervention . Controls were matched to cases on the number of primary care visits in the prior 18 months . Total costs were not statistically different for intervention patients and controls ( $ 8,845 vs $ 10,288 , P=.11 ) , nor were there statistically significant differences in utilization , including hospital admissions and outpatient visits , but patient and provider satisfaction with the intervention was high . This translational effort did not demonstrate the cost savings of the original efficacy trials . Possible explanations for these divergent results may have to do with differences between those who participated and differences between the two delivery systems |
12,228 | 20,709,742 | The analysed studies showed correlation between muscle function estimated by HGS and variables used in the assessment of muscle mass and nutritional status , as well as the prediction of clinical complications .
CONCLUSIONS The analysis indicates that HGS is a useful tool for continuous and systematic assessment of muscle mass related to nutritional status in patients on dialysis . | BACKGROUND Even though h and grip strength ( HGS ) is considered a simple and reliable method to evaluate muscle function and , indirectly , the nutritional status in clinical setting s , there is still no consensus concerning its use in patients with chronic kidney disease ( CKD ) undergoing dialysis .
This study presents a systematic review of the literature on the use of HGS as a parameter for nutritional assessment and a prognostic marker in patients on dialysis . | Elderly patients with end-stage renal disease often have protein and /or caloric malnutrition that severely affects general well-being and mortality . Uremia is associated with resistance to the action of growth hormone ( GH ) . This resistance could be of clinical importance in elderly dialysis patients . In the present study , the effects of GH treatment were assessed in elderly patients receiving chronic hemodialysis . Twenty hemodialysis patients with a mean age of 71.7 years ( range , 53 to 92 years ) were included on a 6-month , r and omized , double-blind , placebo-controlled trial of GH treatment . The dose of GH was 66.7 microgram/kg , administered subcutaneously three times weekly immediately after each dialysis session . Body composition was measured using total-body potassium levels , computed tomography of the lower leg , and bioelectrical impedance analysis . Serum albumin concentrations and h and grip strength were also measured . GH treatment increased the serum concentration of insulin-like growth factor-I ( IGF-I ) , IGF-I/IGF-binding protein-3 ratio , fat-free mass , and the serum concentration of albumin compared with placebo . The number of patients with serum albumin levels less than 40 g/L was reduced by a factor of three in the GH-treated group . H and grip strength increased in response to GH treatment compared with placebo . Six months of GH treatment in elderly hemodialysis patients produced anabolic effects , with improved muscle performance . Also , the number of patients with low albumin levels was markedly reduced , indicating improved nutritional status and /or attenuated catabolism . These are all important beneficial effects for individual patient outcomes BACKGROUND Serum albumin has limitations as a nutritional marker in patients undergoing peritoneal dialysis ( PD ) in that it is affected by inflammation , systemic disease , overhydration , and urinary and dialysate protein loss . H and grip strength is a simple , easily performed bedside test that has been shown to correlate with lean body mass in patients close to inception of dialysis . OBJECTIVE We evaluated the associations of h and grip strength with other clinical factors and examined its relations with mortality and cardiovascular death in PD patients . DESIGN We prospect ively enrolled 233 chronic PD patients and assessed h and grip strength and other variables at baseline and then followed the patients for a mean ( + /-SD ) of 30 + /- 14 mo . RESULTS Baseline h and grip strength was significantly associated with age , sex , height , diabetes , residual glomerular filtration rate ( GFR ) , and hemoglobin but not with C-reactive protein ( CRP ) . After adjustment for age , sex , and height , h and grip strength was most strongly correlated with lean body mass on the basis of creatinine kinetics ( r = 0.334 , P < 0.001 ) , followed by serum albumin and subjective global assessment . Both men and women who died had lower h and grip strengths than did those who remained alive ( P < 0.001 ) . After control for age , sex , diabetes , atherosclerotic vascular disease , GFR , hemoglobin , CRP , and serum albumin , greater h and grip strength was predictive of lower all-cause [ hazards ratio ( HR ) : 0.95 ( 95 % CI : 0.92 , 0.99 ) ; P = 0.005 ] and cardiovascular [ HR : 0.94 ( 0.90 , 0.98 ) ; P = 0.004 ] mortality . CONCLUSIONS H and grip strength not only is a marker of body lean muscle mass but also provides important prognostic information independent of other covariates , including CRP and serum albumin . Our data suggest that h and grip strength may be used in conjunction with serum albumin as a nutrition-monitoring tool in patients undergoing PD BACKGROUND & AIMS Muscle wasting is considered the best marker of protein-energy wasting in end-stage renal disease ( ESRD ) . We tested the usefulness of a simple observer subjective muscle atrophy ( MA ) grading in relation to morbidity and mortality in ESRD patients . METHODS In two different ESRD cohorts ( 265 incident patients starting dialysis and 221 prevalent hemodialysis patients ) , each patient 's degree of MA was visually grade d by a trained nurse on a scale from 1 to 4 as part of the subjective global assessment . This score was confronted with inflammatory and nutritional indexes as well as objective measurements of muscle atrophy . Patients were then prospect ively followed for up to four or six years , depending on the cohort . RESULTS Thirty percent of the incident and 39 % of the prevalent patients presented signs of MA . Across worsening MA scale , nutritional and anthropometric markers of muscle loss were incrementally poorer . Inflammation markers as well as the proportion of women became progressively higher . Female sex , presence of cardiovascular disease , inflammation and low insulin-like growth factor-1 levels were associated with increased significant odd ratios of MA in each cohort . After adjustment for age , sex , inflammation , diabetes , cardiovascular disease , glomerular filtration rate and /or time on hemodialysis , the hazard ratio of death for moderate/severe MA was 2.62 ( 95 % CI : 1.34 , 5.13 ; p=0.001 ) and 3.04 ( 95 % CI : 1.61 , 5.71 ; p=0.0001 ) in the incident and prevalent cohorts respectively . CONCLUSION Increased MA is more common in female dialysis patients and associated with inflammation , poor nutritional and anthropometric status , as well as a 3-fold increased 4 - 6 year mortality . Our data support the use of frequent MA and /or nutritional assessment s in the clinical practice Left ventricular hypertrophy ( LVH ) and inflammation independently increase risk for death in people who receive hemodialysis . A nonr and omized , controlled trial was conducted of the effect of short daily ( 6 sessions/wk of 3 h each ) or conventional ( three sessions/wk of 4 h each ) hemodialysis on LVH and inflammatory factors . A total of 26 short daily hemodialysis and 51 matched conventional hemodialysis patients were enrolled , and baseline and 12-mo measures of echocardiographic left ventricular mass index ( LVMI ) , serum C-reactive protein ( CRP ) , serum calcium and phosphorus , and erythropoietin resistance index were collected . Baseline characteristics were similar between groups except that hemoglobin and serum calcium were lower and serum phosphorus was higher in the short daily hemodialysis group . At 12-mo follow-up , short daily hemodialysis patients experienced a 30 % decrease in LVMI ( 154 + /- 33 to 108 + /- 25 ; P < 0.0001 ) . After adjustment for potential confounders , short daily hemodialysis ( beta = -41.63 , P = 0.03 ) and percentage decrease in serum phosphorus ( beta = -0.12 , P = 0.04 ) predicted a 12-mo decrease in LVMI . Among short daily hemodialysis patients , there were significant reductions in median CRP levels [ 1.22 interquartile range ( IQR ) ( 0.37 to 3.70 ) to 0.05 IQR ( 0.05 to 1.17 ) ; P < 0.01 ] and erythropoietin resistance index [ 19.5 IQR ( 8.6 to 37.6 ) to 10.5 IQR ( 5.5 to 14.6 ) ; P < 0.001 ] . There were no significant changes in LVMI , CRP , or erythropoietin resistance index in the conventional hemodialysis group . Short daily hemodialysis is associated with improved fluid and phosphorus management and a reduction in LVH and inflammatory factors compared with conventional hemodialysis . Future trials are needed to determine whether short daily hemodialysis can reduce morbidity and mortality in this high-risk population The object of this article was to determine the predictive value of risk factors for recurrent falls and the construction of a fall risk model as a contribution to a mobility assessment for the identification of community-dwelling elderly at risk for recurrent falling in general practice . The design was a prospect i ve cohort study ( n = 311 ) . There were four primary health care centers . A sample stratified on previous falls , age , and gender of community-dwelling elderly persons aged 70 years or over ( n = 311 ) was taken from the respondents to a mail question naire ( n = 1660 ) . They were visited at home to assess physical and mental health , balance and gait , mobility and strength . A 36-week follow-up with telephone calls every 6 weeks was conducted . Falls and fall injuries were measured . During follow-up 197 falls were reported by 33 % of the participants : one fall by 17 % and two or more falls by 16 % . Injury due to a fall was reported by 45 % of the fallers : 2 % hip fractures , 4 % other fractures , and 39 % minor injuries . A fall risk model for the prediction of recurrent falls with an area under the curve ( AUC ) of 0.79 , based on logistic regression analysis , showed that the main determinants for recurrent falls were : an abnormal postural sway ( OR 3.9 ; 95 % Cl 1.3 - 12.1 ) , two or more falls in the previous year ( OR 3.1 ; 95 % Cl 1.5 - 6.7 ) , low scores for h and grip strength ( OR 3.1 ; 95 % Cl 1.5 - 6.6 ) , and a depressive state of mind ( OR 2.2 ; 95 % CI 1.1 - 4.5 ) . To facilitate the use of the model for clinical practice , the model was converted to a " desk model " with three risk categories : low risk ( 0 - 1 predictor ) , moderate risk ( two predictors ) , and high risk ( > or =3 predictors ) . A fall risk model converted to a " desk model , " consisting of the predictors postural sway , fall history , h and dynamometry , and depression , provides added value in the identification of community-dwelling elderly at risk for recurrent falling and facilitates the prediction of recurrent falls OBJECTIVE To assess the usefulness of Duruöz 's H and Index ( DHI ) in patients undergoing haemodialysis . METHODS Patients receiving haemodialysis for more than 2 months were recruited r and omly . Demographic , clinical and functional characteristics of patients were evaluated . Functional assessment was performed with DHI , H and Functional Index ( HFI ) , Health Assessment Question naire ( HAQ ) , Purdue Pegboard , grip strength and 3 kinds of pinch strengths . DHI was correlated ( Spearman 's ) with the other functional parameters in assessing the convergent validity and with non-functional parameters in assessing the divergent validity . RESULTS Sixty patients with a mean age of 50.05 were recruited . The average duration of haemodialysis was 55.02 months . DHI is significantly correlated with HAQ , HFI , Purdue Pegboard scores , grip strength and 3 types of pinch strengths while no significant correlation was found with non-functional parameters . CONCLUSIONS DHI is a practical scale which is efficient in assessing accurately the functional disability of the h and in patients receiving haemodialysis |
12,229 | 27,863,608 | CONCLUSIONS Energy healing has demonstrated some improvement in illness symptoms , however high level evidence consistently demonstrating efficacy is lacking . | BACKGROUND Emerging evidence suggests that some people living with non-communicable diseases ( NCDs ) have integrated energy healing into their self-management strategy , however little is known about its efficacy .
PURPOSE To identify energy healing interventions that impacted positively on the symptom management outcomes for patients living in the community with various NCDs . | The purpose of this study was to investigate the effects of offering Therapeutic Touch ( TT ) as an adjunct to cognitive behavioral therapy ( CBT ) for people with chronic pain . Patients were r and omized to relaxation training ( control group ) or TT plus relaxation ( experimental ) . Subsequently , all participants attended a CBT program . Preprogram and postprogram data were examined to identify patterns of change in pain intensity , self-efficacy , unitary power , disability , and perceived distress . In addition , patterns of attrition were examined . Patients in this study who were r and omized to receive TT fared better in terms of enhanced self-efficacy and unitary power , as well as having lower attrition rates . Trends associated TT with less distress and disability . This pilot study suggests that offering TT as an adjunct to CBT may help to improve clinical outcomes , reduce program attrition , and promote unitary power in those who suffer with chronic pain OBJECTIVE Fibromyalgia is a common , chronic pain condition for which patients frequently use complementary and alternative medicine , including Reiki . Our objective was to determine whether Reiki is beneficial as an adjunctive fibromyalgia treatment . DESIGN This was a factorial design ed , r and omized , sham-controlled trial in which participants , data collection staff , and data analysts were blinded to treatment group . SETTING /LOCATION The study setting was private medical offices in the Seattle , Washington metropolitan area . SUBJECTS The subjects were comprised 100 adults with fibromyalgia . INTERVENTION Four ( 4 ) groups received twice-weekly treatment for 8 weeks by either a Reiki master or actor r and omized to use direct touch or no touch ( distant therapy ) . OUTCOME MEASURES The primary outcome was subjective pain as measured by visual analog scale at weeks 4 , 8 , and 20 ( 3 months following end of treatment ) . Secondary outcomes were physical and mental functioning , medication use , and health provider visits . Participant blinding and adverse effects were ascertained by self-report . Improvement between groups was examined in an intention-to-treat analysis . RESULTS Neither Reiki nor touch had any effect on pain or any of the secondary outcomes . All outcome measures were nearly identical among the 4 treatment groups during the course of the trial . CONCLUSION Neither Reiki nor touch improved the symptoms of fibromyalgia . Energy medicine modalities such as Reiki should be rigorously studied before being recommended to patients with chronic pain symptoms Fatigue is an extremely common side effect experienced during cancer treatment and recovery . Limited research has investigated strategies stemming from complementary and alternative medicine to reduce cancer-related fatigue . This research examined the effects of Reiki , a type of energy touch therapy , on fatigue , pain , anxiety , and overall quality of life . This study was a counterbalanced crossover trial of 2 conditions : ( 1 ) in the Reiki condition , participants received Reiki for 5 consecutive daily sessions , followed by a 1-week washout monitoring period of no treatments , then 2 additional Reiki sessions , and finally 2 weeks of no treatments , and ( 2 ) in the rest condition , participants rested for approximately 1 hour each day for 5 consecutive days , followed by a 1-week washout monitoring period of no scheduled resting and an additional week of no treatments . In both conditions , participants completed question naires investigating cancer-related fatigue ( Functional Assessment of Cancer Therapy Fatigue subscale [ FACT-F ] ) and overall quality of life ( Functional Assessment of Cancer Therapy , General Version [ FACT-G ] ) before and after all Reiki or resting sessions . They also completed a visual analog scale ( Edmonton Symptom Assessment System [ ESAS ] ) assessing daily tiredness , pain , and anxiety before and after each session of Reiki or rest . Sixteen patients ( 13 women ) participated in the trial : 8 were r and omized to each order of conditions ( Reiki then rest ; rest then Reiki ) . They were screened for fatigue on the ESAS tiredness item , and those scoring greater than 3 on the 0 to 10 scale were eligible for the study . They were diagnosed with a variety of cancers , most commonly colorectal ( 62.5 % ) cancer , and had a median age of 59 years . Fatigue on the FACT-F decreased within the Reiki condition ( P=.05 ) over the course of all 7 treatments . In addition , participants in the Reiki condition experienced significant improvements in quality of life ( FACT-G ) compared to those in the resting condition ( P < .05 ) . On daily assessment s ( ESAS ) in the Reiki condition , presession 1 versus postsession 5 scores indicated significant decreases in tiredness ( P < .001 ) , pain ( P < .005 ) , and anxiety ( P<.01 ) , which were not seen in the resting condition . Future research should further investigate the impact of Reiki using more highly controlled design s that include a sham Reiki condition and larger sample sizes The purpose of this study was to evaluate the effect of Reiki as an alternative and complementary approach to treating community-dwelling older adults who experience pain , depression , and /or anxiety . Participants ( N = 20 ) were r and omly assigned to either an experimental or wait list control group . The pre- and posttest measures included the Hamilton Anxiety Scale , Geriatric Depression Scale-Short Form , Faces Pain Scale , and heart rate and blood pressure . The research design included an experimental component to examine changes in these measures and a descriptive component ( semi-structured interview ) to elicit information about the experience of having Reiki treatments . Significant differences were observed between the experimental and treatment groups on measures of pain , depression , and anxiety ; no changes in heart rate and blood pressure were noted . Content analysis of treatment notes and interviews revealed five broad categories of responses : Relaxation ; Improved Physical Symptoms , Mood , and Well-Being ; Curiosity and a Desire to Learn More ; Enhanced Self-Care ; and Sensory and Cognitive Responses to Reiki Purpose . This is a pilot study investigating the effect of healing touch ( HT ) on fatigue in breast cancer patients undergoing radiation therapy ( RT ) . Methods / Design . This study presents the results of a within-subjects design r and omized clinical trial where the treatment group was treated with HT , whereas the control group experienced sham therapy . The setting was a university RT clinic . The participants were breast cancer patients treated with lumpectomy or mastectomy , 21 to 75 years old with an Eastern Cooperative Oncology Group ( ECOG ) score of 0 to 2 . The intervention was a 45-minute session of HT or sham therapy once a week during RT . Outcome measures included fatigue , quality of life ( QOL ) , and anxiety/depression . Results . A total of 70 patients were approached , with 41 completing the study . At completion , the HT participants tended to report higher levels of fatigue , statistically significant for interference ( P = .010 ) and usual fatigue ( P = .024 ) . The control group tended to report greater reductions in fatigue relative to their own means than the HT group ( Cohen ’s d = 0.30 to 0.49 vs 0.06 to 0.18 , respectively ) . There were no statistically significant differences between the groups for QOL . Conclusions . Our enrollment and retention indicate that HT is feasible for women during RT . Our pilot findings do not support a beneficial effect of HT on fatigue or QOL . Future research may explore increasing dose and teasing out therapist effect PURPOSE / OBJECTIVES To determine whether provision of Reiki therapy during outpatient chemotherapy is associated with increased comfort and well-being . DESIGN Double-blind , r and omized clinical controlled trial . SETTING Outpatient chemotherapy center . SAMPLE 189 participants were r and omized to actual Reiki , sham Reiki placebo , or st and ard care . METHODS Patients receiving chemotherapy were r and omly placed into one of three groups . Patients received either st and ard care , a placebo , or an actual Reiki therapy treatment . A demographic tool and pre- and post-tests were given before and after chemotherapy infusion . MAIN RESEARCH VARIABLES Reiki therapy , sham Reiki placebo therapy , st and ard care , and self-reported levels of comfort and well-being pre- and postintervention . FINDINGS Although Reiki therapy was statistically significant in raising the comfort and well-being of patients post-therapy , the sham Reiki placebo also was statistically significant . Patients in the st and ard care group did not experience changes in comfort and well-being during their infusion session . CONCLUSIONS The findings indicate that the presence of an RN providing one-on-one support during chemotherapy was influential in raising comfort and well-being levels , with or without an attempted healing energy field . IMPLICATION S FOR NURSING An attempt by clinic nurses to provide more design ated one-to-one presence and support for patients while receiving their chemotherapy infusions could increase patient comfort and well-being Each therapeutic act may be seen as a result of multiple ingredients that may be specific or nonspecific [ 6 ] . Expectations , preferences , motivation , and patient-doctor interactions are examples of variables that may affect treatment outcome [ 6 , 7 ] . The changed spectrum of medical disorders ( shifted toward aging and chronicity ) and the interindividual differences in health priorities make the focus on single diseases potentially misleading , whereas there is growing awareness that the aim of the treatment should refer to personal goals ( from attainment of cure to prevention of recurrence , from removal of functional impairment to alleviation of symptoms ) [ 8 ] . EBM does not do justice to the importance of these interactions and provides an oversimplified and reductionistic view of treatment . Finally , the presence of investigators with substantial financial conflicts of interest in panels concerned with clinical guidelines and the excessive reliance of metaanalyses on industry-funded studies constitute two major sources of bias in literature interpretation [ 1 , 9 ] . Horwitz et al. [ 10 ] developed a method of clinical inquiry within RCT that can enhance the applicability of results to clinical decision making . Reanalyzing the BetaBlocker Heart Attack Trial , they found that propranolol reduced the risk of dying for the ‘ average ’ patient who survived an acute myocardial infa rct ion , whereas it was harmful in a subgroup characterized by specific cotherapy histories . If we accept the possibility that a treatment The gap between clinical guidelines developed by evidence -based medicine ( EBM ) and the real world of clinicians and patients has been widely recognized . There is currently little evidence that EBM has actually improved patient care [ 1 ] . It is thus not surprising that most of the time clinicians rely more on their own experience and that of their colleagues ( tacit knowledge or ‘ mindlines ’ ) than on explicit evidence from research [ 2 ] . Feinstein and Horwitz [ 3 ] were among the first to warn about excessive reliance on r and omized controlled trials ( RCT ) and meta-analyses that were not intended to answer questions about the treatment of individual patients . The results of these types of trials may show comparative efficacy of treatments for the average r and omized patient but not for those whose characteristics , such as severity of symptoms , comorbidity and other clinical features , depart from st and ard presentations [ 3 ] . In addition , meta-analyses often include highly heterogeneous studies and ascribe conflicting results to r and om variability , whereas different outcomes may reflect different patient population s , enrollment and protocol characteristics [ 4 ] . Even though personalized medicine , described as genomicsbased knowledge , has promised to approach each patient as the biological individual he/she is , the practical applications still have a long way to go and neglect of social and behavioral features may actually lead to ‘ depersonalized ’ medicine [ 5 ] . Other limitations have emerged over time . Received : July 11 , 2014 Accepted after revision : July 21 , 2014 Published online : December 24 , Background : Distant healing , a form of spiritual healing , is widely used for many conditions but little is known about its effectiveness . Methods : In order to evaluate distant healing in patients with a stable chronic condition , we r and omised 409 patients with chronic fatigue syndrome ( CFS ) from 14 private practice s for environmental medicine in Germany and Austria in a two by two factorial design to immediate versus deferred ( waiting for 6 months ) distant healing . Half the patients were blinded and half knew their treatment allocation . Patients were treated for 6 months and allocated to groups of 3 healers from a pool of 462 healers in 21 European countries with different healing traditions . Change in Mental Health Component Summary ( MHCS ) score ( SF-36 ) was the primary outcome and Physical Health Component Summary score ( PHCS ) the secondary outcome . Results : This trial population had very low quality of life and symptom scores at entry . There were no differences over 6 months in post-treatment MHCS scores between the treated and untreated groups . There was a non-significant outcome ( p = 0.11 ) for healing with PHCS ( 1.11 ; 95 % CI –0.255 to 2.473 at 6 months ) and a significant effect ( p = 0.027 ) for blinding ; patients who were unblinded became worse during the trial ( –1.544 ; 95 % CI –2.913 to –0.176 ) . We found no relevant interaction for blinding among treated patients in MHCS and PHCS . Expectation of treatment and duration of CFS added significantly to the model . Conclusions : In patients with CFS , distant healing appears to have no statistically significant effect on mental and physical health but the expectation of improvement did improve outcome 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 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 long-term effects of energetic healing were examined in an experimental design employing a 3 x 3 factorial MANOVA on symptoms of psychological depression and self-perceived stress as measured by the Beck Depression Inventory , Beck Hopelessness , and Perceived Stress scales . Forty-six participants were r and omly assigned to 1 of 3 groups : h and s-on Reiki , distance Reiki , or distance Reiki placebo , and remained blind to treatment condition . Each participant received a 1 to 1.5 hour treatment each week for 6 weeks . Pretest data collected prior to treatment demonstrated no preexisting significant differences among groups . Upon completion of treatment , there was a significant reduction in symptoms of psychological distress in treatment groups as compared with controls ( P < .05 ; Eta square ranging from .09-.18 ) , and these differences continued to be present 1 year later ( P < .05 ; Eta square ranging from .12-.44 ) Complementary therapies are increasingly used to reduce side effects of cancer treatment , without evidence for their effectiveness . In a r and omized , prospect i ve , 2-period , crossover intervention study , the authors tested the effects of therapeutic massage ( MT ) and healing touch ( HT ) , in comparison to presence alone or st and ard care , in inducing relaxation and reducing symptoms in 230 subjects . MT and HT lowered blood pressure , respiratory rate ( RR ) , and heart rate ( HR ) . MT lowered anxiety and HT lowered fatigue , and both lowered totalmooddisturbance . Pain ratings were lower after MT and HT , with 4-week nonsteroidal antiinflammatory drug use less during MT . There were no effects on nausea . Presence reduced RR and HR but did not differ from st and ard care on any measure of pain , nausea , mood states , anxiety , or fatigue . MT and HT are more effective than presence alone or st and ard care in reducing pain , mood disturbance , and fatigue in patients receiving cancer chemotherapy BACKGROUND The purpose of this study was to determine if therapeutic touch , an alternative medicine modality , is effective in the treatment of osteoarthritis of the knee . METHODS A single-blinded r and omized control trial was conducted in a family practice center of a community hospital family practice residency program in Pennsylvania . The patients were between the ages of 40 and 80 , had been given a diagnosis of osteoarthritis of at least one knee , had not had knee replacement , and had no other connective tissue disease . The patients were r and omized to therapeutic touch , mock therapeutic touch , or st and ard care . The main outcome measures were pain and its impact , general well-being , and health status measured by st and ardized , vali date d instruments , as well as the qualitative measurement of a Depth interview . RESULTS Twenty-five patients completed the study . The treatment group had significantly decreased pain and improved function as compared with the placebo and control groups . The qualitative Depth interview confirmed this result . CONCLUSION Despite the small numbers , significant differences were found in improvement in function and pain for patients receiving therapeutic touch . A larger study is needed to confirm these results . Alternative therapies can neither be accepted nor rejected without being subjected to the scientific method The aims of this pilot study were to investigate the effects of Healing Touch ( HT ) on the pain level , joint function , mobility , and depression in persons with osteoarthritis ( OA ) of the knee joint(s ) . A r and omized controlled trial using a repeated measures design was used . Cognitively intact persons ( institutionalized and community ) with a diagnosis of OA of the knee joint(s ) received either HT sessions three times per week for 6 weeks ( n = 12 ) or weekly friendly visits ( FV ) ( n = 7 ) . The HT sessions were delivered by a team of two nurses certified as HT practitioners and the FV was conducted by a nurse . All subjects continued to receive their st and ard care including the methods they had been using to relieve their joint pain . The two groups were similar regarding demographic variables , number of knees affected , co-morbidities , pain medications used and outcome variables at baseline . Two pain outcome measures ( intensity and life interference ) produced significant interaction effects . Two joint outcome measures ( extension and extensor lag ) also produced significant interaction effects . Furthermore , the HT group demonstrated significant improvements in 9 of the 12 outcome variables ( 75 % ) while no significant improvements occurred in the FV group . The HT group exhibited sustained effects ( 3 weeks post treatments ) in three outcome variables . The reduction in joint pain and improvement in joint function suggest that biofield therapies could be effective non-pharmacological adjuncts to treatment of OA OBJECTIVE To study over a period of one and a half years the effect of spiritual healing on patients with idiopathic pain syndrome using several psychological and medical parameters . DESIGN R and omized clinical trial . SETTING Outpatient pain clinic . PATIENTS Twenty-four patients with idiopathic chronic pain who had passed a pretreatment psychological interview were allocated r and omly to receive spiritual healing or no active treatment . MAIN OUTCOME MEASURES Medical interview ( Visual Analog Scale and Pain Clinic Investigation Formula ) ; International Association for the Study of Pain ( IASP ) Data Base Outline ; psychological interview ( Hopkin 's Symptom Checklist , Middlesex Hospital Question naire , Beck 's Depression Inventory , Coping Strategy Question naire , Health Locus of Control scale ) . Patients were evaluated at baseline and at 2 weeks posttreatment . Final assessment at 1 year posttreatment was done with a modified form of IASP Data Base Outline . RESULTS There was a minor decrease in analgesic drug intake and an improvement in sleep patterns in patients treated by the healer . Generally , clinical variables remained unchanged . Attitudes toward spiritual healing improved . There was a decrease in the feeling of hopelessness ( p < 0.05 ) and an increased acceptance of psychological factors as reasons for pain ( p < 0.05 ) . Other scores of the psychological tests were unaffected by the healing . However , half ( n = 6 ) of the treated patients felt that spiritual healing gave them some relief . CONCLUSION Spiritual healing appears harmless and was subjectively helpful to some patients suffering from idiopathic chronic pain syndrome At the request of the Confederation of Healing Organizations ( CHO ) the addition of spiritual healing ( SH ) to conventional therapy has been compared with conventional therapy alone in 29 patients with rheumatoid arthritis ( RA ) using a parallel group design . Clinical and biochemical assessment s were recorded at intervals while subjects received a 6-month course of spiritual healing . Initial psychological assessment was also performed . The addition of SH produced no significant improvement in any of the relevant clinical or laboratory parameters assessed ; although groups were not exactly matched at the start , those requesting SH had more active disease . Between-group comparison showed only an improvement in summated change score ( SCS ) in favour of SH at week 16 , which was lost by week 24 . Individuals displaying the most improvement in pain score or SCS with SH did not have a significantly different psychological profile from those patients who showed the most deterioration . Although our study was small the results do not persuade us to proceed to a larger study for which there would be difficulties in study design BACKGROUND Well- design ed trials are required to assess if complementary and alternative medicine ( CAM ) is effective . AIM This study assessed the effectiveness of spiritual healing for asthma . DESIGN OF STUDY R and omised , placebo-controlled trial . SETTING Aberdeen , Scotl and . METHOD This was a single-blind , three-armed r and omised , controlled trial of spiritual healing for asthma , comparing the effectiveness of five sessions of spiritual healing with placebo ( delivered by an actor ) , and with a control group receiving normal care only . The primary outcome measure was the Juniper Asthma Quality of Life Question naire ( AQLQ ) . Secondary outcomes were forced expiratory flow in one second ( FEV1 ) , peak expiratory flow ( PEF ) , HADS ( Hospital Anxiety Depression Scale ) , SF-36 and MYMOP ( Measure Yourself Medical Outcome Profile ) . Baseline and follow-up data were collected . RESULTS Eighty-eight adult patients receiving pharmacological treatment for asthma participated . AQLQ scores improved significantly from baseline and the end of treatment in all groups ( spiritual healing P = 0.008 ; ' sham ' healing P = 0.001 and control P = 0.01 ) but there was no significant difference between groups ( P = 0.57 ) . These improvements were maintained at follow-up 1 for two of the groups ( spiritual healing P = 0.016 ; sham healing P = 0.001 and control P = 0.09 ) but none of the groups showed an improvement at follow-up 2 ( spiritual healing P = 0.161 ; sham healing P = 0.016 and control P = 0.11 ) . Similar proportions of patients in each group showed a clinical ly important improvement in AQLQ score . Analysis of AQLQ scores at end of treatment and both follow-up periods indicated no significance between group differences . No consistent changes were seen in secondary outcome measures , possibly due to the small sample size . CONCLUSION Spiritual healing does not appear to have any specific affect on patient asthma related quality of life Painful diabetic neuropathy ( PDN ) can be refractory to conventional pharmacologic therapy ( 1–3 ) , which may have significant side effects . Reiki is a h and s-on therapy based on the theoretical existence of a bioenergy field intrinsic to the human body ( 4 ) . Reiki practitioners believe that this bioenergy field can be altered by a trained practitioner and that this can ameliorate disabling symptoms . However , its therapeutic efficacy remains unclear ( 5 ) . This trial therefore assessed the efficacy of Reiki therapy to alleviate pain and improve mobility and quality of life in subjects with type 2 diabetes and PDN . A total of 207 subjects with type 2 diabetes and PDN were recruited . Analgesics including anticonvulsants , tricyclic antidepressants , and nonsteroidal antiflammatory agents were permitted and equally distributed across groups , but no dosing adjustments were allowed . Subjects were stratified according to age , diabetes duration , diabetes control , and recruitment site . Written informed consent and ethical approval was obtained . The study design was a r and omized , semidouble – blind , placebo-controlled , 12-week trial . Subjects were r and omized into one of three treatment groups ( Reiki , mimic Reiki , or usual care ) in a 1:1:1 fashion . Mimic practitioners were actors trained to mimic Reiki practitioners in style of practice . Reiki was applied as previously described ( 6 ) . Practitioners PURPOSE Our aim was to explore the effectiveness of energy healing , a commonly used complementary and alternative therapy , on well-being in cancer patients while assessing the possible influence on the results of participating in a r and omized controlled trial . METHODS 247 patients treated for colorectal cancer ( response rate : 31.5 % ) were either ( a ) r and omized to healing ( RH ) or control ( RC ) or ( b ) had self selected the healing ( SH ) or control condition ( SC ) , and completed question naires assessing well-being ( QoL , depressive symptoms , mood , and sleep quality ) , attitude toward complementary and alternative medicine ( CAM ) , and faith/spirituality at baseline , 1 week , and 2 months post-intervention . They also indicated , at baseline , whether they considered QoL , depressive symptoms , mood , and sleep quality as important outcomes to them . RESULTS Multilevel linear models revealed no overall effect of healing on QoL ( p = 0.156 ) , depressive symptoms ( p = 0.063 ) , mood ( p = 0.079 ) , or sleep quality ( p = 0.346 ) in the intervention groups ( RH , SH ) compared with control ( SC ) . Effects of healing on mood were only found for patients who had a positive attitude toward CAM and considered the outcome in question as important ( SH : Regression coefficient : -8.78 ; SE : 2.64 ; CI : -13.96 to -3.61 ; p = 0.001 , and RH : Regression coefficient -7.45 ; SE : 2.76 ; CI : -12.86 to -2.04 ; p = 0.007 ) . CONCLUSION Whereas it is generally assumed that CAMs such as healing have beneficial effects on well-being , our results indicated no overall effectiveness of energy healing on QoL , depressive symptoms , mood , and sleep quality in colorectal cancer patients . Effectiveness of healing on well-being was , however , related to factors such as self- selection and a positive attitude toward the treatment A prospect i ve r and omised trial was carried out to see whether paranormal healing by laying on of h and s might reduce blood pressure in essential hypertension and whether such an effect might be due to a paranormal , psychological , or placebo factor . Patients were r and omised to three treatment groups : paranormal healing by laying on of h and s ( n=40 ) , paranormal healing at a distance ( n=37 ) , and no paranormal healing ( controls ; n=38 ) . Healing at a distance and no paranormal healing were investigated double blind . Systolic and diastolic blood pressures were significantly reduced in all three groups at week 15 ( mean reduction ( 95 % confidence interval ) 17·1 ( 14·0 to 20·2)/8·3 ( 6·6 to 10·0 ) mm Hg ) . Only the successive reductions in diastolic blood pressures among the groups from week to week were significantly different . Each week diastolic pressure was consistently lower ( average 1·9 mm Hg ) after healing at a distance compared with control , but on paired comparison these differences were not significant . Probably week to week variations among the groups accounted for any differences noted . In this study no treatment was consistently better than another and the data can not therefore be taken as evidence of a paranormal effect on blood pressure . Probably the fall in blood pressure in all three groups either was caused by the psychosocial approach or was a placebo effect of the trial itself The purpose of this study was to determine if Therapeutic Touch ( TT ) decreased pain in elders with degenerative arthritis , compared with routine treatment and progressive muscle relaxation ( PMR ) . Eighty-two noninstitutionalized subjects , age 55 or older , were r and omly assigned to TT or PMR treatments . Subjects served as their own controls for 4 weeks and then received six treatments at 1-week intervals . Visual analogue scales ( VAS ) for pain intensity and distress were used . Significant differences from baseline to postsixth treatment were found within groups . TT decreased pain ( t(46 ) = 7.60 , p = < .001 ) and distress ( t(44 ) = 7.08 , p = < .001 ) . PMR decreased pain ( t(36 ) = 6.58 , p = .005 ) and distress ( t(36 ) = 6.90 , p = < .001 ) . Differences in effectiveness existed between the TT and PMR groups ; the pain and distress scores were lower in the PMR group . The differences approached significance for pain , F(2 , 76 ) = 2.8 , p = .06 , and were significant for distress , F(2 , 75 ) = 5.6 , p = .005 BACKGROUND A representative sample of the adults in Engl and , Scotl and and Wales was interviewed to estimate levels of use of complementary or alternative medicines ( CAMs ) and their socio-economic correlates . METHODS The Omnibus survey is a multi- purpose survey carried out in the United Kingdom by the Office for National Statistics on behalf of non-profit making organizations . The survey is carried out in 2 out of 3 months each quarter using a stratified r and om , probability sample of households . An eight- question module was added to the interview schedule of the survey in March 2001 . Topics included practitioner-based use of 23 named CAM therapies in the past 12 months . The result ing data were analysed in conjunction with socio-economic and demographic variables . RESULTS A response rate of 65 per cent ( 1794/2761 ) was achieved . An estimated 10.0 per cent of the population [ 95 per cent confidence interval ( CI ) 8.7 - 11.5 per cent ] had received any CAM therapy from a practitioner in the past year . No individual therapy was used by more than 2 per cent of the sample . An estimated 6.5 per cent ( 95 per cent CI 5.4 - 7.6 ) had used one of the five main therapies : acupuncture , homeopathy , chiropractic , osteopathy or herbal medicine . Estimates of CAM use were similar in Engl and , Scotl and and Wales . There was a significant positive association between CAM use and non-manual social class ( p < 0.002 ) , age left full-time education ( p < 0.001 ) , and gross income over pounds sterling 15,600 ( p < 0.001 ) . More than half ( 52 per cent ) of the respondents that had used CAM in the past year had not told their general practitioner . CONCLUSIONS Strong correlations between the use of CAM and gross socio-economic indicators are demonstrated in the survey . Repeated national surveys of this type could provide a useful vehicle for collecting information about changing patterns of CAM use on a routine basis This pilot study tested the effectiveness of 6 therapeutic touch treatments on the experience of pain and quality of life for persons with fibromyalgia syndrome . Its findings support that subjects who received therapeutic touch had a statistically significant decrease in pain for each pretherapeutic to posttherapeutic touch treatment , as well as significant improvement in quality of life from pre-first to pre-sixth treatment . Therapeutic touch may be an effective treatment for relieving pain and improving quality of life in this specific population of persons with fibromyalgia syndrome CONTEXT Many individuals suffer from various kinds of chronic pain . Some controlled studies on distant healing for chronic pain exist , but no definitive conclusion has been established . OBJECTIVE To study the effects of distant healing performed by a professional Japanese healer on chronic pain . DESIGN A double-blind r and omized controlled study . SETTING Holos University , Fair Grove , Missouri . SUBJECTS People suffering from chronic pain ( not caused by clear organic diseases or that persists long after a reasonable period of healing following injuries or surgery ) were recruited through local radio and newspaper advertising . Subjects were r and omly assigned to a treatment group or control group using a double-blind procedure . INTERVENTIONS All subjects met the healer at the initial session at Holos University . At the session , a 20-minute group meditation was performed . The healer went back to Japan after the session and started distant healing only to the treatment group for a 2-month period . All participants were asked to meditate for 20 minutes every day during this 2-month period . OUTCOME MEASURES The visual analog scale and McGill Pain Question naire . RESULTS A total of 17 subjects were recruited , and 16 subjects completed the study . Comparison of pretreatment and posttreatment visual analog scale indicated a slightly significant effect of distant healing ( P=.056 ) . The Present Pain Intensity Scale showed significant improvement in the treatment group compared to the control group ( P=.0016 ) . The Pain Rating Index showed improvement in the treatment group , but the difference between both groups was not statistically significant ( P=.12 ) OBJECTIVES Although complementary and alternative medicine ( CAM ) use is becoming increasingly prevalent in the United States , knowledge regarding complementary and alternative therapy use in older adults is limited . The purpose s of this study were to ( 1 ) assess the prevalence and patterns of CAM use in a probability-based sample of older adults ; ( 2 ) describe the characteristics of older CAM users ; and ( 3 ) identify factors associated with complementary and alternative medicine use/nonuse . METHODS A cross-sectional survey design was used . An age-stratified sample of community-dwelling adults ages > or=65 ( N=1200 ) was r and omly selected from the Minnesota Driver 's License/ Identification Tape using names from the Twin Cities seven-county metropolitan area . The mailed question naire included items on demographics , health status , health care utilization , CAM modality use , reasons for use , costs , and complementary and alternative therapy use satisfaction . Descriptive statistics , chi-square tests , and regression analysis were performed . RESULTS Overall , 62.9 % ( N=445 ) of the respondents reported use of one or more complementary and alternative medicine modalities with an average of three modalities ( SD+/-1.9 , range 1 - 11 ) . The top five CAM modalities used were nutritional supplements ( 44.3 % ) , spiritual healing/prayer ( 29.7 % ) , megavitamins ( 28.3 % ) , herbal supplements ( 20.7 % ) , and chiropractic ( 17.8 % ) . Maintaining health and treating a health condition were the primary reasons for CAM use . The most common conditions treated were arthritis ( 44.4 % ) and chronic pain ( 23.5 % ) . Demographic variables were not significantly different between CAM users and nonusers . CAM users reported more unhealthy days than nonusers did . Overall satisfaction with CAM use was high ( 80 % ) . Symptoms of a health problem and desire for personal control over health motivated CAM use . The main barriers to CAM use were lack of reason to use and knowledge about CAM . Only 53 % of users disclosed CAM use to their primary care providers . CONCLUSIONS CAM use is common in older adults , especially those with health problems . The widespread use of oral supplements combined with not disclosing CAM use to primary care providers is a concern OBJECTIVE This small-scale study explores the role of expectancy in response to distant healing by testing two hypotheses : 1 ) Participants aware of placement in the healing condition will report greater relief than those aware they are not receiving distant healing ; 2 ) Participants who express belief in distant healing will report greater relief than those expressing disbelief . METHODS Sixty patients were recruited from a rheumatology outpatient clinic , and through online support networks and blogs . Participants were r and omly allocated to one of four conditions , those in the healing condition received distant healing from self-reported healers , while participants in the control condition received no intervention . Half of the participants knew their treatment allocation and half were blinded . The primary outcome measures were the General Health Question naire ( GHQ-12 ) and the Short-form McGill Pain Question naire . The Paranormal Belief Scale and a measure design ed to assess belief in distant healing were given to determine if belief was correlated with healing outcomes . RESULTS Awareness of being a recipient of distant healing appeared to be associated with improved outcomes for those in the healing group . Medium to large improvements in GHQ scores ( d=.76 ) and McGill Pain scores ( d=.45 ) were calculated for the groups aware of their condition . Participants unaware that they were receiving healing showed no evidence of improved outcomes . Belief in healing did not have an effect on self-reported outcomes . CONCLUSIONS Improvements in reported pain and well-being appear to have been caused by knowledge of allocation in the distant healing condition rather than distant healing alone |
12,230 | 28,112,268 | Dose-response analysis indicated a trend of an approximately linear relationship of the Mediterranean diet score with the incident risk of cognitive disorders . | Recent articles have presented inconsistent findings on the impact of Mediterranean diet in the occurrence of cognitive disorders ; therefore , we performed an up date d systematic review and meta- analysis to evaluate the potential association and dose-response pattern with accumulating evidence . | BACKGROUND Adherence to a Mediterranean diet may improve longevity , but relevant data are limited . METHODS We conducted a population -based , prospect i ve investigation involving 22,043 adults in Greece who completed an extensive , vali date d , food-frequency question naire at base line . Adherence to the traditional Mediterranean diet was assessed by a 10-point Mediterranean-diet scale that incorporated the salient characteristics of this diet ( range of scores , 0 to 9 , with higher scores indicating greater adherence ) . We used proportional-hazards regression to assess the relation between adherence to the Mediterranean diet and total mortality , as well as mortality due to coronary heart disease and mortality due to cancer , with adjustment for age , sex , body-mass index , physical-activity level , and other potential confounders . RESULTS During a median of 44 months of follow-up , there were 275 deaths . A higher degree of adherence to the Mediterranean diet was associated with a reduction in total mortality ( adjusted hazard ratio for death associated with a two-point increment in the Mediterranean-diet score , 0.75 [ 95 percent confidence interval , 0.64 to 0.87 ] ) . An inverse association with greater adherence to this diet was evident for both death due to coronary heart disease ( adjusted hazard ratio , 0.67 [ 95 percent confidence interval , 0.47 to 0.94 ] ) and death due to cancer ( adjusted hazard ratio , 0.76 [ 95 percent confidence interval , 0.59 to 0.98 ] ) . Associations between individual food groups contributing to the Mediterranean-diet score and total mortality were generally not significant . CONCLUSIONS Greater adherence to the traditional Mediterranean diet is associated with a significant reduction in total mortality CONTEXT Higher adherence to a Mediterranean-type diet is linked to lower risk for mortality and chronic diseases , but its association with cognitive decline is unclear . OBJECTIVE To investigate the association of a Mediterranean diet with change in cognitive performance and risk for dementia in elderly French persons . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study of 1410 adults ( > or = 65 years ) from Bordeaux , France , included in the Three-City cohort in 2001 - 2002 and reexamined at least once over 5 years . Adherence to a Mediterranean diet ( scored as 0 to 9 ) was computed from a food frequency question naire and 24-hour recall . MAIN OUTCOME MEASURES Cognitive performance was assessed on 4 neuropsychological tests : the Mini-Mental State Examination ( MMSE ) , Isaacs Set Test ( IST ) , Benton Visual Retention Test ( BVRT ) , and Free and Cued Selective Reminding Test ( FCSRT ) . Incident cases of dementia ( n = 99 ) were vali date d by an independent expert committee of neurologists . RESULTS Adjusting for age , sex , education , marital status , energy intake , physical activity , depressive symptomatology , taking 5 medications/d or more , apolipoprotein E genotype , cardiovascular risk factors , and stroke , higher Mediterranean diet score was associated with fewer MMSE errors ( beta = -0.006 ; 95 % confidence interval [ CI ] , -0.01 to -0.0003 ; P = .04 for 1 point of the Mediterranean diet score ) . Performance on the IST , BVRT , or FCSRT over time was not significantly associated with Mediterranean diet adherence . Greater adherence as a categorical variable ( score 6 - 9 ) was not significantly associated with fewer MMSE errors and better FCSRT scores in the entire cohort , but among individuals who remained free from dementia over 5 years , the association for the highest compared with the lowest group was significant ( adjusted for all factors , for MMSE : beta = -0.03 ; 95 % CI , -0.05 to -0.001 ; P = .04 ; for FCSRT : beta = 0.21 ; 95 % CI , 0.008 to 0.41 ; P = .04 ) . Mediterranean diet adherence was not associated with the risk for incident dementia ( fully adjusted model : hazard ratio , 1.12 ; 95 % CI , 0.60 to 2.10 ; P = .72 ) , although power to detect a difference was limited . CONCLUSIONS Higher adherence to a Mediterranean diet was associated with slower MMSE cognitive decline but not consistently with other cognitive tests . Higher adherence was not associated with risk for incident dementia IMPORTANCE Oxidative stress and vascular impairment are believed to partly mediate age-related cognitive decline , a strong risk factor for development of dementia . Epidemiologic studies suggest that a Mediterranean diet , an antioxidant-rich cardioprotective dietary pattern , delays cognitive decline , but clinical trial evidence is lacking . OBJECTIVE To investigate whether a Mediterranean diet supplemented with antioxidant-rich foods influences cognitive function compared with a control diet . DESIGN , SETTING , AND PARTICIPANTS Parallel-group r and omized clinical trial of 447 cognitively healthy volunteers from Barcelona , Spain ( 233 women [ 52.1 % ] ; mean age , 66.9 years ) , at high cardiovascular risk were enrolled into the Prevención con Dieta Mediterránea nutrition intervention trial from October 1 , 2003 , through December 31 , 2009 . All patients underwent neuropsychological assessment at inclusion and were offered retesting at the end of the study . INTERVENTIONS Participants were r and omly assigned to a Mediterranean diet supplemented with extravirgin olive oil ( 1 L/wk ) , a Mediterranean diet supplemented with mixed nuts ( 30 g/d ) , or a control diet ( advice to reduce dietary fat ) . MAIN OUTCOMES AND MEASURES Rates of cognitive change over time based on a neuropsychological test battery : Mini-Mental State Examination , Rey Auditory Verbal Learning Test ( RAVLT ) , Animals Semantic Fluency , Digit Span subtest from the Wechsler Adult Intelligence Scale , Verbal Paired Associates from the Wechsler Memory Scale , and the Color Trail Test . We used mean z scores of change in each test to construct 3 cognitive composites : memory , frontal ( attention and executive function ) , and global . RESULTS Follow-up cognitive tests were available in 334 participants after intervention ( median , 4.1 years ) . In multivariate analyses adjusted for confounders , participants allocated to a Mediterranean diet plus olive oil scored better on the RAVLT ( P = .049 ) and Color Trail Test part 2 ( P = .04 ) compared with controls ; no between-group differences were observed for the other cognitive tests . Similarly adjusted cognitive composites ( mean z scores with 95 % CIs ) for changes above baseline of the memory composite were 0.04 ( -0.09 to 0.18 ) for the Mediterranean diet plus olive oil , 0.09 ( -0.05 to 0.23 ; P = .04 vs controls ) for the Mediterranean diet plus nuts , and -0.17 ( -0.32 to -0.01 ) for the control diet . Respective changes from baseline of the frontal cognition composite were 0.23 ( 0.03 to 0.43 ; P = .003 vs controls ) , 0.03 ( -0.25 to 0.31 ) , and -0.33 ( -0.57 to -0.09 ) . Changes from baseline of the global cognition composite were 0.05 ( -0.11 to 0.21 ; P = .005 vs controls ) for the Mediterranean diet plus olive oil , -0.05 ( -0.27 to 0.18 ) for the Mediterranean diet plus nuts , and -0.38 ( -0.57 to -0.18 ) for the control diet . All cognitive composites significantly ( P < .05 ) decreased from baseline in controls . CONCLUSIONS AND RELEVANCE In an older population , a Mediterranean diet supplemented with olive oil or nuts is associated with improved cognitive function . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N35739639 BACKGROUND Data on the association between dietary patterns and age-related cognitive decline are inconsistent . OBJECTIVE To determine whether dietary patterns assessed by the alternate Mediterranean diet score ( aMED ) , the Healthy Eating Index-2010 ( HEI-2010 ) , the Alternate Healthy Eating Index 2010 ( AHEI-2010 ) , or the Dietary Approach to Stop Hypertension ( DASH ) diet score are associated with cognitive decline in older women , and to examine whether dietary patterns modify the risk for cognitive decline in women with hypertension . DESIGN Prospect i ve , longitudinal cohort study . Food frequency question naires were used to derive dietary patterns at baseline . Hypertension was defined as self-report of current drug therapy for hypertension or clinic measurement of systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg . PARTICIPANTS AND SETTING Postmenopausal women ( N=6,425 ) aged 65 to 79 years who participated in the Women 's Health Initiative Memory Study and were cognitively intact at baseline . MAIN OUTCOME MEASURES Cognitive decline was defined as cases of mild cognitive impairment ( MCI ) or probable dementia ( PD ) . Cases were identified through rigorous screening and expert adjudication . STATISTICAL ANALYSES PERFORMED Cox proportional hazards models with multivariable adjustment were used to estimate the relative risk for developing MCI or PD . RESULTS During a median follow-up of 9.11 years , we documented 499 cases of MCI and 390 of PD . In multivariable analyses we did not detect any statistically significant relationships across quintiles of aMED , HEI-2010 , DASH , and AHEI-2010 scores and MCI or PD ( P values for trend=0.30 , 0.44 , 0.23 , and 0.45 ) . In women with hypertension , we found no significant association between dietary patterns and cognitive decline ( P values for trend=0.19 , 0.08 , 0.07 , and 0.60 ) . CONCLUSIONS Dietary patterns characterized by the aMED , HEI-2010 , AHEI-2010 , or DASH dietary score were not associated with cognitive decline in older women . Adherence to a healthy dietary pattern did not modify the risk for cognitive decline in women with hypertension CONTEXT Both higher adherence to a Mediterranean-type diet and more physical activity have been independently associated with lower Alzheimer disease ( AD ) risk but their combined association has not been investigated . OBJECTIVE To investigate the combined association of diet and physical activity with AD risk . DESIGN , SETTING , AND PATIENTS Prospect i ve cohort study of 2 cohorts comprising 1880 community-dwelling elders without dementia living in New York , New York , with both diet and physical activity information available . St and ardized neurological and neuropsychological measures were administered approximately every 1.5 years from 1992 through 2006 . Adherence to a Mediterranean-type diet ( scale of 0 - 9 ; trichotomized into low , middle , or high ; and dichotomized into low or high ) and physical activity ( sum of weekly participation in various physical activities , weighted by the type of physical activity [ light , moderate , vigorous ] ; trichotomized into no physical activity , some , or much ; and dichotomized into low or high ) , separately and combined , were the main predictors in Cox models . Models were adjusted for cohort , age , sex , ethnicity , education , apolipoprotein E genotype , caloric intake , body mass index , smoking status , depression , leisure activities , a comorbidity index , and baseline Clinical Dementia Rating score . MAIN OUTCOME MEASURE Time to incident AD . RESULTS A total of 282 incident AD cases occurred during a mean ( SD ) of 5.4 ( 3.3 ) years of follow-up . When considered simultaneously , both Mediterranean-type diet adherence ( compared with low diet score , hazard ratio [ HR ] for middle diet score was 0.98 [ 95 % confidence interval { CI } , 0.72 - 1.33 ] ; the HR for high diet score was 0.60 [ 95 % CI , 0.42 - 0.87 ] ; P = .008 for trend ) and physical activity ( compared with no physical activity , the HR for some physical activity was 0.75 [ 95 % CI , 0.54 - 1.04 ] ; the HR for much physical activity was 0.67 [ 95 % CI , 0.47 - 0.95 ] ; P = .03 for trend ) were associated with lower AD risk . Compared with individuals neither adhering to the diet nor participating in physical activity ( low diet score and no physical activity ; absolute AD risk of 19 % ) , those both adhering to the diet and participating in physical activity ( high diet score and high physical activity ) had a lower risk of AD ( absolute risk , 12 % ; HR , 0.65 [ 95 % CI , 0.44 - 0.96 ] ; P = .03 for trend ) . CONCLUSION In this study , both higher Mediterranean-type diet adherence and higher physical activity were independently associated with reduced risk for AD Objective XXXto assess the effect on cognition of a controlled intervention testing Mediterranean diets ( MedDiet ) . Design XXXr and omized trial after 6.5 years of nutritional intervention . Setting Eight primary care centers affiliated to the University of Navarra . Participants A r and om sub sample of 285 participants ( 95 r and omly allocated to each of 3 groups ) of the PREDIMED-NAVARRA trial . All of them were at high vascular risk ( 44.8 % men , 74.1± 5.7 years at cognitive evaluation ) . Interventions Nutritional intervention comparing two MedDiets ( supplemented with extra-virgin olive oil [ EVOO ] or mixed nuts ) versus a low-fat control diet . Participants received intensive education to increase adherence to the intended intervention . Participants allocated to the MedDiet groups received EVOO ( 1 l/week ) or 30 g/day of mixed nuts . Dietary habits were evaluated using a vali date d 137-item food frequency question naire ( FFQ ) . Additionally , adherence to MedDiet was appraised using a 14-item question naire both at baseline and yearly thereafter . Measurements XXXcognitive performance as a main outcome and cognitive status ( normal , mild cognitive impairment [ MCI ] or dementia ) as a secondary outcome were evaluated by two neurologists blinded to group assignment after 6.5 years of nutritional intervention . Results Better post-trial cognitive performance versus control in all cognitive domains and significantly better performance across fluency and memory tasks were observed for participants allocated to the MedDiet+EVOO group . After adjustment for sex , age , education , apolipoprotein E genotype , family history of cognitive impairment/dementia , smoking , physical activity , body mass index , hypertension , dyslipidaemia , diabetes , alcohol and total energy intake , this group also showed lower MCI ( OR=0.34 95 % CI : 0.12–0.97 ) compared with control group . Participants assigned to MedDiet+Nuts group did not differ from controls . Conclusion A long-term intervention with an EVOO-rich MedDiet result ed in a better cognitive function in comparison with a control diet . However , non-significant differences were found for most cognitive domains . Participants allocated to an EVOO-rich MedDiet had less MCI than controls There is evidence from a population -based study of an inverse relationship between monounsaturated fatty acids ( MUFA ) energy intake and age-related cognitive decline ( ARCD ) , while high polyunsaturated fatty acids ( PUFA ) intake was positively associated with cognitive impairment in elderly subjects . We investigated the possible role of MUFA and PUFA on age-related cognitive changes . A population -based , prospect i ve study was carried out on 278 , 186 , and 95 nondemented elderly subjects ( 65 - 84 years ) evaluated for global cognitive functions ( Mini-Mental State Examination , MMSE ) at the first ( 1992 - 1993 ) , second ( 1995 - 1996 ) , and third survey ( 2000 - 2001 ) , respectively , from the r and omized cohort of Casamassima , Bari , Italy ( n=704 ) , one of the eight centers of the Italian Longitudinal Study on Aging ( ILSA ) . MUFA and PUFA intakes were assessed at baseline with a semi-quantitative food frequency question naire . High MUFA and PUFA energy intakes and total energy intake were significantly associated with a better cognitive performance in a 8.5-year follow-up . In this prospect i ve population -based study on older nondemented subjects with a typical Mediterranean diet , high MUFA and PUFA intakes appeared to be protective against ARCD OBJECTIVES We studied the effect of the Mediterranean diet on plasma levels of C-reactive protein ( CRP ) , white blood cell counts , interleukin (IL)-6 , tumor necrosis factor (TNF)-alpha , amyloid A , fibrinogen , and homocysteine . BACKGROUND To the best of our knowledge , the mechanism(s ) by which the Mediterranean diet reduces cardiovascular risk are not well understood . METHODS During the 2001 to 2002 period , we r and omly enrolled 1,514 men ( 18 to 87 years old ) and 1,528 women ( 18 to 89 years old ) from the Attica area of Greece ( of these , 5 % of men and 3 % of women were excluded because of a history of cardiovascular disease ) . Among several factors , adherence to the Mediterranean diet was assessed by a diet score that incorporated the inherent characteristics of this diet . Higher values of the score meant closer adherence to the Mediterranean diet . RESULTS Participants who were in the highest tertile of the diet score had , on average , 20 % lower CRP levels ( p = 0.015 ) , 17 % lower IL-6 levels ( p = 0.025 ) , 15 % lower homocysteine levels ( p = 0.031 ) , 14 % lower white blood cell counts ( p = 0.001 ) , and 6 % lower fibrinogen levels ( p = 0.025 ) , as compared with those in the lowest tertile . The findings remained significant even after various adjustments were made . Borderline associations were found regarding TNF-alpha ( p = 0.076 ) , amyloid A levels ( p = 0.19 ) , and diet score . CONCLUSIONS Adherence to the traditional Mediterranean diet was associated with a reduction in the concentrations of inflammation and coagulation markers . This may partly explain the beneficial actions of this diet on the cardiovascular system OBJECTIVE To determine whether the Mediterranean diet and other dietary variables are predictors of transition from healthy cognitive aging to mild cognitive impairment and cognitive decline . DESIGN Longitudinal . PARTICIPANTS We assessed 1528 individuals , aged 60 - 64 years , who were participating in a prospect i ve epidemiological study of mental health and aging . We tested participants at two time points , 4 years apart , for mild cognitive impairment using either the International Consensus Criteria , impairment on the Clinical Dementia Rating scale ( Clinical Dementia Rating : 0.5 ) , or any of a suite of criteria sets ( any mild cognitive disorder ) . We used logistic regression to assess the dietary predictors of conversion to clinical diagnoses and multiple regression to identify the predictors of cognitive decline ( change in global cognition ) in healthy participants . RESULTS Of the 1528 participants with no cognitive impairment in the first wave of assessment and complete data , 10 participants were diagnosed with mild cognitive impairment , 19 with Clinical Dementia Rating 0.5 , and 37 participants presented with any mild cognitive disorder at follow-up . Adherence to Mediterranean diet was not found to be protective against cognitive decline but excessive caloric intake , and high intake of monounsaturated fats was predictive of mild cognitive impairment . CONCLUSIONS In this large longitudinal investigation of generally healthy individuals Mediterranean diet was not found to be protective of cognitive decline Objective : We sought to determine the relationship of greater adherence to Mediterranean diet ( MeD ) and likelihood of incident cognitive impairment ( ICI ) and evaluate the interaction of race and vascular risk factors . Methods : A prospect i ve , population -based , cohort of individuals enrolled in the Reasons for Geographic and Racial Differences in Stroke ( REGARDS ) Study 2003–2007 , excluding participants with history of stroke , impaired cognitive status at baseline , and missing data on Food Frequency Question naires ( FFQ ) , was evaluated . Adherence to a MeD ( scored as 0–9 ) was computed from FFQ . Cognitive status was evaluated at baseline and annually during a mean follow-up period of 4.0 ± 1.5 years using Six-item-Screener . Results : ICI was identified in 1,248 ( 7 % ) out of 17,478 individuals fulfilling the inclusion criteria . Higher adherence to MeD was associated with lower likelihood of ICI before ( odds ratio [lsqb]OR[rsqb ] 0.89 ; 95 % confidence interval [lsqb]CI[rsqb ] 0.79–1.00 ) and after adjustment for potential confounders ( OR 0.87 ; 95 % CI 0.76–1.00 ) including demographic characteristics , environmental factors , vascular risk factors , depressive symptoms , and self-reported health status . There was no interaction between race ( p = 0.2928 ) and association of adherence to MeD with cognitive status . However , we identified a strong interaction of diabetes mellitus ( p = 0.0134 ) on the relationship of adherence to MeD with ICI ; high adherence to MeD was associated with a lower likelihood of ICI in nondiabetic participants ( OR 0.81 ; 95 % CI 0.70–0.94 ; p = 0.0066 ) but not in diabetic individuals ( OR 1.27 ; 95 % CI 0.95–1.71 ; p = 0.1063 ) . Conclusions : Higher adherence to MeD was associated with a lower likelihood of ICI independent of potential confounders . This association was moderated by presence of diabetes mellitus CONTEXT Healthy lifestyle factors are associated with maintenance of erectile function in men . OBJECTIVE To determine the effect of weight loss and increased physical activity on erectile and endothelial functions in obese men . DESIGN , SETTING , AND PATIENTS R and omized , single-blind trial of 110 obese men ( body mass index > or = 30 ) aged 35 to 55 years , without diabetes , hypertension , or hyperlipidemia , who had erectile dysfunction that was determined by having a score of 21 or less on the International Index of Erectile Function ( IIEF ) . The study was conducted from October 2000 to October 2003 at a university hospital in Italy . INTERVENTIONS The 55 men r and omly assigned to the intervention group received detailed advice about how to achieve a loss of 10 % or more in their total body weight by reducing caloric intake and increasing their level of physical activity . Men in the control group ( n = 55 ) were given general information about healthy food choices and exercise . MAIN OUTCOMES MEASURES Erectile function score , levels of cholesterol and triglycerides , circulating levels of interleukin 6 , interleukin 8 , and C-reactive protein , and endothelial function as assessed by vascular responses to l-arginine . RESULTS After 2 years , body mass index decreased more in the intervention group ( from a mean [ SD ] of 36.9 [ 2.5 ] to 31.2 [ 2.1 ] ) than in the control group ( from 36.4 [ 2.3 ] to 35.7 [ 2.5 ] ) ( P<.001 ) , as did serum concentrations of interleukin 6 ( P = .03 ) , and C-reactive protein ( P = .02 ) . The mean ( SD ) level of physical activity increased more in the intervention group ( from 48 [ 10 ] to 195 [ 36 ] min/wk ; P<.001 ) than in the control group ( from 51 [ 9 ] to 84 [ 28 ] min/wk ; P<.001 ) . The mean ( SD ) IIEF score improved in the intervention group ( from 13.9 [ 4.0 ] to 17 [ 5 ] ; P<.001 ) , but remained stable in the control group ( from 13.5 [ 4.0 ] to 13.6 [ 4.1 ] ; P = .89 ) . Seventeen men in the intervention group and 3 in the control group ( P = .001 ) reported an IIEF score of 22 or higher . In multivariate analyses , changes in body mass index ( P = .02 ) , physical activity ( P = .02 ) , and C-reactive protein ( P = .03 ) were independently associated with changes in IIEF score . CONCLUSION Lifestyle changes are associated with improvement in sexual function in about one third of obese men with erectile dysfunction at baseline Objective To examine associations between frequency of ready-to-eat-cereal ( RTEC ) consumption and cognitive function among elderly men and women of the Cache County Study on Memory Health and Aging in Utah . Design A population -based prospect i ve cohort study established in Cache County , Utah in 1995 . Setting and Participants 3831 men and women > 65 years of age who were living in Cache County , Utah in 1995.MeasurementDiet was assessed using a 142-item food frequency question naire at baseline . Cognitive function was assessed using an adapted version of the Modified Mini-Mental State examination ( 3MS ) at baseline and three subsequent interviews over 11 years . RTEC consumption was defined as daily , weekly , or infrequent use . Results In multivariable models , more frequent RTEC consumption was not associated with a cognitive benefit . Those consuming RTEC weekly but less than daily scored higher on their baseline 3MS than did those consuming RTEC more or less frequently ( 91.7 , 90.6 , 90.6 , respectively ; p-value < 0.001 ) . This association was maintained across 11 years of observation such that those consuming RTEC weekly but less than daily declined on average 3.96 points compared to an average 5.13 and 4.57 point decline for those consuming cereal more or less frequently ( p-value = 0.0009 ) . Conclusion Those consuming RTEC at least daily had poorer cognitive performance at baseline and over 11 years of follow-up compared to those who consumed cereal more or less frequently . RTEC is a nutrient dense food , but should not replace the consumption of other healthy foods in the diets ’ of elderly people . Associations between RTEC consumption , dietary patterns , and cognitive function deserve further study This study tested the potential risk-reduction benefits of Mediterranean Diet ( MD ) and regular exercise training on microvascular activity and cardiorespiratory capacity in postmenopausal women . Fifteen sedentary postmenopausal participants ( age = 54.6 ± 3.6 ) were r and omised into either exercise training or exercise combined with following MD for eight-weeks , and were assessed for their cardiorespiratory capacity , and upper- and lower-limb endothelial cutaneous vascular conductance ( CVC ) test using Laser Doppler Fluximetry ( LDF ) , coupled with measuring endothelium-dependent Acetylcholine Chloride ( Ach ) and -dependent Sodium Nitropurruside ( SNP ) vasodilators . Exercise training improved cardiorespiratory capacity as indicated by ventilatory threshold ( 11.5 ± 2.1 vs. 14.0 ± 3.0 ml·kg-1·min-1 , p < 0.05 ) and improved the microcirculatory perfusion results of CVC for both vasodilators Ach ( p < 0.001 , d = 0.65 ) and SNP ( p = 0.003 , d = 0.53 ) in the lower-limb and ACh ( p = 0.01 , d = 0.41 ) and SNP ( p = 0.03 , d = 0.48 ) in the upper-limb , all ( p < 0.05 ) . However , combining exercise with MD showed a stronger improvement in Ach ( p = 0.02 , d = 0.36 ) of the lower limb , than in exercise alone group . The results suggest that regular moderate exercise improves microcirculatory vascular function and increases exercise tolerance , both are responsible for reducing cardiovascular risk in postmenopausal women . However , combining MD with exercise suggests additional microvascular vasodialiatory improvement , suggesting an effective strategy for further cardiovascular risk-reduction in this high-risk group CONTEXT Limited information exists on the interaction between diet and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ( statins ) and the interaction 's effect on serum lipid and lipoprotein levels , insulin sensitivity , and circulating antioxidant vitamin and provitamin levels . OBJECTIVE To evaluate the separate and combined effects of diet and simvastatin therapy on serum levels of lipids , lipoproteins , antioxidants , and insulin . DESIGN , SETTING , AND PARTICIPANTS R and omized , controlled crossover trial conducted from August 1997 to June 1998 in 120 previously untreated hypercholesterolemic men aged 35 to 64 years who were recruited from the community in Turku , southwestern Finl and . INTERVENTIONS After a 4- to 6-week placebo run-in period , participants were r and omly allocated to a habitual diet ( n = 60 ) or dietary treatment group ( n = 60 ) , and each of these groups was further r and omized in a double-blind crossover fashion to receive simvastatin ( 20 mg/d ) or placebo , each for 12 weeks ( n = 30 in each group ) . The main goals of the dietary treatment were to reduce energy intake from saturated plus trans-unsaturated fats to no more than 10 % by replacing them partly with monounsaturated and polyunsaturated fats rich in omega-3 fatty acids and to increase intake of fruits , vegetables , and dietary fiber . MAIN OUTCOME MEASURES Changes in levels of total , low-density lipoprotein ( LDL ) , and high-density lipoprotein ( HDL ) cholesterol ; triglycerides ; apolipoprotein B ; insulin ; glucose ; and antioxidants at week 12 of each treatment period , compared among the 4 groups . RESULTS Dietary treatment decreased levels of total cholesterol by 7.6 % ( P<.001 ) , LDL cholesterol by 10.8 % ( P<.001 ) , HDL cholesterol by 4.9 % ( P = .01 ) , apolipoprotein B by 5.7 % ( P = .003 ) , serum insulin by 14.0 % ( P = .02 ) , and alpha-tocopherol by 3.5 % ( P = .04 ) . Simvastatin decreased levels of total cholesterol by 20.8 % , LDL cholesterol by 29.7 % , triglycerides by 13.6 % , apolipoprotein B by 22.4 % , alpha-tocopherol by 16.2 % , beta-carotene by 19.5 % , and ubiquinol-10 by 22.0 % ( P<.001 for all ) and increased levels of HDL cholesterol by 7.0 % ( P<.001 ) and serum insulin by 13.2 % ( P = .005 ) . Glucose levels remained unchanged in all groups . The effects of dietary treatment and simvastatin were independent and additive . CONCLUSIONS A modified Mediterranean-type diet rich in omega-3 fatty acids efficiently potentiated the cholesterol-lowering effect of simvastatin , counteracted the fasting insulin-elevating effect of simvastatin , and , unlike simvastatin , did not decrease serum levels of beta-carotene and ubiquinol-10 |
12,231 | 26,180,077 | Although isolated pericardiocentesis can safely deliver immediate symptomatic relief , subsequent catheter drainage or sclerotherapy are required to minimize recurrence .
PBP has been shown to be highly effective and may be particularly useful in managing recurrent effusions . | The present systematic review assessed the safety and efficacy of percutaneous interventions for malignant pericardial effusion ( MPE ) , with primary endpoint of recurrence of pericardial effusion . | PURPOSE Malignant pericardial effusion , although highly variable , is an uncommon complication of cancer . It is often associated with symptoms like dyspnea , chest pain , and cough , which may be severe and disabling . We analyzed the results of our current treatment policy to evaluate the effectiveness and tolerance of a new approach for this disorder . PATIENTS AND METHODS Patients with malignant pericardial effusions were treated with intracavitary thiotepa ( 15 mg on days 1 , 3 , and 5 ) through an indwelling pericardial cannula after extraction of as much pericardial fluid as possible on day 0 . Responses were assessed by clinical examination , computed tomographic ( CT ) scan , and echocardiography before treatment , 1 month after treatment , and every 2 months thereafter . Twenty-three patients with malignant symptomatic pericardial effusion were treated and all were assessable for effectiveness and tolerance of the procedure . RESULTS Nine patients with breast cancer , 11 with lung cancer , two with an unknown primary tumor , and one with metastatic melanoma were treated . In all but three patients , systemic medical treatment was started after completion of intracavitary therapy . Nineteen patients responded to treatment ( 83 % ; 95 % confidence interval , 61 % to 95 % ) with a rapid improvement of symptoms . The median time to pericardial effusion progression was 8.9 months ( range , 1 to 26 ) . No significant side effects were registered , except one patient who had transient grade III thrombocytopenia and leukopenia and one patient who had grade I leukopenia . CONCLUSION A short course of intracavitary treatment with thiotepa is highly effective and well tolerated in the treatment of malignant pericardial effusion OBJECTIVES This study describes the technique , clinical characteristics and results of the first 50 patients undergoing percutaneous balloon pericardiotomy as part of a multicenter registry . BACKGROUND Percutaneous balloon pericardiotomy involves the use of a percutaneous balloon dilating catheter to create a nonsurgical pericardial window . METHODS Patients eligible for percutaneous balloon pericardiotomy had either cardiac tamponade ( n = 36 ) or a moderate to large pericardial effusion ( n = 14 ) . In addition to clinical follow-up , serial echocardiograms and chest X-ray films were obtained . RESULTS The procedure was considered successful in 46 patients after a mean follow-up period of 3.6 + /- 3.3 months . Two patients required an early operation , one for bleeding from a pericardial vessel and one for persistent pericardial catheter drainage . Two patients required a late operation for recurrent tamponade . Minor complications of the procedure included fever in 6 of the first 37 patients ( studied before the prophylactic use of antibiotic agents ) , thoracentesis or chest tube placement in 8 and a small spontaneously resolving pneumothorax in 2 . Despite the short-term success of this procedure , the long-term prognosis of the 44 patients with malignant pericardial disease remained poor ( mean survival time 3.3 + /- 3.1 months ) . CONCLUSIONS Percutaneous balloon pericardiotomy is successful in helping to manage large pericardial effusions , particularly in patients with a malignant condition . It may become the preferred treatment to avoid a more invasive procedure for patients with pericardial effusion and a limited life expectancy We review ed 36 cases of symptomatic malignant pericardial effusion managed with pericardiocentesis at our institution from 1982 to 1989 . There were 13 men and 23 women , aged 49 + /- 12 years ( range , 33 - 76 years ) . The commonest underlying tumours were lung cancer ( 12 cases , 33 % ) and breast cancer ( 11 cases , 30 % ) . Pericardiocentesis was successful as the initial management in 34 of 36 patients ( 94 % ) ; one patient died as a result of the procedure and another required subxiphoid incision and tube drainage of the effusion . When intrapericardial sclerotherapy was performed , only three of 28 patients required repeat pericardiocentesis , and when sclerotherapy was not performed initially , four of seven patients had recurrent symptomatic effusions . Median survival following pericardiocentesis in breast cancer patients was 10 months ( range , 0 - 36 months ) and in all other malignancies was four months ( range , 0 - 12 months ) . We conclude that pericardiocentesis with intrapericardial sclerotherapy provides good local control for symptomatic malignant pericardial effusion in the majority of patients . In spite of this , the median survival of such patients is poor , especially in patients with malignancies other than breast cancer , with few patients surviving more than a few months PURPOSE To compare the clinical efficacy and toxicity of doxycycline and bleomycin as sclerosing agents in the primary management of malignant pericardial effusion ( MPE ) . METHODS Twenty-seven consecutive adult patients referred to a tertiary-care institution for the management of cardiac tamponade and malignancy underwent pericardial drainage through a percutaneously placed pigtail catheter . They were then alternately assigned to undergo bleomycin or doxycycline pericardial sclerosis . RESULTS There were 13 men and 14 women , with a median age of 59 years . They mainly had lung ( 70 % ) and breast cancers ( 11 % ) , and all had clinical and echocardiographic evidence of cardiac tamponade . Although all patients had successfully placed catheters , six were inadvertently dislodged before sclerosis ; 11 underwent bleomycin sclerosis and 10 doxycycline sclerosis . Twenty patients ( one early death ) were assessable . One patient in each group failed to respond to sclerosis with the initial agent , but both were sclerosed successfully with the other agent . Sclerosis was achieved with a median of two instillations for each agent and total median doses of bleomycin 20 mg and doxycycline 1,250 mg . Seventy percent of doxycycline patients developed significant retrosternal pain , compared with no bleomycin patients ( P = .04 ) . Doxycycline patients required a median of 3.5 more days of hospitalization ( 8.5 v 5 ) and 2 more days of pericardial catheterization ( 7 v 5 ) compared with bleomycin patients . Tamponade recurred in one bleomycin patient at 253 days , and in no doxycycline patient . CONCLUSION Although bleomycin and doxycycline are equally effective sclerosing agents , bleomycin is associated with significantly less morbidity and should be the first-line chemical sclerosing agent for malignant pericardial effusions |
12,232 | 26,653,397 | MAIN RESULTS Supportive supervision can increase job satisfaction and health worker motivation .
Evidence is mixed on whether this translates to increased clinical competence and there is little evidence of the effect on clinical outcomes . | BACKGROUND It may be assumed that supportive supervision effectively builds capacity , improves the quality of care provided by frontline health workers , and positively impacts clinical outcomes .
Evidence on the role of supervision in Sub-Saharan Africa has been inconclusive , despite the critical need to maximize the workforce in low-re source setting s. OBJECTIVES To review the published literature from Sub-Saharan Africa on the effects of supportive supervision on quality of care , and health worker motivation and performance . | Millennium Development Goal ( MDG ) 5 commits us to reducing maternal mortality rates by three quarters and MDG 4 commits us to reducing child mortality by two-thirds between 1990 and 2015 . In order to reach these goals , greater access to basic emergency obstetric care ( EmOC ) as well as comprehensive EmOC which includes safe Caesarean section , is needed .. The limited capacity of health systems to meet dem and for obstetric services has led several countries to utilize mid-level cadres as a substitute to more extensively trained and more internationally mobile healthcare workers . Although this does provide greater capacity for service delivery , concern about the performance and motivation of these workers is emerging . We propose that poor leadership characterized by inadequate and unstructured supervision underlies much of the dissatisfaction and turnover that has been shown to exist amongst these mid-level healthcare workers and indeed health workers more generally . To investigate this , we conducted a large-scale survey of 1,561 mid-level cadre healthcare workers ( health workers trained for shorter periods to perform specific tasks e.g. clinical officers ) delivering obstetric care in Malawi , Tanzania , and Mozambique . Participants indicated the primary supervision method used in their facility and we assessed their job satisfaction and intentions to leave their current workplace . In all three countries we found robust evidence indicating that a formal supervision process predicted high levels of job satisfaction and low intentions to leave . We find no evidence that facility level factors modify the link between supervisory methods and key outcomes . We interpret this evidence as strongly supporting the need to strengthen leadership and implement a framework and mechanism for systematic supportive supervision . This will promote better job satisfaction and improve the retention and performance of obstetric care workers , something which has the potential to improve maternal and neonatal outcomes in the countdown to 2015 QUALITY PROBLEM Research in Kenya in the mid-1990s suggested poor quality family planning services and limited access to services . Clinical guidelines for family planning and reproductive health were published in 1991 and up date d in 1997 , but never widely distributed . CHOICE OF SOLUTION Managers and trainers chose intensive , district-level training workshops to disseminate guidelines and up date health workers on guideline content and best practice s. INTERVENTION Training workshops were held in 41 districts in 1999 . Trainees were instructed to up date their untrained co-workers afterwards . As a reinforcement , providers in r and omly selected areas received a ' cascade training package ' of instructional material s and training tips . Providers in 15 r and omly selected clinics also received ' supportive supervision ' visits as a second reinforcement . EVALUATION METHODOLOGY A cluster-r and omized experiment in 72 clinics assessed the overall impact of the training and the marginal benefits of the two reinforcing activities . Research ers and trainers created several dozen indicators of provider knowledge , attitudes , beliefs and practice s. Binomial and multivariate analyses were used to compare changes over time in indicators and in aggregated summary scores . Data from patient interviews were analysed to corroborate provider practice self-reports . Cost data were collected for an economic evaluation . RESULTS Post-test data collected in 2000 showed that quality of care and access increased after the intervention . The cascade training package showed less impact than supportive supervision , but the former was more cost-effective . LESSONS LEARNED Service delivery guidelines , when properly disseminated , can improve family planning practice s in sub-Saharan Africa OBJECTIVES We evaluated an intervention to support health workers after training in Integrated Management of Childhood Illness ( IMCI ) , a strategy that can improve outcomes for children in developing countries by encouraging workers ' use of evidence -based guidelines for managing the leading causes of child mortality . METHODS We conducted a r and omized trial in Benin . We administered a survey in 1999 to assess health care quality before IMCI training . Health workers then received training plus either study supports ( job aids , nonfinancial incentives , and supervision of workers and supervisors ) or usual supports . Follow-up surveys conducted in 2001 to 2004 assessed recommended treatment , recommended or adequate treatment , and an index of overall guideline adherence . RESULTS We analyzed 1244 consultations . Performance improved in both intervention and control groups , with no significant differences between groups . However , training proceeded slowly , and low- quality care from health workers without IMCI training diluted intervention effects . Per- protocol analyses revealed that workers with IMCI training plus study supports provided better care than did those with training plus usual supports ( 27.3 percentage-point difference for recommended treatment ; P < .05 ) , and both groups outperformed untrained workers . CONCLUSIONS IMCI training was useful but insufficient . Relatively inexpensive supports can lead to additional improvements |
12,233 | 27,178,404 | Conclusions A lack of evidence as to the optimal strategy for compression has result ed in a marked variation in clinical practice . | Objectives There is insufficient evidence to inform guidelines on the optimal compression strategy following ablation for varicose veins .
This study aim ed to identify the practice of key opinion leaders performing r and omised clinical trials involving endovenous ablation . | OBJECTIVES Comparison of Reverse Foam Sclerotherapy of the great saphenous vein ( GSV ) combed with sapheno-femoral junction ( SFJ ) ligation to st and ard ( Babcock ) stripping and invagination ( Pin ) stripping in a prospect i ve clinical series . DESIGN Prospect i ve clinical series . MATERIAL S AND METHODS 90 consecutive limbs of 82 patients with incompetence of the GSV result ing in varicose veins were prospect ively r and omised into 3 groups of 30 , treated by SFJ ligation and either reverse foam sclerotherapy , st and ard stripping or invagination stripping of the GSV . Outcomes were assessed post-operatively and at 2-weeks follow-up . Peri-operative blood loss ( 24 hrs ) , analgesic requirement , bruising and residual varicosities were assessed . Bruising was assessed by both patients and independent assessors using question naires . RESULTS SFJ ligation plus reverse foam sclerotherapy of the GSV was associated with significantly less blood loss , bruising and post-op discomfort than either of the stripping techniques . ( p<0.001 , Mann-Whitney ) CONCLUSION St and ard stripping of the GSV and invagination stripping are not associated with major discomfort and problems in the early post-operative period . SFJ ligation and GSV reverse foam sclerotherapy yielded greater patient satisfaction with less post-op bruising and discomfort and reduced analgesic requirements Endovenous laser ablation ( EVLA ) and radiofrequency ablation ( RFA ) are both associated with excellent technical , clinical and patient‐reported outcomes for the treatment of varicose veins . The aim of this study was to compare the techniques in a r and omized clinical trial BACKGROUND Ultrasound-guided foam sclerotherapy and endovenous laser ablation are widely used alternatives to surgery for the treatment of varicose veins , but their comparative effectiveness and safety remain uncertain . METHODS In a r and omized trial involving 798 participants with primary varicose veins at 11 centers in the United Kingdom , we compared the outcomes of foam , laser , and surgical treatments . Primary outcomes at 6 months were disease-specific quality of life and generic quality of life , as measured on several scales . Secondary outcomes included complications and measures of clinical success . RESULTS After adjustment for baseline scores and other covariates , the mean disease-specific quality of life was slightly worse after treatment with foam than after surgery ( P=0.006 ) but was similar in the laser and surgery groups . There were no significant differences between the surgery group and the foam or the laser group in measures of generic quality of life . The frequency of procedural complications was similar in the foam group ( 6 % ) and the surgery group ( 7 % ) but was lower in the laser group ( 1 % ) than in the surgery group ( P<0.001 ) ; the frequency of serious adverse events ( approximately 3 % ) was similar among the groups . Measures of clinical success were similar among the groups , but successful ablation of the main trunks of the saphenous vein was less common in the foam group than in the surgery group ( P<0.001 ) . CONCLUSIONS Quality -of-life measures were generally similar among the study groups , with the exception of a slightly worse disease-specific quality of life in the foam group than in the surgery group . All treatments had similar clinical efficacy , but complications were less frequent after laser treatment and ablation rates were lower after foam treatment . ( Funded by the Health Technology Assessment Programme of the National Institute for Health Research ; Current Controlled Trials number , IS RCT N51995477 . ) OBJECTIVES This study aims to compare the efficacy and side effects of foam sclerotherapy of the saphenous veins with or without post-treatment compression using graduated elastic stockings . DESIGN This is a prospect i ve open r and omised controlled trial conducted in two centres . PATIENTS AND METHODS Sixty patients with incompetent great ( GSV ) or small saphenous veins ( SSV ) underwent ultrasound-guided foam sclerotherapy . R and omisation was conducted immediately after sclerotherapy to two parallel groups , one ( CG ) with compression stockings ( 15 - 20 mmHg worn during the day , for 3 weeks ) and the other ( WCG ) without compression . Efficacy of sclerotherapy and all of the side effects were assessed , including side effects in the treated region . On days 14 and 28 , clinical and duplex ultrasound ( DUS ) assessment s were performed by independent experts . Patients also completed quality of life ( QOL ) , symptom question naires and provided satisfaction scores . RESULTS Five men and 55 women ranging in age from 32 to 78 ( mean 57 years ) years were included : 29 in the WCG and 31 in the CG group . On day 28 , abolition of venous reflux and occlusion of the vein was obtained in 100 % of the cases in both groups . The length of the occluded vein was the same in both groups ( mean 36 cm for the GSV and 30 cm for the SSV ) as was the mean diameter of the occluded vein ( 5 mm ) . Symptoms and QOL question naires showed equivalent improvement in both groups on day 28 compared to pre-treatment assessment s. Side effects were few with no statistical difference between the two groups . Patient satisfaction scores were high in both groups for the outcome of sclerotherapy results , and good or very good for compression in 50 % of the CG cases . CONCLUSION We found no difference between compression and control groups when comparing efficacy , side effects , satisfaction scores , symptoms and QOL . Further studies are required to establish the role of compression in sclerotherapy and to evaluate other compression strategies OBJECTIVES Comparison of sapheno-femoral ligation and stripping ( SFL/S ) versus endovenous laser ablation ( EVLA , 980-nm ) in the treatment of great saphenous vein ( GSV ) insufficiency , using local tumescent anaesthesia . DESIGN R and omised , single centre trial . MATERIAL S AND METHODS Patients with GSV incompetence and varicose veins were r and omised to either SFL/S or EVLA . At days 1 , 2 , 3 , 7 , 10 , and 14 post-treatment , patients completed question naires on pain and quality of life . Recurrent varicose veins were evaluated by Duplex ultrasound ( DUS ) performed at 1 and 6 weeks , and 6 and 12 months . RESULTS 130 legs in 121 patients were treated by SFL/S ( n=68 ) or EVLA ( n=62 ) . Significantly more post-treatment pain was noted after EVLA at days 7 , 10 and 14 ( p<0.01 ; p<0.01 ; p=0.01 ) , more hindrance in mobility at days 7 ( p<0.01 ) and 10 ( p=0.01 ) , and in self care ( p=0.03 ) and daily activities ( p=0.01 ) at day 7 compared to SFL/S. DUS at 1-year follow-up showed 9 % recurrences ( 5/56 ) after EVLA and 10 % ( 5/49 ) after SFL/S. CONCLUSION Both SFL/S and EVLA , using local tumescent anaesthesia , were well tolerated , with no difference in short-term recurrence rate . In the second week after EVLA , patients experienced significantly more pain result ing in restricted mobility , self care and daily activity compared to Introduction : Chronic venous insufficiency is the most common vascular disease in the adult population . However , r and omized clinical trials ( RCTs ) comparing therapeutic options are limited . Patients and Methods : A total of 180 patients with saphenofemoral junction and great saphenous reflux detected on duplex were r and omized to either ultrasound-guided radiofrequency ablation ( RFA ) or st and ard surgical treatment . The study participants blindly chose an assignment card that placed them in either group A ( ultrasound-guided RFA of the great saphenous vein [ GSV ] ; n = 90 ) ; or group B ( surgical management n = 90 ) . Patients were followed up for 24 months . Results : The primary occlusion rate in group A was 94.5 % versus 100 % in group B. Radiofrequency ablation had a lower overall complication rate ( P = .02 ) and shorter post-intervention hospital stay ( P = .001 ) . Kaplan-Meier analysis showed no significant differences in recurrence rates at 24 months follow-up ( P = .45 ) . Radiofrequency ablation was significantly more expensive ( P = .003 ) . Conclusion : Great saphenous vein occlusion was achieved efficiently in 94 % of our group using RFA with minimal complications and obvious advantages as compared to st and ard surgery Endovenous laser ablation ( EVLA ) is a popular minimally invasive treatment for varicose veins . Surgical treatment , featuring junctional ligation and inversion stripping , has shown excellent clinical and cost effectiveness . The clinical effectiveness of both treatments was compared within a r and omized trial AIM Major side effects after endovenous laser ablation ( EVLA ) are pain and bruising . The aim of this study was to compare outcome and side effects after EVLA of incompetent great saphenous veins ( GSV ) with a 1 470 nm diode laser ( Ceralas E , biolitec ) using a power of 15 or 25 W. METHODS Between 28 November 2007 and 15 January 2008 , 40 consecutive patients ( 40 legs ) with an incompetent GSV were treated by EVLA . The patients were r and omized in two groups . In Group A ( 20 patients ) was used a 15-W-power laser and in Group B ( 20 patients ) a 25-W-power laser was used . All patients were re-examined after 1 , 10 and 30 days clinical ly and by Duplex for complications and occlusion in the treated vein segment in a st and ardized way . RESULTS There was no significant difference concerning gender , age , C of CEAP , body mass index or diameter of the treated vein . In Group A a mean of 465 mL tumescence fluid ( TF ) was used and in Group B TF was of 433 mL. In Group A the mean linear endovenous energy density ( LEED ) was 109.7 J/cm and in Group B 132.6 J/cm . The subgroup Bsub included 16 patients of Group B with a comparable mean LEED of 115.8 J/cm . In all groups occlusion of the treated veins was achieved for all patients . The diameter of the GSV reduced at 3 cm below the sapheno-femoral junction from 1.1 to 0.6 cm , 1.0 to 0.6 cm and 0.9 to 0.6 cm respectively in the three groups . The modified CEAP clinical score improved significantly in all groups . In Group A patients have been administered analgesic tablets for a shorter period . There was also a trend to less postinterventional pain and analgesic use in Group A , but it was not significant . Ecchymosis was rare in both groups ( 8 in Group A , 7 in Group B ) . CONCLUSIONS In this prospect i ve r and omized comparative study the power of the laser did not influence the occlusion rate when a high LEED with comparable values was used . In both groups pain and ecchymoses were less frequent in this study with a 1 470 nm diode laser than reported in studies with 810 - 980 nm systems . A lower power level significantly reduced use of analgesic tablets BACKGROUND Great saphenous vein ( GSV ) incompetence is the most common cause of superficial venous insufficiency . Radiofrequency catheter ablation ( RFA ) is superior to conventional ligation and stripping , and endovenous laser treatment ( EVL ) has emerged as an effective alternative to RFA . This r and omized study evaluated RFA and EVL for superficial venous insufficiency due to GSV incompetence and compared early and 1-year results . METHODS Between June 2006 and May 2008 , patients with symptomatic primary venous insufficiency due to GSV incompetence were r and omized to RFA or EVL . Patients with bilateral disease were r and omized for treatment of the first leg and received the alternative method on the other . Pretreatment examination included a leg assessment using the Venous Clinical Severity Score ( VCSS ) and CEAP classification . Patients completed the Chronic Venous Insufficiency Question naire 2 ( CIVIQ2 ) . RFA was performed with the ClosurePlus system ( VNUS Medical Technologies , Sunnyvale , Calif ) . EVL was performed with the EVLT system ( AngioDynamics Inc , Queensbury , NY ) . Early ( 1-week and 1-month ) postoperative results of pain , bruising , erythema , and hematoma were recorded . Duplex ultrasound ( DU ) imaging was used at 1 week and 1 year to evaluate vein status . VCSS scores and CEAP clinical class were recorded at each postoperative visit , and quality of life ( QOL ) using CIVIQ2 was assessed at 1 month and 1 year . RESULTS The study enrolled 118 patients ( 141 limbs ) : 46 ( 39 % ) were r and omized to RFA and 48 ( 40 % ) to EVL , and 24 ( 20 % ) had bilateral GSV incompetence . At 1 week , one patient in the RFA group had an open GSV and was deemed a failure . More bruising occurred in the EVL group ( P = .01 ) at 1 week , but at 1 month , there was no difference in bruising between groups . At 1 year , DU imaging showed evidence of recanalization with reflux in 11 RFA and 2 EVL patients ( P = .002 ) . The mean VCSS score change from baseline to 1 week postprocedure was higher for RFA than EVL ( P = .002 ) , but there was no difference between groups at 1 month ( P = .07 ) and 1 year ( P = .9 ) . Overall QOL mean score improved over time for all patients ( P < .001 ) . CEAP clinical class scores of > or=3 were recorded in 21 RFA ( 44 % ) and 24 EVL patients ( 44 % ) pretreatment , but at 1-year , 9 RFA ( 19 % ) and 12 EVL patients ( 24 % ) had scores of > or=3 ( P < .001 ) . This represented a significant improvement in all patients compared with baseline . CONCLUSION Both methods of endovenous ablation effectively reduce symptoms of superficial venous insufficiency . EVL is associated with greater bruising and discomfort in the perioperative period but may provide a more secure closure over the long-term than RFA OBJECTIVE The aim of this r and omized study was to compare a new method of endovenous saphenous vein obliteration ( Closure System , VNUS Medical Technologies , Inc , Sunnyvale , Calif ) with the conventional stripping operation in terms of short-term recovery and costs . METHODS Twenty-eight selected patients for operative treatment of primary greater saphenous vein tributary varicose veins were r and omly assigned to endovenous obliteration ( n = 15 ) or stripping operation ( n = 13 ) . Postoperative pain was daily assessed during the 1st week and on the 14th postoperative day . The length of sick leave was determined . The R AND -36 health survey was used to assess the patient health-related quality of life . The patient conditions were controlled 7 to 8 weeks after surgery , and patients underwent examination with duplex ultrasonography . The comparison of costs included both direct medical costs and costs result ing from lost of productivity of the patients . Costs that were similar in the study groups were not considered in the analysis . RESULTS All operations were successful , and the complication rates were similar in the two groups . Postoperative average pain was significantly less severe in the endovenous obliteration group as compared with the stripping group ( at rest : 0.7 , st and ard deviation [ SD ] 0.5 , versus 1.7 , SD 1.3 , P = .017 ; on st and ing : 1.3 , SD 0.7 , versus 2.6 , SD 1.9 , P = .026 ; on walking : 1.8 , SD 0.8 , versus 3.0 , SD 1.8 , P = .036 ; with t test ) . The sick leaves were significantly shorter in the endovenous obliteration group ( 6.5 days , SD 3.3 days , versus 15.6 days , SD 6.0 days ; 95 % CI , 5.4 to 12.9 ; P < .001 , with t test ) . Physical function was also restored faster in the endovenous obliteration group . The estimated annual investment costs of the closure operation were US $ 3360 . The other direct medical costs of the Closure operation were about $ 850 , and those of the conventional treatment were $ 360 . With inclusion of the value of the lost working days , the Closure treatment was cost-saving for society , and when 40 % of the patients are retired ( or 60 % of the productivity loss was included ) , the Closure procedure became cost-saving at a level of 43 operations per year . CONCLUSION Endovenous obliteration may offer advantages over the conventional stripping operation in terms of reduced postoperative pain , shorter sick leaves , and faster return to normal activities , and it appears to be cost-saving for society , especially among employed patients . Because the procedure is also associated with shorter convalescence , this new method may potentially replace conventional varicose vein surgery Objectives To evaluate the effect of eccentric compression applied by a new crossed-tape technique on procedure-related pain occurrence after endovenous laser ablation ( ELA ) of the great saphenous vein ( GSV ) . Methods From April 2005 to June 2006 , 200 consecutive ELA procedures were r and omized to receive ( group A : 100 ) or not ( group B : 100 ) an eccentric compression applied in the medial aspect of the thigh . Patients were scheduled for a seven-day examination to assess the level of pain experienced . Pain intensity was measured using a visual analogue scale giving a numerical grade from 0 ( no pain ) to 10 ( worst pain ever ) . Results The intensity of postoperative pain was significantly reduced ( P < 0.001 ) in the eccentric compression group as compared with the non-compression one . Conclusions This technique of eccentric compression greatly reduces the intensity of postoperative pain after ELA of the GSV BACKGROUND Many case series have been published on treatments of varicose veins , but comparative r and omized controlled trials remain sparse . OBJECTIVE To compare the anatomic success rate , frequency of major complications , and quality -of-life improvement of endovenous laser ablation ( EVLA ) , ultrasound-guided foam sclerotherapy ( UGFS ) , and conventional surgery ( CS ) , after 1-year follow-up . METHODS A total of 240 consecutive patients with primary symptomatic great saphenous vein reflux were r and omized to EVLA , UGFS , or CS , consisting of high ligation and short stripping . Primary outcome was anatomic success defined as obliteration or absence of the treated vein on ultrasound examination after 1 year . Secondary outcomes were complications , improvement of the " C " class of the CEAP classification , and improvement of disease-specific ( Chronic Venous Insufficiency Quality -of-Life Question naire ) and general ( EuroQol 5 ) quality -of-life scores . RESULTS More than 80 % of the study population was classified as C2 or C3 venous disease . After 1 year , the anatomic success rate was highest after EVLA ( 88.5 % ) , followed by CS ( 88.2 % ) and UGFS ( 72.2 % ) ( P < .001 ) . The complication rate was low and comparable between treatment groups . All groups showed significant ( P < .001 ) improvement of EuroQol 5 and Chronic Venous Insufficiency Quality -of-Life Question naire scores after therapy ; 84.3 % of all treated patients showed an improvement of the " C " of the CEAP classification . CONCLUSIONS After 1-year follow-up , EVLA is as effective as CS and superior to UGFS according to occlusion on ultrasound duplex . Quality of life improves after treatment in all groups significantly The acute and long-term effect of elastic stockings has been evaluated in 20 patients ( 20 limbs ) with grade 2 venous disease . The sites of venous reflux were determined with colour flow duplex scanning . Air Plethysmography was used to measure the amount of venous reflux and the ejecting capacity of the calf muscle pump . The patients were classified in to two different groups , A and B. Both groups of patients wore elastic stockings for four weeks . In group A ( no. = 9 ) the measurements were done before , during and one day after the removal of the stockings , whereas in group B ( no. = 11 ) the last measurements were done immediately after the removal of the stockings . Patients that showed improvement in their haemodynamics were re-examined a week later . Elastic compression appeared to be beneficial in both groups . The application of the elastic stockings improved reflux and the residual volume fraction in both groups and the ejecting capacity of the calf muscle pump in group B. Immediately after the removal of the stockings ( Group B ) all the measurements regressed to the initial values with the exemption of the residual volume fraction . However , one week later , the latter also regressed to the original value . It is concluded that the beneficial effect of elastic stockings on the venous haemodynamics is present mainly when the stockings are worn . It is completely abolished within a day after their removal Introduction : Endovenous laser ablation ( EVLA ) has been demonstrated to be an effective treatment for lower limb varicose veins in the short and midterm results . This study reports the 5-year outcomes of EVLA technique at different power setting s. Methods : Patients with primary symptomatic , unilateral varicose veins secondary to saphenofemoral junction ( SFJ ) incompetence and great saphenous vein ( GSV ) reflux were recruited and r and omized to either 12W ( intermittent laser withdrawal ) or 14W ( continuous laser withdrawal ) . They were assessed at baseline , 1 , 6 , 12 , 52 , 104 weeks , and 5 years . Outcome measures included : Venous Clinical Severity Score ( VCSS ) , pain scores , time taken to return to normal functions , complications , recurrence , quality of life ( QoL ) , and duplex ultrasound findings . Results : 76 consecutive patients , M : F 30:46 , median age 54(IQR : 37.3 - 59 ) years were r and omized . Intragroup analysis : Significant improvement was seen in both groups in VCSS , pain scores , Aberdeen varicose vein question naire ( AVVQ ) scores , Shortform-36 ( SF-36 ) and Euroqol ( EQ-5D ) domains over the follow-up period ( P < 0.05 ) . Intergroup analysis : Over 5 years , clinical ly recurrent varicosities and duplex detected SFJ incompetence was less frequent and patient satisfaction with cosmetic outcome significantly higher in the 14W group ( P < 0.05 ) . There was no significant difference between the groups in duration of procedure , postoperative pain scores , return to normal functioning , complications , VCSS , disease specific ( AVVQ ) and generic ( SF36 , EQ-5D ) QoL measures ( P > 0.05 ) . Conclusion : Late outcomes following EVLA were superior for the 14W continuous power setting s achieving better long term venous occlusion and lowered recurrence rates without increasing post-operative morbidity . Hence 14W continuous setting should be the energy delivery mode of choice OBJECTIVES There have been few r and omised studies comparing Radiofrequency Ablation(RFA ) with other endovenous techniques . The primary aim of this study was to determine whether RFA of the great saphenous vein ( GSV ) was associated with less pain and bruising than endovenous laser ablation ( EVLA ) . MATERIAL S AND METHODS This trial had two cohorts-- patients with bilateral GSV incompetence causing varicose veins ( VV ) and those with unilateral GSV VVs . In total 87 legs were treated in this study . Limbs in the bilateral group were treated with RFA in one leg and EVLA in the other . In the unilateral group limbs were r and omised to RFA or EVLA . RFA was performed using the Celon RFiTT system ( Teltow , Germany ) . EVLA was performed using an 810 nm Laser ( Biolitec AG , Germany ) . Phlebectomies were performed as required . Primary endpoints were patient assessed pain and bruising measured by visual analogue scale ( VAS ) . Secondary endpoints were patency assessed by duplex ultrasound at 6 weeks and 6 months . RESULTS In the bilateral group , RFA result ed in significantly less pain than EVLA on days 2 - 11 postoperatively . RFA also result ed in significantly less bruising than EVLA on days 3 - 9 . There were no significant differences in mean post operative pain , bruising and activity scores in the unilateral group . Both RFA and EVLA result ed in occlusion rates of 95 % at 10 days postoperatively . CONCLUSIONS RFA was less painful for patients than EVLA and produced less bruising in the postoperative period with comparable success rates but there was no difference in the unilateral group New minimally invasive treatment modalities , such as ultrasound‐guided foam sclerotherapy ( UGFS ) , are becoming more popular . In a multicentre r and omized controlled non‐inferiority trial , the effectiveness and costs of UGFS and surgery for treatment of the incompetent great saphenous vein ( GSV ) were compared Endovenous laser ablation ( EVLA ) is a minimally invasive technique for treating varicose veins due to truncal vein incompetence . This r and omized trial compared EVLA with conventional surgery in patients with primary saphenofemoral and great saphenous vein ( GSV ) reflux Background : Endovenous ablation of varicose veins using radiofrequency ablation ( RFA ) and endovenous laser therapy ( EVLT ) has reported advantages over traditional open surgical treatment . There is little evidence comparing the efficacy and patient-reported outcomes between the 2 endovenous solutions . This study compares the RFA and EVLT strategies in a prospect i ve double-blind clinical trial . Methods : Consecutive patients with primary unilateral great saphenous vein ( GSV ) reflux undergoing endovenous treatment were r and omized to RFA ( VNUS ClosureFAST ) or EVLT ( 810-nm diode laser ) . The primary outcome measure was GSV occlusion at 3 months after treatment . Secondary outcome measures were occlusion at 7 days , postoperative pain , analgesic requirement , and bruising , assessed at day 7 after surgery . Quality of life ( QoL ) was assessed preoperatively and 3 months after surgery using the Aberdeen Varicose Vein Question naire ( AVVQ ) and EQ-5D . Results : A total of 159 patients were r and omized to RFA ( 79 patients ) or EVLT ( 80 patients ) . Groups were well matched for demographics , disease extent , severity , and preoperative QoL. Duplex scanning confirmed 100 % vein occlusion at 1 week in both groups . At 3 months , occlusion was 97 % for RFA and 96 % for EVLT ; P = 0.67 . Median ( interquartile range ) percentage above-knee bruise area was greater after EVLT 3.85 % ( 6.1 ) than after RFA 0.6 % ( 2 ) ; P = 0.0001 . Postoperative pain assessed at each of the first 7 postoperative days was less after RFA ( P = 0.001 ) . Changes in the AVVQ ( P = 0.12 ) and EQ-5D ( P = 0.66 ) at 3 months were similar in both groups . Conclusions : RFA and EVLT offer comparable venous occlusion rates at 3 months after treatment of primary GSV varices ; with neither modality proving superior . RFA is associated with less periprocedural pain , analgesic requirement , and bruising . Registration number : IS RCT N63135694 ( http://www.controlled-trials.com BACKGROUND Following above-knee ( AK ) great saphenous vein ( GSV ) endovenous laser ablation ( EVLA ) 40 % to 50 % patients have residual varicosities . This r and omized controlled trial ( RCT ) assesses whether more extensive GSV ablation enhances their resolution and influences symptom improvement . METHOD Sixty-eight limbs ( 65 patients ) with varicosities and above and below-knee GSV reflux were r and omized to Group A : AK-EVLA ( n = 23 ) ; Group B : EVLA mid-calf to groin ( n = 23 ) ; and Group C : AK-EVLA , concomitant below-knee GSV foam sclerotherapy ( n = 22 ) . Primary outcomes were residual varicosities requiring sclerotherapy ( 6 weeks ) , improvement in Aberdeen varicose vein severity scores ( AVVSS , 12 weeks ) , patient satisfaction , and complication rates . RESULTS EVLA ablated the treated GSV in all limbs . Sclerotherapy requirements were Group A : 14/23 ( 61 % ) ; Group B : 4/23 ( 17 % ) ; and Group C : 8/22 ( 36 % ) ; chi2 = 9.3 ( 2 df ) P = .01 with P(A-B ) = 0.006 ; P(B-C ) = 0.19 ; P(A-C ) = 0.14 . AVVSS scores improved in all groups as follows : A : 14.8 ( 9.3 - 22.6 ) to 6.4 ( 3.2 - 9.1 ) , ( P < .001 ) ; B : 15.8 ( 10.2 - 24.5 ) to 2.5 ( 1.1 - 3.7 ) , ( P < .001 ) ; and C : 15.1 ( 9.0 - 23.1 ) to 4.1 ( 2.3 - 6.8 ) , ( P < .001 ) and P(A-B ) = 0.011 , P(A -C ) = 0.042 . Patient satisfaction was highest in Group B. BK-EVLA was not associated with saphenous nerve injury . CONCLUSIONS Extended EVLA is safe , increases spontaneous resolution of varicosities , and has a greater impact on symptom reduction . Similar benefits occurred after concomitant BK-GSV foam sclerotherapy Introduction : No r and omized clinical trial comparing treatment options for small saphenous vein ( SSV ) incompetence exists , and there is no clear evidence that this axis behaves the same as the great saphenous vein after treatment . This means that the existing literature base , centered on the treatment of great saphenous vein incompetence can not simply be extrapolated to inform the management of SSV insufficiency . This trial compares the gold st and ard of conventional surgery and endovenous laser ablation ( EVLA ) in the management of SSV incompetence . Methods : Patients with unilateral , primary saphenopopliteal junction incompetence and SSV reflux were r and omized equally into parallel groups receiving either surgery or EVLA . Patients were assessed at baseline and weeks 1 , 6 , 12 , and 52 . Outcomes included successful abolition of axial reflux on duplex , visual analog pain scores , recovery time , complication rates , Venous Clinical Severity Score , and quality of life profiling . Results : A total of 106 patients were recruited and r and omized to surgery ( n = 53 ) or EVLA ( n = 53 ) . Abolition of SSV reflux was significantly higher after EVLA ( 96.2 % ) than surgery ( 71.7 % ) ( P < 0.001 ) . Postoperative pain was significantly lower after EVLA ( P < 0.05 ) , allowing an earlier return to work and normal function ( P < 0.001 ) . Minor sensory disturbance was significantly lower in the EVLA group ( 7.5 % ) than in surgery ( 26.4 % ) ( P = 0.009 ) . Both groups demonstrated similar improvements in Venous Clinical Severity Score and quality of life . Conclusion : EVLA produced the same clinical benefits as conventional surgery but was more effective in addressing the underlying pathophysiology and was associated with less periprocedural morbidity allowing a faster recovery . ( Registration number : NCT00841178 . PURPOSE The present study was design ed to address the hypothesis that radiofrequency ( RF ) thermal ablation , as represented by the ClosureFAST system , is associated with improved recovery and quality -of-life ( QOL ) parameters compared with 980-nm endovenous laser ( EVL ) thermal ablation of the great saphenous vein ( GSV ) . MATERIAL S AND METHODS Eighty-seven veins in 69 patients were r and omized to ClosureFAST or 980-nm EVL treatment of the GSV . The study was prospect i ve , r and omized , single-blinded , and carried out at five American sites and one European site . Primary endpoints ( postoperative pain , ecchymosis , tenderness , and adverse procedural sequelae ) and secondary endpoints ( venous clinical severity scores and QOL issues ) were measured at 48 hours , 1 week , 2 weeks , and 1 month after treatment . RESULTS All scores referable to pain , ecchymosis , and tenderness were statistically lower in the ClosureFAST group at 48 hours , 1 week , and 2 weeks . Minor complications were more prevalent in the EVL group ( P = .0210 ) ; there were no major complications . Venous clinical severity scores and QOL measures were statistically lower in the ClosureFAST group at 48 hours , 1 week , and 2 weeks . CONCLUSIONS RF thermal ablation was significantly superior to EVL as measured by a comprehensive array of postprocedural recovery and QOL parameters in a r and omized prospect i ve comparison between these two thermal ablation modalities for closure of the GSV BACKGROUND Endovenous laser ( EVL ) ablation of the great saphenous vein ( GSV ) is thought to minimize postoperative morbidity and reduce work loss compared with high ligation and stripping ( HL/S ) . However , the procedures have not previously been compared in a r and omized trial with parallel groups where both treatments were performed in tumescent anesthesia on an out-patient basis . METHODS Patients with varicose veins due to GSV insufficiency were r and omized to either EVL ( 980 nm ) or HL/S in tumescent anesthesia . Miniphlebectomies were also performed . Patients were examined preoperatively and at 12 days , and 1 , 3 , and 6 months postoperatively . Sick leave , time to normal physical activity , pain score , use of analgesics , Aberdeen score , Medical Outcomes Study Short Form-36 quality -of-life score , Venous Clinical Severity Score ( VCSS ) , and complication rates were investigated . The total cost of the procedures , including lost wages and equipment , was calculated . Cost calculations were based on the st and ard fee for HL/S with the addition of laser equipment and the st and ard salary and productivity level in Denmark . RESULTS A follow-up of 6 months was achieved in 121 patients ( 137 legs ) . The groups were well matched for patient and GSV characteristics . Two HL/S procedures failed , and three GSVs recanalized in the EVL group . The groups experienced similar improvement in quality -of-life scores and VCSS score at 3 months . Only one patient in the HL/S group had a major complication , a wound infection that was treated successfully with antibiotics . The HL/S and EVL groups did not differ in mean time to resume normal physical activity ( 7.7 vs 6.9 calendar days ) and work ( 7.6 vs 7.0 calendar days ) . Postoperative pain and bruising was higher in the HL/S group , but no difference in the use of analgesics was recorded . The total cost of the procedures , including lost wages , was euro 3084 ( $ 3948 US ) in the HL/S and euro 3396 ( $ 4347 US ) in the EVL group . CONCLUSIONS This study suggests that the short-term efficacy and safety of EVL and HL/S are similar . Except for slightly increased postoperative pain and bruising in the HL/S group , no differences were found between the two treatment modalities . The treatments were equally safe and efficient in eliminating GSV reflux , alleviating symptoms and signs of GSV varicosities , and improving quality of life . Long-term outcomes , particularly with respect to recurrence rates , shall be investigated in future studies , including the continuation of the present Background Patients with varicose veins seek medical assistance for many reasons , including esthetic ones . The development of suitable and more flexible instruments , along with less invasive techniques , enables the establishment of new therapeutic procedures . Objective To compare endovenous great saphenous vein photocoagulation with an 810 nm diode laser and the conventional stripping operation in the same patient . Methods Twenty patients selected for operative treatment of primary great saphenous vein insufficiency on duplex scanning were assigned to a bilateral r and om comparison . In all cases , both techniques were performed , one on each lower limb . Clinical ly , evaluation was assessed on the seventh , thirtieth , and sixtieth postoperative days . Patients underwent examination with duplex ultrasonography and air plethysmography during the follow-up . Results Patients who received endovenous photocoagulation presented with the same pain but fewer swellings and less bruising than the stripping side . Most patients indicated that the limb operated on by laser received more benefits than the other . There was only one recanalization and no adverse effects . The venous filling time showed better hemodynamics in both techniques . Conclusion The endovenous great saphenous vein photocoagulation is safe and well tolerated and presents results comparable to those of conventional stripping OBJECTIVES The aim of this study is to compare efficacy , early postoperative morbidity and patient comfort of two laser wavelengths and fibre types in treatment of great saphenous vein ( GSV ) incompetence result ing in varicosities of the lower limb . DESIGN Prospect i ve r and omised clinical trial . MATERIAL S AND METHODS Sixty patients ( 106 limbs ) were r and omised into two groups . They were treated with bare-tip fibres and a 980 nm laser in group 1 and radial fibres and 1470 nm laser in group 2 in order to ablate the GSV . Local pain , ecchymosis , in duration and paraesthesia in treated regions , distance from skin , vein diameter , treated vein length , tumescent anaesthesia volume , delivered energy and patient satisfaction were recorded . Follow-up visits were planned on the 2nd postoperative day , 7th day , 1st , 2nd , 3rd and 6th months . RESULTS Mean GSV diameters at saphenofemoral junction and knee levels were 12.1 S.D. 4.3 mm and 8.2 S.D. 2.4 mm , and 11.8 S.D. 4.1 mm and 7.9 S.D. 2.6 mm respectively in groups 1 and 2 . There were 14 patients with in duration , 13 with ecchymosis and nine minimal paraesthesia in group 1 and no or minimal local pain , minimum ecchymosis or in duration in group 2 . Duration of pain and need for analgesia was also lower in group 2 ( p < 0.05 ) . There was significant difference on postoperative day 2 , day 7 and 1st month control in favour of group 2 in venous clinical severity scores ( VCSS ) . CONCLUSION Treatment of the GSV by endovenous laser ablation using a 1470 nm laser and a radial fibre result ed in less postoperative pain and better VCSS scores in the first month than treatment with a 980 nm laser and a bare-tip fibre PURPOSE The prevalence of reflux in the deep and superficial venous systems in the Edinburgh population and the relationship between patterns of reflux and the presence of venous disease on clinical examination were studied . METHODS A cross-sectional survey was done on men and women ranging in age from 18 to 64 years , r and omly selected from 12 general practice s. The presence of varicose veins and chronic venous insufficiency was noted on clinical examination , as was the duration of venous reflux by means of duplex scanning in 8 vein segments on each leg . Results were compared using cut-off points for reflux duration ( RD ) of 0.5 seconds or more ( RD > /= 0.5 ) and more than 1.0 second ( RD > 1.0 ) to define reflux . RESULTS There were 1566 study participants , 867 women and 699 men . The prevalence of reflux was similar in the right and left legs . The proportion of participants with reflux was highest in the lower thigh long saphenous vein ( LSV ) segment ( 18.6 % in the right leg and 17.5 % in the left leg for RD > /= 0.5 ) , followed by the above knee popliteal segments ( 12.3 % in the right leg and 11.0 % in the left leg for RD > /= 0.5 ) , the below knee popliteal ( 11.3 % in the right leg and 9.5 % in the left leg for RD > /= 0.5 ) , upper LSV ( 10.0 % in the right leg and 10.8 % in the left leg for RD > /= 0.5 ) segments , the common femoral vein segments ( 7.8 % in the right leg and 8.0 % in the left leg for RD > /= 0.5 ) , the lower superficial femoral vein ( SFV ) segments ( 6.6 % in the right leg and 6.4 % in the left leg for RD > /= 0.5 ) , and the upper SFV ( 5.2 % in the right leg and 4.7 % in the left leg for RD > /= 0.5 ) and short saphenous vein ( SSV ) ( 4.6 % in the right leg and 5.6 % in the left leg for an RD > /= 0.5 ) segments . In the superficial vein segments , there was little difference in the occurrence of reflux whether RD > /= 0.5 or RD > 1.0 was used ; but in the different deep vein segments , the prevalence of reflux was 2 to 4 times greater for RD > /= 0.5 rather than RD > 1.0 . Men had a higher prevalence of reflux in the deep vein segments than women , reaching statistical significance ( P < /=.01 ) in 4 of 5 segments for RD > /= 0.5 . In general , the prevalence of reflux increased with age . Those with " venous disease " had a significantly higher prevalence of reflux in all vein segments than those with " no disease " ( P < /=.001 ) . CONCLUSION The prevalence of venous reflux in the general population was related to the presence of " venous disease , " although it was also present in those without clinical ly apparent disease . There was a higher prevalence of reflux in the deep veins in men than the deep veins in women . Follow-up study of the population will determine the extent to which reflux is a predictor of future disease and complications OBJECTIVES Quantify endovenous laser ablation ( EVLA ) with concurrent phlebectomies and ultrasound-guided foam sclerotherapy ( UGFS ) in cost and effectiveness at 3 weeks and 3 months . DESIGN Single-centre , prospect i ve , r and omised controlled trial . PATIENTS One hundred patients ( 100 legs ) , C(2 - 6 ) , age 21 - 78 , M : F 42:58 , with primary varicose veins received either EVLA under local anaesthetic or UGFS . METHODS Assessment s included duplex , Aberdeen varicose vein question naire ( AVVQ ) , venous clinical severity score ( VCSS ) , venous filling index ( VFI ) , visual analogue 7-day pain score and analgesia requirements . Additional treatments with UGFS were performed , if required . Micro-costing , using individually timed treatments , was based on consumables , staff pay and overheads . RESULTS Changes in AVVQ , VCSS and VFI values ( 3 months ) did not demonstrate any significant difference between groups . At 3 months , the above-knee GSV occlusion rate ( without co-existing reflux ) was not significantly different between the groups ( 74 % vs 69 % ; EVLA vs UGFS ; P = .596 ) . Of the 9 haemodynamic failures in each group , 7 EVLA patients and 4 UGFS patients had co-existing cross-sectional above-knee GSV occlusion at some point . However , UGFS significantly outperformed EVLA in cost , treatment duration , pain , analgesia requirements and recovery . CONCLUSIONS UGFS is 3.15 times less expensive than EVLA ( £ 230.24 vs £ 724.72 ) with comparable effectiveness but 56 % ( versus 6 % ) required additional foam ( IS RCT N:03080206 ) INTRODUCTION In this multicenter , r and omized controlled trial , endovenous laser ablation ( EVLA ) is compared with conventional surgery for the treatment of varicose veins based on incompetence of the small saphenous vein and the saphenopopliteal junction ( SPJ ) . METHODS In two Dutch hospitals , 189 patients were enrolled and r and omized to receive EVLA ( 810-nm laser ) or ligation of the SPJ . End points were success rate measured with duplex ultrasound ( 6 weeks post-treatment ) , perioperative pain , quality of life , duration of surgery , difficulty of surgery , complications , cosmetic results , and number of days to resume work and normal activities . Pain was measured on a visual analog scale ( VAS ) . Quality of life was assessed using the Aberdeen Varicose Vein Question naire ( AVVQ ) and Euro Qol-5D . The follow-up duration in this article is 6 weeks . RESULTS One hundred seventy-five patients have been treated and analyzed . One hundred eighteen patients ( 67 % ) underwent EVLA , and 57 patients ( 33 % ) underwent ligation of the SPJ . The patient characteristics were similar in both groups . In the surgery group , 21 % residual incompetence of the SPJ was seen after 6 weeks , compared with 0.9 % in the laser group . Both treatment modalities reduced pain after 6 weeks . One week post-treatment , patients in the EVLA group temporarily experienced more pain compared with the surgery group ( 31 vs 18 on a VAS from 0 to 100 ) . There were no significant differences between the two groups with respect to quality of life . Both treatments did show improvement in quality of life . Also with regard to the cosmetics , there were no differences , aside from the fact that patients rated their scar as more beautiful after EVLA . After EVLA , patients could return to work more quickly . The operation time was longer in the surgery group . After 2 weeks , there were significantly more neurological complications in the surgery group : 18 ( 31 % ) vs 16 ( 17 % ) patients in the EVLA group . Ten percent of patients in the surgery group developed a surgical site infection vs 0 % in the EVLA group . CONCLUSIONS EVLA provides an excellent alternative to conventional surgery in the treatment of symptomatic varicose veins due to an incompetent small saphenous vein with SPJ . EVLA has a superior immediate success rate , is easier and faster , and has fewer complications This r and omized clinical trial compared early outcomes after radiofrequency ablation ( RFA ) and conventional surgery for varicose veins AIM This study is a prospect i ve r and omised controlled trial comparing sapheno-femoral ligation , great saphenous stripping and multiple avulsions with sapheno-femoral ligation and ultrasound guided foam sclerotherapy to the saphenous vein . Primary end points were patient recovery period and quality of life and secondary end points frequency of complications on the two arms of the trial and the cost of the treatment . MATERIAL AND METHOD Sixty patients with primary varicose veins due to GSV incompetence and suitable for day case surgery were r and omly allocated to undergo ultrasound-guided sclerotherapy with sapheno-femoral ligation under local anaesthesia ( n=30 ) or sapheno-femoral ligation , stripping and multiple avulsions under general anaesthesia ( n=30 ) . The study protocol included history , physical examination , assignment of CEAP class and assessment venous clinical severity score ( VCSS ) , completion of the aberdeen vein question naire ( AVQ ) and colour duplex ultrasound . RESULTS All treatments were completed as intended . Median time to return to normal activities was significantly reduced in the foam sclerotherapy group ( 2 days ) compared to the surgical group ( 8 days ) ( p<0.001 , Mann-Whitney ) . AVQ score was also significantly reduced at 3 months by 46 % in the sclerotherapy group , and by 40 % in the conventional surgery group ( p<0.001 , Wilcoxon ) . The time taken to complete treatment was shorter in the foam sclerotherapy plus SFJ ligation group : 45 vs. 85 min ( p<0.001 , Mann-Whitney ) . The overall cost of the procedure in the sclerotherapy group ( 672.97 pounds ) was significantly less compared to conventional surgery ( 1120.64 pounds ) . At 3 weeks , there was no statistical difference in the complication rate between the two groups . At 3 months , median CEAP class dropped from four pre-operatively to one following treatment in both groups and the median VCSS score dropped from five to one in group one and from seven to three in group two ( p<0.001 , Wilcoxon test ) . In group one four patients ( 13 % ) had a recanalised vein which needed further sessions of foam sclerotherapy , result ing in a short-term closure rate of 87 % . CONCLUSION Ultrasound guided sclerotherapy combined with sapheno-femoral ligation was less expensive , involved a shorter treatment time and result ed in more rapid recovery compared to sapheno-femoral ligation , saphenous stripping and phlebectomies This r and omized trial compared four treatments for varicose great saphenous veins ( GSVs ) . The aim of this r and omized single‐centre trial was to compare the 2‐year results of endovenous laser ablation ( EVLA ) and cryostripping for varicose veins OBJECTIVES The goals of this study were to document the prevalence of varicose veins , skin trophic changes , and venous symptoms in a sample of the general population of France , to document their main risk factors , and to assess relationships between them . METHODS This cross-sectional epidemiologic study was carried out in the general population of 4 locations in France : Tarentaise , Grenoble , Nyons , and Toulon . R and om sample s of 2000 subjects per location were interviewed by telephone , and a sub- sample of subjects completed medical interviews and underwent physical examination , and the presence of varicose veins , trophic changes , and venous symptoms was recorded . RESULTS Prevalence of varicose veins , skin trophic changes , and venous symptoms was not statistically different in the 4 locations . In contrast , sex-related differences were found : varicose veins were found in 50.5 % of women versus 30.1 % of men ( P < .001 ) ; trophic skin changes were found in 2.8 % of women versus 5.4 % of men ( P = NS ) , and venous symptoms were found in 51.3 % of women 51.3 % versus 20.4 % of men ( P < .001 ) . Main risk factors for varicose veins were age and family history in both sexes , and pregnancy in women . Female sex was a significant factor only for non-saphenous varicose veins . Varicose veins , age , and pitting edema were the most significant risk factors for trophic skin changes . The risk factors for venous symptoms were female sex , varicose veins , and prolonged sitting or st and ing . A negative relationship with age was found in women . CONCLUSION Our results show a high prevalence of chronic venous disorders of the lower limbs in the general population of France , with no significant geographic variations . They also provide interesting insights regarding the association of varicose veins , skin trophic changes , and venous symptoms OBJECTIVE This clinical trial aim ed to evaluate the clinical results of the use of a tulip fibre versus the use of a bare fibre for endovenous laser ablation . METHODS In a multicentre prospect i ve r and omised trial 174 patients were r and omised for the treatment of great saphenous vein reflux . A duplex scan was scheduled 1 month , 6 months and 1 year postoperatively . Ecchymosis was measured on the 5th postoperative day . In addition , pain , analgesics requirement , postoperative quality of life ( CIVIQ 2 ) and patient satisfaction rate were noted . RESULTS Patients treated with a tulip fibre had significantly less postoperative ecchymosis ( 0.04 vs. 0.21 ; p < 0.001 ) and pain ( 5th day ) ( 1.00 vs. 2.00 ; p < 0.001 ) and had a better postoperative quality of life ( 27 vs. 32 ; p = 0.023 ) . There was no difference in analgesic intake ( p = 0.11 ) and patient satisfaction rate ( p = 0.564 ) . The total occlusion rate at 1 year was 97.02 % and there was no significant difference between the two groups ( p = 0.309 ) . CONCLUSION Using a tulip fibre for EVLA of the great saphenous vein results , when compared with the use of a bare fibre , in equal occlusion rates at 1 year but causes less postoperative ecchymosis and pain and in a better postoperative quality of life |
12,234 | 29,392,460 | Most studies showed that verbal memory and especially story recall was improved after IN insulin administration .
Sometimes the effect was restricted for apoe4 ( − ) patients .
Intranasal insulin did not affect other cognitive functions .
However , there were some positive results in functional status and daily activity .
Conclusions Intranasal insulin improved story recall performance of apoe4 ( − ) patients with AD or MCI .
Other cognitive functions were not affected , but there were some positive results in functional status and daily activity . | Background and aims Due to common pathophysiological findings of Alzheimer ’s disease ( AD ) with diabetes mellitus ( DM ) , insulin has been suggested as a possible treatment of AD or mild cognitive impairment ( MCI ) .
A safe alternative of IV insulin is intranasal ( IN ) insulin .
The aim of this systematic review is to investigate the effects of IN insulin on cognitive function of patients with either AD or MCI . | There is compelling evidence that intranasal administration of regular human insulin ( RH-I ) improves memory in humans . Owing to the reduced tendency of its molecules to form hexamers , the rapid-acting insulin analog insulin aspart ( ASP-I ) is more rapidly absorbed than RH-I after subcutaneous administration . Since after intranasal insulin administration , ASP-I may also be expected to access the brain , we examined whether intranasal ASP-I has stronger beneficial effects on declarative memory than RH-I in humans . Acute ( 40 IU ) and long-term ( 4 × 40 IU/day over 8 weeks ) effects of intranasally administered ASP-I , RH-I , and placebo on declarative memory ( word lists ) were assessed in 36 healthy men in a between-subject design . Plasma insulin and glucose levels were not affected . After 8 weeks of treatment , however , word list recall was improved compared to placebo in both the ASP-I ( p<0.01 ) and the RH-I groups ( p<0.05 ) . ASP-I-treated subjects performed even better than those of the RH-I-treated group ( p<0.05 ) . Our results indicate that insulin-induced memory improvement can be enhanced by using ASP-I. This finding may be especially relevant for a potential clinical administration of intranasal insulin in the treatment of memory disorders like Alzheimer 's disease Background : Long acting insulin detemir administered intranasally for three weeks enhanced memory for adults with Alzheimer ’s disease dementia ( AD ) or amnestic mild cognitive impairment ( MCI ) . The investigation of longer-term administration is necessary to determine whether benefits persist , whether they are similar to benefits provided by regular insulin , and whether either form of insulin therapy affects AD biomarkers . Objective : The present study aim ed to determine whether four months of treatment with intranasal insulin detemir or regular insulin improves cognition , daily functioning , and AD biomarkers for adults with MCI or AD . Methods : This r and omized , double-blind , placebo-controlled trial included an intent-to-treat sample consisting of 36 adults diagnosed with MCI or mild to moderate AD . Participants received placebo ( n = 12 ) , 40 IU of insulin detemir ( n = 12 ) , or 40 IU of regular insulin ( n = 12 ) daily for four months , administered with a nasal delivery device . A cognitive battery was administered at baseline and after two and four months of treatment . MRI was administered for all participants and lumbar puncture for a subset ( n = 20 ) at baseline and four months . The primary outcome was change from baseline to four months on a memory composite ( sum of Z scores for delayed list and story recall ) . Secondary outcomes included : global cognition ( Alzheimer ’s Disease Assessment Scale-Cognition ) , daily functioning ( Dementia Severity Rating Scale ) , MRI volume changes in AD-related regions of interest , and cerebrospinal fluid AD markers . Results : The regular insulin treated group had better memory after two and four months compared with placebo ( p < 0.03 ) . No significant effects were observed for the detemir-assigned group compared with the placebo group , or for daily functioning for either group . Regular insulin treatment was associated with preserved volume on MRI . Regular insulin treatment was also associated with reduction in the tau-P181/Aβ42 ratio . Conclusion : Future research is warranted to examine the mechanistic basis of treatment differences , and to further assess the efficacy and safety of intranasal insulin Mild-to-moderate AD patients were r and omized to placebo or rosiglitazone ( RSG ) 2 , 4 or 8 mg . Primary end points at Week 24 were mean change from baseline in AD Assessment Scale-Cognitive ( ADAS-Cog ) and Clinician 's Interview-Based Impression of Change Plus Caregiver Input global scores in the intention-to-treat population ( N=511 ) , and results were also stratified by apolipoprotein E ( APOE ) genotype ( n=323 ) . No statistically significant differences on primary end points were detected between placebo and any RSG dose . There was a significant interaction between APOE ɛ4 allele status and ADAS-Cog ( P=0.014 ) . Exploratory analyses demonstrated significant improvement in ADAS-Cog in APOE ɛ4-negative patients on 8 mg RSG ( P=0.024 ; not corrected for multiplicity ) . APOE ɛ4-positive patients did not show improvement and showed a decline at the lowest RSG dose ( P=0.012 ; not corrected for multiplicity ) . Exploratory analyses suggested that APOE ɛ4 non-carriers exhibited cognitive and functional improvement in response to RSG , whereas APOE ɛ4 allele carriers showed no improvement and some decline was noted . These preliminary findings require confirmation in appropriate clinical 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 Physical activity may help preserve cognitive function and decrease dementia risk , but epidemiologic findings are inconsistent . The authors conducted a prospect i ve study to determine the association between physical activity and risk of dementia , Alzheimer 's disease , and vascular dementia . The US study population comprised 3,375 men and women aged 65 years or older , free of dementia at baseline , who participated in the Cardiovascular Health Cognition Study in 1992 - 2000 . Leisure-time energy expenditure and an activity index reflecting number of different physical activities were calculated . Analyses were based on Cox proportional hazards models . There were 480 incident cases of dementia over an average of 5.4 years of follow-up . After multivariate adjustment , participants in the highest quartile of physical energy expenditure had a relative risk of dementia of 0.85 ( 95 % confidence interval : 0.61 , 1.19 ) compared with those in the lowest quartile , and participants engaging in > or=4 activities had a relative risk of dementia of 0.51 ( 95 % confidence interval : 0.33 , 0.79 ) compared with those engaging in 0 - 1 activity . These associations were more marked in apolipoprotein E genotype ( APOE ) epsilon4 allele noncarriers but were absent in carriers . A similar pattern was observed for Alzheimer 's disease and vascular dementia . Mechanisms to explain the observed relations deserve further study OBJECTIVE To determine acute effects of intranasal insulin on regional cerebral perfusion and cognition in older adults with type 2 diabetes mellitus ( DM ) . RESEARCH DESIGN AND METHODS This was a proof-of-concept , r and omized , double-blind , placebo-controlled intervention evaluating the effects of a single 40-IU dose of insulin or saline on vasoreactivity and cognition in 15 DM and 14 control subjects . Measurements included regional perfusion , vasodilatation to hypercapnia with 3-Tesla MRI , and neuropsychological evaluation . RESULTS Intranasal insulin administration was well tolerated and did not affect systemic glucose levels . No serious adverse events were reported . Across all subjects , intranasal insulin improved visuospatial memory ( P ≤ 0.05 ) . In the DM group , an increase of perfusion after insulin administration was greater in the insular cortex compared with the control group ( P = 0.0003 ) . Cognitive performance after insulin administration was related to regional vasoreactivity . Improvements of visuospatial memory after insulin administration in the DM group ( R2adjusted = 0.44 , P = 0.0098 ) and in the verbal fluency test in the control group ( R2adjusted = 0.64 , P = 0.0087 ) were correlated with vasodilatation in the middle cerebral artery territory . CONCLUSIONS Intranasal insulin administration appears safe , does not affect systemic glucose control , and may provide acute improvements of cognitive function in patients with type 2 DM , potentially through vasoreactivity mechanisms . Intranasal insulin-induced changes in cognitive function may be related to vasodilatation in the anterior brain regions , such as insular cortex that regulates attention-related task performance . Larger studies are warranted to identify long-term effects and predictors of positive cognitive response to intranasal insulin therapy In previous studies , adults with Alzheimer 's disease ( AD ) showed memory enhancement when plasma insulin levels were raised to 85 microU/ml , whereas normal adults ' memory was unchanged . Degree of memory enhancement was also related to apolipoprotein E ( apoE ) genotype status for AD patients . Response differences between normal and AD groups could reflect dose-response differences for insulin . To examine this question , 22 adults with AD and 15 normal adults received five doses of insulin on separate days in counterbalanced order , result ing in five plasma insulin levels ( 10 , 25 , 35 , 85 and 135 microU/ml ) , while plasma glucose levels of ~100 mg/dl were maintained . Cognitive performance and plasma APP levels were measured after 120 min of infusion . Relative to baseline , AD patients who were not apoE- epsilon 4 homozygotes had improved memory at higher insulin levels of 35 and 85 microuU/ml , whereas normal adults and AD patients who were epsilon 4 homozygotes showed improved memory at insulin levels of 25 microU/ml . Normal adults ' memory was also improved at insulin levels of 85 microU/ml . Plasma APP was lowered for adults with AD without the epsilon 4 allele at higher levels ( 85 microU/ml ) than for normal adults and epsilon 4 homozygotes , who showed decreased APP at the 35 microU/ml level . AD patients with a single epsilon 4 allele showed a different pattern of insulin effects on APP than did other subjects . In general , few effects of insulin were seen at the highest dose for any subject group . These results support a role for insulin in normal memory and APP modulation that follows a curvilinear response pattern , and suggest that AD patients who are not epsilon 4 homozygotes have reduced sensitivity to insulin that may interfere with such modulation BACKGROUND Reduced brain insulin signaling and low CSF-to-plasma insulin ratios have been observed in patients with Alzheimer disease ( AD ) . Furthermore , intracerebroventricular or IV insulin administration improve memory , alter evoked potentials , and modulate neurotransmitters , possibly by augmenting low brain levels . After intranasal administration , insulin-like peptides follow extracellular pathways to the brain within 15 minutes . OBJECTIVE We tested the hypothesis that daily intranasal insulin treatment would facilitate cognition in patients with early AD or its prodrome , amnestic mild cognitive impairment ( MCI ) . The proportion of verbal information retained after a delay period was the planned primary outcome measure . Secondary outcome measures included attention , caregiver rating of functional status , and plasma levels of insulin , glucose , beta-amyloid , and cortisol . METHODS Twenty-five participants were r and omly assigned to receive either placebo ( n = 12 ) or 20 IU BID intranasal insulin treatment ( n = 13 ) using an electronic atomizer , and 24 participants completed the study . Participants , caregivers , and all clinical evaluators were blinded to treatment assignment . Cognitive measures and blood were obtained at baseline and after 21 days of treatment . RESULTS Fasting plasma glucose and insulin were unchanged with treatment . The insulin-treated group retained more verbal information after a delay compared with the placebo-assigned group ( p = 0.0374 ) . Insulin-treated subjects also showed improved attention ( p = 0.0108 ) and functional status ( p = 0.0410 ) . Insulin treatment raised fasting plasma concentrations of the short form of the beta-amyloid peptide ( A beta 40 ; p = 0.0471 ) without affecting the longer isoform ( A beta 42 ) , result ing in an increased A beta 40/42 ratio ( p = 0.0207 ) . CONCLUSIONS The results of this pilot study support further investigation of the benefits of intranasal insulin for patients with Alzheimer disease , and suggest that intranasal peptide administration may be a novel approach to the treatment of neurodegenerative disorders Previous studies have suggested an acutely improving effect of insulin on memory function . To study changes in memory associated with a prolonged increase in brain insulin activity in humans , here we used the intranasal route of insulin administration known to provide direct access of the substance to the cerebrospinal fluid compartment . Based on previous results indicating a prevalence of insulin receptors in limbic and hippocampal regions as well as improvements in memory with systemic insulin administration , we expected that intranasal administration of insulin improves primarily hippocampus dependent declaration memory function . Also , improvements in mood were expected . We investigated the effects of 8 weeks of intranasal administration of insulin ( human regular insulin 4 x 40 IU/d ) on declarative memory ( immediate and delayed recall of word lists ) , attention ( Stroop test ) , and mood in 38 healthy subjects ( 24 males ) in a double blind , between-subject comparison . Blood glucose and plasma insulin levels did not differ between the placebo and insulin conditions . Delayed recall of words significantly improved after 8 weeks of intranasal insulin administration ( words recalled , Placebo 2.92 + /- 1.00 , Insulin 6.20 + /- 1.03 , p < 0.05 ) . Moreover , subjects after insulin reported signs of enhanced mood , such as reduced anger ( p < 0.02 ) and enhanced self-confidence ( p < 0.03 ) . Results indicate a direct action of prolonged intranasal administration of insulin on brain functions , improving memory and mood in the absence of systemic side effects . These findings could be of relevance for the treatment of patients with memory disorders like in Alzheimer 's disease Raising insulin acutely in the periphery and in brain improves verbal memory . Intranasal insulin administration , which raises insulin acutely in the CNS without raising plasma insulin levels , provides an opportunity to determine whether these effects are mediated by central insulin or peripheral processes . Based on prior research with intravenous insulin , we predicted that the treatment response would differ between subjects with ( epsilon4 + ) and without ( epsilon4- ) the APOE-epsilon4 allele . On separate mornings , 26 memory-impaired subjects ( 13 with early Alzheimer 's disease and 13 with amnestic mild cognitive impairment ) and 35 normal controls each underwent three intranasal treatment conditions consisting of saline ( placebo ) or insulin ( 20 or 40 IU ) . Cognition was tested 15 min post-treatment , and blood was acquired at baseline and 45 min after treatment . Intranasal insulin treatment did not change plasma insulin or glucose levels . Insulin treatment facilitated recall on two measures of verbal memory in memory-impaired epsilon4- adults . These effects were stronger for memory-impaired epsilon4- subjects than for memory-impaired epsilon4 + subjects and normal adults . Unexpectedly , memory-impaired epsilon4 + subjects showed poorer recall following insulin administration on one test of memory . These findings suggest that intranasal insulin administration may have therapeutic benefit without the risk of peripheral hypoglycemia and provide further evidence for apolipoprotein E ( APOE ) related differences in insulin metabolism Introduction Intranasal ( IN ) insulin acutely improves verbal memory in mild cognitive impairment (MCI)/Alzheimer ’s disease ( AD ) , but its therapeutic effects may be attenuated in apolipoprotein E4 ( ApoE4 ) carriers . Furthermore , rapid-acting ( RA ) insulins may have superior therapeutic effects compared with regular insulin types . Objectives To measure the safety and efficacy of intranasally delivered RA glulisine in ApoE4 carriers with mild – moderate AD . Methods We performed a double-blinded , r and omized , cross-over study of RA insulin glulisine in nine mild – moderate AD subjects to better underst and the relationship between RA insulin , ApoE4 carrier status and memory performance . Results IN glulisine was well tolerated but failed to have an acute impact on cognition in ApoE4 carriers with AD . Serum insulin levels acutely dropped following treatment , but peripheral glucose levels remained unchanged . Conclusion Larger clinical trials of longer duration are necessary to better underst and the relationships between RA insulin , ApoE4 carrier status and cognitive performance in AD OBJECTIVE Nasal insulin administration is a potential route for intensive insulin management , less invasive and more rapid than subcutaneous injections . Previous studies have shown poor bioavailability ( less than 15 % ) with nasal insulin administration with various absorption enhancers . The aim of the study was to evaluate in type 1 diabetic patients , the metabolic efficacy and local tolerance of a new gelified sprayed nasal insulin containing glychocolate and methylcellulose as absorption promoters . MATERIAL AND METHODS The study was conducted in 16 type 1 diabetic patients ( HbA1c 8.6+/-0.2 % ) in a cross-over trial including 2 six month r and omized periods : a ) NPH twice daily + 3 pre-pr and ial nasal insulin doses + nasal supplementation in case of unexpected hyperglycaemia ; b ) NPH twice daily + 3 pre-pr and ial regular insulin injections . End points were HbA1c levels , hypoglycaemic episodes and tolerance evaluated at month 0 , 2 , 6 and 8 on clinical symptoms and objective nasal assessment s. RESULTS Four patients were withdrawn because of nasal burning ( 3 cases ) and persistent sinusitis ( 1 case ) , and one patient had purulent sinusitis at the month 6 examination . At month 6 , HbA1c levels were comparable ( 8.3 + /- 0.1 vs 8.6 + /- 0.1 % , m + /- SEM , NS ) for nasal and subcutaneous period respectively . The number of hypoglycaemic events was identical during the 2 periods ( 88 episodes ) . Nasal tolerance with the gelified form was better than with the already reported lyophilized form but , when present , symptoms were more marked , suggesting a potentiating additional role of methylcellulose excipient on nasal intolerance . CONCLUSIONS 1 ) Gelified nasal insulin is as efficient as subcutaneous regular insulin in type 1 diabetic patients . 2 ) Other galenic forms should be investigated to improve nasal tolerance and bioavailability OBJECTIVE To examine the effects of intranasal insulin administration on cognition , function , cerebral glucose metabolism , and cerebrospinal fluid biomarkers in adults with amnestic mild cognitive impairment or Alzheimer disease ( AD ) . DESIGN R and omized , double-blind , placebo-controlled trial . SETTING Clinical research unit of a Veterans Affairs medical center . PARTICIPANTS The intent-to-treat sample consisted of 104 adults with amnestic mild cognitive impairment ( n = 64 ) or mild to moderate AD ( n = 40 ) . Intervention Participants received placebo ( n = 30 ) , 20 IU of insulin ( n = 36 ) , or 40 IU of insulin ( n = 38 ) for 4 months , administered with a nasal drug delivery device ( Kurve Technology , Bothell , Washington ) . MAIN OUTCOME MEASURES Primary measures consisted of delayed story recall score and the Dementia Severity Rating Scale score , and secondary measures included the Alzheimer Disease 's Assessment Scale-cognitive subscale ( ADAS-cog ) score and the Alzheimer 's Disease Cooperative Study -activities of daily living ( ADCS-ADL ) scale . A subset of participants underwent lumbar puncture ( n = 23 ) and positron emission tomography with fludeoxyglucose F 18 ( n = 40 ) before and after treatment . RESULTS Outcome measures were analyzed using repeated- measures analysis of covariance . Treatment with 20 IU of insulin improved delayed memory ( P < .05 ) , and both doses of insulin ( 20 and 40 IU ) preserved caregiver-rated functional ability ( P < .01 ) . Both insulin doses also preserved general cognition as assessed by the ADAS-cog score for younger participants and functional abilities as assessed by the ADCS-ADL scale for adults with AD ( P < .05 ) . Cerebrospinal fluid biomarkers did not change for insulin-treated participants as a group , but , in exploratory analyses , changes in memory and function were associated with changes in the Aβ42 level and in the tau protein-to-Aβ42 ratio in cerebrospinal fluid . Placebo-assigned participants showed decreased fludeoxyglucose F 18 uptake in the parietotemporal , frontal , precuneus , and cuneus regions and insulin-minimized progression . No treatment-related severe adverse events occurred . CONCLUSIONS These results support longer trials of intranasal insulin therapy for patients with amnestic mild cognitive impairment and patients with AD . Trial Registration clinical trials.gov Identifier : NCT00438568 AIMS We have evaluated the local tolerance and the metabolic efficacy of a lyophilized nasal insulin preparation in 10 severely hyperglycaemic Type 2 diabetic patients . METHODS The study included two 4-month r and omized periods : ( A ) three prepr and ial doses of nasal insulin secondarily combined with one evening subcutaneous NPH if the desired glycaemic control was not achieved ; ( B ) two NPH injections daily . We assessed : ( i ) diabetes control on monthly HbA1c levels and occurrence of hypoglycaemic events ; ( ii ) local tolerance on clinical symptoms , rhinoscopy , nasal muco-ciliary clearance and nasal biopsies ; ( iii ) insulin absorption at months 0 and 4 . RESULTS One patient was withdrawn because of cough and dizziness after each nasal application . HbA1c was not significantly different at month 4 ( 9.4 + /- 0.5 % vs. 8.8 + /- 0.2 % , A vs. B ) . Blood glucose control remained only fair in the majority of our patients . Nasal insulin was able to replace the daytime fraction of the subcutaneous insulin with a 18 % efficacy . Side-effects included transient nasal hyperactivity ( pruritus , sneezing and rhinorrhoea ) and chronic persistence of nasal crusts . Plasma insulin profiles were not significantly different between months 0 and 4 . CONCLUSIONS The utilization of nasal insulin ( with or without NPH ) was associated with similar diabetes control compared with NPH twice daily . Nasal insulin alone was able to achieve an adequate glycaemic control in three of the 10 patients BACKGROUND Country-specific data on re source use and costs associated with Alzheimer 's disease ( AD ) help inform governments about the increasing need for medical and financial support as the disease increases in prevalence . METHODS GERAS II , a prospect i ve observational study , assessed re source use , costs , and health-related quality of life ( HRQoL ) among patients with AD and their caregivers in Spain . Community-dwelling patients aged ≥55 years with probable AD , and their primary caregivers , were recruited by study investigators during routine clinical practice and assessed as having mild , moderate , or moderately severe/severe ( MS/S ) AD dementia based on patient Mini-Mental State Examination scores . Costs of AD were calculated by applying costs to re source -use data obtained in caregiver interviews using the Re source Utilization in Dementia instrument . Total societal costs included patients ' health and social care costs and caregiver informal care costs . Baseline results are presented . RESULTS Total mean monthly societal costs/patient ( 2013 values ) were € 1514 for mild ( n = 116 ) , € 2082 for moderate ( n = 118 ) , and € 2818 for MS/S AD dementia ( n = 146 ) ( p value < 0.001 between groups ) . Caregiver informal care costs comprised most of the total societal costs and differed significantly between groups ( € 1050 , € 1239 , € 1580 , respectively ; p value = 0.013 ) , whereas patient healthcare costs did not . Across AD dementia severity groups , patient HRQoL ( measured by proxy ) decreased significantly ( p value < 0.001 ) , caregiver subjective burden significantly increased ( p value < 0.001 ) and caregiver HRQoL was similar . CONCLUSIONS Societal costs associated with AD in Spain were largely attributable to caregiver informal care costs and increased with increasing AD dementia severity Glucose is the brain 's principal energy substrate . In Alzheimer 's disease ( AD ) , there appears to be a pathological decrease in the brain 's ability to use glucose . Neurobiological evidence suggests that ketone bodies are an effective alternative energy substrate for the brain . Elevation of plasma ketone body levels through an oral dose of medium chain triglycerides ( MCTs ) may improve cognitive functioning in older adults with memory disorders . On separate days , 20 subjects with AD or mild cognitive impairment consumed a drink containing emulsified MCTs or placebo . Significant increases in levels of the ketone body beta-hydroxybutyrate ( beta-OHB ) were observed 90 min after treatment ( P=0.007 ) when cognitive tests were administered . beta-OHB elevations were moderated by apolipoprotein E ( APOE ) genotype ( P=0.036 ) . For 4 + subjects , beta-OHB levels continued to rise between the 90 and 120 min blood draws in the treatment condition , while the beta-OHB levels of 4- subjects held constant ( P<0.009 ) . On cognitive testing , MCT treatment facilitated performance on the Alzheimer 's Disease Assessment Scale-Cognitive Subscale ( ADAS-cog ) for 4- subjects , but not for 4 + subjects ( P=0.04 ) . Higher ketone values were associated with greater improvement in paragraph recall with MCT treatment relative to placebo across all subjects ( P=0.02 ) . Additional research is warranted to determine the therapeutic benefits of MCTs for patients with AD and how APOE-4 status may mediate beta-OHB efficacy BACKGROUND Intranasally applied insulin is one of the antigen-specific therapies currently tested in clinical type 1 diabetes prevention trials , for example , in the Type 1 Diabetes Prediction and Prevention Study ( DIPP ) . The possibility that the therapy may cause hypoglycaemia or local irritation and the poorly known immunological safety of mucosal application of the antigen in healthy subjects prompted this study . METHODS We used a r and omised , placebo-controlled , double-blinded crossover study design with 3-week treatment periods to study the effects of once-daily intranasal application of human short-acting insulin without absorption-enhancing adjuvants in 20 non-diabetic adults . The selected 60 IU dose of insulin was equivalent to the weight-based dose used for the DIPP children . We investigated self-monitored blood glucose concentrations , nasal insulin effects and induction of diabetes-associated autoantibodies . RESULTS The two treatment periods showed no differences in blood glucose concentrations or in the frequency of blood glucose values higher than 3.0 mmol/L. Of the eight measured hypoglycaemic values , only one , which occurred during placebo therapy , was associated with symptoms . Rhinoscopy revealed no nasal irritation , and mucociliary clearance , nasal airway patency and nasal airflow resistance were not affected by the insulin therapy . Eleven subjects complained of transient nasal stinging or unpleasant odour and one subject reduced the dose because of nasal irritation . The treatment did not induce production of any of the four diabetes-associated autoantibodies . CONCLUSIONS Short-term use of intranasal insulin without absorption enhancers was predominantly well tolerated , the risk of hypoglycaemia was minimal and no objective nasal adverse effects were detected |
12,235 | 28,989,547 | MBIs showed strongest promise for intermediary effects on teacher emotion regulation .
The results of the review are discussed in the context of a model of teacher stress .
Teacher social and emotional competence has implication s for pupil wellbeing through teacher – pupil relationships and effective management of the classroom . | School teachers report high levels of stress which impact on their engagement with pupils and effectiveness as a teacher .
Early intervention or prevention approaches may support teachers to develop positive coping and reduce the experience and impact of stress .
This article review s research on one such approach : mindfulness-based interventions ( MBIs ) for school teachers . | Despite the crucial role of teachers in fostering children 's academic learning and social-emotional well-being , addressing teacher stress in the classroom remains a significant challenge in education . The present study reports results from a r and omized controlled pilot trial of a modified Mindfulness-Based Stress Reduction course ( mMBSR ) adapted specifically for teachers . Results suggest the course may be a promising intervention , with participants showing significant reductions in psychological symptoms and burnout , improvements in observer-rated classroom organization and performance on a computer task of affective attentional bias , and increases in self-compassion . In contrast , control group participants showed declines in cortisol functioning over time and marginally significant increases in burnout . Furthermore , changes in mindfulness were correlated in the expected direction with changes across several outcomes ( psychological symptoms , burnout , sustained attention ) in the intervention group . Implication s of these findings for the training and support of teachers are discussed BACKGROUND Individuals with a history of recurrent depression have a high risk of repeated depressive relapse or recurrence . Maintenance antidepressants for at least 2 years is the current recommended treatment , but many individuals are interested in alternatives to medication . Mindfulness-based cognitive therapy ( MBCT ) has been shown to reduce risk of relapse or recurrence compared with usual care , but has not yet been compared with maintenance antidepressant treatment in a definitive trial . We aim ed to see whether MBCT with support to taper or discontinue antidepressant treatment ( MBCT-TS ) was superior to maintenance antidepressants for prevention of depressive relapse or recurrence over 24 months . METHODS In this single-blind , parallel , group r and omised controlled trial ( PREVENT ) , we recruited adult patients with three or more previous major depressive episodes and on a therapeutic dose of maintenance antidepressants , from primary care general practice s in urban and rural setting s in the UK . Participants were r and omly assigned to either MBCT-TS or maintenance antidepressants ( in a 1:1 ratio ) with a computer-generated r and om number sequence with stratification by centre and symptomatic status . Participants were aware of treatment allocation and research assessors were masked to treatment allocation . The primary outcome was time to relapse or recurrence of depression , with patients followed up at five separate intervals during the 24-month study period . The primary analysis was based on the principle of intention to treat . The trial is registered with Current Controlled Trials , IS RCT N26666654 . FINDINGS Between March 23 , 2010 , and Oct 21 , 2011 , we assessed 2188 participants for eligibility and recruited 424 patients from 95 general practice s. 212 patients were r and omly assigned to MBCT-TS and 212 to maintenance antidepressants . The time to relapse or recurrence of depression did not differ between MBCT-TS and maintenance antidepressants over 24 months ( hazard ratio 0·89 , 95 % CI 0·67 - 1·18 ; p=0·43 ) , nor did the number of serious adverse events . Five adverse events were reported , including two deaths , in each of the MBCT-TS and maintenance antidepressants groups . No adverse events were attributable to the interventions or the trial . INTERPRETATION We found no evidence that MBCT-TS is superior to maintenance antidepressant treatment for the prevention of depressive relapse in individuals at risk for depressive relapse or recurrence . Both treatments were associated with enduring positive outcomes in terms of relapse or recurrence , residual depressive symptoms , and quality of life . FUNDING National Institute for Health Research ( NIHR ) Health Technology Assessment ( HTA ) programme , and NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula UNLABELLED RATIONALE , AIMS & OBJECTIVE : Tools for the assessment of the quality of research studies tend to be specific to a particular research design ( e.g. r and omized controlled trials , or qualitative interviews ) . This makes it difficult to assess the quality of a body of research that addresses the same or a similar research question but using different approaches . The aim of this paper is to describe the development and preliminary evaluation of a quality assessment tool that can be applied to a method ologically diverse set of research articles . METHODS The 16-item quality assessment tool ( QATSDD ) was assessed to determine its reliability and validity when used by health services research ers in the disciplines of psychology , sociology and nursing . Qualitative feedback was also gathered from mixed- methods health research ers regarding the comprehension , content , perceived value and usability of the tool . RESULTS Reference to existing widely used quality assessment tools and experts in systematic review confirmed that the components of the tool represented the construct of ' good research technique ' being assessed . Face validity was subsequently established through feedback from a sample of nine health research ers . Inter-rater reliability was established through substantial agreement between three review ers when applying the tool to a set of three research papers ( κ = 71.5 % ) , and good to substantial agreement between their scores at time 1 and after a 6-week interval at time 2 confirmed test-retest reliability . CONCLUSIONS The QATSDD shows good reliability and validity for use in the quality assessment of a diversity of studies , and may be an extremely useful tool for review ers to st and ardize and increase the rigour of their assessment s in review s of the published papers which include qualitative and quantitative work Positive psychology has flourished in the last 5 years . The authors review recent developments in the field , including books , meetings , courses , and conferences . They also discuss the newly created classification of character strengths and virtues , a positive complement to the various editions of the Diagnostic and Statistical Manual of Mental Disorders ( e. g. , American Psychiatric Association , 1994 ) , and present some cross-cultural findings that suggest a surprising ubiquity of strengths and virtues . Finally , the authors focus on psychological interventions that increase individual happiness . In a 6-group , r and om-assignment , placebo-controlled Internet study , the authors tested 5 purported happiness interventions and 1 plausible control exercise . They found that 3 of the interventions lastingly increased happiness and decreased depressive symptoms . Positive interventions can supplement traditional interventions that relieve suffering and may someday be the practical legacy of positive psychology This prospect i ve study with 464 older adolescents ( 14 to 19 years at Time 1 ; 16 to 21 years at Time 2 ) tested the structural paths of influence through which perceived self-efficacy for affect regulation operates in concert with perceived behavioral efficacy in governing diverse spheres of psychosocial functioning . Self-efficacy to regulate positive and negative affect is accompanied by high efficacy to manage one 's academic development , to resist social pressures for antisocial activities , and to engage oneself with empathy in others ' emotional experiences . Perceived self-efficacy for affect regulation essentially operated mediationally through the latter behavioral forms of self-efficacy rather than directly on prosocial behavior , delinquent conduct , and depression . Perceived empathic self-efficacy functioned as a generalized contributor to psychosocial functioning . It was accompanied by prosocial behavior and low involvement in delinquency but increased vulnerability to depression in adolescent females Parents and teachers of children with special needs face unique social-emotional challenges in carrying out their caregiving roles . Stress associated with these roles impacts parents ' and special educators ' health and well-being , as well as the quality of their parenting and teaching . No rigorous studies have assessed whether mindfulness training ( MT ) might be an effective strategy to reduce stress and cultivate well-being and positive caregiving in these adults . This r and omized controlled study assessed the efficacy of a 5-week MT program for parents and educators of children with special needs . Participants receiving MT showed significant reductions in stress and anxiety and increased mindfulness , self-compassion , and personal growth at program completion and at 2 months follow-up in contrast to waiting-list controls . Relational competence also showed significant positive changes , with medium-to-large effect sizes noted on measures of empathic concern and forgiveness . MT significantly influenced caregiving competence specific to teaching . Mindfulness changes at program completion mediated outcomes at follow-up , suggesting its importance in maintaining emotional balance and facilitating well-being in parents and teachers of children with developmental challenges Cultivating Awareness and Resilience in Education ( CARE for Teachers ) is a mindfulness-based professional development program design ed to reduce stress and improve teachers ' performance and classroom learning environments . A r and omized controlled trial examined program efficacy and acceptability among a sample of 50 teachers r and omly assigned to CARE or waitlist control condition . Participants completed a battery of self-report measures at pre- and postintervention to assess the impact of the CARE program on general well-being , efficacy , burnout/time pressure , and mindfulness . Participants in the CARE group completed an evaluation of the program after completing the intervention . ANCOVAs were computed between the CARE group and control group for each outcome , and the pretest scores served as a covariate . Participation in the CARE program result ed in significant improvements in teacher well-being , efficacy , burnout/time-related stress , and mindfulness compared with controls . Evaluation data showed that teachers viewed CARE as a feasible , acceptable , and effective method for reducing stress and improving performance . Results suggest that the CARE program has promise to support teachers working in challenging setting s and consequently improve classroom environments |
12,236 | 25,701,456 | Elderly PCNSL patients benefit from HD-MTX-based therapy , especially if combined with oral alkylating agents .
More aggressive HD-MTX protocol s do not seem to improve outcome .
WBRT may improve outcome , but is associated with increased risk for neurological side-effects . | BACKGROUND To investigate prognosis and effects of first-line therapy in elderly primary central nervous system lymphoma ( PCNSL ) patients . | BACKGROUND To improve survival of elderly patients with primary central nervous system lymphoma ( PCNSL ) , we conducted a phase II study with high-dose methotrexate ( MTX ) combined with procarbazine and CCNU . To reduce neurotoxicity , whole-brain irradiation was reserved for patients not responding to chemotherapy . PATIENTS AND METHODS High-dose MTX was applied on days 1 , 15 , and 30 , procarbazine on days 1 - 10 , and CCNU on day 1 . Study treatment comprised up to three 45-day cycles . There was no lower limit of Karnofsky performance status ( KPS ) . RESULTS Thirty patients with PCNSL ( n = 29 ) or primary ocular lymphoma ( n = 1 ) were included ( median age 70 years , range 57 - 79 years ) . The median initial KPS was 60 % ( range 30%-90 % ) . Best documented response in 27 assessable patients were 12 of 27 ( 44.4 % ) complete remissions , 7 of 27 ( 25.9 % ) partial remissions , and 8 of 27 ( 29.6 % ) disease progressions . Two patients died of probable treatment-related causes . With a median follow-up of 78 months ( range 34 - 105 ) , the 5-year overall survival is 33 % . Eight of 30 patients ( 26.7 % ) are currently alive and well , six without signs of leukoencephalopathy . CONCLUSION The combination of high-dose MTX with procarbazine and CCNU is feasible and effective and results in a low rate of leukoencephalopathy . Comorbidity and toxicity remain of concern when treating PCNSL in elderly patients 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 PURPOSE A multicenter , phase II study of single-agent , intravenous methotrexate in newly diagnosed non-AIDS-related primary CNS lymphoma was conducted in the New Approaches to Brain Tumor Therapy ( NABTT ) CNS Consortium . METHODS Methotrexate ( 8 g/m(2 ) ) was initially administered every 2 weeks . The primary end point was radiographic CR or PR , as defined by st and ard radiographic criteria , and secondary end points were survival and drug-related toxicity . RESULTS Twenty-five patients were enrolled with a mean age of 60 years and median Karnofsky Performance Score of 80 . Three of 14 patients who underwent lumbar puncture had malignant cells on CSF cytopathology , and five of 25 patients had ocular involvement . Two patients could not be evaluated for the primary end point because of the absence of measurable disease in one and death before radiologic imaging in another . All patients have completed the treatment program or progressed . Among 23 patients , there were 12 CR ( 52 % ) , five PR ( 22 % ) , one ( 4 % ) with stable disease , and five progressions ( 22 % ) while on therapy . Seven patients died of tumor progression , and two died of other causes . Median progression-free survival was 12.8 months . Median overall survival for the entire group had not been reached at 22.8 + months . The toxicity of this regimen was modest , with no grade 3 or 4 toxicity in 13 of 25 patients , grade 3 toxicity in eight of 25 patients , and grade 4 toxicity in four of 25 patients after 287 cycles of chemotherapy . CONCLUSION These results indicate that high-dose methotrexate is associated with modest toxicity and a radiographic response proportion ( 74 % ) comparable to more toxic regimens BACKGROUND High-dose methotrexate is the st and ard of care for patients with newly diagnosed primary CNS lymphoma . The role of whole brain radiotherapy is controversial because delayed neurotoxicity limits its acceptance as a st and ard of care . We aim ed to investigate whether first-line chemotherapy based on high-dose methotrexate was non-inferior to the same chemotherapy regimen followed by whole brain radiotherapy for overall survival . METHODS Immunocompetent patients with newly diagnosed primary CNS lymphoma were enrolled from 75 centres and treated between May , 2000 , and May , 2009 . Patients were allocated by computer-generated block r and omisation to receive first-line chemotherapy based on high-dose methotrexate with or without subsequent whole brain radiotherapy , with stratification by age ( < 60 vs ≥60 years ) and institution ( Berlin vs Tübingen vs all other sites ) . The biostatistics centre assigned patients to treatment groups and informed local centres by fax ; physicians and patients were not masked to treatment group after assignment . Patients enrolled between May , 2000 , and August , 2006 , received high-dose methotrexate ( 4 g/m(2 ) ) on day 1 of six 14-day cycles ; thereafter , patients received high-dose methotrexate plus ifosfamide ( 1·5 g/m(2 ) ) on days 3 - 5 of six 14-day cycles . In those assigned to receive first-line chemotherapy followed by radiotherapy , whole brain radiotherapy was given to a total dose of 45 Gy , in 30 fractions of 1·5 Gy given daily on weekdays . Patients allocated to first-line chemotherapy without whole brain radiotherapy who had not achieved complete response were given high-dose cytarabine . The primary endpoint was overall survival , and analysis was per protocol . Our hypothesis was that the omission of whole brain radiotherapy does not compromise overall survival , with a non-inferiority margin of 0·9 . This trial is registered with Clinical Trials.gov , number NCT00153530 . FINDINGS 551 patients ( median age 63 years , IQR 55 - 69 ) were enrolled and r and omised , of whom 318 were treated per protocol . In the per- protocol population , median overall survival was 32·4 months ( 95 % CI 25·8 - 39·0 ) in patients receiving whole brain radiotherapy ( n=154 ) , and 37·1 months ( 27·5 - 46·7 ) in those not receiving whole brain radiotherapy ( n=164 ) , hazard ratio 1·06 ( 95 % CI 0·80 - 1·40 ; p=0·71 ) . Thus our primary hypothesis was not proven . Median progression-free survival was 18·3 months ( 95 % CI 11·6 - 25·0 ) in patients receiving whole brain radiotherapy , and 11·9 months ( 7·3 - 16·5 ; p=0·14 ) in those not receiving whole brain radiotherapy . Treatment-related neurotoxicity in patients with sustained complete response was more common in patients receiving whole brain radiotherapy ( 22/45 , 49 % by clinical assessment ; 35/49 , 71 % by neuroradiology ) than in those who did not ( 9/34 , 26 % ; 16/35 , 46 % ) . INTERPRETATION No significant difference in overall survival was recorded when whole brain radiotherapy was omitted from first-line chemotherapy in patients with newly diagnosed primary CNS lymphoma , but our primary hypothesis was not proven . The progression-free survival benefit afforded by whole brain radiotherapy has to be weighed against the increased risk of neurotoxicity in long-term survivors The Nordic Lymphoma Group has conducted a phase ll trial in newly diagnosed primary central nervous system lymphoma patients applying an age-adjusted multi-agent immunochemotherapy regimen , which in elderly patients included temozolomide maintenance treatment . Patients aged 18–75 years were eligible . Thirty-nine patients aged 18–65 years and 27 patients aged 66–75 years were enrolled . The median age of the two age groups was 55 and 70 years , respectively . The overall response rate was 73.8 % for the entire cohort : 69.9 % in the younger and 80.8 % in the elderly subgroup . With a median follow up of 22 months , the 2-year overall survival probability was 60.7 % in patients aged 65 years or under and 55.6 % in patients aged over 65 years ( P=0.40 ) . The estimated progression-free survival at two years was 33.1 % ( 95%CI : 19.1%–47.9 % ) in patients aged under 65 years and 44.4 % ( 95%CI : 25.6%–61.8 % ) in the elderly subgroup ( P=0.74 ) . Median duration of response was ten months in the younger subgroup , and not reached in the elderly patient subgroup ( P=0.33 ) . Four patients aged 64–75 years ( 6 % ) died from treatment-related complications . Survival in the two age groups was similar despite a de-escalation of induction treatment in patients aged over 65 years . Duration of response in elderly patients receiving maintenance temozolomide was longer than in the younger age subgroup . While toxicity during induction is still of concern , especially in the elderly patients , we conclude from these data that de-escalation of induction therapy in elderly primary central nervous system lymphoma patients followed by maintenance treatment seems to be a promising treatment strategy . ( clinical trials.gov identifier:01458730 BACKGROUND The dose of high-dose methotrexate ( HDMTX ) in elderly patients often has to be reduced , result ing in a loss of treatment efficacy . We evaluated HDMTX-related toxicity with special regard to age distribution in patients with primary central nervous system lymphoma ( PCNSL ) in a phase IV multicenter trial . PATIENTS AND METHODS One hundred and fifty-four patients ( median age 61 years ; 89 patients > 60 years old , 21 patients > 70 years old ) received 619 HDMTX cycles . Toxicity was evaluated prospect ively using the WHO classification . Unless a reduced dose was required after calculating a decreased glomerular filtration rate ( GFR ) , the patients received 4 g/m(2 ) HDMTX followed by leucovorin rescue . RESULTS Toxicity was generally mild with toxicities of WHO grade > or =3 usually < 10 % . The differences in the incidence and severity of toxicity were not statistically significant between patients > 60 years and < or = 60 years old . The same was true for therapy termination owing to MTX toxicity and for delayed serum MTX clearance . Dose reduction significantly differed between patients < or = 60 years and those > 60 years old ( 18 % versus 44 % ; P = 0.001 ) . CONCLUSIONS HDMTX is a safe treatment for PCNSL patients regardless of age , with adherence to dose reduction determined by calculating the GFR before each treatment cycle BACKGROUND This prospect i ve multicentric phase II study aim ed to confirm the results of the C5R protocol of high-dose methotrexate (MTX)-based chemotherapy ( CT ) for immunocompetent primary central nervous system lymphoma . PATIENTS AND METHODS A total of 99 patients received age-adapted CT ( C5R protocol ) followed by radiotherapy . Patients younger than 61 years ( group 1 , n = 45 ) received the full C5R with MTX , doxorubicin , vincristine , cyclophosphamide , and cytarabine . Patients aged 61 - 70 years ( group 2 , n = 36 ) received reduced doses . Patients older than 70 years ( group 3 , n = 18 ) received four courses of MTX , cyclophosphamide , and etoposide . RESULTS Median age was 63 years and 51 % of patients had performance status of more than one . Seventeen patients died of toxicity during CT . Complete response was achieved in 56 % , 53 % , and 28 % of patients in groups 1 , 2 , and 3 , respectively . With a median follow-up of 83 months , the 5-year progression-free survival was 31 % , 28 % , and 11 % and the 5-year overall survival 42 % , 31 % , and 17 % for groups 1 , 2 , and 3 , respectively . Leukoencephalopathy occurred in 32 % of assessable patients , in both group 1 and groups 2 - 3 . CONCLUSION The C5R protocol was feasible in the multicentric setting with favorable long-term survival in patients younger than 60 years . Despite dose adaptation , results in older patients were disappointing BACKGROUND Chemotherapy with high-dose methotrexate is the conventional approach to treat primary CNS lymphomas , but superiority of polychemotherapy compared with high-dose methotrexate alone is unproven . We assessed the effect of adding high-dose cytarabine to methotrexate in patients with newly diagnosed primary CNS lymphoma . METHODS This open , r and omised , phase 2 trial was undertaken in 24 centres in six countries . 79 patients with non-Hodgkin lymphoma exclusively localised into the CNS , cranial nerves , or eyes , aged 18 - 75 years , and with Eastern Cooperative Oncology Group performance status of 3 or lower and measurable disease were central ly r and omly assigned by computer to receive four courses of either methotrexate 3.5 g/m(2 ) on day 1 ( n=40 ) or methotrexate 3.5 g/m(2 ) on day 1 plus cytarabine 2 g/m(2 ) twice a day on days 2 - 3 ( n=39 ) . Both regimens were administered every 3 weeks and were followed by whole-brain irradiation . The primary endpoint was complete remission rate after chemotherapy . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00210314 . FINDINGS All r and omly assigned participants were analysed . After chemotherapy , seven patients given methotrexate and 18 given methotrexate plus cytarabine achieved a complete remission , with a complete remission rate of 18 % ( 95 % CI 6 - 30 ) and 46 % ( 31 - 61 ) , respectively , ( p=0.006 ) . Nine patients receiving methotrexate and nine receiving methotrexate plus cytarabine achieved a partial response , with an overall response rate of 40 % ( 25 - 55 ) and 69 % ( 55 - 83 ) , respectively , ( p=0.009 ) . Grade 3 - 4 haematological toxicity was more common in the methotrexate plus cytarabine group than in the methotrexate group ( 36 [ 92 % ] vs six [ 15 % ] ) . Four patients died of toxic effects ( three vs one ) . INTERPRETATION In patients aged 75 years and younger with primary CNS lymphoma , the addition of high-dose cytarabine to high-dose methotrexate provides improved outcome with acceptable toxicity compared with high-dose methotrexate alone . FUNDING Swiss Cancer League The prospect i ve multicenter NOA‐03 trial , conducted by the Neuro‐Oncology Working Group ( NOA ) of the German Cancer Society , was initiated to define the feasibility and efficacy of single‐agent high‐dose methotrexate therapy without concomitant radiotherapy in immunocompetent patients with primary central nervous system lymphoma . Thirty‐seven patients ( median age , 60 years ) received 179 biweekly courses of 8g/m2 methotrexate . Response was assessed after 3 and 6 courses . We had planned to enter 105 patients into the trial . Since fewer than the projected 18 of 37 patients achieved a complete response after an intermediate analysis , the trial was closed . In intention‐to‐treat analysis , 11 of 37 patients ( 29.7 % ) achieved complete response , whereas 14 of 37 patients ( 37.8 % ) were found to have progressive disease . The median relapse‐free survival among complete response patients was 13.7 months . Multivariate logistic regression analysis revealed that corticosteroid application during the first methotrexate course was associated with complete response . The regimen was well tolerated , but , unlike previously reported results , the activity of high‐dose methotrexate was only moderate Background Treatment for primary CNS lymphoma ( PCNSL ) in the elderly is associated with lower response rates and higher risks of acute and late delayed toxicity as compared to younger patients . Temozolomide has emerged as a new alternative treatment for PCNSL and constitutes an attractive option for the elderly because of its favorable toxicity profile . In this study we report outcomes of a consecutive series of PCNSL elderly patients initially treated with an innovative regimen combining methotrexate and temozolomide without radiotherapy or intra-thecal chemotherapy . Methods Histologically confirmed newly-diagnosed PCNSL patients older than 60 years were included . An induction chemotherapy was initially given ( methotrexate 3 g /m2 on days 1 , 10 , and 20 , and temozolomide 100 mg/m2 on days 1–5 ) . Patients achieving a partial or complete response proceeded to a maintenance phase ( up to 5 monthly cycles of methotrexate 3 g/m2 on day 1 , and temozolomide 100 mg/m2 days 1–5 ) . Non-responders were treated on an individual basis . Results Among the 23 included patients , a complete response was observed in 55 % , and disease progressed in the other 45 % . Median event-free survival was 8 months , and median overall survival was 35 months . Grade s 3 or 4 toxicities included nephrotoxicity in three patients , and hematotoxicity in five ; no neurotoxicity has been observed to date . One patient died while on treatment from complications of intestinal obstruction . Conclusion Our efficacy results are comparable to other reported regimens , with the advantages of a favorable toxicity profile , and absence of intra-thecal chemotherapy . Prospect i ve , controlled studies are warranted to confirm such results Prior studies have suggested that pre-irradiation methotrexate (MTX)-based chemotherapy improves duration of response and survival in primary central nervous system lymphoma ( PCNSL ) . To circumvent the potential emergence of drug resistance , we combined high-dose MTX with agents highly active against systemic lymphoma . Patients received three week cycles of CHOD ( cyclophosphamide 750 mg/m2 , doxorubicin 50 mg/m2 , and vincristine 1.4 mg/m2 [ 2 mg maximum ] on day 1 ; dexamethasone 10 mg/m2 days 1–5 ) , and MTX ( 3.5 gm/m2 ) with leucovorin rescue on day 8 ( or on recovery from the CHOD nadir ) . Whole brain irradiation ( WBRT ) was planned after at least three cycles . Eighteen patients were treated . Complete responses were seen in eleven patients , and partial responses in three . Four progressed during therapy , three succumbing to progressive disease and one subsequently responding to WBRT Response duration was 37.5 months in those responding to therapy . The time to progression for all eighteen patients was 19.5 months . Medial survival was 25.5 months . Disease-free survival was 50 % at 38 months in MCHOD responders . Grade 3 or 4 myelotoxicity was seen in 19 of 50 cycles . There were three instances of neutropenic fever , three of azotemia , two of deep vein thrombosis , and one each of community-acquired pneumonia , intracranial hemorrhage , superior vena cava syndrome , and hepatotoxicity . Late radiation-related toxicities were seen in two patients . Pre-irradiation MCHOD has activity against PCNSL , but appears to be no better than MTX monotherapy and has greater toxicity BACKGROUND The combination of high doses of methotrexate ( MTX ) and cytarabine ( araC ) is the st and ard chemotherapy for patients with primary CNS lymphoma ( PCNSL ) . The addition of an alkylating agent could improve MTX-araC efficacy because it is active against quiescent G0 cells and increases antimetabolites cytotoxicity . A pilot experience with high doses of MTX , araC , and thiotepa ( MAT regimen ) was performed to investigate feasibility and efficacy of adding an alkylating agent . With respect to MTX-araC combination , araC dose was halved to minimize toxicity . Herein , we report tolerability , activity , and efficacy of MAT regimen and compare these results to those previously reported with MTX/ara-C combination . METHODS Twenty HIV-negative patients with PCNSL treated with MAT regimen and whole-brain irradiation and selected according to eligibility criteria of the International Extranodal Lymphoma Study Group ( IELSG ) # 20 trial were analyzed . RESULTS Patient characteristics of MAT and MTX-araC series were similar . G4 hematologic toxicity was common after MAT chemotherapy , with dose reductions in 60 % of patients , infections in 20 % , G4 non-hematologic toxicity in 15 % , and one ( 5 % ) toxic death . Response after chemotherapy was complete in four patients ( clinical response rate , 20 % ; 95 % confidence interval , 3%-37 % ) and partial in three ( overall response rate , 35 % ; 95 % confidence interval , 15%-55 % ) . Fifteen patients experienced failure and 16 died ( median follow-up , 26 months ) , with a 2-year overall survival of 24 % ± 9 % . CONCLUSIONS MAT and MTX-araC combinations showed similar tolerability , whereas araC dose reduction was associated with a remarkably lower efficacy , hiding any potential benefit of thiotepa . Four doses of araC 2 g/m(2 ) per course are recommended in patients with PCNSL PURPOSE Concerns regarding neurocognitive toxicity of whole-brain radiotherapy ( WBRT ) have motivated development of alternative , dose-intensive chemotherapeutic strategies as consolidation in primary CNS lymphoma ( PCNSL ) . We performed a multicenter study of high-dose consolidation , without WBRT , in PCNSL . Objectives were to determine : one , rate of complete response ( CR ) after remission induction therapy with methotrexate , temozolomide , and rituximab ( MT-R ) ; two , feasibility of a two-step approach using high-dose consolidation with etoposide plus cytarabine ( EA ) ; three , progression-free survival ( PFS ) ; and four , correlation between clinical and molecular prognostic factors and outcome . PATIENTS AND METHODS Forty-four patients with newly diagnosed PCNSL were treated with induction MT-R , and patients who achieved CR received EA consolidation . We performed a prospect i ve analysis of molecular prognostic biomarkers in PCNSL in the setting of a clinical trial . RESULTS The rate of CR to MT-R was 66 % . The overall 2-year PFS was 0.57 , with median follow-up of 4.9 years . The 2-year time to progression was 0.59 , and for patients who completed consolidation , it was 0.77 . Patients age > 60 years did as well as younger patients , and the most significant clinical prognostic variable was treatment delay . High BCL6 expression correlated with shorter survival . CONCLUSION CALGB 50202 demonstrates for the first time to our knowledge that dose-intensive consolidation for PCNSL is feasible in the multicenter setting and yields rates of PFS and OS at least comparable to those of regimens involving WBRT . On the basis of these encouraging results , an intergroup study has been activated comparing EA consolidation with myeloablative chemotherapy in this r and omized trial in PCNSL , in which neither arm involves WBRT Treatment of primary central nervous system lymphoma ( PCNSL ) in elderly patients remains unsatisfactory . To develop a new high‐dose methotrexate (HD‐MTX)‐based regimen including idarubicin , a phase 1 multicenter dose escalation study was conducted to determine the maximum‐tolerated dose ( MTD ) of idarubicin . Thirty‐five immunocompetent patients with PCNSL were enrolled . The median age was 65 years ( range , 60–70 years ) . MTX and vindesine ( VDS ) were given at the fixed dose of 3 g/m2 ( 6‐hr intravenous [ IV ] ) and 3 mg/m2 IV on day 1 , respectively . Prednisolone ( PRED ) was given at the fixed dose of 60 mg/m2 ( IV or orally ) on days 1–5 . Idarubicin was escalated in increments of 2 mg/m2 with doses ranging from 12–18 mg/m2 IV on day 1 . Treatment was repeated three times every 3 weeks . Dose‐limiting toxicity ( DLT ) was defined as grade 4 neutropenia for more than 7 days , thrombocytopenia grade 4 or nonhaematological toxicity more than grade 2 . The MTD of idarubicin was reached at 16 mg/m2 . At this level , the main haematological toxicities were thrombocytopenia grade 4 : 5 % and neutropenia grade 3 or 4 ( 52 % ) ; the main nonhaematological toxicities were grade 3 or 4 infectious disease ( 5 % ) and grade 2 renal failure ( 9 % ) . For the study population , median overall and progression‐free survival were 19 and 13 months , respectively . Our study suggests that the MTD of idarubicin in combination with HD‐MTX , VDS , and PRED , should be 16 mg/m2 . Further studies will be necessary to challenge a st and ard treatment in elderly patients with PCNSL . Am . J. Hematol . 89:1024–1029 , 2014 . © 2014 Wiley Periodicals , The authors assessed MATILDE chemotherapy followed by response-tailored radiation therapy in 41 patients aged 70 years or younger with primary CNS lymphoma in a Phase II trial . With response rates of 76 % after MATILDE and 83 % after chemotherapy with or without radiation therapy , this was an active strategy , particularly in low- to intermediate-risk patients ( International Extranodal Lymphoma Study Group [ IELSG ] score ) . Myelosuppression was the dose-limiting toxicity , with 9.5 % of lethal complications . After a median follow-up of 49 months , a plateau in the survival curve ( 5-year overall survival : 41 ± 7 % ) was obtained PURPOSE The use of preradiotherapy ( RT ) methotrexate ( MTX ) has improved disease control and survival in patients with primary CNS lymphoma ( PCNSL ) . The reported protocol was design ed to optimize and enhance the chemotherapeutic component of treatment . PATIENTS AND METHODS Fifty-two patients were treated with five cycles of high-dose MTX 3.5 g/m(2 ) , procarbazine 100 mg/m(2)/d , and vincristine 1.4 mg/m(2 ) . Thirty patients received whole-brain RT ( 45 Gy ) . Twenty-two older patients deferred RT to diminish the risk of delayed neurotoxicity ; these patients are compared with 12 older patients who completed the entire treatment regimen . Most patients ( n = 35 ) received high-dose cytarabine after RT . RESULTS Objective response rate to the induction chemotherapy regimen was 90 % ; overall median survival is 60 months . Grade 3 or 4 myelosuppression was seen in 30 patients , primarily in association with cytarabine ; grade 3 nephrotoxicity due to MTX was seen in two patients . Older patients had similar median survival with or without the addition of RT : 32 versus 33 months , respectively . However , late neurotoxicity was significantly more common in those older patients who received RT ( P : = .00004 ) . Patients younger than 60 years who received the complete treatment regimen have not reached median disease-free or overall survival . CONCLUSION Increasing the dose of MTX and adding procarbazine and vincristine improved disease control and overall survival in patients with newly diagnosed PCNSL . Younger patients in particular fared extremely well with this treatment regimen . In older patients , deferring whole-brain RT did not compromise overall survival but did reduce treatment-related toxicity Chemotherapy plus radiation therapy ( RT ) for primary CNS lymphoma ( PCNSL ) has significantly improved patient survival over RT alone , but there are late neurologic sequelae of RT , particularly in the elderly . We treated 13 patients over age 50 years ( mean age 74 years ) with chemotherapy alone as initial treatment for PCNSL . All received methotrexate ( MTX ) and procarbazine ; in addition , five received thiotepa , four vincristine , and four vincristine and cytarabine . Ten achieved a complete response ( CR ) , 2 a partial response ( PR ) , and 1 progressed through treatment . Two patients with ocular lymphoma responded to MTX , procarbazine , and vincristine . Four of six patients who relapsed after achieving a CR or PR were treated with additional chemotherapy or RT , three achieved a CR and one a PR . Five patients remain in CR at 7.5 to 30 months , one is alive at 35 months but with progressive disease , six died of PCNSL at 5 to 30.5 months , and one died in CR of sulfur allergy 2 months after diagnosis . The Karnofsky Performance Status improved in 11 of 13 patients with treatment . Cognitive deficits were present in nine patients at diagnosis and improved in eight of these nine after chemotherapy . Only one patient developed new cognitive deficits , due to progressive tumor and possibly MTX leukoencephalopathy . Chemotherapy alone for PCNSL is effective in the elderly and eliminates the risk of RT-related neurotoxicity . RT can salvage those who relapse after chemotherapy . NEUROLOGY 1996;46 : 435 - BACKGROUND Primary central nervous system lymphoma ( PCNSL ) is an aggressive extranodal non-Hodgkin lymphoma confined to the central nervous system . In this article , we report the results of a pilot trial adding rituximab to the established regimen consisting of methotrexate , procarbazine , and lomustine ( R-MCP ) . DESIGN AND METHODS PCNSL patients ≥65 years without Karnofsky performance score ( KPS ) limit were included . R-MCP regimen consisted of rituximab ( 375 mg/m(2 ) i.v . on days -6 , 1 , 15 , and 29 ) , methotrexate ( 3 g/m(2 ) i.v . , days 2 , 16 , and 30 ) followed by folinic rescue , procarbazine ( 60 mg/m(2 ) orally , days 2 - 11 ) , and lomustine ( 110 mg/m(2 ) orally , day 2 ) . A maximum of three 43-day cycles were applied . Primary end point was response to treatment obtained by magnetic resonance imaging . Secondary end points were overall survival ( OS ) and progression-free survival ( PFS ) . RESULTS Twenty-eight patients were included ( median age 75 , median KPS 60 % ) . Best documented response : complete remission in 18 of 28 ( 64 % ) , partial remission in 5 of 28 ( 18 % ) , stable disease in 1 of 28 ( 4 % ) , and progressive disease in 2 of 28 ( 7 % ) patients . Response was not assessed in two patients . Two treatment-associated deaths were observed . After a median follow-up of 36 months , the 3-year PFS and OS was 31 % . CONCLUSION R-MCP regimen is well tolerated and active in elderly patients with newly diagnosed PCNSL PURPOSE The purpose of this study was to analyze prognostic factors for patients with newly diagnosed primary CNS lymphoma ( PCNSL ) in order to establish a predictive model that could be applied to the care of patients and the design of prospect i ve clinical trials . PATIENTS AND METHODS Three hundred thirty-eight consecutive patients with newly diagnosed PCNSL seen at Memorial Sloan-Kettering Cancer Center ( MSKCC ; New York , NY ) between 1983 and 2003 were analyzed . St and ard univariate and multivariate analyses were performed . In addition , a formal cut point analysis was used to determine the most statistically significant cut point for age . Recursive partitioning analysis ( RPA ) was used to create independent prognostic classes . An external validation set obtained from three prospect i ve Radiation Therapy Oncology Group ( RTOG ) PCNSL clinical trials was used to test the RPA classification . RESULTS Age and performance status were the only variables identified on st and ard multivariate analysis . Cut point analysis of age determined that patients age < or = 50 years had significantly improved outcome compared with older patients . RPA of 282 patients identified three distinct prognostic classes : class 1 ( patients < 50 years ) , class 2 ( patients > or = 50 ; Karnofsky performance score [ KPS ] > or = 70 ) and class 3 ( patients > or = 50 ; KPS < 70 ) . These three classes significantly distinguished outcome with regard to both overall and failure-free survival . Analysis of the RTOG data set confirmed the validity of this classification . CONCLUSION The MSKCC prognostic score is a simple , statistically powerful model with universal applicability to patients with newly diagnosed PCNSL . We recommend that it be adopted for the management of newly diagnosed patients and incorporated into the design of prospect i ve clinical trials PURPOSE A multicenter phase II study was conducted to assess the efficacy of rituximab , methotrexate , procarbazine , and vincristine ( R-MPV ) followed by consolidation reduced-dose whole-brain radiotherapy ( rdWBRT ) and cytarabine in primary CNS lymphoma . PATIENTS AND METHODS Patients received induction chemotherapy with R-MPV ( five to seven cycles ) ; those achieving a complete response ( CR ) received rdWBRT ( 23.4 Gy ) , and otherwise , st and ard WBRT was offered ( 45 Gy ) . Consolidation cytarabine was given after the radiotherapy . The primary end point was 2-year progression-free survival ( PFS ) in patients receiving rdWBRT . Exploratory end points included prospect i ve neuropsychological evaluation , analysis of magnetic resonance imaging ( MRI ) white matter changes using the Fazekas scale , and evaluation of the apparent diffusion coefficient ( ADC ) as a prognostic factor . RESULTS Fifty-two patients were enrolled , with median age of 60 years ( range , 30 to 79 years ) and median Karnofsky performance score of 70 ( range , 50 to 100 ) . Thirty-one patients ( 60 % ) achieved a CR after R-MPV and received rdWBRT . The 2-year PFS for this group was 77 % ; median PFS was 7.7 years . Median overall survival ( OS ) was not reached ( median follow-up for survivors , 5.9 years ) ; 3-year OS was 87 % . The overall ( N = 52 ) median PFS was 3.3 years , and median OS was 6.6 years . Cognitive assessment showed improvement in executive function ( P < .01 ) and verbal memory ( P < .05 ) after chemotherapy , and follow-up scores remained relatively stable across the various domains ( n = 12 ) . All examined MRIs ( n = 28 ) displayed a Fazekas score of ≤ 3 , and no patient developed scores of 4 to 5 ; differences in ADC values did not predict response ( P = .15 ) , PFS ( P = .27 ) , or OS ( P = .33 ) . CONCLUSION R-MPV combined with consolidation rdWBRT and cytarabine is associated with high response rates , long-term disease control , and minimal neurotoxicity PURPOSE To assess the efficacy and toxicity of chemotherapy alone in patients older than 60 years with primary CNS lymphoma . PATIENTS AND METHODS Fifty patients with a median age of 72 years and a median Karnofsky performance score ( KPS ) of 50 were eligible for this multicenter phase II study . The protocol consisted of high-dose methotrexate ( MTX ) , lomustine , procarbazine , methylprednisolone , and intrathecal chemotherapy with MTX and cytarabine . The patients received one induction cycle ; if objective response was achieved , five additional maintenance cycles were administered every 6 weeks . The median follow-up of patients was 3 years . RESULTS Twenty four patients ( 48 % ) achieved an objective response ( compete response [ CR ] , 42 % ; partial response , 6 % ) , with a median duration of CR of 27 months ( range , 3 to 47 + months ) . Overall median survival time was 14.3 months , and 1-year progression-free survival was 40 % ( 95 % confidence interval [ CI ] , 26 % to 53 % ) . Myelosuppression was the most frequent side effect , with grade 3 to 4 neutropenia in 19 % of patients . One patient died during chemotherapy , as a result of pulmonary embolism . Most patients improved or preserved their cognitive functions ( 47 % and 45 % of the patients , respectively ) and KPS ( 36 % and 52 % of the patients , respectively ) until relapse , whereas cognitive and KPS decline attributed to delayed treatment neurotoxicity occurred in 8 % and 12 % patients , respectively . CONCLUSION In the elderly , this chemotherapy regimen compares favorably with radiotherapy ( RT ) alone and reduces considerably the risk of delayed neurotoxicity associated with combined chemoradiotherapy . Chemotherapy alone is an appropriate strategy in older patients to delay or avoid RT The role of chemotherapy in the treatment of patients with primary central nervous system lymphoma ( PCL ) remains unclear , with no r and omized trials available to aid in the interpretation of the current data . The Medical Research Council therefore conducted the current r and omized trial to assess the impact on survival of postradiotherapy chemotherapy with cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) in nonimmunocompromised adult patients with pathologically proven PCL |
12,237 | 12,076,496 | Apart from one study which showed a slight but statistically significant difference in total cholesterol in the low fat group at one year follow-up , there were no significant differences between the dietary groups for other outcome measures such as serum lipids , blood pressure and fasting plasma glucose .
REVIEW ER 'S CONCLUSIONS The review suggests that fat-restricted diets are no better than calorie restricted diets in achieving long term weight loss in overweight or obese people .
Overall , participants lost slightly more weight on the control diets but this was not significantly different from the weight loss achieved through dietary fat restriction and was so small as to be clinical ly insignificant | BACKGROUND Overweight and obesity are global health problems contributing to an ever increasing noncommunicable disease burden .
Calorie restriction can achieve short-term weight loss but the weight loss has not been shown to be sustainable in the long-term .
An alternative approach to calorie restriction is to lower the fat content of the diet .
However , the long-term effects of fat-restricted diets on weight loss have not been established .
OBJECTIVES To assess the effects of advice on low-fat diets as a means of achieving sustained weight loss , using all available r and omised clinical trials .
Since we were particularly interested in the ability of participants to sustain weight loss over a longer period of time , we focused on studies of ' free living ' men and women who were given dietary advice rather than provision of food or money to purchase food . | Recent evidence suggests that dietary fat intake may be more strongly associated than total energy intake to the development and maintenance of obesity . The objective of this study was to determine whether dietary fat restriction would promote more favorable changes in body weight , body composition , resting metabolic rate ( RMR ) , eating behavior , and dietary adherence than calorie restriction . Sixty-five obese women and 15 obese men were recruited and r and omly assigned to calorie restriction ( 1000–1200 kcal/day ) or fat restriction ( 22–26 g/day ) . Subjects participated in a 24-week behavioral weight loss program . Fortyeight subjects completed assessment s at all four time points — baseline and 6 , 12 , and 18 months . Weight loss was significantly greater in the low calorie ( LC ) group ( −11.2 versus −6.1 kg , p<.001 ) and was maintained better at the 18-month assessment ( −7.5 versus −1.8 kg , p≤.001 ) . There was a significantly greater decrease in percent body fat and RMR for the LC group with only percent body fat still significantly lower at 18 months . Subjects in the LC group consumed significantly fewer calories , less carbohydrates , and the same amount of fat as those in the low fat ( LF ) condition , however , calorie and carbohydrate intake were decreasing for LF subjects by the 12- and 18-month assessment s. There were no long-term differences in most measured predictors of dietary adherence . Dietary fat restriction did not prove to be superior to calorie restriction , thus strengthening the public health message that calories do count The role of dietary fat in the regulation of energy intake was assessed by manipulating a conventional diet and measuring spontaneous food consumption . Twenty-four women each consumed a sequence of three 2-wk dietary treatments in which 15 - 20 % , 30 - 35 % , or 45 - 50 % of the energy was derived from fat . These diets consisted of foods that were similar in appearance and palatability but differed in the amount of high-fat ingredients used . Relative to their energy consumption on the medium-fat diet , the subjects spontaneously consumed an 11.3 % deficit on the low-fat diet and a 15.4 % surfeit on the high-fat diet ( p less than 0.0001 ) , result ing in significant changes in body weight ( p less than 0.001 ) . A small amount of caloric compensation did occur ( p less than 0.02 ) , which was greatest in the leanest subjects ( p less than 0.03 ) . These results suggest that habitual , unrestricted consumption of low-fat diets may be an effective approach to weight control In a prospect i ve , r and omised , controlled trial to determine whether comprehensive lifestyle changes affect coronary atherosclerosis after 1 year , 28 patients were assigned to an experimental group ( low-fat vegetarian diet , stopping smoking , stress management training , and moderate exercise ) and 20 to a usual-care control group . 195 coronary artery lesions were analysed by quantitative coronary angiography . The average percentage diameter stenosis regressed from 40.0 ( SD 16.9)% to 37.8 (16.5)% in the experimental group yet progressed from 42.7 (15.5)% to 46.1 (18.5)% in the control group . When only lesions greater than 50 % stenosed were analysed , the average percentage diameter stenosis regressed from 61.1 (8.8)% to 55.8 (11.0)% in the experimental group and progressed from 61.7 (9.5)% to 64.4 (16.3)% in the control group . Overall , 82 % of experimental-group patients had an average change towards regression . Comprehensive lifestyle changes may be able to bring about regression of even severe coronary atherosclerosis after only 1 year , without use of lipid-lowering drugs This r and omised controlled trial examined anthropometric changes and cardiovascular benefits of six months of weight management in 110 free living women , aged 18–68 y and BMI 25–50 kg/m2 , who received 1200 kcal/d diet treatments of either high ( 58 % energy , n=57 ) or low ( 35 % energy , n=53 ) carbohydrate ( CHO ) content . Body weight , plasma total , HDL and LDL cholesterol , triglyceride and blood pressure were measured . Examination at three months showed women on high CHO lost ( mean±s.e.m . ) 4.3±0.5 kg and those on low CHO lost 5.6±0.6 kg of body weight . Changes in risk factors did not significantly differ between the two diet treatments throughout the study . However those on high CHO diets significantly lowered their plasma total cholesterol by 0.33 mmol/l ( 95 % CI : 0.10 , 0.55 ) , LDL cholesterol by 0.23 mmol/l ( 0.02 , 0.43 ) and HDL cholesterol by 0.05 mmol/l ( 0.03 , 0.10 ) , while women on low CHO diets lowered only plasma triglyceride by 0.28 mmol/l ( 0.08 , 0.48 ) . Blood pressure did not change significantly on either diet . After six months , women on high CHO lost 5.6±0.8 kg and those on low CHO lost 6.8±0.8 kg . On the high CHO diet , total cholesterol remained significantly below the baseline value at 0.34 mmol/l ( 0.13 , 0.56 ) , triglyceride was significantly lowered by 0.27 mmol/l ( 0.10 , 0.45 ) , and HDL cholesterol returned to the baseline value . On the low CHO diet , triglyceride remained the only risk factor to be significantly improved . A subgroup of 46 postmenopausal women lost significantly ( P<0.05 ) more weight on the low CHO diet than high CHO diet . In conclusion , these results provided some support for preferring a high CHO diet to a lower CHO approach in weight management , from the point of view of risk reduction , but do not indicate a consistently more rapid weight loss with either diet OBJECTIVE The aim of this r and omized trial was to compare the effects of a behavioral intervention focusing on either calorie restriction alone or calorie plus fat restriction on weight loss and changes in lipids and glycemic control in individuals with non-insulin-dependent diabetes mellitus ( NIDDM ) or a family history of diabetes . RESEARCH DESIGN AND METHODS We recruited 44 obese women with NIDDM and 46 obese women with a family history of NIDDM and r and omly assigned these subjects to calorie restriction ( CAL ) or to calorie plus fat restriction ( CAL + FAT ) . All subjects participated in a 16-week behavioral weight loss program , with training in diet , exercise , and behavior modification . Subjects assigned to the CAL condition were given a 1,000−1,500 kcal/day goal and self-monitored calories consumed . Subjects assigned to the CAL + FAT condition had the same calorie goal , but were also given a fat goal ( grams of fat/day ) , to produce a diet with < 20 % of calories from fat ; this group monitored both calories and fat grams . RESULTS Among NIDDM subjects , weight loss of the subjects in the CAL+FAT condition was significantly > subjects in the CAL condition ( 7.7 vs. 4.6 kg ) and the CAL+FAT condition group also maintained their weight loss better at the 1-year follow-up ( 5.2 vs. 1.0 kg ) . Significant decreases in glucose , high-density lipoprotein ( HDL ) cholesterol , and total cholesterol were seen after 16 weeks of treatment among NIDDM subjects ; these changes were similar in CAL and CAL+FAT groups , but a greater proportion of subjects in CAL condition required oral hypoglycemic medication . At the 1-year follow-up , all parameters had returned to baseline . No significant differences in weight loss or physiological changes were seen between CAL and CAL+FAT conditions in subjects with a family history of diabetes . CONCLUSIONS These results suggest that using the combination of calorie and fat restriction may help promote weight loss in obese NIDDM patients . No other long-term benefits of this regimen were observed OBJECTIVE : We investigated the prevalence of overweight and obesity and their relationships with the main cardiovascular risk factors in the population of Ventimiglia di Sicilia , a rural village in Southern Italy characterized by low cholesterol levels and by a low incidence of early coronary heart disease mortality . We related all deaths to body weight and fat distribution during an 8 y follow-up . DESIGN : Cross-sectional and prospect i ve observational study .SUBJECTS : A total of 835 free-living individuals , 363 males and 472 females , of age between 20 and 69 y. MEASUREMENTS : In all participants body weight , waist-to-hip ratio ( WHR ) , cardiovascular risk factors and plasma lipids were measured . During the follow-up , total and cardiovascular deaths were registered . RESULTS : We found a high overall prevalence of subjects with overweight or obesity ( respectively 45.0 % and 27.7 % ) , with great differences among classes of age . As expected , body weight and fat distribution were associated with diabetes , hypertension , dyslipidemia and with a worsening of lipid profile . During the follow-up we registered 37 total and 11 cardiovascular deaths . All-cause and cardiovascular mortality risks were , respectively , 1.64 ( 95 % CI 0.65–4.15 ) and 2.71 ( 95 % CI 0.29–25.26 ) in subjects with a body mass index ( BMI ) of 27–29.99 kg/m2 and 2.45 ( 95 % CI 1.03–5.87 ) and 5.36 ( 95 % CI 1.41–62.01 ) in subjects with a BMI of≥30 kg/m2 in comparison with participants with a BMI of < 27 kg/m2 , and 3.48 ( 95 % CI 1.46–8.30 ) and 4.55 ( 95 % CI 1.12–18.40 ) in subjects with a WHR higher than the median in comparison with individuals with a WHR lower than the median . CONCLUSION : The Ventimiglia di Sicilia Study highlights the great importance of overweight and obesity as a public health issue in a rural population and indicates that it is necessary to consider the impact of body weight and fat distribution on both total and CHD mortality Quantification of the excess mortality from all causes associated with obesity remains controversial . In this paper , 6,193 obese patients , those with a body mass index ( weight (kg)/height (m)2 ( BMI ) ) range of 25 - 74 kg/m2 , recruited from 1961 to 1994 in Düsseldorf , Germany , were followed for a mean time of 14 ( st and ard deviation , 8.2 ) years , yielding 87,179 observed patient-years . During the study period , 1,028 patients ( 16.6 % ) died . The entire cohort was grouped into approximate quartiles according to BMI : group 1 , BMI from 25 to < 32 ; group 2 , BMI from 32 to < 36 ; group 3 , BMI from 36 to < 40 ; group 4 , BMI > or = 40 kg/m2 . The following risk ratios were estimated by means of Cox proportional hazards models using the lowest BMI group as reference category : group 2 for men , 1.02 ( 95 % confidence interval 0.76 - 1.37 ) ; for women , 1.23 ( 95 % confidence interval 0.96 - 1.58 ) ; group 3 for men , 1.50 ( 95 % confidence interval 1.09 - 2.06 ) ; for women , 1.33 ( 95 % confidence interval 1.03 - 1.73 ) ; and group 4 for men , 2.10 ( 95 % confidence interval 1.53 - 2.88 ) ; for women , 2.25 ( 95 % confidence interval 1.78 - 2.84 ) . The following st and ardized mortality ratios were calculated by using the respective geographic area ( the Federal State of North Rhine Westphalia ) as reference population : group 1 for men , 1.26 ( 95 % confidence interval 0.98 - 1.61 ) ; for women , 1.00 ( 95 % confidence interval 0.81 - 1.23 ) ; group 2 for men , 1.31 ( 95 % confidence interval 1.09 - 1.57 ) ; for women , 1.20 ( 95 % confidence interval 1.02 - 1.40 ) ; group 3 for men , 1.92 ( 95 % confidence interval 1.53 - 2.38 ) ; for women , 1.27 ( 95 % confidence interval 1.07 - 1.50 ) ; and group 4 for men , 3.05 ( 95 % confidence interval 2.47 - 3.73 ) ; for women , 2.31 ( 95 % confidence interval 2.04 - 2.60 ) . In addition to age , sex , and BMI , Cox proportional hazards models revealed systolic blood pressure , glucose intolerance , diabetes , and smoking as significant independent mortality risk factors , whereas cholesterol was not significant . In this prospect i ve study of a large cohort of obese persons , morbid obesity ( BMI of > or = 40 kg/m2 ) was a strong predictor of premature death . Excess mortality risks associated with gross obesity ( BMI from 32 to < 40 kg/m2 ) were considerably lower than hitherto assumed ; moderate degrees of obesity ( BMI from 25 to < 32 kg/m2 ) were not significantly associated with excess mortality OBJECTIVE Assessment of body composition in relation to the habitual diet and after a six month dietary intervention . DESIGN After a baseline measurement subjects were r and omly assigned to either a group consuming reduced-fat products or a group consuming full-fat products for six months . SUBJECTS 108 women and 109 men , equally distributed over the age range 19 - 35 with BMI between 21 and 28 , and the age range 36 - 55 with BMI between 24 and 30 . MEASUREMENTS Food intake was measured by three day dietary record , body composition by deuterium dilution . RESULTS At baseline , explained variance of % body fat on age and fat-carbohydrate ratio in the diet together were 17 % ( P < 0.0001 ) and 36 % ( P < 0.0001 ) for women and men , respectively , and on diet alone 7 - 8 % ( P < 0.01 ) independent of gender . The diet intervention caused on average a change in fat intake and body fat mass in subjects of the reduced-fat group of -5 + /- 29 g/d ( P < 0.05 ) and -0.1 + /- 2.1 kg ( ns ) , respectively , and of + 23 + /- 31 g/d ( P < 0.0001 ) and + 0.5 + /- 2.3 kg ( P < 0.05 ) in subjects of the full-fat group . The change in the fat content of the diet was positively related to a change in energy intake ( fat-carbohydrate ratio : R2 = 0.15 , P < 0.0001 ; g fat : R2 = 0.70 , P < 0.0001 ) , the latter explaining 5 % of the variation in the change in body fat mass ( P < 0.001 ) . Subjects changing the fat content of the diet showed a consequent change in body fat mass only when energy intake changed as well . CONCLUSION The fat content of the diet has an effect on body fat as a function of the effect of dietary fat on energy intake The low-fat group consumed significantly fewer calories from fat and more calories from carbohydrate at both 6 and 12 months than the low-calorie group , but their fat intake was still about twice their goal at both 6 months ( 39 gm per day ) and 12 months ( 46 gm per day ) . The low-calorie group achieved their fat goal of 30 % of calorie intake , but they consumed from 300 to 700 kcal more than their calorie goal . Caloric intake , physical activity , palatability , satiety , quality of life , and weight loss were not significantly different by treatment . Two studies , which gave patients hypocaloric diets of varying fat and carbohydrate content ( fat calories 10 % to 45 % ) for from 10 to 12 weeks , found no effect of diet composition on weight loss . In addition , one study , which gave patients a low-fat , energy-unrestricted diet ( fat calories 19 % ) , reported a weight loss of 10.1 lb at 16 to 20 weeks and 5.7 lb at 9 to 12 months , which is similar to that seen in the low-fat group in the this study . Most of the decrease in fat intake ( 90 % ) in the low-fat group result ed from a reduction in intake of fat from fat and oils ; meat , fish , and poultry ; dairy products ; and sweets . The dietary changes in the low-fat group are consistent with those found in one study , which prescribed a 15 % fat calorie diet to women with breast cancer . Intake of vitamin C increased in the low-fat group and decreased in the low-calorie group . This difference was significant and was caused by an increased intake of fruits and vegetables in the low-fat group and a decreased consumption of fruits in the low-calorie group . Calcium intake decreased significantly more in the low-calorie group because of a decreased intake of dairy foods OBJECTIVE to evaluate the effectiveness of dietary counseling focusing on fat reduction ( 20 g/day ) compared to calorie reduction ( 1000 to 1200 kcal/day ) in promoting long-term weight loss in moderately obese women . DESIGN One hundred and twenty-two women were r and omized to one of the two treatment groups and received intensive dietary counseling in groups of 20 over a period of 18 months . RESULTS Among 74 women completing the study , weight losses at 6 months averaged 10.2 lb ( n = 39 ) in the fat counseling group and 8.1 lb ( n = 35 ) in the calorie counseling group . Average weight returned to baseline levels in both groups over the succeeding 12 months despite continued intervention . CONCLUSION Although these data provide little support for the immediate clinical utility of low-fat dietary counseling in obesity treatment , the observation that women in the low-fat group were more compliant with treatment directions , rated the diet as being more palatable , and experienced greater reduction in binge eating scores suggests that this approach warrants further study . In addition , time dependent covariance analysis showed that change in fat intake predicted weight change better than change in total energy intake , thus reinforcing the idea that dietary fat may be an important factor in the etiology and treatment of obesity CONTEXT : Long-term success in weight loss with dietary treatment has been elusive . OBJECTIVE : To evaluate a diet moderate in fat based on the Mediterranean diet compared to a st and ard low-fat diet for weight loss when both were controlled for energy . DESIGN : A r and omized , prospect i ve 18 month trial in a free-living population . PATIENTS : A total of 101 overweight men and women ( 26.5–46 kg/m2).INTERVENTION : ( 1 ) Moderate-fat diet ( 35 % of energy ) ; ( 2 ) low-fat diet ( 20 % of energy).MAIN OUTCOME MEASUREMENTS : Change in body weight . RESULTS : After 18 months , 31/50 subjects in the moderate-fat group , and 30/51 in the low fat group were available for measurements . In the moderate-fat group , there were mean decreases in body weight of 4.1 kg , body mass index of 1.6 kg/m2 , and waist circumference of 6.9 cm , compared to increases in the low-fat group of 2.9 kg , 1.4 kg/m2 and 2.6 cm , respectively ; P≤0.001 between the groups . The difference in weight change between the groups was 7.0 kg . ( 95 % CI 5.3 , 8.7 ) . Only 20 % ( 10/51 ) of those in the low-fat group were actively participating in the weight loss program after 18 months compared to 54 % ( 27/50 ) in the moderate-fat group , ( P<0.002 ) . The moderate-fat diet group was continued for an additional year . The mean weight loss after 30 months compared to baseline was 3.5 kg ( n=19 , P=0.03 ) . CONCLUSIONS : A moderate-fat , Mediterranean-style diet , controlled in energy , offers an alternative to a low-fat diet with superior long-term participation and adherence , with consequent improvements in weight loss OBJECTIVE Dietary fat restriction is currently being promoted as a weight loss strategy . However , previous investigations suggest that fat restriction alone may not be more beneficial than total energy restriction for the treatment of obesity . The purpose of this project was to assess whether an energy-restricted or fat-restricted diet was more effective at promoting weight loss , improving eating behaviors , and reducing barriers to dietary adherence . RESEARCH METHODS AND PROCEDURES Eighty individuals ( 15 men and 65 women ) were r and omized into the two treatment conditions . Subjects were 120 % to 140 % of ideal body weight and 25 years to 45 years old . Treatment consisted of 24 weeks of dietary fat ( 22 g/day to 26 g/day ) or energy restriction ( 4,186 kJ/day to 5,023 kJ/day ) , including behavior modification and exercise . Body weight change , dietary intake , eating behaviors , and barriers to adherence were measured at baseline and after treatment . RESULTS Results show that subjects in the energy-restricted condition lost over twice as much weight as those in the fat-restricted group ( 11.5 kg vs. 5.2 kg ) . Additionally , subjects in the low-energy condition had greater improvements in eating behavior scores , enhanced feelings of wellness , a greater distaste for dietary fat , and no more pronounced feelings of deprivation than did those in the fat-restricted condition . DISCUSSION An energy-restricted diet produces greater short-term weight loss than dietary fat restriction without many of the negative consequences commonly attributed to reducing energy intake CONTEXT The effect of age on excess mortality from all causes associated with obesity is controversial . Few studies have investigated the association between body mass index ( BMI , calculated as weight in kilograms divided by the square of height in meters ) , age , and mortality , with sufficient numbers of subjects at all levels of obesity . OBJECTIVE To assess the effect of age on the excess mortality associated with all degrees of obesity . DESIGN Prospect i ve cohort study . SETTING AND PARTICIPANTS A total of 6193 obese patients with mean ( SD ) BMI of 36.6 ( 6.1 ) kg/m2 and mean ( SD ) age of 40.4 ( 12.9 ) years who had been referred to the obesity clinic of Heinrich-Heine University , Düsseldorf , Germany , between 1961 and 1994 . Median follow-up time was 14.8 years . MAIN OUTCOME MEASURE All-cause mortality through 1994 among 6053 patients for whom follow-up data were available ( 1028 deaths ) analyzed as st and ardized mortality ratios ( SMRs ) using the male-female population of the geographic region ( North Rhine Westphalia ) as reference . RESULTS The cohort was grouped into approximate quartiles according to age ( 18 - 29 , 30 - 39 , 40 - 49 , and 50 - 74 years ) and BMI ( 25 to < 32 , 32 to < 36 , 36 to < 40 , and > or = 40 kg/m2 ) at baseline . The SMRs showed a significant excess mortality with an SMR for men of 1.67 ( 95 % confidence interval , 1.51 - 1.85 ; P<.001 ) and an SMR for women of 1.45 ( 95 % confidence interval , 1.34 - 1.57 ; P<.001 ) . The excess mortality associated with obesity declined with age . For men , the SMRs of the 4 age groups were 2.46 , 2.30 , 1.99 , and 1.31 , respectively ; for women , they were 1.81 , 2.10 , 1.70 , and 1.26 , respectively ( Poisson trend test , P<.001 ) . The SMRs increased with BMI but , within each BMI group , the SMRs decreased with age . The lowest SMRs ( for men , 1.01 ; for women , 0.91 ) were obtained for patients older than 50 years with BMI s of 25 to less than 32 kg/m2 . Thus , older men and women at a BMI range of 25 to less than 32 kg/m2 had no excess mortality . The highest SMRs ( for men , 4.22 ; for women , 3.79 ) were calculated for the patients aged 18 to 29 years with a BMI of 40 kg/m2 or higher . CONCLUSIONS In this large cohort of obese persons , risk of death increased with body weight , but obesity-related excess mortality declined with age at all levels of obesity Abstract Objectives : To compare importance of rate of initial weight loss for long term outcome in obese patients and to compare efficacy of two different weight maintenance programmes . Design : Subjects were r and omised to either rapid or slow initial weight loss . Completing patients were re-r and omised to one year weight maintenance programme of ad lib diet or fixed energy intake diet . Patients were followed up one year later . Setting : University research department in Copenhagen , Denmark . Subjects : 43 ( 41 women ) obese adults ( body mass index 27 - 40 ) who were otherwise healthy living in or around Copenhagen . Interventions : 8 weeks of low energy diet ( 2 MJ/day ) or 17 weeks of conventional diet ( 5 MJ/day ) , both supported by an anorectic compound ( ephedrine 20 mg and caffeine 200 mg thrice daily ) ; one year weight maintenance programme of ad lib , low fat , high carbohydrate diet or fixed energy intake diet ( ≤7.8 MJ/day ) , both with reinforcement sessions 2 - 3 times monthly . Main outcome measures : Mean initial weight loss and proportion of patients maintaining a weight loss of > 5 kg at follow up . Results : Mean initial weight loss was 12.6 kg ( 95 % confidence interval 10.9 to 14.3 kg ) in rapid weight loss group and 12.6 ( 9.9 to 15.3 ) kg in conventional diet group . Rate of initial weight loss had no effect on weight maintenance after 6 or 12 months of weight maintenance or at follow up . After weight maintenance programme , the ad lib group had maintained 13.2 ( 8.1 to 18.3 ) kg of the initial weight loss of 13.5 ( 11.4 to 15.5 ) kg , and the fixed energy intake group had maintained 9.7 ( 6.1 to 13.3 ) kg of the initial 13.8 ( 11.8 to 15.7 ) kg weight loss ( group difference 3.5 ( -2.4 to 9.3 ) kg ) . Regained weight at follow up was greater in fixed energy intake group than in ad lib group ( 11.3 ( 7.1 to 15.5 ) kg v 5.4 ( 2.3 to 8.6 ) kg , group difference 5.9 ( 0.7 to 11 . 1 ) kg , P<0.03 ) . At follow up , 65 % of ad lib group and 40 % of fixed energy intake group had maintained a weight loss of > 5 kg ( P<0.07 ) . Conclusion : Ad lib , low fat , high carbohydrate diet was superior to fixed energy intake for maintaining weight after a major weight loss . The rate of the initial weight loss did not influence long term outcome . Key messages Obesity has reached epidemic proportions in the Western world , but weight loss reverses almost all the health hazards of obesity Obese patients lose weight when they keep strictly to an energy restricted diet , but weight losses tend not to be maintained in the long term We conducted an intensive one year weight maintenance programme ( comparing an ad lib , low fat , high carbohydrate diet with a fixed energy intake diet ) after a major weight loss ( eight weeks of low energy diet or 17 weeks of conventional diet ) The rate of initial weight loss did not influence the long term outcome The ad lib , low fat diet was superior in maintaining weight loss during weight maintenance programme and at one year follow OBJECTIVE --To test whether a fat reduced diet rich in soluble dietary fibre , antioxidant vitamins , and minerals reduces complications and mortality after acute myocardial infa rct ion . DESIGN --R and omised , single blind , controlled trial . SETTING -- Primary and secondary care research centre for patients with myocardial infa rct ion . SUBJECTS--505 patients with suspected acute myocardial infa rct ion . Those with definite or possible acute myocardial infa rct ion and unstable angina based on World Health Organisation criteria were assigned to diet A ( n = 204 ) or diet B ( n = 202 ) within 24 - 48 hours of infa rct ion . INTERVENTIONS --Both groups were advised to follow a fat reduced diet . Group A was also advised to eat more fruit , vegetables , nuts , and grain products . MAIN OUTCOME MEASURES --Mortality from cardiac disease and other causes . Serum lipid concentrations and compliance with diet . RESULTS --Blood lipoprotein concentrations and body weight fell significantly in patients in group A compared with those in group B ( cholesterol fell by 0.74 mmol/l in group A v 0.32 mmol/l in group B , 95 % confidence interval of difference 0.14 to 0.70 , and weight by 7.1 v 3.0 kg , 0.52 to 7.68 ) . The incidence of cardiac events was significantly lower in group A than group B ( 50 v 82 patients , p less than 0.001 ) . Group A also had lower total mortality ( 21 v 38 died , p less than 0.01 ) than group B. CONCLUSIONS --Comprehensive dietary changes in conjunction with weight loss immediately after acute myocardial infa rct ion may modulate blood lipoproteins and significantly reduce complications and mortality after one year OBJECTIVE To compare the effects of two weight loss interventions , diet or exercise , on changes in bone , fat and lean tissue . DESIGN Prospect i ve , long term , worksite , r and omised and controlled weight-loss study using a low fat diet ad libitum or moderate aerobic exercise . SUBJECTS 66 overweight men ( mean age 43.4 + /- 5.7 y , BMI 29.0 + /- 2.6 kg/m2 ) . MEASUREMENTS Body weight , lean mass , fat mass , bone mass ( BMC ) , bone mineral density ( BMD ) by dual-energy X-ray absorptiometry . RESULTS Dieters lost 1.4 % BMC ( 1.5 % BMD ) with 6.4 kg weight loss ; there was no significant change in BMC ( or in BMD ) in exercisers ( 2.6 kg weight loss ) or in control subjects ( no weight change ) . Changes in BMC were correlated with fat loss with both interventions : 11.7 g BMC /kg fat loss in dieters , 11.4 g BMC change/kg fat loss in exercisers . CONCLUSION BMC loss with diet-induced weight loss reflects loss of weight and especially loss of body fat . Further study to determine whether similar BMC loss will accompany equivalent weight loss induced by exercise is needed 16 202 men , aged 40 - 49 years , were screened for coronary risk factors , Of these , 1232 healthy , normotensive men at high risk of coronary heart disease ( CHD ) were selected for a 5-year r and omised trial to show whether lowering of serum lipids and cessation of smoking could reduce the incidence of CHD . Men were admitted to the trial if they had serum cholesterol levels of 7.5 - 9.8 mmol/l ( 290 - 380 ) mg/dl ) , coronary risk scores ( based on cholesterol levels , smoking habits , and blood pressure ) in the upper quartile of the distribution , and systolic blood pressures below 150 mm Hg ( mean of two measurements ) . The men in the intervention group were recommended to lower their blood lipids by change of diet and to stop smoking . Mean serum cholesterol concentrations were approximately 13 % lower in the intervention group than in the control group during the trial ( based on the difference between the mean of 3 prer and omisation values and the mean of yearly values during the trial ) . Mean fasting serum triglycerides fell by 20 % in the intervention group compared with controls . 80 % of the men in both groups smoked tobacco daily at the start of the study . The mean tobacco consumption per man decreased by 45 % more in the intervention group than in the control group . However , only 25 % of the smokers in the intervention group completely stopped smoking compared with 17 % in the control group . Diagnosis of events of cardiovascular disease during the study was made blindly according to predefined criteria by two cardiologists not involved in the study . At the end of the observation period the incidence of myocardial infa rct ion ( fatal and non-fatal ) and sudden death was 47 % lower in the intervention group than in the controls ( p = 0.028 , two-tailed log rank test ) . When the incidence of strokes was added , the difference between the groups was still significant . It is concluded that in healthy middle-aged men at high risk of CHD advice to change eating habits and to stop smoking significantly reduced the incidence of the first event of myocardial infa rct ion and sudden death . Statistical analysis , by Cox 's proportional hazards model shows that the reduction in incidence in the intervention group is correlated with the reduction in total cholesterol and to a lesser extent with smoking reduction Among 135 overweight subjects , we conducted a three-month r and omized controlled trial of two sets of dietary advice , each providing approximately 1,000 calories per day but differing in fiber , carbohydrate , and fat content . Information on weight and eating habits , as well as measures of lipoprotein and glucose metabolism were obtained at entry and one and three months later . We found that dieters given low carbohydrate/low fiber dietary advice tended to lose more weight than those given a higher carbohydrate/higher fiber regimen ( 5.0 vs 3.7 kg on average at three months ) . This pattern was particularly marked among women , and among participants who were under age 40 or of lower social class . There were no differences between the diet groups in the proportion complaining of hunger but , in general , members of the low carbohydrate group complained of more problems in dieting . There were only minor differences in the serum lipoprotein patterns during the diet period . In view of these results , we believe previous cl aims of the benefits of fiber for weight loss may have been overstated |
12,238 | 30,625,375 | Differences in survival were not explained by follow-up time , age at diagnosis , gender , or cognitive score .
There is consistent evidence for higher and earlier mortality in DLB compared to AD . | OBJECTIVE To synthesize the evidence across longitudinal studies comparing survival in dementia with Lewy bodies ( DLB ) and Alzheimer 's disease ( AD ) . | Background Dementia due to Alzheimer ’s disease ( AD ) and dementia with Lewy bodies ( DLB ) are the two most common neurodegenerative causes of dementia . They commonly occur together , especially in older people , but clinical identification of these diseases in dementia is difficult in such circumstances . We therefore conducted a study using cases with both comprehensive prospect i ve clinical assessment s and complete neuropathological examination to determine if it is possible to identify such mixed cases clinical ly and to determine features which may identify DLB in the presence of AD dementia . Methods At Newcastle Brain Bank we identified subjects who had a clinical diagnosis of dementia and who also had autopsy diagnoses of pure AD , pure DLB , or mixed AD+DLB . All subjects had undergone prospect i ve longitudinal clinical assessment s. Mixed AD+DLB patients met neuropathological criteria for both DLB ( limbic/neocortical Lewy body disease ) and AD ( Braak stage V/VI and CERAD B/C ) . The records of these subjects were carefully review ed by two specialists in old-age psychiatry blind to autopsy findings to determine baseline and final clinical diagnoses based on these detailed records . The presence of characteristic Lewy body symptoms and other clinical information was also recorded . Results Of 59 subjects included , 19 were AD , 18 DLB , and 22 mixed AD+DLB . At baseline no subjects were correctly identified as having mixed AD+DLB and by final diagnosis only 23 % were identified . The only symptom which helped in identifying the presence of Lewy body disease in the context of a mixed AD+DLB dementia was complex visual hallucinations . Conclusions Whilst the identification of DLB in the context of a dementia with an AD pattern is difficult , the emergence of complex visual hallucinations in the context of such a degenerative dementia suggests the presence of Lewy body disease and should encourage a careful assessment . Biomarkers appear likely to be necessary to help improve identification of different disease subtypes underlying dementia Background Falls are a major cause of morbidity and mortality in dementia , but there have been no prospect i ve studies of risk factors for falling specific to this patient population , and no successful falls intervention/prevention trials . This prospect i ve study aim ed to identify modifiable risk factors for falling in older people with mild to moderate dementia . Methods and Findings 179 participants aged over 65 years were recruited from outpatient clinics in the UK ( 38 Alzheimer 's disease ( AD ) , 32 Vascular dementia ( VAD ) , 30 Dementia with Lewy bodies ( DLB ) , 40 Parkinson 's disease with dementia ( PDD ) , 39 healthy controls ) . A multifactorial assessment of baseline risk factors was performed and fall diaries were completed prospect ively for 12 months . Dementia participants experienced nearly 8 times more incident falls ( 9118/1000 person-years ) than controls ( 1023/1000 person-years ; incidence density ratio : 7.58 , 3.11–18.5 ) . In dementia , significant univariate predictors of sustaining at least one fall included diagnosis of Lewy body disorder ( proportional hazard ratio ( HR ) adjusted for age and sex : 3.33 , 2.11–5.26 ) , and history of falls in the preceding 12 months ( HR : 2.52 , 1.52–4.17 ) . In multivariate analyses , significant potentially modifiable predictors were symptomatic orthostatic hypotension ( HR : 2.13 , 1.19–3.80 ) , autonomic symptom score ( HR per point 0–36 : 1.055 , 1.012–1.099 ) , and Cornell depression score ( HR per point 0–40 : 1.053 , 1.01–1.099 ) . Higher levels of physical activity were protective ( HR per point 0–9 : 0.827 , 0.716–0.956 ) . Conclusions The management of symptomatic orthostatic hypotension , autonomic symptoms and depression , and the encouragement of physical activity may provide the core elements for the most fruitful strategy to reduce falls in people with dementia . R and omised controlled trials to assess such a strategy are a priority Auteur(s ) : Jacques Boddaert , Marc Verny La responsabilite de la maladie d’Alzheimer ( MA ) dans les gr and es causes de mortalite a ete suggeree par differentes etudes , et differents facteurs pejoratifs ont ete rapportes , tels que le sexe masculin , la severite initiale de la maladie , l’existence de troubles du comportement , de deambulation ou de chutes , et la presence de signes extrapyramidaux . Les donnees de la litterature sont assez variables , selon que l’on parle de debut de la maladie , et dans ce cas selon les criteres que l’on retient pour le definir , ou de date du diagnostic . De meme , l’evolutivite du declin cognitif doit etre prise en compte , comme le confirme l’etude de Hui et al. sur 354 patients avec une MA suivis sur une periode 4 ans [ 1 ] . Degre de complexite supplementaire chez le gr and vieillard polypathologique , les nombreuses comorbidites associees jouent probablement un role determinant dans la survie de ces patients , et parler de survie de la MA dem and e une prise en compte de tous ces parametres confondants . Wolfson et al. , a partir de la Canadian study of health and aging ( CSHA ) , avaient etudie la survie de la MA en 2001 en considerant le debut de la maladie d’Alzheimer diagnostique par 3 questions de la Camdex ( Cambridge examination for mental disorders of the elderly ) . Ces auteurs avaient rapporte une mediane de survie de 3,1 ans chez des patients âges ( 83 + /- 7 ans ) avec MA , en utilisant des ajustements pour le biais de duree d’evolution , le sexe , le niveau d’education et l’âge au moment du diagnostic , qui restait , apres regression logistique , le facteur de plus mauvais pronostic [ 2 ] . Recemment , Larson et al. ont publie de nouveaux result ats sur le sujet [ 3 ] . Il s’agit d’une etude observationnelle prospect i ve , a partir de 23 000 patients âges de 60 ans ou plus engages dans un programme de sante , suivis de 1987 a 1996 , permettant d’etudier l’histoire naturelle de la MA dans les cas incidents . Durant la periode de l’etude , 970 patients ont ete explores pour un syndrome dementiel . Parmi eux , 521 nouveaux cas de MA ont ete diagnostiques , comprenant 431 cas probables et 90 cas de MA possible selon les criteres du DSM-III-R et NINCDS-ADRDA , avec un suivi moyen de 5,2 ± 3,1 ans . Les scores au MMS au moment du diagnostic se repartissaient en 17 % entre 25 et 30 , 24 % entre 22 et 24 , 30 % entre 18 et 21 et 30 % ≤ 17 . Les scores relativement bas de MMS ( 60 % ≤ 21 ) sont dus aux modes de recrutement ( patients entrant dans le registre s’ils recevaient des soins ) et a ceux du reperage des symptomes de demence ( troubles mnesiques , confusion ou deambulation ... ) . La mediane de survie des patients a partir du diagnostic de la maladie etait influencee par de nombreux facteurs . Elle passait de 4,2 ans pour les hommes a 5,7 ans pour les femmes , confirmant le caractere pejoratif du sexe masculin . Concernant les comorbidites , cette etude soulignait le role d’une cardiopathie ischemique ( p < 0,001 ) , d’une insuffisance cardiaque ( p < 0,001 ) , du diabete ( p = 0,04 ) et d’un antecedent d’accident vasculaire cerebral ( p = 0,026 ) associes . Par contre , l’hypertension arterielle , consideree comme representant un facteur de declin de la MA , n’influencait pas la maladie . En analyse multivariee , ajustee pour l’âge , le sexe , l’origine ethnique , l’existence d’une cardiopathie ischemique , d’une insuffisance cardiaque et d’un diabete , le deces etait correle : 1 ) au score MMSE au moment du diagnostic ( ≤ 17 : hazard ratio 2,67 [ 1,94 - 3,66 ] , p < 0,001 ) ; 2 ) au score DRS ( entre 5,5 et 17 : hazard ratio 2,04 [ 1,54 - 2,71 , p < 0,001 ) ; 3 ) aux signes frontaux ( hazard ratio 1,27 [ 1,03 - 1,55 ] , p = 0,022 ) ; 4 ) aux signes extrapyramidaux ( hazard ratio 1,35 [ 1,03 - 1,76 ] , p = 0,028 ) ; 5 ) aux troubles de l’humeur ( hazard ratio 1,4 [ 1,12 - 1,76 ] , p = 0,004 ) , 6/ a la deambulation ( hazard ratio 1,45 [ 1,02 - 2,08 ] , p = 0,04 ) . Le declin de plus de 5 points de MMS par an etait egalement associe a une mortalite augmentee . En comparant les result ats de l’etude aux donnees de la mortalite dans la population des Etats-Unis , les patients atteints d’une MA avaient constamment une reduction de l’esperance de vie . Les causes de deces ne sont pas rapportees . La correlation inverse entre mortalite et score au MMS reflete probablement la duree d’evolution de la maladie et l’on peut s’interroger sur l’impact d’une prise en charge globale et plus encore medicamenteuse chez ces patients . Cette etude souligne l ’ importance des comorbidites dans la MA du sujet âge , et est utile pour le clinicien , en particulier pour decider de la mise en place de therapeutiques lourdes . De plus , la mise en evidence de facteurs pejoratifs associes permet de cibler une population plus a risque et d’adapter au mieux surveillance et traitements . La limitation principale de cette etude concerne le mode de recrutement et le caractere non representatif de la population dans son ensemble . De nouvelles etudes , idealement en population , devront preciser la duree de vie des malades atteints d’une maladie d’Alzheimer et evaluer l’impact sur la survie des therapeutiques symptomatiques de la MA ou des traitements des comorbidites . 1 . Hui JS , Wilson RS , Bennett DA , Bienias JL , Gilley DW , Evans DA . Rate of cognitive decline and mortality in Alzheimer ’s disease . Neurology 2003 ; 61 : 1356 - 61 . 2 . Wolfson C , Wolfson DB , Asgharian M , M’Lan CE , Ostbye T , Rockwood K , et al. Clinical Progression of Dementia Study Group . A reevaluation of the duration of survival after the onset of dementia . N Engl J Med 2001 ; 344 : 1111- 6 . 3 . Larson EB , Shadlen MF , Wang L , McCormick WC , Bowen JD , Teri L , et al. Survival after initial diagnosis of Alzheimer disease . Ann Intern Med 2004 ; 140 : 501 - 9 Introduction Autonomic dysfunction is a well-known feature in neurodegenerative dementias , especially common in α-synucleinopathies like dementia with Lewy bodies and Parkinson 's disease with dementia . The most common symptoms are orthostatic hypotension , incontinence and constipation , but its relevance in clinical practice is poorly understood . There are no earlier studies addressing the influence of autonomic dysfunction on clinical course and survival . The aim of this study was to investigate the frequency of the three most common features of autonomic dysfunction and analyze how it affects survival . Methods Thirty patients with dementia with Lewy bodies and Parkinson 's disease with dementia were included in this prospect i ve , longitudinal follow-up study . Presence of incontinence and constipation was recorded at baseline . Blood pressure was measured at baseline , after 3 months and after 6 months according to st and ardized procedures , with 5 measurements during 10 minutes after rising . Orthostatic hypotension was defined using consensus definitions and persistent orthostatic hypotension was defined as 5 or more measurements with orthostatic hypotension . Difference in survival was analyzed 36 months after baseline . Results There was a high frequency of persistent orthostatic blood pressure ( 50 % ) , constipation ( 30 % ) and incontinence ( 30 % ) . Patients with persistent orthostatic hypotension had a significantly shorter survival compared to those with no or non-persistent orthostatic hypotension ( Log rank x2 = 4.47 , p = 0.034 ) . Patients with constipation and /or urinary incontinence , in addition to persistent orthostatic hypotension , had a poorer prognosis compared to those with isolated persistent orthostatic hypotension or no orthostatic hypotension ( Log rank x2 = 6.370 , p = 0.041 ) . Discussion According to our findings , the identification of autonomic dysfunction seems to be of great importance in clinical practice , not only to avoid falls and other complications , but also as a possible predictor of survival BACKGROUND Poor cognitive function and depressive symptoms are common in the elderly , frequently coexist , and are interrelated . Both risk factors are independently associated with mortality . Few studies have comprehensively described how the combination of poor cognitive function and depressive symptoms affect the risk for mortality . Our aim was to examine whether the combination of varying levels of cognitive function and depressive symptoms affect the risk of mortality in community-living elderly adults . METHODS We studied 6301 elderly adults ( mean age , 77 years ; 62 % women ; 81 % white ) enrolled in the Asset and Health Dynamics Among the Oldest Old ( AHEAD ) study , a prospect i ve study of community-living participants conducted from 1993 to 1995 . Cognitive function and depressive symptoms were measured using two vali date d measures developed for the AHEAD study . On each measure , participants were divided into tertiles representing the best , middle , and worst scores , and then placed into one of nine mutually exclusive groups ranging from best functioning on both measures to worst functioning on both measures . Mortality rates were assessed in each of the nine groups . Cox proportional hazards models were used to control for potentially confounding characteristics such as demographics , education , income , smoking , alcohol consumption , comorbidity , and baseline functional impairment . RESULTS During 2 years of follow-up , 9 % ( 548 ) of the participants died . Together , cognitive function and depressive symptoms differentiated between elderly adults at markedly different risk for mortality , ranging from 3 % in those with the best function on both measures to 16 % in those with the worst function on both measures ( p < .001 ) . Furthermore , for each level of cognitive function , more depressive symptoms were associated with higher mortality rates , and for each level of depressive symptoms , worse cognitive function was associated with higher mortality rates . In participants with the best cognitive function , mortality rates were 3 % , 5 % , and 9 % in participants with low , middle , and high depressive symptoms , respectively ( p < .001 for trend ) . The corresponding rates were 6 % , 7 % , and 12 % in participants with the middle level of cognitive function ( p < .001 for trend ) , and 10 % , 13 % , and 16 % in participants with the worst level of cognitive function ( p < .001 for trend ) . After adjustment for confounders , participants with the worst function on both measures remained at considerably higher risk for death than participants with the best function on both measures ( adjusted hazard ratio , 3.1 ; 95 % confidence interval , 2.0 - 4.7 ) . CONCLUSIONS Cognitive function and depressive symptoms can be used together to stratify elderly adults into groups that have significantly different rates of death . These two risk factors are associated with an increased risk in mortality in a progressive , additive manner BACKGROUND AND PURPOSE The aim of this study was to determine whether dementia with Lewy bodies ( DLB ) progres-ses more rapidly than Alzheimer disease ( AD ) and to compare survival after dementia onset and mortality in both dementia groups . MATERIAL AND METHODS A medical records analysis of AD ( n = 183 ) and DLB ( n = 51 ) patients was performed to determine age at onset of symptoms , the date of first presentation to the psychiatric services , dementia severity at diagnosis ( MMSE score ) , and mean disease duration before diagnosis . Categorical data regarding vascular risk factors were collected . Projected decline rate ( MMSE/year ) , survival rate after the diagnosis of dementia , mean survival time after diagnosis and mortality rate were calculated and compared between DLB and AD groups . RESULTS The comparison of clinical and demographic parameters revealed no significant differences between groups , apart from a more pronounced decline rate in the DLB group . Diabetes , and to a lesser extent hypertension , influenced survival in AD , but not in DLB subjects . Overall , however , the difference in mortality rates and survival time between DLB and AD subjects can not be attributed to the presence of any vascular risk factor analysed . DLB , independently of the presence of vascular risk factors , seems to be a more aggressive disorder than AD , when mortality and survival time are taken into account . CONCLUSIONS More rapid progression of cognitive decline and shorter duration of dementia were found in DLB in this naturalistic study . The findings may have important implication s for the management and treatment of DLB and should be confirmed in prospect i ve studies A pathology typical of dementia with Lewy bodies ( DLB ) has been demonstrated to increase mortality to a greater extent than the pathology of Alzheimer ’s disease ( AD ) . However , mortality in DLB has also been shown to increase with concomitant AD pathology . Furthermore , in a recent publication , we showed that there is a robust and specific increase in CSF calcium and magnesium in DLB patients compared to both AD patients and controls . Thus , in order to explore the influence of CSF AD markers and trace element concentrations on mortality in DLB , we undertook a longitudinal prospect i ve study of 47 clinical ly diagnosed DLB patients and 157 AD patients as well as 49 healthy volunteers . Both AD and DLB patients showed an increased mortality compared to the healthy controls ( relative risk : 10 and 8 , respectively ; p < 0.001 ) . Increased levels of CSF total tau were associated with increased mortality among the DLB patients ( p < 0.05 ) , but not among the AD patients or controls . Gender , age , MMSE score , Aβ42 concentration and phosphorylated tau , and CSF trace element concentrations did not influence survival in the obtained models OBJECTIVE To develop and vali date an approach that uses clinical features that can be determined in a st and ard patient visit to estimate the length of time before an individual patient with Alzheimer disease ( AD ) requires care equivalent to nursing home placement or dies . DESIGN Prospect i ve cohort study of 236 patients , followed up semiannually for up to 7 years . A second validation cohort of 105 patients was also followed . SETTING Three AD research centers . PATIENTS All patients met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer 's Disease and Related Disorders Association ( NINCDS-ADRDA ) criteria for probable AD and had mild dementia at the initial visit . INTERVENTION Predictive features , ascertained at the initial visit , were sex , duration of illness , age at onset , modified Mini-Mental State Examination ( mMMS ) score , and the presence or absence of extrapyramidal signs or psychotic features . MAIN OUTCOME MEASURES ( 1 ) Requiring the equivalent of nursing home placement and ( 2 ) death . RESULTS Prediction algorithms were constructed for the 2 outcomes based on Cox proportional hazard models . For each algorithm , a predictor index is calculated based on the status of each predictive feature at the initial visit . A table that specifies the number of months in which 25 % , 50 % , and 75 % of patients with any specific predictor index value are likely to reach the end point is then consulted . Survival curves for time to need for care equivalent to nursing home placement and for time to death derived from the algorithms for selected predictor indexes fell within the 95 % confidence b and s of actual survival curves for patients . When the predictor variables from the initial visit for the validation cohort patients were entered into the algorithm , the predicted survival curves for time to death fell within the 95 % confidence b and s of actual survival curves for the patients . CONCLUSIONS The prediction algorithms are a first but promising step toward providing specific prognoses to patients , families , and practitioners . This approach also has clear implication s for the design and interpretation of clinical trials in patients with AD BACKGROUND Delirium is a disorder affecting consciousness , which gives rise to core clinical features and associated symptoms . Older patients are particularly prone , owing to higher rates of pre-existing cognitive impairment , frailty , co-morbidity and polypharmacy . OBJECTIVES The aim of this study was to investigate the hypotheses that delirium affects the most vulnerable older adults and is associated with long-term adverse health outcome . METHODS This prospect i ve cohort study evaluated 278 medical patients aged > or = 75 years admitted acutely to a district general hospital in South Wales . Patients were screened for delirium at presentation and on alternate days throughout their hospital stay . Assessment s also included illness severity , preadmission cognition , co-morbidity and functional status . Patients were followed for 5 years to determine rates of institutionalisation and mortality . Number of days in hospital in the 4 years prior to and 5 years after index admission were recorded . RESULTS Delirium was detected in 103 patients and excluded in 175 . Median time to death was 162 days ( interquartile range 21 - 556 ) for those with delirium compared with 1,444 days ( 25 % mortality 435 days , 75 % mortality>5 years ) for those without ( P < 0.001 ) . After adjusting for multiple confounders , delirium was associated with an increased risk of death ( hazard ratio range 2.0 - 3.5 ; P < or = 0.002 ) . Institutionalisation was higher in the first year following delirium ( P = 0.03 ) . While those with delirium tended to be older with more preadmission cognitive impairment , greater functional dependency and more co-morbidity , they did not spend more days in hospital in the 4 years prior to index admission . CONCLUSIONS Delirium is associated with high rates of institutionalisation and an increased risk of death up to 5 years after index event . Prior to delirium , individuals seem to compensate for their vulnerability . The impact of delirium itself , directly or indirectly , may convert vulnerability into adverse outcome Objective : To determine whether dementia with Lewy bodies ( DLB ) progresses more rapidly than Alzheimer disease ( AD ) . Methods : We compared 315 participants ( 63 with DLB and 252 with AD ) enrolled in a prospect i ve longitudinal study of memory and aging with annual clinical and cognitive assessment s and followed until death . The main outcome measure was dementia progression to institutionalization and death . Neuropathologic examinations were performed on all participants in this study . Subject classification ( DLB vs AD ) was based on neuropathology . Results : Patients with DLB had an increased risk of mortality vs patients with AD ( hazard ratio [ HR ] 1.88 , 95 % CI : 1.4 to 2.5 ) . The median survival time for DLB was 78.0 years and for AD was 84.6 years ( χ2 = 19.9 , p < 0.001 ) with significant modification effects due to gender ( HR 1.51 , 95 % CI : 1.0 to 2.3 ) and the presence of at least 1 APOE ε4 allele ( HR 1.50 , 95 % CI : 1.0 to 2.2 ) . Survival after dementia onset was also different between DLB and AD ( 7.3 vs 8.5 years ; χ2 = 5.4 , p < 0.02 ) . DLB cases had similar risks of institutionalization and survival in long-term care facilities to AD cases . Self-reports of depression and the presence of extrapyramidal signs were important covariates . The rate of cognitive decline as measured by psychometric performance and clinical staging methods did not differ between DLB and AD . Conclusions : Dementia with Lewy bodies ( DLB ) increases the risk of mortality compared with Alzheimer disease ( AD ) , but the two groups did not differ in rate of cognitive decline . The greater risk for noncognitive disease progression for DLB compared with AD suggests clinical ly meaningful differences for the two disorders Objectives : To quantify the rate of cognitive decline on the Mini-Mental State Examination ( MMSE ) in autopsy-diagnosed Lewy body variant ( LBV ) of Alzheimer 's disease ( AD ) cases . We hypothesized that LBV patients would have a faster cognitive decline and shorter survival compared with patients with pure AD . Background : Prior reports have shown extrapyramidal signs to be associated with a poorer prognosis in AD . It has been suggested that LBV is often characterized by a rapidly progressive course . Few data are available regarding the rate of cognitive decline in autopsy-confirmed LBV dementia cases . Methods : We search ed the data bases of the University of California-San Diego Alzheimer 's Disease Research Center and the Consortium to Establish a Registry in Alzheimer 's Disease ( CERAD ) for dementia cases with 1 ) an autopsy diagnosis of definite or probable AD ( CERAD criteria ) with concomitant Lewy bodies and 2 ) longitudinal MMSE assessment s. This result ed in a series of 40 LBV cases and 148 AD cases without Lewy bodies , with comparable baseline MMSE scores , age , and education . The rate of cognitive decline was calculated as the baseline MMSE - final MMSE . Methods were devised to reduce floor effects on the MMSE . Results : The average rate of cognitive decline was -5.8 ± 4.5 points/y in LBV and -4.1 ± 3.0 points/y in AD ( t-test , p < 0.01 ) . The LBV group declined a similar amount on the MMSE ( means , -10.0 versus -9.6 points ) over a significantly shorter time interval ( 1.9 versus 2.7 years ; p = 0.005 ) than did AD patients . At baseline , the mean MMSE scores were nearly identical ( 18.2 in LBV ; 17.8 in AD ) , but on follow-up examinations approximately 1 , 2 , and 3 years later , there were intergroup mean differences of 1.8 points ( two-tailed p = 0.19 ) , 4.2 points ( p = 0.04 ) , and 5.6 points ( p = 0.03 ) , respectively . The LBV cases had shorter survival time from the onset of cognitive symptoms ( 7.7 ± 3.0 years versus 9.3 ± 3.5 years ; p = 0.007 ) and a shorter mean survival after entry/baseline , which was of marginal significance ( 3.6 versus 4.1 years ; p = 0.11 ) . Conclusions : This study demonstrates that LBV is characterized by a faster cognitive decline and accelerated mortality compared with AD |
12,239 | 32,220,763 | Hygiene promotion programmes are likely to be most successful if they use multi-modal approaches , combining infrastructural improvement with ' soft ' hygiene promotion which addresses a range of determinants rather than just education about disease transmission | BACKGROUND Hygiene promotion interventions are likely to be more effective if they target the determinants of h and washing behaviour .
Synthesis of the evidence on the determinants of h and washing behaviour is needed to enable practitioners to use evidence in hygiene promotion programming .
PURPOSE To identify , define and categorise the determinants of h and washing behaviour in domestic setting s and to appraise the quality of this evidence . | One-quarter of neonatal deaths are attributed to infections . Maternal h and washing with soap may prevent neonatal sepsis . We examined impact of intensive h and washing promotion on h and washing behavior of mothers of neonates . In Matlab , Bangladesh , we r and omly allocated pregnant women at 28–32 weeks ' gestation to intensive h and washing promotion or control . Behavior change communicators used a participatory approach to motivate maternal h and washing with soap and provided soap and h and washing stations . In the neonatal period , we observed soap and water at h and washing places and , at the end of the neonatal period , we estimated impact on maternal h and washing by structured observation . Among 253 women enrolled , intervention households were between 5.7 and 15.2 times as likely as control households to have soap and water present at the h and washing station in the baby 's sleeping area . Intervention mothers washed h and s with soap 4.1 times as frequently as controls ( 95 % CI 2.55–6.59 ) ; h and washing with soap at recommended times was infrequent in both intervention ( 9 % ) and control ( 2 % ) groups . Intensively promoting h and washing with soap result ed in increased availability of soap and water at h and washing places , but only a modest increase in maternal h and washing with soap . Novel approaches to motivating h and washing behavior to protect newborns should be developed and evaluated BACKGROUND Effective prevention and control of diarrhoea requires caregivers to comply with a suite of proven measures , including exclusive breastfeeding , h and washing with soap , correct use of oral rehydration salts , and zinc administration . We aim ed to assess the effect of a novel behaviour change intervention using emotional drivers on caregiver practice of these behaviours . METHODS We did a cluster r and omised controlled trial in Lusaka Province , Zambia . A r and om sample of 16 health centres ( clusters ) were selected from a sampling frame of 81 health centres in three of four districts in Lusaka Province using a computerised r and om number generator . Each cluster was r and omly assigned 1:1 to either the intervention-clinic events , community events , and radio messaging-or to a st and ard care control arm , both for 6 months . Primary outcomes were exclusive breastfeeding ( self-report ) , h and washing with soap ( observation ) , oral rehydration salt solution preparation ( demonstration ) , and zinc use in diarrhoea treatment ( self-report ) . We measured outcome behaviours at baseline before start of intervention and 4 - 6 weeks post-intervention through repeat cross-sectional surveys with mothers of an infant younger than 6 months and primary caregivers of a child younger than 5 years with recent diarrhoea . We compared outcomes on an intention-to-treat population between intervention and control groups adjusted for baseline behaviour . The study was registered with Clinical Trials.gov , number NCT02081521 . FINDINGS Between Jan 20 and Feb 3 , 2014 , we recruited 306 mothers of an infant aged 0 - 5 months ( 156 intervention , 150 st and ard care ) and 343 primary caregiver of a child aged 0 - 59 months with recent diarrhoea ( 176 intervention , 167 st and ard care ) at baseline . Between Oct 20 to Nov 7 , 2014 , we recruited 401 mothers of an infant 0 - 5 months ( 234 intervention , 167 st and ard care ) and 410 primary caregivers of a child 0 - 59 months with recent diarrhoea ( 257 intervention , 163 st and ard care ) at endline . Intervention was associated with increased prevalence of self-reported exclusive breastfeeding of infants aged 0 - 5 months ( adjusted difference 10·5 % , 95 % CI 0·9 - 19·9 ) . Other primary outcomes were not affected by intervention . Cluster intervention exposure ranged from 11 - 81 % , measured by participant self-report with verification questions . Comparison of control and intervention clusters with coverage greater than 35 % provided strong evidence of an intervention effect on oral rehydration salt solution preparation and breastfeeding outcomes . INTERPRETATION The intervention may have improved exclusive breastfeeding ( assessed by self-reporting ) , but intervention effects were diluted in clusters with low exposure . Complex caregiver practice s can improve through interventions built around human motives , but these must be implemented more intensely . FUNDING Absolute Return for Kids ( ARK ) and Comic Relief Background H and washing is a cost-effective way of preventing communicable diseases such as respiratory and food-borne illnesses . However , h and washing rates are low in developing countries . Target 7C of the seventh Millennium Development Goals was to increase by half the proportion of people with sustainable access to safe drinking water and basic sanitation by 2015 . Studies have found that better access to improved water sources and sanitation is associated with higher rates of h and washing . Objective Our goal was to describe h and washing behaviour and identify the associated factors in Vietnamese households . Design Data from 12,000 households participating in the Vietnam Multiple Indicator Cluster Survey 2011 were used . The survey used a multistage sampling method to r and omly select 100 clusters and 20 households per cluster . Self-administered question naires were used to collect data from a household representative . Demographic variables , the presence of a specific place for h and washing , soap and water , access to improved sanitation , and access to improved water sources were tested for association with h and washing behaviour in logistic regression . Results Almost 98 % of households had a specific place for h and washing , and 85 % had cleansing material s and water at such a place . The prevalence of h and washing in the sample was almost 85 % . Educational level , ethnicity of the household head , and household wealth were factors associated with h and washing practice ( p<0.05 ) . Those having access to an improved sanitation facility were more likely to practise h and washing [ odds ratio (OR)=1.69 , 95 % confidence interval ( CI ) : 1.37–2.09 , p<0.001 ] , as were those with access to improved water sources ( OR=1.74 , 95 % CI : 1.37–2.21 , p<0.001 ) . Conclusions Households with low education , low wealth , belonging to ethnic minorities , and with low access to improved sanitation facilities and water sources should be targeted for interventions implementing h and washing practice . In addition , the availability of soap and water at h and washing sites should be increased and practical teaching programs should be deployed in order to increase h and washing rates BACKGROUND Diarrhoea and respiratory infections are the two biggest causes of child death globally . H and washing with soap could substantially reduce diarrhoea and respiratory infections , but prevalence of adequate h and washing is low . We tested whether a scalable village-level intervention based on emotional drivers of behaviour , rather than knowledge , could improve h and washing behaviour in rural India . METHODS The study was done in Chittoor district in southern And hra Pradesh , India , between May 24 , 2011 , and Sept 10 , 2012 . Eligible villages had a population of 700 - 2000 people , a state-run primary school for children aged 8 - 13 years , and a preschool for children younger than 5 years . 14 villages ( clusters ) were selected , stratified by population size ( < 1200 vs > 1200 ) , and r and omly assigned in a 1:1 ratio to intervention or control ( no intervention ) . Clusters were enrolled by the study manager . R and om allocation was done by the study statistician using a r and om number generator . The intervention included community and school-based events incorporating an animated film , skits , and public pledging ceremonies . Outcomes were measured by direct observation in 20 - 25 households per village at baseline and at three follow-up visits ( 6 weeks , 6 months , and 12 months after the intervention ) . Observers had no connection with the intervention and observers and participant households were told that the study was about domestic water use to reduce the risk of bias . No other masking was possible . The primary outcome was the proportion of h and washing with soap at key events ( after defecation , after cleaning a child 's bottom , before food preparation , and before eating ) at all follow-up visits . The control villages received a shortened version of the intervention before the final follow-up round . Outcome data are presented as village-level means . FINDINGS H and washing with soap at key events was rare at baseline in both the intervention and control groups ( 1 % [ SD 1 ] vs 2 % [ 1 ] ) . At 6 weeks ' follow-up , h and washing with soap at key events was more common in the intervention group than in the control group ( 19 % [ SD 21 ] vs 4 % [ 2 ] ; difference 15 % , p=0·005 ) . At the 6-month follow-up visit , the proportion h and washing with soap was 37 % ( SD 7 ) in the intervention group versus 6 % ( 3 ) in the control group ( difference 31 % ; p=0·02 ) . At the 12-month follow-up visit , after the control villages had received the shortened intervention , the proportion h and washing with soap was 29 % ( SD 9 ) in the intervention group and 29 % ( 13 ) in the control group . INTERPRETATION This study shows that substantial increases in h and washing with soap can be achieved using a scalable intervention based on emotional drivers . FUNDING Wellcome Trust , SHARE Background We analyzed data from the baseline assessment of a large intervention project to describe typical h and washing practice s in rural Bangladesh , and compare measures of h and cleanliness with household characteristics . Methods We r and omly selected 100 villages from 36 districts in rural Bangladesh . Field workers identified 17 eligible households per village using systematic sampling . Field workers conducted 5-hour structured observations in 1000 households , and a cross-sectional assessment in 1692 households that included spot checks , an evaluation of h and cleanliness and a request that residents demonstrate their usual h and washing practice s after defecation . Results Although 47 % of caregivers reported and 51 % demonstrated washing both h and s with soap after defecation , in structured observation , only 33 % of caregivers and 14 % of all persons observed washed both h and s with soap after defecation . Less than 1 % used soap and water for h and washing before eating and /or feeding a child . More commonly people washed their h and s only with water , 23 % after defecation and 5 % before eating . Spot checks during the cross sectional survey classified 930 caregivers ( 55 % ) and 453 children ( 28 % ) as having clean appearing h and s. In multivariate analysis economic status and water available at h and washing locations were significantly associated with h and cleanliness among both caregivers and children . Conclusions A minority of rural Bangladeshi residents washed both h and s with soap at key h and washing times , though rinsing h and s with only water was more common . To realize the health benefits of h and washing , efforts to improve h and washing in these communities should target adding soap to current h and rinsing practice Background In Bangladesh diarrhoeal disease and respiratory infections contribute significantly to morbidity and mortality . H and washing with soap reduces the risk of infection ; however , h and washing rates in infrastructure-restricted setting s remain low . H and washing stations – a dedicated , convenient location where both soap and water are available for h and washing – are associated with improved h and washing practice s. Our aim was to identify a locally feasible and acceptable h and washing station that enabled frequent h and washing for two subsequent r and omized trials testing the health effects of this behaviour . Methods We conducted formative research in the form of household trials of improved practice s in urban and rural Bangladesh . Seven c and i date h and washing technologies were tested by nine to ten households each during two iterative phases . We conducted interviews with participants during an introductory visit and two to five follow up visits over two to six weeks , depending on the phase . We used the Integrated Behavioural Model for Water , Sanitation and Hygiene ( IBM-WASH ) to guide selection of c and i date h and washing stations and data analysis . Factors presented in the IBM-WASH informed thematic coding of interview transcripts and context ualized feasibility and acceptability of specific h and washing station design s. Results Factors that influenced selection of c and i date design s were market availability of low cost , durable material s that were easy to replace or replenish in an infrastructure-restricted and shared environment . Water storage capacity , ease of use and maintenance , and quality of material s determined the acceptability and feasibility of specific h and washing station design s. After examining technology , psychosocial and context ual factors , we selected a h and washing system with two different water storage capacities , each with a tap , st and , basin , soapy water bottle and detergent powder for pilot testing in preparation for the subsequent r and omized trials . Conclusions A number of context ual , psychosocial and technological factors influence use of h and washing stations at five aggregate levels , from habitual to societal . In interventions that require a h and washing station to facilitate frequent h and washing with soap , elements of the technology , such as capacity , durability and location(s ) within the household are key to high feasibility and acceptability . More than one h and washing station per household may be required . IBM-WASH helped guide the research and research in-turn helped vali date the framework In this study , we report on the results of a trial of an intervention to improve five food hygiene behaviors among mothers of young children in rural Nepal . This novel intervention targeted five behaviors ; cleanliness of serving utensils , h and washing with soap before feeding , proper storage of cooked food , and thorough reheating and water treatment . Based on formative research and a creative process using the Behavior-Centered Design approach , an innovative intervention package was design ed and delivered over a period of 3 months . The intervention activities included local rallies , games , rewards , storytelling , drama , competitions linking with emotional drivers of behavior , and “ kitchen makeovers ” to disrupt behavior setting s. The effect of the package on behavior was evaluated via a cluster-r and omized before – after study in four villages with four villages serving as controls . The primary outcome was the difference in the mean cluster level proportions of mothers directly observed practicing all five food hygiene behaviors . The five targeted food hygiene behaviors were rare at baseline ( composite performance of all five behaviors in intervention 1 % [ st and ard deviation ( SD ) = 2 % ] and in control groups 2 % [ SD = 2 % ] ) . Six weeks after the intervention , the target behaviors were more common in the intervention than in the control group ( 43 % [ SD = 14 % ] versus 2 % [ SD = 2 % ] , P = 0.02 ) during follow-up . The intervention appeared to be equally effective in improving all five behaviors in all intervention clusters . This study shows that a theory-driven , systematic approach employing emotional motivators and modifying behavior setting s was capable of substantially improving multiple food hygiene behaviors in Nepal ABSTRACT Background : As the Millennium Development Goals ended , and were replaced by the Sustainable Development Goals , efforts have been made to evaluate the achievements and performance of official development assistance ( ODA ) in the health sector . In this study , we explore trends in the expansion of water and sanitation coverage in developing countries and the performance of ODA . Design : We explored ine quality across developing countries by income level , and investigated how ODA for water and sanitation was committed by country , region , and income level . Changes in ine quality were tested via slope changes by investigating the interaction of year and income level with a likelihood ratio test . A r and om effects model was applied according to the results of the Hausman test . Results : The slope of the linear trend between economic level and sanitation coverage has declined over time . However , a r and om effects model suggested that the change in slope across years was not significant ( e.g. for the slope change between 2000 and 2010 : likelihood ratio χ2 = 2.49 , probability > χ2 = 0.1146 ) . A similar pro-rich pattern across developing countries and a non-significant change in the slope associated with different economic levels were demonstrated for water coverage . Our analysis shows that the ine quality of water and sanitation coverage among countries across the world has not been addressed effectively during the past decade . Our findings demonstrate that the countries with the least coverage persistently received far less ODA per capita than did countries with much more extensive water and sanitation coverage , suggesting that ODA for water and sanitation is poorly targeted . Conclusion : The most deprived countries should receive more attention for water and sanitation improvements from the world health community . A strong political commitment to ODA targeting the countries with the least coverage is needed at the global level ABSTRACT This study compared structured observation with a 24 h pictorial recall of household activities ( ‘ sticker diary ’ ) to measure the prevalence of h and washing with soap ( HWWS ) in the community . The study was done within a cluster-r and omised trial evaluating a h and washing promotion programme in Bihar , India . HWWS at key occasions in mothers and school children was measured by structured observation in 299 households from 32 villages . Sticker diaries recalling common activities , including personal hygiene , were used to measure HWWS in 299 households from a further 20 villages . Sticker diary HWWS prevalence estimates were about 13 % points higher than structured observation estimates , but the differences varied by the type of h and washing occasion . This study confirms structured observation as the method of choice for the study of h and washing behaviours . The sticker diary method may be useful in large-scale surveys . Sticker diaries may overestimate HWWS at important occasions , but probably less so than conventional question naire tools BACKGROUND Poor sanitation in peri-urban areas is a growing public health problem . We tested a scalable , dem and -side behaviour change intervention to motivate l and lords to improve the quality of shared toilets within their plots . METHODS We did a residential plot-r and omised controlled trial in a peri-urban community in Lusaka , Zambia . We enrolled adult resident l and lords on plots where at least one tenant lived . We allocated l and lords 1:1 to intervention and control arms on the basis of a r and om number sequence . The intervention was developed using the Behaviour Centred Design approach and consisted of a series of group meetings design ed to motivate sanitation quality improvement as a way to build wealth and reduce on-plot conflict ; no subsidies or material s were provided . The control group received no intervention . The four primary outcomes were having a rotational cleaning system in place ( to improve hygiene ) ; having a solid door on the toilet used by tenants with an inside lock ( for privacy ) ; having an outside lock ( for security ) ; and having a sealed toilet ( to reduce smell and contamination ) . We measured outcomes 1 month before the start of the intervention and 4 months after the end of the intervention . Data collectors measuring outcomes were blinded to group assignment . We analysed outcomes by intention to treat , including all l and lords with study -end results . Because the outcomes were assumed to not be independent , we used a family-wise error rate of 0·05 to calculate an adjusted significance level of 0·0253 . This study was registered with Clinical Trials.gov , number NCT03174015 . FINDINGS Between June 9 and July 6 , 2017 , 1085 l and lords were enrolled and r and omly assigned to the intervention ( n=543 ) or the control group ( n=542 ) . The intervention was delivered from Aug 1 , 2017 , and evaluated from Feb 15 to March 5 , 2018 . Analysis was based on the 474 intervention and 454 control l and lords surveyed at study end . The intervention was associated with improvements in the prevalence of cleaning rotas ( relative risk 1·16 , 95 % CI 1·05 - 1·30 ; p=0·0011 ) , inside locks ( 1·34 , 1·10 - 1·64 ; p=0·00081 ) , outside locks ( 1·27 , 1·06 - 1·52 ; p=0·0028 ) , and toilets with simple covers or water seals ( 1·25 , 1·04 - 1·50 ; p=0·0063 ) . INTERPRETATION It is possible to improve the structural quality and cleanliness of shared sanitation by targeting l and lords with a scalable , theory-driven behaviour change intervention without subsidy or provision of the relevant infrastructure . FUNDING Sanitation and Hygiene Applied Research for Equity OBJECTIVE To investigate the effectiveness of a hygiene promotion intervention based on germ awareness in increasing h and washing with soap on key occasions ( after faecal contact and before eating ) in rural Indian households . METHODS Cluster r and omised trial of a hygiene promotion intervention in five intervention and five control villages . H and washing was assessed through structured observation in a r and om sample of 30 households per village . Additionally , soap use was monitored in a sub- sample of 10 households per village using electronic motion detectors embedded in soap bars . RESULTS The intervention reached 40 % of the target population . Germ awareness increased as well as reported h and washing ( a possible indicator of perceived social norms ) . Observed h and washing with soap on key occasions was rare ( 6 % ) , especially after faecal contact ( 2 % ) . Observed h and washing with soap on key occasions did not change 4 weeks after the intervention in either the intervention arm ( -1 % , 95 % CI -2%/+0.3 % ) , or the control arm ( + 0.4 % , 95 % CI -1%/+2 % ) . Data from motion detectors indicated a significant but small increase in overall soap use in the intervention arm . We can not confidently identify the nature of this increase except to say that there was no change in a key measure of h and washing after defecation . CONCLUSION The intervention proved scalable and effective in raising hygiene awareness . There was some evidence of an impact on soap use but not on the primary outcome of h and washing at key times . However , the results do not exclude that changes in knowledge and social norms may lay the foundations for behaviour change in the longer term OBJECTIVE To investigate increased h and hygiene practice in response to the p and emic influenza A/H1N1 ( pH1N1 ) and its associated psychosocial factors in the Taiwanese general population . METHODS A national telephone survey using r and om digit dialing was conducted on October 28 - 30 , 2009 in Taiwan , result ing in a final sample of 1079 participants aged 15 or older . RESULTS Seventy-seven per cent reported that they increased h and hygiene practice during the pH1N1 epidemic . Multivariate logistic regression analysis showed that increased h and hygiene practice was associated with health beliefs that pH1N1 was more transmissible than avian influenza ( OR = 1.42 ) ; that pH1N1 was slightly more severe in Taiwan compared with other countries ( OR = 1.59 ) ; that h and washing was very effective in preventing pH1N1 ( OR = 3.12 ) , and that h and washing after contact with possibly pH1N1-contaminated objects/surfaces was not very difficult ( OR = 2.14 ) or not difficult at all ( OR = 2.49 ) . CONCLUSIONS These findings suggest that future campaigns to promote preventive health behaviour in the public should consider communicating evidence -based information concerning the effectiveness of the recommended preventive behaviour , comparing the emerging epidemic with prior local outbreaks , and not overplaying the seriousness of the disease with fear tactics OBJECTIVE It is unclear how best to go about improving child feeding practice s. We studied the effect of a novel behaviour change intervention , Gerakan Rumpi Sehat ( the Healthy Gossip Movement ) , on infant and young child feeding practice s in peri-urban Indonesia . METHODS The pilot intervention was design ed based on the principles of a new behaviour change theory , Behaviour Centred Design ( BCD ) . It avoided educational messaging in favour of employing emotional drivers of behaviour change , such as affiliation , nurture and disgust and used television commercials , community activations and house-to-house visits as delivery channels . The evaluation took the form of a 2-arm cluster r and omised trial with a non-r and omised control arm . One intervention arm received TV only , while the other received TV plus community activations . The intervention components were delivered over a 3-month period in 12 villages in each arm , each containing an average of 1300 households . There were two primary outcomes : dietary diversity of complementary food and the provision of unhealthy snacks to children aged 6 - 24 months . RESULTS Dietary diversity scores increased by 0.8 points in the arm exposed to TV adverts only ( 95 % CI : 0.4 - 1.2 ) and a further 0.2 points in the arm that received both intervention components ( 95 % CI : 0.6 - 1.4 ) . In both intervention arms , there were increases in the frequency of vegetable and fruit intake . We found inconsistent evidence of an effect on unhealthy snacking . CONCLUSION The study suggests that novel theory-driven approaches which employ emotional motivators are capable of having an effect on improving dietary diversity and the regularity of vegetable and fruit intake among children aged 6 - 24 months . Mass media can have a measurable effect on nutrition-related behaviour , but these effects are likely to be enhanced through complementary community activations . Changing several behaviours at once remains a challenge H and washing with soap prevents diarrhea and respiratory disease , but it is rarely practice d in high-need setting s. Among 100 r and omly selected villages in rural Bangladesh , field workers enrolled 10 households per village and observed and recorded household activities for 5 hours . Field workers observed 761 h and washing opportunities among household members in 527 households who had just defecated or who cleaned a child 's anus who had defecated . In the final multivariate analysis , having water available at the place to wash h and s after toileting ( odds ratio = 2.2 , 95 % confidence interval 1.3 , 4.0 ) and having soap available at the place to wash h and s after toileting ( odds ratio = 2.1 , 95 % confidence interval 1.3 , 3.4 ) were associated with washing both h and s with soap after fecal contact . Interventions that improve the presence of water and soap at the design ated place to wash h and s would be expected to improve h and washing behavior and health |
12,240 | 23,259,703 | Recent evidence demonstrates that when SMBG is ' structured ' , incorporated as part of a complex intervention , and embedded within education and collaborative care , improvements in average blood glucose levels result .
In contrast , studies that do not apply SMBG systematic ally , or that assess a low frequency SMBG regimen that precludes identification and interpretation of SMBG patterns , are not clinical ly effective .
CONCLUSIONS It is the quality , not quantity , of SMBG that makes a difference to outcomes for people with non-insulin-treated T2DM . | BACKGROUND There is debate in the literature about the effectiveness of self-monitoring of blood glucose ( SMBG ) for people with type 2 diabetes ( T2DM ) who do not use insulin .
Several recent systematic review s and meta-analyses conclude that SMBG does not have any clinical benefit for this group .
OBJECTIVE We critically appraise the available evidence , and argue whether SMBG is warranted for people with non-insulin-treated T2DM . | OBJECTIVE To assess the effectiveness of structured blood glucose testing in poorly controlled , noninsulin-treated type 2 diabetes . RESEARCH DESIGN AND METHODS This 12-month , prospect i ve , cluster-r and omized , multicenter study recruited 483 poorly controlled ( A1C ≥7.5 % ) , insulin-naïve type 2 diabetic subjects from 34 primary care practice s in the U.S. Practice s were r and omized to an active control group ( ACG ) with enhanced usual care or a structured testing group ( STG ) with enhanced usual care and at least quarterly use of structured self-monitoring of blood glucose ( SMBG ) . STG patients and physicians were trained to use a paper tool to collect/interpret 7-point glucose profiles over 3 consecutive days . The primary end point was A1C level measured at 12 months . RESULTS The 12-month intent-to-treat analysis ( ACG , n = 227 ; STG , n = 256 ) showed significantly greater reductions in mean ( SE ) A1C in the STG compared with the ACG : −1.2 % ( 0.09 ) vs. −0.9 % ( 0.10 ) ; Δ = −0.3 % ; P = 0.04 . Per protocol analysis ( ACG , n = 161 ; STG , n = 130 ) showed even greater mean ( SE ) A1C reductions in the STG compared with the ACG : −1.3 % ( 0.11 ) vs. −0.8 % ( 0.11 ) ; Δ = −0.5 % ; P < 0.003 . Significantly more STG patients received a treatment change recommendation at the month 1 visit compared with ACG patients , regardless of the patient ’s initial baseline A1C level : 179 ( 75.5 % ) vs. 61 ( 28.0 % ) ; < 0.0001 . Both STG and ACG patients displayed significant ( P < 0.0001 ) improvements in general well-being ( GWB ) . CONCLUSIONS Appropriate use of structured SMBG significantly improves glycemic control and facilitates more timely/aggressive treatment changes in noninsulin-treated type 2 diabetes without decreasing GWB Objectives To assess the effect of self monitoring of blood glucose concentrations on glycaemic control and psychological indices in patients with newly diagnosed type 2 diabetes mellitus . Design Prospect i ve r and omised controlled trial of self monitoring versus no monitoring ( control ) . Setting Hospital diabetes clinics . Participants 184 ( 111 men ) people aged < 70 with newly diagnosed type 2 diabetes referred to the participating diabetes clinics . Major exclusion criteria were secondary diabetes , insulin treatment , previous self monitoring of blood glucose . Interventions Participants were r and omised to self monitoring or no monitoring ( control ) groups for one year with follow-up at three monthly intervals . Both groups underwent an identical structured core education programme . The self monitoring group received additional education on monitoring . Main outcome measures Between group differences in HbA1c , psychological indices , use of oral hypoglycaemic drugs , body mass index ( BMI ) , and reported hypoglycaemia rates . Results 96 patients ( 55 men ) were r and omised to monitoring and 88 ( 56 men ) to control . There were no baseline differences in mean ( SD ) age ( 57.7 ( 11.0 ) in monitoring group v 60.9 ( 11.5 ) in control group ) or HbA1c ( 8.8 (2.1)% v 8.6 (2.3)% , respectively ) . Those in the monitoring group had a higher baseline BMI ( 34 ( 7 ) v 32 ( 6.2 ) ) . There were no significant differences between groups at any time point ( 12 months values given ) in HbA1c ( 6.9 (0.8)% v 6.9 (1.2)% , P=0.69 ; 95 % confidence interval for difference −0.25 % to 0.38 % ) , BMI ( 33.1 ( 6.4 ) v 31.8 ( 6.0 ) ; adjusted for baseline BMI , P=0.32 ) , use of oral hypoglycaemic drugs , or reported incidence of hypoglycaemia . Monitoring was associated with a 6 % higher score on the depression subscale of the well-being question naire ( P=0.01 ) . Conclusions In patients with newly diagnosed type 2 diabetes self monitoring of blood glucose concentration has no effect on glycaemic control but is associated with higher scores on a depression subscale . Trial registration IS RCT N 49814766 OBJECTIVE To investigate the effect of meal-related self-monitoring of blood glucose on glycemic control and well-being in non-insulin-treated type 2 diabetic patients . RESEARCH DESIGN AND METHODS This 6-month study , which included 6 months of follow-up , adopted a prospect i ve , multicenter , r and omized controlled design . Subjects were r and omized to two groups : one group used a blood glucose-monitoring device , kept a blood glucose/eating diary , and received st and ardized counseling ; the control group received nonst and ardized counseling on diet and lifestyle . The primary efficacy parameter was the change in HbA(1c ) . Secondary efficacy variables included changes in body weight , lipids , and microalbumin and changes in treatment satisfaction and well-being . RESULTS In the per- protocol analysis , the use of a self-monitoring blood glucose device significantly reduced HbA(1c ) levels by 1.0 + /- 1.08 % compared with 0.54 + /- 1.41 % for the control group ( P = 0.0086 ) ; subgroup analysis showed three types of responders . Body weight , total cholesterol , and microalbumin improved when using a glucometer , but there was no statistically significant difference between the two groups . Treatment satisfaction increased in both groups to a similar extent ( P = 0.9 ) . Self-monitoring result ed in a marked improvement of general well-being with significant improvements in the subitems depression ( P = 0.032 ) and lack of well-being ( P = 0.02 ) . CONCLUSIONS Meal-related self-monitoring of blood glucose within a structured counseling program improved glycemic control in the majority of non-insulin-treated type 2 diabetic patients in this study . The finding of three types of responders will be important for future planning of counseling and educational interventions AIM To determine if therapeutic management programmes for type 2 diabetes that include self-monitoring of blood glucose ( SMBG ) result in greater reductions in glycated haemoglobin ( HbA1c ) compared with programmes without SMBG in non-insulin requiring patients . METHODS Multicentre , r and omized , parallel-group trial . A total of 610 patients were r and omized to SMBG or non-SMBG groups . Patients in both groups received the same oral antidiabetic therapy using a gliclazide modified release (MR)-based regimen for 27 weeks . The primary efficacy end-point was the difference between groups in HbA1c at the end of observation . RESULTS A total of 610 patients were r and omized : 311 to the SMBG group and 299 to the non-SMBG group . HbA1c decreased from 8.12 to 6.95 % in the SMBG group and from 8.12 to 7.20 % in the non-SMBG group ; between-group difference was 0.25 % ( 95 % CI : 0.06 , 1.03 ; p = 0.0097 ) . Symptoms suggestive of mild to moderate hypoglycaemia was the most commonly reported adverse event , reported by 27 ( 8.7 % ) and 21 ( 7.0 % ) patients in the SMBG and non-SMBG groups , respectively ; the incidence of symptomatic hypoglycaemia was lower in the SMBG group . CONCLUSION In patients with type 2 diabetes , the application of SMBG as an adjunct to oral antidiabetic agent therapy results in further reductions in HbA1c Objective To determine whether self monitoring , alone or with instruction in incorporating the results into self care , is more effective than usual care in improving glycaemic control in non-insulin treated patients with type 2 diabetes . Design Three arm , open , parallel group r and omised trial . Setting 48 general practice s in Oxfordshire and South Yorkshire . Participants 453 patients with non-insulin treated type 2 diabetes ( mean age 65.7 years ) for a median duration of three years and a mean haemoglobin A1c level of 7.5 % . Interventions St and ardised usual care with measurements of HbA1c every three months as the control group ( n=152 ) , blood glucose self monitoring with advice for patients to contact their doctor for interpretation of results , in addition to usual care ( n=150 ) , and blood glucose self monitoring with additional training of patients in interpretation and application of the results to enhance motivation and maintain adherence to a healthy lifestyle ( n=151 ) . Main outcome measure HbA1c level measured at 12 months . Results At 12 months the differences in HbA1c level between the three groups ( adjusted for baseline HbA1c level ) were not statistically significant ( P=0.12 ) . The difference in unadjusted mean change in HbA1c level from baseline to 12 months between the control and less intensive self monitoring groups was −0.14 % ( 95 % confidence interval −0.35 % to 0.07 % ) and between the control and more intensive self monitoring groups was −0.17 % ( −0.37 % to 0.03 % ) . Conclusions Evidence is not convincing of an effect of self monitoring blood glucose , with or without instruction in incorporating findings into self care , in improving glycaemic control compared with usual care in reasonably well controlled non-insulin treated patients with type 2 diabetes . Trial registration Current Controlled Trials IS RCT N47464659 The goal of this study was to compare the relative efficacy and cost of self-monitoring of blood glucose ( SMBG ) with routine urine testing in the management of patients with type II ( non-insulin-dependent ) diabetes mellitus not treated with insulin . Fifty-four patients with type II diabetes mellitus , not treated with insulin , who had inadequate glucose control on diet aloneor diet and oral hypoglycemic agents were studied . Patients performed SMBG or urine glucose testing as part of a st and ardized treatment program that also included diet and exercise counseling . During the 6-mo study , both the urine-testing and SMBG groups showed similar improvement in glycemic control ; within each group , there were significant improvements in fasting plasma glucose ( reduction of 1.4 ± 3.2 mM , P < 0.03 ) and glycosylated hemoglobin ( reduction of 2.0 ± 3.4 % , P < 0.01 ) levels . Seventeen ( 31 % ) of54 patients actually normalized their glycosylated hemoglobin values , 9 in the urine-testing group and 8 in the SMBG group . Comparisons between the urine-testing and SMBG groups showed no significant differences in mean fasting plasma glucose ( P > 0.86 ) , glycosylated hemoglobin ( P > 0.95 ) , or weight ( P < 0.19 ) . In patients with type II diabetes mellitus not treated with insulin , SMBG is no more effective , but is 8–12 times more expensive , thanurine testing in facilitating improved glycemic control . Our results do not support widespread use of SMBG in diabetic patients not treated with insulin A diabetes protocol characterized by self-monitoring of blood glucose was introduced in four general practice s with the aim of making the frequency of consultations dependent on the metabolic regulation and emphasizing body weight reduction . The feasibility of the programme was investigated and the results after 1 year were compared with those of conventional care in four control practice s. In the experimental practice s , 13 patients switched from a medical specialist 's to a general practitioner 's supervision , 20 remained under supervision of their GP and 33 started self-monitoring . The self-monitoring rate , the consultation frequency according to protocol , the low number of dropouts and inadequate referrals and adherence to the therapeutic scheme showed that the protocol was feasible for both the GPs and the patients . At the initial assessment , the regulation of the diabetes was worse in patients of the experimental group , compared with those of the control group ( mean HbA1 9.7 % vs 8.9 % ; p less than 0.05 ) . On average , patients in the experimental group ( n = 56 ) lost 0.4 kg of body weight , whereas those in the control group ( n = 73 ) gained 0.1 kg ( n.s . ) . The mean change in HbA1 , adjusted for the initial value , was -0.4 % in the experimental and + 0.5 % in the control group ( p less than 0.05 ) . The results of the protocol can be attributed to a combination of greater participation of the patient , the individualized consultation frequency and the prescription of oral hypoglycaemic agents according to body weight development Objective To assess the cost effectiveness of self monitoring of blood glucose alone or with additional training in incorporating the results into self care , in addition to st and ardised usual care for patients with non-insulin treated type 2 diabetes . Design Incremental cost utility analysis from a healthcare perspective . Data on re source use from the r and omised controlled diabetes glycaemic education and monitoring ( DiGEM ) trial covered 12 months before baseline and 12 months of trial follow-up . Quality of life was measured at baseline and 12 months using the EuroQol EQ-5D question naire . Setting Primary care in the United Kingdom . Participants 453 patients with non-insulin treated type 2 diabetes . Interventions St and ardised usual care ( control ) compared with additional self monitoring of blood glucose alone ( less intensive self monitoring ) or with training in self interpretation of the results ( more intensive self monitoring ) . Main outcome measures Quality adjusted life years and healthcare costs ( sterling in 2005 - 6 prices ) . Results The average costs of intervention were £ 89 ( € 113 ; $ 179 ) for st and ardised usual care , £ 181 for less intensive self monitoring , and £ 173 for more intensive self monitoring , showing an additional cost per patient of £ 92 ( 95 % confidence interval £ 80 to £ 103 ) in the less intensive group and £ 84 ( £ 73 to £ 96 ) in the more intensive group . No other significant cost difference was detected between the groups . An initial negative impact of self monitoring on quality of life occurred , averaging −0.027 ( 95 % confidence interval−0.069 to 0.015 ) for the less intensive self monitoring group and −0.075 ( −0.119 to −0.031 ) for the more intensive group . Conclusions Self monitoring of blood glucose with or without additional training in incorporating the results into self care was associated with higher costs and lower quality of life in patients with non-insulin treated type 2 diabetes . In light of this , and no clinical ly significant differences in other outcomes , self monitoring of blood glucose is unlikely to be cost effective in addition to st and ardised usual care . Trial registration Current Controlled Trials IS RCT N47464659 Background The value and utility of self-monitoring of blood glucose ( SMBG ) in non-insulin treated T2DM has yet to be clearly determined . Findings from studies in this population have been inconsistent , due mainly to design differences and limitations , including the prescribed frequency and timing of SMBG , role of the patient and physician in responding to SMBG results , inclusion criteria that may contribute to untoward floor effects , subject compliance , and cross-arm contamination . We have design ed an SMBG intervention study that attempts to address these issues . Methods / design The Structured Testing Program ( STeP ) study is a 12-month , cluster-r and omised , multi-centre clinical trial to evaluate whether poorly controlled ( HbA1c ≥ 7.5 % ) , non-insulin treated T2DM patients will benefit from a comprehensive , integrated physician/patient intervention using structured SMBG in US primary care practice s. Thirty-four practice s will be recruited and r and omly assigned to an active control group ( ACG ) that receives enhanced usual care or to an enhanced usual care group plus structured SMBG ( STG ) . A total of 504 patients will be enrolled ; eligible patients at each site will be r and omly selected using a defined protocol . Anticipated attrition of 20 % will yield a sample size of at least 204 per arm , which will provide a 90 % power to detect a difference of at least 0.5 % in change from baseline in HbA1c values , assuming a common st and ard deviation of 1.5 % . Differences in timing and degree of treatment intensification , cost effectiveness , and changes in patient self-management behaviours , mood , and quality of life ( QOL ) over time will also be assessed . Analysis of change in HbA1c and other dependent variables over time will be performed using both intent-to-treat and per protocol analyses . Trial results will be available in 2010 . Discussion The intervention and trial design builds upon previous research by emphasizing appropriate and collaborative use of SMBG by both patients and physicians . Utilization of per protocol and intent-to-treat analyses facilitates a comprehensive assessment of the intervention . Use of practice site cluster-r and omisation reduces the potential for intervention contamination , and inclusion criteria ( HbA1c ≥ 7.5 % ) reduces the possibility of floor effects . Inclusion of multiple dependent variables allows us to assess the broader impact of the intervention , including changes in patient and physician attitudes and behaviours . Trial Registration Current Controlled Trials NCT00674986 OBJECTIVE The Internet is used worldwide as a communication tool . To improve the quality of diabetes control , we investigated the effectiveness of an Internet-based blood glucose monitoring system ( IBGMS ) on controlling the changes in HbA(1c ) levels . RESEARCH DESIGN AND METHODS We conducted a r and omized clinical trial involving 110 patients who visited the outpatient clinic at the Kangnam St. Mary 's Hospital for 3 months . The study subjects were treated with IBGMS for 12 weeks , and the control group received the usual outpatient management over the same period . HbA(1c ) and other laboratory tests were performed twice , once at the beginning of the study and again at the end of the study . RESULTS The test results from the beginning of the study established that there were no significant differences between the two groups with respect to age , sex , diabetes duration , BMI , blood pressure , HbA(1c ) , and other laboratory data . On follow-up examination 12 weeks later , HbA(1c ) levels were significantly decreased from 7.59 to 6.94 % within the intervention group ( P < 0.001 ) . At the end of the study , HbA(1c ) levels in the intervention group were significantly lower than in the control group after adjusting the baseline HbA(1c ) ( 6.94 vs. 7.62 % ; P < 0.001 , respectively ) . Among patients with baseline HbA(1c ) < 7.0 % , the patients in the intervention group had lower HbA(1c ) than those in the control group ( 6.38 vs. 6.99 % ; P < 0.05 ) . Among the patients with a baseline HbA(1c ) > or = 7.0 % , the difference between the two groups appeared more obvious : HbA(1c ) levels at the end of the study were 8.12 % . CONCLUSIONS This new IBGMS result ed in a significant reduction of HbA(1c ) during the study period . We propose that this IBGMS be used as a method for improving diabetes control 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 % Objective Recommendations on the frequency of self-monitoring of blood glucose ( SMBG ) vary widely among physicians treating patients with type 2 diabetes ( T2D ) . Aim of this study was to investigate two testing regimen of SMBG in patients with stable metabolic control . Research Design and Methods Patients with T2D treated with oral antidiabetic drugs were r and omized to two groups : either one SMBG ( low ) or four SMBG ( high ) per week . Subjects were followed up after 3 , 6 and 12 months . Primary outcome parameter was the change in HbA1c between baseline and 6 months . Primary outcome criterion was tested by a one-sided t- test for non- inferiority . Secondary outcome parameters were safety , compliance and HbA1c at 3 and 12 months . Results There were no differences in the 202 subjects for demographic and sociodemographic parameters and drug treatment . HbA1c ( % ) at baseline was similar in both groups ( 7.2±1.4 vs. 7.2±1.0 ) . Non- inferiority was demonstrated for the low group ( p = 0.0022 ) with a difference from baseline to 6 months of 0.24 in the low and of 0.16 in the high group . Compliance with the testing regimen was 82–90 % in both groups . There were no statistical significant differences for compliance , HbA1c at 3 and 12 months and serious adverse events ( SAE ) . Conclusion One SMBG per week is as sufficient and safe as four SMBG per week to maintain HbA1c in non-insulin treated T2D close to metabolic target . The results of this study are in contrast to current international consensus guidelines . Trial Registration Controlled-Trials.com IS RCT OBJECTIVE —To investigate the long-term effectiveness of the Internet-based glucose monitoring system ( IBGMS ) on glucose control in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS —We conducted a prospect i ve , r and omized , controlled trial in 80 patients with type 2 diabetes for 30 months . The intervention group was treated with the IBGMS , while the control group made conventional office visits only . HbA1c ( A1C ) was performed at 3-month intervals . For measuring of the stability of glucose control , the SD value of A1C levels for each subject was used as the A1C fluctuation index ( HFI ) . RESULTS —The mean A1C and HFI were significantly lower in the intervention group ( n = 40 ) than in the control group ( n = 40 ) . ( A1C [ mean ± SD ] 6.9 ± 0.9 vs. 7.5 ± 1.0 % , P = 0.009 ; HFI 0.47 ± 0.23 vs. 0.78 ± 0.51 , P = 0.001 ; intervention versus control groups , respectively ) . Patients in the intervention group with a basal A1C ≥7 % ( n = 27 ) had markedly lower A1C levels than corresponding patients in the control group during the first 3 months and maintained more stable levels throughout the study ( P = 0.022 ) . Control patients with a basal A1C < 7 % ( n = 15 ) showed the characteristic bimodal distribution of A1C levels , whereas the A1C levels in the intervention group remained stable throughout the study with low HFI . CONCLUSIONS —Long-term use of the IBGMS has proven to be superior to conventional diabetes care systems based on office visits for controlling blood glucose and achieving glucose stability BACKGROUND Frequent blood glucose ( BG ) monitoring is a critical component of diabetes management , yet many barriers exist to consistent monitoring . METHODS In this r and omized controlled trial , we sought to determine if an educational manual , the Blood Sugar Monitoring Owner 's Manual ( BGMOM ) , could increase adherence to BG monitoring by helping patients form realistic expectations and responses to BG monitoring results . The 199 participants were recruited from a multidisciplinary diabetes clinic and had high-risk diabetes ( hemoglobin A(1C ) > or=8.0 % ) ; 35 % had type 1 diabetes mellitus . Participants were r and omized to 1 of 3 groups : BGMOM intervention ( BGM+ ) , attention control ( BG meter only [ MT ] ) , or st and ard care ( SC ) . The BGM+ and MT groups received BG meters and meter education ; the BGM+ group also received BGMOM booklets . The SC group received usual care . Data gathered during 6 months of follow-up included BG monitoring frequency and hemoglobin A(1C ) measurement . RESULTS Monitoring frequency increased significantly in the BGM+ group ( 1.9 + /- 1.3 to 2.8 + /- 1.5 times daily , P<.001 ) but only slightly in the MT group ( 1.7 + /- 1.3 to 2.0 + /- 1.3 times daily ) . The BGM+ group experienced the greatest improvement in hemoglobin A(1C ) level ( BGM+ : -0.13 + /- 1.28 ; MT : -0.04 + /- 1.31 ; SC : 0.04 + /- 1.10 ) . Further , a higher percentage of those in the BGM+ group ( 61 % ) improved their glycemic control compared with the other groups ( 44 % ; P = .05 ) . Finally , the BGM+ group displayed the most knowledge about the definition of hemoglobin A(1C ) ( P = .04 ) and reported the least amount of negative affect about out-of-range BG monitoring results ( P = .03 ) . CONCLUSION As an adjunct to st and ard diabetes education and support , a manual such as the BGMOM can help optimize BG monitoring and glycemic control To study if self-monitoring of glucose , urinary or capillary , could help them to improve their metabolic control through better compliance to diet and /or hypoglycaemic agents , 208 non-insulin-treated poorly controlled diabetic patients were r and omized to : group A -- regular HbA1c determinations but no self-monitoring , group B -- self-urine glucose monitoring , twice every other day , group C -- self blood glucose monitoring , twice every other day , and followed six months . At the end of the study period , the decrease of HbA1c over six months -- main endpoint -- was not significantly different between the three groups ( mean + /- SEM ; group A : -0.5 + /- 0.2 % ; group B : -0.1 + /- 0.3 % ; group C : -0.4 + /- 0.3 % ) . However , the degree of compliance to blood glucose self-monitoring in group C appeared to relate to the outcome : a significant correlation was found between the number of blood glucose strips used and the decrease of HbA1c ( r = .36 , p less than .02 ) . We conclude that regular self-monitoring has no definite advantage over the usual management for improving metabolic control in non-insulin-treated diabetic patients , though it may possibly help patients ready to comply with its use Self-monitoring of blood glucose ( SBGM ) is widely recommended for both type 1 and type 2 diabetic patients despite the lack of evidence of benefit in glucose control or as an aid in weight loss in type 2 subjects . This study tested the hypothesis that combined use of SMBG and dietary carbohydrate ( CHO ) counting , using the blood monitoring results to shape dietary CHO quotas , is beneficial in managing type 2 diabetes . Twenty-three over-weight ( body mass index , BMI 27.5–44 kg/m2 ) patients aged 40–75 participated in a 28-week behavioral weight control program . Baseline hemoglobin HbA 1c ranged between 9.5 % and 13.5 % ( normal range 5.5%–7.7 % ) . Subjects were matched for weight , sex , and HbAlc and assigned to small ( 4–8 participants ) groups which met weekly for 12 weeks and then monthly for 16 weeks . After 8 weeks , the group were r and omized either to continue the behavioral program or to have SMBG and dietary CHO counting . Glucose monitoring was performed 6 times daily ( pre- and 2h postpr and ially ) for the first month , focusing on the meal increment and correlating this to dietary CHO intake . Weight loss was identical in both groups during the year of follow-up . The HbA1c level showed a progressive decline in experimental subjects ( P<0.05 ) , whereas there was no improvement in control subjects OBJECTIVE : To assess the effectiveness of a pharmaceutical care model on the management of non-insulin-dependent diabetes mellitus ( NIDDM ) in urban African-American patients . DESIGN : Eligible patients were r and omized to either a pharmacist intervention or control group and followed over a 4-month period . Patients in the intervention group received diabetes education , medication counseling , instructions on dietary regulation , exercise , and home blood glucose monitoring , and evaluation and adjustment of their hypoglycemic regimen . Patients in the control group continued to receive st and ard medical care provided by their physicians . SETTING : A university-affiliated internal medicine outpatient clinic . PARTICIPANTS : The study population consisted of urban African-American patients with NIDDM currently attending the clinic . MAIN OUTCOME MEASURES : Primary outcome measures included fasting plasma glucose and glycated hemoglobin concentrations . Secondary outcome endpoints included blood pressure , serum creatinine , creatinine clearance , microalbumin to creatinine ratio , total cholesterol , triglycerides , high-density lipoprotein , and low-density lipoprotein concentrations . Quality -of-life assessment s were performed in both groups at baseline and at the end of the study . RESULTS : Thirty-nine patients ( 17 intervention , 22 control ) completed the study . The intervention group consisted of 12 women and 5 men with a mean ± SD age of 59 ± 12 years , total body weight ( TBW ) of 93 ± 22 kg , body mass index ( BMI ) of 34 ± 7 kg/m2 , and duration of NIDDM 6.8 ± 6.5 years . The control group consisted of 15 women and 7 men with a mean age of 65 ± 12 years , TBW of 88 ± 19 kg , BMI of 33 ± 7 kg/m2 , and a duration of NIDDM of 6.2 ± 4.8 y. Significant improvement in glycated hemoglobin ( p = 0.003 ) and fasting plasma glucose ( p = 0.015 ) was achieved in the intervention group . No change in glycemia was observed in the control subjects . Statistically significant differences in the final glycated hemoglobin ( p = 0.003 ) and fasting plasma glucose ( p = 0.022 ) concentrations were noted between groups . No significant changes in blood pressure control , lipid profile , renal function parameters , weight , or quality -of-life measures were noted within or between groups . CONCLUSIONS : Our data demonstrate the effectiveness of pharmaceutical care in the reduction of hyperglycemia associated with NIDDM in a group of urban African-American patients This study tested the hypothesis that follow-up intervention ( by telephone calls and home visit ) affects compliance in patients with non-insulin-dependent diabetes mellitus ( NIDDM ) . Sixty NIDDM patients were r and omly assigned to two groups — a control group , which received the st and ard protocol ( 3-day educational program and a review session 1 month after the program ) ; and an intervention group , which received the st and ard protocol as well as a series offour telephone calls and one home visit by a registered nurse over a 3-month period . Compliance to prescribed regimens was determined by analyzing three sets of data : changes in pre- to post study glycosylated hemoglobin ( HbA1c ) values ; changes in pre- to post study weight ; and frequency with which self-monitoring of blood glucose ( SMBG ) was practice d. Results showed that SMBG practice was significantly better for the intervention group . No significant differences were seen in post study HbA 1c values and weight changes between the two groups . Follow-up inter vention by telephone calls and home visit can enhance patient compliance to certain aspects of the prescribed diabetes management plan BACKGROUND Intensive treatment of patients with Type 2 diabetes mellitus ( T2DM ) from the moment of diagnosis facilitates β-cell recovery . Self-monitoring of blood glucose (SMBG)-based educational and pharmacological intervention may be better than conventional HbA1c algorithms in the treatment of newly diagnosed T2DM . METHODS Newly diagnosed T2DM patients were r and omized to either an SMBG-based intervention or an HbA1c-based control group ( n = 99 and 62 , respectively ) and were followed for 1 year . RESULTS Higher rates of diabetes regression ( HbA1c < 6 % on metformin alone ) and remission ( HbA1c between 6.0 % and 6.4 % ) were achieved in the intervention compared with the control group ( 39 % vs 5 % ( P < 0.001 ) and 37 % vs 30 % ( P < 0.01 ) , respectively ) . Furthermore , significantly greater reductions in median HbA1c ( 6.6 % to 6.1 % ; P < 0.05 ) and body mass index ( 29.6 - 27.9 kg/m(2 ) ; P < 0.001 ) were seen in the intervention over the 1 year of therapy . The percentage of patients achieving a lifestyle score > 12 was significantly greater in the SMBG compared with the control group ( 38.4 % vs 9.7 % respectively ; P < 0.001 ) . An inverse correlation was observed between SMBG and HbA1c levels ( P < 0.04 ) . CONCLUSIONS The results indicate that SMBG-based structured educational and pharmacological programs empower patients to achieve nutritional and physical activity goals , and encourage physicians and patients to use SMBG to optimize therapy . We believe that the concept of intensive treatment of T2DM patients should be modified ; instead of referring to the type of treatment ( insulin use ) , the term should reflect the intensity with which we work to reach glucose objectives BACKGROUND We evaluated how a structured patient/physician self-monitoring of blood glucose ( SMBG ) intervention influenced the timing , frequency , and effectiveness of primary care physicians ' treatment changes with type 2 diabetes mellitus ( T2DM ) patients over 12 months . METHODS The Structured Testing Program ( STeP ) study was a cluster-r and omized , multicenter trial with 483 poorly controlled , insulin-naive T2DM subjects . Primary care practice s were r and omized to the Active Control Group ( ACG ) or the Structured Testing Group ( STG ) , the latter of which included quarterly review of structured SMBG results . STG patients used a paper tool that graphs seven-point glucose profiles over 3 consecutive days ; physicians received a treatment algorithm based on SMBG patterns . Impact of structured SMBG on physician treatment modification recommendations ( TMRs ) and glycemic outcomes was examined . RESULTS More STG than ACG patients received a TMR at each study visit ( P < 0.0001 ) . Of patients who received at least one TMR , STG patients demonstrated a greater reduction in glycated hemoglobin A1c ( HbA1c ) than ACG patients ( -1.2 % vs. -0.8 % , P < 0.03 ) . Patients with a baseline HbA1c ≥8.5 % who received a TMR at the Month 1 visit experienced greater reductions in HbA1c ( P = 0.002 ) than patients without an initial TMR . More STG than ACG patients were started on incretins ( P < 0.01 ) and on thiazolidinediones ( P = 0.004 ) . The number of visits with a TMR was unrelated to HbA1c change over time . CONCLUSIONS Patient-provided SMBG data contribute to glycemic improvement when blood glucose patterns are easy to detect , and well-trained physicians take timely action . Collaborative use of structured SMBG data leads to earlier , more frequent , and more effective TMRs for poorly controlled , non-insulin-treated T2DM subjects INTRODUCTION Patients with T2DM often view self-monitoring of blood glucose ( SMBG ) as burdensome and pointless , which may affect their broader attitudes toward diabetes management . We examined how a structured SMBG protocol influenced diabetes self-efficacy and autonomous motivation over time , and linked these to changes in glycemic control . MATERIAL S AND METHODS The Structured Testing Program ( STeP ) is a 12-month , two-arm , cluster-r and omized trial that assessed the efficacy of structured SMBG in 483 insulin-naïve T2DM patients . Measures included : Confidence in Diabetes Self-Care for Type 2 patients ( CIDS-T2 ) , Diabetes-related Autonomous Motivation ( DRAM ) , self-management behaviors and HbA1c . RESULTS Intent-to-treat ( ITT ) and per- protocol ( PP ) analyses showed significant increases in CIDS-T2 scores over time ( main effects p<0.0001 ) . PP analysis showed significant between-group differences ( p<0.05 ) , with adherent STG patients displaying greater CIDS-T2 improvement than ACG patients . PP analyses showed main and between-group effects in DRAM with similar findings . Changes in CIDS-T2 were related to HbA1c changes over time ; no self-management variable mediated this relationship . CIDS-T2 and HbA1c displayed a significant time-concordant relationship . DISCUSSION Structured SMBG leads to significant increases in self-confidence and autonomous motivation associated with diabetes self-management . Changes in self-confidence are linked to changes in glycemic control and share a time-concordant relationship AIMS To estimate the efficacy of a self-monitoring-based disease management strategy in patients with Type 2 diabetes treated with oral agent monotherapy . METHODS This was an open-label , r and omized , pilot study , primarily led by diabetes nurses . Patients were r and omly allocated to either a self-monitoring-based disease management strategy or usual care ( ratio 3:1 ) and followed up for 6 months . Education was centred on how to modify lifestyle according self-monitoring readings . Self-monitoring of blood glucose results were discussed during monthly telephone contact . The primary endpoint was mean change in HbA(1c ) levels , estimated with an ANOVA for repeated measures . All analyses were intention to treat . RESULTS Three diabetic clinics recruited 62 patients , of whom five were lost to follow-up . At baseline , both groups had a mean HbA(1c ) value of 7.9 % ± 0.6 % ( 63 ± 6 mmol/mol ) . After 6 months , mean HbA(1c ) reduction was 1.2 ± 0.1 % ( -13 ± 1 mmol/mol ) in the intervention group and 0.7 ± 0.2 (-8 ± 2 mmol/mol ) in the control group , with an absolute mean difference between groups of -0.5 % ( 95 % CI -0.9 to -0.0 % ; P = 0.04 ) ( -5 mmol/mol , 95 % CI -10 to 0 ) . At study end , 61.9 % of patients in the intervention group and 20.0 % in the control group reached the target level of HbA(1c ) < 7.0 % ( < 53 mmol/mol ) ( P = 0.005 ) . Body weight reduction was significantly greater in the intervention group than in the control group ( between-group absolute mean difference : -3.99 kg ; 95 % CI -7.26 to -0.73 ; P = 0.02 ) . Therapy changes were more frequent in the control group . CONCLUSIONS A self-monitoring disease management strategy , primarily led by diabetes nurses and allowing a timely and efficient use of self-monitoring readings , is able to improve metabolic control , primarily through lifestyle modifications leading to weight loss OBJECTIVES To determine whether self-monitoring of blood glucose ( SMBG ) , either alone or with additional instruction in incorporating the results into self-care , is more effective than usual care in improving glycaemic control in non-insulin-treated diabetes . DESIGN An open , parallel group r and omised controlled trial . SETTING 24 general practice s in Oxfordshire and 24 in South Yorkshire , UK . PARTICIPANTS Patients with non-insulin-treated type 2 diabetes , aged > or = 25 years and with glycosylated haemoglobin ( HbA1c ) > or = 6.2 % . INTERVENTIONS A total of 453 patients were individually r and omised to one of : ( 1 ) st and ardised usual care with 3-monthly HbA1c ( control , n = 152 ) ; ( 2 ) blood glucose self-testing with patient training focused on clinician interpretation of results in addition to usual care ( less intensive self-monitoring , n = 150 ) ; ( 3 ) SMBG with additional training of patients in interpretation and application of the results to enhance motivation and maintain adherence to a healthy lifestyle ( more intensive self-monitoring , n = 151 ) . MAIN OUTCOME MEASURES The primary outcome was HBA1c at 12 months , and an intention-to-treat analysis , including all patients , was undertaken . Blood pressure , lipids , episodes of hypoglycaemia and quality of life , measured with the EuroQol 5 dimensions ( EQ-5D ) , were secondary measures . An economic analysis was also carried out , and question naires were used to measure well-being , beliefs about use of SMBG and self-reports of medication taking , dietary and physical activities , and health-care re source use . RESULTS The differences in 12-month HbA1c between the three groups ( adjusted for baseline HbA1c ) were not statistically significant ( p = 0.12 ) . The difference in unadjusted mean change in HbA1c from baseline to 12 months between the control and less intensive self-monitoring groups was -0.14 % [ 95 % confidence interval ( CI ) -0.35 to 0.07 ] and between the control and more intensive self-monitoring groups was -0.17 % ( 95 % CI -0.37 to 0.03 ) . There was no evidence of a significantly different impact of self-monitoring on glycaemic control when comparing subgroups of patients defined by duration of diabetes , therapy , diabetes-related complications and EQ-5D score . The economic analysis suggested that SMBG result ed in extra health-care costs and was unlikely to be cost-effective if used routinely . There appeared to be an initial negative impact of SMBG on quality of life measured on the EQ-5D , and the potential additional lifetime gains in quality -adjusted life-years , result ing from the lower levels of risk factors achieved at the end of trial follow-up , were outweighed by these initial impacts for both SMBG groups compared with control . Some patients felt that SMBG was helpful , and there was evidence that those using more intensive self-monitoring perceived diabetes as having more serious consequences . Patients using SMBG were often not clear about the relationship between their behaviour and the test results . CONCLUSIONS While the data do not exclude the possibility of a clinical ly important benefit for specific subgroups of patients in initiating good glycaemic control , SMBG by non-insulin-treated patients , with or without instruction in incorporating findings into self-care , did not lead to a significant improvement in glycaemic control compared with usual care monitored by HbA1c levels . There was no convincing evidence to support a recommendation for routine self-monitoring of all patients and no evidence of improved glycaemic control in predefined subgroups of patients |
12,241 | 26,344,844 | Thus , our systematic review revealed little evidence upon which to make recommendations for treatment of DFIs . | null | null |
12,242 | 29,718,969 | Interventions had some significant positive effects mostly for veterans adjusting to civilian life and other family members . | Exposure to stressful and potentially traumatic experiences is a risk for military personnel and for some this may increase susceptibility to reduced well-being .
The aim of this systematic review was to examine the effectiveness of interventions to promote the well-being of military personnel adjusting to civilian life . | BACKGROUND The effectiveness of post-deployment screening for mental disorders has not been assessed in a r and omised controlled trial . We aim ed to assess whether post-deployment screening for post-traumatic stress disorder ( PTSD ) , depression , anxiety , or alcohol misuse was effective . We defined screening as the presumptive identification of a previously unrecognised disorder using tests to distinguish those who probably had the disorder from those who probably did not so that those people with a probable disorder could be referred appropriately , and assessed effectiveness and consequences for help-seeking by the odds ratio at follow-up between those receiving tailored help-seeking advice and those who received general mental health advice . METHODS We did a cluster r and omised controlled trial among Royal Marines and Army personnel in the UK military after deployment to Afghanistan . Platoons were r and omly assigned ( 1:1 initially , then 2:1 ) by stratified block r and omisation with r and omly varying block sizes of two and four to the screening group , which received tailored help-seeking advice , or the control group , which received general mental health advice . Initial assessment took place 6 - 12 weeks after deployment ; follow-up assessment s were done 10 - 24 months later . Follow-up measures were the PTSD Checklist-Civilian Version , Patient Health Question naire-9 , Generalised Anxiety Disorder-7 scale , Alcohol Use Disorder Identification Test ( AUDIT ) , and self-reported help-seeking from clinical and welfare providers comparing those receiving tailored advice and those receiving only general advice . All participants and all investigators other than the person who analysed the data were masked to allocation . The primary outcomes were PTSD , depression or generalised anxiety disorder , and alcohol misuse at follow-up . A key secondary outcome was assessment of whether post-deployment screening followed by tailored advice would modify help-seeking behaviour . Comparisons were made between screening and control groups , with primary analyses by intention to treat . This trial is registered with the IS RCT N Registry , number IS RCT N19965528 . FINDINGS Between Oct 24 , 2011 , and Oct 31 , 2014 , 434 platoons comprising 10 190 personnel were included : 274 ( 6350 personnel ) in the screening group and 160 ( 3840 personnel ) in the control group . 5577 ( 88 % ) of 6350 personnel received screening and 3996 ( 63 % ) completed follow-up , whereas 3149 ( 82 % ) of 3840 received the control question naire and 2369 ( 62 % ) completed follow-up . 1958 ( 35 % ) of 5577 personnel in the screening group declined to see the tailored advice , but those with PTSD ( 83 % ) or anxiety or depression ( 84 % ) were more likely than non-cases ( 64 % ) to view the advice ( both p<0·0001 ) . At follow-up , there were no significant differences in prevalence between groups for PTSD ( adjusted odds ratio 0·92 , 95 % CI 0·75 - 1·14 ) , depression or anxiety ( 0·91 , 0·71 - 1·16 ) , alcohol misuse ( 0·88 , 0·73 - 1·06 ) , or seeking support for mental disorders ( 0·92 , 0·78 - 1·08 ) . INTERPRETATION Post-deployment screening for mental disorders based on tailored advice was not effective at reducing prevalence of mental health disorders nor did it increase help-seeking . Countries that have implemented post-deployment screening programmes for mental disorders should consider monitoring the outcomes of their programmes . FUNDING The US Army Medical Research and Materiel Comm and -Military Operational Medicine Research Program ( USAMRMC-MOMRP ) Acceptance and commitment therapy ( ACT ) has previously been shown to alter stigmatizing attitudes and to be relatively useful for psychologically inflexible participants . The present study is the first to bring those two findings together by comparing ACT to an education intervention for reducing stigma toward people with psychological disorders , and examining whether results differ for psychologically inflexible versus flexible individuals . A sample of college students ( N = 95 ) was r and omly assigned to a 2(1)2h ACT or educational workshop . Measures were taken before and after the workshop and at a 1-month follow-up . ACT reduced mental health stigma significantly regardless of participants ' pre-treatment levels of psychological flexibility , but education reduced stigma only among participants who were relatively flexible and non-avoidant to begin with . Acceptance could be an important avenue of exploration for stigma research ers This article reports pilot data from phase I of a project to develop and evaluate a self-directed program of integrative therapies for National Guard personnel and significant relationship partners to support reintegration and resilience after return from Iraq or Afghanistan . Data are reported on 43 dyads . Intervention was an integrated multimedia package of guided meditative , contemplative , and relaxation exercises ( CD ) and instruction in simple massage techniques ( DVD ) to promote stress reduction and interpersonal connectedness . A repeated measures design with st and ardized instruments was used to establish stability of baseline levels of relevant mental health domains ( day 1 , day 30 ) , followed by the intervention and assessment s 4 and 8 weeks later . Significant improvements in st and ardized measures for post-traumatic stress disorder , depression , and self-compassion were seen in both veterans and partners ; and in stress for partners . Weekly online reporting tracked utilization of guided exercises and massage . Veterans reported significant reductions in ratings of physical pain , physical tension , irritability , anxiety/worry , and depression after massage , and longitudinal analysis suggested declining baseline levels of tension and irritability . Qualitative data from focus groups and implication s for continued development and a phase II trial are discussed Background : Many veterans deployed after 9/11/2001 are impacted by subthreshold levels of post-traumatic stress , anxiety , or other psychological health problems that may interfere with successful reintegration . Conventional treatments , including medication and trauma-focused individual psychotherapies , may not be optimally adapted , accepted , or effective to treat these subsyndromal symptoms . Methods : We developed “ Resilient Warrior , ” a 4-session , group-based , mind-body stress-management and resilience program targeted to build skills and assessed whether its format was accessible and acceptable , and potentially efficacious , to support resilience among service members . Results : From April 2014 to October 2014 , 15 participants ( 53.3 % women ; mean age=36.6 y ; SD=6.2 ) were surveyed for program acceptability and feasibility and completed self-reported psychological health outcomes before and after program participation . The majority ( 71.4 % ) of participants reported that the program included the right number of sessions , and all of them reported that it was helpful and relevant and that they would recommend it to others . While changes in self-reported resilience were only marginal , participation was associated with improvements in depressive symptoms , perceived stress , anxiety , and general sense of self efficacy . Conclusion : These pilot data provide preliminary support that “ Resilient Warrior , ” a group-based , stress reduction and resilience program , may improve psychological health in service members even when delivered in community setting s. R and omized controlled trials with longer follow-up periods are needed to establish efficacy and effectiveness for this program OBJECTIVE Anger and aggression are serious problems for a significant proportion of veterans who have served in combat . While prior research has suggested that cognitive behavioral treatments may be effective for anger problems , there are few controlled studies of anger treatment in veterans and no studies of anger treatment focusing exclusively on veterans from the Iraq and Afghanistan wars . This r and omized pilot study compared an adapted cognitive behavioral intervention ( CBI ) to a supportive intervention ( SI ) control condition for the treatment of anger problems in veterans returning from deployment in Iraq or Afghanistan . METHODS 25 veterans with warzone trauma , problems with anger , and one or more additional hyperarousal symptoms were r and omized and 23 started treatment ( CBI , n = 12 ; SI , n = 11 ) . Outcome measures were administered at pre- and post- treatment and at 3 months post-treatment . RESULTS CBI was associated with significantly more improvement than SI on measures of anger and interpersonal functioning . Gains were maintained at follow-up . CONCLUSIONS Findings suggest that CBI may be more effective than an active control providing psychoeducation , relaxation , and supportive therapy for treating anger problems in returning veterans . The findings need to be replicated in an adequately powered and more diverse sample The decade long conflicts in Iraq and Afghanistan have placed considerable strain on military families . Given robust data showing high rates of deployment-related psychological health problems in spouses and children , and the near absence of evidence -based psychological health programs for military families in the community , interventions are urgently needed to support and strengthen spouses as they adjust to deployment transitions and military life experiences . This Phase 1 pilot study evaluated the feasibility and acceptability of a resiliency intervention for military spouses in civilian communities ( HomeFront Strong ; HFS ) , and generated preliminary efficacy data regarding impacts on psychological health and adjustment . Through two group cohorts , 14 women completed the intervention , with 10 women providing pre- and postgroup assessment data . Findings support feasibility of the intervention and high rates of program satisfaction . Participants reported learning new strategies and feeling more knowledgeable in their ability to use effective coping skills for managing deployment and military-related stressors . Participation in HFS was also associated with reduction in levels of anxiety and perceived stress , and improvements in life satisfaction and life engagement . HFS is a promising community-based intervention for military spouses design ed to enhance resiliency , reduce negative psychological health symptoms , and improve coping BACKGROUND The Cochrane Collaboration is strongly encouraging the use of a newly developed tool , the Cochrane Collaboration Risk of Bias Tool ( CCRBT ) , for all review groups . However , the psychometric properties of this tool to date have yet to be described . Thus , the objective of this study was to add information about psychometric properties of the CCRBT including inter-rater reliability and concurrent validity , in comparison with the Effective Public Health Practice Project Quality Assessment Tool ( EPHPP ) . METHODS Both tools were used to assess the method ological quality of 20 r and omized controlled trials included in our systematic review of the effectiveness of knowledge translation interventions to improve the management of cancer pain . Each study assessment was completed independently by two review ers using each tool . We analysed the inter-rater reliability of each tool 's individual domains , as well as final grade assigned to each study . RESULTS The EPHPP had fair inter-rater agreement for individual domains and excellent agreement for the final grade . In contrast , the CCRBT had slight inter-rater agreement for individual domains and fair inter-rater agreement for final grade . Of interest , no agreement between the two tools was evident in their final grade assigned to each study . Although both tools were developed to assess ' quality of the evidence ' , they appear to measure different constructs . CONCLUSIONS Both tools performed quite differently when evaluating the risk of bias or method ological quality of studies in knowledge translation interventions for cancer pain . The newly introduced CCRBT assigned these studies a higher risk of bias . Its psychometric properties need to be more thoroughly vali date d , in a range of research fields , to underst and fully how to interpret results from its application Background Veterans with history of deployment in the Global War on Terror face significant and ongoing challenges with high prevalences of adverse psychological , physical , spiritual , and family impacts . Together , these challenges contribute to an emerging public health crisis likely to extend well into the future . Innovative approaches are needed that reach veterans and their family members with strategies they can employ over time in their daily lives to promote improved adjustment and well-being . Objective The objective of this study was to evaluate effects of use of a Web-based , self-directed program of instruction in mind- and body-based wellness skills to be employed by Global War on Terror veterans and their significant relationship partners on mental health and wellness outcomes associated with postdeployment readjustment . Methods We recruited 160 veteran-partner dyads in 4 regions of the United States ( San Diego , CA ; Dallas , TX ; Fayetteville , NC ; and New York , NY ) through publicity by the Iraq and Afghanistan Veterans of America to its membership . Dyads were r and omly allocated to 1 of 4 study arms : Mission Reconnect ( MR ) program alone , MR plus the Prevention and Relationship Enhancement Program ( PREP ) for Strong Bonds weekend program for military couples , PREP alone , and waitlist control . We administered a battery of st and ardized and investigator-generated instruments assessing mental health outcomes at baseline , 8 weeks , and 16 weeks . Dyads in the MR arms were provided Web-based and mobile app video and audio instruction in a set of mindfulness-related stress reduction and contemplative practice s , as well as partner massage for reciprocal use . All participants provided weekly reports on frequency and duration of self-care practice s for the first 8 weeks , and at 16 weeks . Results During the first 8-week reporting period , veterans and partners assigned to MR arms used some aspect of the program a mean of 20 times per week , totaling nearly 2.5 hours per week , with only modest declines in use at 16 weeks . Significant improvements were seen at 8 and 16 weeks in measures of posttraumatic stress disorder , depression , sleep quality , perceived stress , resilience , self-compassion , and pain for participants assigned to MR arms . In addition , significant reductions in self-reported levels of pain , tension , irritability , anxiety , and depression were associated with use of partner massage . Conclusions Both veterans and partners were able to learn and make sustained use of a range of wellness practice s taught in the MR program . Home-based , self-directed interventions may be of particular service to veterans who are distant from , averse to , or prohibited by schedule from using professional services . Leveraging the partner relationship may enhance sustained use of self-directed interventions for this population . Use of the MR program appears to be an accessible , low-cost approach that supports well-being and reduces multiple symptoms among post-9/11 veterans and their partners . Trial Registration Clinical trials.gov NCT01680419 ; https:// clinical trials.gov/ct2/show/NCT01680419 ( Archived by WebCite at http://www.webcitation.org/6jJuadfzj OBJECTIVE Combat exposure can increase the risk of subsequent psychological ill-health in armed forces ( AF ) personnel . A U.S. postdeployment psycho-educational intervention , Battlemind , showed a beneficial effect on mental health in U.S. military personnel exposed to high combat levels . We evaluated the effectiveness of an anglicized version of postdeployment Battlemind . METHOD Battlemind was adapted for the United Kingdom . The main amendments were to sections about carrying weapons , driving , and alcohol misuse . The anglicized Battlemind was compared with the U.K. st and ard postdeployment brief in a cluster r and omized controlled trial . At baseline , 2,443 U.K. AF personnel returning from Afghanistan via Cyprus completed question naires about their combat experiences and mental health . Of these , 1,616 ( 66 % ) completed 6-month follow-up question naires . We used the Posttraumatic Stress Disorder Checklist ( PCL-C ) to measure probable posttraumatic stress disorder and the General Health Question naire ( GHQ-12 ) to measure common mental disorders . Secondary outcomes included alcohol misuse , assessed with the Alcohol Use Disorders Identification Test ( AUDIT ) , and binge drinking . Mixed-effects models were used to account for possible cluster effects . RESULTS We did not find a difference in mental health or overall AUDIT score . Those who received Battlemind versus the st and ard brief were less likely to report binge drinking , although the effect size was small ( adjusted odds ratio = 0.73 , 95 % CI [ 0.58 , 0.92 ] ) . CONCLUSIONS The anglicized Battlemind did not improve mental health but had a modest impact on the reporting of binge drinking . Alcohol misuse is problematic in military population s ; therefore , an intervention that reduces binge drinking may be helpful We examined the efficacy of a brief , accessible , nonstigmatizing online intervention-writing expressively about transitioning to civilian life . U.S. Afghanistan and Iraq war veterans with self-reported reintegration difficulty ( N = 1,292 , 39.3 % female , M = 36.87 , SD = 9.78 years ) were r and omly assigned to expressive writing ( n = 508 ) , factual control writing ( n = 507 ) , or no writing ( n = 277 ) . Using intention to treat , generalized linear mixed models demonstrated that 6-months postintervention , veterans who wrote expressively experienced greater reductions in physical complaints , anger , and distress compared with veterans who wrote factually ( ds = 0.13 to 0.20 ; ps < .05 ) and greater reductions in PTSD symptoms , distress , anger , physical complaints , and reintegration difficulty compared with veterans who did not write at all ( ds = 0.22 to 0.35 ; ps ≤ .001 ) . Veterans who wrote expressively also experienced greater improvement in social support compared to those who did not write ( d = 0.17 ) . Relative to both control conditions , expressive writing did not lead to improved life satisfaction . Secondary analyses also found beneficial effects of expressive writing on clinical ly significant distress , PTSD screening , and employment status . Online expressive writing holds promise for improving health and functioning among veterans experiencing reintegration difficulty , albeit with small effect sizes BACKGROUND Road traffic accidents are the leading cause of death for service personnel from the United Kingdom ( UK ) . Little is known about the pattern of risky driving by these service personnel . METHODS Cross-sectional data ( collected postdeployment , between June 2004 and March 2006 ) were analyzed from a large , r and omly selected cohort of military personnel from the UK . These analyses were limited to regular-service personnel who were drivers ( n=8,127 ; 7,443 men and 684 women ) . " Risky driving " ( not wearing a seatbelt , speeding , or both ) was examined . Analyses were then repeated but restricted to those with experience of deployment to Iraq ( n=4,611 ) . All analyses were undertaken during 2007 . RESULTS Nineteen percent of armed forces personnel from the UK were defined as risky drivers . Risky driving was associated with being of young age ; being male ; being in the Army ; childhood adversity ; being deployed to Iraq ; having a combat role ; and being separated , divorced , or widowed . Restricting analyses to those deployed to Iraq revealed that risky driving was associated with increasing exposure to traumatic events and low in-theater morale . CONCLUSIONS There are clear sociodemographic associations of risk-taking behaviors in the military population , and the study 's results imply that risky driving is more common in drivers who had deployed OBJECTIVE We evaluated the effectiveness of Strength at Home Friends and Families ( SAH-F ) , a dyadic group intervention to prevent relational aggression and its negative consequences , in a community-based sample of service members/veterans and significant others who reported relational difficulties . METHOD Participants included 70 veterans and their loved ones . Recruitment was conducted from October 2010 through March 2012 . Participants completed an initial assessment that included measures of relational aggression and functioning , depressive symptoms , and posttraumatic stress disorder ( PTSD ) symptoms . Participants were enrolled in the 10-week SAH-F targeting social information-processing mechanisms hypothesized to underlie the relationship between trauma and aggression and were reassessed at program completion and 3 months after intervention . RESULTS Significant reductions in psychological aggression were seen both at program completion and at 3-month follow-up for both veterans ( st and ardized mean gain effect size [ ESsg ] = -0.45 , P < .05 ) and significant others ( ESsg = -0.30 , P < .05 ) . Perpetration of physical aggression remained low after pretreatment and did not increase . Relationship adjustment reported by significant others , but not veterans , indicated a significant improvement from pretreatment to program completion ( ESsg = 0.33 , P < .05 ) . Significant ( P < .05 ) decreases in depressive symptoms were observed from pretreatment to program completion for veterans ( ESsg = -0.30 , P < .05 ) and significant others ( ESsg = -0.55 , P < .05 ) , and significant decreases in PTSD symptoms were observed from pretreatment to follow-up for veterans and significant others ( ESsg = -0.52 , P < .05 ) . CONCLUSIONS Results provide support for the effectiveness of SAH-F in reducing relational aggression in military member/significant other dyads and enhancing relationship quality and mental health Research ers have found that there is an increase in mental heath problems as a result of military-related traumatic events , and such problems increase in the months following return from combat . Nevertheless , research ers have not assessed the impact of early intervention efforts with this at-risk population . In the present study , the authors compared different early interventions with 2,297 U.S. soldiers following a year-long deployment to Iraq . Platoons were r and omly assigned to st and ard postdeployment stress education , Battlemind debriefing , and small and large group Battlemind training . Results from a 4-month follow-up with 1,060 participants showed those with high levels of combat exposure who received Battlemind debriefing reported fewer posttraumatic stress symptoms , depression symptoms , and sleep problems than those in stress education . Small group Battlemind training participants with high combat exposure reported fewer posttraumatic stress symptoms and sleep problems than stress education participants . Compared to stress education participants , large group Battlemind training participants with high combat exposure reported fewer posttraumatic stress symptoms and lower levels of stigma and , regardless of combat exposure , reported fewer depression symptoms . Findings demonstrate that brief early interventions have the potential to be effective with at-risk occupational groups The current study tested the effectiveness of a brief expressive writing intervention on the marital adjustment of 102 military couples recently reunited following a deployment to Iraq or Afghanistan . Active duty soldiers and their spouses were r and omly assigned to write about either their relationship or a nonemotional topic on 3 occasions on a single day . The result ing design included 4 couple-level writing topic conditions : soldier-expressive/spouse-expressive , soldier-expressive/spouse-control , soldier-control/spouse-expressive , and soldier-control/spouse-control . Participants completed marital adjustment measures before writing , 1 month , and 6 months after writing . When soldiers , but not spouses , did expressive writing , couples increased in marital satisfaction over the next month , particularly if the soldier had had high combat exposure |
12,243 | 29,061,310 | RESULTS The selected articles have shown that the implementation of physical activity programs ( aerobic , resistance , flexibility and combined exercises ) , and programs based on a higher intake of vegetables , grains , legumes , fruits , unsaturated fatty acids , as well as consumption of foods with low glycaemic index , calorie restriction , intake of probiotics , vitamin D supplementation and educational sessions about diabetes improves blood glucose levels , as well as the lipid profile , in patients with type 2 diabetes .
Physical activity and dietary programs are fundamental in the treatment and metabolic control of type 2 diabetes mellitus | OBJECTIVES Evaluate the effectiveness of the implementation of independently or combined dietary and physical activity programs on the blood glucose values and lipid profile in patients with type 2 diabetes , including participants aged 60 years and over . | Abbreviations ACCORD Action to Control Cardiovascular Risk in Diabetes ADVANCE Action in Diabetes and Vascular Disease : Preterax and Diamicron Modified-Release Controlled Evaluation AGI α-Glucosidase inhibitor CAD Coronary artery disease CKD Chronic kidney disease CVD Cardiovascular disease DPP-4 Dipeptidyl peptidase IV GIP Glucose-dependent insulinotropic peptide GLP-1 Glucagon-like peptide 1 NPH Neutral protamine Hagedorn TZD Thiazolidinedione UKPDS UK Prospect i ve Diabetes Study VADT Veterans Affairs Diabetes OBJECTIVE Low vitamin D levels predict the development of diabetes . This double-blind , r and omized , control study in subjects with prediabetes and hypovitaminosis D evaluated whether high doses of vitamin D for 1 year affected insulin secretion , insulin sensitivity , and the development of diabetes . RESEARCH DESIGN AND METHODS A total of 1,551 subjects ≥40 years of age not known to have diabetes were screened with A1C levels . Subjects with A1C levels of 5.8–6.9 % underwent an oral glucose tolerance test ( OGTT ) . Subjects with prediabetes and 25-OH vitamin D ( 25-OHD ) levels < 30 ng/mL were r and omized to receive weekly placebo ( n = 53 ) or vitamin D ( n = 56 ) with doses based on body weight and baseline 25-OHD levels . OGTTs were performed 3 , 6 , 9 , and 12 months later . Insulin secretion and sensitivity were measured , and the proportion of subjects developing diabetes was assessed . RESULTS 25-OHD levels rapidly rose from 22 to nearly 70 ng/mL after vitamin D supplementation with a mean weekly dose of 88,865 IU . There were no differences between the placebo and vitamin D groups regarding fasting plasma glucose , 2-h glucose , or insulin secretion and sensitivity or in the percent developing diabetes or returning to normal glucose tolerance . No subjects experienced increased serum or urinary calcium levels . At 12 months , A1C levels were significantly slightly less ( 0.2 % ) in the vitamin D group . CONCLUSIONS In individuals with prediabetes and hypovitaminosis D , doses of vitamin D supplementation design ed to raise serum 25-OHD levels into the upper-normal range for 1 year had no effect on insulin secretion , insulin sensitivity , or the development of diabetes compared with placebo administration BACKGROUND & AIMS Type 2 diabetes has been associated with dysbiosis and one of the possible routes to restore a healthy gut microbiota is by the regular ingestion of probiotics . We aim ed to investigate the effects of probiotics on glycemic control , lipid profile , inflammation , oxidative stress and short chain fatty acids in T2D . METHODS In a double-blind , r and omized , placebo-controlled trial , 50 volunteers consumed daily 120 g/d of fermented milk for 6 wk . Participants were assigned into two groups : probiotic group , consuming fermented milk containing Lactobacillus acidophilus La-5 and Bifidobacterium animalis subsp lactis BB-12 ( 109 colony-forming units/d , each ) and control group , consuming conventional fermented milk . Anthropometric measurements , body composition , fasting blood and faecal sample s were taken at baseline and after 6 wk . RESULTS 45 subjects out of 50 ( 90 % ) completed follow-up . After 6 wk , there was a significant decrease in fructosamine levels ( -9.91 mmol/L ; p = 0.04 ) and hemoglobin A1c tended to be lower ( -0.67 % ; p=0.06 ) in probiotic group . TNF-α and resistin were significantly reduced in probiotic and control groups ( -1.5 and -1.3 pg/mL , -.1 and -2.8 ng/mL , respectively ) , while IL-10 was significantly reduced ( - 0.65 pg/mL ; p < 0.001 ) only in the control group . Fecal acetic acid was increased in both groups ( 0.58 and 0.59 % in probiotic and control groups , respectively ; p < 0.01 ) . There was a significant difference between groups concerning mean changes of HbA1c ( + 0.31 for control group vs -0.65 for probiotic group ; p=0.02 ) , total cholesterol ( + 0.55 for control group vs -0.15 for probiotic group ; p=0.04 ) and LDL-cholesterol ( + 0.36 for control group vs -0.20 for probiotic group p=0.03 ) . CONCLUSIONS Probiotic consumption improved the glycemic control in T2D subjects , however , the intake of fermented milk seems to be involved with others metabolic changes , such as decrease in inflammatory cytokines ( TNF-α and resistin ) and increase in the acetic acid Aims The aim of this study was to compare the effects of calorie-restricted vegetarian and conventional diabetic diets alone and in combination with exercise on insulin resistance , visceral fat and oxidative stress markers in subjects with Type 2 diabetes . Methods A 24-week , r and omized , open , parallel design was used . Seventy-four patients with Type 2 diabetes were r and omly assigned to either the experimental group ( n = 37 ) , which received a vegetarian diet , or the control group ( n = 37 ) , which received a conventional diabetic diet . Both diets were isocaloric , calorie restricted ( -500 kcal/day ) . All meals during the study were provided . The second 12 weeks of the diet were combined with aerobic exercise . Participants were examined at baseline , 12 weeks and 24 weeks . Primary outcomes were : insulin sensitivity measured by hyperinsulinaemic isoglycaemic clamp ; volume of visceral and subcutaneous fat measured by magnetic resonance imaging ; and oxidative stress measured by thiobarbituric acid reactive substances . Analyses were by intention to treat . Results Forty-three per cent of participants in the experimental group and 5 % of participants in the control group reduced diabetes medication ( P < 0.001 ) . Body weight decreased more in the experimental group than in the control group [ –6.2 kg ( 95 % CI –6.6 to –5.3 ) vs. –3.2 kg ( 95 % CI –3.7 to –2.5 ) ; interaction group × time P = 0.001 ] . An increase in insulin sensitivity was significantly greater in the experimental group than in the control group [ 30 % ( 95 % CI 24.5–39 ) vs. 20 % ( 95 % CI 14–25 ) , P = 0.04 ] . A reduction in both visceral and subcutaneous fat was greater in the experimental group than in the control group ( P = 0.007 and P = 0.02 , respectively ) . Plasma adiponectin increased ( P = 0.02 ) and leptin decreased ( P = 0.02 ) in the experimental group , with no change in the control group . Vitamin C , superoxide dismutase and reduced glutathione increased in the experimental group ( P = 0.002 , P < 0.001 and P = 0.02 , respectively ) . Differences between groups were greater after the addition of exercise training . Changes in insulin sensitivity and enzymatic oxidative stress markers correlated with changes in visceral fat . Conclusions A calorie-restricted vegetarian diet had greater capacity to improve insulin sensitivity compared with a conventional diabetic diet over 24 weeks . The greater loss of visceral fat and improvements in plasma concentrations of adipokines and oxidative stress markers with this diet may be responsible for the reduction of insulin resistance . The addition of exercise training further augmented the improved outcomes with the vegetarian diet BACKGROUND Lifestyle changes soon after diagnosis might improve outcomes in patients with type 2 diabetes mellitus , but no large trials have compared interventions . We investigated the effects of diet and physical activity on blood pressure and glucose concentrations . METHODS We did a r and omised , controlled trial in southwest Engl and in adults aged 30 - 80 years in whom type 2 diabetes had been diagnosed 5 - 8 months previously . Participants were assigned usual care ( initial dietary consultation and follow-up every 6 months ; control group ) , an intensive diet intervention ( dietary consultation every 3 months with monthly nurse support ) , or the latter plus a pedometer-based activity programme , in a 2:5:5 ratio . The primary endpoint was improvement in glycated haemoglobin A(1c)(HbA(1c ) ) concentration and blood pressure at 6 months . Analysis was done by intention to treat . This study is registered , number IS RCT N92162869 . FINDINGS Of 593 eligible individuals , 99 were assigned usual care , 248 the diet regimen , and 246 diet plus activity . Outcome data were available for 587 ( 99 % ) and 579 ( 98 % ) participants at 6 and 12 months , respectively . At 6 months , glycaemic control had worsened in the control group ( mean baseline HbA(1c ) percentage 6·72 , SD 1·02 , and at 6 months 6·86 , 1·02 ) but improved in the diet group ( baseline-adjusted difference in percentage of HbA(1c ) -0·28 % , 95 % CI -0·46 to -0·10 ; p=0·005 ) and diet plus activity group ( -0·33 % , -0·51 to -0·14 ; p<0·001 ) . These differences persisted to 12 months , despite less use of diabetes drugs . Improvements were also seen in bodyweight and insulin resistance between the intervention and control groups . Blood pressure was similar in all groups . INTERPRETATION An intensive diet intervention soon after diagnosis can improve glycaemic control . The addition of an activity intervention conferred no additional benefit . FUNDING Diabetes UK and the UK Department of Health OBJECTIVE To analyze the effects of a home-based physical exercise program on quality of life , metabolic control , and anthropometric and biochemical parameters in people over 60 years of age with type 2 diabetes mellitus . METHODS Eighty-four Spanish patients aged over 60 years were finally r and omized to participate in a home-based , combined physical exercise program ( aerobic and anaerobic exercises ) or to receive conventional treatment for diabetes . At 6 months , effects on quality of life ( EuroQoL question naire ) . HbA1c , fasting glucose , hypoglycemic events , weight , BMI , waist circumference , blood pressure , and biochemical parameters were assessed . RESULTS Mean age of study participants was 66.7 ( 8.0 ) years . Patients in the exercise group showed an improved quality of life at six months based on EuroQol : 0.48 ( 0.38 ) vs 0.66 ( 0.35 ) and analogic scale 67.97 ( 18.92 ) vs 76.26 ( 20.14 ) . An improved glycemic control was also seen : HbA1c 6.35 vs 6.0 % and fasting glucose 151.2 ( 36.7 ) vs 137.6 ( 23.5 ) mg/dL , as well as a weight reduction by 1.7 kg . Hypoglycemic events did not increase . No benefits were seen in the control group . Ten subjects withdrew from the study before 6 months . CONCLUSIONS A home-based physical exercise program improves quality of life , glycemic control , and weight in type 2 diabetic patients older than 60 years Background : Diabetes is a global health problem in the world . Probiotic food has anti-diabetic property . The aim of this trial was to determine the effect of probiotic fermented milk ( kefir ) on glucose and lipid profile control in patients with type 2 diabetes mellitus . Methods : This r and omized double-blind placebo-controlled clinical trial was conducted on 60 diabetic patients aged 35 to 65 years . Patients were r and omly and equally ( n=30 ) assigned to consume either probiotic fermented milk ( kefir ) or conventional fermented milk ( dough ) for 8 weeks . Probiotic group consumed 600 ml/day probiotic fermented milk containing Lactobacillus casei , Lactobacillus acidophilus and Bifidobacteria and control group consumed 600 ml/day conventional fermented milk . Blood sample s tested for fasting blood glucose , HbA1C , triglyceride ( TG ) , total cholesterol , HDL-C and LDL-C at the baseline and end of the study . Results : The comparison of fasting blood glucose between two groups after intervention was statistically significant ( P=0.01 ) . After intervention , reduced HbA1C compared with the baseline value in probiotic fermented milk group was statistically significant ( P=0.001 ) , also the HbA1C level significantly decreased in probiotic group in comparison with control group ( P=0.02 ) adjusting for serum levels of glucose , baseline values of HbA1c and energy intake according to ANCOVA model . Serum triglyceride , total cholesterol , LDL-cholesterol and HDL- cholesterol levels were not shown significant differences between and within the groups after intervention . Conclusion : Probiotic fermented milk can be useful as a complementary or adjuvant therapy in the treatment of diabetes Hypovitaminosis D is a growing problem that may affect as many as 57 % of Americans . Although this deficiency is commonly seen as a threat to bone health , a rapidly exp and ing collection of studies describe its impact on blood glucose control . With the prevalence of type 2 diabetes ( T2D ) ever increasing , linking hypovitaminosis D to the development or pathology of this chronic disease may unveil a novel approach to controlling its costly and debilitating complications . To further clarify this relationship , a pilot clinical trial ( NCT00985361 ; Clinical Trials.gov ) was undertaken to examine the effects of daily vitamin D supplementation on HbA1c in patients with uncontrolled T2D . The present study was a prospect i ve r and omized single-blind placebo-controlled study conducted in northwestern Ohio . The institutional review boards of the sites approved the study , all patients provided written informed consent and all study procedures conformed to the provisions of the Declaration of Helsinki . Recruitment began on 1 October 2009 and was completed on 31 December 2009 . Patients aged 21–75 years with uncontrolled T2D , defined as HbA1c > 7 % , were eligible for inclusion in the study . Patients with gestational diabetes , malabsorption syndrome , an estimated creatinine clearance < 30 mL ⁄min or those who had been treated with > 400 IU ⁄day vitamin D at any time in the previous year were excluded from the study . Eligible patients were r and omized in a 1:1 manner to receive either 2000 IU vitamin D3 ( cholecalciferol ) or 500 mg vitamin C ( ascorbic acid ) daily by mouth . It has been shown previously that 500 mg ⁄day vitamin C has no effect on HbA1c in patients with T2D and it served as the placebo in the present study . At the initial visit , a blood sample was collected to enable determination of baseline serum HbA1c . Then , vitamin D or vitamin C tablets were dispensed to the patients in vials , concealing the identity of the tablets . Follow-up telephone calls occurred at Weeks 4 and 8 . At Week 12 , final HbA1c levels were determined and a tablet count was performed to evaluate patient adherence . The primary endpoint was a comparison of mean change in HbA1c from baseline to Week 12 between the vitamin D and vitamin C groups . Secondary endpoints included an evaluation of adverse events and a subgroup analysis of mean changes in HbA1c according to baseline HbA1c levels . Our power analysis showed that a total of 26 patients would need to be enrolled in the study to detect a 0.35 % difference in HbA1c after 12 weeks of treatment and all data were examined using a modified intention-to-treat analysis . Of the 114 patients screened , 55 patients did not meet study criteria and 22 patients declined to provide consent . Eighteen patients were r and omized to the vitamin C group and 19 were r and omized to the vitamin D group . Eleven patients did not complete the full study protocol , of which five were included in the intention-to-treat analysis . At baseline , the two study groups were not significantly different with regard to mean age , sex , baseline diabetes medications , or mean baseline HbA1c . Overall , the mean ( ±SD ) age in the vitamin D and C groups was 53.8 ± 9.2 and 55.3 ± 7.8 years , respectively . Female patients made up 62.5 % and 53.3 % of the vitamin D and C groups , respectively . The mean ( ±SD ) baseline HbA1c in the vitamin D and C groups was 8.6 ± 1.2 % and Correspondence Mate M. Soric , Northeast Ohio Medical University College of Pharmacy , 4209 State Route 44 , PO Box 95 , Rootstown , OH 44272 , USA . Tel : + 1 330 325 6226 Fax : + 1 330 325 5951 Email : [email protected] * NCT00985361 , Clinical Trials.gov . Received 6 October 2011 ; accepted 13 October 2011 . doi : 10.1111/j.1753 - 0407.2011.00164.x Journal of Diabetes 4 ( 2012 ) OBJECTIVE Fat intake , especially monounsaturated fatty acid ( MUFA ) , has been liberalized in diabetic diets to preserve HDL cholesterol and improve glycemic control , yet the exact sources have not been clearly defined . Therefore , we assessed the effect of mixed nut consumption as a source of vegetable fat on serum lipids and HbA1c in type 2 diabetes . RESEARCH DESIGN AND METHODS A total of 117 type 2 diabetic subjects were r and omized to one of three treatments for 3 months . Supplements were provided at 475 kcal per 2,000-kcal diet as mixed nuts ( 75 g/day ) , muffins , or half portions of both . The primary outcome was change in HbA1c . RESULTS The relative increase in MUFAs was 8.7 % energy on the full-nut dose compared with muffins . Using an intention-to-treat analysis ( n = 117 ) , full-nut dose ( mean intake 73 g/day ) reduced HbA1c ( −0.21 % absolute HbA1c units , 95 % CI −0.30 to −0.11 , P < 0.001 ) with no change after half-nut dose or muffin . Full-nut dose was significantly different from half-nut dose ( P = 0.004 ) and muffin ( P = 0.001 ) , but no difference was seen between half-nut dose and muffins . LDL cholesterol also decreased significantly after full-nut dose compared with muffin . The LDL cholesterol reduction after half-nut dose was intermediate and not significantly different from the other treatments . Apolipoprotein ( apo ) B and the apoB : apoA1 ratio behaved similarly . Nut intake related negatively to changes in HbA1c ( r = −0.20 , P = 0.033 ) and LDL cholesterol ( r = −0.24 , P = 0.011 ) . CONCLUSIONS Two ounces of nuts daily as a replacement for carbohydrate foods improved both glycemic control and serum lipids in type 2 diabetes OBJECTIVE To assess the effect of exercise training on insulin sensitivity and plasma ceramides in obesity and type 2 diabetes ( T2D ) . METHODS Twenty-four adults with obesity and normal glucose tolerance ( NGT , n = 14 ) or diabetes ( n = 10 ) were studied before and after a 12-week supervised exercise-training program ( 5 days/week , 1 h/day , 80 - 85 % of maximum heart rate ) . Changes in body composition were assessed using hydrostatic weighing and computed tomography . Peripheral tissue insulin sensitivity was assessed by a 40 mU/m(2 ) /min hyperinsulinemic euglycemic clamp . Plasma ceramides ( C14:0 , C16:0 , C18:0 , C18:1 , C20:0 , C24:0 , and C24:1 ) were quantified using electrospray ionization t and em mass spectrometry after separation with HPLC . RESULTS Plasma ceramides were similar for the subjects with obesity and NGT and the subjects with diabetes , despite differences in glucose tolerance . Exercise significantly reduced body weight and adiposity and increased peripheral insulin sensitivity in both groups ( P < 0.05 ) . In addition , plasma C14:0 , C16:0 , C18:1 , and C24:0 ceramide levels were reduced in all subjects following the intervention ( P < 0.05 ) . Decreases in total ( r = -0.51 , P = 0.02 ) and C14:0 ( r = -0.56 , P = 0.009 ) ceramide were negatively correlated with the increase in insulin sensitivity . CONCLUSIONS Ceramides are linked to exercise training-induced improvements in insulin sensitivity , and plasma C14:0 ceramide may provide a specific target for investigating lipid-related insulin resistance in obesity and T2D CONTEXT Exercise guidelines for individuals with diabetes include both aerobic and resistance training although few studies have directly examined this exercise combination . OBJECTIVE To examine the benefits of aerobic training alone , resistance training alone , and a combination of both on hemoglobin A(1c ) ( HbA(1c ) ) in individuals with type 2 diabetes . DESIGN , SETTING , AND PARTICIPANTS A r and omized controlled trial in which 262 sedentary men and women in Louisiana with type 2 diabetes and HbA(1c ) levels of 6.5 % or higher were enrolled in the 9-month exercise program between April 2007 and August 2009 . INTERVENTION Forty-one participants were assigned to the nonexercise control group , 73 to resistance training 3 days a week , 72 to aerobic exercise in which they expended 12 kcal/kg per week ; and 76 to combined aerobic and resistance training in which they expended 10 kcal/kg per week and engaged in resistance training twice a week . Main Outcome Change in HbA(1c ) level . Secondary outcomes included measures of anthropometry and fitness . RESULTS The study included 63.0 % women and 47.3 % nonwhite participants who were a mean ( SD ) age of 55.8 years ( 8.7 years ) with a baseline HbA(1c ) level of 7.7 % ( 1.0 % ) . Compared with the control group , the absolute mean change in HbA(1c ) in the combination training exercise group was -0.34 % ( 95 % confidence interval [ CI ] , -0.64 % to -0.03 % ; P = .03 ) . The mean changes in HbA(1c ) were not statistically significant in either the resistance training ( -0.16 % ; 95 % CI , -0.46 % to 0.15 % ; P = .32 ) or the aerobic ( -0.24 % ; 95 % CI , -0.55 % to 0.07 % ; P = .14 ) groups compared with the control group . Only the combination exercise group improved maximum oxygen consumption ( mean , 1.0 mL/kg per min ; 95 % CI , 0.5 - 1.5 , P < .05 ) compared with the control group . All exercise groups reduced waist circumference from -1.9 to -2.8 cm compared with the control group . The resistance training group lost a mean of -1.4 kg fat mass ( 95 % CI , -2.0 to -0.7 kg ; P < .05 ) and combination training group lost a mean of -1.7 ( -2.3 to -1.1 kg ; P < .05 ) compared with the control group . CONCLUSIONS Among patients with type 2 diabetes mellitus , a combination of aerobic and resistance training compared with the nonexercise control group improved HbA(1c ) levels . This was not achieved by aerobic or resistance training alone . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00458133 PROJECT Chromium is an essential nutrient involved in normal carbohydrate and lipid metabolism . It influences glucose metabolism by potentiating the action as taking part in insulin signal amplification mechanism . A placebo-controlled single blind , prospect i ve study was carried out to investigate the effect of chromium supplementation on blood glucose , HbA(1)C and lipid profile in newly onset patients with type-2 diabetes . PROCEDURE Total 40 newly onset type-2 diabetics were selected and after 1 month stabilization further r and omly divided into two groups viz . study group and placebo group . The study group received 9 g brewer 's yeast ( 42 μg Cr ) daily and the other placebo group received yeast devoid of chromium for 3 months . Subjects were instructed not to change their normal eating and living habits . Fasting blood glucose , HbA(1)C and lipid profile were analyzed at beginning and completion of the study . RESULTS Results revealed that fasting blood glucose level significantly reduced in the subjects consuming yeast supplemented with chromium ( 197.65±6.68 to 103.68±6.64 mg/dL ; p<0.001 ) . HbA(1)C values improved significantly from 9.51±0.26 % to 6.86±0.28 % ; p<0.001 indicating better glycaemic control . In experimental group total cholesterol , TG and LDL levels were also significantly reduced from 199.66±3.11 to 189.26±3.01 mg/dL ; p<0.02 , 144.94±8.31 to 126.01±8.26 ; p<0.05 and 119.19±1.71 to 99.58±1.10 ; p<0.001 respectively . CONCLUSIONS These data demonstrate beneficial effect of chromium supplementation on glycaemic control and lipid variables in subjects with newly onset type-2 diabetes Aim /hypothesisIn people with type 2 diabetes , exercise improves glucose control ( as reflected in HbA1c ) and physical fitness , but it is not clear to what extent these exercise-induced improvements are correlated with one another . We hypothesised that reductions in HbA1c would be related : ( 1 ) to increases in aerobic fitness and strength respectively in patients performing aerobic training or resistance training ; and ( 2 ) to changes in strength and aerobic fitness in patients performing aerobic and resistance training . Methods We r and omly allocated 251 type 2 diabetes patients to aerobic , resistance , or aerobic plus resistance training , or to a sedentary control group . Peak oxygen consumption ( $ $ \mathop {V}\limits^\cdot { { \text{O}}_{\text{2 peak } } } $ $ ) , workload , treadmill time and ventilatory threshold measurements from maximal treadmill exercise testing were measured at baseline and 6 months . Muscular strength was measured as the maximum weight that could be lifted eight times on the leg press , bench press and seated row exercises . Results With aerobic training , significant associations were found between changes in both $ $ \mathop {V}\limits^\cdot { { \text{O}}_{\text{2 peak } } } $ $ ( p = 0.040 ) and workload ( p = 0.022 ) , and changes in HbA1c . With combined training , improvements in $ $ \mathop {V}\limits^\cdot { { \text{O}}_{\text{2 peak } } } $ $ ( p = 0.008 ) , workload ( p = 0.034 ) and ventilatory threshold ( p = 0.003 ) were significantly associated with changes in HbA1c . Increases in strength on the seated row ( p = 0.006 ) and in mid-thigh muscle cross-sectional area ( p = 0.030 ) were significantly associated with changes in HbA1c after resistance exercise , whereas the association between increases in muscle cross-sectional area and HbA1c in participants doing aerobic plus resistance exercise ( p = 0.059 ) was of borderline significance . Conclusions /interpretationThere appears to be a link between changes in fitness and HbA1c . The improvements in cardiorespiratory fitness with aerobic training may be a better predictor of changes in HbA1c than improvements in strength Objectives Obesity is a known risk factor for type 2 diabetes ( T2D ) . We conducted a case – control study to assess the association between body mass index ( BMI ) and the risk of being diagnosed with T2D in the United States . Methods We selected adults ( ≥ 18 years old ) who were diagnosed with T2D ( defined by ICD-9-CM diagnosis codes or use of anti-diabetic medications ) between January 2004 and October 2011 ( “ cases ” ) from an electronic health records data base provided by an integrated health system in the Middle Atlantic region . Twice as many individuals enrolled in the health system without a T2D diagnosis during the study period ( “ controls ” ) were selected based on age , sex , history of cardiac comorbidities or hyperinflammatory state ( defined by C-reactive protein and erythrocyte sedimentation rate ) , and use of psychiatric or beta blocker medications . BMI was measured during one year prior to the first observed T2D diagnosis ( for cases ) or a r and omly assigned date ( for controls ) ; individuals with no BMI measure or BMI < 18.5 kg/m2 were excluded . We assessed the impact of increased BMI ( overweight : 25–29.9 kg/m2 ; Obesity Class I : 30–34.9 kg/m2 ; Obesity Class II : 35–39.9 kg/m2 ; Obesity Class III : ≥40 kg/m2 ) , relative to normal BMI ( 18.5–24.9 kg/m2 ) , on a T2D diagnosis using odds ratios ( OR ) and relative risks ( RR ) estimated from multiple logistic regression results . Results We included 12,179 cases ( mean age : 55 , 43 % male ) and 25,177 controls ( mean age : 56 , 45 % male ) . We found a positive association between BMI and the risk of a T2D diagnosis . The strength of this association increased with BMI category ( RR [ 95 % confidence interval ] : overweight , 1.5 [ 1.4–1.6 ] ; Obesity Class I , 2.5 [ 2.3–2.6 ] ; Obesity Class II , 3.6 [ 3.4–3.8 ] ; Obesity Class III , 5.1 [ 4.7–5.5 ] ) . Conclusions BMI is strongly and independently associated with the risk of being diagnosed with T2D . The incremental association of BMI category on the risk of T2D is stronger for people with a higher BMI relative to people with a lower BMI Objective Epidemiological studies have provided evidence of an association between vitamin D insufficiency and type 2 diabetes . Vitamin D levels have decreased among Inuit in Greenl and , and type 2 diabetes is increasing . We hypothesized that the decline in vitamin D could have contributed to the increase in type 2 diabetes , and therefore investigated associations between serum 25(OH)D3 as a measure of vitamin D status and glucose homeostasis and glucose intolerance in an adult Inuit population . Methods 2877 Inuit ( ≥18 years ) r and omly selected for participation in the Inuit Health in Transition study were included . Fasting- and 2hour plasma glucose and insulin , C-peptide and HbA1c were measured , and associations with serum 25(OH)D3 were analysed using linear and logistic regression . A sub sample of 330 individuals who also donated a blood sample in 1987 , were furthermore included . Results After adjustment , increasing serum 25(OH)D3 ( per 10 nmol/L ) was associated with higher fasting plasma glucose ( 0.02 mmol/L , p = 0.004 ) , 2hour plasma glucose ( 0.05 nmol/L , p = 0.002 ) and HbA1c ( 0.39 % , p<0.001 ) , and with lower beta-cell function ( -1.00 mmol/L , p<0.001 ) . Serum 25(OH)D3 was positively associated with impaired fasting glycaemia ( OR : 1.08 , p = 0.001 ) , but not with IGT or type 2 diabetes . Conclusions Our results did not support an association between low vitamin D levels and risk of type 2 diabetes . Instead , we found weak positive associations between vitamin D levels and fasting- and 2hour plasma glucose levels , HbA1c and impaired fasting glycaemia , and a negative association with beta-cell function , underlining the need for determination of the causal relationship Low-glycaemic index diets reduce glycated Hb ( HbA1c ) in patients with type 2 diabetes , but require intensive dietary support . Using a liquid meal replacement with a low glycaemic response ( GR ) may be an alternative dietary approach . In the present study , we investigated whether breakfast replacement with a low-GR liquid meal would reduce postpr and ial glycaemia and /or improve long-term glycaemia . In the present r and omised , controlled , cross-over design , twenty patients with type 2 diabetes consumed either a breakfast replacement consisting of an isoenergetic amount of Glucerna SR or a free-choice breakfast for 3 months . Postpr and ial AUC levels were measured using continuous glucose measurement at home . After the 3-month dietary period , meal profiles and oral glucose tolerance were assessed in the clinical setting . The low-GR liquid meal replacement reduced the AUC of postpr and ial glucose excursions at home compared with a free-choice control breakfast ( estimated marginal mean 141 ( 95 % CI 114 , 174 ) v. estimated marginal mean 259 ( 95 % CI 211 , 318 ) mmol × min/l ; P= 0·0002 ) . The low-GR liquid meal replacement also reduced glucose AUC levels in the clinical setting compared with an isoenergetic control breakfast ( low GR : median 97 ( interquartile range ( IQR ) 60 - 188 ) mmol × min/l ; control : median 253 ( IQR 162 - 386 ) mmol × min/l ; P < 0·001 ) . However , the 3-month low-GR liquid meal replacement did not affect fasting plasma glucose , HbA1c or lipid levels , and even slightly reduced oral glucose tolerance . In conclusion , the low-GR liquid meal replacement is a potential dietary approach to reduce postpr and ial glycaemia in patients with type 2 diabetes . However , clinical trials into the effects of replacing multiple meals on long-term glycaemia in poorly controlled patients are required before a low-GR liquid meal replacement can be adopted as a dietary approach to the treatment of type 2 diabetes Diabetes complications are the main reasons behind morbidity and mortality preventable by healthy diet and physical activity . There are few studies about the effect of aerobic exercises on insulin resistance in human . Also various training protocol s are associated with different results . Since approaches to decrease insulin resistance may be followed by more effectiveness treatment , this study assessed the effect of aerobic exercise on insulin resistance in Type 2 Diabetes Mellitus . In this r and omized clinical trial , 53 Type 2 diabetic women were r and omly divided into two groups as exercise ( n=27 ) and control ( n=26 ) . The exercise protocol included warm-up by stretching and flexibility exercises for 10 m , followed by walking for 30 m with maximum intensity 60 % increase in heart rate and then stretching in the seated position for 10 m , 3 times a week for 8 weeks . Resistance to insulin was assessed using Homeostasis Model Assessment of Insulin Resistance ( HOMA-IR ) . Significant differences have been observed in insulin resistance , fasting glucose and plasma insulin between the groups after 8 weeks . There were significant differences in waist and hip circumference , BMI , plasma insulin and insulin resistance within the groups over time . In addition , the changes in waist and hip circumference , FBS , plasma insulin and insulin resistance had significant interaction with the time between the groups . The current exercise protocol has been effective in lowering plasma glucose ( p = 0.05 ) , insulin levels ( p = 0.000 ) and insulin resistance ( p = 0.02 ) . It seems that aerobic exercises training promote the effectiveness of medical treatment in Type 2 Diabetes Mellitus The aim of this study was to provide reliable information on dyslipidaemias , to estimate the trend of the prevalence of dyslipidaemias and other selected cardiovascular disease ( CVD ) risk factors at population level , and to evaluate the risk of all-cause and CVD mortality in relation to presence of mixed dyslipidaemias and other CVD risk factors . Methods Data from the five surveys ( 1983–2008 ) are presented . A r and om sample of 9,209 subjects aged 45–64 was selected for statistical analysis . During follow-up there were 1653 death cases from any cause , 864 deaths from CVD . Estimates of hazard ratios ( HR ) and 95 % confidence intervals ( CI ) were based on the multivariate Cox proportional hazards regression for all-cause mortality and CVD mortality . Results During 25 year period the prevalence of normal total cholesterol level ( < 5.2 mmol/L ) significantly increased only in women ; triglycerides and high density lipoprotein ( HDL ) cholesterol did not change in men and women . Findings in our longitudinal study showed that in men and women mixed dyslipidaemias ( HDL cholesterol < 1.03 mmol/L plus triglycerides ≥1.70 mmol/L ) significantly increased the risk for all-cause and CVD mortality ( respectively in men HR = 1.30 ; HR = 1.15 , in women HR = 1.83 ; HR = 2.13 ) . These mixed dyslipidaemia combinations combination with the other risk factors such as arterial hypertension , high fasting glucose level increased all-cause and CVD mortality risk in men and women ; while , these mixed dyslipidaemias plus smoking increased all-cause and CVD mortality risk only in men compared to never smokers without these dyslipidaemias ( respectively HR = 1.89 ; HR = 1.92 ) ; and these dyslipidaemias plus obesity increased all-cause and CVD mortality risk in women ( respectively HR = 2.25 ; HR = 2.39 ) and CVD mortality risk in men ( HR = 1.72 ) , as compared to responders without obesity and these dyslipidaemias . Conclusion Mixed dyslipidaemias ( reduced HDL cholesterol plus elevated triglycerides ) significantly increased the risk for all-cause and CVD mortality in this Lithuanian population aged 45–64 years The aim of the present study was to determine the effects of a 4-week exercise training intervention on blood glucose , insulin sensitivity , BMI ( body mass index ) and cardiorespiratory fitness in patients with Type 2 diabetes , and to identify and establish criteria for patients who are more likely to improve their blood glucose from short-term exercise training . A r and omized , controlled trial of exercise training , comprising two supervised and one non-supervised sessions of individualized cardiorespiratory and resistance exercise per week , was performed in 132 healthy patients with Type 2 diabetes ( exercise training group , n=68 ) , with the aim of accumulating a minimum of 150 min of moderate-intensity exercise for 4 weeks . BMI , waist circumference , blood pressure , blood lipid profile , blood glucose , insulin , insulin sensitivity [ calculated by HOMA(IR ) ( homoeostasis model assessment of insulin resistance ) and QUICKI ( quantitative insulin check index ) ] , beta-cell function ( calculated by HOMA(beta-Cell ) ) , HbA(1c ) ( glycated haemoglobin ) and VO(2max ) ( maximal oxygen consumption ) were measured at baseline and at 4 weeks . The exercise training group had significant improvements in VO(2max ) , BMI and triacylglycerols ( triglycerides ) . There were no significant changes in blood glucose , HOMA(IR ) , QUICKI or HOMA(beta-Cell ) . Decreases in blood glucose were significantly predicted by baseline blood glucose and HbA(1c ) , with these variables accounting for 15.9 % of the change in blood glucose ( P<0.001 ) . ROC ( receiver operator characteristic ) curve analysis revealed that patients with a blood glucose > 8.85 mmol/l ( sensitivity=73 % , specificity=78 % ) and HbA(1c ) > 7.15 % ( sensitivity=79 % , specificity=60 % ) were more likely to achieve a clinical ly significant decrease in blood glucose . In conclusion , in apparently healthy patients with Type 2 diabetes , a 4-week exercise intervention improved cardiorespiratory fitness , BMI and triacylglycerols . Elevated blood glucose and HbA(1c ) predicted improvements in blood glucose Background While current recommendations on exercise type and volume have strong experimental bases , there is no clear evidence from large-sized studies indicating whether increasing training intensity provides additional benefits to subjects with type 2 diabetes . Objective To compare the effects of moderate-to-high intensity ( HI ) versus low-to-moderate intensity ( LI ) training of equal energy cost , i.e. exercise volume , on modifiable cardiovascular risk factors . Design Pre-specified sub- analysis of the Italian Diabetes and Exercise Study ( IDES ) , a r and omized multicenter prospect i ve trial comparing a supervised exercise intervention with st and ard care for 12 months ( 2005–2006 ) . Setting Twenty-two outpatient diabetes clinics across Italy . Patients Sedentary patients with type 2 diabetes assigned to twice-a-week supervised progressive aerobic and resistance training plus exercise counseling ( n = 303 ) . Interventions Subjects were r and omized by center to LI ( n = 142 , 136 completed ) or HI ( n = 161 , 152 completed ) progressive aerobic and resistance training , i.e. at 55 % or 70 % of predicted maximal oxygen consumption and at 60 % or 80 % of predicted 1-Repetition Maximum , respectively , of equal volume . Main Outcome Measure(s ) Hemoglobin ( Hb ) A1c and other cardiovascular risk factors ; 10-year coronary heart disease ( CHD ) risk scores . Results Volume of physical activity , both supervised and non-supervised , was similar in LI and HI participants . Compared with LI training , HI training produced only clinical ly marginal , though statistically significant , improvements in HbA1c ( mean difference −0.17 % [ 95 % confidence interval −0.44,0.10 ] , P = 0.03 ) , triglycerides ( −0.12 mmol/l [ −0.34,0.10 ] , P = 0.02 ) and total cholesterol ( −0.24 mmol/l [ −0.46 , −0.01 ] , P = 0.04 ) , but not in other risk factors and CHD risk scores . However , intensity was not an independent predictor of reduction of any of these parameters . Adverse event rate was similar in HI and LI subjects . Conclusions Data from the large IDES cohort indicate that , in low-fitness individuals such as sedentary subjects with type 2 diabetes , increasing exercise intensity is not harmful , but does not provide additional benefits on cardiovascular risk factors . Trial Registration www . IS RCT N.org IS RCT N-04252749 Background Pedometer-based physical activity programs have been typically delivered in a group format by a behavioral expert . An alternative strategy that builds on existing interactions is delivery through individual consultation by a general practitioner ( GP ) . These two delivery strategies have not been directly compared . Purpose To compare effectiveness of a 12-week physical activity ( PA ) intervention for type 2 diabetes patients delivered by a trained GP via an individual consultation or as group delivery by a behavioral expert . MethodS ixty-seven primary care participants ( mean age = 67.4 years , 70 % male ) from three Belgian general practice s were r and omized into three different treatment arms : ( 1 ) individual consultation ( n = 22 ) with three PA contacts with the patient 's GP ; ( 2 ) group counseling ( n = 21 ) with three PA group sessions delivered by a behavioral expert ; and ( 3 ) a control arm ( n = 24 ) receiving no intervention . Participant inclusion criteria were ≤80 years ; 25–35 kg/m² ; ≤12 % HbA1c and reporting no PA limitations . Outcome measures were pedometer-determined steps/day , self-reported PA , and health parameters ( weight , body mass index , waist circumference , total cholesterol , fasting glucose , and HbA1c ) . Results Group counseling participants increased 1,706 steps/day over baseline significantly ( p ≤ 0.05 ) more than other treatment arms . Moreover , they increased their self-reported PA ( + 82 min/day ) , while control arm participants showed a decrease in PA ( p ≤ 0.05 ) . Participants of the individual consultation had a decrease in waist circumference ( −1.4 cm ) and HbA1c ( −0.32 % ) and a lower increase in total cholesterol ( + 7.2 mg/dl ) compared to the other treatment arms ( all p ≤ 0.05 ) . Conclusion Group counseling in type 2 diabetes patients improved PA , whereas individual consultations had an impact on some health outcomes on the short-term Background : A prospect i ve , nonblinded and nonr and omized controlled trial was conducted to test the hypothesis that vitamin D supplementation would improve glycemic control in patients with type 1 diabetes mellitus who have vitamin D deficiency . Patients and Methods :0 Eighty patients with type 1 diabetes mellitus who had 25-hydroxyvitamin D levels less than 50 nmol/L were assigned to receive 4000 IU of vitamin D3 . Calcium supplements were provided to ensure a total calcium intake of 1200 mg/d . Glycosylated hemoglobin and 25-hydroxyvitamin D levels were measured at baseline and at 12 weeks . Results : There was a significant difference in mean ( SD ) glycosylated hemoglobin level ( % ) between the groups that achieved 25-hydroxyvitamin D levels of < 35.4 nmol/L , 35.4 - 51 nmol/L and > 51 nmol/L at 12 weeks ( P=.02 ) . There was a significant difference in glycosylated hemoglobin change from baseline between the groups that achieved 25-hydroxyvitamin D levels of < 35.4 nmol/L , 35.4 - 51 nmol/L and > 51 nmol/L at 12 weeks ( P=.04 ) . There was a significant difference in 25-hydroxyvitamin D level between the groups that achieved glycosylated hemoglobin levels of < 7.8 , 7.8 - 9.9 and > 9.9 at 12 weeks ( P=.001 ) . Patients were more likely to achieve lower glycosylated hemoglobin levels at 12 weeks if they had higher 25-hydroxyvitamin D levels at 12 weeks ( r=-0.4 , P=.001 ) . Conclusions : There was an observed effect of vitamin D supplementation on glycemic control in vitamin D-replete , type 1 diabetes mellitus patients . Further studies are needed to determine if these findings are applicable OBJECTIVE To examine the effect of supervised exercise on traditional and nontraditional cardiovascular risk factors in sedentary , overweight/obese insulin-treated subjects with type 2 diabetes from the Italian Diabetes Exercise Study ( IDES ) . RESEARCH DESIGN AND METHODS The study r and omized 73 insulin-treated patients to twice weekly supervised aerobic and resistance training plus structured exercise counseling ( EXE ) or to counseling alone ( CON ) for 12 months . Clinical and laboratory parameters were assessed at baseline and at the end of the study . RESULTS The volume of physical activity was significantly higher in the EXE versus the CON group . Values for hemoglobin A1c , BMI , waist circumference , high-sensitivity C-reactive protein , blood pressure , LDL cholesterol , and the coronary heart disease risk score were significantly reduced only in the EXE group . No major adverse events were observed . CONCLUSIONS In insulin-treated subjects with type 2 diabetes , supervised exercise is safe and effective in improving glycemic control and markers of adiposity and inflammation , thus counterbalancing the adverse effects of insulin on these parameters Tomatoes are a rich source of lycopene , β-carotene , potassium , vitamin C , flavonoids , folate and vitamin E that may provide protection against the development of type 2 diabetic patients , so the present study was undertaken to evaluate the effects of tomato intake on serum glucose , homocysteine , apolipoprotein ( apo ) B , apoA-I and blood pressure in type 2 diabetic patients . In a quasi-experimental study , 32 type 2 diabetes patients received 200 g raw tomato daily for 8 weeks . Serum glucose enzymatically , apoB and apoA-I immunoturbidometrically and homocysteine by high-performance liquid chromatography were measured at the beginning and end of 8 weeks . There were significant decreases in systolic and diastolic blood pressure and also a significant increase in apoA-I at the end of study compared with initial values ( P = 0.0001 , P = 0.0001 and P = 0.013 , respectively ) . In conclusion , 200 g raw tomato per day had a favored effect on blood pressure and apoA-I so it might be beneficial for reducing cardiovascular risk associated with type 2 diabetes AIM The effects of exercise intervention and to assess its long-term efficacy in preventing subsequent cardiovascular events in patients with type 2 diabetes were little known on r and omized controlled trial . METHODS Thirty-eight type 2 diabetic patients ( 21 men and 17 women ) were assigned to either the exercise group ( n=21 ) or the control group without exercise training ( n=17 ) by simple r and omization . The exercise training group was scheduled for aerobic and resistance exercise programs for 3 months . After the 3-month , we investigated endothelial function , insulin resistance , adipocytokines and inflammatory markers . The endothelial function was evaluated by examining a flow-mediated endothelium-dependent vasodilatation ( FMD ) . Furthermore , we followed the incidence of cardiovascular events for 24 months . RESULTS After 3-month , HbA1C was decreased significantly in both groups . FMD was increased from 7.3+/-4.7 % to 10.9+/-6.2 % only in the exercise group ( p<0.05 ) . Long-term follow-up data showed that the control group developed cardiovascular events more frequently than did the exercise group ( p<0.05 ) . CONCLUSIONS Exercise improves endothelial dysfunction independently of glycemic control and insulin sensitivity in patients with type 2 diabetes . The beneficial effects of 3-month exercise to reduce cardiovascular events persist for 24 months Dietary therapy is the mainstay of treatment for diabetes . This study examined the effect of a low glycemic index ( GI ) multi-nutrient supplement , consumed in place of breakfast , on glycemic control in patients with type 2 diabetes mellitus ( T2DM ) . A total of 71 participants were r and omized at a 2:1 ratio into either a breakfast replacement group or a normal breakfast group for a 12-week interventional study . The primary outcome measure was change in hemoglobin A1c ( HbA1c ) . Nutrition status and somatometry were studied as secondary outcomes . The breakfast replacement group displayed a −0.2 % absolute reduction in HbA1c ( 95 % CI ( confidence interval ) , −0.38 % to −0.07 % , p = 0.004 ) , while the HbA1c of the control group increased 0.3 % ( 95 % CI , 0.1 % to 0.5 % , p = 0.005 ) . The baseline Mini Nutritional Assessment score for both groups was 26.0 and no significant changes occurred following intervention . However , there was a statistically significant difference in body mass index between the treatment and control groups ( p = 0.032 ) due to the weight gain in the control group ( increased 0.5 kg , 95 % CI was 0.2 to 0.9 , p = 0.007 ) . These data suggest that breakfast replacement with a low GI multi-nutrient supplement can improve glycemic and weight control in T2DM BACKGROUND Low serum 25-hydroxyvitamin D [ 25(OH)D ] concentrations have been associated with insulin resistance , the metabolic syndrome , and type 2 diabetes . Because many non-Western immigrants in the Netherl and s are vitamin D deficient , obese , and at high risk of diabetes , vitamin D supplementation may contribute to prevent diabetes and insulin resistance . OBJECTIVE We examined the effect of vitamin D supplementation on insulin sensitivity and β cell function in overweight , vitamin D-deficient , non-Western immigrants at high risk of diabetes . DESIGN The study was a 16-wk , r and omized , placebo-controlled trial . A total of 130 non-Western immigrants with prediabetes ( fasting glucose concentration > 5.5 mmol/L or r and om glucose concentration from 7.8 to 11.1 mmol/L ) and vitamin D deficiency ( serum 25[OH]D concentration < 50 nmol/L ) were r and omly assigned after stratification by sex to receive either cholecalciferol ( 1200 IU/d ) or a placebo for 16 wk . All participants received 500 mg Ca/d as calcium carbonate . The primary outcome was the difference in the area under the curve of insulin and glucose after a 75-g oral-glucose-tolerance test after 4 mo of treatment . Secondary outcomes were insulin-sensitivity variables , β cell-function variables , and metabolic syndrome . RESULTS Mean serum 25(OH)D concentrations increased significantly in the vitamin D compared with placebo groups . After 4 mo of therapy , the mean between-group difference was 38 nmol/L ( 95 % CI : 32.1 , 43.9 nmol/L ; P < 0.001 ) . There was no significant effect on insulin sensitivity and β cell function . In a post hoc analysis , when patients with diabetes at baseline were excluded , a significant increase in the insulinogenic index was observed in participants who obtained a 25(OH)D concentration ≥60 nmol/L ( P = 0.040 ) . CONCLUSIONS Vitamin D supplementation in non-Western vitamin D-deficient immigrants with prediabetes did not improve insulin sensitivity or β cell function or change the incidence of metabolic syndrome . However , after the exclusion of diabetic subjects , an improvement in the insulinogenic index was observed in participants who obtained a 25(OH)D concentration ≥60 nmol/L. This trial was registered at trialregister.nl as NTR1827 BACKGROUND & AIMS Vitamin D supplementation has the potential to alleviate the cardiovascular damage in diabetic patients . The present study was design ed to evaluate long term impact of high doses of vitamin D on arterial properties , glucose homeostasis , adiponectin and leptin in patients with type 2 diabetes mellitus . METHODS AND RESULTS In r and omized , placebo-controlled study 47 diabetic patients were assigned into two groups : Group 1 received oral daily supplementation with vitamin D at a dose of 1000 U/day for 12 months . Group 2 received matching placebo capsules . Blood sampling for metabolic parameters , including fasting glucose , lipid profile , HbA1C , insulin , hs-CRP , 25 OH Vit D , adiponectin and leptin was performed at baseline and at the end of the study . Insulin resistance was assessed by homeostasis model assessment ( HOMA-IR ) . Central aortic augmentation index ( AI ) was evaluated using SphygmoCor . RESULTS The two groups were similar at baseline in terms of hemodynamic parameters . After 12 months , AI decreased significantly during the treatment period in patients received vitamin D ( p < 0.0001 ) and did not change in placebo group . Glucose homeostasis parameters , leptin as well as leptin adiponectin ratio did not change in both groups . 25 OH Vit D level significantly increased ( p = 0.022 ) and circulating adiponectin marginally increased ( p = 0.065 ) during 12 month treatment period in active treatment and did not change in placebo group . CONCLUSIONS High doses of vitamin D supplementation in diabetic patients was associated with significant decrease in AI during one year treatment . This beneficial vascular effect was not associated with improvement in glucose homeostasis parameters The comparative effects of aerobic and resistance exercise on triglyceride-rich lipoproteins including remnant lipoproteins are controversial . This study examined exercise effect on remnant-like lipoprotein particle cholesterol ( RLP-C ) in type 2 diabetes . Participants were r and omized to control ( Control ) , aerobic ( Aerobic ) , resistance ( Resistance ) , or both ( Combined ) exercise groups . Baseline and 6-month fasting RLP-C and apolipoprotein B48 concentrations were measured . Data analysis was on an intention-to-treat basis . At 6 months , RLP-C was lower in all groups ; ΔRLP-C mg/dl , ( 95 % confidence interval ) , Control -3.91 , ( -6.21 to -1.6 ) , p=0.001 ; Aerobic -3.89 , ( -6.41 to -1.36 ) , p=0.003 , Resistance -7.52 , ( -9.89 to -5.15 ) , p=0.0001 , Combined -7.50 , ( -9.87 to -5.13 ) , p=0.0001 . Total triglycerides were significantly lower in Resistance and Combined groups only ; -17.7mg/dl ( -32.8 to -2.7 ) , p=0.02 and -27.5 ( -42.5 to -11.5 ) , p=0.001 , respectively . Inter-group comparisons showed no difference in RLP-C change between Aerobic and Control and a significant difference in RLP-C change only where groups incorporating resistance exercise were compared with those without . There was no significant difference in RLP-C change between Resistance and Combined . Inter-group comparisons of total triglycerides change were significant only between Combined and Control . Changes in apolipoprotein B48 were not significant in inter-group comparisons . In conclusion , our data indicate that resistance exercise training , not aerobic , lowers RLP-C in type 2 diabetes . This effect was not revealed by changes in total triglycerides and apolipoprotein B48 . The discordance between changes in RLP-C and apolipoprotein B48 in response to resistance exercise may indicate ( a ) a decrease in VLDL remnant and not chylomicron remnant particle number and /or ( b ) a depletion of cholesterol in chylomicron and /or VLDL remnants PURPOSE Type 2 diabetes is associated with increased risk of cardiovascular disease and elevated C-reactive protein ( CRP ) levels . Aerobic exercise training has been shown to improve CRP ; however , there are limited data evaluating the effect of other exercise training modalities ( aerobic , resistance , or combination training ) in individuals with type 2 diabetes . METHODS Participants ( n = 204 ) were r and omized to an aerobic exercise ( aerobic ) , resistance exercise ( resistance ) , or a combination of both ( combination ) for 9 months . CRP was evaluated at baseline and at follow-up . RESULTS Baseline CRP was correlated with fat mass , waist circumference , body mass index , and VO(2peak ) ̇(P < 0.05 ) . CRP was not reduced after aerobic ( 0.16 mg·L(-1 ) , 95 % confidence interval ( CI ) = -1.0 to 1.3 mg·L(-1 ) ) , resistance ( -0.03 mg·L(-1 ) , 95 % CI = -1.1 to 1.0 mg·L(-1 ) ) , or combination ( -0.49 mg·L(-1 ) , 95 % CI = -1.5 to 0.6 mg·L(-1 ) ) training compared to control ( 0.35 mg·L(-1 ) , 95 % CI = -1.0 to 1.7 mg·L(-1 ) ) . Changes in fasting glucose ( r = 0.20 , P = 0.009 ) , glycated hemoglobin ( HbA1c ) ( r = 0.21 , P = 0.005 ) , and fat mass ( r = 0.19 , P = 0.016 ) were associated with reductions in CRP but not with change in fitness or weight ( P > 0.05 ) . There were significant trends observed for CRP among tertiles of change in HbA1c ( P = 0.009 ) and body fat ( P = 0.040 ) . CONCLUSIONS Aerobic , resistance , or a combination of both did not reduce CRP levels in individuals with type 2 diabetes . However , exercise-related improvements in HbA1c , fasting glucose , and fat mass were associated with reductions in CRP Cohort studies are equivocal regarding a relationship between regular nut consumption and reduced risk of type 2 diabetes mellitus . Although acute trials show reductions in postpr and ial glycemia in healthy individuals ingesting 60 to 90 g almonds , trials have not been conducted using a single serving of almonds ( 28 g ) in individuals with type 2 diabetes mellitus . This r and omized crossover trial examined the impact of one serving of almonds at mealtime on postpr and ial glycemia , insulinemia , and plasma glucagon-like peptide-1 in healthy individuals and individuals with type 2 diabetes mellitus . On 2 occasions separated by at least 1 week , 19 adults ( including 7 adults with type 2 diabetes mellitus ) consumed a st and ardized evening meal and fasted overnight before ingesting the test meal ( bagel , juice , and butter ) with or without almonds . A small pilot study ( 6 - 7 subjects per group ) was also conducted to observe whether chronic almond ingestion ( 1 serving 5 d/wk for 12 weeks ) lowered hemoglobin A(1c ) in individuals with type 2 diabetes mellitus . A st and ard serving of almonds reduced postpr and ial glycemia significantly in participants with diabetes ( -30 % , P = .043 ) but did not influence glycemia in participants without diabetes ( -7 % , P = .638 ) . Insulinemia and glucagon-like peptide-1 at 30 minutes postmeal were not impacted by almond ingestion for either group . In the pilot study , regular almond ingestion for 12 weeks reduced hemoglobin A(1c ) by 4 % ( P = .045 for interaction ) but did not influence fasting glucose concentrations . These data show that modest almond consumption favorably improves both short-term and long-term markers of glucose control in individuals with uncomplicated type 2 diabetes mellitus BACKGROUND & AIMS To investigate the relationship between levels of 25-hydroxyvitamin D and the incidence of type 2 diabetes in a Spanish population . METHODS We undertook a population -based prospect i ve study in a population from southern Spain . The first phase of the study ( 1996 - 1998 ) included 1226 individuals . Of this original cohort , 988 persons were reassessed in 2002 - 2004 and 961 in 2005 - 2007 . Measurements were made of 25-hydroxyvitamin D and intact parathyroid hormone in 2002 - 2004 and an oral glucose tolerance test was done in three time points . RESULTS The incidence of diabetes in subjects with 25-hydroxyvitamin D levels ≤ 18.5 ng/mL ( percentile 25 ) was 12.4 % vs 4.7 % in subjects with levels > 18.5 ng/mL. The likelihood of having diabetes during the four years of follow-up was significantly lower in the subjects with higher levels of 25-hydroxyvitamin D [ OR = 0.17 ( 0.05 - 0.61 ) ] . None of the subjects with levels higher than 30 ng/mL developed diabetes . CONCLUSION In this prospect i ve study , we found a significant inverse association between serum 25-hydroxyvitamin D levels and the risk for type 2 diabetes in a population from the south of Spain OBJECTIVE This double-blind , r and omized , controlled trial evaluated whether 12 months of high-dose vitamin D2 supplementation improved insulin sensitivity and secretion and glycemic status . METHODS African-American males ( AAM ) with prediabetes ( glycosylated hemoglobin [ A1C ] 5.7 - 6.4 % ) , hypovitaminosis D ( 25-hydroxyvitamin D [ 25OHD ] 5 - 29 ng/mL ) , and prevalent medical problems were supplemented with vitamin D3 ( 400 IU/day ) and then r and omized to weekly placebo or vitamin D2 ( 50,000 IU ) . The primary outcome was the change in oral glucose insulin sensitivity ( OGIS , from an oral glucose tolerance test [ OGTT ] ) after 12 months of treatment . Secondary outcomes included other glycemic indices , A1C , and incident diabetes . RESULTS Baseline characteristics were similar in vitamin D-supplemented ( n = 87 ) and placebo ( n = 86 ) subjects completing the trial with average concentrations 14.4 ng/mL , 362 mL × min(-1 ) × m(-2 ) , and 6.1 % for 25OHD , OGIS and A1C , respectively . After 12 months , the vitamin D-supplemented group had a change in serum 25OHD + 35 versus + 6 ng/mL for placebo , P<.001 ; OGIS + 7.8 versus -16.0 mL × min(-1 ) × m(-2 ) for placebo , P = .026 ; and A1C -0.01 versus + 0.01 % for placebo , P = .66 . Ten percent of subjects in both groups progressed to diabetes . A posthoc analysis of participants with baseline impaired fasting glucose ( IFG ) showed that more subjects in the vitamin D subgroup ( 31.6 % ) than placebo ( 8.3 % ) returned to normal glucose tolerance , but the difference did not reach significance ( P = .13 ) . CONCLUSION The trial does not provide evidence that 12 months of high-dose D2 repletion improves clinical ly relevant glycemic outcomes in subjects with prediabetes and hypovitaminosis D ( NCT01375660 ) |
12,244 | 23,884,616 | The overall efficacy of specific therapies for BPD is promising . | INTRODUCTION Over the past 20 years , several studies have established the efficacy of different forms of psychotherapy for borderline personality disorders ( BPD ) .
However , existing research has used a wide range of outcomes measures which makes it difficult to quantify data and to compare interventions .
This review has been design ed to analyse the evidence from r and omized controlled trials ( RCT ) through a qualitative approach . | BACKGROUND A r and omized clinical trial was conducted to evaluate whether the superior performance of dialectical behavior therapy ( DBT ) , a psychosocial treatment for borderline personality disorder , compared with treatment-as-usual in the community , is maintained during a 1-year posttreatment follow-up . METHODS We analyzed 39 women who met criteria for borderline personality disorder , defined by Gunderson 's Diagnostic Interview for Borderline Personality Disorder and DSM-III-R criteria , and who had a history of parasuicidal behavior . Subjects were r and omly assigned either to 1 year of DBT , a cognitive behavioral therapy that combines individual psychotherapy with group behavioral skills training , or to treatment-as-usual , which may or may not have included individual psychotherapy . Efficacy was measured on parasuicidal behavior ( Parasuicide History Interview ) , psychiatric inpatient days ( Treatment History Interview ) , anger ( State-Trait Anger Scale ) , global functioning ( Global Assessment Scale ) , and social adjustment ( Social Adjustment Scale -- Interview and Social Adjustment Scale -- Self-Report ) . Subjects were assessed at 6 and 12 months into the follow-up year . RESULTS Comparison of the two conditions revealed that throughout the follow-up year , DBT subjects had significantly higher Global Assessment Scale scores . During the initial 6 months of the follow-up , DBT subjects had significantly less parasuicidal behavior , less anger , and better self-reported social adjustment . During the final 6 months , DBT subjects had significantly fewer psychiatric inpatient days and better interviewer-rated social adjustment . CONCLUSION In general , the superiority of DBT over treatment-as-usual , found in previous studies at the completion of 1 year of treatment , was retained during a 1-year follow-up Dialectical behaviour therapy ( DBT ) has proven to be an effective treatment in borderline personality disorder ( BPD ) . However , the effectiveness in BPD of DBT skills training ( DBT-ST ) alone is not known . This study aim ed at comparing the efficacy of DBT-ST and st and ard group therapy ( SGT ) for out patients with BPD . Sixty patients meeting the DSM-IV diagnostic criteria for BPD , as assessed by two semi-structured diagnostic interviews , were included in a 3-month , single-blind r and omised controlled trial . A total of 13 weekly group psychotherapy sessions of 120 min of either SGT or DBT-ST were conducted . Assessment s were carried out every 2 weeks by two blinded evaluators . Observer-rater , self-report scales and behavioural reports were used as outcome measures . DBT-ST was associated with lower dropout rates , 34.5 % compared to 63.4 % with SGT . It was superior to SGT in improving several mood and emotion areas , such as : depression , anxiety , irritability , anger and affect instability . A reduction in general psychiatric symptoms was also observed . Three-months weekly DBT-ST proved useful . This therapy was associated with greater clinical improvements and lower dropout rates than SGT . DBT-ST seems to play a role in the overall improvement of BPD seen with st and ard DBT intervention . It allows straightforward implementation in a wide range of mental health setting s and provides the additional advantage that it is cost effective OBJECTIVE The aim of this article is to examine whether st and ard Dialectical Behavior Therapy ( DBT ) ( 1 ) can be successfully implemented in a mixed population of borderline patients with or without comorbid substance abuse ( SA ) , ( 2 ) is equally efficacious in reducing borderline symptomatology among those with and those without comorbid SA , and ( 3 ) is efficacious in reducing the severity of the substance use problems . METHOD The implementation of DBT is examined qualitatively . The impact of comorbid SA on its efficacy , as well as on its efficacy in terms of reducing SA , is investigated in a r and omized clinical trial comparing DBT with treatment-as-usual ( TAU ) in 58 female borderline patients with ( n = 31 ) and without ( n = 27 ) SA . RESULTS St and ard DBT can be applied in a group of borderline patients with and without comorbid SA . Major implementation problems did not occur . DBT result ed in greater reductions of severe borderline symptoms than TAU , and this effect was not modified by the presence of comorbid SA . St and ard DBT , as it was delivered in our study , however , had no effect on SA problems . CONCLUSIONS St and ard DBT can be effectively applied with borderline patients with comorbid SA problems , as well as those without . St and ard DBT , however , is not more efficacious than TAU in reducing substance use problems . We propose that , rather than developing separate treatment programs for dual diagnosis patients , DBT should be " multitargeted . " This means that therapists ought to be trained in addressing a range of severe manifestations of personality pathology in the impulse control spectrum , including suicidal and self-damaging behaviors , binge eating , and SA This study tests the effectiveness of adding an eight-month , thirty-session schema-focused therapy ( SFT ) group to treatment-as-usual ( TAU ) individual psychotherapy for borderline personality disorder ( BPD ) . Patients ( N=32 ) were r and omly assigned to SFT-TAU and TAU alone . Dropout was 0 % SFT , 25 % TAU . Significant reductions in BPD symptoms and global severity of psychiatric symptoms , and improved global functioning with large treatment effect sizes were found in the SFT-TAU group . At the end of treatment , 94 % of SFT-TAU compared to 16 % of TAU no longer met BPD diagnosis criteria ( p<.001 ) . This study supports group SFT as an effective treatment for BPD that leads to recovery and improved overall functioning Motive-oriented therapeutic relationship ( MOTR , also called complementary therapeutic relationship ) was postulated to be a particularly helpful therapeutic ingredient in the early-phase treatment of patients with personality disorders , in particular borderline personality disorder ( BPD ) . The present pilot study of r and omized controlled trial using an add-on design aims to investigate the effects of MOTR in early-phase treatment ( up to session 10 ) , with BPD patients on therapeutic alliance , session impact , and outcome . In total , N = 25 patients participated in the study . BPD patients were r and omly allocated to a manual-based investigation process in 10 sessions or to the same investigation process infused with MOTR . Adherence ratings were performed and yielded satisfactory results . The results suggested a specific effectiveness of MOTR on the interpersonal problem area , on the quality of the therapeutic alliance and the quality of the therapeutic relationship , as rated by the patient . These results may have important clinical implication s for the early-phase treatment of patients presenting with BPD OBJECTIVE This study aim ed to evaluate the success of implementing outpatient schema focused therapy ( ST ) for borderline patients in regular mental healthcare and to determine the added value of therapist telephone availability outside office hours in case of crisis ( TTA ) . METHODS To enhance the implementation , the following adaptations regarding the original ST protocol were applied : a reduction in the frequency and duration of the therapy ; training therapists of eight regular healthcare centers in ST with a structured and piloted program supported by a set of films ( DVDs ) with examples of ST techniques ; training and supervision given by Dutch experts . Telephone availability outside office hours was r and omly allocated to 50 % of the therapists of each treatment center . Patient 's outcome measures were assessed with a semi-structured interview and self-report measures on BPD , quality of life , general psychopathology and an ST question naire , before , during and after treatment . RESULTS Data on 62 DSM-IV defined BPD patients were available . Intention-to-treat analyses showed that after 1.5 years of ST 42 % of the patients had recovered from BPD . No added value of therapist telephone availability ( TTA ) was found on the BPDSI score nor on any other measure after 1.5 years of ST . CONCLUSIONS ST for BPD can be successfully implemented in regular mental healthcare . Treatment results and dropout were comparable to a previous clinical trail . No additional effect of extra crisis support with TTA outside office hours ST was found BACKGROUND Transference-focused psychotherapy is a manualised treatment for borderline personality disorder . AIMS To compare transference-focused psychotherapy with treatment by experienced community psychotherapists . METHOD In a r and omised controlled trial ( NCT00714311 ) 104 female out- patients were treated for 1 year with either transference-focused psychotherapy or by an experienced community psychotherapist . RESULTS Significantly fewer participants dropped out of the transference-focused psychotherapy group ( 38.5 % v. 67.3 % ) and also significantly fewer attempted suicide ( d = 0.8 , P = 0.009 ) . Transference-focused psychotherapy was significantly superior in the domains of borderline symptomatology ( d = 1.6 , P = 0.001 ) , psychosocial functioning ( d = 1.0 , P = 0.002 ) , personality organisation ( d = 1.0 , P = 0.001 ) and psychiatric in-patient admissions ( d = 0.5 , P = 0.001 ) . Both groups improved significantly in the domains of depression and anxiety and the transference-focused psychotherapy group in general psychopathology , all without significant group differences ( d = 0.3 - 0.5 ) . Self-harming behaviour did not change in either group . CONCLUSIONS Transference-focused psychotherapy is more efficacious than treatment by experienced community psychotherapists in the domains of borderline symptomatology , psychosocial functioning , and personality organisation . Moreover , there is preliminary evidence for a superiority in the reduction of suicidality and need for psychiatric in-patient treatment Background Structured psychotherapy is recommended as the preferred treatment of personality disorders . A substantial group of patients , however , has no access to these therapies or does not benefit . For those patients who have no ( longer ) access to psychotherapy a Collaborative Care Program ( CCP ) is developed . Collaborative Care originated in somatic health care to increase shared decision making and to enhance self management skills of chronic patients . Nurses have a prominent position in CCP 's as they are responsible for optimal continuity and coordination of care . The aim of the CCP is to improve quality of life and self management skills , and reduce destructive behaviour and other manifestations of the personality disorder . Methods / design Quantitative and qualitative data are combined in a comparative multiple case study . This makes it possible to test the feasibility of the CCP , and also provides insight into the preliminary outcomes of CCP . Two treatment conditions will be compared , one in which the CCP is provided , the other in which Care as Usual is offered . In both conditions 16 patients will be included . The perspectives of patients , their informal carers and nurses are integrated in this study . Data ( question naires , documents , and interviews ) will be collected among these three groups of participants . The process of treatment and care within both research conditions is described with qualitative research methods . Additional quantitative data provide insight in the preliminary results of the CCP compared to CAU . With a stepped analysis plan the ' black box ' of the application of the program will be revealed in order to underst and which characteristics and influencing factors are indicative for positive or negative outcomes . Discussion The present study is , as to the best of our knowledge , the first to examine Collaborative Care for patients with severe personality disorders receiving outpatient mental health care . With the chosen design we want to examine how and which elements of the CC Program could contribute to a better quality of life for the patients .Trial registration Netherl and s Trial Register ( NTR ) : A r and omized controlled trial was conducted to determine whether a manual-based psychodynamic treatment , labeled dynamic deconstructive psychotherapy ( DDP ) , would be feasible and effective for individuals with co-occurring borderline personality disorder ( BPD ) and alcohol use disorder . Thirty participants were assessed every 3 months during a year of treatment with either DDP or treatment as usual ( TAU ) in the community . DDP participants showed statistically significant improvement in parasuicide behavior , alcohol misuse , institutional care , depression , dissociation , and core symptoms of BPD , and treatment retention was 67 % to 73 % . Although TAU participants received higher average treatment intensity , they showed only limited change during the same period . The results support the feasibility , tolerability , and efficacy of DDP for the co-occurring subgroup and highlight the need for further research . ( PsycINFO Data base Record ( c ) 2010 APA , all rights reserved ) BACKGROUND Longer-term follow-up of patients with borderline personality disorder have found favourable clinical outcomes , with long-term reduction in symptoms and diagnosis . AIMS We examined the 6-year outcome of patients with borderline personality disorder who were r and omised to 1 year of cognitive-behavioural therapy for personality disorders ( CBT-PD ) or treatment as usual ( TAU ) in the BOSCOT trial , in three centres across the UK ( trial registration : IS RCT N86177428 ) . METHOD In total , 106 participants met criteria for borderline personality disorder in the original trial . Patients were interviewed at follow-up by research assistants masked to the patient 's original treatment group , CBT-PD or TAU , using the same measures as in the original r and omised trial . Statistical analyses of data for the group as a whole are based on generalised linear models with repeated measures analysis of variance type models to examine group differences . RESULTS Follow-up data were obtained for 82 % of patients at 6 years . Over half the patients meeting criteria for borderline personality disorder at entry into the study no longer did so 6 years later . The gains of CBT-PD over TAU in reduction of suicidal behaviour seen after 1-year follow-up were maintained . Length of hospitalisation and cost of services were lower in the CBT-PD group compared with the TAU group . CONCLUSIONS Although the use of CBT-PD did not demonstrate a statistically significant cost-effective advantage , the findings indicate the potential for continued long-term cost-offsets that accrue following the initial provision of 1 year of CBT-PD . However , the quality of life and affective disturbance remained poor The outcome of a r and omized controlled trial of cognitive behavior therapy in addition to treatment as usual ( CBT plus TAU ) compared with TAU alone ( TAU ) in one hundred and six participants meeting diagnostic criteria for borderline personality disorder is described . We anticipated that CBT plus TAU would decrease the number of participants with in-patient psychiatric hospitalizations or accident and emergency room contact or suicidal acts over twelve months treatment and twelve months follow-up , compared with TAU . We also anticipated that CBT plus TAU would lead to improvement in a range of secondary outcomes of mental health and social functioning compared to TAU . Of the 106 participants r and omized , follow-up data on 102 ( 96 % ) was obtained at two years . Those r and omized to CBT were offered an average of 27 sessions over 12 months and attended on average 16 ( range 0 to 35 ) . We found that the global odds ratio of a participant in the CBT plus TAU group compared with the TAU alone group having any of the outcomes of a suicidal act , in-patient hospitalization , or accident and emergency contact in the 24 months following r and omization was 0.86 ( 95 % confidence interval [ CI ] 0.45 to 1.66 , p = 0.66 ) . The corresponding global odds ratio , excluding accident and emergency room contact , was 0.75 ( 95 % CI 0.37 to 1.54 , p = 0.44 ) . In terms of the number of suicidal acts , there was a significant reduction over the two years in favor of CBT plus TAU over TAU , with a mean difference of -0.91 ( 95 % CI -1.67 to -0.15 , p = 0.020 ) . Across both treatment arms there was gradual and sustained improvement in both primary and secondary outcomes , with evidence of benefit for the addition of CBT on the positive symptom distress index at one year , and on state anxiety , dysfunctional beliefs and the quantity of suicidal acts at two year follow-up . CBT can deliver clinical ly important changes in relatively few clinical sessions in real clinical setting OBJECTIVE The authors sought to evaluate the clinical efficacy of dialectical behavior therapy compared with general psychiatric management , including a combination of psychodynamically informed therapy and symptom-targeted medication management derived from specific recommendations in APA guidelines for borderline personality disorder . METHOD This was a single-blind trial in which 180 patients diagnosed with borderline personality disorder who had at least two suicidal or nonsuicidal self-injurious episodes in the past 5 years were r and omly assigned to receive 1 year of dialectical behavior therapy or general psychiatric management . The primary outcome measures , assessed at baseline and every 4 months over the treatment period , were frequency and severity of suicidal and nonsuicidal self-harm episodes . RESULTS Both groups showed improvement on the majority of clinical outcome measures after 1 year of treatment , including significant reductions in the frequency and severity of suicidal and nonsuicidal self-injurious episodes and significant improvements in most secondary clinical outcomes . Both groups had a reduction in general health care utilization , including emergency visits and psychiatric hospital days , as well as significant improvements in borderline personality disorder symptoms , symptom distress , depression , anger , and interpersonal functioning . No significant differences across any outcomes were found between groups . CONCLUSIONS These results suggest that individuals with borderline personality disorder benefited equally from dialectical behavior therapy and a well-specified treatment delivered by psychiatrists with expertise in the treatment of borderline personality disorder A r and omized clinical trial was conducted to evaluate whether Dialectical Behavior Therapy ( DBT ) , an effective cognitive-behavioral treatment for suicidal individuals with borderline personality disorder ( BPD ) , would also be effective for drug-dependent women with BPD when compared with treatment-as-usual ( TAU ) in the community . Subjects were r and omly assigned to either DBT or TAU for a year of treatment . Subjects were assessed at 4 , 8 , and 12 months , and at a 16-month follow-up . Subjects assigned to DBT had significantly greater reductions in drug abuse measured both by structured interviews and urinalyses throughout the treatment year and at follow-up than did subjects assigned to TAU . DBT also maintained subjects in treatment better than did TAU , and subjects assigned to DBT had significantly greater gains in global and social adjustment at follow-up than did those assigned to TAU . DBT has been shown to be more effective than treatment-as-usual in treating drug abuse in this study , providing more support for DBT as an effective treatment for severely dysfunctional BPD patients across a range of presenting problems Background Individuals affected by severe Borderline Personality Disorder ( BPD ) are often heavy users of Mental Health Services ( MHS ) . Short-term treatments currently used in BPD therapy are useful to target disruptive behaviors but they are less effective in reducing heavy MHS use . Therefore , alternative short-term treatments , less complex than long-term psychodynamic psychotherapies but specifically oriented to BPD core problems , need to be developed to reduce MHS overuse . This study aim ed to evaluate the efficacy of adding Sequential Brief Adlerian Psychodynamic Psychotherapy ( SB-APP ) to Supervised Team Management ( STM ) in BPD treatment compared to STM alone in a naturalistic group of heavy MHS users with BPD . Effectiveness was evaluated 6 times along a two-year follow-up . Methods Thirty-five out patients who met inclusion criteria were r and omly assigned to two treatment groups ( STM = 17 ; SB-APP = 18 ) and then compared . Clinical Global Impression ( CGI ) and CGI-modified ( CGI-M ) for BPD , Global Assessment of Functioning ( GAF ) , State-Trait Anger Expression Inventory ( STAXI ) , and Symptom Checklist-90 Revised ( SCL-90-R ) were administered at T1 , T3 , T6 , T12 , T18 and T24 . At T12 the Working Alliance Inventory-Short Form ( WAI-S ) was also completed . At the one-year follow-up , SB-APP group did not receive any additional individual psychological support . MHS team was specifically trained in BPD treatment and had regular supervisions . Results All patients improved on CGI , GAF , and STAXI scores after 6 and 12 months , independently of treatment received . SB-APP group showed better outcome on impulsivity , suicide attempts , chronic feelings of emptiness , and disturbed relationships . We found a good stabilization at the one year follow-up , even after the interruption of brief psychotherapy in the SB-APP group . Conclusions Although STM for BPD applied to heavy MHS users was effective in reducing symptoms and improving their global functioning , adding a time-limited and focused psychotherapy was found to achieve a better outcome . In particular , focusing treatment on patients ' personality with a specific psychotherapeutic approach ( i.e. SB-APP ) seemed to be more effective than STM alone . Trial Registration Clinical Trials.gov : BACKGROUND Dialectical behaviour therapy ( DBT ) is widely considered to be a promising treatment for borderline personality disorder ( BPD ) . However , the evidence for its efficacy published thus far should be regarded as preliminary . AIMS To compare the effectiveness of DBT with treatment as usual for patients with BPD and to examine the impact of baseline severity on effectiveness . METHOD Fifty-eight women with BPD were r and omly assigned to either 12 months of DBT or usual treatment in a r and omised controlled study . Participants were recruited through clinical referrals from both addiction treatment and psychiatric services . Outcome measures included treatment retention and the course of suicidal , self-mutilating and self-damaging impulsive behaviours . RESULTS Dialectical behaviour therapy result ed in better retention rates and greater reductions of self-mutilating and self-damaging impulsive behaviours compared with usual treatment , especially among those with a history of frequent self-mutilation . CONCLUSIONS Dialectical behaviour therapy is superior to usual treatment in reducing high-risk behaviours in patients with BPD Background : To date , there have been no studies comparing cognitive therapy ( CT ) with Rogerian supportive therapy ( RST ) in borderline personality disorder . Method : Sixty-five DSM-IV borderline personality disorder out patients were recruited at 2 centres : Lyon and Marseille . Thirty-three patients were r and omly allocated to CT and 32 to RST . The therapists were the same in both groups . Both treatments shared the same duration ( 1 year ) and amount of therapy . Assessment by independent evaluators utilised the Clinical Global Impression ( CGI ) Scale , the Hamilton Depression Scale , Beck Depression Inventory , Beck Anxiety Inventory , Hopelessness Scale , Young Schema Question naire II , Eysenck Impulsivity Venturesomeness Empathy ( IVE ) Inventory , a self-harming behaviours checklist and scales measuring quality of life and the therapeutic relationship . The response criterion was a score of 3 or less on the CGI , associated with a Hopelessness Scale score of < 8 . Results : No patient committed suicide during the trial . Fifty-one patients were evaluated at week 24 , 38 at week 52 and 21 at week 104 . Cognitive therapy retained the patients in therapy for a longer time . The response criterion found no significant between-group differences at any measurement point in the completers . However , at week 24 , CT was better than RST on the Hopelessness Scale , IVE scale and regarding the therapeutic relationship . At week 104 , the CGI improvement ( patient and evaluator ) was significantly better in CT than in RST . High baseline depression and impulsivity predicted dropouts . Conclusions : CT retained the patients in therapy longer , showed earlier positive effects on hopelessness and impulsivity , and demonstrated better long-term outcomes on global measures of improvement OBJECTIVE The aim of this study was to determine whether the substantial gains made by patients with borderline personality disorder following completion of a psychoanalytically oriented partial hospitalization program , in comparison to patients treated with st and ard psychiatric care , were maintained over an 18-month follow-up period . METHOD Forty-four patients who participated in the original study were assessed every 3 months after completion of the treatment phase . Outcome measures included frequency of suicide attempts and acts of self-harm , number and duration of inpatient admissions , service utilization , and self-reported measures of depression , anxiety , general symptom distress , interpersonal functioning , and social adjustment . RESULTS Patients who completed the partial hospitalization program not only maintained their substantial gains but also showed a statistically significant continued improvement on most measures in contrast to the patients treated with st and ard psychiatric care , who showed only limited change during the same period . CONCLUSIONS The superiority of psychoanalytically oriented partial hospitalization over st and ard psychiatric treatment found in a previous r and omized , controlled trial was maintained over an 18-month follow-up period . Continued improvement in social and interpersonal functioning suggests that longer-term changes were stimulated This paper describes the rationale for a r and omized controlled trial , comparing cognitive behavior therapy in addition to treatment as usual with treatment as usual alone , for borderline personality disorder . Previous pioneering r and omized controlled trials of psychotherapies have suffered from method ological weaknesses and have not always been reported clearly to allow adequate evaluation of either the individual study or comparisons across studies to be undertaken . We report on the recruitment and r and omization , design , and conduct of an ongoing r and omized controlled trial of one hundred and six patients with borderline personality disorder . Primary and secondary hypotheses and their planned analyses are stated . The baseline characteristics of 106 patients meeting diagnostic criteria for borderline personality disorder are described We conducted a r and omized controlled trial to evaluate whether dialectical behavior therapy ( DBT ) , a treatment that synthesizes behavioral change with radical acceptance strategies , would be more effective for heroin-dependent women with borderline personality disorder ( N = 23 ) than Comprehensive Validation Therapy with 12-Step ( CVT + 12S ) , a manualized approach that provided the major acceptance-based strategies used in DBT in combination with participation in 12-Step programs . In addition to psychosocial treatment , subjects also received concurrent opiate agonist therapy with adequate doses of LAAM ( thrice weekly ; modal dose 90/90/130 mg ) . Treatment lasted for 12 months . Drug use outcomes were measured via thrice-weekly urinalyses and self-report . Three major findings emerged . First , results of urinalyses indicated that both treatment conditions were effective in reducing opiate use relative to baseline . At 16 months post-r and omization ( 4 months post-treatment ) , all participants had a low proportion of opiate-positive urinalyses ( 27 % in DBT ; 33 % in CVT + 12S ) . With regard to between-condition differences , participants assigned to DBT maintained reductions in mean opiate use through 12 months of active treatment while those assigned to CVT + 12S significantly increased opiate use during the last 4 months of treatment . Second , CVT + 12S retained all 12 participants for the entire year of treatment , compared to a 64 % retention rate in DBT . Third , at both post-treatment and at the 16-month follow-up assessment , subjects in both treatment conditions showed significant overall reductions in level of psychopathology relative to baseline . A noteworthy secondary finding was that DBT participants were significantly more accurate in their self-report of opiate use than were those assigned to CVT + 12S CONTEXT Borderline personality disorder is a severe and chronic psychiatric condition , prevalent throughout health care setting s. Only limited effects of current treatments have been documented . OBJECTIVE To compare the effectiveness of schema-focused therapy ( SFT ) and psychodynamically based transference-focused psychotherapy ( TFP ) in patients with borderline personality disorder . DESIGN A multicenter , r and omized , 2-group design . SETTING Four general community mental health centers . PARTICIPANTS Eighty-eight patients with a Borderline Personality Disorder Severity Index , fourth version , score greater than a predetermined cutoff score . INTERVENTION Three years of either SFT or TFP with sessions twice a week . MAIN OUTCOME MEASURES Borderline Personality Disorder Severity Index , fourth version , score ; quality of life ; general psychopathologic dysfunction ; and measures of SFT/TFP personality concepts . Patient assessment s were made before r and omization and then every 3 months for 3 years . RESULTS Data on 44 SFT patients and 42 TFP patients were available . The sociodemographic and clinical characteristics of the groups were similar at baseline . Survival analyses revealed a higher dropout risk for TFP patients than for SFT patients ( P = .01 ) . Using an intention-to-treat approach , statistically and clinical ly significant improvements were found for both treatments on all measures after 1- , 2- , and 3-year treatment periods . After 3 years of treatment , survival analyses demonstrated that significantly more SFT patients recovered ( relative risk = 2.18 ; P = .04 ) or showed reliable clinical improvement ( relative risk = 2.33 ; P = .009 ) on the Borderline Personality Disorder Severity Index , fourth version . Robust analysis of covariance ( ANCOVA ) showed that they also improved more in general psychopathologic dysfunction and measures of SFT/TFP personality concepts ( P<.001 ) . Finally , SFT patients showed greater increases in quality of life than TFP patients ( robust ANCOVAs , P=.03 and P<.001 ) . CONCLUSIONS Three years of SFT or TFP proved to be effective in reducing borderline personality disorder-specific and general psychopathologic dysfunction and measures of SFT/TFP concepts and in improving quality of life ; SFT is more effective than TFP for all measures OBJECTIVE This study compared the effectiveness of psychoanalytically oriented partial hospitalization with st and ard psychiatric care for patients with borderline personality disorder . METHOD Thirty-eight patients with borderline personality disorder , diagnosed according to st and ardized criteria , were allocated either to a partially hospitalized group or to a st and ard psychiatric care ( control ) group in a r and omized controlled design . Treatment , which included individual and group psychoanalytic psychotherapy , was for a maximum of 18 months . Outcome measures included the frequency of suicide attempts and acts of self-harm , the number and duration of inpatient admissions , the use of psychotropic medication , and self-report measures of depression , anxiety , general symptom distress , interpersonal function , and social adjustment . Data analysis used repeated measures analysis of covariance and nonparametric tests of trend . RESULTS Patients who were partially hospitalized showed a statistically significant decrease on all measures in contrast to the control group , which showed limited change or deterioration over the same period . An improvement in depressive symptoms , a decrease in suicidal and self-mutilatory acts , reduced inpatient days , and better social and interpersonal function began at 6 months and continued until the end of treatment at 18 months . CONCLUSIONS Psychoanalytically oriented partial hospitalization is superior to st and ard psychiatric care for patients with borderline personality disorder . Replication is needed with larger groups , but these results suggest that partial hospitalization may offer an alternative to inpatient treatment OBJECTIVE Recurrent suicidal behavior is a defining characteristic of borderline personality disorder . Although most patients achieve remission of suicidal behavior over time , as many as 10 % die by suicide , raising the question of whether there is a high-risk suicidal subtype . The authors conducted a longitudinal study of suicidal behavior in borderline personality disorder patients to identify prospect i ve predictors of suicide attempts and to characterize those patients at highest risk for suicide completion . METHOD Demographic and diagnostic characteristics and clinical and psychosocial risk factors assessed at baseline were examined for predictive association with medically significant suicide attempts using Cox proportional hazards models . The authors defined prospect i ve predictors for participants who completed 6 or more years in the study and compared the data to those of earlier intervals . RESULTS Among 90 participants , 25 ( 27.8 % ) made at least one suicide attempt in the interval , and most attempts occurred in the first 2 years . The risk of suicide attempt was increased by low socioeconomic status , poor psychosocial adjustment , family history of suicide , previous psychiatric hospitalization , and absence of any outpatient treatment before the attempt . Higher global functioning scores at baseline decreased this risk . CONCLUSIONS Risk factors predictive of suicide attempt change over time . Acute stressors such as major depressive disorder were predictive only in the short term ( 12 months ) , while poor psychosocial functioning had persistent and long-term effects on suicide risk . Half of borderline patients have poor psychosocial outcomes despite symptomatic improvement . A social and vocational rehabilitation model of treatment is needed to decrease suicide risk and optimize long-term outcomes This study examines the efficacy of a short-term individual therapy , Manual Assisted Cognitive Treatment ( MACT ) , which was developed to treat parasuicidal ( suicidal or self-harming ) patients . In this trial , MACT was modified to focus on deliberate self-harm ( DSH ) in patients with borderline personality disorder ( BPD ) . Thirty BPD patients who were engaged in DSH while in ongoing treatments , i.e. , treatment-as-usual ( TAU ) , were r and omly assigned to receive MACT ( N = 15 ) or not . DSH and level of suicide ideation were assessed at the baseline , at completion of the MACT intervention , and six months later . Results indicated that MACT was associated with significantly less frequent DSH upon completion of the intervention and with significantly decreased DSH frequency and severity at the six months follow-up . Moreover , MACT 's contribution to reducing DSH frequency and severity was greater than the contribution by the amount of concurrent treatments . In contrast , MACT did not affect the level of suicide ideation and time-to-repeat of DSH . In conclusion , MACT seems to be a promising intervention for DSH in patients with BPD . More definitive studies are needed Borderline personality disorder ( BPD ) and deliberate self-harm are clinical ly important conditions for which additional economically and clinical ly feasible interventions are needed . Literature on both the emotion regulating and experientially avoidant function of self-harm and the role of emotional dysfunction in BPD provided the rationale for developing a group intervention targeting emotion dysregulation among self-harming women with BPD . This study provides preliminary data on the efficacy of this new , 14-week , emotion regulation group intervention , design ed to teach self-harming women with BPD more adaptive ways of responding to their emotions so as to reduce the frequency of their self-harm behavior . Participants were matched on level of emotion dysregulation and lifetime frequency of self-harm and r and omly assigned to receive this group in addition to their current outpatient therapy ( N = 12 ) , or to continue with their current outpatient therapy alone for 14 weeks ( N = 10 ) . Results indicate that the group intervention had positive effects on self-harm , emotion dysregulation , experiential avoidance , and BPD-specific symptoms , as well as symptoms of depression , anxiety , and stress . Participants in the group treatment condition evidence d significant changes over time on all measures , and reached normative levels of functioning on most . While these preliminary results are promising , the study 's limitations require their replication in a larger-scale r and omized controlled trial Psychoanalytically oriented day hospital therapy , later manualized and named mentalization-based treatment ( MBT ) , has proven to be a ( cost- ) effective treatment for patients with severe borderline personality disorder and a high degree of psychiatric comorbidity ( BPD ) in the United Kingdom ( UK ) . As to yet it has not been shown whether manualized day hospital MBT would yield similar results when conducted by an independent institute outside the UK . We investigated the applicability and treatment outcome of 18-month , manualized day hospital MBT in the Netherl and s by means of a prospect i ve cohort study with 45 Dutch patients with severe BPD and a high degree of comorbid Axis I and Axis II disorders . Outcomes were assessed each six months . Symptom distress , social and interpersonal functioning , and personality pathology and functioning all improved significantly , with effect sizes between 0.7 and 1.7 . Suicide attempts , acts of self-harm , and care consumption were also significantly reduced . The results indicate that MBT can effectively be implemented in an independent treatment institute outside the UK . This study also supports the clinical effectiveness of manualized day hospital MBT in patients with severe BPD and a high degree of psychiatric comorbidity Objective : Deliberate self-harm ( DSH ) , general hospital admission and psychiatric hospital admission are common in women meeting criteria for borderline personality disorder ( BPD ) . Dialectical behaviour therapy ( DBT ) has been reported to be effective in reducing DSH and hospitalization . Method : A r and omized controlled trial of 73 female subjects meeting criteria for BPD was carried out with intention-to-treat analyses and per- protocol analyses . The intervention was DBT and the control condition was treatment as usual plus waiting list for DBT ( TAU+WL ) , with outcomes measured after 6 months . Primary outcomes were differences in proportions and event rates of : any DSH ; general hospital admission for DSH and any psychiatric admission ; and mean difference in length of stay for any hospitalization . Secondary outcomes were disability and quality of life measures . Results : Both groups showed a reduction in DSH and hospitalizations , but there were no significant differences in DSH , hospital admissions or length of stay in hospital between groups . Disability ( days spent in bed ) and quality of life ( Physical , Psychological and Environmental domains ) were significantly improved for the DBT group . Conclusion : DBT produced non-significant reductions in DSH and hospitalization when compared to the TAU+WL control , due in part to the lower than expected rates of hospitalization in the control condition . Nevertheless , DBT showed significant benefits for the secondary outcomes of improved disability and quality of life scores , a clinical ly useful result that is also in keeping with the theoretical constructs of the benefits of DBT A r and omized clinical trial was conducted to evaluate the effectiveness of a cognitive-behavioral therapy , ie , dialectical behavior therapy , for the treatment of chronically parasuicidal women who met criteria for borderline personality disorder . The treatment lasted 1 year , with assessment every 4 months . The control condition was " treatment as usual " in the community . At most assessment points and during the entire year , the subjects who received dialectical behavior therapy had fewer incidences of parasuicide and less medically severe parasuicides , were more likely to stay in individual therapy , and had fewer inpatient psychiatric days . There were no between-group differences on measures of depression , hopelessness , suicide ideation , or reasons for living although scores on all four measures decreased throughout the year CONTEXT Dialectical behavior therapy ( DBT ) is a treatment for suicidal behavior and borderline personality disorder with well-documented efficacy . OBJECTIVE To evaluate the hypothesis that unique aspects of DBT are more efficacious compared with treatment offered by non-behavioral psychotherapy experts . DESIGN One-year r and omized controlled trial , plus 1 year of posttreatment follow-up . SETTING University outpatient clinic and community practice . PARTICIPANTS One hundred one clinical ly referred women with recent suicidal and self-injurious behaviors meeting DSM-IV criteria , matched to condition on age , suicide attempt history , negative prognostic indication , and number of lifetime intentional self-injuries and psychiatric hospitalizations . INTERVENTION One year of DBT or 1 year of community treatment by experts ( developed to maximize internal validity by controlling for therapist sex , availability , expertise , allegiance , training and experience , consultation availability , and institutional prestige ) . MAIN OUTCOME MEASURES Trimester assessment s of suicidal behaviors , emergency services use , and general psychological functioning . Measures were selected based on previous outcome studies of DBT . Outcome variables were evaluated by blinded assessors . RESULTS Dialectical behavior therapy was associated with better outcomes in the intent-to-treat analysis than community treatment by experts in most target areas during the 2-year treatment and follow-up period . Subjects receiving DBT were half as likely to make a suicide attempt ( hazard ratio , 2.66 ; P = .005 ) , required less hospitalization for suicide ideation ( F(1,92 ) = 7.3 ; P = .004 ) , and had lower medical risk ( F(1,50 ) = 3.2 ; P = .04 ) across all suicide attempts and self-injurious acts combined . Subjects receiving DBT were less likely to drop out of treatment ( hazard ratio , 3.2 ; P < .001 ) and had fewer psychiatric hospitalizations ( F(1,92 ) = 6.0 ; P = .007 ) and psychiatric emergency department visits ( F(1,92 ) = 2.9 ; P = .04 ) . CONCLUSIONS Our findings replicate those of previous studies of DBT and suggest that the effectiveness of DBT can not reasonably be attributed to general factors associated with expert psychotherapy . Dialectical behavior therapy appears to be uniquely effective in reducing suicide attempts OBJECTIVE The purpose of this study was to determine whether severe personality disorders improve or deteriorate with intensive inpatient treatment . METHODS Overall 216 patients diagnosed as having personality disorders by DSM-III-R criteria were prospect ively monitored at two private psychiatric hospitals from admission through discharge to one-year follow-up . RESULTS Substantial positive change in the sample was recorded at discharge , and the improvements held up at one-year follow-up . The proportion of patients with scores of 50 or more on the Global Assessment Scale was 3.7 percent at the time of admission . By discharge the proportion had increased to 55.1 percent , and by one-year follow-up it had risen to 66.3 percent . CONCLUSIONS These results suggest that patients with severe personality disorders benefit from intensive inpatient treatment . We found no evidence that hospitalization of such patients is associated with regression or deterioration of function Objective : Combined treatment with interpersonal psychotherapy ( IPT ) and antidepressants ( ADs ) has been found more effective than single pharmacotherapy in patients with major depression and concomitant borderline personality disorder ( BPD ) . The aim of our study is to investigate whether combined treatment with a modified version of IPT is still superior to ADs when treating patients with a single diagnosis of BPD . Method : Fifty-five consecutive out patients with a Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , Text Revision , diagnosis of BPD were enrolled . They were r and omly assigned to 2 treatment arms for 32 weeks : fluoxetine 20 to 40 mg per day plus clinical management ; and fluoxetine 20 to 40 mg per day plus IPT adapted to BPD ( IPT-BPD ) . Eleven patients ( 20 % ) discontinued treatment owing to noncompliance . Forty-four patients completed the treatment period . They were assessed at baseline , and at week 16 and 32 with : a semi-structured interview for demographic and clinical variables ; Clinical Global Impression Scale ( CGI-S ) ; Hamilton Depression Rating Scale ( HDRS ) ; Hamilton Anxiety Rating Scale ( HARS ) ; Social and Occupational Functioning Assessment Scale ( SOFAS ) ; BPD Severity Index ( BPD-SI ) ; and a question naire for quality of life ( Satisfaction Profile [ SAT-P ] ) . A univariate general linear model was performed with 2 factors : duration and type of treatment . P values of less than 0.05 were considered significant . Results : Remission rates did not differ significantly between subgroups . Duration , but not type of treatment , had a significant effect on CGI-S , HDRS , SOFAS , and total BPD-SI score changes . Combined therapy was more effective on the HARS ; the items : interpersonal relationships , affective instability , and impulsivity of BPD-SI ; and the factors : psychological functioning and social functioning of SAT-P. Conclusions : Combined therapy with adapted IPT was superior to fluoxetine alone in BPD patients , concerning a few core symptoms of the disorder , anxiety , and quality of life OBJECTIVE This r and omized controlled trial tested the effectiveness of an 18-month mentalization-based treatment ( MBT ) approach in an outpatient context against a structured clinical management ( SCM ) outpatient approach for treatment of borderline personality disorder . METHOD Patients ( N=134 ) consecutively referred to a specialist personality disorder treatment center and meeting selection criteria were r and omly allocated to MBT or SCM . Eleven mental health professionals equal in years of experience and training served as therapists . Independent evaluators blind to treatment allocation conducted assessment s every 6 months . The primary outcome was the occurrence of crisis events , a composite of suicidal and severe self-injurious behaviors and hospitalization . Secondary outcomes included social and interpersonal functioning and self-reported symptoms . Outcome measures , assessed at 6-month intervals , were analyzed using mixed effects logistic regressions for binary data , Poisson regression models for count data , and mixed effects linear growth curve models for self-report variables . RESULTS Substantial improvements were observed in both conditions across all outcome variables . Patients r and omly assigned to MBT showed a steeper decline of both self-reported and clinical ly significant problems , including suicide attempts and hospitalization . CONCLUSIONS Structured treatments improve outcomes for individuals with borderline personality disorder . A focus on specific psychological processes brings additional benefits to structured clinical support . Mentalization-based treatment is relatively undem and ing in terms of training so it may be useful for implementation into general mental health services . Further evaluations by independent research groups are now required OBJECTIVE The authors conducted a 2-year prospect i ve naturalistic follow-up study to evaluate posttreatment clinical outcomes in out patients who were r and omly selected to receive 1 year of either dialectical behavior therapy or general psychiatric management for borderline personality disorder . METHOD Patients were assessed by blind raters 6 , 12 , 18 , and 24 months after treatment . The clinical effectiveness of treatment was assessed on measures of suicidal and nonsuicidal self-injurious behaviors , health care utilization , general symptom distress , depression , anger , quality of life , social adjustment , borderline psychopathology , and diagnostic status . The authors conducted between-group comparisons using generalized estimating equation , mixed-effects models , or chi-square statistics , depending on the distribution and nature of the data . RESULTS Both treatment groups showed similar and statistically significant improvements on the majority of outcomes 2 years after discharge . The original effects of treatment did not diminish for any outcome domain , including suicidal and nonsuicidal self-injurious behaviors . Further improvements were seen on measures of depression , interpersonal functioning , and anger . However , even though two-thirds of the participants achieved diagnostic remission and significant increases in quality of life , 53 % were neither employed nor in school , and 39 % were receiving psychiatric disability support after 36 months . CONCLUSIONS One year of either dialectical behavior therapy or general psychiatric management was associated with long-lasting positive effects across a broad range of outcomes . Despite the benefits of these specific treatments , one important finding that replicates previous research is that participants continued to exhibit high levels of functional impairment . The effectiveness of adjunctive rehabilitation strategies to improve general functioning deserves additional study Dialectical Behaviour Therapy ( DBT ) is considered one of the most promising treatments for borderline personality disorder ( BPD ) . Recently , we reported significantly positive effects of 12 months DBT on parasuicidal behaviour and impulsivity in a mixed group of female BPD patients with and without substance abuse . Fifty-eight women with BPD were r and omly assigned to either 52 weeks of DBT or treatment as usual ( TAU ) . Follow-up assessment took place at 78 weeks , i.e. , 6 months after discontinuation of DBT . Participants were clinical referrals from addiction treatment and psychiatric services . Outcome measures included parasuicidal behaviour , impulsivity and substance abuse . Six months after treatment discontinuation , the benefits of DBT over TAU in terms of lower levels of parasuicidal and impulsive behaviours , and in alcohol use , sustained . No differences between the treatment conditions were found for drug abuse . In conclusion , DBT seems to have a sustained effect on some of the core symptoms of BPD and on alcohol problems in a mixed population of female borderline patients with and without substance abuse problems OBJECTIVE Systems Training for Emotional Predictability and Problem Solving ( STEPPS ) is a 20-week manual-based group treatment program for out patients with borderline personality disorder that combines cognitive behavioral elements and skills training with a systems component . The authors compared STEPPS plus treatment as usual with treatment as usual alone in a r and omized controlled trial . METHOD Subjects with borderline personality disorder were r and omly assigned to STEPPS plus treatment as usual or treatment as usual alone . Total score on the Zanarini Rating Scale for Borderline Personality Disorder was the primary outcome measure . Secondary outcomes included measures of global functioning , depression , impulsivity , and social functioning ; suicide attempts and self-harm acts ; and crisis utilization . Subjects were followed 1 year posttreatment . A linear mixed-effects model was used in the analysis . RESULTS Data pertaining to 124 subjects ( STEPPS plus treatment as usual [ N=65 ] ; treatment as usual alone [ N=59 ] ) were analyzed . Subjects assigned to STEPPS plus treatment as usual experienced greater improvement in the Zanarini Rating Scale for Borderline Personality Disorder total score and subscales assessing affective , cognitive , interpersonal , and impulsive domains . STEPPS plus treatment as usual also led to greater improvements in impulsivity , negative affectivity , mood , and global functioning . These differences yielded moderate to large effect sizes . There were no differences between groups for suicide attempts , self-harm acts , or hospitalizations . Most gains attributed to STEPPS were maintained during follow-up . Fewer STEPPS plus treatment as usual subjects had emergency department visits during treatment and follow-up . The discontinuation rate was high in both groups . CONCLUSIONS STEPPS , an adjunctive group treatment , can deliver clinical ly meaningful improvements in borderline personality disorder-related symptoms and behaviors , enhance global functioning , and relieve depression |
12,245 | 30,326,948 | Conclusions This review identifies a list of metrics to monitor site performance within multicentre r and omised trials . | Background Large multicentre trials are complex and expensive projects .
A key factor for their successful planning and delivery is how well sites meet their targets in recruiting and retaining participants , and in collecting high- quality , complete data in a timely manner .
Collecting and monitoring easily accessible data relevant to performance of sites has the potential to improve trial management efficiency .
The aim of this systematic review was to identify metrics that have either been proposed or used for monitoring site performance in multicentre trials . | Background Excessive protocol violations ( PV ) , which can be defined as preventable mistakes in study conduct , may result in patient harm and introduce errors into a clinical trial 's results leading to flawed trial conclusions .The purpose of this project was to gain a better underst and ing of reported PVs , to describe current practice with regards to the use of methods for the reduction of PVs and to investigate relationships between clinical trial characteristics and PVs . Methods We review ed 80 clinical trials conducted across a broad range of medical specialties published in four major general medical journals ( The Lancet , NEJM , JAMA , BMJ ) . Eligible papers were identified using a PubMed search . For each included trial , two authors independently abstract ed information on trial characteristics , PV reporting and PV rates and interventions used to reduce PVs . PVs were categorised into one of five distinct types : enrolment , r and omisation , study intervention , patient compliance and data collection errors . Associations between PVs and study characteristics were investigated using logistic regression . Results Eighty clinical trials ( 20 from each journal ) were identified from 101 consecutive PubMed abstract s. The median number of participants was 701 ( range : 20 to 162 , 367 ) and the median number of participating sites was 15 ( range : 1 to 701 ) . Nineteen percent ( 15/80 ) of included trials were single centre trials . The median study duration was 24 months ( range : 5.81 - 127 months ) and 74 % ( 59/80 ) of included trials were primarily academic funded . Thirty two percent ( 26/80 ) of included trials failed to provide explicit reporting of any type of PV and none ( 0/80 ) of the trials provided explicit reporting of all five types of PVs . Larger clinical trials ( more patients , more sites , longer duration , more complex management structure ) were more likely to have more complete reporting of PV's . Only 9 % ( 7/80 ) of trials reported the use of a specific study method to prevent PVs . Use of a run-in phase was the only method reported . Conclusions PVs are under-reported . Although the CONSORT statement provides guidance on the reporting of PVs , reporting requirements are not explicit for all types of PVs . As a first step towards improved reporting by authors , we recommend the CONSORT statement highlight the importance of PVs by making reporting requirements more explicit Background Compliance with Good Clinical Practice ( GCP ) guidelines should ensure the safety of trial participants and the reliability of trial results . Over the last decade , increasing emphasis has been placed on the role of costly on-site monitoring and source data verification as processes to demonstrate that GCP is being followed , despite a lack of empirical evidence that these are effective . Purpose To assess whether findings from on-site monitoring of a recent international multi-centre clinical trial could have been identified using central data review and other central ised monitoring techniques . Methods Findings documented in a sample of site monitoring reports , and Programme Management Board Executive ( PMBe ) reports , from the Microbicides Development Programme ( MDP ) 301 trial – a r and omised placebo-controlled trial of a microbicide gel to prevent vaginally acquired HIV infection conducted in four countries in East and Southern Africa – were extracted and individually assessed to determine whether they could have been detected in the trial data base or through other central means . Results Four site visit reports contained 268 monitoring findings from a review of 104 participant files covering 324 study visits . Of the 268 findings , 76 ( 28.4 % ) were also identified in the study data base . Central checks , had these been in place ( such as central receipt and review of back-translated documents , enrolment and testing logs , informed consent , and more complex data base queries ) , could have identified a further 179 ( 66.8 % ) ; 13 ( 4.9 % ) other findings ( all minor ) could have been identified through a review of the participant folder at site . The four PMBe reports review ed included six major and three critical findings from a review of over 1000 participant files : only two of these ( both major ) were assessed as unlikely to be identified using central monitoring techniques . Limitations The study data used were not collected with this retrospective review in mind . It suggests that prospect i ve work is needed to compare monitoring practice s in real time . Conclusions While there may be some categories of findings that it is not possible to identify central ly , the very large majority of findings review ed in this analysis could be identified using central monitoring strategies . These data suggest that with better central and targeted on-site monitoring , it should be possible to identify and address most protocol and procedural compliance issues without performing intensive and costly routine on-site data monitoring Background Review ing clinical trial site performance identifies strategies to control outcomes . Performance across 5 geographical regions ( 36 sites across Asia , Australia , Europe , North America and Latin America ) was investigated in a study that r and omised 322 HIV-infected individuals . Methods Regional performance was compared using descriptive analysis for time to site opening , recruitment , quality of data and laboratory sample s. Follow-up consisted of 10 visits ( 96 weeks ) , electronic data collection ( EDC ) within 7 days of a visit and serious adverse events ( SAEs ) reported within 24 hours of site awareness . Results Median days to site opening was 250 ( 188 to 266 ) , ranging from 177 ( 158 to 200 ) ( Australia ) to 265 ( 205 to 270 ) ( Europe ) . Median days to ethics and regulatory approval was 182 ( 120 to 241 ) and 218 ( 182 to 341 ) days , respectively . Within regions , time to approval ranged from 187 ( 91 to 205 ) days ( Australia ) to 276 ( 175 to 384 ) days ( Europe ) . Time to first r and omisation ranged from 282 ( 250 to 313 ) days ( Australia ) to 426 ( 420 to 433 ) days ( North America).Recruitment was lower than forecasted in Asia , Australia , Europe and North America at 89 % , 77 % , 91 % and 43 % , respectively . The converse was true in Latin America where despite ethics , regulatory and contractual delays , recruitment was 104 % of predicted . Median days to EDC was 7 ( 3 to 16 ) , ranging from 3 ( 1 to 16 ) ( Asia ) to 13 ( 8 to 14 ) days ( North America ) . Median days for initial SAE su bmi ssion to sponsor was 6 ( 2 to 20 ) , ranging from 4 ( 2 to 18 ) ( Latin America ) to 24 ( 5 to 46 ) days ( Australia ) . Sites took longer to su bmi t final reports , overall median of 28 ( 7 to 91 ) days , ranging from 7 days ( Australia ) to 67 ( 23 to 103 ) days ( Europe ) . Conclusions Population availability and time to ethics and regulatory approvals influence recruitment ; therefore accurate feasibility assessment s are critical to site selection . Time to ethics and regulatory approval may not limit site inclusion if compensated by rapid recruitment . Identifying potential delays and methods for reduction can decrease time and costs for sponsors . Trial registration Clinical Trials . Gov identifier : NCT00335322 . Date of registration : 8 June Background Monitoring in r and omized trials is recommended as part of International Conference on Harmonisation Good Clinical Practice st and ards . On-site monitoring in multicentre trials is common but is costly and can be inefficient . Central statistical monitoring can be used to detect unusual data patterns , identify intentional or unintentional trial misconduct , and to prioritise on-site visits and additional training . Motivated by an ongoing international multicentre clinical trial of over 25,000 r and omized participants with electronic data capture , we developed key risk indicator ( KRI ) methods for central statistical monitoring in multicentre trials Large r and omized trials are required to provide reliable evidence of the typically moderate benefit of most interventions . To be affordable , such trials need to be simple ; to be widely applicable , they need to be close to normal clinical practice . However , current regulations and guidelines have hugely increased trial complexity , effectively becoming barriers to their design and conduct . Key barriers include inadequate funding , overly complex regulations producing needlessly complex trial procedures , excessive monitoring , over restrictive interpretation of privacy laws without evidence of subject benefit , and inadequate underst and ing of methodology . Complex regulations result in multiple ethics approvals for a multi-center study , unnecessary complexity in the study protocol , delays in securing regulatory approval , and cumbersome regulatory procedures , even for drugs widely used in clinical practice . The type of detailed safety monitoring currently needed in trials of new drugs is being applied indiscriminately to all studies including a simpler and basic level of monitoring that constitutes good practice in most trials could be agreed on , with that level being exceeded only in specific instances . More evidence about the pros and cons of alternative approaches to data quality monitoring would help inform this process . Complex procedures in the form of multiple-page consent forms , overzealous monitoring of side effects and adverse events , source data verification , and over-restrictive approaches to protocol amendments , can impede , rather than facilitate , trial objectives . Finally , further education on the nuances and functions of r and omisation would facilitate trial conduct , and reduce the need for burdensome complexity . A radical re-evaluation of existing trial guidelines is needed , based on a clear underst and ing of the important principles of r and omized trials , with the objective of eliminating unnecessary documentation and reporting without sacrificing validity or safety . Research ers should encourage public debate about how best to strike the balance between regulation and cost . Clinical Trials 2008 ; 5 : 40—48 . |
12,246 | 19,821,411 | Capsaicin , either as repeated application of a low dose ( 0.075 % ) cream , or a single application of a high dose ( 8 % ) patch may provide a degree of pain relief to some patients with painful neuropathic conditions .
Local skin irritation , which is often mild and transient but may lead to withdrawal , is common .
Systemic adverse effects are rare . | BACKGROUND Topical creams with capsaicin are used to treat pain from a wide range of chronic conditions including neuropathic pain .
Following application to the skin capsaicin causes enhanced sensitivity to noxious stimuli , followed by a period with reduced sensitivity and , after repeated applications , persistent desensitisation .
There is uncertainty about the efficacy and tolerability of capsaicin for treating painful chronic neuropathies .
OBJECTIVES To review the evidence from controlled trials on the efficacy and tolerability of topically applied capsaicin in chronic neuropathic pain in adults . | BACKGROUND The limitations of current treatments for postherpetic neuralgia ( PHN ) have led to the investigation of localised , non-systemic alternatives . NGX-4010 , a high-concentration ( 8 % ) capsaicin dermal patch , was developed to treat patients with neuropathic pain . We report the results of a r and omised , double blind , 12-week study of the efficacy and safety of one application of NGX-4010 in patients with PHN . METHODS In this multicentre , double-blind , parallel-group trial , 402 patients were r and omly assigned to one 60-min application of NGX-4010 ( 640 microg/cm(2 ) [ 8 % capsaicin ] ) or a low-concentration capsaicin control patch ( 3.2 microg/cm(2 ) [ 0.04 % capsaicin ] ) . Patients were aged 18 - 90 years , had had postherpetic neuralgia for at least 6 months , and had an average baseline numeric pain rating scale ( NPRS ) score of 3 to 9 . The primary efficacy endpoint was percentage change in NPRS score from baseline to weeks two to eight . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00115310 . FINDINGS Patients who were r and omly assigned to NGX-4010 ( n=206 ) had a significantly greater reduction in pain during weeks two to eight than did patients who had the control patch ( n=196 ) . The mean changes in NPRS score were -29.6%vs -19.9 % ( difference -9.7 % , 95 % CI -15.47 to -3.95 ; p=0.001 ) . 87 ( 42 % ) patients who received NGX-4010 and 63 ( 32 % ) controls had a 30 % or greater reduction in mean NPRS score ( odds ratio [ OR ] 1.56 , 95 % CI 1.03 to 2.37 ; p=0.03 ) . The patients who had NGX-4010 had significant improvements in pain during weeks two to 12 ( mean change in NPRS score -29.9%vs -20.4 % , difference -9.5 , -15.39 to -3.61 ; p=0.002 ) . Transient blood pressure changes associated with changes in pain level were recorded on the day of treatment , and short-lasting erythema and pain at the site of application were common , self-limited , and generally mild to moderate in the NGX-4010 group and less frequent and severe in the controls . INTERPRETATION One 60-min application of NGX-4010 provided rapid and sustained pain relief in patients with postherpetic neuralgia . No adverse events were associated with treatment except for local reactions at the site of application and those related to treatment-associated pain Abstract Variability in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size Uncontrolled studies have indicated that topically applied capsaicin may be a safe and effective treatment for postherpetic neuralgia . In a double-blind study 32 elderly patients with chronic postherpetic neuralgia were treated with either capsaicin cream or its vehicle for a 6-week period . Response to treatment was evaluated by visual analogue scales of pain and of pain relief , together with changes in a categoric pain scale and in a physician 's global evaluation . Significantly greater relief in the capsaicin-treated group compared with vehicle was observed for all efficacy variables . After 6 weeks almost 80 % of capsaicin-treated patients experienced some relief from their pain . Because capsaicin avoids problems with drug interactions and systemic toxicity , we suggest that topical capsaicin be considered for initial management of postherpetic neuralgia Eighteen patients with the post-mastectomy pain syndrome ( PMPS ) form the basis of this study . PMPS probably occurs in a minority of women after mastectomy . The onset of persistent pain usually occurred immediately or very shortly after the operation . The pain location or sensory findings implied involvement of the territories of other cutaneous branches of the intercostal nerves as well as the intercostobrachial nerve . A variety of treatment approaches were unsatisfactory . Twelve of 14 patients completing treatment with topical 0.025 % capsaicin showed improvement after 4 weeks and 8 ( 57 % ) were judged to be good or excellent responses . Six months after the trial 's completion 50 % of those followed continued to have good pain relief . This therapy should now be subjected to a r and omized , double-blind , placebo-controlled trial An 8-week , double-blind , vehicle-controlled study was conducted to determine the effectiveness of topical capsaicin 0.075 % cream in relieving pain associated with diabetic neuropathy . Patients were selected who experienced moderate to very severe pain , which interfered with sleep or activities on a daily basis , and who were unresponsive or intolerant to conventional therapy . The results after 8 weeks showed a statistically significant difference in favor of the capsaicin-treated patients , with 90 % of these patients improved . The results of this study indicate that topical capsaicin 0.075 % cream is safe and effective in managing painful diabetic neuropathy CONTEXT R and omized trials with adequate sample size offer an opportunity to assess the safety of new medications in a controlled setting ; however , generalizable data on drug safety reporting are sparse . OBJECTIVE To scrutinize the completeness of safety reporting in r and omized trials . DESIGN , SETTING , AND PATIENTS Survey of safety reporting in 192 r and omized drug trials 7 diverse topics with sample sizes of at least 100 patients and at least 50 patients in a study arm ( N = 130074 patients ) . Trial reports were identified from comprehensive meta-analyses in 7 medical areas . MAIN OUTCOME MEASURES Adequate reporting of specific adverse effects and frequency and reasons for withdrawals due to toxic effects ; article space allocated to safety reporting and predictors of such reporting . RESULTS Severity of clinical adverse effects and laboratory-determined toxicity was adequately defined in only 39 % and 29 % of trial reports , respectively . Only 46 % of trials stated the frequency of specific reasons for discontinuation of study treatment due to toxicity . For these 3 parameters , there was significant heterogeneity in rates of adequate reporting across topics ( P = .003 , P<.001 , and P = .02 , respectively ) . Overall , the median space allocated to safety results was 0.3 page . A similar amount of space was devoted to contributor names and affiliations ( P = .16 ) . On average , the percentage of space devoted to safety in the results section was 9.3 % larger in trials involving dose comparisons than in those that did not ( P<.001 ) and 3.8 % smaller in trials reporting statistically significant results for efficacy outcomes ( P = .047 ) . CONCLUSIONS The quality and quantity of safety reporting vary across medical areas , study design s , and setting s but they are largely inadequate . Current st and ards for safety reporting in r and omized trials should be revised to address this inadequacy We assessed the quality of assessment and reporting of adverse effects in r and omized , double-blind clinical trials of single-dose acetaminophen or ibuprofen compared with placebo in moderate to severe postoperative pain . Reports were identified by systematic search ing of a number of bibliographic data bases ( e.g. , MEDLINE ) . Information on adverse effect assessment , severity and reporting , patient withdrawals , and anesthetic used was extracted . Compliance with former guidelines for adverse effect reporting was noted . Fifty-two studies were included ; two made no mention of adverse effects . No method of assessment was given in 19 studies . Twenty trials failed to report the type of anesthetic used , eight made no mention of patient withdrawals , and nine did not state the severity of reported adverse effects . Only two studies described the method of assessment of adverse effect severity . When all adverse effect data were pooled , significantly more adverse effects were reported with active treatment than with placebo . For individual adverse effects , there was no difference between active ( acetaminophen 1000 mg or ibuprofen 400 mg ) and placebo ; the exception was significantly more somnolence/drowsiness with ibuprofen 400 mg . Ninety percent of trials reporting somnolence/drowsiness with ibuprofen 400 mg were in dental pain . All studies published after 1994 complied with former guidelines for adverse effect reporting . Different methods of assessing adverse effects produce different reported incidence : patient diaries yielded significantly more adverse effects than other forms of assessment . We recommend guidelines for reporting adverse effect information in clinical trials PURPOSE A minority of cancer survivors develops long-term postsurgical neuropathic pain . Based on evidence that capsaicin , the pungent ingredient in hot chili peppers , might be useful for treating neuropathic pain , we developed the present clinical trial . PATIENTS AND METHODS Ninety-nine assessable patients with postsurgical neuropathic pain were entered onto this study . After stratification , patients were to receive 8 weeks of a 0.075 % capsaicin cream followed by 8 weeks of an identical-appearing placebo cream , or vice versa . A capsaicin/placebo cream was to be applied to the painful site four times daily . Treatment evaluation was performed by patient-completed weekly question naires . RESULTS During the first 8-week study period , the capsaicin-cream arm was associated with substantially more skin burning , skin redness , and coughing ( P < .0001 for each ) . Nonetheless , treatment was stopped for patient refusal or toxicity just as often while patients were receiving the placebo as compared with the capsaicin . The capsaicin cream arm had substantially more pain relief ( P = .01 ) after the first 8 weeks , with an average pain reduction of 53 % versus 17 % . On completion of the 16-week study period , patients were asked which treatment period was most beneficial . Of the responding patients , 60 % chose the capsaicin arm , 18 % chose the placebo arm , and 22 % chose neither ( P = .001 ) . CONCLUSION A topical capsaicin cream decreases postsurgical neuropathic pain and , despite some toxicities , is preferred by patients over a placebo by a three-to-one margin among those expressing a preference Distal symmetrical peripheral neuropathy ( DSPN ) is a particularly distressing pain syndrome associated with human immunodeficiency virus ( HIV ) disease . Capsaicin has been found to be effective in relieving pain associated with other neuropathic pain syndromes , and is mentioned as a possible topical adjuvant analgesic for the relief of DSPN . This multicenter , controlled , r and omized , double-masked clinical trial studied patients with HIV-associated DSPN and compared measures of pain intensity , pain relief , sensory perception , quality of life , mood , and function for patients who received topical capsaicin to the corresponding measures for patients who received the vehicle only . Twenty-six subjects were enrolled in the study . At the end of 1 week , subjects receiving capsaicin tended to report higher current pain scores than did subjects receiving the vehicle ( Mann-Whitney test ; P = 0.042 ) . The dropout rate was higher for the capsaicin group ( 67 % ) than for the vehicle group ( 18 % ) ( chi 2 test of association ; P = 0.014 ) . There were no other statistically significant differences between the capsaicin and vehicle groups with respect to current pain , worst pain , pain relief , sensory perception , quality of life , mood , or function at study entry or at any time during the 4-week trial . These results suggest capsaicin is ineffective in relieving pain associated with HIV-associated DSPN Atypical odontalgia is a distressing and unusual chronic orofacial pain condition . It is often difficult to diagnose because it is associated with a lack of clinical and radiographic abnormalities . The condition is poorly understood on a pathophysiological basis , and patients often undergo repetitive and unnecessary dental procedures in attempts to alleviate pain . In this study , 50 patients diagnosed with odontalgia were evaluated by pharmacological procedures , including topical anesthetic application and phentolamine infusion . Results of these pharmacological procedures suggest that atypical odontalgia is a neuropathic pain of the oral cavity that may have a component of sympathetically maintained pain . Therapeutic trials of topical capsaicin were carried out to assess its efficacy for pain reduction . Topical capsaicin was effective in most patients & NA ; We have completed a 12‐week double‐blind , placebo‐controlled r and omized study on the efficacy of the application of capsaicin ( CAPS ) cream ( 0.075 % ) in the treatment of chronic distal painful polyneuropathy . Forty patients were enrolled and 39 completed the study . The 2 limbs were r and omly assigned to CAPS or placebo ( PLAC ) . The cream was applied 4 times a day . The first tube contained the active PLAC , methyl nicotinate . In the final 4 weeks ( single‐blind wash‐out phase ) , PLAC was administered bilaterally . Efficacy was evaluated using the following scales : ( 1 ) investigator global , ( 2 ) patient global , ( 3 ) visual analog ( VAS ) of pain severity , ( 4 ) VAS of pain relief , ( 5 ) activities of daily living , and ( 6 ) allodynia . Patients were examined at onset and at monthly intervals using a neurologic disability scale , nerve conduction studies , computer‐assisted sensory examination for vibration and thermal cooling and warming , QSART ( quantitative sudomotor axon reflex test ) and quantitative flare response . There was no statistical evidence of efficacy of CAPS cream over PLAC for any of the pain indices . At early time points ( 1–4 weeks ) , there were a small number of indices that favored the PLAC . The percent of limbs that improved on the investigator 's global scale were 51.3 vs. 53.8 at 4 weeks , 56.4 vs. 64.1 at 8 weeks and 59 vs. 66.7 at 12 weeks for CAPS vs. PLAC ; no statistically significant difference was found . All the safety indices showed no difference between sides . We interpret the early hyperalgesia on the CAPS side as being responsible for the better performance of PLAC at early time points . The large percentage of limbs that improved may be a pronounced PLAC response & NA ; A data base of r and omised clinical trials ( RCTs ) in pain research published from 1950 to 1990 was created following an extensive literature search . By applying a refined MEDLINE search strategy from 1966 to 1990 and by h and ‐ search ing more than 1 000 000 pages of a total of 40 biomedical journals published during the period 1950–1990 , more than 8000 RCTs were identified . The RCTs were published in more than 800 journals and over 85 % appeared between 1976 and 1990 . If the trend of the last 15 years persists , a total of more than 15 000 RCTs will be published in pain relief by the year 2000 . A detailed description of methods to ensure efficient use of re sources during the identification , retrieval and management of the information in pain relief and other fields is given . Emphasis is made on the importance of refining MEDLINE search strategies , on the use of volunteers to h and ‐ search journals and on careful monitoring of each of the steps of the process . The potential uses of the data base to guide clinical and research decisions are discussed Summary In order to evaluate the efficacy , time-course of action and predictors of response to topical capsaicin , 39 patients with chronic post-herpetic neuralgia ( PHN ) , median duration 24 months , were treated with 0.025 % capsaicin cream for 8 weeks . During therapy the patients rated their pain on a visual analogue scale ( VAS ) and a verbal outcome scale . A follow-up investigation was performed 10–12 months after study onset on the patients who had improved . Nineteen patients ( 48.7 % ) substantially improved after the 8-week trial ; 5 ( 12.8 % ) discontinued therapy due to side-effects such as intolerable capsaicin-induced burning sensations ( 4 ) or mastitis ( 1 ) ; 15 ( 38.5 % ) reported no benefit . The decrease in VAS ratings was significant after 2 weeks of continuous application . Of the responders 72.2 % were still improved at the follow-up ; only one-third of them had continued application irregularly . Treatment effect was not dependent on patient 's age , duration or localization of PHN ( trigeminal involvement was excluded ) , sensory disturbance or pain character . Treatment response was not correlated with the incidence , time-course or severity of capsaicin-induced burning . If confirmed in controlled trials , the long-term results of this open , non-r and omized study might indicate that the analgesic effect of capsaicin in PHN is mediated by both interference with neuropeptide metabolism and morphological changes ( perhaps degeneration ) of nociceptive afferents Twelve informed and consenting patients were studied to determine the influence of capsaicin , the pungent component of the red pepper , on trigeminal neuralgia . All of these patients had idiopathic trigeminal neuralgia . These patients were followed up for 1 yr after the topical application over the painful area of 1.0 g of capsaicin three times a day for several days . Six patients had complete and four patients had partial relief of pain ; the remaining two patients had no relief of pain . Of the 10 patients who were responsive to therapy , four had relapses of pain in 95 - 149 days . There were no relapses following the second therapy for the remainder of the year . We conclude that the topical application of capsaicin is frequently successful in relieving the pain from trigeminal neuralgia OBJECTIVE To investigate why , in spite of a vast variety of treatment agents , the alleviation of pain in patients with diabetic neuropathy is difficult . Previous studies have not used a treatment algorithm based on anatomic site and neuropathophysiological source of the neuropathic pain . RESEARCH DESIGN AND METHODS A model that categorizes the types of pain into three groups ( superficial , deep , and muscular ) was applied in 75 diabetic patients with chronic ( > 12 mo ) painful distal symmetrical polyneuropathy in a controlled case series . Twenty-two patients were untreated and 53 patients were treated with imipramine ± mexiletine for deep pain , capsaicin for superficial pain , and stretching exercises and metaxalone ± piroxican for muscular pain . Each type of pain was scored separately on a scale of 0 ( none ) to 19 ( worst ) , and the total of all three types was used as an index of overall pain . Ability to sleep through the night was scored by a scale of 1 ( never ) to 5 ( always ) . RESULTS No significant differences were observed in initial pain scores , sleep scores , demographics , biochemistries , or physical findings between the two groups . After 3 mo a significant improvement in scores was noted in the treated but not the untreated patients . In addition , a significant difference was found in the change of scores between the treated and untreated patients : total pain ( −18 ± 2 vs. 0 ± 2 ) , deep pain ( −7 ± 1 vs. 0 ± 1 ) , superficial pain ( −5 ± 1 vs. 0 ± 1 ) , muscular pain ( −6 ± 1 vs. 0 ± 1 ) , and sleep ( 1.2 ± 0.2 vs. 0.2 ± 0.2 ) , all P < 0.0001 . In treated patients 21 % became pain-free ( total pain < 2 ) , 66 % had improvement ( decrease in total pain > 5 , but not total elimination of painful symptoms ) , and 13 % were considered treatment failures ( a decrease in total pain of < or = 5 ) . This compares with 0 ( P < 0.02 ) , 10 ( P < 0.0001 ) , and 90 % ( P < 0.0001 ) , respectively , in the untreated patients . CONCLUSIONS This study presents a new rationale and hypothesis for the successful treatment of chronic painful diabetic peripheral neuropathy . It uniquely bases the treatment algorithm on the types and sources of the pain AIMS To assess the analgesic efficacy of topical administration of 3.3 % doxepin hydrochloride , 0.025 % capsaicin and a combination of 3 . 3 % doxepin and 0.025 % capsaicin in human chronic neuropathic pain . METHODS A r and omized , double-blind , placebo-controlled study of 200 consenting adult patients . Patients applied placebo , doxepin , capsaicin or doxepin/capsaicin cream daily for 4 weeks . Patients recorded on a daily basis overall pain , shooting , burning , paraesthesia and numbness using a 0 - 10 visual analogue scale during the week prior to cream application ( baseline levels ) and for the 4 week study period . Side-effects and desire to continue treatment were also recorded . RESULTS Overall pain was significantly reduced by doxepin , capsaicin and doxepin/capsaicin to a similar extent . The analgesia with doxepin/capsaicin was of more rapid onset . Capsaicin significantly reduced sensitivity and shooting pain . Burning pain was increased by doxepin and by capsaicin and to a lesser extent by doxepin/capsaicin . Side-effects were minor . One patient requested to continue placebo cream , 17 doxepin cream , 13 capsaicin and 9 the combination of doxepin and capsaicin . CONCLUSIONS Topical application of 3.3 % doxepin , 0.025 % capsaicin and 3.3 % doxepin/0 . 025 % capsaicin produces analgesia of similar magnitude . The combination produces more rapid analgesia Abstract One way to ensure adequate sensitivity for analgesic trials is to test the intervention on patients who have established pain of moderate to severe intensity . The usual criterion is at least moderate pain on a categorical pain intensity scale . When visual analogue scales ( VAS ) are the only pain measure in trials we need to know what point on a VAS represents moderate pain , so that these trials can be included in meta‐ analysis when baseline pain of at least moderate intensity is an inclusion criterion . To investigate this we used individual patient data from 1080 patients from r and omised controlled trials of various analgesics . Baseline pain was measured using a 4‐point categorical pain intensity scale and a pain intensity VAS under identical conditions . The distribution of the VAS scores was examined for 736 patients reporting moderate pain and for 344 reporting severe pain . The VAS scores corresponding to moderate or severe pain were also examined by gender . Baseline VAS scores recorded by patients reporting moderate pain were significantly different from those of patients reporting severe pain . Of the patients reporting moderate pain 85 % scored over 30 mm on the corresponding VAS , with a mean score of 49 mm . For those reporting severe pain 85 % scored over 54 mm with a mean score of 75 mm . There was no difference between the corresponding VAS scores of men and women . Our results indicate that if a patient records a baseline VAS score in excess of 30 mm they would probably have recorded at least moderate pain on a 4‐point categorical scale & NA ; This paper describes a r and omized parallel trial of topical 0.075 % capsaicin versus vehicle ( placebo ) in the postmastectomy pain syndrome ( PMPS ) . The study was double‐blind in design ; however , this was compromised by the burning sensation induced by capsaicin . We could not demonstrate a significant difference in the visual analogue scale ( VAS ) for steady pain although a trend was present . A significant difference was found , however , in the VAS for jabbing pain , in category pain severity scales , and in overall pain relief scales in favour of capsaicin . Five of 13 patients on capsaicin were categorized as good‐to‐excellent responses with 8 ( 62 % ) having 50 % or greater improvement . Only 1 of 10 cases had a good response to vehicle with 3 rated as 50 % or better Background : HIV-associated distal sensory polyneuropathy ( HIV-DSP ) is a painful condition with limited effective treatment . Capsaicin desensitizes cutaneous nociceptors result ing in reduced pain . We report a placebo-controlled study of a high-concentration capsaicin dermal patch ( NGX-4010 ) for the treatment of painful HIV-DSP . Methods : This double-blind multicenter study r and omized 307 patients with painful HIV-DSP to receive NGX-4010 or control , a low-concentration capsaicin patch . After application of a topical anesthetic , NGX-4010 or control was applied once for 30 , 60 , or 90 minutes to painful areas on the feet . The primary efficacy endpoint was percent change in Numeric Pain Rating Scale ( NPRS ) from baseline in mean “ average pain for past 24 hours ” scores from weeks 2 to 12 . Results : A single NGX-4010 application result ed in a mean pain reduction of 22.8 % during weeks 2 to 12 as compared to a 10.7 % reduction for controls ( p = 0.0026 ) . Following a transient treatment-related pain increase , pain was reduced ; significant improvement was apparent by week 2 and continued throughout the controlled 12-week observation period . Mean pain reductions in the NGX-4010 30- , 60- and 90-minute groups were 27.7 % , 15.9 % , and 24.7 % ( p = 0.0007 , 0.287 , and 0.0046 vs control ) . One third of NGX-4010-treated patients reported ≥30 % pain decrease from baseline as compared to 18 % of controls ( p = 0.0092 ) . Self-limited , mild-to-moderate local skin reactions were commonly observed . Conclusions : A single NGX-4010 application was safe and provided at least 12 weeks of pain reduction in patients with HIV-associated distal sensory polyneuropathy . These results suggest that NGX-4010 could provide a promising new treatment for painful HIV neuropathy |
12,247 | 18,498,383 | CONCLUSIONS In adults with chronic periodontitis only minor differences in treatment effects were observed between the treatment strategies | OBJECTIVES To systematic ally review the effectiveness of full-mouth treatment concepts for chronic periodontitis . | A classical treatment for chronic adult periodontitis consists of four to six consecutive sessions of scaling and root planing at a 1- to 2-week interval . Such a so-called " quadrant or sextant therapy " might result in a reinfection of a previously disinfected area by bacteria from an untreated region . The purpose of this study was to investigate , over an 8-month period , the clinical benefits of full-mouth disinfection within a 24-hour period in the control of chronic periodontitis . Ten adult patients with advanced chronic periodontitis were r and omly assigned to a test and a control group . The control group received the st and ard scheme of initial periodontal therapy , consisting of scaling and root planing of the four quadrants was performed within 24 hours and immediately followed by a thorough supra- and subgingival chlorhexidine application to limit any transfer of bacteria . The latter involved tongue brushing with a 1 % chlorhexidine gel for 60 seconds , mouthrinsing with a 0.2 % chlorhexidine solution twice for 60 seconds , repeated subgingival irrigation of all pockets with a 1 % chlorhexidine gel ( 3 times within 10 minutes ) , and mouthrinsing twice daily with a 0.2 % chlorhexidine solution during 2 weeks . In addition , both groups received thorough oral hygiene instructions . The plaque index , gingival index , probing depth , gingival recession , and bleeding on probing were recorded prior to professional cleaning and at 1 , 2 , 4 , and 8 months afterwards . Although the test group scored higher plaque indices than the control group , especially at months 2 and 4 , the gingival index and bleeding tendency showed similar improvements with time . However , when the gingival/plaque ratio was considered , the latter was lower in the test group at all follow-up visits . For pockets > or = 7 mm , full-mouth disinfection showed a significantly ( P = 0.01 ) higher reduction in probing depth at each follow-up visit with , at month 8 , a reduction of 4 mm ( from 8 mm to 4 mm ) , in comparison to 3 mm ( from 8 mm to 5 mm ) for the classical therapy . The increase in gingival recession in the full-mouth disinfection group remained below 0.7 mm , while in the control group it reached 1.9 mm after 8 months . This result ed in a gain of clinical attachment level of 3.7 mm for the test group versus 1.9 mm for the control group . A radiographical examination also indicated a superior improvement for the test group when compared to the control group . This pilot study suggests that a full-mouth disinfection in one day results in an improved clinical outcome in chronic periodontitis as compared to scalings per quadrant at 2-week intervals over several weeks A treatment for periodontal infections often consists of consecutive rootplanings ( per quadrant , at a 1- to 2-week interval ) , without a proper disinfection of the remaining intra-oral niches ( untreated pockets , tongue , saliva , mucosa and tonsils ) . Such an approach , could theoretically lead to a reinfection of previously-treated pockets . The present study aims to examine the effect of a full-mouth disinfection on the microbiota in the above-mentioned niches . Moreover , the clinical benefit of such an approach was investigated . 16 patients with severe periodontitis were r and omly allocated to a test and a control group . The patients from the control group were scaled and rootplaned , per quadrant , at 2-week intervals and obtained oral hygiene instructions . The patients from the test group received a full-mouth disinfection consisting of : scaling and rootplaning of all pockets in 2 visits within 24 h , in combination with tongue brushing with 1 % chlorhexidine gel for 1 min , mouth rinsing with a 0.2 % chlorhexidine solution for 2 min and subgingival irrigation of all pockets ( 3x in 10 min ) with 1 % chlorhexidine gel . Besides oral hygiene , the test group rinsed 2x daily with 0.2 % chlorhexidine and sprayed the tonsils with a 0.2 % chlorhexidine for 2 months . Plaque sample s ( pockets , tongue , mucosa and saliva ) were taken at baseline and after 2 and 4 months , and changes in probing depth , attachment level and bleeding on probing were reported . The full-mouth disinfection result ed in a statistically significant additional reduction/elimination of periodontopathogens , especially in the subgingival pockets , but also in the other niches . These microbiological improvements were reflected in a statistically-significant higher probing depth reduction and attachment gain in the test patients . These findings suggest that a disinfection of all intra-oral niches within a short time span leads to significant clinical and microbiological improvements for up to 4 months OBJECTIVES The beneficial effects of the one-stage , full-mouth disinfection remain controversial in the scientific literature . This might be due to the fact that an entire mouth disinfection with the use of antiseptics has been confused with a full-mouth scaling and root planing . This parallel , single blind RCT study aim ed to compare several full-mouth treatment strategies with each other . MATERIAL AND METHODS Seventy-one patients with moderate periodontitis were r and omly allocated to one of the following treatment strategies : scaling and root planing , quadrant by quadrant , at two-week intervals ( negative control , NC ) , full-mouth scaling and root planing within 2 consecutive days ( FRP ) , or three one-stage , full-mouth disinfection ( FM ) protocol s within 2 consecutive days applying antiseptics to all intra-oral niches for periopathogens using as antiseptics : chlorhexidine ( FMCHX ) for 2 months , amine fluoride/stannous fluoride for 2 months ( FMF ) , or chlorhexidine for 2 months followed by amine fluoride/stannous fluoride for another 6 months ( FMCHX+F ) . At baseline and after 2 , 4 , and 8 a series of periodontal parameters were recorded . RESULTS All treatment strategies result ed in significant ( p<0.05 ) improvements of all clinical parameters over the entire duration of the study . Inter-treatment differences were often encountered . The NC group nearly always showed significant smaller improvements than the two CHX groups . The differences between the FRP or FM groups , and the two CHX groups only sporadically reached a statistical significance . CONCLUSION These observations indicate that the benefits of the " OSFMD " protocol are partially due to the use of the antiseptics and partially to the completion of the therapy in a short time Previous studies using correlation or regression analysis have showed that treatment effects measured by the change in clinical parameters are often associated with baseline values of the same parameters . These studies , however , have a method ological weakness . Correlation/regression between baseline measures and the derived change variable invali date s the statistical procedures of testing the null hypothesis : that the coefficient of correlation/regression is zero . This is due to the phenomenon of mathematical coupling . To investigate the impact that this has on the observed correlation/regression coefficient when in reality this is zero , we used r and om simulations of hypothetical data to model the treatment of periodontal pockets . Results showed a strong probability of obtaining statistically significant correlation/regression coefficients . To separate this artificial effect of mathematical coupling from the true underlying biological relationship , one must apply appropriate analytical strategies to re-evaluate previous evidence within the periodontal literature BACKGROUND / AIMS Recent studies reported significant additional clinical and microbiological improvements when severe adult periodontitis was treated by means of a " one-stage full-mouth " disinfection instead of a st and ard treatment strategy with consecutive root planings quadrant per quadrant . The one stage full-mouth disinfection procedure involves scaling and root planing of all pockets within 24 h in combination with an extensive application of chlorhexidine to all intra-oral niches such as periodontal pockets , tongue dorsum , tonsils ( chairside , and at home for 2 months ) . This study aims to examine the relative importance of the use of chlorhexidine in the one stage full-mouth disinfection protocol . METHODS Therefore , 3 groups of 12 patients each with advanced periodontitis were followed , both from a clinical and microbiological point of view , over a period of 8 months . The patients from the control group were scaled and root planed , quadrant per quadrant . at two-week intervals . The 2 other groups underwent a one stage full-mouth scaling and root planing ( all pockets within 24 h ) with ( Fdis ) or without ( FRp = full-mouth root planing ) the adjunctive use of chlorhexidine . At baseline and after 1 , 2 , 4 and 8 months , the following clinical parameters were recorded : plaque and gingivitis indices , probing depth , bleeding on probing and clinical attachment level . Microbiological sample s were taken from different intra-oral niches ( tongue , mucosa , saliva and pooled sample s from single- and multi-rooted teeth ) . The sample s were cultured on selective and non-selective media in order to evaluate the number of CFU/ml for the key-periodontopathogens . At baseline , an anonymous question naire was given to the patients to record the perception of each treatment ( post operative pain , fever , swelling etc . ) . RESULTS All 3 treatment strategies result ed in significant improvements for all clinical parameters , but the Fdis and FRp patients reacted always significantly more favourably than the control group , with an additional probing depth reduction of + /- 1.5 mm and an additional gain in attachment of + /- 2 mm ( for pockets > or = 7 mm ) . Also from a microbiological point of view both the FRp and Fdis patients showed additional improvements when compared to the control group , as well in the reduction of spirochetes and motile organisms as in the number of CFU/ml of the key-pathogens , especially when the subgingival plaque sample s were considered . The differences between FRp and Fdis patients were negligible . CONCLUSIONS These findings suggest that the benefits of a " one-stage full-mouth disinfection " in the treatment of patients suffering from severe adult periodontitis probably results from the full-mouth scaling and root planing within 24 h rather than the beneficial effect of chlorhexidine . The raise in body temperature the second day after the full-mouth scaling and root planing seems to indicate a Shwartzman reaction OBJECTIVES The aim of this study was to determine whether same-day full-mouth scaling and root planing ( FM-SRP ) and quadrant scaling and root planing ( Q-SRP ) result ed in variations in the systemic humoral immune response dynamics ( antibody titres and avidity ) during active treatment and 3 and 6 months post-therapy . MATERIAL S AND METHODS Forty patients with chronic periodontitis were recruited into this study . Subjects were r and omised into two groups and received either scaling and root planing quadrant by quadrant at 2-weekly intervals ( Q-SRP group ) or same-day full-mouth scaling and root planing ( FM-SRP group ) . Clinical measurements and serum sample s were obtained at baseline and approximately 6 weeks after the last clinical intervention ( R1 ) and 6 months after the initiation of therapy ( R2 ) . Furthermore , serum sample s were obtained from each patient undergoing therapy ( Q-SRP and FM-SRP ) at 3 bi-weekly instances so as to determine the short-term effects of each session of scaling and root planing on the dynamics of the humoral immune response . Serum antibody titre was assayed by enzyme-linked immunosorbent assay ( ELISA ) and antibody avidity was measured by thiocyanate dissociation against five putative periodontal pathogens : Porphyromonas gingivalis ; Actinobacillus actinomycetemcomitans ; Prevotella intermedia ; Treponema denticola and Bacteroides forsythus . RESULTS Both therapies result ed in similar antibody titre reductions against the majority of the organisms tested and although there was a distinct trend for antibody avidity to increase following therapy , this was not found to be statistically significant , reflecting marked inter-individual variation . In addition , no evidence emerged from this study to support increased antibody titres following the active phases of both treatment approaches due to an inoculation effect . Nevertheless , significant short-term increases in antibody avidity to most test bacteria were noted for both treatment strategies . CONCLUSION Both therapies were associated with a reduction in antibody titres and an increase in the binding ability or avidity of antibodies , but there was a marked inter-subject variability and statistical significance was reached for only some of the test bacteria . No significant differences in the humoral antibody dynamics were found between the two treatment approaches BACKGROUND The aim of the present study was to evaluate the effectiveness of non-surgical mechanical instrumentation at 2 different time intervals on short-term healing and to assess patient reactions following non-surgical periodontal therapy . METHODS The study population consisted of 100 patients with moderate periodontal disease . Patients were equally distributed into 2 groups , treated daily or weekly . The daily group received full-mouth daily scaling and root planing for 4 consecutive days . The weekly group was treated once a week for 4 weeks . All patients were asked for objective ( lymphadenopathy , aphthous stomatitis , and edema ) and subjective ( fatigue , pain , pruritus , burning sensation , and dentinalgia ) reactions . Clinical measurements of plaque index ( PI ) , gingival index ( GI ) , probing depth ( PD ) , bleeding on probing ( BOP ) , and gingival recession ( GR ) were taken at baseline and 3 months after treatment . All of the objective and subjective reactions were recorded after each treatment session . RESULTS The results of our study revealed a significant decrease in PI , GI , BOP , and PD measurements at the end of the third month , but no significant changes in GR . The incidence of subjective and objective reactions was higher in the daily treated group compared to those in the weekly group . Most of these complaints were observed after the third treatment session . CONCLUSIONS Within the limits of this study , no differences were observed between the study groups when the clinical parameters were evaluated . However , taking the subjective and objective reactions into consideration , the smallest time interval for non-surgical periodontal procedures might be 1 week BACKGROUND The aim of the present study was to evaluate the clinical effects of one-stage periodontal debridement with an ultrasonic instrument , associated with 0.5 % povidone (pvp)-iodine irrigation in patients with chronic periodontitis . METHODS Forty-five patients were r and omly assigned into three groups : the control group ( CG ) received quadrant root planing at 1-week intervals over four consecutive sessions ; the periodontal debridement plus pvp-iodine group ( PD-PIG ) received a 45-minute full-mouth debridement with an ultrasonic instrument , associated with 0.5 % pvp-iodine irrigation ; and the periodontal debridement group ( PDG ) received a 45-minute full-mouth periodontal debridement with an ultrasonic instrument , associated with NaCl irrigation . RESULTS At the 3-month evaluation , the mean probing depth ( PD ) reduction in CG was 2.51+/-0.52 mm , 2.53+/-0.50 mm in PD-PIG , and 2.58+/-0.60 mm in PDG ( P<0.05 ) . The clinical attachment level ( CAL ) analysis showed a statistically significant gain in all groups compared to baseline ( 1.87+/-0.56 mm [ CG ] , 1.94+/-0.70 mm [ PD-PIG ] , and 1.99+/-0.92 mm [ PDG ] ) . Intergroup analysis of PD and CAL at 1 and 3 months showed no differences ( P>0.05 ) . The N-benzoyl-L-arginine-p-nitroanilide ( BAPNA ) test showed a significant reduction in trypsin activity only during the first month ( P<0.05 ) ; at 3 months there were no differences compared to baseline ( P=0.80 ) . CONCLUSION This study provides no evidence that pvp-iodine is effective as an adjunct for one-stage periodontal debridement In a st and ard periodontal treatment strategy with consecutive root planings ( per quadrant at a one- to two-week interval ) , re-infection of a disinfected area might occur before completion of the treatment . This study examines , both clinical ly and microbiologically , whether a full-mouth disinfection within 24 hours significantly improves the outcome of periodontal treatment . Ten patients with advanced chronic periodontitis were r and omly allocated to a test and a control group . The patients from the control group received scalings and root planings as well as oral hygiene instructions per quadrant at two-week intervals . Full-mouth disinfection in the test group was sought by the removal of all plaque and calculus ( in two visits within 24 hours ) . In addition , at each of these visits , the tongue was brushed with a 1 % chlorhexidine gel for one min and the mouth rinsed with a 0.2 % chlorhexidine solution for two min . Furthermore , subgingival chlorhexidine ( 1 % ) irrigation was performed in all pockets . The recolonization of the pockets was retarded by oral hygiene and 0.2 % chlorhexidine rinses during two weeks . The clinical parameters were recorded , and plaque sample s were taken from the right upper quadrant at baseline and after one and two months . The test group patients showed a significantly higher reduction in probing depth for deep pockets at both follow-up visits ( p < 0.05 ) . At the one-month visit , differential phase-contrast microscopy revealed significantly lower proportions of spirochetes and motile rods in the test group ( p = 0.01 ) . Culturing showed that the test group harbored significantly fewer pathogenic organisms at one month ( p = 0.005 ) . At two months , the same sites harbored singificantly more " beneficial " bacteria ( p = 0.02 ) . Moreover , all sites of the test group initially harboring P. gingivalis ( 6/10 ) became negative after treatment . These findings suggest that it is possible to achieve a significant improvement of the treatment outcome ( both microbiologically and clinical ly ) with a one-stage full-mouth disinfection BACKGROUND The aim of this r and omized controlled clinical trial was to determine the effects of single-visit full-mouth ultrasonic debridement versus quadrant-wise therapy . MATERIAL AND METHODS Thirty-six subjects with chronic periodontitis , were r and omly allocated to three groups -- quadrant-wise ultrasonic debridement , single-visit full-mouth ultrasonic debridement with povidone iodine and single-visit full-mouth ultrasonic debridement with water . Whole-mouth plaque , bleeding on probing ( BOP ) , pocket depth and attachment level were recorded before treatment and 1 , 3 and 6 months post-treatment . Plaque and saliva sample s were collected for microbiological analysis . RESULTS After treatment , all groups showed significant improvement in clinical parameters . Full-mouth treatments result ed in similar improvements in full-mouth mean plaque percentage , probing pocket depth and probing attachment level as conventional therapy . When data were analysed based on pocket depth and tooth type , there was no difference between groups in probing depth reduction or attachment gains . The full-mouth groups demonstrated greater reduction in BOP% and number of pockets > or = 5 mm and the total treatment time was significantly shorter . The detection frequencies of periodontal pathogens in plaque and saliva showed slight changes with no difference between groups . CONCLUSION Single-visit full-mouth mechanical debridement may have limited additional benefits over quadrant-wise therapy in the treatment of periodontitis , but can be completed in a shorter time AIM To evaluate the clinical efficacy of ( i ) a single session of " full-mouth ultrasonic debridement " ( Fm-UD ) as an initial periodontal treatment approach and ( ii ) re-instrumentation of periodontal pockets not properly responding to initial subgingival instrumentation . METHODS Forty-one patients , having on the average 35 periodontal sites with probing pocket depth ( PPD ) > or = 5 mm , were r and omly assigned to two different treatment protocol s following stratification for smoking : a single session of full-mouth subgingival instrumentation using a piezoceramic ultrasonic device ( EMS PiezonMaster 400 , A+PerioSlim tips ) with water coolant ( Fm-UD ) or quadrant scaling/root planing ( Q-SRP ) with h and instruments . At 3 months , all sites with remaining PPD > or = 5 mm were subjected to repeated debridement with either the ultrasonic device or h and instruments . Plaque , PPD , relative attachment level ( RAL ) and bleeding following pocket probing ( BoP ) were assessed at baseline , 3 and 6 months . Primary efficacy variables were percentage of " closed pockets " ( PPD < or = 4 mm ) , and changes in BoP , PPD and RAL . RESULTS The percentage of " closed pockets " was 58 % at 3 months for the Fm-UD approach and 66 % for the Q-SRP approach ( p>0.05 ) . Both treatment groups showed a mean reduction in PPD of 1.8 mm , while the mean RAL gain amounted to 1.3 mm for Fm-UD and 1.2 mm for Q-SRP ( p>0.05 ) . The re-treatment at 3 months result ed in a further mean PPD reduction of 0.4 mm and RAL gain of 0.3 mm at 6 months , independent of the use of ultrasonic or h and instruments . The efficiency of the initial treatment phase ( time used for instrumentation/number of pockets closed ) was significantly higher for the Fm-UD than the Q-SRP approach : 3.3 versus 8.8 min . per closed pocket ( p<0.01 ) . The efficiency of the re-treatment session at 3 months was 11.5 min . for ultrasonic and 12.6 min . for h and instrumentation ( p>0.05 ) . CONCLUSION The results demonstrated that a single session of Fm-UD is a justified initial treatment approach that offers tangible benefits for the chronic periodontitis patient OBJECTIVES To determine the clinical effects of full mouth compared with quadrant wise scaling and root planing . METHOD Twenty patients with chronic periodontitis ( > or = 2 teeth per quadrant with probing pocket depths ( PPD ) > or = 5 mm and bleeding on probing ( BOP ) were r and omized into a test group treated in two sessions with subgingival scaling and root planing within 24 h ( full-mouth root planing ( FMRP ) ) and a control group treated quadrant by quadrant in four sessions in intervals of 1 week ( quadrant root planing ( QRP ) ) . PPD , relative attachment level ( RAL ) and BOP were recorded at baseline , 3 and 6 months . RESULTS Analysing first quadrant data , in moderately deep pockets ( 5 mm < or = PPD < 7 mm ) there was no evidence for a difference ( FMRP-QRP ) between both groups for PPD reduction ( mean : -0.128 mm ; CI : [ -0.949 , 0.693 ] ; p=0.747 ) , RAL gain ( mean : 0.118 mm ; CI : [ -0.763 , 1.000 ] ; p=0.781 ) , and BOP reduction ( mean : -20.1 % ; CI : [ -44.3 , 4.2 ] ; p=0.099 ) . Likewise , no significant differences between treatments were found for initially deep pockets ( PPD > or = 7 mm ) , neither for first quadrant nor for whole mouth data . CONCLUSION The results of the present study demonstrated equally favourable clinical results following both treatment modalities BACKGROUND A st and ard treatment strategy for periodontal infections often consists of 4 consecutive sessions of scaling and root planing ( per quadrant , at 1- to 2-week intervals ) , without proper disinfection of the remaining intra-oral niches for periodontopathogens . This could theoretically lead to a reinfection of previously disinfected pockets by bacteria from an untreated region/niche . This study aim ed to investigate , over an 8-month period , the clinical benefits of a one stage full-mouth disinfection in the control of severe periodontitis . METHODS Sixteen patients with early-onset periodontitis and 24 patients with severe adult periodontitis were r and omly assigned to test and control groups . The control group was scaled and root planed , per quadrant , at 2-week intervals and given st and ard oral hygiene instructions . A one stage full-mouth disinfection ( test group ) was sought by scaling and root planing the 4 quadrants within 24 hours in combination with the application of chlorhexidine to all intra-oral niches for periodontopathogens . Besides oral hygiene , the test group also rinsed twice daily with a 0.2 % chlorhexidine solution and sprayed the tonsils with a 0.2 % chlorhexidine spray , for 2 months . The plaque index , gingival index , probing depth , bleeding on probing , gingival recession , and clinical attachment level were recorded at baseline and at 1 , 2 , 4 , and 8 months afterwards . RESULTS The one stage full-mouth disinfection result ed , in comparison to the st and ard therapy , in a significant ( P < 0.001 ) additional probing depth reduction and gain in attachment up to 8 months . For initial pockets > or = 7 mm , the " additional " probing depth reduction at the 8 month follow-up was 1.2 mm for single-rooted and 0.9 mm for multi-rooted teeth , with corresponding additional gains in attachment of 1.0 mm and 0.8 mm , respectively . The additional improvements were observed for all subgroups ( adult periodontitis , generalized early-onset cases , smokers ) , with the largest differences in the non-smoking adult periodontitis patients . CONCLUSIONS These findings suggest that a one stage full-mouth disinfection results in an improved clinical outcome for the treatment of chronic adult or early-onset periodontitis as compared to scaling and root planing per quadrant at 2-week intervals |
12,248 | 19,588,437 | In the absence of r and omised evidence of efficacy for oral acemetacin in acute postoperative pain , we can not , at present , make any conclusions regarding its effectiveness . | BACKGROUND Acemetacin is a non-steroidal anti-inflammatory drug ( NSAID ) licensed for use in rheumatic disease and other musculoskeletal disorders in the UK , and widely available in other countries worldwide .
This review sought to evaluate the efficacy and safety of oral acemetacin in acute postoperative pain , using clinical studies of patients with established pain , and with outcomes measured primarily over 6 hours using st and ard methods .
This type of study has been used for many decades to establish that drugs have analgesic properties .
OBJECTIVES To assess the efficacy of single dose oral acemetacin in acute postoperative pain , and any associated adverse events . | Abstract Variability in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size Abstract A previously established relationship for deriving dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics has been tested using an independent data set . Individual patient information from 18 RCTs of parallel‐group design in acute postoperative pain ( after abdominal , gynaecological and oral surgery ) was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with > 50%maxTOTPAR for the different treatments . The relationship between the measures was investigated in 85 treatments with over 3400 patients . In 80 of 85 treatments ( 94 % ) agreement between calculated and actual number of patients with > 50%maxTOTPAR was within four patients per treatment and in 72 ( 85 % ) was within three ( average of 40 patients per treatment , range 21–58 patients ) . Summing the positive and negative differences between actual and calculated numbers of patients with > 50%maxTOTPAR gave an average difference of 0.30 patients per treatment arm . Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events , such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data in acute pain studies enables data published as means to be used for quantitative systematic review s which require data in dichotomous form & NA ; Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events — such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data , at least in acute pain models , indicates that more meaningful overviews or meta‐ analysis may be possible . This study investigated the relationship between continuous and dichotomous analgesic measures in a set of individual patient data , and then used that relationship to derive dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics . Individual patient information from 13 RCTs of parallel‐group and crossover design in acute postoperative pain was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with greater than 50 % pain relief ( > 50%maxTOTPAR ) for the different treatments . The relationship between the measures was investigated in 45 actual treatments and 10 000 treatments simulated using the underlying actual distribution ; 1283 patients had 45 separate treatments . Mean % maxTOTPAR correlated with the proportion of patients with > 50%maxTOTPAR ( r2 = 0.90 ) . The relationship calculated from all the 45 treatments predicted to within three patients the number of patients with more than 50 % pain relief in 42 of 45 treatments , and 98.8 % of 10 000 simulated treatments . For seven effective treatments , actual numbers‐needed‐to‐treat ( NNT ) to achieve > 50%maxTOTPAR compared with placebo were very similar to those derived from calculated data & NA ; A data base of r and omised clinical trials ( RCTs ) in pain research published from 1950 to 1990 was created following an extensive literature search . By applying a refined MEDLINE search strategy from 1966 to 1990 and by h and ‐ search ing more than 1 000 000 pages of a total of 40 biomedical journals published during the period 1950–1990 , more than 8000 RCTs were identified . The RCTs were published in more than 800 journals and over 85 % appeared between 1976 and 1990 . If the trend of the last 15 years persists , a total of more than 15 000 RCTs will be published in pain relief by the year 2000 . A detailed description of methods to ensure efficient use of re sources during the identification , retrieval and management of the information in pain relief and other fields is given . Emphasis is made on the importance of refining MEDLINE search strategies , on the use of volunteers to h and ‐ search journals and on careful monitoring of each of the steps of the process . The potential uses of the data base to guide clinical and research decisions are discussed The effect of 5 days ' treatment with indomethacin , acemethacin and proglumethacin on the gastroduodenal mucosa was endoscopically evaluated in healthy volunteers . In a r and omised double-blind crossover system 16 subjects received 50 mg t.i.d . indomethacin and 60 mg t.i.d . acemethacin , and a further 16 volunteers received 50 mg t.i.d . indomethacin and 150 mg t.i.d . proglumethacin . After 5 days both proglumethacin and acemethacin caused significantly less gastroduodenal lesions than indomethacin . Possible reasons for the apparently better gastro-duodenal tolerability of both indomethacin derivatives are discussed Abstract One way to ensure adequate sensitivity for analgesic trials is to test the intervention on patients who have established pain of moderate to severe intensity . The usual criterion is at least moderate pain on a categorical pain intensity scale . When visual analogue scales ( VAS ) are the only pain measure in trials we need to know what point on a VAS represents moderate pain , so that these trials can be included in meta‐ analysis when baseline pain of at least moderate intensity is an inclusion criterion . To investigate this we used individual patient data from 1080 patients from r and omised controlled trials of various analgesics . Baseline pain was measured using a 4‐point categorical pain intensity scale and a pain intensity VAS under identical conditions . The distribution of the VAS scores was examined for 736 patients reporting moderate pain and for 344 reporting severe pain . The VAS scores corresponding to moderate or severe pain were also examined by gender . Baseline VAS scores recorded by patients reporting moderate pain were significantly different from those of patients reporting severe pain . Of the patients reporting moderate pain 85 % scored over 30 mm on the corresponding VAS , with a mean score of 49 mm . For those reporting severe pain 85 % scored over 54 mm with a mean score of 75 mm . There was no difference between the corresponding VAS scores of men and women . Our results indicate that if a patient records a baseline VAS score in excess of 30 mm they would probably have recorded at least moderate pain on a 4‐point categorical scale |
12,249 | 29,665,028 | Metaregression analysis found no significant association between the effect of music interventions and age , sex , choice and timing of music , and type of anaesthesia .
CONCLUSION Music interventions significantly reduce anxiety and pain in adult surgical patients | BACKGROUND This study aim ed to evaluate anxiety and pain following perioperative music interventions compared with control conditions in adult patients . | Music is a method nurses can use to help relieve pain , however little is known about its effectiveness across cultures . In this study , Western music was tested for its effectiveness in reducing postoperative pain in 38 Taiwanese patients , and its acceptability was explored . A pretest and post-test experimental design was used with visual analogue scales to measure sensation and distress of pain . Before surgery , subjects were r and omly assigned to receive tape recorded music or the usual care . Those who were assigned to the music group chose among 5 types of sedative music . On postoperative Day 1 and Day 2 , the effectiveness of the tape-recorded music was investigated during 15 minutes of rest in bed . Patients were interviewed on Day 3 to determine their liking for the music , its calming effects , and the helpfulness of the music . Repeated measures analysis of variance showed a significant interaction between time and group in the distress of pain on Day 1 , but not on Day 2 , and in pain sensation on Day 2 , but not Day 1 . Subjects from Taiwan were similar to subjects in a previous study in the United States in their liking for the music , and in reports of the helpfulness of the music for pain sensation and distress , but fewer Taiwanese found the music calming , and they had different choices : more chose harp music and fewer chose jazz than subjects in the U.S. study , and some would prefer Buddhist hymns or popular songs heard in Taiwan . Findings support the use of culturally acceptable music in addition to analgesic medication for the sensation and distress of postoperative pain BACKGROUND The conduct of r and omized , controlled trials of nonpharmacologic treatments presents specific challenges that are not adequately addressed in trial reports . OBJECTIVE To develop an extension of the CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement for trials of nonpharmacologic treatments . DESIGN A consensus meeting was organized to develop an extension of the CONSORT Statement that addresses r and omized trials of nonpharmacologic treatments . To prepare for the meeting , a survey was conducted to identify the specific issues for discussion . SETTING Consensus meeting in Paris , France . PARTICIPANTS A total of 33 experts attended the meeting . The experts were method ologists ( n = 17 ) ; surgeons ( n = 6 ) ; editors ( n = 5 ) ; and clinicians involved in rehabilitation ( n = 1 ) , psychotherapy ( n = 2 ) , education ( n = 1 ) , and implantable devices ( n = 1 ) . MEASUREMENTS Experts indicated which of the 22 items on the CONSORT checklist should be modified or which additional items should be added specifically for nonpharmacologic treatments . During a 3-day consensus meeting , all items were discussed and additional method ological issues related to nonpharmacologic research were identified . RESULTS The consensus was that 11 items on the CONSORT checklist needed some modifications for nonpharmacologic trials : item 1 ( title and abstract ) , item 3 ( participants ) , item 4 ( interventions ) , item 7 ( sample size ) , item 8 ( r and omization ) , item 11 ( blinding ) , item 12 ( statistical methods ) , item 13 ( participant flow ) , item 15 ( baseline data ) , item 20 ( discussion : interpretation ) , and item 21 ( generalizability ) . In addition , the meeting participants added 1 item related to implementation of the intervention . LIMITATION Evidence was not always available to support the inclusion of each checklist item . CONCLUSION The methods and processes used to develop this extension could be used for other reporting guidelines . The use of this extension to the CONSORT Statement should improve the quality of reporting r and omized , controlled trials assessing nonpharmacologic treatments BACKGROUND Postoperative pain and anxiety are common in cardiac surgery patients . Studies have suggested that music can decrease anxiety in hospitalized patients . Primary Study Objective This study focused on the efficacy and feasibility of special music , which included nature sounds , for pain and anxiety . METHODS / DESIGN In this r and omized controlled trial , postoperative cardiovascular surgery patients were r and omly assigned to a music group to receive 20 minutes of st and ard postoperative care and music twice daily on postoperative days 2 through 4 or to a control group to receive 20 minutes of st and ard care with a quiet resting period twice daily on postoperative days 2 through 4 . SETTING Cardiovascular surgical unit of Saint Marys Hospital , Rochester , Minnesota . PARTICIPANTS One hundred patients completed the study ( music group , n = 49 ; control group , n = 51 ) . Intervention The music was delivered through CD players in the patients ' rooms . PRIMARY OUTCOME MEASURES Pain , anxiety , satisfaction , and relaxation were evaluated from visual analog scales . RESULTS Data showed a significant decrease in mean ( SD ) pain scores after the second session of day 2 for the music group ( change , ? 1.4 [ 1.4 ] ) compared with the control group ( change , ? 0.4 [ 1.4 ] ) ( P = .001 ) . Mean relaxation scores improved more at the first session of day 2 for the music group ( change , 1.9 [ 2.7 ] ) compared with the control group ( change , 0.3 [ 2.9 ] ) ( P = .03 ) . The music group also showed lower anxiety and increased satisfaction overall , but these differences were not statistically significant . No major barriers to using the therapy were identified . CONCLUSION Recorded music and nature sounds can be integrated into the postoperative care of cardiovascular surgery patients . The recordings may provide an additional means for addressing common symptoms of pain and anxiety while providing a means of relaxation for these patients Background : The instability of cardiovascular indices and anxiety disorders are common among patients undergoing coronary artery bypass graft ( CABG ) and could interfere with their recovery . Therefore , improving the cardiovascular indices and anxiety is essential . Objectives : This study aim ed to investigate the effect of music therapy on anxiety and cardiovascular indices in patients undergoing CABG . Patients and Methods : In this r and omized controlled trial , 60 patients hospitalized in the cardiovascular surgical intensive care unit of Shahid Beheshti Hospital in Qom city , Iran , in 2013 were selected using a consecutive sampling method and r and omly allocated into the experimental and control groups . In the experimental group , patients received 30 minutes of light music , whereas in the control group , patients had 30 minutes of rest in bed . The cardiovascular indices and anxiety were measured immediately before , immediately after and half an hour after the study . Data were analyzed using the chi-square test and repeated measures analysis of variance . Results : Compared to the immediately before intervention , the mean anxiety scores immediately after and 30 minutes after the intervention were significantly lower in the experimental group ( P < 0.037 ) while it did not significantly change in the control group . However , there were no significant differences regarding the cardiovascular indices in the three consecutive measurements ( P > 0.05 ) . Conclusions : Music therapy is effective in decreasing anxiety among patients undergoing CABG . However , the intervention was not effective on cardiovascular indices . Music can effectively be used as a non-pharmacological method to manage anxiety after CABG Pre‐operative anxiety is common and often significant . Ambulatory surgery challenges our pre‐operative goal of an anxiety‐free patient by requiring people to be ‘ street ready ’ within a brief period of time after surgery . Recently , it has been demonstrated that music can be used successfully to relieve patient anxiety before operations , and that audio embedded with tones that create binaural beats within the brain of the listener decreases subjective levels of anxiety in patients with chronic anxiety states . We measured anxiety with the State‐Trait Anxiety Inventory question naire and compared binaural beat audio ( Binaural Group ) with an identical soundtrack but without these added tones ( Audio Group ) and with a third group who received no specific intervention ( No Intervention Group ) . Mean [ 95 % confidence intervals ] decreases in anxiety scores were 26.3%[19–33 % ] in the Binaural Group ( p = 0.001 vs. Audio Group , p < 0.0001 vs. No Intervention Group ) , 11.1%[6–16 % ] in the Audio Group ( p = 0.15 vs. No Intervention Group ) and 3.8%[0–7 % ] in the No Intervention Group . Binaural beat audio has the potential to decrease acute pre‐operative anxiety significantly Many patients in the Surgical Holding Area become stressed and anxious . In a hospital setting music reduces patients ' anxiety . This study determined that music can reduce the anxiety and stress of patients in the Surgical Holding Area . In this study , one group of subjects listed to music while a second group did not . Subjects who listened to music while in the Surgical Holding Area had significantly less stress and anxiety than did those who did not listen to music . Both groups spent similar lengths of time in the Surgical Holding Area . The results strongly suggest that if music were available to all patients in the Surgical Holding Area , most would select this option , and they would experience less anxiety Background Due to the strong reduction in the length of hospital stays in the last decade , the period of in-hospital postoperative care is limited . After discharge from the hospital , guidance and monitoring on recovery and resumption of ( work ) activities are usually not provided . As a consequence , return to normal activities and work after surgery is hampered , leading to a lower quality of life and higher costs due to productivity loss and increased health care consumption . Objective With this study we aim to evaluate whether an eHealth care program can improve perioperative health care in patients undergoing commonly applied abdominal surgical procedures , leading to accelerated recovery and to a reduction in costs in comparison to usual care . Methods This is a multicenter r and omized , single-blinded , controlled trial . At least 308 patients between 18 and 75 years old who are on the waiting list for a laparoscopic cholecystectomy , inguinal hernia surgery , or laparoscopic adnexal surgery for a benign indication will be included . Patients will be r and omized to an intervention or control group . The intervention group will have access to an innovative , perioperative eHealth care program . This intervention program consists of a website , mobile phone app , and activity tracker . It aims to improve patient self-management and empowerment by providing guidance to patients in the weeks before and after surgery . The control group will receive usual care and will have access to a nonintervention ( st and ard ) website consisting of the digital information brochure about the surgical procedure being performed . Patients are asked to complete question naires at 5 moments during the first 6 months after surgery . The primary outcome measure is time to return to normal activities based on a patient-specific set of 8 activities selected from the Patient-Reported Outcomes Measurement Information System ( PROMIS ) physical functioning item bank version 1.2 . Secondary outcomes include social participation , self-rated health , duration of return to work , physical activity , length of recovery , pain intensity , and patient satisfaction . In addition , an economic evaluation alongside this r and omized controlled trial will be performed from the societal and health care perspective . All statistical analyses will be conducted according to the intention-to-treat principle . Results The enrollment of patients started in September 2015 . The follow-up period will be completed in February 2017 . Data cleaning and analyses have not begun as of the time this article was su bmi tted . Conclusions We hypothesize that patients receiving the intervention program will resume their normal activities sooner than patients in the control group and costs will be lower . Clinical Trial Netherl and s Trial Registry NTC4699 ; http://www.trialregister.nl/trialreg/admin/ rct view.asp?TC=4699 ( Archived by WebCite at http://www.webcitation.org/6mcCBZmwy Background : Music , as a non-pharmacological and inexpensive nursing intervention , can be used easily as a complementary technique in reducing pain along with other methods . While some studies have demonstrated pain to decrease after music , others found music to be ineffective on pain . Objectives : The aim of this study was to investigate the effect of music on postoperative pain in patients under open heart surgery . Patients and Methods : A quasi-experimental study was performed on 60 patients under open heart surgery referred to ICU of Shahid Beheshti hospital in Kashan city . Patients were r and omly divided into two groups including experimental and control groups . Patients in music group listened to nonverbal music for 30 minutes after surgery by headphones . The control group did not receive any intervention other than routine care . Before and after intervention , pain intensity was measured and recorded by visual analog scale in two groups . Data was analyzed using Chi-Square and t-tests . Results : Before intervention , the mean of pain intensity was 6.32 ± 0.21 and 6.10 ± 0.21 for experimental and control groups , respectively ; and the difference was not significant ( P = 0.21 ) . After intervention , the mean of pain intensity was 3.11 ± 0.12 and 5.81 ± 0.38 for experimental and control groups , respectively ; and the difference was significant ( P = 0.04 ) . Conclusions : Listening to the relaxant music can reduce postoperative pain . It is suggested that relaxant music be used as a complementary method in patients in order to reduce prospect i ve pain BACKGROUND High levels of anxiety during surgery are associated with poorer post-surgical outcomes . This prospect i ve , non-blinded r and omized controlled trial aim ed to compare the effectiveness of four intraoperative distraction interventions for anxiety and pain management during minimally invasive venous surgery under local anaesthetic . METHODS 407 patients presenting with varicose veins at a private clinic , were r and omized to one of four intraoperative distraction interventions or treatment as usual . All participants received endovenous thermoablation and /or phlebectomies of varicose veins . After losses to follow-up , 398 participants were entered into the analysis . Participants were r and omly allocated to one of the following intraoperative distraction techniques : patient selected music ( n = 85 ) , patient selected DVD ( n = 85 ) , interaction with nurses ( n = 81 ) , touch ( stress balls ) ( n = 80 ) or treatment as usual ( TAU , n = 76 ) . The state scale of the STAI , the Short-form McGill pain question naire and numeric rating scales were used to assess intraoperative pain and anxiety . RESULTS Intraoperative anxiety ratings were significantly lower when participants interacted with nurses , used stress balls or watched a DVD during surgery compared to treatment as usual . Intraoperative pain ratings were significantly lower than treatment as usual when participants interacted with nurses or used stress balls during surgery . Patients ' satisfaction was not significantly impacted by intraoperative distractions . CONCLUSIONS The use of simple intraoperative distraction techniques , particularly interacting with nurses , using stress balls or watching a DVD during surgery conducted under local anaesthetic can significantly improve patients ' experiences Background : Pain is a common phenomenon after surgery . Cardiac surgeries are no exception and patients generally experience acute pain after these surgeries . Inadequate pain management after cardiac surgery predisposes patients to many complications . Therefore , the aim of this study was to determine the effects of listening to preferred music on pain intensity after open heart surgery . Material s and Methods : This study was a r and omized clinical trial ( RCT ) conducted in open heart intensive care unit ( ICU ) of a university hospital in Sari , Iran . A total of 60 patients who were scheduled to undergo open heart surgery were r and omly allocated in two groups . Patients in the intervention group ( n = 30 ) listened to their preferred music by headphones for 30 minutes , whereas those in the control group ( n = 30 ) did not listen to music . Using a Numerical Rating Scale ( NRS ) , pain intensity was measured among the patients before the intervention , and immediately , 30 minutes and one hour after the intervention . Data was analyzed by Chi-square test , student 's t-test and repeated measures analysis of variance ( ANOVA ) . Findings : Mean pain intensity in the intervention group before , immediately after , 30 minutes and one hour after the intervention were 5.8 , 3.1 , 2.5 and 2.4 , respectively . Corresponding numbers in the control group were 4.7 , 4.7 , 4.8 and 4.9 , respectively . Repeated measures ANOVA showed music to significantly reduce pain intensity ( p = 0.0001 ) Conclusions : Music can be effective as a non-pharmacological , inexpensive , non-invasive and side effect free method for pain management after open heart surgery The anticipation of surgery has been recognized as a stressful event that produces anxiety for most patients ( Kapnoullas 1988 ) . Even minor surgical procedures can produce anxiety in patients ; this in turn can affect their postoperative recovery and lead to a risk of physiological complications ( Swindale 1989 ) . Thus , preoperative anxiety is identified as one of the common nursing diagnoses or problems for surgical patients The ambient noise of monitors , other patients , and staff in the postanesthesia care unit/operating room may elevate levels of anxiety . The purpose of our study was to determine the effect of music versus noise-blocking headphones on the level of anxiety in women undergoing gynecologic same-day surgery . Institutional Review Board approval was obtained . The women were approached for consent and r and omized to usual care , music with headphones , or headphones only . Preoperative and postoperative anxiety was rated on a scale of 0 to 10 . Music/headphones were continued throughout surgery and removed when Aldrete level of consciousness equaled 2 . The 119 women had a mean age of 38.8 ( st and ard deviation=2.2 ) years . Of interest , 51 ( 45 % ) reported very low preoperative anxiety ( 0 - 3/10 ) and were excluded . All groups experienced a drop in anxiety from pre- to postoperative status , but the usual care group had the least improvement ( P<.05 ) . The music group experienced the lowest postoperative anxiety scores ; the headphone group had a greater change overall . Music is a relatively inexpensive intervention , easy to administer , and noninvasive BACKGROUND Guided imagery and music can reportedly reduce pain and anxiety during surgery , but no comparative study has been performed for cutaneous surgery to our knowledge . OBJECTIVES We sought to determine whether short-contact recorded guided imagery or relaxing music could reduce patient pain and anxiety , and surgeon anxiety , during cutaneous surgical procedures . METHODS Subjects were adults undergoing excisional surgery for basal and squamous cell carcinoma . R and omization was to guided imagery ( n = 50 ) , relaxing music ( n = 54 ) , or control group ( n = 51 ) . Primary outcomes were pain and anxiety measured using visual analog scale and 6-item short-form of the State-Trait Anxiety Inventory , respectively . Secondary outcomes were anxiety of surgeons measured by the 6-item short-form of the State-Trait Anxiety Inventory and physical stress of patients conveyed by vital signs , respectively . RESULTS There were no significant differences in subjects ' pain , anxiety , blood pressure , and pulse rate across groups . In the recorded guided imagery and the relaxing music group , surgeon anxiety was significantly lower than in the control group . LIMITATIONS Patients could not be blinded . CONCLUSION Short-contact recorded guided imagery and relaxing music appear not to reduce patient pain and anxiety during excisional procedures under local anesthetic . However , surgeon anxiety may be reduced when patients are listening to such recordings BACKGROUND The relief of post-cesarean delivery pain is important . Good pain relief improves mobility and reduces the risk of thromboembolic disease , which may have been increased during pregnancy . Pain may impair the mother 's ability to optimally care for her infant in the immediate postpartum period and may adversely affect early interactions between mother and infant . It is necessary , therefore that pain relief be safe and effective and results in no adverse neonatal effects during breast-feeding . Music may be considered as a potential method of post cesarean pain therapy due to its noninvasiveness and lack of side effects . In this study we evaluated the effect of intraoperative music under general anesthesia for reducing the postoperative morphine requirements after cesarean section . METHODS In a double blind placebo-controlled trial , 100 women ( ASA I ) scheduled for elective cesarean section under general anesthesia , were r and omly allocated into two groups of fifty . After st and ardization of anesthesia , patients in the music group were exposed to a compact disk of Spanish guitar after induction of anesthesia up to the time of wound dressing . In the control group patients were exposed to white music . Post operative pain and anxiety were evaluated by visual analog scale ( VAS ) up to six hours after discharge from PACU . Morphine was given intravenously for reducing pain to VAS < or = 3 postoperatively . RESULTS There was not statistically significant difference in VAS for pain between two groups up to six hours postoperatively ( P>0.05 ) . In addition , morphine requirements were not different between two groups at different time intervals up to six hours postoperatively ( P>0.05 ) . There were not statistically significant difference between two groups regarding postoperative anxiety score and vomiting frequency ( P>0.05 ) . CONCLUSION As per conditions of this study , intraoperative Spanish music was not effective in reducing postoperative pain after cesarean section . In addition postoperative morphine requirement , anxiety , and vomiting were not affected by the music during general anesthesia 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 aim of this r and omized controlled trial was to determine the effect of jaw relaxation , music and the combination of relaxation and music on postoperative pain after major abdominal surgery during ambulation and rest on postoperative days 1 and 2 . Opioid medication provided for pain , following abdominal surgery , does not always give sufficient relief and can cause undesired side effects . Thus , additional interventions such as music and relaxation may provide more complete relief . Previous studies have found mixed results due to small sample sizes and other method ological problems . In a rigorous experimental design , 500 subjects aged 18 - 70 in five Midwestern hospitals were r and omly assigned by minimization to a relaxation , music , relaxation plus music , or control group . Interventions were taught preoperatively and tested postoperatively . The same amount of time was spent with subjects in the control group . Pain was measured with the visual analogue sensation and distress of pain scales . Demographic and surgical variables , and milligrams of parenteral or oral opioids in effect at the time of testing were not significantly different between the groups , nor did they correlate with pain scores . Controlling for pretest sensation and distress , orthogonal a priori contrasts and multivariate analysis of covariance indicated that the three treatment groups had significantly less pain than the controls , ( P = 0.028 - 0.000 ) which was confirmed by the univariate analysis of covariance ( P = 0.018 - 0.000 ) . Post hoc multivariate analysis revealed that the combination group had significantly less sensation and distress of pain than the control group on all post-tests ( P = 0.035 - 0.000 ) , and the relaxation and music groups had significantly less on all tests ( P = 0.022 - 0.000 ) except after ambulation . At post ambulation those using relaxation did not have significantly less pain than the controls on both days and those using music did not on day 1 , although there were some univariate effects . A corresponding significant decrease in mastery of the interventions from pre to post ambulation suggests the need for reminders to focus on the intervention during this increased activity . Physicians and nurses preparing patients for surgery and caring for them afterward , should encourage patients to use relaxation and music as adjuvants to medication for postoperative pain BACKGROUND After cesarean section surgery , routine pharmacologic methods of analgesia -- opioids and benzodiazepines -- may impair the immediate close contact of mother and neonate for their sedative and emetic effects . OBJECTIVES The aim of this study was to explore the effect of patient-selected music on postoperative pain , anxiety , opioid requirement , and hemodynamic profile . METHODS A total of 80 patients , American Society of Anesthesiologists ( ASA ) physical status I-II , scheduled to undergo general anesthesia and elective cesarean section surgery were enrolled . Patients were r and omly allocated to receive 30 minutes of music or silence via headphones postoperatively . Pain and anxiety were measured with a visual analogue scale . Total postoperative morphine requirement as well as blood pressure and heart rate were recorded after the intervention period . RESULTS Pain score and postoperative cumulative opioid consumption were significantly lower among patients in the music group ( p < 0.05 ) , while there were no group differences in terms of anxiety score , blood pressure , or heart rate ( p > 0.05 ) . CONCLUSIONS Postoperative use of patient-selected music in cesarean section surgery would alleviate the pain and reduce the need for other analgesics , thus improving the recovery and early contact of mothers with their children STUDY OBJECTIVE To determine whether playing music or blocking noise can reduce bispectral index ( BIS ) values during propofol sedation . DESIGN Prospect i ve , r and omized , single-blinded study . SETTING Operating room . PATIENTS 63 ASA physical status I and II patients , aged 55 to 75 years , undergoing total knee replacement . INTERVENTIONS Patients were divided into three groups : noise , silence , and music . After induction of combined spinal-epidural anesthesia , sedation was begun with 1.2 mug/mL of propofol in a target-controlled infusion . In the silence group , patients ' ears were packed tightly to block ambient noise , whereas patient-selected music was applied to patients in the music group . Patients in the noise group were exposed to ambient operating room noise . MEASUREMENTS Bispectral index measurement was recorded 7 times during operation . Ambient room noise was recorded at the same time sequence . MAIN RESULTS Sound level was highest when the saw ( T3 , 80.25 dB ) and the impact device ( T4 , 80.98 dB ) were in use . Bispectral index scores in the silence group during those times ( T3 , 68.5 vs 76.9 , P = 0.025 , and T4 , 67.6 vs 78 , P = 0.005 ) were lower than in the noise group . However , BIS scores were similar in the noise and music groups . Preoperative anxiety level , postoperative comfort level , and pain scores were similar in all groups . CONCLUSION Blocking noise is more effective than playing music in reducing BIS scores during propofol sedation in a noisy environment 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 most effective approach to managing patients ' pain in the immediate postoperative period may include a combination of pharmacologic agents and noninvasive , nonpharmacologic interventions . In this study , nurse research ers evaluated the effect of music on pain and anxiety levels and selected physiologic parameters of two groups of patients who were emerging and recovering from anesthesia . Patients in the treatment group listened to music through head-phones during the last 30 minutes of their surgical procedures and during the first hour in the postanesthesia care unit ( PACU ) . Patients in the control group had identical surgical procedures , received the same preoperative medications , and were managed with the same anesthesia protocol but did not listen to music in the OR or PACU . No differences existed between the two patient groups in the variables measured ; however , patients in the treatment group stated that music helped them relax and functioned as a distracter OBJECTIVES The aim of this study was first to find out the effect of music therapy on postoperative analgesia and second to determine the duration of its effect . METHODS Seventy patients who were undergoing elective cesarean delivery were enrolled . The patients were r and omly allocated into two groups as follows : In Group 1 , patients listened to music through a headphone for one hour after surgery , while in Group 2 , patients did not listen to any music during the same period . In the postanesthesia care unit , patients were connected to a Patient Controlled Analgesia ( PCA ) device . The PCA device ( tramadol 3 mg/ml ) was set to deliver a bolus of 20 mg , with a lockout interval of 15 min and 4-hour maximal dose of 150 mg . Postoperative pain was assessed with a visual analog scale ( VAS ) and consumption of tramadol was recorded at 4 , 8 , 12 , 16 , 20 and 24 hours . RESULTS There was a significant decrease in Group 1 with respect to PCA delivery frequency at the 4th hour postoperatively ( p<0.05 ) . Concerning the postoperative tramadol consumption , values measured at the 4th hour were significantly lower in Group 1 ( p<0.05 ) . The total amount of tramadol consumption and additional analgesic use in the postoperative 24 hours were again lower in Group 1 when compared with Group 2 ( p<0.05 ) . All VAS values were lower in Group 1 when compared with Group 2 ( p<0.05 ) . CONCLUSION We suggest that music therapy given after surgery decreases postoperative pain in the first 24 hours and the analgesic consumption during the first four hours BACKGROUND Many studies have pointed to strategies to cope with patient anxiety in colposcopy . Evidence shows that patients experienced considerable distress with the large loop excision of transformation zone ( LLETZ ) procedure and suitable interventions should be introduced to reduce anxiety . This study aim ed to investigate the effects of music therapy in patients undergoing LLETZ . MATERIAL S AND METHODS A r and omized controlled trial was conducted with patients undergoing LLETZ performed under local anesthesia in an out patient setting at Ramathibodi Hospital , Bangkok , Thail and , from February 2015 to January 2016 . After informed consent and demographic data were obtained , we assessed the anxiety level using State Anxiety Inventory pre and post procedures . Music group patients listened to classical songs through headphones , while the control group received the st and ard care . Pain score was evaluated with a visual analog scale ( VAS ) . Statistical analysis was conducted using Pearson Chi-square , Fisher 's Exact test and T-Test and p-values less than 0.05 were considered statistically significant . RESULTS A total of 73 patients were enrolled and r and omized , result ing in 36 women in the music group and 37 women in the non-music control group . The preoperative mean anxiety score was higher in the music group ( 46.8 VS 45.8 points ) . The postoperative mean anxiety scores in the music and the non-music groups were 38.7 and 41.3 points , respectively . VAS was lower in music group ( 2.55 VS 3.33 ) . The percent change of anxiety was greater in the music group , although there was no significant difference between two groups . CONCLUSIONS Music therapy did not significantly reduce anxiety in patients undergoing the LLETZ procedure . However , different interventions should be developed to ease the patients ' apprehension during this procedure Background Complementary therapies ( CT ) , such as relaxation technique , massage , guided imagery , and accupuncture have shown to benefit patients undergoing surgery . The aim of this study was to determine the feasibility of using audio relaxation technique ( ART ) , music intervention ( MI ) , nature video application with music ( NVAM ) , and nature video application without music ( NVA ) delivered via mobile technologies in a clinical setting . Secondary , the effects of ART , MI , NVAM and NVA on patients ’ state anxiety , pain perception , and perceived self-efficacy in healing were determined . Methods A r and omized clinical trial ( RCT ) involving 105 same day surgery ( SDS ) patients , who were assigned to an ART ( n = 25 ) , MI ( n = 25 ) , NVAM ( n = 15 ) , NVA ( n = 16 ) , or a control group ( n = 24 ) were assessed for state anxiety , self-reported pain , and self-efficacy four days prior to surgery , immediately prior and following a surgical intervention , and day five post-operative . Results ANOVA found no statistically significant differences in anxiety scores ; pain , or perceived self-efficacy between the five groups . Matched pairs t-Test revealed all participants had an increase in anxiety from pre-op to day 10 follow-up ; a significant change in pain levels from pre-op to day 10 follow-up ; and all participants had a significant increase in general self-efficacy from pre-op to day 10 follow-up . Mean pain level scores from day 1 to pre-op showed a significant decrease in pain for the ART group and NVAM group . Matched pairs t-Test for self-efficacy scores indicated the MI group and the NVA group had significant increases in self-efficacy . A significant decrease in anxiety from pre-op to day 10 for participants reporting a prior history of anxiety and for those reporting prior history of taking anti-anxiety medications . Conclusions Despite the non-significant findings between the five groups , at any measurement point , there were valuable trends toward significance and confirmed feasibility in a clinical setting . Among the groups there were statistically significant findings for all interventions on anxiety , pain , and self-efficacy . The feasability of the implementation of novel interventions of NVAM and NVAM adds to clinical practice and the CT literature .Trial registration Clinical Trials.gov Identifier : NCT02236455 ( September 4 , 2014 There is increasing interest in evaluating the use of nonpharmacologic interventions such as music to minimize potential adverse effects of anxiety-reducing medications . This study used a quasi-experimental design to evaluate the effects of a perioperative music intervention ( provided continuously throughout the preoperative , intraoperative , and postoperative periods ) on changes in mean arterial pressure ( MAP ) , heart rate , anxiety , and pain in women with a diagnosis of breast cancer undergoing mastectomy . A total of 30 women were assigned r and omly to a control group or to the music intervention group . Findings indicated that women in the intervention group had a greater decrease in MAP and anxiety with less pain from the preoperative period to the time of discharge from the recovery room compared with women in the control group . Music is a noninvasive and low-cost intervention that can be easily implemented in the perioperative setting , and these findings suggest that perioperative music can reduce MAP , anxiety , and pain among women undergoing mastectomy for breast cancer Abstract Open‐heart surgery patients report anxiety and pain with chair rest despite opioid analgesic use . The effectiveness of non‐pharmacological complementary methods ( sedative music and scheduled rest ) in reducing anxiety and pain during chair rest was tested using a three‐group pretest – posttest experimental design with 61 adult postoperative open‐heart surgery patients . Patients were r and omly assigned to receive 30 min of sedative music ( N=19 ) , scheduled rest ( N=21 ) , or treatment as usual ( N=21 ) during chair rest . Anxiety , pain sensation , and pain distress were measured with visual analogue scales at chair rest initiation and 30 min later . Repeated measures MANOVA indicated significant group differences in anxiety , pain sensation , and pain distress from pretest to posttest , P<0.001 . Univariate repeated measures ANOVA ( P≤0.001 ) and post hoc dependent t‐tests indicated that in the sedative music and scheduled rest groups , anxiety , pain sensation , and pain distress all decreased significantly , P<0.001–0.015 ; while in the treatment as usual group , no significant differences occurred . Further , independent t‐tests indicated significantly less posttest anxiety , pain sensation , and pain distress in the sedative music group than in the scheduled rest or treatment as usual groups ( P<0.001–0.006 ) . Thus , in this r and omized control trial , sedative music was more effective than scheduled rest and treatment as usual in decreasing anxiety and pain in open‐heart surgery patients during first time chair rest . Patients should be encouraged to use sedative music as an adjuvant to medication during chair rest Purpose The aim of this study was to evaluate the effects of perioperative psychological and music interventions in elderly patients undergoing elective surgery on anxiety , post-operative pain , and changes in heart rate variability ( HRV ) to ascertain if perioperative psychological and music interventions can affect overall anxiety levels . Material s and Methods Fourty elderly patients undergoing elective surgery were r and omized to two groups ; one group received psychological and music intervention , and the other was the control . The intervention group underwent psychological intervention and listening to music for 30 min before surgery . Results The mean change in HRV as determined by low frequency ( LF ) power measurements . After the intervention , the ratio of mean LF to high frequency ( HF ) power decreased significantly in the intervention group compared to before the intervention ( p<0.05 ) . In the control group , mean LF measurements and the ratio of LF : HF did not change significantly . In the intervention group , mean HF power was significantly higher after the procedure than before ( p<0.01 ) . Moreover , the mean self-rating anxiety score of the intervention group decreased after the procedure compared to before ( p<0.05 ) . The mean visual analogue score of the intervention group 6 hours after surgery was significantly lower than that of the control group ( p<0.01 ) . Conclusion Perioperative psychological and music interventions can reduce anxiety and postoperative pain in elderly patients Anecdotal reports support research findings in documenting the high incidence of negative postoperative outcomes after gynecologic ( GYN ) laparoscopic surgery . Three outcome measures , postoperative pain , postoperative nausea and vomiting ( PONV ) , and length of stay , have received considerable attention . Two nursing interventions frequently suggested for their positive effects are guided imagery and music therapy . An experimental pilot study was conducted to determine the effects of these nursing inventions on postoperative pain , PONV , and length of stay for GYN laparoscopic patients ( n = 84 ) . During the perioperative period , patients were r and omly assigned to one of 3 interventions : guided imagery audiotapes ( GI ) , music audiotapes ( MU ) , or st and ard care ( C ) , and outcome measures were evaluated . Results indicated that patients in both the guided imagery and music groups had significantly less pain on PACU discharge to home than the patients in the control group . These findings suggest that both guided imagery and music are effective strategies in improving pain , a difference that becomes apparent when the patient is ready to be discharged . It is possible that these interventions act as distractions in reducing the report of negative postoperative outcomes The purpose of this study was to examine the effects of music listening in older adults following hip or knee surgery . Acute confusion and pain after surgery can increase length of stay and reduce function . Study results demonstrate a reduction in acute confusion and pain and improved ambulation and higher satisfaction scores in older adults who listened to music BACKGROUND All surgery provokes various degrees of anxiety for patients . The environment leading up to surgery can affect anxiety levels . We performed a prospect i ve r and omized study to compare environmental factors around the time of cataract surgery in order to identify interventions that would minimize stress for patients . METHODS Patients scheduled to undergo cataract surgery at a university-affiliated hospital in Winnipeg were r and omly assigned to 1 ) receive orally administered lorazepam or a placebo before surgery ; 2 ) listen to relaxing music through headphones or routine background noise before surgery ; 3 ) walk ( or go by wheelchair if unable to walk ) to the operating room or go by stretcher ; and 4 ) listen to relaxing music through headphones or routine background noise during surgery . R and omization for part 1 was double blind ; for parts 2 and 3 the surgeon and anesthetist were blinded , but the patient was not . Patients were asked to rate their anxiety , sedation , nausea and pain on arrival at the preoperative area , about 30 minutes after arrival , on arrival in the operating room and on arrival in the postoperative area , on a visual analogue scale grade d from 0 ( " None " [ or " Wide awake " in the case of sedation ] ) to 10 ( " Worst possible " [ or " Asleep " in the case of sedation ] ) . Patient satisfaction and willingness to repeat the exact same form of treatment were also rated . RESULTS Of the 19 surgeons in the department 18 agreed to participate ; I withdrew during the study . Data were collected for 144 patients aged 26 to 93 years . Anxiety was highest on arrival at the institution and decreased progressively thereafter . Oral sedation and listening to music before surgery were associated with decreased anxiety and increased levels of sedation ( p = 0.002 ) . Walking to the operating room provided no benefit over going by stretcher . Listening to music through headphones during surgery was not accepted by many patients and , when used , negatively affected the surgeon 's assessment of the patient 's ability to cooperate . Surgeons reported movement more often among patients who received oral sedation than among those who did not ( chi2 = 0.01 ) . Levels of pain and nausea were extremely low in all patients , and satisfaction was very high . Patients who received regional local anesthesia had less pain and higher satisfaction than those who received topical anesthesia . Willingness to repeat the same treatment was extremely high . INTERPRETATION For patients undergoing cataract surgery , efforts should be directed toward reducing anxiety on arrival at the institution , when it is highest , and not just during surgery . Oral sedation and listening to music before surgery appear to be beneficial . Listening to music through headphones during surgery was not found to be advantageous Joint lavage for knee osteoarthritis is an invasive procedure that can be stressful and painful . We aim ed to assess the impact of music therapy on perioperative anxiety , pain and tolerability of the procedure in patients undergoing joint lavage performed with two needles . We r and omized all patients diagnosed with knee osteoarthritis and undergoing joint lavage in our department from November 2009 to October 2010 to an experimental group listening to recorded music or a control group receiving no music intervention . Perioperative anxiety and pain related to the procedure were self-reported on a visual analogic scale ( 0–100 mm visual analog scale [ VAS ] ) , and heart rate and blood pressure were measured during the procedure . Tolerability was assessed on a four- grade scale directly after the procedure . We included 62 patients ( 31 in each group ) . Mean age was 68.8 ± 12.6 years ( 72 % females ) . As compared with the control group , the music group had lower levels of perioperative anxiety ( 40.3 ± 31.1 vs. 58.2 ± 26.3 mm ; p = 0.046 ) and pain related to the procedure ( 26.6 ± 16.2 vs. 51.2 ± 23.7 mm ; p = 0.0005 ) . Moreover , heart rate was lower in the music group ( 69.5 ± 11.4 vs. 77.2 ± 13.2 ; p = 0.043 ) but not diastolic or systolic blood pressure . Tolerability was higher in the music group ( p = 0.002 ) . Music is a simple and effective tool to alleviate pain and anxiety in patients undergoing joint lavage for knee osteoarthritis Depression and anxiety are associated with increased risk of postoperative cardiac events and death in patients who have undergone coronary artery bypass graft surgery . These risks persist even several months after the procedure . Guided imagery has been used with cardiac surgery patients for some time and with numerous anecdotal reports of considerable benefit . In addition , this therapy is low-cost and easy to implement , and the literature holds ample evidence for its efficacy in symptom reduction in various patient population s. It was thus hypothesized that preoperative use of guided imagery would reduce postoperative distress in patients undergoing coronary artery bypass graft . Fifty-six patients scheduled to undergo coronary artery bypass graft at Columbia University Medical Center were r and omized into 3 groups : guided imagery , music therapy , and st and ard care control . Patients in the imagery and music groups listened to audiotapes preoperatively and intraoperatively . All patients completed psychological , complementary medicine therapies use , and other assessment s preoperatively and at 1 week and 6 months postoperatively . Only preoperative distress was predictive of postoperative distress at follow-up . Use of complementary medicine therapies was high in all groups and this fact , in addition to the small sample size , may have accounted for the lack of significant relationship between imagery and postoperative distress . Regardless , this complementary and alternative medicine therapy remains palatable to patients . Given its efficacy in other patient population s , it is worth exploring its potential utility for this population with a larger sample BACKGROUND : Music reduces stress responses in awake subjects . However , there remains controversy about the role of music or therapeutic suggestions during general anesthesia and postoperative recovery . We thus tested the hypothesis that intraoperative exposure to soothing music reduces the end-tidal concentration of sevoflurane ( ETSevo ) necessary to maintain bispectral index ( BIS ) near 50 during laparoscopic surgery . METHODS : Forty patients , aged 40–60 yrs , ASA I and II , undergoing laparoscopic hernias or cholecystectomy under general anesthesia were studied . All patients were connected to a BIS monitor . Anesthesia was induced with fentanyl 2 & mgr;g/kg , sevoflurane in oxygen , rocuronium ( 0.6 mg/kg ) , and maintained with sevoflurane in oxygen and 50 % nitrous oxide , with an infusion of fentanyl ( 1 & mgr;g · kg−1 · h−1 ) . Sevoflurane was titrated to maintain BIS near 50 throughout the procedure . Patients were r and omly assigned to either listen to music or not . RESULTS : The ETSevo necessary to maintain a BIS near 50 was virtually identical in patients who listened to music ( 1.29 ± 0.33 % ) and those who did not ( 1.27 ± 0.33 % , P = 0.84 ) . Patients who listened to music reported slightly less pain , but the difference was not statistically significant . Mean arterial blood pressure was slightly higher in patients who listened to music ( 101 ± 11 mm Hg ) than in those who did not ( 94 ± 10 mm Hg , P = 0.040 ) . CONCLUSIONS : The end-tidal concentration of sevoflurane required to maintain BIS near 50 during laparoscopic cholecystectomy was virtually identical in patients exposed to music or not . Although previous work suggests that music reduces preoperative stress and may be useful during sedation , our results do not support the use of music during surgery Objective —To determine whether minimum clinical ly significant difference in visual analogue scale ( VAS ) pain score varies according to the severity of pain reported . Method — Prospect i ve descriptive study of adult patients in an urban emergency department ( ED ) . On presentation to the ED , patients marked the level of their pain on a 100 mm , non-hatched VAS scale . At 20 minute intervals thereafter they were asked to give a verbal categorical rating of their pain as “ a lot better ” , “ a little better ” , “ much the same ” , “ a little worse ” or “ much worse ” and to mark the level of pain on a VAS scale of the same type as used previously . It was pre-defined that patients with VAS pain scores of 30 mm or less would be categorised as having mild pain , those with scores of 70 mm or more were categorised as having severe pain and those from 31 mm to 69 mm , moderate pain . The minimal clinical ly significant difference ( MCSD ) in VAS pain score was defined as the mean difference between current and preceding scores when the subject reported “ a little worse ” or “ a little better ” pain . Results —156 patients were enrolled in the study , yielding 88 evaluable comparisons where pain was rated as “ a little better ” or “ a little worse ” . The MCSD in VAS score in the group overall was 12 mm ( 95%CI 9 mm to 15 mm ) . MCSD in VAS score for the “ mild pain ” group was 11 mm ( 95%CI 4 mm to 18 mm ) , for the “ moderate pain ” group 14 mm ( 95%CI 10 mm to 18 mm ) and for the severe pain group , 10 mm ( 95%CI 6 mm to 14 mm ) . There is no statistical difference between the MCSD in VAS score between the severity groups . Conclusions —The MCSD in VAS pain score does not differ with the severity of pain being experienced Abstract The authors evaluated the efficacies of audio-recorded hypnosis with background music and music without hypnosis in the reduction of emotional and physical disturbances in patients scheduled for breast biopsy in comparison with a control group . A total of 75 patients were r and omly assigned to 3 different groups and evaluated at baseline and before and after breast biopsy using visual analog scales of stress , pain , depression , anxiety , fatigue , optimism , and general well-being . The results showed that , before breast biopsy , the music group presented less stress and anxiety , whereas the hypnosis with music group presented reduced stress , anxiety , and depression and increased optimism and general well-being . After the biopsy , the music group presented less anxiety and pain , whereas the hypnosis group showed less anxiety and increased optimism BACKGROUND While waiting for surgery , patients often exhibit fear and anxiety . Music is thought to be an alternative to medication to relieve anxiety . However , due to concerns about infection control , devices other than headphones may be considered for this purpose . OBJECTIVES The purpose of this study was to determine the anxiety-relieving effect of broadcast versus headphone music playing for patients awaiting surgery . DESIGN A r and omized controlled clinical study . SETTING The waiting area of an operating theater of a metropolitan teach hospital in Taiwan . PARTICIPANTS Alert adult with age between 20 and 65 years old waiting for surgery without premedications . METHODS A total of 167 patients were r and omly assigned to the headphone , broadcast and control groups . Both the headphone and the broadcast groups were provided with the same instrumental music , while the control group did not listen to any music . The tools for measuring anxiety were visual analogue scale ( VAS ) ranging from " not anxious at all " to " extremely anxious " and heart rate variability ( HRV ) . RESULTS The VAS score exhibited a significant decrease for both the headphone and broadcast groups . The low frequency and low-to-high frequency LF/HF ratio of the broadcast and headphone groups were significantly lower than those of the control group . None of the heart rate variables showed significant differences between the broadcast group and the headphone group . CONCLUSION Both headphone and broadcast music are effective for reducing the preoperative patient 's anxiety in the waiting room . RELEVANCE TO CLINICAL PRACTICE In order to take infection control into account , broadcast speakers can substitute for headphones for playing music to lower the anxiety level of patients waiting for surgery This study investigated the effect of humorous and musical distraction on preoperative anxiety among 46 patients scheduled for same day , elective , nondiagnostic surgery . Preoperative anxiety was measured with a horizontal visual analog scale after treatment group subjects listened to either a humorous audiotape or a tranquil music audiotape for 20 minutes and control group subjects received no intervention . Results show no significant difference between the group anxiety means . This study provides no evidence that humor or music decreases preoperative anxiety , but it also shows no evidence that perioperative nurses should avoid using humor or music as nursing interventions OBJECTIVE The purpose of this study was to investigate the music therapy ( MT ) effect in levels of intraoperative anxiety in patients undergoing crossectomy with stripping of the great saphenous vein and to assess the efficacy , safety , and feasibility of this alternative therapy as a complement of st and ard intraoperative care . MATERIAL AND METHODS The study is a simple blind , controlled , parallel groups , prospect i ve r and omized clinical trial . Patients were allocated by means of r and omized controlled sampling . The study was performed in the surgery room of Getafe University Hospital in Madrid . The study was carried out in 40 patients , 20 r and omized to the experimental group and 20 r and omized to the control group , with an age range from 27 to 70 years . The control group was given intraoperative routine attention , and the experimental group was given an MT passive intervention that consisted of audition of musical fragments during varicose veins surgery . These pieces previously showed relaxing actions on the cardiovascular system . The anxiety levels were measured by means of pre- and postsurgical question naires by a blinded investigator for the study arm to which the patients had been r and omized . Heart rate and systolic and diastolic blood pressures were determined during the intervention , and adrenaline and noradrenaline plasma levels were determined before and after the surgical procedure . RESULTS The majority of the patients in the MT group ( 95 % ) and st and ard care group ( 90 % ) completed the study . There were no statistical differences between the control and experimental groups in heart rate gradient or systolic and diastolic blood pressures measured after the intervention . The anxiety state and the stress feeling scale score after surgery were significantly inferior in the MT group ( 94.7 % vs 57.9 % decrease in anxiety levels , P < .05 , and stress score of 1.31 vs 2.36 , P < .05 , respectively ) . The adverse events ratio was low and occurred with similar frequency in both groups . CONCLUSIONS The MT intervention was easily implemented in the context of nursing care received during varicose vein surgery and was positively accepted and valued by the majority of the patients . MT is a safe procedure that is proved to reduce anxiety and stress in the study patients Purpose Music has long been known to reduce anxiety , minimize the need for sedatives , and make patients feel more at ease . The purpose of the study was to evaluate the effect of music in elderly out patients undergoing elective cataract surgery with retrobulbar block and monitored anaesthetic care using fentanyl or alfentanil and midazolam . Methods One hundred and twenty one patients were prospect ively and r and omly assigned to hear relaxing suggestions , white noise , operating room noise or relaxing music via audio-cassette headphones . Vital signs were documented before and after retrobulbar block and every 15 min thereafter . Anxiety was assessed using the State-Trait Anxiety Inventory ( STAI ) before and after surgery . Visual analogue scales ( VAS ) were used to assess anxiety and patient satisfaction postoperatively with a st and ardized question naire . Between group comparisons were made using Chi-Square , or ANOVA , where appropriate . Results There were no differences between groups in STAI or anxiety VAS scores at any time . Differences were noted in systolic blood pressure , but not in other vital signs . Patients ’ ratings of the whole operative experience , satisfaction with the tape played , general level of relaxation and preference for the chosen tape for subsequent surgery were different ( music > relaxing suggestions > white noise and OR noise , P < 0.05 ) . Conclusions Elderly patients undergoing cataract surgery under retrobulbar block were more satisfied with their experience if they heard relaxing music , rather than relaxing suggestions or white noise or OR noise . The type of auditory stimuli to which the patients were exposed did not influence the level of anxiety . RésuméObjectifOn sait depuis longtemps que la musique réduit l’anxiété , diminue le besoin de sédatifs , et procure du confort au patient . L’objectif de cette étude était d’évaluer l’influence de la musique chez des patients âgés opérés pour une cataracte en chirurgie ambulatoire réglée sous bloc rétrobulbaire associé à du fentanyl ou de l’alfentanil avec midazolam et sous surveillance anesthésique . MéthodesCent vingt et un patients étaient prospect ivement et aléatoirement assignés à entendre avec des écouteurs une vidéocassette qui transmettait un langage relaxant , le silence , les bruits d’une salle d’opération ou une musique reposante . Les signes vitaux étaient enregistrés avant et après le bloc rétrobulbaire et à toutes les 15 min par la suite . L’anxiété était évaluée sur l’inventaire des traits d’anxiété ( STAI ) avant et après la chirurgie . Une échelle visuelle analogue ( EVA ) servait à évaluer l’anxiété alors que le degré de satisfaction postopératoire était estimé sur un question naire st and ard . Les groupes étaient comparés avec le chi-carré ou l’ANOVA selon le cas . RésultatsII n’a jamais eu de différences entre les groupes pour le STAI et à l’EVA . Quant aux signes vitaux , on n’a observé des différences que pour la pression artérielle systolique . L’évaluation de l’expérience chirurgicale par le patient , sa satisfaction de la b and e magnétique écoutée , son degré de relaxation et sa préférence pour la b and e qu’il choisirait pour une chirurgie à venir était différents ( musique > langage relaxant > silence et bruits de la salle d’opération , P < 0,05 ) . Conclusion Des patients âgés soumis à une chirurgie pour cataracte sous bloc rétrobulbaire ont été plus satisfaits de leur expérience s’ils entendaient de la musique reposante plutôt qu’un langage relaxant , le silence ou les bruits d’une salle d’opération PURPOSE Patients undergoing impacted m and ibular third molar ( IMTM ) extraction often have severe perioperative anxiety , which may lead to increased perceptions of pain and vital sign instability throughout surgery . Intraoperational musical interventions have been used during operations to decrease patient anxiety levels . We investigated the anxiolytic effects of musical intervention during surgical extraction of an IMTM . We tested the hypothesis that musical intervention would have positive effects on patients ' vital signs , anxiety levels , and perceptions of pain . PATIENTS AND METHODS We recruited 219 patients with IMTM surgery to participate in this study . Participants were r and omly assigned to a music-treated group ( 106 subjects ) or a control group ( 113 subjects ) . In a preoperative meeting , patient demographic data were collected , and the patients ' favorite songs were selected . For the music-treated group , their selected music was played from the time of arrival to the operating room until the end of the operation . Perioperative anxiety and perceptions of pain were assessed using the Dental Anxiety Scale and the Visual Analog Scale , respectively . Patients ' vital signs ( blood pressure , heart rate , and respiratory rate ) were monitored throughout the surgery . One-way analysis of covariance using perioperative anxiety as a covariant was performed to compare intraoperative anxiety levels and perioperative perceptions of pain between the 2 groups . Repeated measures analysis of variance was used to compare changes in vital signs across surgical stages between the 2 groups . RESULTS Vital signs changed significantly throughout surgery according to the stage of the procedure . For both groups , vital signs increased from baseline and reached peak values at the time of the initial incision and then decreased quickly and plateaued within normal limits . There were no significant differences between groups in blood pressure ; however , the music-treated group showed a significantly smaller change in heart rate than the control group . The music-treated group reported significantly less intraoperative anxiety than the nonmusic-treated control group when controlling for preoperative anxiety levels ( F = 4.226 , P < .05 ) . CONCLUSION These results support the hypothesis that the use of patient-chosen music during surgical extraction of an IMTM significantly lowers patient intraoperative anxiety levels Background : Most postoperative patients have unrelieved pain despite the use of patient-controlled analgesia . Nurses need additional effective modalities . Relaxation and music ( RM ) , in addition to analgesics , have been shown to reduce pain more than do analgesics alone . Objectives : The objectives of the study were to test an intervention of patient teaching for pain management ( PT ) and compare it with RM for immediate and general effects on postoperative pain . Methods : Patients having abdominal surgery and receiving patient-controlled analgesia aged 18 - 75 years ( n = 517 ) were r and omized to four groups : PT , RM , a combination ( PTRM ) , and a control . A 2 × 2 factorial design was used to assess PT-Effects and RM-Effects . Immediate effects on pain were measured on visual analogue sensation and distress scales before and after five 20-min tests in the first 2 days . Because participants also listened independently , general nonimmediate effects were examined at eight other times . Results : Using multivariate analysis of covariance with contrasts and pretest control , immediate RM-Effects on pain were found at Day 1 a.m. ( p < .001 ) , Day 1 p.m. ( p = .04 ) , and Day 2 a.m. ( p = .04 ) . No PT-Effects or nonimmediate RM-Effects were found . Discussion : Patient teaching did not result in less pain and did not support the theoretical proposition that PT reduces pain . However , the immediate RM-Effects supported the proposition that nonpharmacological adjuvants to analgesics can ease pain without adding side effects Music therapy has been used in multiple health care setting s to reduce patient pain , anxiety , and stress . However , few available studies have investigated its effect on pain among breast cancer patients after radical mastectomy . The aim of this study was to explore the effects of music therapy on pain reduction in patients with breast cancer after radical mastectomy . This r and omized controlled trial was conducted at the Surgical Department of Oncology Center , First Affiliated Hospital of Xi’an Jiaotong University from March to November 2009 . A total of 120 breast cancer patients who received Personal Controlled Analgesia ( PCA ) following surgery ( mastectomy ) were r and omly allocated to two groups , an intervention group and a control group ( 60 patients in each group ) . The intervention group accepted music therapy from the first day after radical mastectomy to the third admission to hospital for chemotherapy in addition to the routine nursing care , while the control group received only routine nursing care . Pain scores were measured at baseline and three post-tests using the General Question naire and Chinese version of Short-Form of McGill Pain Question naire . The primary endpoint was the change in the Pain Rating Index ( PRI-total ) score from baseline . Music therapy was found to reduce the PRI-total score in the intervention group significantly compared with the control group with a mean difference ( 95 % CI ) of −2.38 ( −2.80 , −1.95 ) , −2.41 ( −2.85 , −1.96 ) , and −1.87 ( −2.33 , −1.42 ) for the 1st , 2nd , and 3rd post-tests , respectively . Similar results were found for Visual Analogue Scale ( VAS ) and Present Pain Intensity ( PPI ) scores . The findings of the study provide some evidence that music therapy has both short- and long-term positive effects on alleviating pain in breast cancer patients following radical mastectomy Purpose : This study was design ed to determine whether music or music in combination with therapeutic suggestions in the intra‐operative period under general anaesthesia could improve the recovery of hysterectomy patients Ambulatory surgery can create significant anxiety . This prospect i ve study measured whether music can influence anxiety and perioperative sedative requirements in out patients undergoing surgery with spinal anesthesia . We also evaluated the correlation between two anxiety measures , the State-Trait Anxiety Inventory test ( STAI ) and the 0- to 10-cm visual analog scale ( VAS 0–10 ) , with 0 meaning complete relaxation and 10 the worst feeling of anxiety possible . Fifty unpremedicated patients were r and omly assigned to listen to music of their choice via headset during the perioperative period ( Group I ) or to have no music ( Group II ) . All participants used patient-controlled IV midazolam sedation and underwent repeated evaluations of their anxiety level with the STAI and the VAS 0–10 . Midazolam requirements during surgery ( Group I , 0.6 ± 0.7 versus Group II , 1.3 ± 1.1 mg;P < 0.05 ) and for the whole perioperative period ( Group I , 1.2 ± 1.3 versus Group II , 2.5 ± 2.0 mg;P < 0.05 ) were smaller in patients listening to music . Anxiety levels , measured with STAI or VAS 0–10 , were similar in both groups . The Spearman ’s coefficient values between STAI and VAS 0–10 ranged from 0.532 to 0.687 . We conclude that patients listening to music require less midazolam to achieve a similar degree of relaxation as controls and that measures of anxiety obtained from the STAI and the VAS 0–10 are positively , but only moderately , correlated Purpose To investigate the anxiolytic effects of binaural beat embedded audio in patients undergoing cataract surgery under local anesthesia . Methods This prospect i ve RCT included 141 patients undergoing cataract surgery under local anesthesia . The patients were r and omized into three groups ; the Binaural beat music group ( BB ) , the plain music intervention group ( MI ) , and a control group ( ear phones with no music ) . Blood pressure ( BP ) and heart rate were measured on admission , at the beginning of and 20 min after the start of the operation . Peri-operative anxiety level was assessed using the State-Trait Anxiety Inventory question naire ( STAI ) . Results The BB and MI groups comprised 44 patients each and the control group 47 . Patients in the MI group and BB group showed significant reduction of STAI state scores after music intervention compared with the control group ( P<0.001 ) but the difference was not significant between the MI and BB group ( STAI-S score MI group −7.0 , BB group −9.0 , P=0.085 ) . Systolic BP was significantly lower in both MI ( P=0.043 ) and BB ( 0.040 ) groups although there was no difference between the two groups ( P=1.000 ) . A significant reduction in heart rate was seen only in the BB group ( BB vs control P=0.004 , BB vs MI P=0.050 , MI vs control P=0.303 ) . Conclusion Music , both with and without binaural beat , was proven to decrease anxiety level and lower systolic BP . Patients who received binaural beat audio showed additional decrease in heart rate . Binaural beat embedded musical intervention may have benefit over musical intervention alone in decreasing operative anxiety Background : Cardiac surgery is a common interventional procedure for ischemic and valvular heart disease . Cardiac surgery is accompanied by postoperative pain and anxiety . The use of music therapy has been shown to reduce pain , anxiety , and physiological parameters in patients having surgical procedures . Objectives : To compare the effects of music therapy versus a quiet , uninterrupted rest period on pain intensity , anxiety , physiological parameters , and opioid consumption after cardiac surgery . Subjects and methods : An experimental design was used . A total sample of 86 patients ( 69.8 % males ) were r and omized to 1 of 2 groups ; 50 patients received 20 minutes of music ( intervention ) , whereas 36 patients had 20 minutes of rest in bed ( control ) . Anxiety , pain , physiologic parameters , and opioid consumption were measured before and after the 20-minute period . Results : A significant reduction in anxiety ( P ≤ .001 ) and pain ( P = .009 ) was demonstrated in the group that received music compared with the control group , but no difference was observed in systolic blood pressure ( P = .17 ) , diastolic blood pressure ( P = .11 ) , or heart rate ( P = .76 ) . There was no reduction in opioid usage in the 2 groups . Conclusions : Patients recovering from cardiac surgery may benefit from music therapy AIMS AND OBJECTIVES The objective of this study was to evaluate the effects of musical intervention on preoperative anxiety and vital signs in patients undergoing day surgery . BACKGROUND Studies and systematic meta-analyses have shown inconclusive results of the efficacy of music in reducing preoperative anxiety . We design ed a study to provide additional evidence for its use in preoperative nursing care . DESIGN R and omised , controlled study . METHOD Patients ( n = 183 ) aged 18 - 65 admitted to our outpatient surgery department were r and omly assigned to either the experimental group ( music delivered by earphones ) or control group ( no music ) for 20 minutes before surgery . Anxiety , measured by the State-Trait Anxiety Inventory , and vital signs were measured before and after the experimental protocol . RESULTS A total of 172 patients ( 60 men and 112 women ) with a mean age of 40·90 ( SD 11·80 ) completed the study . The largest number ( 35·7 % ) was undergoing elective plastic surgery and 76·7 % of the total reported previous experience with surgery . Even though there was only a low-moderate level of anxiety at the beginning of the study , both groups showed reduced anxiety and improved vital signs compared with baseline values ; however , the intervention group reported significantly lower anxiety [ mean change : -5·83 ( SD 0·75 ) vs. -1·72 ( SD 0·65 ) , p < 0·001 ] on the State-Trait Anxiety Inventory compared with the control group . CONCLUSIONS Patients undergoing day surgery may benefit significantly from musical intervention to reduce preoperative anxiety and improve physiological parameters . RELEVANCE TO CLINICAL PRACTICE Finding multimodal approaches to ease discomfort and anxiety from unfamiliar unit surroundings and perceived risks of morbidity ( e.g. disfigurement and long-term sequelae ) is necessary to reduce preoperative anxiety and subsequent physiological complications . This is especially true in the day surgery setting , where surgical admission times are often subject to change and patients may have to accommo date on short notice or too long a wait that may provoke anxiety . Our results provide additional evidence that musical intervention may be incorporated into routine nursing care for patients undergoing minor surgery BACKGROUND The study objective was to explore the effect of music as an adjunct to local anesthesia on pain and anxiety during first-trimester surgical abortion . Secondary outcomes included patient satisfaction and coping . STUDY DESIGN We conducted a r and omized controlled pilot study of 26 women comparing music and local anesthesia to local anesthesia alone . We assessed pain , anxiety and coping with 11-point verbal numerical scales . Patient satisfaction was measured via a 4-point Likert scale . RESULTS In the music group , we noted a trend toward a faster decline in anxiety postprocedure ( p=.065 ) . The music group reported better coping than the control group ( mean±S.D. , 8.5±2.3 and 6.2±2.8 , respectively ; p<.05 ) . Both groups reported similarly high satisfaction scores . There were no group differences in pain . CONCLUSIONS Music as an adjunct to local anesthesia during surgical abortion is associated with a trend toward less anxiety postprocedure and better coping while maintaining high patient satisfaction . Music does not appear to affect abortion pain BACKGROUND Many patients undergoing Mohs micrographic surgery ( MMS ) experience anxiety and stress . Although music has been proven to reduce anxiety and promote relaxation in other fields of medicine , scant research investigates the effect of music on anxiety during MMS . OBJECTIVES To determine whether music can reduce anxiety in patients undergoing MMS . METHODS AND MATERIAL S An open‐labeled r and omized controlled trial was conducted to assess anxiety before and after listening to music . Subjects undergoing MMS were r and omly allocated to listen to self‐selected music ( n = 50 ) or to have surgery without music ( n = 50 ) . Anxiety was measured using the State‐Trait Anxiety Inventory ( STAI ) and on a visual analog scale ( VAS ) . RESULTS Subjects in the music group experienced statistically significantly lower STAI and VAS scores than those in the control group . STAI and VAS scores were significantly lower in subjects who underwent MMS for the first time . Anxiety measures did not correlate with sex or type of skin cancer . CONCLUSION Listening to self‐selected music reduces anxiety in patients undergoing MMS , especially those who undergo MMS for the first time . Presenting patients the opportunity to listen to music is a simple strategy to minimize anxiety during MMS AIM This paper reports a study to test the hypothesis that day surgery patients who listen to music during their preoperative wait will have statistically significantly lower levels of anxiety than patients who receive routine care . BACKGROUND Although previous day surgery research suggests that music effectively reduces preoperative anxiety , method ological issues limit the generalizability of results . METHODS In early 2004 , a r and omized controlled trial design was conducted to assess anxiety before and after listening to patient preferred music . Participants were allocated to an intervention ( n=60 ) , placebo ( n=60 ) or control group ( n=60 ) . Pre- and post-test measures of anxiety were carried out using the State-Trait Anxiety Inventory . RESULTS Music statistically significantly reduced the state anxiety level of the music ( intervention ) group . No relationships were found between socio-demographic or clinical variables such as gender or type of surgery . CONCLUSION The findings support the use of music as an independent nursing intervention for preoperative anxiety in patients having day surgery BACKGROUND : Data on the effect of Hemisync ® sounds on perioperative analgesic requirements are scant . METHODS : We r and omized surgical out patients into a treatment group that received Hemisync sounds ( n = 20 ) , a music group that received music ( n = 20 ) , and a control group that had a blank cassette tape ( n = 20 ) . All subjects underwent a controlled st and ardized propofol-nitrous-vecuronium and fentanyl general anesthesia . RESULTS : The treatment group had significantly reduced intraoperative fentanyl consumption ( P < 0.05 ) . Postoperatively , pain visual analog scale scores were significantly lower in the Hemisync group at 1 h ( P = 0.02 ) and 24 h ( P = 0.005 ) . Subjects in the Hemisync group were also discharged earlier ( P = 0.048 ) . CONCLUSION : The use of Hemisync sounds before and during general anesthesia reduces intraoperative analgesic requirements , postoperative pain scores , and discharge time PURPOSE Preoperative anxiety affects patients both physically and psychologically . It may also influence the patient 's perioperative experience and result in reduced patient satisfaction with care and potentially delayed recovery . Previous research indicates that patients who listen to music in the perioperative setting experience less anxiety than patients who do not listen to music . Research does not address the duration of music required to effectively reduce anxiety in this population . DESIGN A r and omized control trial was used . METHODS Two intervention groups ( 15-minute music and 30-minute music ) and one control group ( no music ) were compared . FINDINGS Patients ( n = 133 ) demonstrated less anxiety after listening to either 15 or 30 minutes of music ( P < .0001 ) . Patients ( n = 47 ) who listened to 15 minutes of music demonstrated less anxiety than those who did not listen to music ( P = .005 ) , whereas patients ( n = 41 ) who listened to 30 minutes of music demonstrated less anxiety than those who did not listen to music ( P < .001 ) . CONCLUSIONS Listening to as little as 15 minutes of music preoperatively is an effective method to reduce anxiety in patients who are about to have surgery AIM The present authors examined the effects of listening to music on psychophysiological parameters ( blood pressure , heart rate , and respiratory rate ) during preoperative and postoperative days and determined whether listening to music could lower pain intensity and opioid dosage during postoperative days in patients who underwent total knee replacements . METHODS This was a two group repeated measures design for 30 subjects aged 53 - 85 years who were scheduled for total knee replacement . Subjects were r and omly assigned to either a music group or a control group . Psychophysiological parameters were obtained from patients ' monitors . A visual analog scale was used to assess postoperative pain . Opioid dosage was recorded and converted to st and ardized units . Mann-Whitney U-test and generalized estimating equation analysis were used to compare groups . RESULTS Respiratory rates while in the surgical waiting area were lower for the music group than for the control group ( P = 0.02 ) . There was no significant difference between these groups for blood pressure , heart rate , pain intensity , or opioid dosage . However , a within-group comparison showed that systolic blood pressure in the music group was significantly and consistently decreased during postoperative recovery ( Wald = 9.21 , P = 0.007 ) . CONCLUSION These results suggest that listening to music stabilized systolic blood pressure in patients during postoperative recovery . However , the effects of music on psychophysiological parameters , pain intensity , and opioid dosage in a surgical setting require further research The purpose of this experimental study was to determine the effects of second and third day postoperative music interventions ( music , music video ) on pain and sleep in 96 postoperative patients having CABG surgery . The Verbal Rating Scale scores obtained before and after each 30-minute session showed that pain decreased over time for all three groups with no difference across groups . The McGill Pain Question naire ( MPQ ) was administered before session 1 and after session 2 , and results indicated that Sensory , Affective , and Present Pain Intensity subscales showed no group difference for pain ; however , pain decreased from Day 2 to Day 3 for all three groups . For the evaluative component of pain , those in the music group had significantly ( F [ 2,93 ] = 4.74 , p < .05 ) lower scores on postoperative Day 2 than the rest period control group . Effects of the intervention on sleep as measured by the Richard Sleep Question naire indicated that the video group had significantly ( F [ 2 , 92 ] = 3.18 , p < .05 ) better sleep scores than the control group on the third morning . These findings lend some support for selected music interventions The effect of intra‐operative compared to postoperative music on postoperative pain was evaluated in a controlled trial . In all , 151 patients undergoing day case surgery for inguinal hernia repair or varicose vein surgery under general anaesthesia were r and omly allocated to three groups : group 1 listened to music intra‐operatively , group 2 listened to music postoperatively and group 3 , the control group , listened to ‘ white noise ’ . The anaesthetic and postoperative analgesic techniques were st and ardised . Pain was assessed using a numeric rating scale ( 0–10 ) and patients requirements for postoperative morphine , paracetamol and ibuprofen was recorded . The effect of music on nausea , fatigue and anxiety was also investigated . The results showed that patients exposed to music intra‐operatively or postoperatively reported significantly lower pain intensity at 1 and 2 h postoperatively and patients in the postoperative music group required less morphine at 1 h compared to the control group . No differences were noted in the other variables . This study demonstrates that there is a short‐term pain‐reducing effect of music therapy however , the beneficial effects do not differ if the patient is exposed to music intra‐operatively or postoperatively The purpose of the study was to investigate the effects of music therapy on women 's physiologic measures , level of anxiety , and satisfaction during cesarean delivery . Sixty-four women who were planning to have a cesarean delivery were r and omly divided into an experimental and a control group . The experimental group received routine care and music therapy , whereas the control group received routine care only . Our results indicated that compared to the control group the experimental group had significantly lower anxiety and a higher level of satisfaction regarding the cesarean experience . No significant differences were found between the two groups in any of the physiological indexes . This controlled study provides evidence that music therapy can reduce anxiety and create a more satisfying experience for women undergoing cesarean delivery The purpose of this study was to determine if listening to music or having a quiet rest period just before and just after the first ambulation on postoperative day 1 can reduce pain and /or anxiety or affect mean arterial pressure , heart rate , respiratory rate , and /or oxygen saturation in patients who underwent a total knee arthroplasty . Fifty-six patients having a total knee arthroplasty were r and omly assigned to either a music intervention group or a quiet rest group . A visual analog scale was used to measure pain and anxiety . Physiologic measures , including blood pressure , heart rate , oxygen saturation , and respiratory rate , were also obtained . Statistical findings between groups indicated that the music group 's decrease in pain and anxiety was not significantly different from the comparison rest group 's decrease in pain ( F = 1.120 ; p = .337 ) or anxiety ( F = 1.566 ; p = .206 ) at any measurement point . However , statistical findings within groups indicated that the sample had a statistically significant decrease in pain ( F = 6.699 ; p = .001 ) and anxiety ( F = 4.08 ; p = .013 ) over time . Results of this research provide evidence to support the use of music and /or a quiet rest period to decrease pain and anxiety . The interventions pose no risks and have the benefits of improved pain reports and decreased anxiety . It potentially could be opioid sparing in some individuals , limiting the negative effects from opioids . Nurses can offer music as an intervention to decrease pain and anxiety in this patient population with confidence , knowing there is evidence to support its efficacy PURPOSE To examine effects of music therapy and progressive muscle relaxation training on depression , anxiety and length of hospital stay in Chinese female breast cancer patients after radical mastectomy . METHODS A total of 170 patients were r and omly allocated to the intervention group ( n = 85 ) receiving music therapy and progressive muscle relaxation training plus routine nursing care and the control group ( n = 85 ) receiving routine nursing care . Music therapy and progressive muscle relaxation training were performed twice a day within 48 h after radical mastectomy , once in the early morning ( 6a.m.-8a.m . ) and once in the evening ( 9p.m.-11p.m . ) , for 30 min per session until discharged from the hospital . RESULTS A general linear model with univariate analysis showed that the intervention group patients had significant improvement in depression and anxiety in the effects of group ( F = 20.31 , P < 0.001 ; F = 5.41 , P = 0.017 ) , time ( F = 56.64 , P < 0.001 ; F = 155.17 , P < 0.001 ) and group*time interaction ( F = 6.91 , P = 0.009 ; F = 5.56 , P = 0.019 ) . The intervention group patients had shorter length of hospital stay ( 12.56 ± 1.03 ) than that of the control group ( 17.01 ± 2.46 ) with statistical significance ( F = 13.36 , P < 0.001 ) . CONCLUSION Music therapy and progressive muscle relaxation training can reduce depression , anxiety and length of hospital stay in female breast cancer patients after radical mastectomy OBJECTIVE To evaluate the effects of music played preoperatively in women undergoing elective cesarean delivery . METHODS Sixty women undergoing elective cesarean delivery were r and omized to a study group or a control group . Those in the study group listened to music for 30 minutes before surgery . All women underwent heart rate variability analysis and scored their anxiety and pain levels using the Self-Rating Anxiety Scale and a visual analog pain scale . RESULTS In the study group the mean HRV , as measured by the low frequency power ( LF ) value and the LF to high frequency power ( LF/HF ) ratio during Holter assessment , was significantly less after the music intervention but was not significantly changed in the control group . Moreover , the mean HF value was significantly increased and the mean anxiety score was significantly decreased after the music intervention but not in the control group . Finally , the mean pain score obtained 6 hours after surgery was significantly lower in the study than in the control group . CONCLUSION A preoperative music intervention can reduce anxiety and pain in women undergoing cesarean delivery Introduction : Patients who await surgery often suffer from fear and anxiety , which can be prevented by anxiolytic drugs . Relaxing music may be an alternative treatment with fewer adverse effects . This r and omised clinical trial compared pre‐operative midazolam with relaxing music BACKGROUND Patients scheduled to invasive medical procedures experience high levels of anxiety , which may lead to increased perceptions of pain and vital sign instability throughout . AIMS To examine the effect of a music intervention ( MI ) on stress hormones , physiologic parameters , pain , and anxiety state before and during port catheter placement procedures ( PCPPs ) . METHODS We conducted a prospect i ve , r and omized , controlled study in 100 oncology patients , who were r and omly assigned to an MI group ( n=50 ) or a control group ( n=50 ) . The effects of music were assessed by determination of serum cortisol and adrenocorticotropic hormone ( ACTH ) levels , heart and respiratory rate ( HR , RR ) and systolic and diastolic blood pressure ( SBP , DBP ) , on arrival in the surgical intervention room , as well as immediately prior to and immediately after the PCPP , in both groups . Furthermore , pain and anxiety levels were identified using visual analogue scale and state-trait anxiety inventory scales . RESULTS On arrival , there were no differences between the patients in terms of serum cortisol and ACTH levels , HR , RR , SBP , DBP and anxiety levels . There were significant reductions in hormone levels ( p<0.05 for all ) , HR ( p<0.001 ) , RR ( p<0.001 ) , SBP ( p<0.05 ) and DBP ( p<0.05 ) , immediately prior to and immediately after the PCPP in participants in the MI group compared to those in the control group . Furthermore , music led to a significant reduction in pain ( p<0.05 ) and anxiety scores ( p<0.05 ) in the MI group compared to control group . CONCLUSION During invasive medical procedures , MI significantly decreases stress hormone levels , physiological parameters , acute procedural pain and anxiety BACKGROUND Music has served as an auxiliary analgesic in perioperative setting s. This study evaluates the impact of intraoperative music added to routine pain control measures during first trimester surgical abortion . STUDY DESIGN We analyzed data from 101 women r and omized to undergo abortion with routine pain control measures only ( ibuprofen and paracervical block ) or with the addition of intraoperative music via headphones . The primary outcome was the change in preoperative and postoperative pain scores on a 100-mm visual analog scale . Secondary outcomes included change in anxiety and vital signs , and satisfaction . RESULTS Baseline characteristics were similar between groups . The magnitude of increase in pain scores was greater in the intervention than in the control group ( + 51.0 mm versus + 39.3 mm , p=.045 ) . Overall pain control was rated as good or very good by 70 % of the intervention and 75 % of the control group ( p=.65 ) . CONCLUSIONS Intraoperative music added to routine pain control measures increases pain reported during abortion AIMS To evaluate the effects of music listening on pain intensity and pain distress on the first and second postoperative days in abdominal surgery patients and the long-term effects of music on the third postoperative day . BACKGROUND Music has been found to relieve pain intensity in surgery patients . There are only a few studies on music intervention in abdominal surgery . Music intervention studies assessing multidimensional pain such as pain intensity and pain distress are also scarce . DESIGN Prospect i ve clinical study with two parallel groups . METHODS Patients undergoing elective abdominal surgery ( n = 168 ) were divided into either a music group ( n = 83 ) or a control group ( n = 85 ) . Patients assessed pain intensity and pain distress in bed rest , during deep breathing and in shifting position once in the evening of the operation day and on the first and second postoperative days in the morning , at noon and in the evening . On the third postoperative day , the patients assessed their pain intensity and pain distress only once . RESULTS In the music group , the patients ' pain intensity and pain distress in bed rest , during deep breathing and in shifting position were significantly lower on the second postoperative day compared with control group of patients . On the third postoperative day , when long-term effects of music on pain intensity and pain distress were assessed , there were no significant differences between music and control groups . CONCLUSION This study demonstrates that the use of music alleviates pain intensity and pain distress in bed rest , during deep breathing and in shifting position after abdominal surgery on the second postoperative day . Music intervention is safe , inexpensive and easily used to improve the healing environment for abdominal surgery patients . RELEVANCE TO CLINICAL PRACTICE Music intervention should be offered as an adjunct alternative to pharmacological pain relief after abdominal surgery in nursing practice OBJECTIVE To examine the effectiveness of music listening on pain , anxiety , and vital signs among patients after thoracic surgery in China . DESIGN AND SETTING A r and omized controlled clinical trial was conducted in the thoracic surgery department of two tertiary hospitals in Wuhan , China . 112 patients were recruited and r and omly assigned to either experimental ( n=56 ) or control ( n=56 ) group respectively . INTERVENTION The experimental group received st and ard care and a 30-min soft music intervention for 3 days , while the control group received only st and ard care . Measures include pain , anxiety , vital signs ( blood pressure , heart rate and respiratory rate ) , patient controlled analgesia , and diclofenac sodium suppository use . RESULTS The experimental group showed statistically significant decrease in pain , anxiety , systolic blood pressure and heart rate over time compared to the control group , but no significant difference were identified in diastolic blood pressure , respiratory rate , patient controlled analgesia and diclofenac sodium suppository use . CONCLUSION The findings provide further evidence to support the practice of music therapy to reduce postoperative pain and anxiety , and lower systolic blood pressure and heart rate in patients after thoracic surgery in China Patients undergoing total knee arthroplasty ( TKA ) often experience a difficult recovery due to severe postoperative pain . Using a multimodal pain management protocol , a blinded , r and omized , placebo-controlled study was design ed to evaluate the efficacy of patient-selected music on reducing perceived pain . Thirty patients undergoing primary unilateral TKA were enrolled and r and omized into the music group ( 15 patients ) or the control group ( 15 patients ) . Postoperative pain scores , assessed with the visual analog scale , indicated the music group experienced less pain at 3 and 24 hours postoperatively than did the nonmusic group ( at 3 hours : 1.47+/-1.39 versus 3.87+/-3.44 , P=.01 ; at 24 hours : 2.41+/-1.67 versus 4.03+/-2.89 , P=.04 ) . Intraoperative music provides an inexpensive nonpharmacological option to further reduce postoperative pain The purpose of this study was to determine the effect of music listening on postoperative anxiety and intubation time in patients undergoing cardiovascular surgery . Coronary artery disease and valvular heart disease affect approximately 15 million Americans and 5 million persons in the U.K. annually , with the majority of these patients being older adults . The anxiety experienced before , during and after surgery increases cardiovascular workload , thereby prolonging recovery time . Music listening as a nursing intervention has shown an ability to reduce anxiety . The study used a r and omized control trial design . Sixty adults older than 65 years were r and omly assigned to the control and the experimental groups . The experimental group listened to music during and after surgery , while the control group received st and ard postoperative care . The Spielberger State Trait Anxiety Inventory was administered to both groups before surgery and 3 days postoperatively . The mean of the differences between scores was compared using analysis of variance . Differences in mean intubation time were measured in both groups . Older adults who listened to music had lower scores on the state anxiety test ( F = 5.57 , p = .022 ) and had significantly fewer minutes of postoperative intubation ( F = 5.45 , p = .031 ) after cardiovascular surgery . Older adults undergoing cardiovascular surgery who listen to music had less anxiety and reduced intubation time than those who did not This study examined the effect of music on pain , hemodynamic variables , and respiration in the PACU , and the impact of music on patients ' recall of their PACU experience . Sixty patients scheduled for thyroid , parathyroid , or breast surgery under general anesthesia were studied . Patients were r and omly assigned into three groups : group 1 , control , not wearing headphones ; group 2 , wearing headphones but hearing no music ; and group 3 , wearing headphones and listening to music . A visual analogue pain scale was used to rate patients ' perception of pain . There was no difference in pain level , morphine requirement , hemodynamics , respiration , or length of stay in the PACU among the 3 groups , yet the music group was able to wait significantly longer before requiring analgesia on the nursing unit . Patients who listened to music perceived their PACU experience as significantly more pleasant than the patients in the other two groups as recalled both 1 day and 1 month later Management of pain in the immediate postoperative period is a major concern of postanesthesia nurses . Music is a nursing intervention with the potential to decrease patient perception of pain in the PACU . The purpose of this study was to examine the effect of the use of music on the level of patient pain in the immediate postoperative period . A quasi-experimental study design was used with three study groups . All patients scheduled for elective abdominal hysterectomies using a general anesthesia technique were eligible for participation in the study . The setting is a PACU in a community hospital in a suburban area . Subjects were asked to rate their pain level every 15 minutes while in the PACU using two valid and reliable measures , a verbal pain rating scale and a graphic numeric pain intensity scale . Repeated measures of analysis of variance showed no differences in level of pain between groups or over time In the present prospect i ve , r and omized controlled trial , 110 unpremedicated patients undergoing orthopedic surgery under regional anesthesia were r and omly divided into 5 groups , with 22 patients in each . During the operation , group 1 listened to a pre-recorded explanation and music , group 2 listened to a subliminal sound , group 3 received propofol by patient-controlled sedation ( PCS ) , group 4 received intravenous midazolam , and group 5 was the control group . Patients in the midazolam group were significantly more se date d than the control group at 1 hr into the operation . The group that listened to an explanation and music were significantly less satisfied than the propofol group at the end of the operation and 30 min . postoperatively . An incremental cost-effectiveness ratio showed that if explanation and music are used instead of propofol it would save 299.53 baht per patient , but the patient satisfaction score will be 17.26 points lower than if the more expensive drug is used Pharmacological methods to improve postoperative pain are well documented , but an increasing interest in nonpharmacological methods has stimulated research in this field . Traditional and pharmacological interventions to relieve perioperative anxiety and pain are being challenged by an increasing dem and for more holistic approaches . This study tested the hypothesis that listening to music preoperatively and postoperatively would affect patients ' experience of pain , nausea , and well-being and have an impact on their vital signs . The authors conclude that a period of peaceful rest before and after surgery reduces patient anxiety Background To determine whether music influences intraoperative sedative and analgesic requirements , two r and omized controlled trials were performed . Methods In phase 1 , 35 adults undergoing urologic procedures with spinal anesthesia and patient‐controlled intravenous propofol sedation were r and omly assigned to hear favorable intraoperative music via headset or to have no music . In phase 2 , 43 adults undergoing lithotripsy treatment of renal or ureteral calculi and receiving patient‐controlled intravenous opioid analgesia were r and omly assigned to either a music or no‐music group . The effect of music on sedatives and analgesics requirements , recovery room duration , and adverse outcomes was assessed . Results In phase 1 , patients in the music group required significantly less propofol for sedation than patients in the control group ( 0 [ 0–150 ] mg vs. 90 [ 0–240 ] mg , median[range ] ; P < 0.001 ) . These findings persisted after adjusting for duration of surgery ( 0.3 + /‐ 0.1 mg/min vs. 1.6 + /‐ 0.4 mg/min ; P < 0.001 ) . Similarly , in phase 2 , patients who listened to music had a significant reduction in alfentanil requirements ( 1,600 [ 0–4,250 ] [ micro sign]g vs. 3,900 [ 0–7,200 ] [ micro sign]g ; P = 0.005 ) . This persisted after adjusting for duration of surgery ( 52 + /‐ 9 [ micro sign]g/min vs. 119 + /‐ 16 [ micro sign]g/min , mean + /‐ SD , P < 0.001 ) . Duration of stay in the postanesthesia care unit and the rate of adverse events was similar in both groups ( P = NS ) . Conclusions Use of intraoperative music in awake patients decreases patient‐controlled sedative and analgesic requirements . It should be noted , however , that patients in the no‐music group did not use a headset during operation . Thus , the decrease in sedative and analgesic requirements could be caused by elimination of ambient operating room noise and not by the effects of music PURPOSE To investigate the effect of live and recorded perioperative music therapy on anesthesia requirements , anxiety levels , recovery time , and patient satisfaction in women experiencing surgery for diagnosis or treatment of breast cancer . PATIENTS AND METHODS Between 2012 and 2014 , 207 female patients undergoing surgery for potential or known breast cancer were r and omly assigned to receive either patient-selected live music ( LM ) preoperatively with therapist-selected recorded music intraoperatively ( n=69 ) , patient-selected recorded music ( RM ) preoperatively with therapist-selected recorded music intraoperatively ( n=70 ) , or usual care ( UC ) preoperatively with noise-blocking earmuffs intraoperatively ( n=68 ) . RESULTS The LM and the RM groups did not differ significantly from the UC group in the amount of propofol required to reach moderate sedation . Compared with the UC group , both the LM and the RM groups had greater reductions ( P<.001 ) in anxiety scores preoperatively ( mean changes [ and st and ard deviation : -30.9 [ 36.3 ] , -26.8 [ 29.3 ] , and 0.0 [ 22.7 ] ) , respectively . The LM and RM groups did not differ from the UC group with respect to recovery time ; however , the LM group had a shorter recovery time compared with the RM group ( a difference of 12.4 minutes ; 95 % CI , 2.2 to 22.5 ; P=.018 ) . Satisfaction scores for the LM and RM groups did not differ from those of the UC group . CONCLUSION Including music therapy as a complementary modality with cancer surgery may help manage preoperative anxiety in a way that is safe , effective , time-efficient , and enjoyable Background : This study was design ed to determine whether music ( M ) , or music in combination with therapeutic suggestions ( M/TS ) could improve the postoperative recovery in the immediate postoperative in daycare surgery The physiological and psychological stress that brain tumor patients undergo during the entire surgical experience can considerably affect several aspects of their hospitalization . The purpose of this study was to examine the effects of live music therapy on quality of life indicators , amount of medications administered and length of stay for persons receiving elective surgical procedures of the brain . Subjects ( N = 27 ) were patients admitted for some type of surgical procedure of the brain . Subjects were r and omly assigned to either the control group receiving no music intervention ( n = 13 ) or the experimental group receiving pre and postoperative live music therapy sessions ( n = 14 ) . Anxiety , mood , pain , perception of hospitalization or procedure , relaxation , and stress were measured using a self-report Visual Analog Scale ( VAS ) for each of the variables . The documented administration of postoperative pain medications ; the frequency , dosage , type , and how it was given was also compared between groups . Experimental subjects live and interactive music therapy sessions , including a pre-operative session and continuing with daily sessions until the patient was discharged home . Control subjects received routine hospital care without any music therapy intervention . Differences in experimental pretest and posttest scores were analyzed using a Wilcoxon Matched-Pairs Signed-Rank test . Results indicated statistically significant differences for 4 of the 6 quality of life measures : anxiety ( p = .03 ) , perception of hospitalization ( p = .03 ) , relaxation ( p = .001 ) , and stress ( p = .001 ) . No statistically significant differences were found for mood ( p > .05 ) or pain ( p > .05 ) levels . Administration amounts of nausea and pain medications were compared with a Two-Way ANOVA with One Repeated Measure result ing in no significant differences between groups and medications , F(1 , 51 ) = 0.03 ; p > .05 . Results indicate no significant differences between groups for length of stay ( t = .97 , df = 25 , p > .05 ) . This research study indicates that live music therapy using patient-preferred music can be beneficial in improving quality of life indicators such as anxiety , perception of the hospitalization or procedure , relaxation , and stress in patients undergoing surgical procedures of the brain Music may decrease the anxiety experienced by patients before surgery . Previous studies of this issue were hindered with multiple method ological problems . In this investigation , we examined this hypothesis while using a rigorous study design and objective outcome measures . Adult patients undergoing anesthesia and surgery were r and omly assigned to two study groups . Subjects in Group 1 ( n = 48 ) listened to a 30-min patient-selected music session , and subjects in Group 2 ( n = 45 ) received no intervention . By using self-report vali date d behavioral ( State-Trait Anxiety Inventory ) and physiological measures of anxiety ( heart rate , blood pressure , and electrodermal activity and serum cortisol , epinephrine , and norepinephrine ) , patients were evaluated before , during , and after administration of the intervention . We found that after intervention , subjects in the Music group reported significantly lower anxiety levels as compared with the Control group ( F1,91 = 15.4 , P = 0.001 ) . That is , the postintervention anxiety level of subjects in the Music group decreased by 16 % as compared with the preintervention level , whereas the anxiety level of the Control group did not change significantly . Two-way repeated- measures analysis of variance performed for the electrodermal activity , blood pressure , heart rate , cortisol , and catecholamine data demonstrated no group difference and no time × group interaction ( P = not significant ) . In conclusion , under the conditions of this study , patients who listened to music before surgery reported lower levels of state anxiety . Physiological outcomes did not differ , however , between the two study groups Liver and kidney transplant recipients report elevated psychological distress following transplant in comparison to other types of organ transplant recipients . Negative affective states can lead to immune dysregulation and adverse health behaviors , and therefore may contribute to disease . In contrast , positive affective states can broaden individuals ' thoughts and actions to promote the accumulation of coping re sources . Coping strategies have traditionally been conceived of as being either problem-focused or emotion-focused in nature , while contemporary theory and research supports a different division : approach-oriented strategies versus avoidance-oriented strategies . Emotional expression and processing may function as an approach-oriented coping strategy . Emotional-approach coping relates to the use of emotional expression , awareness and underst and ing to facilitate coping with significant life stressors . The current study evaluated the impact of music therapy with and without a specific emphasis on emotional-approach coping . This r and omized , controlled trial aim ed to use Active Music Engagement with Emotional-Approach Coping to improve well-being in post-operative liver and kidney transplant recipients ( N = 29 ) . Results indicated that music therapy using Emotional-Approach Coping led to significant increases in positive affect , music therapy using Active Music Engagement led to significant decreases in pain , and both conditions led to significant decreases in negative affect , an indicator of perceived stress/anxiety OBJECTIVE To evaluate the effect of bed rest with music on the first postoperative day to decrease stress for patients who have undergone heart surgery . METHODS A repeated- measures r and omized controlled trial was used . The study took place in a cardiothoracic intermediary unit of a university hospital in Sweden . Fifty-eight patients who had undergone open coronary artery bypass grafting or aortic valve replacement surgery were included . Stress response was assessed by determining the serum cortisol , heart rate , respiratory rate , mean arterial pressure , arterial oxygen tension , arterial oxygen saturation , and subjective pain and anxiety levels . At 12:00 noon on postoperative day 1 , patients were allocated to receive 30 minutes of uninterrupted bed rest with music and then 30 minutes of bed rest or alternatively 60 minutes of uninterrupted bed rest . The music was soft and relaxing , included different melodies in new-age style , played with a volume at 50 to 60 dB , and distributed through a music pillow connected to an MP3 player . RESULTS After 30 minutes of bed rest , there was a significant difference in s-cortisol levels between the groups ; 484 . 4 mmol/L in the music group versus 618.8 mmol/L in the control group ( P < .02 ) . However , this difference in s-cortisol levels was not found 30 minutes later ( ie , after a total of 60 minutes ) . There was no difference in heart rate , respiratory rate , mean arterial pressure , arterial oxygen tension , arterial oxygen saturation , and subjective pain and anxiety levels between the groups . CONCLUSION There is sufficient practical evidence of stress reduction to suggest that a proposed regimen of listening to music while resting in bed after open heart surgery be put into clinical use This experimental study compared the effects of jaw relaxation and music , individually and combined , on sensory and affective pain following surgery . Abdominal surgical patients ( N = 84 ) were r and omly assigned to four groups : relaxation , music , a combination of relaxation and music , and control . Interventions were taught preoperatively and used by subjects during the first ambulation after surgery . Indicators of the sensory component of pain were sensation and 24-hour narcotic intake . Indicator of the affective component of pain were distress and anxiety of pain . With preambulatory sensation , distress , narcotic intake , and preoperative anxiety as covariates , the four groups were compared using orthogonal a priori contrasts and analysis of covariance . The interventions were neither effective nor significantly different from one another during ambulation . However , after keeping the taped interventions for 2 postoperative days , 89 % of experimental subjects reported them helpful for sensation and distress of pain Background and objectives : This r and omized controlled trial was design ed to evaluate , first , whether intra‐ or postoperative music therapy could influence stress and immune response during and after general anaesthesia and second , if there was a different response between patients exposed to music intra‐ or postoperatively . Method : Seventy‐five patients undergoing open hernia repair as day care surgery were r and omly allocated to three groups : intraoperative music , postoperative music and silence ( control group ) . Anaesthesia and postoperative analgesia were st and ardized and the same surgeon performed all the operations . Stress response was assessed during and after surgery by determining the plasma cortisol and blood glucose levels . Immune function was evaluated by study ing immunoglobulin A ( IgA ) levels . Patients ' postoperative pain , anxiety , blood pressure ( BP ) , heart rate ( HR ) and oxygen saturation were also studied as stress markers . Results : There was a significantly greater decrease in the level of cortisol in the postoperative music group vs. the control group ( 206 and 72 mmol L−1 decreases , respectively ) after 2 h in the post anaesthesia care unit . The postoperative music group had less anxiety and pain and required less morphine after 1 h compared with the control group . In the postoperative music group the total requirement of morphine was significantly lower than in the control group . The intraoperative music group reported less pain after 1 h in the post anaesthesia care unit . There was no difference in IgA , blood glucose , BP , HR and oxygen saturation between the groups . Conclusion : This study suggests that intraoperative music may decrease postoperative pain , and that postoperative music therapy may reduce anxiety , pain and morphine consumption Acute post‐operative pain is a predictor in the development of chronic pain after laparoscopic cholecystectomy . Music has been shown to reduce surgical stress . In a r and omized , clinical trial , we wanted to test the hypothesis that perioperative and post‐operative soft music reduces pain , nausea , fatigue and surgical stress in patients undergoing laparoscopic cholecystectomy as day surgery OBJECTIVE Postoperative pain is caused by surgical injury and trauma ; is stressful to patients ; and includes a series of physiologic , psychological , and behavioral reactions . Effective postoperative analgesia helps improve postoperative pain , perioperative safety , and hospital discharge rates . This study aim ed to observe the influence of postoperative intravenous sufentanil patient-controlled analgesia combined with music therapy versus sufentanil alone on hemodynamics and analgesia in patients with lung cancer . METHODS This was a r and omized parallel study performed in 60 patients in American Society of Anesthesiologists class I or II undergoing lung cancer resection at the Affiliated Cancer Hospital of Xiangya School of Medicine , Central South University . Patients were r and omly assigned to a music therapy ( MT ) group and a control ( C ) group . The MT group underwent preoperative and postoperative music intervention while the C group did not . Both groups received intravenous patient-controlled sufentanil analgesia . The primary outcome was the visual analogue scale ( VAS ) score at 24 hours after surgery . The secondary outcomes included hemodynamic changes ( systolic blood pressure , diastolic blood pressure , heart rate ) , changes on the Self-Rating Anxiety Scale ( SAS ) , total consumption of sufentanil , number of uses , sedation , and adverse effects . The postoperative sufentanil dose and analgesia frequency were recorded . RESULTS Compared with the C group , the MT group had significantly lower VAS score , systolic and diastolic blood pressure , heart rate , and SAS score within 24 hours after surgery ( p < 0.01 ) . In addition , postoperative analgesia frequency and sufentanil dose were reduced in the MT group ( p < 0.01 ) . CONCLUSIONS Combined music therapy and sufentanil improves intravenous patient-controlled analgesia effects compared with sufentanil alone after lung cancer surgery . Lower doses of sufentanil could be administered to more effectively improve patients ' cardiovascular parameters AIM OF THE STUDY To test the effects of music intervention on pre-operative anxiety in Chinese males undergoing transurethral resection of the prostate . RATIONALE No studies have measured the effects of music intervention in reducing pre-operative anxiety for patients with transurethral resection of the prostate ( TURP ) . Previous studies have examined the effects of music on pre-operative anxiety but have not examined the possible effects of the presence of a carer as an independent variable in pre-operative anxiety levels of patients in addition to the music intervention . The cultural validity of applying a music intervention to the reduction of pre-operative anxiety was also investigated . DESIGN A quasi-experimental design with three groups : music intervention , nurse presence and control group . METHOD Thirty patients having TURP were r and omly assigned ( n = 10 each group ) to one of the three groups . Pre- and post-test measures of systolic and diastolic blood pressure , heart rate and state anxiety using the Chinese State-Trait Anxiety Inventory ( C-STAI ) were obtained for the three groups . RESULTS The findings showed that the music intervention significantly reduced all blood pressure levels for the patients . A reduction in state anxiety level was also found for the music intervention group . No significant reductions in blood pressure , heart rate and state anxiety level were found in the nurse presence and control groups . CONCLUSION The results support the cross-cultural validity of using a music intervention in pre-operative anxiety reduction , in this case for TURP patients waiting in the theatre holding area OBJECTIVE To examine the influence during the early postoperative period of selected nursing interventions on mood and anxiety of patients undergoing heart surgery . DESIGN Prospect i ve , repeated measures , quasiexperimental , r and om assignment . SETTING The cardiovascular intensive care and progressive care units of a midwestern community hospital were used as the setting for this study . PATIENTS Ninety-six patients who underwent elective , heart bypass surgery ; the mean age of the subjects was 67 years , with an age range of 37 to 84 years . Most subjects were men ( n = 65 , 68 % ) . OUTCOME MEASURES Physiologic measures of anxiety and mood include blood pressure and heart rate . Additional measures included the use of Spielberger 's state-trait anxiety inventory ( STAI ) and patient verbal ratings of both mood and anxiety with use of a numeric rating scale ( NRS ) . INTERVENTION Patients were r and omly assigned to one of three groups : ( 1 ) music therapy , ( 2 ) music-video therapy , or ( 3 ) scheduled rest group . Subjects in the groups received their assigned 30-minute intervention at two episodes on postoperative days 2 and 3 . Subjects had physiologic measures of blood pressure and heart rate measured immediately before the intervention and at 10-minute intervals throughout the intervention . Mood and anxiety were evaluated by having subjects use a NRS ( i.e. , 0 to 10 ) to give rating of mood and anxiety immediately before and after each session . Anxiety was further measured with the STAI . A baseline measure of STAI was taken before surgery ; patients also completed the " state " anxiety tool before the intervention session on postoperative day 2 and on completion of the session on postoperative day 3 . RESULTS With use of an analysis of covariance ( ANCOVA ) , subjects ' mood ratings showed significant improvement in mood among subjects in the " music intervention " group after the second intervention when controlling for the preintervention rating of mood , F(2 , 87 ) = 4.33 , p = 0.016 . However , no significant differences were reported for anxiety ratings as measured by the NRS and state anxiety instruments . With use of repeated measures analysis of variance ( ANOVA ) , there were no significant interactions between the intervention groups and time for any of the physiologic variables . However , there were significant main effects over time for heart rate and systolic and diastolic blood pressure , which indicated a generalized physiologic relaxation response . CONCLUSIONS Although none of the three interventions was overwhelmingly superior , the overall response by all intervention groups demonstrated a generalized relaxation response . It is also important to note that there was reduced anxiety and improved mood within all three groups BACKGROUND R and omized trials can show whether a treatment effect is statistically significant and can describe the size of the effect . There are , however , no vali date d methods available for establishing the clinical relevance of these outcomes . Recently , it was proposed that a st and ardized mean difference ( SMD ) of 0.50 be used as cutoff for clinical relevance in the treatment of depression . METHODS We explore what the effect size means and why the size of an effect has little bearing on its clinical relevance . We will also examine how the " minimally important difference , " as seen from the patient perspective , may be helpful in deciding where the cutoff for clinical relevance should be placed for a given condition . RESULTS Effect sizes in itself can not give an indication of the clinical relevance of an intervention because the outcome itself determines the clinical relevance and not only the size of the effects . The " minimal important difference " ( MID ) could be used as a starting point for pinpointing the cutoff for clinical relevance . A first , rough attempt to implement this approach for depression result ed in a tentative clinical relevance cutoff of SMD = 0.24 . Using this cutoff , psychotherapy , pharmacotherapy , and combined treatment have effect sizes above this cutoff . DISCUSSION Statistical outcomes can not be equated with clinical relevance . The " MID " may be used for pinpointing the cutoff for clinical relevance , but more work in this area is needed PURPOSE To compare effects of music , white noise , and ambient ( background ) noise on patient anxiety and sedation . DESIGN Open , parallel , and r and omized controlled trial . METHODS Seventy-five patients aged 18 to 60 years who were scheduled for surgical procedures under spinal anesthesia were r and omly assigned to ambient noise ( Group O ) , white noise ( Group B ) , or music groups ( Group M ) . We evaluated patients ' anxiety and sedation levels via the Observer 's Assessment of Alertness/Sedation ( OAA/S ) scale and the State-Trait Anxiety Inventory ( STAI ) question naire . FINDING At 5 minutes before surgery , the STAI-State Anxiety Inventory ( SA ) value was significantly lower in Group M than the other groups . At 30-minute recovery , Group M showed significantly lower STAI-SA values than the other groups . Patient satisfaction was highest in Group M. OAA/S values were not significantly different between groups during any period ( P > .05 ) . CONCLUSIONS We suggest that patient-selected music reduces perioperative anxiety and contributes to patient satisfaction during the perioperative period |
12,250 | 26,105,973 | Meta-analyses showed that there is no significant difference between oral and SC insulin in controlling HbA1c , FBG , 1 and 2 h postpr and ial blood glucose and producing Cmax of insulin ( P > 0.05 ) ; however oral insulin had faster action as indicated by the shorter Tmax , compared to SC insulin ( P < 0.05 ) .
Conclusion This systematic review and meta- analysis showed that oral insulin is comparable to SC insulin with regard to glycemic efficacy and safety . | Introduction A systematic review and meta- analysis of interventional studies was conducted to compare the efficacy and safety of oral insulin versus subcutaneous ( SC ) insulin in diabetic patients . | Repeated ingestion of insulin has been suggested as an immune tolerization therapy to prevent immune-mediated ( type 1 ) diabetes . We performed a placebo-controlled , two-dose , oral insulin tolerance trial in newly diagnosed ( < 2 years ) diabetic patients who had required insulin replacement for less than 4 weeks and were found to have cytoplasmic islet cell autoantibodies ( ICAs ) . No oral hypoglycemic agents were permitted during the trial . Endogenous insulin reserves were estimated at six-month intervals by plasma C-peptide responses to a mixed meal . Positive ICAs were found in 262 ( 31 % ) of the 846 patients screened . Of the 197 who agreed to participate , 187 could be followed for 6 to 36 months . Endogenous insulin retention was dependent upon initial stimulated C-peptide response , age at diabetes onset , and numbers of specific islet cell autoantibodies found . Oral insulin improved plasma C-peptide responses in patients diagnosed at ages greater than 20 years , best seen at the low ( 1 mg/day ) over the high ( 10 mg/day ) insulin dose ( P = .003 and P = .01 , respectively ) . In patients diagnosed before age 20 years , the 1 mg dose was ineffective , whereas the 10 mg dose actually accelerated C-peptide loss ( P = .003 ) . There were no adverse effects . If confirmed , these findings suggest that diabetic patients over age 20 years with ICA evidence of late-onset immune-mediated diabetes should be considered for oral insulin at 1 mg/day to better retain endogenous insulin secretion Aims /hypothesis . Induction of tolerance to insulin is achievable in animal models of Type I ( insulin-dependent ) Diabetes mellitus by oral treatment with this hormone , which can lead to prevention of the disease . In the Diabetes Prevention Trial of Type I diabetes ( DPT-1 ) , oral insulin is given with the aim of preventing disease insurgence . We investigated whether if given at diagnosis of Type I diabetes in humans , oral insulin can still act as a tolerogen and therefore preserve residual beta-cell function , which is known to be substantial at diagnosis . Methods . A double-blind trial was carried out in patients ( mean age ± SD : 14 ± 8 years ) with recent-onset Type I diabetes to whom oral insulin ( 5 mg daily ) or placebo was given for 12 months in addition to intensive subcutaneous insulin therapy . A total of 82 patients with clinical Type I diabetes ( < 4 weeks duration ) were studied . Basal C peptide and glycated haemoglobin were measured and the insulin requirement monitored every 3 months up to 1 year . Insulin antibodies were also measured in 27 patients treated with oral insulin and in 18 patients receiving placebo at the beginning of the trial and after 3 , 6 and 12 months of treatment . Results . The trial was completed by 80 patients . Overall and without distinction between age at diagnosis , at 3 , 6 , 9 and 12 months baseline mean C-peptide secretion in patients treated with oral insulin did not differ from that of those patients treated with placebo . In patients younger than 15 years a tendency for lower C-peptide values at 9 and 12 months was observed in the oral insulin group . Insulin requirement at 1 year was similar between the two groups as well as the percentage of glycated haemoglobin . Finally , IgG insulin antibodies were similar in the two groups at each time point . Conclusion /interpretation . The results of this study indicate that the addition of 5 mg of oral insulin does not modify the course of the disease in the first year after diagnosis and probably does not statistically affect the humoral immune response against insulin . [ Diabetologia ( 2000 ) 43 : 1000–1004 OBJECTIVE The objectives of this exploratory study were to assess the postpr and ial glucose-lowering effects and evaluate the safety and tolerability of single , escalating doses of an oral insulin product , hexyl-insulin monoconjugate 2 ( HIM2 ) , in patients with type 2 diabetes . Subcutaneous insulin and oral placebo were also administered for comparison . RESEARCH DESIGN AND METHODS Eighteen patients with type 2 diabetes were enrolled in this r and omized , single-blind , placebo-controlled , three-way crossover , dose-escalation study . A single dose of each of the following study drugs was administered to each patient on 3 separate days : oral HIM2 ( at one of three dose levels : 0.375 , 0.5 , or 1.0 mg/kg ) , subcutaneous regular insulin ( 8 units Humulin R ) , and oral placebo . At 30 min after dosing , patients ingested a st and ardized test meal ( 16 oz/720 calories of Boost Plus ) . Serial blood sample s were collected for determination of plasma glucose and insulin concentrations during the 4-h postdose period . RESULTS The mean glucose area under the curve for 0 to 240 min ( AUC(0 - 240 ) ) values were lower following administration of 0.5 and 1.0 mg/kg HIM2 vs. placebo ( 1,097.1 vs. 1,196.9 and 801.1 vs. 992.1 mg x h(-1 ) x dl(-1 ) , respectively ) . This difference was statistically significant at the 1.0-mg/kg HIM2 dose level . Insulin exposure , as measured by insulin AUC(0 - 240 ) values , for the 0.375- , 0.5- , and 1.0-mg/kg dose levels of HIM2 were 169.9 , 193.1 , and 230.8 micro U x h(-1 ) x ml(-1 ) , respectively ; insulin AUC(0 - 240 ) values for placebo were 165.8 , 196.1 , and 169.2 micro U x h(-1 ) x ml(-1 ) , respectively . The mean glucose AUC(0 - 240 ) values were similar following administration of 0.5 and 1.0 mg/kg HIM2 vs. subcutaneous insulin ( 1,097.1 vs. 1,048.0 and 801.1 vs. 875.2 mg x h(-1 ) x dl(-1 ) , respectively ) . For pooled data from the 0.5- and 1.0-mg/kg dose groups , the HIM2/subcutaneous insulin ratios for the 2-h postpr and ial glucose concentration ( 0.97 , 95 % CI 0.90 - 1.06 ) , maximum postpr and ial glucose concentration ( 0.99 , 95 % CI 0.93 - 1.06 ) , and glucose AUC(0 - 240 ) ( 0.98 , 95 % CI 0.9 - 1.06 ) were within 10 % of unity , implying glucodynamic equivalence . Although HIM2 ( 0.5 and 1.0 mg/kg ) and subcutaneous insulin ( 8 units ) provided comparable control of postpr and ial plasma glucose concentrations , HIM2 result ed in peripheral insulin concentrations that were lower than subcutaneous insulin ( mean insulin AUC(0 - 240 ) of 193.1 vs. 233.6 and 230.8 vs. 270.3 micro U x h(-1 ) x ml(-1 ) , respectively ) . CONCLUSIONS Single , oral doses of HIM2 were safe and well tolerated . HIM2 ( 0.5 and 1.0 mg/kg ) was more effective than placebo and as effective as subcutaneous regular insulin ( 8 units ) at controlling postpr and ial glycemia with respect to the following parameters : 2-h postpr and ial glucose concentration , maximum glucose concentration , and glucose AUC(0 - 240 ) . This occurred even though peripheral insulin concentrations were lower following the administration of HIM2 ( 0.5 and 1.0 mg/kg ) than subcutaneous insulin . Thus , HIM2 therapy may control postpr and ial glycemia without causing peripheral hyperinsulinemia in patients with type 2 diabetes The unpredictable behavior of uncontrolled type 1 diabetes often involves frequent swings in blood glucose levels that impact maintenance of a daily routine . An intensified insulin regimen is often unsuccessful , while other therapeutic options , such as amylin analog injections , use of continuous glucose sensors , and islet or pancreas transplantation are of limited clinical use . In efforts to provide patients with a more compliable treatment method , Oramed Pharmaceuticals tested the capacity of its oral insulin capsule ( ORMD-0801 , 8 mg insulin ) in addressing this resistant clinical state . Eight Type I diabetes patients with uncontrolled diabetes ( HbA1c : 7.5–10 % ) were monitored throughout the 15-day study period by means of a blind continuous glucose monitoring device . Baseline patient blood glucose behavior was monitored and recorded over a five-day pretreatment screening period . During the ensuing ten-day treatment phase , patients were asked to conduct themselves as usual and to self-administer an oral insulin capsule three times daily , just prior to meal intake . CGM data sufficient for pharmacodynamics analyses were obtained from 6 of the 8 subjects . Treatment with ORMD-0801 was associated with a significant 24.4 % reduction in the frequencies of glucose readings > 200 mg/dL ( 60.1±7.9 % pretreatment vs. 45.4±4.9 % during ORMD-0801 treatment ; p = 0.023 ) and a significant mean 16.6 % decrease in glucose area under the curve ( AUC ) ( 66055±5547 mg/dL/24 hours vs. 55060±3068 mg/dL/24 hours , p = 0.023 ) , with a greater decrease during the early evening hours . In conclusion , ORMD-0801 oral insulin capsules in conjunction with subcutaneous insulin injections , well tolerated and effectively reduced glycemia throughout the day . Trial Registration Clinical trials.gov NCT00867594 An effective , orally administered insulin product would be of substantial benefit in the treatment of patients with diabetes mellitus . This phase I/II clinical trial was the first to investigate the safety and effectiveness of a single oral dose of a modified human insulin in controlling postpr and ial plasma glucose levels in patients with type 1 diabetes mellitus who were receiving basal continuous subcutaneous insulin infusion ( CSII ) therapy . Fourteen patients with type 1 diabetes mellitus were evaluated in an open-label , 2-center , dose-escalation , nonr and omized study of oral hexyl-insulin monoconjugate 2 ( HIM2 ) . After an overnight fast and prior to receiving a st and ardized meal ( 50 % carbohydrates , 30 % fat , 20 % proteins ; 650 calories ) , the patients received either no additional insulin ( day 1 ) , or 0.5 to 1.0 mg/kg of HIM2 ( day 2 ) . All patients received a basal insulin regimen by CSII throughout the study . Blood sample s were collected for determination of glucose and insulin levels for 240 minutes post-dose . The postpr and ial glucose excursion versus time curves showed clear reductions in glucose values after both HIM2 doses ( day 2 ) relative to no treatment ( day 1 ) , although the differences in the reductions were not statistically significant . When the data for both HIM2 doses were pooled , a statistically significant effect of HIM2 on glucose excursion ( as measured by AUCex(30 - 240 ) ) was observed . Mean + /- SD values for AUCex(30 - 240 ) were 501.35 + /- 124.1 mg . h/dL after no treatment and 375.81 + /- 215.5 mg . h/dL after HIM2 ( Wilcoxon signed-rank test , P = .042 ) . The results of this study suggest that oral HIM2 , when added to a basal insulin regimen , was safe and may prove effective in controlling postpr and ial hyperglycemia in patients with type 1 diabetes mellitus . Further clinical investigation is necessary AIM The objective of the study was to establish the dose response of IN-105 tablets and explore a possible therapeutic window in type 2 diabetes subjects poorly controlled on metformin . METHODS The primary objective was to examine the effect of sequential single ascending doses of IN-105 on the plasma glucose concentration under fed conditions . All subjects received , sequentially , matching placebo , 10 , 15 , 20 and 30 mg IN-105 tablets in five consecutive periods . Tablets were administered 20 min prior to meal in all the periods . Plasma levels of immunoreactive insulin , C-peptide and glucose were measured up to 180 min from the time of dosing . The changes in postpr and ial glucose levels at 120 min in response to IN-105 administration were also compared against those of placebo . RESULTS Changes in glucose from baseline ( mean + /- s.d . ) at 140 min ( 2 h postpr and ial ) were 94.84 + /- 22.3 , 79.45 + /- 43.00 , 70.68 + /- 35.71 , 63.47 + /- 42.75 and 53.06 + /- 47.27 mg/dL , respectively , and exhibited linear dose-response . The insulin C(max ) values were found to be 50.8 + /- 26.0 mU/L for placebo , 100.3 + /- 66.7 with 10 mg IN-105 , 177.69 + /- 150.3 with 15 mg IN-105 , 246.2 + /- 245.2 with 20 mg IN-105 and 352.5 + /- 279.3 mU/L with 30 mg of IN-105 . CONCLUSIONS IN-105 absorption is proportional to the dose administered . The 2-h postpr and ial glucose excursion was reduced in a dose proportional manner . Circulating C-peptide levels were found to be suppressed in proportion to the IN-105 exposure . IN-105 reduces glucose excursion despite lower endogenous insulin secretion . IN-105 seems to have a wide therapeutic window as no clinical hypoglycaemia was observed at any of the doses studied BACKGROUND Oral insulin spray is a new , noninjectable method of insulin delivery . This system delivers an aerosol of uniform-sized droplets containing regular human insulin at a high velocity into the oropharyngeal cavity for local transmucosal absorption . OBJECTIVE The purpose of this study was to compare the pharmacokinetic and pharmacodynamic properties of single-dose oral insulin spray and SC insulin injection in healthy subjects . METHODS Healthy male volunteers aged 21 to 25 years participated in this open-label study conducted at the Diabetes Unit , Hadassah-Hebrew University Hospital , Jerusalem , Israel . Subjects presented at 2 visits separated by 7 to 14 days . At both visits , the euglycemic clamp technique was used to maintain a constant blood glucose level . At one visit , subjects received regular human insulin 0.1 U/kg by SC injection . At the other visit , subjects received 15 puffs ( 150 U ) of oral insulin spray . The pharmacokinetic ( insulin absorption ) and pharmacodynamic ( glucose uptake ) properties of the drugs were evaluated using blood analyses over the subsequent 360 minutes . RESULTS Six volunteers were enrolled ( mean [ SD ] age , 22.8 [ 1.2 ] years ; mean [ SD ] body mass index , 23.2 [ 2.2 ] kg/m(2 ) ) . The mean ( SD ) baseline-corrected C(max ) was significantly higher with oral insulin spray compared with SC insulin ( 54.0 [ 20.3 ] vs 30.8 [ 6.1 ] microU/mL ; P = 0.028 ) . Mean ( SD ) T(max ) was significantly shorter with oral insulin spray compared with SC insulin ( 23.3 [ 5.2 ] vs 83.3 [ 42.2 ] minutes ; P = 0.027 ) . The mean ( SD ) time to maximal metabolic effect ( maximum glucose infusion rate [ GIR(max ) ] ) ( 44.2 [ 8.6 ] vs 100.0 [ 35.6 ] minutes ) and late time to half-maximal effect ( 101.0 [ 41.0 ] vs 257.2 [ 27.8 ] minutes ) were shorter with oral insulin spray compared with SC insulin ( both , P = 0.028 ) . The baseline-corrected GIR(max ) ( 6.8 [ 3.3 ] vs 6.2 [ 2.3 ] mg/kg . min ) and glucose consumption ( 396.7 [ 178.0 ] vs 432.1 [ 226.0 ] mg/kg ) during the 120 minutes after study drug administration were comparable between oral and SC insulin , respectively . CONCLUSIONS In this study in a small , selected population of healthy male subjects under euglycemic conditions , oral insulin spray was associated with a higher C(max ) , shorter T(max ) , and faster time to peak glucose uptake compared with SC insulin . The short T(max ) and the 120-minute duration of effect of oral insulin spray suggest it may be a promising alternative for fulfilling meal-related insulin requirements in persons with diabetes OBJECTIVE This study evaluated the pharmacokinetic and pharmacodynamic properties and dose-response effects of an oral insulin spray formulation compared with those of subcutaneously injected regular insulin and placebo in patients with type 1 diabetes mellitus . METHODS This was a single-center , r and omized , single-blind , open-label , 5-way crossover study in which patients with type 1 diabetes received 5 , 10 , and 20 puffs of the oral insulin spray ; regular insulin 0.1 U/kg SC ; and placebo spray . The pharmacokinetic parameters of interest were the maximum serum insulin concentration ( Ins-C(max ) ) ; the incremental insulin AUC from 0 to 120 minutes ( Ins-AUC(0 - 120 ) ) , from 0 to 240 minutes , and from 0 to 360 minutes ; and the time to maximum serum insulin concentration ( Ins-T(max ) ) . The pharmacodynamic parameters of interest were the maximum glucose infusion rate ( GIR(max ) ) ; the incremental glucose AUC from 0 to 120 minutes ( GIR-AUC(0 - 120 ) ) , from 0 to 240 minutes , and from 0 to 360 minutes ; the time to maximum GIR ( GIR-T(max ) ) ; the time to early half-maximal GIR ( early T50 % ) ; and the time to late half-maximal GIR ( late T50 % ) . Pharmacokinetic and pharmacodynamic parameters were assessed using the euglycemic clamp technique . RESULTS The study enrolled 6 white men with type 1 diabetes ( mean [ SD ] age , 37.5 [ 16.2 ] years , mean weight , 82.7 [ 17.0 ] kg ) . Ins-T(max ) was shorter for 5 , 10 , and 20 puffs of oral insulin spray than for SC insulin ( 26.7 [ 13.7 ] , 29.2 [ 7.4 ] , 23.3 [ 5.2 ] , and 142.5 [ 73.2 ] min , respectively ; P < 0.05 ) . There was no effect of dose on Ins-T(max ) . The Ins-AUC(0 - 120 ) for 5 , 10 , and 20 puffs of oral insulin spray ( 304.8 [ 277.9 ] , 689.2 [ 353.0 ] , and 1808.8 [ 1252.6 ] microU/mL per min , respectively ; P < 0.05 ) and the corresponding Ins-Ca(max ) ( 12.9 [ 8.7 ] , 26.7 [ 14.5 ] , and 47.6 [ 40.1 ] microU/mL ; P < 0.05 ) suggested a dose-response relationship . Five , 10 , and 20 puffs of oral insulin spray had an earlier onset of action than SC insulin ( early T50 % : 23.3 [ 15.1 ] , 28.3 [ 12.3 ] , 31.2 [ 111.8 ] , and 87.0 [ 39.6 ] min , respectively ; P < 0.05 ) , an earlier maximal effect ( GIR-T(max ) : 40.0 [ 23.7 ] , 45.8 [ 22.7 ] , 44.2 [ 5.8 ] , and 145.0 [ 43.7 ] min ; P < 0.05 ) , and a shorter duration of action ( late T50 % : 56.5 [ 31.0 ] , 70.2 [ 12.9 ] , 75.5 [ 6.0 ] , and 290.8 [ 84.0 ] min ; P < 0.05 ) . Dose-dependent increases in maximal metabolic effect were observed with 5 , 10 , and 20 puffs : the GIR(max ) was 0.9 ( 0.5 ) , 2.0 ( 1.3 ) , and 3.9 ( 2.5 ) mg/kg per minute , respectively ( P < 0.05 ) , and the GIR-AUC(0 - 120 ) was 39.6 ( 34.9 ) , 76.8 ( 67.4 ) , and 189.1 ( 163.0 ) mg/kg per minute ( P < 0.05 ) . CONCLUSIONS In this study in patients with type 1 diabetes , oral insulin spray had a faster onset and shorter duration of action than subcutaneously injected regular insulin . A dose-response relationship was noted in the metabolic effect and absorption of oral insulin spray OBJECTIVE Proof-of-concept study of evaluation of metabolic effect of novel oral spray insulin ( Oralin ) formulation at breakfast time in subjects with type 2 diabetes on multiple daily injections . RESEARCH DESIGN AND METHODS This was an open-label , crossover , r and omized study in ( n = 23 ) subjects with type 2 diabetes on multiple daily injections . Subjects received each treatment , in r and om order , 3 to 7 days apart-a daily dose of SC injection ( 0.1 u/kg ) on one occasion and Oralin spray ( 100 u ) at time 0 min on another occasion . Subjects were given a st and ard breakfast containing 360 cal ( Sustacal liquid meal ) 10 min after the dose . Blood sample s were taken at regular intervals to measure glucose , insulin , and C-peptide . RESULTS The 30- and 60-min postpr and ial glucose levels were significantly lowered with Oralin versus that with the injection treatment ( 146 + /- 5 mg/dL Oralin vs 184 + /- 7 mg/dL injection at 30 min and 192 + /- 6 mg/dL Oralin vs 236 + /- 9 mg/dL injection , p < 0.003 at 60 min ) . The rise in serum insulin levels was significantly higher ( Cmax = 98 + /- 6 uU/mL for Oralin at 30 min vs 65 + /- 3 uU/ml injection , p < 0.001 ) . The reduction in C-peptide was greater in Oralin during the first 60 min ( 1.38 + /- 0.21 ng/mL Oralin vs 1.75 + /- 0.38 ng/mL injection , p < 0.001 ) . CONCLUSIONS This proof-of-concept study results demonstrated that Oralin could be used as meal insulin in place of mealtime-insulin injections in subjects with type 2 diabetes to regulate the postpr and ial glucose levels AIM R and omized , open , single-centre , two-way crossover study comparing the pharmacokinetic ( PK ) and pharmacodynamic ( PD ) properties of subcutaneous ( sc ) regular human insulin ( Actrapid ) and oral insulin in a capsule form ( Capsulin ) . METHODS Sixteen persons ( 12 males ) with type 2 diabetes on oral hypoglycaemic agents ( OHAs ) participated . Mean ( s.d . ) age 60.2 ( 5.5 ) years , BMI 28.3 ( 3.4 ) kg/m(2 ) , haemoglobin A(1c ) ( HbA(1c ) ) 7.4 % ( 1.1 ) . Two 6-h isoglycaemic glucose clamp studies were conducted 11 days apart . All subjects received in r and om order 12U sc Actrapid on one clamp study day and either 150U or 300U Capsulin ( Cap ) on the other day . Glucose infusion rates ( GIRs ) , plasma insulin and C-peptide concentrations were determined throughout each 6-h isoglycaemic clamp . Between the clamp study days , all patients received 150U Capsulin twice daily , dropping all their st and ard OHAs apart from metformin . Self-monitored blood glucose ( SMBG ) levels were taken four times a day between the clamp study days . RESULTS Administration of either Actrapid or Capsulin ( 150 and 300U ) increased GIRs reaching a maximum values at approximately 280 - 330 min . Overall values for maximum GIR values were higher for Actrapid than either dose of Capsulin ( p < 0.05 ) . The significantly greater systemic insulin concentrations following Actrapid were reflected in the AUC(0 - 6 h ) ( 910 + /- 270 vs. 472 + /- 245 pmol h/L ; 950 + /- 446 vs. 433 + /- 218 pmol h/L ; both p < 0.05 for Actrapid vs. 150U Capsulin and 300U Capsulin respectively ) . No difference was observed between 150U and 300U Capsulin . During the repeat-dosing period , good safety and tolerability were observed with Capsulin , and SMBG levels remained stable . At the post study visit , significant falls in HbA(1c ) , weight and triglycerides were observed . CONCLUSIONS Administration of the oral insulin Capsulin preparation demonstrated a significant hypoglycaemic action over a period of 6 h associated with only a small increase in circulating plasma insulin concentrations |
12,251 | 26,148,790 | Conclusions The findings of this review indicate that behavioural interventions can encourage colorectal adenoma patients to improve their diet .
This review was not however able to clearly characterise effective interventions promoting increased physical activity in this patient group . | Background Little is known about colorectal adenoma patients ’ ability to adhere to behavioural interventions promoting a change in diet and physical activity .
This review aim ed to examine health behaviour intervention programmes promoting change in diet and /or physical activity in adenoma patients and characterise interventions to which this patient group are most likely to adhere . | Results from case-control studies and prospect i ve studies suggest that diet is involved in the causation of large bowel cancer either as initiator , promoter or inhibitor of carcinogenesis . Available data are not sufficient to serve as a basis for firm specific dietary advice . In the present situation it is attractive to investigate available hypotheses within the frame work of intervention trials . The adenoma appears to be one of the most appropriate end point of intervention studies . Several arguments indicate that the adenoma-carcinoma sequence is a multistep process . Colorectal cancer could possibly be prevented by intervening in the development of a small adenoma or in the growth into a large adenoma . Four intervention trials have been published so far . One of them suggest a protective effect of antioxidants vitamins on adenoma recurrence and three of them conclude to the absence of effect of these vitamins . A protective effect of lactulose on adenoma recurrence has also been suggested . Three studies are currently evaluating the effect of calcium supplementation on adenoma recurrence or growth of calcium supplementation , three studies the effect of fibre supplements , two studies the effect of antioxidants ( one of them with calcium ) and two studies the effect of diet intervention . The results of these studies will be available within three years BACKGROUND The Polyp Prevention Trial ( PPT ) was a multicenter r and omized clinical trial design ed to determine the effects of a high-fiber ( 4.30 g/MJ ) , high-fruit- and -vegetable ( 0.84 servings/MJ ) , low-fat ( 20 % of energy from fat ) diet on the recurrence of adenomatous polyps in the large bowel . OBJECTIVE Our goal was to determine whether the PPT intervention plan could effect change in 3 dietary goals and to examine the intervention 's effect on the intake of other food groups and nutrients . DESIGN Participants with large-bowel adenomatous polyps diagnosed in the past 6 mo were r and omly assigned to either the intervention ( n = 1037 ) or the control ( n = 1042 ) group and remained in the trial for 4 y. Three dietary assessment instruments were used to measure dietary change : food-frequency question naires ( in 100 % of the sample ) , 4-d food records ( in a 20 % r and om cohort ) , and 24-h dietary recalls ( in a 10 % r and om sample ) . RESULTS Intervention participants made and sustained significant changes in all PPT goals as measured by the dietary assessment instruments ; the control participants ' intakes remained essentially the same throughout the trial . The absolute differences between the intervention and control groups over the 4-y period were 9.7 % of energy from fat ( 95 % CI : 9.0 % , 10.3 % ) , 1.65 g dietary fiber/MJ ( 95 % CI : 1.53 , 1.74 ) , and 0.27 servings of fruit and vegetables/MJ ( 95 % CI : 0.25 , 0.29 ) . Intervention participants also reported significant changes in the intake of other nutrients and food groups . The intervention group also had significantly higher serum carotenoid concentrations and lower body weights than did the control group . CONCLUSION Motivated , free-living individuals , given appropriate support , can make and sustain major dietary changes over a 4-y period Adherence determinants and key adherence research issues are discussed for three types of r and omized controlled trials : pharmacological , dietary , and physical activity . This article highlights theoretical and method ological limitations that have hampered the ability to identify patients at risk for poor treatment compliance . Control Clin Trials Objective To evaluate the impact of a diet and physical activity intervention ( BeWEL ) on weight change in people with a body mass index > 25 weight (kg)/height (m)2 at increased risk of colorectal cancer and other obesity related comorbidities . Design Multicentre , parallel group , r and omised controlled trial . Setting Four Scottish National Health Service health boards . Participants 329 overweight or obese adults ( aged 50 to 74 years ) who had undergone colonoscopy after a positive faecal occult blood test result , as part of the national bowel screening programme , and had a diagnosis of adenoma confirmed by histopathology . 163 were r and omised to intervention and 166 to control . Intervention Participants were r and omised to a control group ( weight loss booklet only ) or 12 month intervention group ( three face to face visits with a lifestyle counsellor plus monthly 15 minute telephone calls ) . A goal of 7 % reduction in body weight was set and participants received a personalised energy prescription ( 2508 kJ ( 600 kcal ) below that required for weight maintenance ) and bodyweight scales . Motivational interviewing techniques explored self assessed confidence , ambivalence , and personal values concerning weight . Behavioural strategies included goal setting , identifying intentions of implementation , self monitoring of body weight , and counsellor feedback about reported diet , physical activity , and weight change . Main outcome measures The primary outcome was weight change over 12 months . Secondary outcomes included changes in waist circumference , blood pressure , fasting cardiovascular biomarkers , and glucose metabolism variables , physical activity , diet , and alcohol consumption . Results At 12 months , data on the primary outcome were available for 148 ( 91 % ) participants in the intervention group and 157 ( 95 % ) in the control group . Mean weight loss was 3.50 kg ( SD 4.91 ) ( 95 % confidence interval 2.70 to 4.30 ) in the intervention group compared with 0.78 kg ( SD 3.77 ) ( 0.19 to 1.38 ) in the control group . The group difference was 2.69 kg ( 95 % confidence interval 1.70 to 3.67 ) . Differences between groups were significant for waist circumference , body mass index , blood pressure , blood glucose level , diet , and physical activity . No reported adverse events were considered to be related to trial participation . Conclusions Significant weight loss can be achieved by a diet and physical activity intervention initiated within a national colorectal cancer screening programme , offering considerable potential for risk reduction of disease in older adults . Trial registration Current Controlled Trials IS RCT N53033856 Westernization or industrialization leads to an increase in rates of colon cancer , which is the second leading cause of malignant death in the United States [ 1 ] . Although the precise causes of colon cancer remain unclear , a diet high in red meat or animal fat and low in fruits and vegetables appears to increase the risk for this malignancy [ 2 , 3 ] . It is perhaps less well recognized that an inverse association between physical activity and risk for colon cancer has been seen in studies of occupational activity only [ 4 - 12 ] and of both job-related and recreational activity [ 13 - 23 ] . In addition , many studies have found an association between body mass and elevated risk for colon cancer in men ; this association is weaker in women [ 24 - 33 ] . The fact that the association is stronger in men suggests that the abdominal distribution of adiposity typical in men may be an important component of enhanced risk . More limited evidence suggests that height , which may be a proxy for a person 's net energy intake during childhood and adolescence , is related to a higher risk for colon cancer [ 33 - 35 ] . We examine the association between physical activity , obesity , and attained height in relation to risk for colon cancers and their precursory adenomas in a large cohort of male health professionals in the United States . Waist and hip circumferences were available for a subcohort of the study population . We address the hypotheses that physical inactivity , obesity , and height increase the risk for colon cancer and adenoma independently of each other and of diet , and that the abdominal pattern of obesity is an additional independent risk factor . Methods Study Population The Health Professionals Follow-up Study [ 36 ] was started in 1986 ; in that year , 51 529 male dentists , optometrists , osteopaths , podiatrists , pharmacists , and veterinarians in the United States between 40 and 75 years of age responded to a mailed question naire . They reported on their leisure-time physical activity ( described below ) ; current body weight ; weight at age 21 years ; height ; history of cancer and other medical conditions ; parental history of various diseases , including colorectal cancer ; and use of aspirin and other nonsteroidal anti-inflammatory medications . They also reported dietary and alcohol intake using a vali date d [ 37 , 38 ] , semi-quantitative food-frequency question naire . We mailed an optional question naire in 1987 to assess waist and hip circumferences . In 1988 , 1990 , and 1992 , we up date d exposure information and ascertained newly diagnosed medical conditions and history of colonoscopy or sigmoidoscopy , including the indications for endoscopy : bleeding in stool , positive results from tests for occult fecal blood , abdominal pain , diarrhea or constipation , family history of colorectal cancer , routine screening without symptoms , or follow-up [ 39 ] . Most of the deaths in the cohort were reported by family members or by the postal system in response to the follow-up question naires . We also used the National Death Index to identify deaths among nonrespondents [ 40 ] . Assessment of Physical Activity The 1986 question naire included a section about mainly recreational or leisure-time physical activity . The reliability and validity of question naires design ed to assess physical activity have been investigated [ 41 - 43 ] . A question naire such as the one used in our cohort was evaluated in a cohort of U.S. nurses and was found to provide useful information [ 44 ] , and similar results were found during a similar validation study done within the Health Professionals cohort ( Chasan-Taber S. Personal communication ) . Participants reported the average time per week spent doing each of eight moderate and vigorous activities , choosing from among 10 possible responses that ranged from 0 minutes to 11 or more hours per week . The specific activities listed were walking or hiking outdoors ( including walking during golf ) ; jogging ( slower than 10 minutes/mile ) ; running ( 10 minutes/mile or faster ) ; bicycling ( including that done on a stationary machine ) ; lap swimming ; tennis , squash , or racquetball ; and calisthenics or rowing . In addition , each respondent reported the number of flights of stairs he climbed daily and his usual walking pace . The reported time spent at each activity per week was multiplied by its typical energy expenditure requirements expressed in metabolic equivalents ( METs ) [ 45 ] to yield a MET-hour score . One MET , which is the energy expended by sitting quietly , is equivalent to 3.5 mL of oxygen uptake per kilogram of body weight per minute for a 70-kg adult . For example , 1 hour per week of running contributed 10.2 MET-hours , 1 hour of tennis contributed 6 MET-hours , and 1 hour of walking at a moderate pace contributed 3.2 MET-hours . Body weight was excluded from the derivation of energy expenditure from physical activity to avoid confounding the expenditure variable by body weight . If more than one published intensity level was available for a given activity , the moderate or general MET value was chosen . An average MET value was assigned to the categories that listed more than one activity , such as rowing or calisthenics , and squash or racquetball . Assessment of Anthropometric Variables Each man reported his current weight and height and his weight at age 21 years on the 1986 question naire . In 1987 , we mailed an optional question naire once to obtain additional exposure information , including body circumference measurements . We instructed each participant to measure ( to the nearest quarter inch ) his waist at the umbilicus and his hips at the largest circumference between the waist and thighs while st and ing and without measuring over bulky clothing [ 46 ] . We provided a tape measure and an illustration to help st and ardize the measurements . Sixty-five percent of the cohort responded . We used the Quetelet index ( kilograms/height in meters2 ) as a measure of total adiposity , waist-to-hip ratio to measure relative distribution of fat , and waist circumference to estimate total abdominal fat . Although the waist-to-hip ratio has been used more widely , waist circumference provides an estimate of absolute abdominal adiposity , the component most closely related to important metabolic abnormalities , including hyperinsulinemia , hypertension , and high triglyceride levels . To remove extraneous variation in the waist circumference because of height ( taller men tend to have larger waist circumferences due to their larger body size rather than to obesity ) , we adjusted waist for height using residual analysis [ 47 ] . We first regressed waist on height using multiple linear regression and then added the residual to the average waist size ( 37.4 inches ) for a man of average height ( 70 inches ) to convert this measure back to the initial scale . This conversion created for each man a st and ardized waist circumference unconfounded by height . We evaluated the precision of self-reported anthropometric measures among 123 cohort members who were part of a dietary validation study [ 46 ] . Trained technicians paid the sub study participants two visits , approximately 6 months apart , to measure current weight and waist and hip circumferences . The Pearson correlation between self-report and the average of the technicians ' two measurements was 0.97 for weight , 0.95 for waist circumference , 0.88 for hip circumference , and 0.69 for waist-to-hip ratio . The men 's self- measurements of their waist circumferences were 0.36 inches greater , their self- measurements of hip circumferences were 0.78 inches smaller , and their self- measurements of weight were 2.3 pounds less than the technician 's measurements . Identification of Patients with Colorectal Cancers In 1988 , 1990 , and 1992 , we asked each participant whether cancer had been diagnosed during the previous 2 years . The response rate to the follow-up question naires was 94 % through 31 January 1992 . When a participant ( or a decedent 's next-of-kin ) reported a diagnosis of cancer of the colon or rectum , we sought permission to obtain hospital records and pathology reports . A study physician , blinded to exposure information , review ed all medical records received and extracted data about histologic type , anatomic location , and stage of the cancer . Proximal colon cancers were defined as those from the cecum to and including the splenic flexure , and distal colon cancers were defined as those in the descending and sigmoid colon . We confirmed 249 new cases of colorectal adenocarcinoma ( excluding carcinoma in situ ) , 90 % by medical records and the remainder with corroborating information about diagnosis and treatment from the cohort member . Two hundred three cancers were in the colon and 46 were in the rectum . Identification of Patients with Colorectal Adenomas and Controls Because more than 90 % of the adenomas were diagnosed during endoscopic procedures for screening or for unrelated gastrointestinal conditions , we restricted the adenoma analysis to men who had had a colonoscopy or sigmoidoscopy . This was done to reduce the potential for detection bias . Most procedures were sigmoidoscopies ; thus , we analyzed only adenomas of the distal colorectum . Although we did not examine proximal colon adenomas , this should not have biased inferences for the distal colorectum . However , different causes for proximal adenomas may exist . A total of 12 879 men who did not meet any of the exclusion criteria ( see Data Analysis ) reported having had an endoscopy between 1986 and 1992 . In 1993 , we sent a mailing to a r and om sample of 200 controls ( men who reported negative results from an endoscopy ) to confirm that they did not have adenomas . After one mailing , 140 ( 70 % ) controls granted us permission to review the medical records of their endoscopic procedure ; none had an unreported , histologically confirmed adenoma . We were able to recontact 96 % of the men who reported a diagnosis of polyp , and we received medical records in response to more than 96 % of the requests sent to medical record departments , BACKGROUND & AIMS In human and animal studies , nonsteroidal anti-inflammatory drugs have been associated with a reduced risk of colorectal neoplasia . Although the underlying mechanisms are unknown , inhibition of cyclooxygenase ( COX ) , particularly COX-2 , is thought to play a role . We conducted a r and omized , placebo-controlled , double-blind trial to assess whether use of the selective COX-2 inhibitor rofecoxib would reduce the risk of colorectal adenomas . METHODS We r and omized 2587 subjects with a recent history of histologically confirmed adenomas to receive daily placebo or 25 mg rofecoxib . R and omization was stratified by baseline use of cardioprotective aspirin . Colonoscopic follow-up evaluation was planned for 1 and 3 years after r and omization . The primary end point was all adenomas diagnosed during 3 years ' treatment . In a modified intent-to-treat analysis , we computed the relative risk of any adenoma after r and omization , using Mantel-Haenszel statistics stratified by low-dose aspirin use at baseline . RESULTS Adenoma recurrence was less frequent for rofecoxib subjects than for those r and omized to placebo ( 41 % vs 55 % ; P < .0001 ; relative risk [ RR ] , 0.76 ; 95 % confidence interval [ CI ] , 0.69 - 0.83 ) . Rofecoxib also conferred a reduction in risk of advanced adenomas ( P < .01 ) . The chemopreventive effect was more pronounced in the first year ( RR , 0.65 ; 95 % CI , 0.57 - 0.73 ) than in the subsequent 2 years ( RR , 0.81 ; 95 % CI , 0.71 - 0.93 ) . As reported previously , rofecoxib was associated with increased risks of significant upper gastrointestinal events and serious thrombotic cardiovascular events . CONCLUSIONS In this r and omized trial , rofecoxib significantly reduced the risk of colorectal adenomas , but also had serious toxicity High vegetable and fruit ( V&F ) consumption has been associated with a lower risk of several cancers . However , little is known about the ability of individuals to increase their intakes markedly . In this 1-year r and omized , controlled diet intervention study of men and women with a recent history of adenomas , the intervention group ( n = 100 ) was asked to increase V&F intake to at least eight servings per day ; the control group ( n = 101 ) continued eating their usual diet . End-point measures included V&F intake assessed by 3-day diet records , plasma carotenoids , serum lipids , urinary sodium and potassium , and body weight . The intervention group increased their daily V&F intake an average of 5.5 servings over 1 year ; the control group had an average decrease of 0.5 servings per day ( P < 0.001 ) . Plasma total carotenoids , alpha-carotene , beta-carotene , beta-cryptoxanthin , and lutein/zeaxanthin were each statistically significantly elevated over baseline ( 11 - 54 % ) in the intervention group compared with the control group over the duration of follow-up ( P < 0.001 ) . Urinary potassium excretion was elevated 14 % over baseline in the intervention group compared with no change in the control group ( P < 0.001 ) . Modest decreases in the intervention but not the control group were observed for total and low-density lipoprotein cholesterol . Plasma lycopene , triglycerides , high-density lipoprotein cholesterol , body weight , and urinary sodium were not affected by the intervention . V&F intake was significantly increased in this motivated population at higher risk of colon cancer and maintained for at least 12 months , as assessed using diet records and an ensemble of biomarkers The manuscript examines the influence of context ual factors on whether and for whom a colon polyp diagnosis might be a teachable moment , as indicated by engagement with a proactively delivered intervention . Baseline and 8-month follow-up data were analyzed from a two-site behavioral intervention trial with patients in Massachusetts and North Carolina , USA who had recently undergone polypectomy for pre-cancerous colon polyps and were r and omized to a behavior change intervention condition ( N=591 ) . Intervention " buy-in " was used as an indicator of response consistent with the polyp identification serving as a teachable moment . Cancer worry , personal risk , health-related self-identity and other sociodemographic factors were tested to predict intervention buy-in . As predicted , those who were most worried about colon cancer were most likely to engage in the intervention . One indicator of personal risk , number of risk behaviors , was significantly and negatively associated with buy-in . Predictors of intervention buy-in and cancer worry were not consistent . We recommend that exp and ed measures of affect and health-related self-identity should be considered in future research to underst and the motivational potential of health events for increasing engagement in effective behavior change interventions Background : This report examines the outcome data for Project PREVENT , a two-site r and omized control trial design ed to reduce behavioral risk factors for colorectal cancer among individuals who have been diagnosed with adenomatous colon polyps . Methods : The study sample included 1,247 patients with recent diagnosis of adenomatous colorectal polyps . Within 4 weeks following the polypectomy , participants completed a baseline survey by telephone , and were r and omized to either Usual Care ( UC ) or the PREVENT intervention , which was design ed to target multiple risk factors . The intervention consisted of a telephone-delivered intervention plus tailored material s , and focused on the six primary behavioral risk factors for colorectal cancer , including red meat consumption , fruit and vegetable intake , multivitamin intake , alcohol , smoking , and physical inactivity . Results : Participation in the PREVENT intervention was associated with a significantly greater reduction in prevalence of multiple risk factors for colorectal cancer compared with UC . Only about one third of UC participants dropped any risk factors during the study period , compared with almost half of the PREVENT participants . PREVENT participants were also significantly more likely to change more than one behavior than UC participants . Conclusions : The PREVENT intervention was effective in helping patients change multiple risk factors . These results provide further support that more comprehensive interventions that move beyond emphasis on a single risk factor are acceptable to patient population s , can result in improvements , and are cost effective Colorectal cancer screening forms part of Scotl and 's cancer reduction strategy . Screened participants , who had undergone colonoscopy and had adenoma(s ) removed , were invited to participate in the bowel health to better health ( BHBH ) programme . BHBH tested the hypothesis that a minimal contact lifestyle intervention could prove effective in promoting changes in diet and activity . Baseline and follow-up question naires on lifestyle and psycho-social measures were undertaken in adults r and omised to BHBH or a comparison group ( CG ) . The 3-month intervention comprised personalised lifestyle advice , goal - setting and social support to promote increases in physical activity , fibre , fruit and vegetables . Response rate to BHBH was 51 % . BHBH participants ( n 32 ) increased their intake of fibre ( DINE FFQ scores 30 ( sd 11)-41 ( sd 13 ) ) significantly ( P < 0.001 ) more than the CG ( n 30 ; 31 ( sd 8)-30 ( sd 11 ) . No significant differences between the groups were detected for changes in fruits , vegetables and moderate activity . At baseline , only one participant from each study arm , met the target recommendations for fibre , fruit and vegetable intakes and physical activity . At follow up a significant number of BHBH participants , 15 ( 47 % ) compared to 4 ( 13 % ) of the CG were achieving all three lifestyle recommendations ( chi2 ( 1 , n 62 ) = 8.196 , P = 0.006 ) . If sustained , the positive behaviour change achieved through this intervention has the potential to impact on the progression of chronic disease risk including CVD BACKGROUND Evidence suggests that a high proportion of perimenopausal and postmenopausal women experience vasomotor symptoms ( hot flushes/night sweats ) that can be severe and disruptive and which are the principal reason for seeking medical intervention . Hormone therapy ( HT ) is known to be an effective treatment for troublesome hot flushes/night sweats but research has raised questions about the safety of HT and there have been negative high profile media reports about its use . Consequently many women are seeking alternatives and exercise might be one such option but there is a lack of high quality evidence on its effectiveness . AIMS This RCT initially aims to investigate the feasibility/acceptability of two exercise interventions identified from our previous preference study in 165 women , and if found to be feasible/acceptable , continue to recruit sufficient women ( n=261 ) to examine the effect of these interventions on hot flushes/night sweats and other outcomes relevant to menopausal women . METHOD We aim to recruit inactive perimenopausal and menopausal symptomatic women not using HT and r and omise them to one of two exercise interventions or usual care for six months . RESULTS We will assess outcomes at baseline and 6 and 12 months from r and omisation . CONCLUSION We hope this RCT will contribute towards increasing the evidence regarding the question of whether exercise is an effective treatment for vasomotor symptoms in women not taking HT R and omized controlled trials are recognized as having the strongest type of study design for generating evidence on prevention of disease . They are , however , the most labor- and time-intensive and costly to conduct . Intervention studies on the recurrence of colorectal adenomas might serve as a model with relevance to the etiology of not only large bowel cancer but also other sites of neoplastic development . The results of intervention studies assessing the effect of calcium , antioxidants and fiber on the recurrence of colorectal adenomas have been conflicting , showing a beneficial effect in some cases but not others . There are method ological issues in intervention trials for colorectal cancer , regarding study subjects , end point , dose , interaction , duration and timing , and compliance , for example . Although relatively few trials have been conducted to investigate the effects of an explicit dietary change on the recurrence of adenoma , results obtained so far have demonstrated that modifying the lifestyle may reduce the risk of chronic diseases including cancer . Furthermore , recent progress in molecular epidemiology has allowed clarification of many of the molecular mechanisms underlying susceptibility . Eventually , it may be possible to target intervention programs to genetically susceptible individuals , including molecular targeting , for the prevention of cancer |
12,252 | 28,322,294 | However , we found no significant improvement in HOMA-IR following treatment with DPP-4 inhibitors as mono-therapy or as add-on therapy .
In conclusion , DPP-4 inhibitors as monotherapy or as add-on therapy significantly improved beta-cell function but had no significant effect on insulin resistance in type 2 diabetes | Dipeptidyl peptidase-4 ( DPP-4 ) inhibitors are a novel family of glucose-lowering agents .
Accumulating evidence suggests that DPP-4 inhibitors preserve pancreatic beta-cell function , but results in previous studies have been inconsistent . | Aims : Assess the efficacy and safety of saxagliptin added to a submaximal sulphonylurea dose vs. uptitration of sulphonylurea monotherapy in patients with type 2 diabetes and inadequate glycaemic control with sulphonylurea monotherapy . Methods and patients : A total of 768 patients ( 18–77 years ; HbA1c screening ≥ 7.5 to ≤ 10.0 % ) were r and omised and treated with saxagliptin 2.5 or 5 mg in combination with glyburide 7.5 mg vs. glyburide 10 mg for 24 weeks . Blinded uptitration glyburide was allowed in the glyburide-only arm to a maximum total daily dose of 15 mg . Efficacy analyses were performed using ANCOVA and last-observation-carried-forward methodology . Results : At week 24 , 92 % of glyburide-only patients were uptitrated to a total glyburide dose of 15 mg/day . Saxagliptin 2.5 and 5 mg provided statistically significant adjusted mean decreases from baseline to week 24 vs. uptitrated glyburide , respectively , in HbA1c ( −0.54 % , −0.64 % vs. + 0.08 % ; both p < 0.0001 ) and fasting plasma glucose ( −7 , −10 vs. + 1 mg/dl ; p = 0.0218 and p = 0.002 ) . The proportion of patients achieving an HbA1c < 7 % was greater for saxagliptin 2.5 and 5 mg vs. uptitrated glyburide ( 22.4 % and 22.8 % vs. 9.1 % ; both p < 0.0001 ) . Postpr and ial glucose area under the curve was reduced for saxagliptin 2.5 and 5 mg vs. uptitrated glyburide ( −4296 and −5000 vs. + 1196 mg·min/dl ; both p < 0.0001 ) . Adverse event occurrence was similar across all groups . Reported hypoglycaemic events were not statistically significantly different for saxagliptin 2.5 ( 13.3 % ) and 5 mg ( 14.6 % ) vs. uptitrated glyburide ( 10.1 % ) . Conclusion : Saxagliptin added to submaximal glyburide therapy led to statistically significant improvements vs. uptitration of glyburide alone across key glycaemic parameters and was generally well tolerated Background DA-1229 is a novel , potent and selective dipeptidyl peptidase-4 ( DPP-IV ) inhibitor that is orally bioavailable . We aim ed to evaluate the optimal dose , efficacy and safety of DA-1229 , in Korean subjects with type 2 diabetes mellitus suboptimally controlled with diet and exercise . Methods We enrolled 158 patients ( mean age , 53 years and a mean BMI , 25.6 kg/m2 ) . The mean baseline fasting plasma glucose level , HbA1c and duration of diabetes were 8.28 mmol/L , 7.6 % ( 60 mmol/mol ) and 3.9 years , respectively . After 2 or 6 weeks of an exercise and diet program followed by 2 weeks of a placebo period , the subjects were r and omized into one of four groups for a 12-week active treatment period : placebo , 2.5 , 5 or 10 mg of DA-1229 . Results All three doses of DA-1229 significantly reduced HbA1c from baseline compared to the placebo group ( −0.09 in the placebo group vs. −0.56 , −0.66 and −0.61 % in 2.5 , 5 and 10-mg groups , respectively ) but without any significant differences between the doses . Insulin secretory function , as assessed by homeostasis model assessment β-cell , the insulinogenic index , 2-h oral glucose tolerance test ( OGTT ) C-peptide and post-OGTT C-peptide area under the curve (AUC)0–2h , significantly improved with DA-1229 treatment . The incidence of adverse events was similar between the treatment groups and DA-1229 did not affect body weight or induce hypoglycaemic events . Conclusions DA-1229 monotherapy ( 5 mg for 12 weeks ) improved HbA1c , fasting plasma glucose level , OGTT results and β-cell function . This drug was well tolerated in Korean subjects with type 2 diabetes mellitus . © 2014 The Authors . Diabetes/Metabolism Research and Review s published by John Wiley & Sons , Ltd. DA-1229 is a novel , potent and selective DPP-IV inhibitor that is orally bioavailable . In a pharmacodynamic study , more than 80 % of DPP-IV was inhibited by a single dose of 5 mg or higher of DA-1229 , and this level of inhibition was maintained for at least 24 h after a single dose of 10 mg or higher of DA-1229 . This phase II clinical trial was design ed to evaluate the efficacy and safety of oral DA-1229 and to determine the optimal dose to use for a phase III clinical study in Korean subjects with type 2 diabetes UNLABELLED Inhibition of dipeptidyl peptidase-4 enhances the activity of incretin hormones , improving glycemic control in subjects with type 2 diabetes . This twelve-week r and omized , double-masked , placebo-controlled study assessed the efficacy and tolerability of the specific and potent oral dipeptidyl peptidase-4 inhibitor , vildagliptin ( 25 mg , bid , n=70 ) VS . placebo ( bid , n=28 ) in previously diet-treated subjects with type 2 diabetes . St and ardized meal tests were performed at baseline and endpoint . The between-group difference in adjusted mean change in HbA1c from baseline to endpoint was - 0.6 + /- 0.2 % ( p=0.0012 ) for the whole cohort ( baseline 8.0 % ) and -1.2 % for subjects with baseline HbA1c 8.0 - 9.5 % . Fasting glucose and mean pr and ial glucose were reduced by 1.1 + /- 0.4 ( p=0.0043 ) and 1.9 + /- 0.5 mmol/l ( p < 0.0001 ) , respectively . The between-group differences in corrected insulin response at peak glucose and mean pr and ial C-peptide were + 0.06 + /- 0.02 ( p=0.0258 ) and + 0.10 + /- 0.03 nmol/l ( p=0.0031 ) , respectively . Vildagliptin had no effect on fasting lipid levels or body weight . The incidence of adverse events was similar in subjects receiving placebo ( 71.4 % ) and vildagliptin ( 55.7 % ) . CONCLUSION monotherapy with vildagliptin is well tolerated and improves glycemic control in diet-treated subjects with type 2 diabetes . Concomitant improvements in beta-cell function were also observed . Subjects with higher baseline HbA1c levels showed greater response AIM To assess the safety and efficacy of the potent and selective dipeptidyl peptidase-4 inhibitor linagliptin 5 mg when given for 24 weeks to patients with type 2 diabetes who were either treatment-naive or who had received one oral antidiabetes drug ( OAD ) . METHODS This multicentre , r and omized , parallel group , phase III study compared linagliptin treatment ( 5 mg once daily , n = 336 ) with placebo ( n = 167 ) for 24 weeks in type 2 diabetes patients . Before r and omization , patients pretreated with one OAD underwent a washout period of 6 weeks , which included a placebo run-in period during the last 2 weeks . Patients previously untreated with an OAD underwent a 2-week placebo run-in period . The primary endpoint was the change in HbA1c from baseline after 24 weeks of treatment . RESULTS Linagliptin treatment result ed in a placebo-corrected change in HbA1c from baseline of -0.69 % ( p < 0.0001 ) at 24 weeks . In patients with baseline HbA1c ≥ 9.0 % , the adjusted reduction in HbA1c was 1.01 % ( p < 0.0001 ) . Patients treated with linagliptin were more likely to achieve a reduction in HbA1c of ≥0.5 % at 24 weeks than those in the placebo arm ( 47.1 and 19.0 % , respectively ; odds ratio , OR = 4.2 , p < 0.0001 ) . Fasting plasma glucose improved by -1.3 mmol/l ( p < 0.0001 ) with linagliptin vs. placebo , and linagliptin produced an adjusted mean reduction from baseline after 24 weeks in 2-h postpr and ial glucose of -3.2 mmol/l ( p < 0.0001 ) . Statistically significant and relevant treatment differences were observed for proinsulin/insulin ratio ( p = 0.025 ) , Homeostasis Model Assessment -%B ( p = 0.049 ) and disposition index ( p = 0.0005 ) . There was no excess of hypoglycaemic episodes with linagliptin vs. placebo and no patient required third-party intervention . Mild or moderate renal impairment did not influence the trough plasma levels of linagliptin . CONCLUSIONS Monotherapy with linagliptin produced a significant , clinical ly meaningful and sustained improvement in glycaemic control , accompanied by enhanced parameters of β-cell function . The safety profile of linagliptin was comparable with that of placebo AIMS This study was conducted to compare the glycaemic efficacy and safety of initial combination therapy with the fixed-dose combination of sitagliptin and metformin versus metformin monotherapy in drug-naive patients with type 2 diabetes . METHODS This double-blind study ( 18-week Phase A and 26-week Phase B ) r and omized 1250 drug-naÏve patients with type 2 diabetes [ mean baseline haemoglobin A1c ( HbA1c ) 9.9 % ] to sitagliptin/metformin 50/500 mg bid or metformin 500 mg bid ( uptitrated over 4 weeks to achieve maximum doses of sitagliptin/metformin 50/1000 mg bid or metformin 1000 bid ) . Results of the primary efficacy endpoint ( mean HbA1c reductions from baseline at the end of Phase A ) are reported herein . RESULTS At week 18 , mean change from baseline HbA1c was -2.4 % for sitagliptin/metformin FDC and -1.8 % for metformin monotherapy ( p < 0.001 ) ; more patients treated with sitagliptin/metformin FDC had an HbA1c value < 7 % ( p < 0.001 ) versus metformin monotherapy . Changes in fasting plasma glucose were significantly greater with sitagliptin/metformin FDC ( -3.8 mmol/l ) versus metformin monotherapy ( -3.0 mmol/l ; p < 0.001 ) . Homeostasis model assessment of β-cell function ( HOMA-β ) and fasting proinsulin/insulin ratio were significantly improved with sitagliptin/metformin FDC versus metformin monotherapy . Baseline body weight was reduced by 1.6 kg in each group . Both treatments were generally well tolerated with a low and similar incidence of hypoglycaemia . Abdominal pain ( 1.1 and 3.9 % ; p = 0.002 ) and diarrhoea ( 12.0 and 16.6 % ; p = 0.021 ) occurred significantly less with sitagliptin/metformin FDC versus metformin monotherapy ; the incidence of nausea and vomiting was similar in both groups . CONCLUSION Compared with metformin monotherapy , initial treatment with sitagliptin/metformin FDC provided superior glycaemic improvement with a similar degree of weight loss and lower incidences of abdominal pain and diarrhoea BACKGROUND Type 2 diabetes mellitus ( T2DM ) is a significant burden in China , where approximately 114 million patients have been diagnosed with diabetes . Chinese patients present with prominent β-cell failure , with result ing deficiency in insulin secretion , particularly early phase insulin secretion leading to postpr and ial hyperglycemia . Sitagliptin , a selective once-daily oral dipeptidyl peptidase-4 inhibitor , has been shown to improve glycemic control as monotherapy and in combination with other antihyperglycemic agents , including sulfonylureas and metformin . METHODS This was a multicenter r and omized double-blind placebo-controlled study conducted in China . The study assessed the safety and efficacy of the addition of sitagliptin 100 mg once daily versus placebo on changes from baseline at Week 24 in HbA1c , fasting plasma glucose ( FPG ) and 2-h post-meal glucose ( PMG ) . Patients were aged 18 - 79 years , had T2DM with inadequate glycemic control , and were taking a sulfonylurea , with or without metformin . RESULTS After 24 weeks , sitagliptin reduced HbA1c , FPG , and 2-h PMG significantly more than placebo ( between-treatment differences : -0.61 % , -16.8 mg/dL , and -32.9 mg/dL , respectively ; P < 0.001 for all ) . The addition of sitagliptin was generally well tolerated , with a comparable incidence of adverse events and drug-related adverse events in both treatment groups . The sitagliptin group had a higher incidence of symptomatic hypoglycemia than the placebo group ( 25/248 [ 10.1 % ] vs 13/249 [ 5.2 % ] , respectively ; P = 0.042 ) . CONCLUSIONS Sitagliptin 100 mg once daily significantly improved glycemic control in Chinese patients with T2DM who had inadequate glycemic control with sulfonylurea , with or without metformin therapy . The addition of sitagliptin was generally well tolerated . ( clinical trials.gov : NCT01590771 ) AIMS The efficacy and safety of the dipeptidyl peptidase-4 inhibitor , linagliptin , added to ongoing metformin therapy , were assessed in patients with Type 2 diabetes who had inadequate glycaemic control ( HbA(1c ) ≥ 7.5 to ≤ 10 % ; ≥ 58.5 to ≤ 85.8 mmol/mol ) with metformin alone . METHODS Patients ( n=333 ) were r and omized to receive double-blind linagliptin ( 1 , 5 or 10 mg once daily ) or placebo or open-label glimepiride ( 1 - 3 mg once daily ) . The primary outcome measure was the change from baseline in HbA(1c ) at week 12 in patients receiving combination therapy compared with metformin alone . RESULTS Twelve weeks of treatment result ed in a mean ( sem ) placebo-corrected lowering in HbA(1c ) levels of 0.40 % ( ± 0.14 ) ; 4.4 mmol/mol ( ± 1.5 ) for 1 mg linagliptin , 0.73 % ( ± 0.14 ) ; 8.0 mmol/mol ( ± 1.5 ) for 5 mg , and 0.67 % ( ± 0.14 ) ; 7.3 mmol/mol ( ± 1.5 ) for 10 mg . Differences between linagliptin and placebo were statistically significant for all doses ( 1 mg , P = 0.01 ; 5 mg and 10 mg , P < 0.0001 ) . The change in mean ( sem ) placebo-corrected HbA(1c ) from baseline was -0.90 % ( ± 0.13 ) ; -9.8 mmol/mol ( ± 1.4 ) for glimepiride . Adjusted and placebo-corrected mean changes in fasting plasma glucose were -1.1 mmol/l for linagliptin 1 mg ( P = 0.002 ) , -1.9 mmol/l for 5 mg and -1.6 mmol/l for 10 mg ( both P < 0.0001 ) . One hundred and six ( 43.1 % ) patients reported adverse events ; the incidence was similar across all five groups . There were no hypoglycaemic events for linagliptin or placebo , whereas three patients ( 5 % ) receiving glimepiride experienced hypoglycaemia . CONCLUSIONS The addition of linagliptin to ongoing metformin treatment in patients with Type 2 diabetes was well tolerated and result ed in significant and clinical ly relevant improvements in glycaemic control , with 5 mg linagliptin being the most effective dose BACKGROUND Few studies have assessed the use of new oral anti-diabetic agents in Asian population s. This study assesses the efficacy and safety of saxagliptin versus placebo in Asian patients with type 2 diabetes mellitus ( T2DM ) . MATERIAL S AND METHODS Five hundred sixty-eight drug-naïve adult patients with T2DM and glycated haemoglobin levels ( HbA(1c ) ) of 7.0 - 10.0 % ( 53 - 86 mmol/mol ) were r and omized 1 : 1 to receive saxagliptin 5 mg daily or placebo . Efficacy endpoints included changes from baseline to week 24 in HbA(1c ) , fasting plasma glucose ( FPG ) , post-pr and ial glucose area under the curve from 0 to 180 min ( PPG AUC(0 - 180 ) ) , and the proportion of patients achieving HbA(1c ) < 7.0 % ( 53 mmol/mol ) . Adverse events ( AEs ) and serious AEs ( SAEs ) were evaluated . RESULTS Saxagliptin provided statistically significant adjusted mean decreases from baseline to week 24 compared with placebo , respectively , in HbA(1c ) ( -0.84 % [ -9 mmol/mol ] versus -0.34 % [ -4 mmol/mol ] ; p < 0.0001 ) , FPG ( -0.90 versus -0.17 mmol/L ; p < 0.0001 ) , and PPG AUC(0 - 180 ) ( -417 versus -235 mmol · min/L ; p = 0.0010 ) . A significantly greater proportion of patients achieved a therapeutic glycaemic response ( HbA(1c ) < 7.0 % [ 53 mmol/mol ] ) with saxagliptin ( 45.8 % ) versus placebo ( 28.8 % ; p < 0.0001 ) . The proportions of patients who experienced ≥1 AE ( excluding hypoglycaemia ) was 43.3 % for saxagliptin and 35.6 % for placebo . Few patients in either treatment group experienced an SAE ( 2.8 % , saxagliptin ; 1.4 % , placebo ) . A low proportion of patients reported hypoglycaemic events ( 1.8 % , saxagliptin ; 0.7 % , placebo ) . CONCLUSIONS Saxagliptin improved glycaemic control and was well tolerated in drug-naïve Asian patients with T2DM AIMS /HYPOTHESIS Vildagliptin is a selective dipeptidyl peptidase IV inhibitor that augments meal-stimulated levels of biologically active glucagon-like peptide-1 . Chronic vildagliptin treatment decreases postpr and ial glucose levels and reduces hemoglobin A1c in type 2 diabetic patients . However , little is known about the mechanism(s ) by which vildagliptin promotes reduction in plasma glucose concentration . METHODS Sixteen patients with type 2 diabetes ( age , 48+/-3 yr ; body mass index , 34.4+/-1.7 kg/m2 ; hemoglobin A1c , 9.0+/-0.3 % ) participated in a r and omized , double-blind , placebo-controlled trial . On separate days patients received 100 mg vildagliptin or placebo at 1730 h followed 30 min later by a meal tolerance test ( MTT ) performed with double tracer technique ( 3-(3)H-glucose iv and 1-(14)C-glucose orally ) . RESULTS After vildagliptin , suppression of endogenous glucose production ( EGP ) during 6-h MTT was greater than with placebo ( 1.02+/-0.06 vs. 0.74+/-0.06 mg.kg-1.min-1 ; P=0.004 ) , and insulin secretion rate increased by 21 % ( P=0.003 ) despite significant reduction in mean plasma glucose ( 213+/-4 vs. 230+/-4 mg/dl ; P=0.006 ) . Consequently , insulin secretion rate ( area under the curve ) divided by plasma glucose ( area under the curve ) increased by 29 % ( P=0.01 ) . Suppression of plasma glucagon during MTT was 5-fold greater with vildagliptin ( P<0.02 ) . The decline in EGP was positively correlated ( r=0.55 ; P<0.03 ) with the decrease in fasting plasma glucose ( change=-14 mg/dl ) . CONCLUSIONS During MTT , vildagliptin augments insulin secretion and inhibits glucagon release , leading to enhanced suppression of EGP . During the postpr and ial period , a single dose of vildagliptin reduced plasma glucose levels by enhancing suppression of EGP The stimulation of insulin vs. inhibition of glucagon secretion in relation to the antidiabetic action of glucagon-like peptide-1 ( GLP-1 ) is not established . Here , the influence of a 4-wk increase in circulating GLP-1 by inhibition of dipeptidyl peptidase-4 ( DPP-4 ) on 24-h glucose and insulin and glucagon responses to breakfast was studied in subjects with dietary controlled diabetes [ age : 65 + /- 8 yr ( SD ) , body mass index : 27.3 + /- 3.3 kg/m(2 ) , fasting plasma glucose : 9.0 + /- 1.3 mmol/liter ] . Compared with placebo ( n = 19 ) , a specific DPP-4 inhibitor [ ( 1-[[(3-hydroxy-1-adamantyl ) amino ] acetyl]-2-cyano-(S)-pyrrolidine ) ( LAF237 ) ; 100 mg daily , n = 18 ] reduced fasting glucose by 0.70 mmol/liter ( P = 0.037 ) , 4-h pr and ial glucose excursion by 1.45 mmol/liter ( P < 0.001 ) , and mean 24-h glucose by 0.93 mmol/liter ( P < 0.001 ) . Baseline and postpr and ial active GLP-1 were increased by LAF237 . The glucagon response to breakfast was reduced by LAF237 ( glucagon levels at 60 min were 88 + /- 8 pg/ml before treatment vs. 77 + /- 5 pg/ml after ; P = 0.001 ) . In contrast , the overall insulin levels were not altered . The 4-wk reduction in glucagon correlated with the reduction in 2-h glucose ( r = 0.61 ; P = 0.008 ) . No such association was observed for insulin . Thus , improved metabolic control by DPP-4 inhibition in type 2 diabetes is seen in association with reduced glucagon levels and , despite the lower glycemia , unaltered insulin levels BACKGROUND Little is known about the timing of changes in glucose metabolism before occurrence of type 2 diabetes . We aim ed to characterise trajectories of fasting and postload glucose , insulin sensitivity , and insulin secretion in individuals who develop type 2 diabetes . METHODS We analysed data from our prospect i ve occupational cohort study ( Whitehall II study ) of 6538 ( 71 % male and 91 % white ) British civil servants without diabetes mellitus at baseline . During a median follow-up period of 9.7 years , 505 diabetes cases were diagnosed ( 49.1 % on the basis of oral glucose tolerance test ) . We assessed retrospective trajectories of fasting and 2-h postload glucose , homoeostasis model assessment ( HOMA ) insulin sensitivity , and HOMA beta-cell function from up to 13 years before diabetes diagnosis ( diabetic group ) or at the end of follow-up ( non-diabetics ) . FINDINGS Multilevel models adjusted for age , sex , and ethnic origin confirmed that all metabolic measures followed linear trends in the group of non-diabetics ( 10,989 measurements ) , except for insulin secretion that did not change during follow-up . In the diabetic group ( 801 measurements ) , a linear increase in fasting glucose was followed by a steep quadratic increase ( from 5.79 mmol/L to 7.40 mmol/L ) starting 3 years before diagnosis of diabetes . 2-h postload glucose showed a rapid increase starting 3 years before diagnosis ( from 7.60 mmol/L to 11.90 mmol/L ) , and HOMA insulin sensitivity decreased steeply during the 5 years before diagnosis ( to 86.7 % ) . HOMA beta-cell function increased between years 4 and 3 before diagnosis ( from 85.0 % to 92.6 % ) and then decreased until diagnosis ( to 62.4 % ) . INTERPRETATION In this study , we show changes in glucose concentrations , insulin sensitivity , and insulin secretion as much as 3 - 6 years before diagnosis of diabetes . The description of biomarker trajectories leading to diabetes diagnosis could contribute to more-accurate risk prediction models that use repeated measures available for patients through regular check-ups . FUNDING Medical Research Council ( UK ) ; Economic and Social Research Council ( UK ) ; British Heart Foundation ( UK ) ; Health and Safety Executive ( UK ) ; Department of Health ( UK ) ; National Institute of Health ( USA ) ; Agency for Health Care Policy Research ( USA ) ; the John D and Catherine T MacArthur Foundation ( USA ) ; and Academy of Finl and ( Finl and ) 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 OBJECTIVE : To evaluate the effect of dipeptidyl-peptidase-4 ( DPP-4 ) inhibitor vildagliptin on high sensitivity C-reactive protein ( hsCRP ) and arterial stiffness ( AS ) in patients with type 2 diabetes ( T2DM ) . DESIGN : Sixty-four drug-naive diabetic patients , with inadequate glycemic control , participated in this r and omized , open-label study . Half of the patients received metformin 1700 mg/d and the other half of them received metformin 1700 mg/d plus vildagliptin 100 mg/d . AS was measured by carotid-femoral Pulse Wave Velocity ( cfPWV ) . Body weight ( BW ) , body mass index ( BMI ) , blood pressure ( BP ) , hsCRP , glycosylated hemoglobin ( HbA1c ) , fasting plasma glucose ( FPG ) , lipid profile , albumin/creatinine ratio ( ACR ) , fasting insulin , C-peptide , homeostasis model assessment of insulin resistance ( HOMA-IR ) and homeostasis model assessment of β-cell function ( HOMA-β ) were also assessed at baseline and after 6 months . RESULTS : Vildagliptin in combination with metformin had a beneficial influence on hsCRP , HbA1c , C-peptide and HOMA-β index ( p < 0.05 ) but had no effect on cfPWV , BP , BW , BMI , lipid profile , ACR and HOMA-IR compared with metformin alone ( p = NS ) . CONCLUSIONS : We have found that the addition of vildagliptin to metformin for a period of six months decreased hsCRP , improved glycemic control and β-cell function but had no effect on AS in drug-naive patients with T2DM OBJECTIVE Liraglutide ( glucagon-like peptide-1 [ GLP-1 ] receptor agonist ) and sitagliptin ( dipeptidyl peptidase-4 inhibitor ) are approved in Japan for treating type 2 diabetes mellitus ( T2DM ) . We compared the efficacy and safety of adding liraglutide or sitagliptin to a sulfonylurea in Japanese T2DM patients . METHODS Patients aged 18 to < 80 years with hemoglobin A1c ( HbA1c ; National Glycohemoglobin St and ardization Program [ NGSP ] ) of 6.9 - 9.4 % , body mass index ≤35 kg/m(2 ) , and treatment with a sulfonylurea and /or one or two non-sulfonylurea oral antidiabetic drugs for greater than or equal to eight weeks before enrollment were eligible . Patients were r and omized in an open-label manner to either 0.9 mg/day liraglutide ( n = 50 ) or 50 - 100 mg/day sitagliptin ( n = 49 ) and were treated for 24 weeks . Non-sulfonylureas were discontinued before r and omization . Patients using other oral antidiabetic drugs started sulfonylurea treatment . The primary endpoint was the change in HbA1c from baseline to Week 24 . RESULTS HbA1c decreased in both groups , and the reduction was significantly greater throughout in the liraglutide group except for Week 24 ( 0.59 ± 0.80 vs. 0.24 ± 0.94 % ; P = 0.0525 ) . Fasting plasma glucose ( FPG ) decreased significantly in the liraglutide group compared with the sitagliptin group ( -21.15 ± 31.22 vs. + 0.46 ± 39.39 mg/dL ; P = 0.0014 ) . Homeostasis model assessment of β cell function and C-peptide increased significantly in the liraglutide group but not in the sitagliptin group . Hypoglycemic symptoms and adverse events occurred in four and nine patients , respectively , in the liraglutide group , and in two and five patients , respectively , in the sitagliptin group . CONCLUSION Treatment with liraglutide or sitagliptin together with a sulfonylurea improved HbA1c in Japanese T2DM patients in primary care . Both drugs were associated with low rates of adverse events and hypoglycemia . The improvement in β cell function probably contributed to the improvement in glycemic control in the liraglutide group AIM To assess the efficacy and safety of a 24-week treatment with sitagliptin , a highly selective once-daily oral dipeptidyl peptidase-4 ( DPP-4 ) inhibitor , in patients with type 2 diabetes who had inadequate glycaemic control [ glycosylated haemoglobin ( HbA(1c ) ) > or=7.5 % and < or=10.5 % ] while on glimepiride alone or in combination with metformin . METHODS After a screening , diet/exercise run-in and drug wash-off period , a glimepiride + /- metformin dose titration/stabilization period and a 2-week , single-blind placebo run-in , 441 patients ( of ages 18 - 75 years ) were r and omized to receive the addition of sitagliptin 100 mg once daily or placebo in a 1 : 1 ratio for 24 weeks . Of these patients , 212 were on glimepiride ( > or=4 mg/day ) monotherapy and 229 were on glimepiride ( > or=4 mg/day ) plus metformin ( > or=1,500 mg/day ) combination therapy . Patients exceeding pre-specified glycaemic thresholds during the double-blind treatment period were provided open-label rescue therapy ( pioglitazone ) until study end . The primary efficacy analysis evaluated the change in HbA(1c ) from baseline to Week 24 . Secondary efficacy endpoints included fasting plasma glucose ( FPG ) , 2-h post-meal glucose and lipid measurements . RESULTS Mean baseline HbA(1c ) was 8.34 % in the sitagliptin and placebo groups . After 24 weeks , sitagliptin reduced HbA(1c ) by 0.74 % ( p < 0.001 ) relative to placebo . In the subset of patients on glimepiride plus metformin , sitagliptin reduced HbA(1c ) by 0.89 % relative to placebo , compared with a reduction of 0.57 % in the subset of patients on glimepiride alone . The addition of sitagliptin reduced FPG by 20.1 mg/dl ( p < 0.001 ) and increased homeostasis model assessment -beta , a marker of beta-cell function , by 12 % ( p < 0.05 ) relative to placebo . In patients who underwent a meal tolerance test ( n = 134 ) , sitagliptin decreased 2-h post-pr and ial glucose ( PPG ) by 36.1 mg/dl ( p < 0.001 ) relative to placebo . The addition of sitagliptin was generally well tolerated , although there was a higher incidence of overall ( 60 vs. 47 % ) and drug-related adverse experiences ( AEs ) ( 15 vs. 7 % ) in the sitagliptin group than in the placebo group . This was largely because of a higher incidence of hypoglycaemia AEs ( 12 vs. 2 % , respectively ) in the sitagliptin group compared with the placebo group . Body weight modestly increased with sitagliptin relative to placebo ( + 0.8 vs. -0.4 kg ; p < 0.001 ) . CONCLUSIONS Sitagliptin 100 mg once daily significantly improved glycaemic control and beta-cell function in patients with type 2 diabetes who had inadequate glycaemic control with glimepiride or glimepiride plus metformin therapy . The addition of sitagliptin was generally well tolerated , with a modest increase in hypoglycaemia and body weight , consistent with glimepiride therapy and the observed degree of glycaemic improvement AIM To assess the efficacy and safety of alogliptin added to pioglitazone versus pioglitazone monotherapy , in Japanese patients with type 2 diabetes who achieved inadequate glycaemic control on pioglitazone plus diet/exercise . METHODS Patients were stabilized on pioglitazone 15 or 30 mg/day plus diet/exercise during a 16-week screening period . Patients with HbA1c of 6.9 - 10.4 % were r and omized to 12 weeks ' double-blind treatment with alogliptin 12.5 or 25 mg once daily or placebo , added to their stable pioglitazone regimen . The primary endpoint was the change in HbA1c from baseline to week 12 . Patients had an option to continue in a 40-week , open-label extension study , with those originally r and omized to alogliptin remaining on the same dosage regimen while patients treated with placebo were r and omly allocated to alogliptin 12.5 or 25 mg ( added to their stable pioglitazone ) . RESULTS The change from baseline in HbA1c after 12 weeks was significantly greater with alogliptin 12.5 mg added to pioglitazone and alogliptin 25 mg added to pioglitazone than with placebo added to pioglitazone ( -0.91 and -0.97 % vs. -0.19 % ; p < 0.0001 ) . Responder rates ( HbA1c < 6.9 % and HbA1c < 6.2 % ) and changes in fasting and postpr and ial blood glucose levels showed a similar positive trend in terms of glycaemic control . The benefits seen with alogliptin were sustained during the 40-week extension period . Alogliptin added to pioglitazone was generally well tolerated ; hypoglycaemia was infrequent and increases in body weight were minor . CONCLUSIONS Once-daily alogliptin was effective and generally well tolerated when given as add-on therapy to pioglitazone in Japanese patients with type 2 diabetes who achieved inadequate glycaemic control on pioglitazone plus lifestyle measures . Clinical benefits were maintained for 52 weeks AIMS To evaluate the efficacy and safety of linagliptin 5 and 10 mg vs. placebo and voglibose in Japanese patients with type 2 diabetes mellitus ( T2DM ) . METHODS This study enrolled patients with inadequately controlled T2DM who were previously treated with one or two oral antidiabetics or were drug naÏve . After a 2 to 4-week washout and placebo run-in , 561 patients were r and omized ( 2 : 2 : 2 : 1 ) to double-blind treatment with linagliptin 5 or 10 mg qd , voglibose 0.2 mg tid or placebo . The primary endpoint was the change from baseline in haemoglobin A1c ( HbA1c ) with linagliptin vs. placebo after 12 weeks and vs. voglibose after 26 weeks . RESULTS Baseline characteristics were well balanced across treatment groups ( overall mean HbA1c was 8.01 % ) . The adjusted mean ( 95 % confidence interval ) treatment differences at week 12 were -0.87 % ( -1.04 , -0.70 ; p < 0.0001 ) and -0.88 % ( -1.05 , -0.71 ; p < 0.0001 ) for linagliptin 5 and 10 mg vs. placebo and at week 26 were -0.32 % ( -0.49 , -0.15 ; p = 0.0003 ) and -0.39 % ( -0.56 , -0.21 ; p < 0.0001 ) for linagliptin 5 and 10 mg vs. voglibose . At week 12 , mean HbA1c was 7.58 , 7.48 and 8.34 % in patients receiving linagliptin 5 mg , linagliptin 10 mg and placebo , respectively . At week 26 , mean HbA1c was 7.63 % with linagliptin 5 mg , 7.50 % with linagliptin 10 mg and 7.91 % with voglibose . Drug-related adverse event rates were comparable across treatment groups over 12 weeks ( 9.4 % linagliptin 5 mg , 8.8 % linagliptin 10 mg and 10.0 % placebo ) and 26 weeks ( 11.3 % linagliptin 5 mg , 10.6 % linagliptin 10 mg and 18.5 % voglibose ) . There were no documented cases of hypoglycaemia . CONCLUSIONS Linagliptin showed superior glucose-lowering efficacy and comparable safety and tolerability to both placebo and voglibose in Japanese patients with T2DM Background Experimental studies have suggested that dipeptidyl peptidase-4 ( DPP-4 ) inhibitors provide cardiovascular protective effects . We performed a r and omized study to evaluate the effects of sitagliptin added on to the conventional therapy compared with conventional therapy alone ( diet , exercise , and /or drugs , except for incretin-related agents ) on the intima-media thickness ( IMT ) of the carotid artery , a surrogate marker for the evaluation of atherosclerotic cardiovascular disease , in people with type 2 diabetes mellitus ( T2DM ) . Methods and Findings We used a multicenter PROBE ( prospect i ve , r and omized , open label , blinded endpoint ) design . Individuals aged ≥30 y with T2DM ( 6.2 % ≤ HbA1c < 9.4 % ) were r and omly allocated to receive either sitagliptin ( 25 to 100 mg/d ) or conventional therapy . Carotid ultrasound was performed at participating medical centers , and all parameters were measured in a core laboratory . Of the 463 enrolled participants with T2DM , 442 were included in the primary analysis ( sitagliptin group , 222 ; conventional therapy group , 220 ) . Estimated mean ( ± st and ard error ) common carotid artery IMT at 24 mo of follow-up in the sitagliptin and conventional therapy groups was 0.827 ± 0.007 mm and 0.837 ± 0.007 mm , respectively , with a mean difference of −0.009 mm ( 97.2 % CI −0.028 to 0.011 , p = 0.309 ) . HbA1c level at 24 mo was significantly lower with sitagliptin than with conventional therapy ( 6.56 % ± 0.05 % versus 6.72 % ± 0.05 % , p = 0.008 ; group mean difference −0.159 , 95 % CI −0.278 to −0.041 ) . Episodes of serious hypoglycemia were recorded only in the conventional therapy group , and the rate of other adverse events was not different between the two groups . As it was not a placebo-controlled trial and carotid IMT was measured as a surrogate marker of atherosclerosis , there were some limitations of interpretation . Conclusions In the PROLOGUE study , there was no evidence that treatment with sitagliptin had an additional effect on the progression of carotid IMT in participants with T2DM beyond that achieved with conventional treatment . Trial Registration University Hospital Medical Information Network Clinical Trials Registry OBJECTIVE This 24-week trial assessed the efficacy and safety of saxagliptin as add-on therapy in patients with type 2 diabetes with inadequate glycemic control with metformin alone . RESEARCH DESIGN AND METHODS This was a r and omized , double-blind , placebo-controlled study of saxagliptin ( 2.5 , 5 , or 10 mg once daily ) or placebo plus a stable dose of metformin ( 1,500–2,500 mg ) in 743 patients ( A1C ≥7.0 and ≤10.0 % ) . Efficacy analyses were performed using an ANCOVA model using last observation carried forward methodology on primary ( A1C ) and secondary ( fasting plasma glucose [ FPG ] and postpr and ial glucose [ PPG ] area under the curve [ AUC ] ) end points . RESULTS Saxagliptin ( 2.5 , 5 , and 10 mg ) plus metformin demonstrated statistically significant adjusted mean decreases from baseline to week 24 versus placebo in A1C ( −0.59 , −0.69 , and −0.58 vs. + 0.13 % ; all P < 0.0001 ) , FPG ( −14.31 , −22.03 , and −20.50 vs. + 1.24 mg/dl ; all P < 0.0001 ) , and PPG AUC ( −8,891 , −9,586 , and −8,137 vs. −3,291 mg · min/dl ; all P < 0.0001 ) . More than twice as many patients achieved A1C < 7.0 % with 2.5 , 5 , and 10 mg saxagliptin versus placebo ( 37 , 44 , and 44 vs. 17 % ; all P < 0.0001 ) . β-Cell function and postpr and ial C-peptide , insulin , and glucagon AUCs improved in all saxagliptin treatment groups at week 24 . Incidence of hypoglycemic adverse events and weight reductions were similar to those with placebo . CONCLUSIONS Saxagliptin once daily added to metformin therapy was generally well tolerated and led to statistically significant improvements in glycemic indexes versus placebo added to metformin in patients with type 2 diabetes inadequately controlled with metformin alone CONTEXT Due to the natural progression of type 2 diabetes ( T2D ) , most patients require combination therapy to maintain glycemic control . OBJECTIVE Our objective was to evaluate efficacy and safety of saxagliptin plus thiazolidinedione ( TZD ) in patients with T2D and inadequate glycemic control on TZD monotherapy . DESIGN The study was a multicenter , r and omized , double-blind , placebo (PBO)-controlled phase 3 trial conducted from March 13 , 2006 , to October 15 , 2007 . SETTING Patients were recruited from 172 outpatient centers . PATIENTS Patients with inadequately controlled T2D [ glycosylated hemoglobin ( HbA(1c ) ) 7.0 - 10.5 % ] , 18 - 77 yr , receiving stable TZD monotherapy ( pioglitazone 30 or 45 mg or rosiglitazone 4 or 8 mg ) for at least 12 wk before screening were eligible . INTERVENTIONS A total of 565 patients were r and omized and treated with saxagliptin ( 2.5 or 5 mg ) or PBO , once daily , plus stable TZD dose for 24 wk . MAIN OUTCOME MEASURES Primary outcome was change in HbA(1c ) from baseline to wk 24 . Secondary outcomes were change from baseline to wk 24 in fasting plasma glucose , proportion of patients achieving HbA(1c ) less than 7.0 % , and postpr and ial glucose area under the curve . RESULTS At 24 wk , saxagliptin ( 2.5 and 5 mg ) plus TZD demonstrated statistically significant adjusted mean decreases vs. PBO in HbA(1c ) [ -0.66 % ( P = 0.0007 ) and -0.94 % ( P < 0.0001 ) vs. -0.30 % ] and fasting plasma glucose [ -0.8 mmol/liter ( P = 0.0053 ) and -1 mmol/liter ( P = 0.0005 ) vs. -0.2 mmol/liter ] . Proportion of patients achieving HbA(1c ) less than 7.0 % was greater for saxagliptin ( 2.5 and 5 mg ) plus TZD vs. PBO [ 42.2 % ( P = 0.001 ) and 41.8 % ( P = 0.0013 ) vs. 25.6 % ] . Postpr and ial glucose area under the curve was significantly reduced [ -436 mmol x min/liter ( saxagliptin 2.5 mg plus TZD ) and -514 mmol x min/liter ( saxagliptin 5 mg plus TZD ) vs. -149 mmol x min/liter ( PBO ) ] . Saxagliptin was generally well tolerated ; adverse event occurrence and reported hypoglycemic events were similar across all groups . CONCLUSIONS Saxagliptin added to TZD provided statistically significant improvements in key parameters of glycemic control vs. TZD monotherapy and was generally well tolerated Aims /hypothesisThe aim of this study was to assess the efficacy and safety of sitagliptin ( MK-0431 ) as monotherapy in patients with type 2 diabetes mellitus and inadequate glycaemic control ( HbA1c ≥7 % and ≤10 % ) on exercise and diet . Methods A total of 521 patients aged 27–76 years with a mean baseline HbA1c of 8.1 % were r and omised in a 1:2:2 ratio to treatment with placebo , sitagliptin 100 mg once daily , or sitagliptin 200 mg once daily , for 18 weeks . The efficacy analysis was based on an all- patients -treated population using an analysis of covariance , excluding data obtained after glycaemic rescue . Results After 18 weeks , HbA1c was significantly reduced with sitagliptin 100 mg and 200 mg compared with placebo ( placebo-subtracted HbA1c reduction : −0.60 % and −0.48 % , respectively ) . Sitagliptin also significantly decreased fasting plasma glucose relative to placebo . Patients with higher baseline HbA1c ( ≥9 % ) experienced greater placebo-subtracted HbA1c reductions with sitagliptin ( −1.20 % for 100 mg and −1.04 % for 200 mg ) than those with HbA1c < 8 % ( −0.44 % and −0.33 % , respectively ) or ≥8 % to 8.9 % ( −0.61 % and −0.39 % , respectively ) . Homeostasis model assessment beta cell function index and fasting proinsulin : insulin ratio , markers of insulin secretion and beta cell function , were significantly improved with sitagliptin . The incidence of hypoglycaemia and gastrointestinal adverse experiences was not significantly different between sitagliptin and placebo . Sitagliptin had a neutral effect on body weight . Conclusions /interpretationSitagliptin significantly improved glycaemic control and was well tolerated in patients with type 2 diabetes mellitus who had inadequate glycaemic control on exercise and diet Efficacy and tolerability of sitagliptin , a dipeptidyl peptidase-4 inhibitor , were assessed in Japanese patients with type 2 diabetes . In a multicenter , double-blind , r and omized , placebo-controlled trial in Japan , 151 patients with inadequate glycemic control [ HbA(1c ) > or = 6.5 % to < 10 % , fasting plasma glucose ( FPG ) > or = 126 to < or = 240 mg/dL ] were r and omized to once-daily sitagliptin 100 mg or placebo for 12 weeks . After 12 weeks , the least squares ( LS ) mean change from baseline HbA(1c ) was -0.65 % ( 95 % CI : -0.80 , -0.50 ) with sitagliptin versus 0.41 % ( 0.26 , 0.56 ) with placebo [ between-group difference=-1.05 % ( -1.27 , -0.84 ) ; p<0.001 ] . LS mean change from baseline FPG was -22.5mg/dL ( 95 % CI : -28.0 , -17.0 ) with sitagliptin versus 9.4 mg/dL ( 3.9 , 14.9 ) with placebo [ between-group difference=-31.9 mg/dL ( 95 % CI : -39.7,-24.1 ) ; p<0.001 ] . More patients achieved HbA(1c ) < 7 % or < 6.5 % with sitagliptin than with placebo ( p<0.001 ) . Following a meal tolerance test , 2-h postpr and ial glucose was significantly reduced with sitagliptin relative to placebo . Clinical and laboratory adverse experiences were similar between treatments , with no reported hypoglycemia adverse events with sitagliptin . Body weight was unchanged relative to baseline in the sitagliptin group ( -0.1 kg ) , but significantly ( p<0.01 ) different relative to the placebo group ( -0.7 kg ) . In this study , once-daily sitagliptin 100 mg for 12 weeks improved fasting and postpr and ial glycemic control and was generally well tolerated in Japanese patients with type 2 diabetes AIM To assess the efficacy , safety and dose-response relationship of once-daily teneligliptin , a novel dipeptidyl peptidase-4 inhibitor , in Japanese patients with type 2 diabetes mellitus ( T2DM ) inadequately controlled with diet and exercise . METHODS In this r and omized , double-blind , placebo-controlled , parallel-group study , patients ( n = 324 ) were r and omized to receive teneligliptin 10 , 20 or 40 mg , or placebo , once daily before breakfast for 12 weeks . The primary endpoint was the change in haemoglobin (Hb)A1c from baseline to week 12 . RESULTS All teneligliptin-treated groups showed significantly greater reductions in HbA1c and fasting plasma glucose ( FPG ) than did the placebo group . The differences between the teneligliptin 10 , 20 or 40 mg groups and the placebo group for the change in HbA1c were -0.9 [ least-squares ( LS ) mean ; 95 % confidence interval : -1.0 , -0.7 ] , -0.9 ( -1.1 , -0.7 ) and -1.0 ( -1.2 , -0.9)% , respectively ( all , p < 0.001 ) . The respective LS means for FPG were -17.8 ( -23.4 , -12.1 ) , -16.9 ( -22.6 , -11.2 ) and -20.0 ( -25.7 , -14.3 ) mg/dl ( all , p < 0.001 ) . There were no significant differences in HbA1c among the three doses of teneligliptin . The incidence of adverse events and adverse drug reactions was similar in each group . The incidence of hypoglycaemia was not significantly different among the four groups . CONCLUSIONS Treatment with teneligliptin for 12 weeks provided significant and clinical ly meaningful reductions in HbA1c and FPG across the dose range studied and was generally well tolerated in Japanese patients with T2DM Abstract Objective : To compare the efficacy and safety of alogliptin and placebo as add-on therapy in Japanese patients with type 2 diabetes who experienced inadequate glycemic control on voglibose plus diet/exercise therapy . Research design and methods : During an 8 week screening phase , patients aged ≥20 years were stabilized on voglibose 0.2 mg three times daily plus diet/exercise therapy . Those with HbA1c between ≥6.9 % and < 10.4 % were r and omly assigned to 12 weeks ’ double-blind treatment with once daily alogliptin 12.5 or 25 mg , or placebo . The primary endpoint was the change in HbA1c at 12 weeks from baseline . Patients then entered an open-label , 40 week extension trial ( patients in the placebo group were r and omly allocated to alogliptin 12.5 or 25 mg ) . Clinical trials registration : www . clinical trials.gov ; pivotal trial NCT01263483 ; Long term trial NCT01263509 . Results : Least square mean change in HbA1c after 12 weeks ’ therapy from baseline ( primary endpoint ) was significantly greater in the alogliptin 12.5 mg ( −0.96 % ; P < 0.0001 ) and 25 mg ( −0.93 % ; P < 0.0001 ) groups compared with placebo ( + 0.06 % ) . This was associated with statistically significant improvements in other measures of glycemic control , in particular sustained reductions in fasting plasma glucose and postpr and ial plasma glucose . These benefits were maintained for the duration of the 1 year study and , importantly , they were achieved without detrimental effects on tolerability/safety . In particular , there was no increase in the rate of hypoglycemia and almost no changes in mean body weight . Conclusions : Addition of once daily alogliptin to voglibose monotherapy in Japanese patients with uncontrolled type 2 diabetes produced clinical ly significant improvements in glycemic control , and was well tolerated BACKGROUND To assess the efficacy of a vildagliptin and metformin combination therapy to a metformin monotherapy in type 2 diabetes mellitus patients . METHODS Sixty-one patients with diabetes inadequately controlled by a metformin monotherapy were r and omized to treatment with a combination therapy of vildagliptin 100 mg and a metformin versus metformin monotherapy . This was a 12-week r and omized parallel group study . During the study we assessed parameters of glycemic and lipid metabolism as well as the treatment effects on the release of proinflammatory and antiinflammatory cytokines . RESULTS Compared with baseline values we observed a significant improvement of glycaemic parameters such as HbA1c , FPG , PPG , FPI , HOMA-IR and HOMA-β index as well as decrease of TCh , TG and LDL and an increase of HDL with the greatest extent of vildagliptin plus a low-dose metformin therapy group . A metformin combination therapy significantly decreased such inflamation parameters as hs-CRP , ox-LDL , TNF-α and IL-1β levels relative to monotherapies . All treatments were well tolerated and there was no incidence of hypoglycaemia . CONCLUSIONS Vildagliptin added to an ongoing metformin therapy allows to achieve better metabolic control parameters in comparison with a metformin monotherapy and the combination treatment is well tolerated and has a low risk of serious adverse effects Abstract Objective : To compare the efficacy and safety of different dosages of alogliptin with that of placebo and voglibose in drug-naïve Japanese patients with type 2 diabetes inadequately controlled by diet and exercise . Research design and methods : In the double-blind , placebo-controlled phase of this two-part study , 480 patients aged ≥20 years with type 2 diabetes mellitus ( HbA1c ≥6.9 % to < 10.4 % ) were r and omized to monotherapy with alogliptin 6.25 , 12.5 , 25 or 50 mg once daily , placebo , or voglibose 0.2 mg three times daily for a period of 12 weeks . In a subsequent open-label , long-term extension phase , patients continued on the same treatment for an additional 40 weeks ( patients in the placebo group were reassigned equally to one of the four alogliptin dosages ) . Main outcome measures : The primary efficacy endpoint was the change in HbA1c from the baseline value at week 12 of treatment . Safety endpoints were the occurrence of adverse events , vital sign measurements , physical examination and ECG findings , and laboratory test results recorded over the entire 52-week period . Results : HbA1c was dose-dependently reduced by alogliptin , and the changes versus baseline were statistically significant with all four dosages in comparison with both placebo and voglibose . In addition , changes in fasting plasma glucose and postpr and ial plasma glucose AUC0–2h values were significantly greater with all four dosages of alogliptin in comparison with placebo . The incidence of adverse events with alogliptin over 52 weeks was not dose-dependent and was lower than with voglibose . Hypoglycemia occurred infrequently and was generally rated as mild . Changes in body weight with alogliptin were minimal ( < 0.5 kg ) and not clinical ly meaningful . Conclusions : Alogliptin was well tolerated and dose-dependently improved glycemic parameters in patients with type 2 diabetes inadequately controlled on diet and exercise AIMS To examine the efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in persons with Type 2 diabetes mellitus inadequately controlled [ HbA(1c ) 53 - 86 mmol/mol ( 7.0 - 10.0 % ) ] by metformin and sulphonylurea combination treatment . METHODS A multi-centre , 24-week , r and omized , double-blind , parallel-group study in 1058 patients comparing linagliptin ( 5 mg once daily ) and placebo when added to metformin plus sulphonylurea . The primary endpoint was the change in HbA(1c ) after 24 weeks . RESULTS At week 24 , the linagliptin placebo-corrected HbA(1c ) adjusted mean change from baseline was -7 mmol/mol ( -0.62 % ) [ 95 % CI -8 to -6 mmol/mol ( -0.73 to -0.50 % ) ; P < 0.0001 ] . More participants with baseline HbA(1c ) ≥ 53 mmol/mol ( ≥ 7.0 % ) achieved an HbA(1c ) < 53 mmol/mol ( < 7.0 % ) with linagliptin compared with placebo ( 29.2 % vs. 8.1 % , P < 0.0001 ) . Fasting plasma glucose was reduced with linagliptin relative to placebo ( -0.7 mmol/l , 95 % CI -1.0 to -0.4 ; P<0.0001 ) . Improvements in homeostasis model assessment of β-cell function were seen with linagliptin ( P<0.001 ) . The proportion of patients who reported a severe adverse event was low in both groups ( linagliptin 2.4 % ; placebo 1.5 % ) . Symptomatic hypoglycaemia occurred in 16.7 and 10.3 % of the linagliptin and placebo groups , respectively . Hypoglycaemia was generally mild or moderate ; severe hypoglycaemia was reported in 2.7 and 4.8 % of the participants experiencing hypoglycaemic episodes in the linagliptin and placebo groups , respectively . No significant weight changes were noted . CONCLUSIONS In patients with Type 2 diabetes , adding linagliptin to metformin given in combination with a sulphonylurea significantly improved glycaemic control and this was well tolerated . Linagliptin could provide a valuable treatment option for individuals with inadequate glycaemic control despite ongoing combination therapy with metformin and a sulphonylurea AIM The objective of this study was to evaluate the optimal dose , efficacy and safety of a novel dipeptidyl peptidase-4 ( DPP-IV ) inhibitor , LC15 - 0444 , in Korean subjects with type 2 diabetes mellitus treated by diet and exercise . METHODS This study was a double-blind , r and omized , multicenter and parallel-group , dose-range finding study . We enrolled 145 patients ( 91 men and 54 women ) with a median age of 53 years and a median body mass index of 25.1 kg/m(2 ) . The median baseline fasting plasma glucose ( FPG ) was 8.1 mmol/l , the median HbA1c was 7.9 % and the median time since the diagnosis of diabetes was 3 years . After 2 weeks of an exercise/diet programme followed by 2 weeks of a placebo period , the subjects were r and omized to one of the four following groups for a 12-week active treatment period : placebo and 50 , 100 or 200 mg of LC15 - 0444 . RESULTS All three doses of LC15 - 0444 significantly reduced the HbA1c from baseline compared to the placebo group ( -0.06 vs. -0.98 , -0.74 and -0.78 % in the placebo and 50 , 100 and 200 mg groups , respectively ) , without a significant difference between the doses . Subjects with a higher baseline HbA1c ( ≥8.5 % ) had a greater reduction in HbA1c . Insulin secretory function , as assessed using homeostasis model assessment -beta cell , C-peptide and the insulinogenic index , improved significantly with LC15 - 0444 treatment . Insulin sensitivity , as assessed using homeostasis model assessment -insulin resistance , also improved significantly after 12 weeks of treatment . The 50 and 200 mg groups had significantly reduced total cholesterol and low-density lipoprotein cholesterol levels at 12 weeks compared to the placebo group . No dosage of LC15 - 0444 affected weight or waist circumference . The incidences of adverse events were similar in all study subjects . CONCLUSIONS LC15 - 0444 monotherapy ( 50 mg for 12 weeks ) improved the HbA1c , FPG level , oral glucose tolerance test results , β-cell function and insulin sensitivity measures , and was well tolerated in Korean subjects with type 2 diabetes AIMS To compare the efficacy , safety and tolerability of linagliptin or placebo administered for 24 weeks in combination with pioglitazone in patients with type 2 diabetes mellitus ( T2DM ) exhibiting insufficient glycaemic control ( HbA1c 7.5 - 11.0 % ) . METHODS Patients were r and omized to receive the initial combination of 30 mg pioglitazone plus 5 mg linagliptin ( n = 259 ) or pioglitazone plus placebo ( n = 130 ) , all once daily . The primary endpoint was change from baseline in HbA1c after 24 weeks of treatment , adjusted for baseline HbA1c and prior antidiabetes medication . RESULTS After 24 weeks of treatment , the adjusted mean change ( ±s.e . ) in HbA1c with the initial combination of linagliptin plus pioglitazone was -1.06 % ( ±0.06 ) , compared with -0.56 % ( ±0.09 ) for placebo plus pioglitazone . The difference in adjusted mean HbA1c in the linagliptin group compared with placebo was -0.51 % ( 95 % confidence interval [ CI ] -0.71 , -0.30 ; p < 0.0001 ) . Reductions in fasting plasma glucose ( FPG ) were significantly greater for linagliptin plus pioglitazone than with placebo plus pioglitazone ; -1.8 and -1.0 mmol/l , respectively , equating to a treatment difference of -0.8 mmol/l ( 95 % CI -1.2 , -0.4 ; p < 0.0001 ) . Patients taking linagliptin plus pioglitazone , compared with those receiving placebo plus pioglitazone , were more likely to achieve HbA1c of < 7.0 % ( 42.9 vs. 30.5 % , respectively ; p = 0.0051 ) and reduction in HbA1c of ≥0.5 % ( 75.0 vs. 50.8 % , respectively ; p < 0.0001 ) . β-cell function , exemplified by the ratio of relative change in adjusted mean HOMA-IR and disposition index , improved . The proportion of patients that experienced at least one adverse event was similar for both groups . Hypoglycaemic episodes ( all mild ) occurred in 1.2 % of the linagliptin plus pioglitazone patients and none in the placebo plus pioglitazone group . CONCLUSION Initial combination therapy with linagliptin plus pioglitazone was well tolerated and produced significant and clinical ly meaningful improvements in glycaemic control . This combination may offer a valuable additive initial treatment option for T2DM , particularly where metformin either is not well tolerated or is contraindicated , such as in patients with renal impairment OBJECTIVE To determine if reduction in serum insulin with dapagliflozin plus saxagliptin or dapagliflozin add-on to metformin contributed to increased insulin clearance and to assess the effects of these treatments on β-cell function . METHODS Patients ( glycated hemoglobin , 8 to 12 % ; 64 to 108 mmol/mol ) were r and omized to 24-week , double-blind treatment with saxagliptin 5 mg/day plus dapagliflozin 10 mg/day ( n = 179 ) , saxagliptin 5 mg/day plus placebo ( n = 176 ) , or dapagliflozin 10 mg/day plus placebo ( n = 179 ) added to metformin . C-peptide to insulin ratio was used as an index of insulin clearance during a meal tolerance test , and β-cell function was evaluated by Homeostasis Model Assessment 2 . RESULTS At 24 weeks , compared with baseline , saxagliptin + dapagliflozin and saxagliptin + placebo increased mean ( 95 % confidence interval [ CI ] ) C-peptide area under the curve ( AUC0 - 180 min ) ( 40.2 [ 9.2 to 71.3 ] ng/mL and 95.4 [ 63.4 to 127.4 ] ng/mL , respectively ) ; no change was noted with dapagliflozin + placebo ( 14.5 [ -17.6 to 46.8 ] ng/mL ) . Insulin AUC was reduced from baseline with saxagliptin + dapagliflozin ( -1,120.4 [ -1,633.9 to -606.9 ] μU/mL ) and dapagliflozin + placebo ( -1,018.6 [ -1550.5 to -486.8 ] μU/mL ) but increased with saxagliptin + placebo ( 661.2 [ 131.1 to 1,191.3 ] μU/mL ) . C-peptide to insulin ratio did not change versus baseline with saxagliptin + placebo but increased after saxagliptin + dapagliflozin and dapagliflozin + placebo , largely due to decreased insulin AUC with dapagliflozin . All treatments improved β-cell function ( mean change [ 95 % CI ] from baseline , saxagliptin+dapagliflozin : 20.6 % [ 16.5 % to 24.8 % ] ; dapagliflozin + placebo : 17.0 % [ 12.7 % to 21.4 % ] ; saxagliptin + placebo : 11.0 % [ 6.6 % to 15.5 % ] ) . CONCLUSION Increased C-peptide to insulin ratio with saxagliptin + dapagliflozin and dapagliflozin + placebo add-on to metformin compared with saxagliptin + placebo add-on to metformin suggests that dapagliflozin increases insulin clearance and may contribute to lower circulating insulin . All treatments improved β-cell function , with the greatest improvements with saxagliptin + dapagliflozin and dapagliflozin + placebo . ABBREVIATIONS A1c = glycated hemoglobin AUC0 - 180 min = area under the curve from 0 to 180 minutes HOMA-2β = homeostasis model assessment -2 β-cell function SGLT-2 = sodium-glucose cotransporter-2 T2D = type 2 diabetes The aim of this study was to assess the efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor , sitagliptin , in patients with type 2 diabetes who have inadequate glycaemic control on diet and exercise . In a r and omised , double-blind , placebo- and active-controlled study , 743 patients with type 2 diabetes and a mean baseline HbA(1c ) of 7.9 % were r and omised to receive one of six treatments for 12 weeks : placebo , sitagliptin 5 , 12.5 , 25 or 50 mg b.i.d . , or glipizide 5 mg/day ( electively titrated up to 20 mg/day ) . At week 12 , treatment with sitagliptin at all doses tested led to a significant ( p < 0.001 ) reduction in HbA(1c ) relative to placebo , with the largest reductions occurring in the 50-mg b.i.d . group . The placebo-subtracted differences in HbA(1c ) for the sitagliptin dose groups ranged from -0.38 % to -0.77 % in a dose-dependent manner , and -1.00 % in the glipizide group . Sitagliptin also produced significant reductions in fasting plasma glucose and mean daily glucose across the dose range studied . Sitagliptin treatment was well tolerated and result ed in no significant weight change relative to placebo . There was a modest weight gain observed with glipizide treatment relative to placebo . Hypoglycaemia adverse experiences were reported with the highest incidence in the glipizide group ( 17 % ) compared with the placebo ( 2 % ) or sitagliptin groups ( 0 - 4 % , not dose-dependent ) . In summary , in this study sitagliptin improved glycaemic control , with 50 mg b.i.d . being the most effective dose , and was generally well-tolerated in patients with type 2 diabetes AIM /HYPOTHESIS To assess the safety and efficacy of initial combination therapy with sitagliptin and pioglitazone compared with pioglitazone monotherapy in drug-naïve patients with type 2 diabetes . METHODS A total of 520 patients were r and omised to initial combination therapy with sitagliptin 100 mg q.d . and pioglitazone 30 mg q.d . or pioglitazone 30 mg q.d . monotherapy for 24 weeks . RESULTS Initial combination therapy with sitagliptin and pioglitazone led to a mean reduction from baseline in A1C of -2.4 % compared with -1.5 % for pioglitazone monotherapy ( p<0.001 ) . Mean reductions from baseline were greater in patients with a baseline A1C≥10 % ( -3.0 % with combination therapy vs. -2.1 % with pioglitazone monotherapy ) compared with patients with a baseline A1C<10 % ( -2.0 % with combination therapy vs. -1.1 % with pioglitazone monotherapy ) . Sixty percent of patients in the combination therapy group vs. 28 % in the pioglitazone monotherapy group had an A1C of < 7 % at week 24 ( p<0.001 ) . Fasting plasma glucose decreased by -63.0 mg/dl ( -3.5 mmol/l ) in the combination therapy group compared with -40.2 mg/dl ( -2.2 mmol/l ) for pioglitazone monotherapy ( p<0.001 ) , and 2-h post meal glucose decreased by -113.6 mg/dl ( -6.3 mmol/l ) with combination therapy compared with -68.9 mg/dl ( -3.8 mmol/l ) for pioglitazone monotherapy ( p<0.001 ) . Measures related to β-cell function also improved significantly with combination therapy compared with pioglitazone monotherapy . Combination therapy was generally well-tolerated compared with pioglitazone monotherapy , with similar incidences of hypoglycemia ( 1.1 % and 0.8 % , respectively ) , gastrointestinal adverse events ( 5.7 % and 6.9 % , respectively ) , and oedema ( 2.7 % and 3.5 % , respectively ) . CONCLUSION /INTERPRETATION Initial combination therapy with sitagliptin and pioglitazone substantially improved glycemic control and was generally well-tolerated compared with pioglitazone monotherapy ABSTRACT Objective : Sitagliptin , an oral , potent , and selective dipeptidyl peptidase-4 ( DPP‑4 ) inhibitor was evaluated as once-daily monotherapy in a 12-week r and omized , double-blind , placebo-controlled , parallel group , dose-ranging study . Additionally , the glycemic response to sitagliptin 100 mg daily was evaluated as a once-daily ( 100 mg once-daily ) or twice-daily ( 50 mg twice-daily ) dosing regimen . Research design and methods : In a multinational , double-blind , r and omized , placebo-controlled , parallel-group , dose-range finding study , 555 patients , 23–74 years of age , with HbA1c of 6.5–10.0 % were r and omized to one of five treatment groups : placebo , sitagliptin 25 , 50 or 100 mg once-daily , or sitagliptin 50 mg twice-daily for 12 weeks . The efficacy analysis was based on the all- patients -treated population using an ANCOVA model . Results : Mean baseline HbA1c ranged from 7.6 to 7.8 % across treatment groups , with 29 % of all patients with values ≤ 7 % . After 12 weeks , treatment with all doses of sitagliptin significantly ( p < 0.05 ) reduced HbA1c by –0.39 to –0.56 % and fasting plasma glucose by –11.0 to –17.2 mg/dLrelative to placebo , with the greatest reduction observed in the 100-mg once-daily group . Mean daily glucose was significantly ( p < 0.05 ) reduced by –14.0 to –22.6 mg/dL with all doses of sitagliptin relative to placebo . HOMA‑β was significantly ( p < 0.05 ) increased by 11.3–15.2 with all sitagliptin doses relative to placebo . QUICKI and HOMA‑IR were not significantly changed with sitagliptin treatment . There were no significant differences observed between the sitagliptin 100 mg once-daily and 50 mg twice-daily groups for any parameter . For sitagliptin , the incidence of adverse events of hypoglycemia was low , with one event in each of the 25- and 50-mg once-daily and 50-mg twice-daily treatment groups and two events in the 100 mg once-daily treatment group . There was no mean change in body weight with sitagliptin relative to placebo . Study duration may be a limitation because the extent of the glycemic response and the safety and tolerability may not have been fully eluci date d in this 12-week study . Conclusion : Sitagliptin monotherapy improved indices of glycemic control compared to placebo and was generally well-tolerated in patients with type 2 diabetes . The glycemic response to treatment with sitagliptin 100 mg/day was similar between the sitagliptin 100-mg once-daily and 50-mg twice-daily dose regimens OBJECTIVE To examine the effects of dipeptidyl peptidase-IV ( DPP-4 ) inhibition on meal-related beta-cell function and insulin sensitivity over 52 weeks in type 2 diabetes . RESEARCH DESIGN AND METHODS In a 12-week core study , placebo ( n = 51 ) or vildagliptin ( n = 56 ; 50 mg OD ) was added to metformin treatment ( 1.5 - 3.0 mg/day ) . A 40-week extension followed in 71 patients . Meal tests were performed at 0 , 12 , 24 , and 52 weeks ; glucose , insulin , and C-peptide were evaluated . RESULTS In subjects completing 52 weeks with participation in all meal tests ( n = 57 ) , HbA(1c ) ( A1C ) decreased in the vildagliptin/metformin group ( VM group , n = 31 ) but increased in the placebo/metformin group ( PM group , n = 26 ; between-group difference -1.0 + /- 0.2 % ; P < 0.001 ; baseline of all subjects combined 7.7 + /- 0.1 % ) . Also , fasting glucose decreased in the VM group but increased in the PM group ( difference -0.9 + /- 0.3 mmol/l , P = 0.016 ; baseline 9.8 + /- 0.3 mmol/l ) . Insulin secretion ( postmeal suprabasal area under the 0- to 30-min C-peptide curve divided by the 30-min increase in glucose ) was increased in the VM group but was reduced in the PM group ( difference + 0.011 + /- 0.03 pmol/l 30 min/mmol/l , P = 0.018 ; baseline 0.036 + /- 0.02 ) . Insulin sensitivity during meal ingestion ( oral glucose insulin sensitivity ) increased in the VM group but was not altered in the PM group ( difference + 27 + /- 4 ml x min(-1 ) x m(-2 ) , P = 0.036 ; baseline 246 + /- 6 ) . Insulin secretion related to insulin sensitivity ( adaptation index ) increased in the VM group but decreased in the PM group ( difference + 3.2 + /- 1.0 , P = 0.040 ; baseline 9.1 + /- 0.5 ) . The change in adaptation index correlated to the change in A1C ( r = -0.39 , P = 0.004 ) . CONCLUSIONS This study presents evidence that DPP-4 inhibition by vildagliptin when added to metformin in type 2 diabetes over 52 weeks improves beta-cell function along with improved postmeal insulin sensitivity OBJECTIVE To assess the 54-week efficacy and safety of initial combination therapy with sitagliptin and metformin in patients with type 2 diabetes and inadequate glycemic control ( HbA(1c ) 7.5 - 11 % ) on diet and exercise . METHODS AND MATERIAL S This was multinational study conducted at 140 clinical sites in 18 countries . Following an initial 24-week , double-blind , placebo-controlled period , patients entered a double-blind continuation period for an additional 30 weeks . Following the week 24 evaluation , patients remained on their previously assigned active , oral treatments : sitagliptin 50 mg b.i.d . + metformin 1000 mg b.i.d . ( S100 + M2000 ) , sitagliptin 50 mg b.i.d . + metformin 500 mg b.i.d . ( S100 + M1000 ) , metformin 1000 mg b.i.d . ( M2000 ) , metformin 500 mg b.i.d . ( M1000 ) , and sitagliptin 100 mg q.d . ( S100 ) . Patients initially r and omized to placebo were switched to M2000 ( design ated PBO/M2000 ) at week 24 . This report summarizes the overall safety and tolerability data for the 54-week study and presents efficacy results for patients r and omized to continuous treatments who entered the 30-week continuation period . RESULTS Of the 1091 r and omized patients , 906 completed the 24-week placebo-controlled phase and 885 patients continued into the 30-week continuation period ( S100 + M2000 n = 161 , S100+M1000 n = 160 , M2000 n = 153 , M1000 n = 147 , S100 n = 141 , PBO/M2000 n = 123 ) . At baseline , patients included in the efficacy analysis had mean age of 54 years , mean BMI of 32 kg/m(2 ) , mean HbA(1c ) of 8.7 % ( 8.5 - 8.8 % across groups ) , and mean duration of type 2 diabetes of 4 years . At week 54 , in the all- patients -treated analysis of continuing patients , least-squares ( LS ) mean changes in HbA(1c ) from baseline were -1.8 % ( S100 + M2000 ) , -1.4 % ( S100 + M1000 ) , -1.3 % ( M2000 ) , -1.0 % ( M1000 ) , and -0.8 % ( S100 ) . The proportions of continuing patients with an HbA(1c ) < 7 % at week 54 were 67 % ( S100 + M2000 ) , 48 % ( S100 + M1000 ) , 44 % ( M2000 ) , 25 % ( M1000 ) , and 23 % ( S100 ) . For the patients completing treatment through week 54 , LS mean changes in HbA(1c ) from baseline were -1.9 % ( S100 + M2000 ) , -1.7 % ( S100 + M1000 ) , -1.6 % ( M2000 ) , -1.2 % ( M1000 ) , and -1.4 % ( S100 ) . Glycemic response was generally durable over time across treatments . All treatments improved measures of beta-cell function ( e.g. , HOMA-beta , proinsulin/insulin ratio ) . Mean body weight decreased from baseline in the combination and metformin monotherapy groups and was unchanged from baseline in the sitagliptin monotherapy group . The incidence of hypoglycemia was low ( 1 - 3 % ) across treatment groups . The incidence of gastrointestinal adverse experiences with the co-administration of sitagliptin and metformin was similar to that observed with metformin alone . LIMITATIONS The patient population evaluated in the 54-week efficacy analysis was a population of patients who entered the continuation period without receiving glycemic rescue therapy in the 24-week placebo-controlled period . Because the baseline HbA(1c ) inclusion criteria ranged from 7.5 to 11 % and the glycemic rescue criterion was an HbA(1c ) > 8 % after week 24 , there was a greater likelihood of glycemic rescue in the monotherapy groups ; this led to more missing data in the continuation all- patients -treated population ( CAPT ) analysis and fewer patients contributing to the completers analysis in the monotherapy groups . CONCLUSIONS In this study , initial treatment with sitagliptin , metformin , or the combination therapy of sitagliptin and metformin provided substantial and durable glycemic control , improved markers of beta-cell function , and was generally well-tolerated over 54 weeks in patients with type 2 diabetes AIM To assess the addition of sitagliptin to ongoing metformin therapy in patients with type 2 diabetes who were inadequately controlled [ haemoglobin A(1c ) ( HbA(1c ) ) 7 - 11 % ] on metformin monotherapy . METHODS Patients ( n = 273 ) on metformin ( > /=1500 mg/day ) were r and omized to receive the addition of once-daily placebo , sitagliptin 100 mg or rosiglitazone 8 mg in a 1 : 1 : 1 ratio for 18 weeks . The efficacy analysis was based on the all- patients -treated population using an analysis of co-variance with change in HbA(1c ) from baseline as the primary endpoint . RESULTS The mean baseline HbA(1c ) was 7.7 % for the entire cohort . After 18 weeks , both active add-on therapies led to greater improvements in HbA(1c ) from baseline : -0.73 % for sitagliptin ( p < 0.001 vs. placebo ) and -0.79 % for rosiglitazone compared with -0.22 % for placebo . No difference was observed between the sitagliptin and rosiglitazone treatments ( 0.06 % [ 95 % confidence interval ( CI ) : -0.14 to 0.25 ] ) . The proportion of patients achieving an HbA(1c ) < 7 % was greater with sitagliptin ( 55 % ) and rosiglitazone ( 63 % ) compared with placebo ( 38 % ) . Body weight increased from baseline with rosiglitazone ( 1.5 kg ) compared with body weight reduction with sitagliptin ( -0.4 kg ) and placebo ( -0.8 kg ) . The difference in body weight between the sitagliptin and rosiglitazone groups was 1.9 kg ( 95 % CI : 1.3 - 2.5 ) . In a prespecified analysis , the proportion of patients experiencing a greater than 3-kg increase in body weight was 21 % in the rosiglitazone group compared with 2 % in both the sitagliptin and placebo groups . Both active treatments were generally well tolerated , with no increased risk of hypoglycaemia or gastrointestinal adverse events compared with placebo . CONCLUSIONS In this 18-week study , the addition of sitagliptin was effective and well tolerated in patients with type 2 diabetes inadequately controlled with metformin monotherapy . Treatment with sitagliptin produced similar reductions in HbA(1c ) compared with the addition of rosiglitazone CONTEXT Sitagliptin is an inhibitor of the enzyme dipeptidyl peptidase-IV ( DPP-IV ) , which de grade s the incretins , glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide , and thus , sitagliptin increases their bioavailability . The stimulation of insulin and the suppression of glucagon secretion that follow exert a glucose lowering effect and hence its use as an antidiabetic drug . Because DPP-IV is expressed as CD26 on cell membranes and because CD26 mediates proinflammatory signals , we hypothesized that sitagliptin may exert an antiinflammatory effect . PATIENTS AND METHODS Twenty-two patients with type 2 diabetes were r and omized to receive either 100 mg daily of sitagliptin or placebo for 12 wk . Fasting blood sample s were obtained at baseline and at 2 , 4 , and 6 hours after a single dose of sitagliptin and at 2 , 4 , 8 , and 12 wk of treatment . RESULTS Glycosylated hemoglobin fell significantly from 7.6 ± 0.4 to 6.9 ± 3 % in patients treated with sitagliptin . Fasting glucagon-like peptide-1 concentrations increased significantly , whereas the mRNA expression in mononuclear cell of CD26 , the proinflammatory cytokine , TNFα , the receptor for endotoxin , Toll-like receptor (TLR)-4 , TLR-2 , and proinflammatory kinases , c-Jun N-terminal kinase-1 and inhibitory-κB kinase ( IKKβ ) , and that of the chemokine receptor CCR-2 fell significantly after 12 wk of sitagliptin . TLR-2 , IKKβ , CCR-2 , and CD26 expression and nuclear factor-κB binding also fell after a single dose of sitagliptin . There was a fall in protein expression of c-Jun N-terminal kinase-1 , IKKβ , and TLR-4 and in plasma concentrations of C-reactive protein , IL-6 , and free fatty acids after 12 wk of sitagliptin . CONCLUSIONS These effects are consistent with a potent and rapid antiinflammatory effect of sitagliptin and may potentially contribute to the inhibition of atherosclerosis . The suppression of CD26 expression suggests that sitagliptin may inhibit the synthesis of DPP-IV in addition to inhibiting its action BACKGROUND New therapeutic approaches are needed to improve glycemic control in patients with type 2 diabetes ( T2D ) , a progressive disorder that often requires combination therapy . The present study assessed the efficacy and safety of sitagliptin as add-on therapy to metformin and rosiglitazone in patients with T2D . METHODS The present study was a r and omized double-blind placebo-controlled parallel-group 54-week study conducted at 41 sites across North and South America , Europe , and Asia in 278 patients with HbA1c ranging from ≥7.5 % to ≤11.0 % despite ongoing combination therapy with metformin ( ≥1500 mg/day ) and rosiglitazone ( ≥4 mg/day ) . Patients were r and omized ( 2:1 ) to receive sitagliptin 100 mg or placebo once daily . The main outcome measure was change from baseline in HbA1c at Week 18 . RESULTS Mean baseline HbA1c was 8.8 % . The mean placebo-adjusted change from baseline in HbA1c with sitagliptin treatment was -0.7 % ( P < 0.001 ) at Week 18 and -0.8 % ( P < 0.001 ) at Week 54 . There were also significant ( P < 0.001 ) reductions in 2-h post-meal glucose and fasting plasma glucose compared with placebo at Weeks 18 and 54 . Significantly higher proportions of sitagliptin- than placebo-treated patients had HbA1c<7.0 % at Weeks 18 ( 22 % vs 9 % ; P = 0.003 ) and 54 ( 26 % vs 14 % ; P = 0.015 ) . Changes in body weight and the rates of adverse events overall , hypoglycemia , and gastrointestinal adverse events were similar in the sitagliptin and placebo groups during the 54-week study . CONCLUSIONS In patients with T2D , the addition of sitagliptin for 54 weeks to ongoing therapy with metformin and rosiglitazone improved glycemic control and was generally well tolerated compared with placebo AIM To evaluate the efficacy and safety of the potent and selective dipeptidyl peptidase-4 ( DPP-4 ) inhibitor linagliptin administered as add-on therapy to metformin in patients with type 2 diabetes with inadequate glycaemic control . METHODS This 24-week , r and omized , placebo-controlled , double-blind , parallel-group study was carried out in 82 centres in 10 countries . Patients with HbA1c levels of 7.0 - 10.0 % on metformin and a maximum of one additional antidiabetes medication , which was discontinued at screening , continued on metformin ≥1500 mg/day for 6 weeks , including a placebo run-in period of 2 weeks , before being r and omized to linagliptin 5 mg once daily ( n = 524 ) or placebo ( n = 177 ) add-on . The primary outcome was the change from baseline in HbA1c after 24 weeks of treatment , evaluated with an analysis of covariance ( ANCOVA ) . RESULTS Mean baseline HbA1c and fasting plasma glucose ( FPG ) were 8.1 % and 9.4 mmol/l , respectively . Linagliptin showed significant reductions vs. placebo in adjusted mean changes from baseline of HbA1c ( -0.49 vs. 0.15 % ) , FPG ( -0.59 vs. 0.58 mmol/l ) and 2hPPG ( -2.7 vs. 1.0 mmol/l ) ; all p < 0.0001 . Hypoglycaemia was rare , occurring in three patients ( 0.6 % ) treated with linagliptin and five patients ( 2.8 % ) in the placebo group . Body weight did not change significantly from baseline in both groups ( -0.5 kg placebo , -0.4 kg linagliptin ) . CONCLUSIONS The addition of linagliptin 5 mg once daily in patients with type 2 diabetes inadequately controlled on metformin result ed in a significant and clinical ly meaningful improvement in glycaemic control without weight gain or increased risk of hypoglycaemia The efficacy and safety of sitagliptin as monotherapy were evaluated in Chinese , Indian , and Korean patients with type 2 diabetes inadequately controlled by diet and exercise . In a r and omized , placebo-controlled , double-blind , 18-week trial , 530 patients with HbA(1c ) > or=7.5 % and < or=11.0 % ( mean baseline 8.7 % ) received sitagliptin 100 mg once daily or placebo . Compared with placebo , sitagliptin significantly ( p<0.001 ) reduced mean HbA(1c ) ( -1.0 % ) , fasting plasma glucose ( -1.7 mmol/L ) , and 2-h postpr and ial glucose ( -3.1 mmol/L ) , and a significantly ( p<0.001 ) greater proportion of sitagliptin-treated versus placebo-treated patients achieved HbA(1c ) < 7 % ( 20.6 % versus 5.3 % , respectively ) at study end . Efficacy of sitagliptin was demonstrated in each country . Sitagliptin was generally well-tolerated . Clinical adverse events ( AEs ) were reported in 23.3 % and 15.2 % of sitagliptin-treated and placebo-treated patients , respectively . The difference was primarily due to increased gastrointestinal AEs in the sitagliptin group , most of which were mild and resolved on study drug . Serious AEs , discontinuations due to AEs , and drug-related AEs occurred with a low incidence in both groups . No hypoglycemia was reported . In conclusion , in this study , sitagliptin monotherapy for 18 weeks significantly improved glycemic control and was well-tolerated in patients with type 2 diabetes from China , India , and Korea AIMS To study the effects of saxagliptin , a dipeptidyl peptidase-4 inhibitor , on glycaemic stability and β-cell function in the SAVOR-TIMI 53 trial . METHODS We r and omized 16,492 patients with type 2 diabetes ( T2D ) to saxagliptin or placebo , added to current antidiabetic medications , and followed them for a median of 2.1 years . Glycaemic instability was defined by : ( i ) a glycated haemoglobin ( HbA1c ) increase of ≥ 0.5 % post-r and omization ; ( ii ) the initiation of new antidiabetic medications for ≥ 3 months ; or ( iii ) an increase in dose of oral antidiabetic medication or ≥ 25 % increase in insulin dose for ≥ 3 months . β-cell function was assessed according to fasting homeostatic model 2 assessment of β-cell function ( HOMA-2β ) values at baseline and at year 2 in patients not treated with insulin . RESULTS Compared with placebo , participants treated with saxagliptin had a reduction in the development of glycaemic instability ( hazard ratio 0.71 ; 95 % confidence interval 0.68 - 0.74 ; p < 0.0001 ) . In participants treated with saxagliptin compared with placebo , the occurrence of an HbA1c increase of ≥ 0.5 % was reduced by 35.2 % ; initiation of insulin was decreased by 31.7 % and the increases in doses of an oral antidiabetic drug or insulin were reduced by 19.5 and 23.5 % , respectively ( all p < 0.0001 ) . At 2 years , HOMA-2β values decreased by 4.9 % in participants treated with placebo , compared with an increase of 1.1 % in those treated with saxagliptin ( p < 0.0001 ) . CONCLUSIONS Saxagliptin improved glycaemia and prevented the reduction in HOMA-2β values . Saxagliptin may reduce the usual decline in β-cell function in T2D , thereby slowing diabetes progression BACKGROUND In recent years , increasing evidence suggests a potential importance of telomere biology in type 2 diabetes . The aim of this study was to determine whether sitagliptin , a medicine generally used in diabetes , can influence the telomere and telomerase in newly diagnosed type 2 diabetic patients . METHODS Type 2 diabetic patients ( T2D , n = 38 ) and non-diabetic subjects ( control , n = 31 ) were r and omly selected from the outpatient of Tongji Hospital , Tongji Medical College , Huazhong university of Science and Technology . Leukocyte telomere length ratio was measured using a quantitative polymerase chain reaction and was analysed . Telomerase activity was measured by polymerase chain reaction enzyme-linked immunosorbent assay method . Peripheral insulin resistance ( homeostasis model assessment ) was calculated from fasting plasma glucose and fasting plasma insulin . RESULTS Telomere length of the type 2 diabetic patients ( 1.58 ± 0.57 ) was significantly shorter than those of control subjects ( 3.98 ± 0.90 ) and was significantly elongated after intervention by sitagliptin . There was no significant difference between the T2D and control group in telomerase activity , and the treatment of sitagliptin in T2D group showed no significant effect on the telomerase activity . CONCLUSIONS In type 2 diabetes patients , leukocyte telomere length is significantly reduced , whereas the telomerase activity seems less influenced . Sitagliptin might protect β-cells in the pancreas by elongating the telomere length Abstract Objectives : To evaluate the efficacy and safety of linagliptin in Chinese patients with type 2 diabetes mellitus ( T2DM ) inadequately controlled by metformin and sulphonylurea . Research design and methods : Data for a pre-defined Chinese subgroup who participated in a Phase III r and omised , placebo-controlled , 24 week trial ( NCT00602472 ) were analysed . The primary endpoint was change in HbA1c from baseline to 24 weeks . Apart from safety endpoints , secondary endpoints included changes in FPG and measures of insulin secretion and resistance . Results : A total of 192 Chinese patients with T2DM participated in the pre-defined analysis ; 144 and 48 patients received linagliptin or placebo , respectively , added to metformin and sulphonylurea . Baseline characteristics ( mean [ ±SD ] ) for linagliptin and placebo were similar : HbA1c : 8.1 % ( ±0.85 ) and 8.1 % ( ±0.84 ) ; body mass index : 25.9 ( ±3.2 ) and 25.6 ( ±3.4 ) kg/m2 , respectively . Placebo-corrected mean ( ±SE ) change in HbA1c from baseline at 24 weeks was −0.68 % ( 0.14 ) with linagliptin-based treatment ( 95 % CI : −0.96 to −0.39 ; P < 0.0001 ) . Placebo-corrected mean ( ±SE ) change in FPG from baseline at 24 weeks with linagliptin was −18.8 ( 6.5 ) mg/dL ( −1.0 [ 0.4 ] mmol/L ; 95 % CI : −31.7 to −5.9 ; P = 0.0044 ) . Overall adverse event ( AE ) rates with linagliptin and placebo including background medication were similar ( 38.9 % and 43.8 % , respectively ) . Drug-related AEs were reported by 12.5 % and 2.1 % of linagliptin and placebo patients , respectively . Differences were due to hypoglycaemia ( 10.4 % and 0.0 % , respectively ) . No severe hypoglycaemia was reported in either group of this sub- population . Conclusion : Linagliptin in combination with metformin and sulphonylurea has a favourable safety profile and is an efficacious and well tolerated treatment option for Chinese patients with inadequately controlled T2DM . Reduction of sulphonylurea dose should be considered to minimise risk of hypoglycaemia . Although the findings of this pre-specified sub- analysis may be limited by the number of patients in the subgroup , the results were generally consistent with those for the overall population . Clinical Trials identifier : Clinical Trials.gov identifier : NCT00602472 The objectives of this study is to evaluate the efficacy and safety of alogliptin versus very low fat/calorie traditional Japanese diet ( non-inferiority trial ) as an initial therapy for newly diagnosed , drug naïve subjects with type 2 diabetes ( T2DM ) . Study design was prospect i ve , r and omized , non-double-blind , controlled trial . The study was conducted at outpatient units of municipal hospital . Patients were newly diagnosed , drug naïve patients who visited the outpatient units . The patients r and omly received 12.5–25 mg/day alogliptin ( n = 25 ) or severe low calorie traditional Japanese diet ( n = 26 ) . The procedure of this trial was assessed by the consoli date d st and ards of reporting trials statement . The primary end point was the change of HbA1c at 3 months . Secondary end points included the changes of fasting blood glucose , insulin , homeostasis model assessment -R ( HOMA-R ) , HOMA-B , body mass index ( BMI ) , and lipid parameters . Similar , significant reductions of HbA1c levels were observed in both groups ( from 10.51 to 8.74 % for alogliptin and from 10.01 to 8.39 % for traditional Japanese diet ) without any clinical ly significant adverse events . In the alogliptin group , some subjects ( 16 % ) had mild hypoglycemic evens which could be managed by taking glucose drinks by themselves . HOMA-B significantly increased in both groups with varying degrees , whereas HOMA-R significantly decreased only in the Japanese diet group . Atherogenic lipids , such as , total cholesterol , non-high density lipoprotein cholesterol , and low density lipoprotein cholesterol levels significantly decreased in both groups . BMI had no change in the alogliptin group , whereas it significantly decreased in the Japanese diet group . ( 1 ) Concerning its glycemic efficacy , alogliptin is effective and non-inferior to traditional Japanese diet as an initial therapeutic option for newly diagnosed T2DM . However , regarding the reductions of body weight and insulin resistance , traditional Japanese diet is superior . ( 2 ) Both alogliptin and traditional Japanese diet have favorable effects on atherogenic lipid profiles AIMS To evaluate the efficacy and safety of alogliptin added to metformin versus metformin monotherapy in Japanese patients with type 2 diabetes who achieved inadequate glycaemic control on metformin ( 500 or 750 mg/day ) + diet/exercise . METHODS In a r and omized , double-blind trial , 288 patients with type 2 diabetes mellitus T2DM received either 12.5 or 25 mg alogliptin once daily + metformin or placebo + metformin for 12 weeks . Thereafter , 276 patients continued on one of the two alogliptin dosages + metformin in an open-label extension for 40 weeks . The primary efficacy endpoint in the r and omized , double-blind phase was the change in HbA1c from baseline ( week 0 ) to the end of treatment ( week 12 ) . The primary endpoint during the long-term extension phase was adverse events . RESULTS After 12 weeks both dosages of alogliptin + metformin produced significantly greater changes from baseline in HbA1c than placebo ( metformin monotherapy : with changes in LS means - 0.55 and - 0.64 % vs. 0.22 % , respectively ; p < 0.0001 ) . Incidences of adverse effects were comparable between groups , with no increases in hypoglycaemia . Over 52 weeks , there were no safety or tolerability concerns with alogliptin when added to metformin . CONCLUSIONS Alogliptin 12.5 and 25 mg once daily was safe and effective when added to metformin ( 500 or 750 mg/day ) in Japanese patients with inadequately controlled type 2 diabetes on metformin alone ABSTRACT Objective : To evaluate the efficacy and safety of once-daily saxagliptin monotherapy in treatment-naïve patients with type 2 diabetes ( T2D ) and inadequate glycemic control . Research design and methods : This study included a main treatment cohort ( MTC ) with 401 patients ( HbA1c ≥ 7 % and ≤10 % ) r and omized and treated with oral saxagliptin 2.5 , 5 , or 10 mg once daily or placebo for 24 weeks and a separate open-label cohort ( OLC ) with 66 patients ( HbA1c > 10 % and ≤12 % ) who received saxagliptin 10 mg once daily for 24 weeks . Primary endpoint was HbA1c change from baseline to week 24 . Secondary endpoints included change from baseline to week 24 in fasting plasma glucose ( FPG ) , proportion of patients achieving HbA1c < 7 % , and changes in postpr and ial glucose area-under-the-curve ( PPG-AUC ) . Efficacy analyses for continuous variables were performed using an ANCOVA model with last-observation-carried-forward methodology . Results : In the MTC , saxagliptin demonstrated statistically significant decreases in adjusted mean HbA1c changes from baseline ( mean , 7.9 % ) to week 24 ( −0.43 % , −0.46 % , −0.54 % ) for saxagliptin 2.5 , 5 , and 10 mg , respectively , vs. + 0.19 % for placebo ( all p < 0.0001 ) . Adjusted mean FPG was significantly reduced from baseline ( −15 , −9 , −17 mg/dL ) for saxagliptin 2.5 , 5 , and 10 mg , respectively , vs. + 6 mg/dL for placebo ( p = 0.0002 , p = 0.0074 , p < 0.0001 , respectively ) . More saxagliptin-treated patients achieved HbA1c < 7 % at week 24 ( 35 % [ p = NS ] , 38 % [ p = 0.0443 ] , 41 % [ p = 0.0133 ] ) for saxagliptin 2.5 , 5 , and 10 mg , respectively , than placebo ( 24 % ) . PPG-AUC was reduced for saxagliptin 2.5 , 5 , and 10 mg ( −6868 , −6896 , −8084 mg·min/dL , respectively ) vs. placebo ( −647 mg·min/dL ) with statistical significance demonstrated for saxagliptin 5 mg ( p = 0.0002 ) and 10 mg ( p < 0.0001 ) . HbA1c , FPG , and PPG-AUC reductions were also observed in the OLC at 24 weeks . In the MTC , adverse event frequency was similar across all study arms . No cases of confirmed hypoglycemia ( symptoms , with fingerstick glucose ≤50 mg/dL ) were observed in either cohort . Saxagliptin was not associated with weight gain . Study limitations included the lack of a control group for the OLC and the use of prespecified rescue criteria , which limited the exposure time during which patients could remain on their originally r and omized medication without the introduction of additional antihyperglycemic rescue treatment . Conclusions : Once-daily saxagliptin monotherapy for 24 weeks was generally well tolerated and demonstrated clinical ly meaningful reductions in key parameters of glycemic control vs. placebo . Trial Registration : Clinical Trials |
12,253 | 22,743,065 | Meta- analysis using this methodology concluded that there is no benefit for periodontal treatment to reduce complications of pregnancy . | For 15 years , the investigation of a relationship between periodontal diseases and complications of pregnancy is explored , and allowed the publication of conflicting results .
This work is a literature review of articles of high level of evidence , which aims to clarify the impact of treatment of periodontal disease on pregnancy .
The contradictions found in the different studies have led some authors of meta- analysis to allocate the RCT per groups of power , based on their methodology . | The aim of this study was to compare changes in periodontal status in a Swedish population over a period of 20 years . Cross-sectional studies were carried out in Jönköping County in 1973 , 1983 , and 1993 . Individuals were r and omly selected from the following age groups : 20 , 30 , 40 , 50 , 60 , and 70 years . A total of 600 individuals were examined in 1973 , 597 in 1983 , and 584 in 1993 . The number of dentate individuals was 537 in 1973 , 550 in 1983 , and 552 in 1993 . Based on clinical data and full mouth intra-oral radiographs , all individuals were classified into 5 groups according to the severity of the periodontal disease experience . Individuals were classified as having a healthy periodontium ( group 1 ) , gingivitis without signs of alveolar bone loss ( group 2 ) , moderate alveolar bone loss not exceeding 1/3 of the normal alveolar bone height ( group 3 ) , severe alveolar bone loss ranging between 1/3 and 2/3 of the normal alveolar bone height ( group 4 ) , or alveolar bone loss exceeding 2/3 of the normal bone height and angular bony defects and /or furcation defects ( group 5 ) . During these 20 years , the number of individuals in groups 1 and 2 increased from 49 % in 1973 to 60 % in 1993 . In addition , there was a decrease in the number of individuals in group 3 , the group with moderate periodontal bone loss . Groups 4 and 5 comprised 13 % of the population and showed no change in general between 1983 and 1993 . The individuals comprising these groups in 1993 , however , had more teeth than those who comprised these groups in 1983 ; on the average , the individuals in disease group 4 had 4 more teeth and those in disease group 5 , 2 more teeth per subject . In 1973 , these 2 groups were considerably smaller , probably because of wider indications for tooth extraction s and fewer possibilities for periodontal care which meant that many of these individuals had become edentulous and were not placed in a group . Individuals in groups 3 , 4 , and 5 were subdivided according to the number of surfaces ( % ) with gingivitis and periodontal pockets ( > or = 4 mm ) . In 1993 , 20 % , 42 % . and 67 % of the individuals in groups 3 , 4 , and 5 respectively were classified as diseased and in need of periodontal therapy with > 20 % bleeding sites and > 10 % sites with periodontal pockets > or = 4 mm . In conclusion , an increase in the number of individuals with no marginal bone loss and a decrease in the number of individuals with moderate alveolar bone loss can be seen . The prevalence of individuals in the severe periodontal disease groups ( 4 , 5 ) was unchanged during the last 10 years ; however , the number of teeth per subject increased BACKGROUND One hypothesis to explain the association between periodontal disease ( PD ) preterm/low birth weight ( PT/LBW ) is that PT/LBW may be indirectly mediated through translocation of bacteria or bacterial products in the systemic circulation . Transient bacteremias occur in subjects with marginal periodontitis or with gingivitis , and it is possible that bacteria and their products may reach the placental membranes hematogenously and provide the inflammatory effect to induce preterm labor . The effect of gingivitis as a potential risk factor for PT/LBW has still not been studied . A r and omized controlled trial was undertaken to determine the effect of routine plaque control and scaling on the pregnancy outcomes in women with gingivitis . METHODS Eight hundred seventy ( 870 ) pregnant women with gingivitis , aged 18 to 42 , were enrolled while receiving prenatal care in Santiago , Chile . Women were r and omly assigned in a two-to-one fashion to either a treatment group ( N = 580 ) , receiving periodontal treatment before 28 weeks of gestation or to a control group ( N = 290 ) , receiving periodontal treatment after delivery . Periodontal therapy consisted of plaque control , scaling , and daily rinsing with 0.12 % clorhexidine . Maintenance therapy was provided every 2 to 3 weeks until delivery , and consisted of oral hygiene instruction and supragingival plaque removal by instrumentation , as needed . The primary outcomes assessed were delivery at less than 37 weeks of gestation or an infant weighing less than 2,500 g. RESULTS Of the 870 women enrolled , 36 women ( 27 in the treatment group and nine in the control group ) were excluded from the analyses for different reasons . The incidence of PT/LBW in the treatment group was 2.14 % ( 12/560 ) and in the control group , 6.71 % ( 19/283 ) ( odds ratio [ OR ] 3.26 ; 95 % confidence interval [ CI ] 1.56 to 6.83 ; P = 0.0009 ) . Multivariate logistic regression analysis showed that , after adjusting for several known risk factors for PT/LBW , women with gingivitis were at a higher risk of PT/LBW than women who received periodontal treatment ( OR 2.76 ; 95%CI 1.29 to 5.88 ; P = 0.008 ) . CONCLUSIONS Periodontal treatment significantly reduced the PT/LBW rate in this population of women with pregnancy-associated gingivitis . Within the limitions of this study , we conclude that gingivitis appears to be an independent risk factor for PT/LBW for this population Periodontitis has been associated with adverse pregnancy outcomes . Results from intervention studies are few and controversial . The present study assessed the effects of non-surgical periodontal treatment in the occurrence of adverse pregnancy outcomes . Two hundred forty-six eligible women were r and omly divided into two groups : periodontitis intervention ( n = 122 ; undergoing non-surgical treatment during gestation ) and periodontitis control ( n = 124 ; not treated during gestation ) . Univariate analysis was performed and estimates of relative risk were reported . Data from 225 women were analyzed . No differences for preterm birth ( p = 0.721 ) , low birth weight ( p = 0.198 ) , and preterm low birth weight ( p = 0.732 ) rates were observed . Relative risk estimates for preterm birth , low birth weight , and preterm low birth weight in the periodontitis intervention group were 0.915 ( 95 % CI 0.561–1.493 ) , 0.735 ( 95 % CI 0.459–1.179 ) , and 0.927 ( 0.601–1.431 ) , respectively . Non-surgical periodontal treatment during the second semester of gestation did not reduce the risk for preterm birth , low birth weight , and preterm low birth weight Considering the high prevalence of preterm birth ( PTB ) and low birth weight ( LBW ) and their complications as well as the role played by periodontal disease in their incidence and the lack of any report of periodontal therapy on these problems in Iran , the goal of the present research was to determine the effects of periodontal treatment on PLBW incidence among women with moderate or advanced periodontitis who were referred to Javaheri hospital ( 2004 - 2005 ) . This clinical trial research was conducted on 30 pregnant women age ranging from 18 - 35 years old , with moderate or advanced periodontitis . Fifteen subjects r and omly underwent the first phase of periodontal treatment including scaling , root planning and the use of 0.2 % chlorhexidine mouth rinse for one week . None of these steps were taken for the controls . After necessary follow ups , the effect of periodontal treatment on birth term and birth weight were analyzed statistically . This research was conducted on 30 subjects , 15 controls and 15 cases in study group . In the control group , the observed rate of PLBW was 26.7 % whereas among periodontally treated group , phase I , PLBW infant was not observed ( P < 0.05 ) . Infants birth weight were ( 3059.3 - 389.7 ) gms in study group and ( 3371 - 394.2 ) gms in the control group and respectively ( P < 0.05 ) . Periodontal therapy , phase I , results in a reduction in PLBW incidence rate . Therefore , the application of such a simple method among periodontally diseased pregnant women is recommended BACKGROUND Few studies have examined the potential effects of periodontal treatment during pregnancy on pregnancy outcomes , periodontal status , and inflammatory biomarkers . METHODS A r and omized , delayed-treatment , controlled pilot trial was conducted to evaluate the effects of second-trimester scaling and root planing and the use of a sonic toothbrush on the rate of preterm delivery ( < 37 weeks gestation ) . Secondary outcome measures included changes in periodontal status , levels of eight oral pathogens , levels of gingival crevicular fluid ( GCF ) interleukin-1beta ( IL-1beta ) , prostagl and in E(2 ) ( PGE(2 ) ) , 8-isoprostane ( 8-iso ) , and IL-6 , and serum levels of IL-6 , soluble intercellular adhesion molecule 1 ( sICAM1 ) , 8-isoprostane , soluble glycoprotein 130 ( sGP130 ) , IL-6 soluble receptor ( IL-6sr ) , and C-reactive protein ( CRP ) . Logistic regression models were used to test for effects of treatment on preterm delivery . Secondary outcomes were analyzed by analysis of covariance adjusting for subject baseline values . RESULTS Periodontal intervention result ed in a significantly decreased incidence odds ratio ( OR ) for preterm delivery ( OR = 0.26 ; 95 % confidence interval = 0.08 to 0.85 ) , adjusting for baseline periodontal status which was unbalanced after r and omization . Pregnancy without periodontal treatment was associated with significant increases in probing depths , plaque scores , GCF IL-1beta , and GCF IL-6 levels . Intervention result ed in significant improvements in clinical status ( attachment level , probing depth , plaque , gingivitis , and bleeding on probing scores ) and significant decreases in levels of Prevotella nigrescens and Prevotella intermedia , serum IL-6sr , and GCF IL-1beta . CONCLUSIONS Results from this pilot study ( 67 subjects ) provide further evidence supporting the potential benefits of periodontal treatment on pregnancy outcomes . Treatment was safe , improved periodontal health , and prevented periodontal disease progression . Preliminary data show a 3.8-fold reduction in the rate of preterm delivery , a decrease in periodontal pathogen load , and a decrease in both GCF IL-1beta and serum markers of IL-6 response . However , further studies will be needed to substantiate these early findings BACKGROUND A recent clinical trial ( Obstetrics and Periodontal Therapy [ OPT ] Study ) demonstrated that periodontal therapy during pregnancy improved periodontal outcomes but failed to impact preterm birth . The present study evaluated seven target bacteria , Aggregatibacter actinomycetemcomitans ( previously Actinobacillus actinomycetemcomitans ) , Porphyromonas gingivalis , Treponema denticola , Tannerella forsythia ( previously T. forsythensis ) , Prevotella intermedia , Campylobacter rectus , and Fusobacterium nucleatum , in subgingival dental plaque of pregnant women in the OPT Study and their association with birth outcomes . METHODS Pregnant women were r and omly assigned to receive periodontal treatment before 21 weeks ' gestation or after delivery . Subgingival plaque was sample d at baseline ( 13 to 16 weeks ; 6 days of gestation ) and at 29 to 32 weeks . We analyzed subgingival plaque sample s from women who experienced fetal loss , delivered a live preterm infant ( preterm women ) , or delivered a full-term infant ( full-term women ) . Sample s were analyzed using quantitative polymerase chain reaction . Associations between preterm birth and bacterial counts and percentages were tested using multiple linear regression . RESULTS No significant differences were observed at baseline between preterm and full-term women for any measured bacterial species or group of species , after accounting for multiple comparisons . Changes in bacterial counts and proportions during pregnancy also were not associated with birth outcomes . In full-term and preterm women , periodontal therapy significantly reduced ( P < 0.01 ) counts of all target species except for A. actinomycetemcomitans . CONCLUSIONS In pregnant women with periodontitis , non-surgical periodontal therapy significantly reduced levels of periodontal pathogens . Baseline levels of selected periodontal pathogens or changes in these bacteria result ing from therapy were not associated with preterm birth BACKGROUND Preterm low birth weight was reported to be related to periodontal infections that might influence the fetus-placenta complex . The aim of this study was to provide periodontal treatment for pregnant women and to evaluate if this treatment can interfere with pregnancy duration and weight of the newborn . METHODS The sample consisted of 450 pregnant women who were under prenatal care at a polyclinic in Três Corações , Brazil . Women with risk factors , such as systemic alterations ( ischemic cardiopathy , hypertension , tuberculosis , diabetes , cancer , anemia , seizure , psychopathology , urinary tract infection , sexually transmitted diseases , asthma , and human immunodeficiency virus ) , and /or users of alcohol , tobacco , and drugs were excluded from the study . Data related to age , socioeconomic level , race , marital status , number of previous pregnancies , and previous preterm delivery also were evaluated . Initially , the sample was divided into two groups : 122 healthy patients ( group 1 ) and 328 patients with periodontal disease ( group 2 ) . In group 2 , 266 patients underwent treatment and 62 patients dropped out . After mothers gave birth , pregnancy duration and the weight of all infants were analyzed and recorded . RESULTS There was no statistical difference between the healthy and treated groups . However , there was a difference in the non-treated group , with a 79 % incidence of preterm low birth weight . Educational level , previous preterm birth , and periodontal disease were related significantly to preterm delivery ( P < 0.001 ) . CONCLUSION Periodontal disease was related significantly to preterm low birth weight OBJECTIVE : To investigate whether treating periodontal disease prevents preterm birth and other major complications of pregnancy . METHODS : This single-center trial was conducted across six obstetric sites in metropolitan Perth , Western Australia . Pregnant women identified by history to be at risk ( n=3,737 ) were examined for periodontal disease . Approximately 1,000 women with periodontal disease were allocated at r and om to receive periodontal treatment commencing around 20 weeks of gestation ( n=542 ) or 6 weeks after the pregnancy was completed ( controls ; n=540 ) . The treatment included mechanical removal of oral biofilms together with oral hygiene instruction and motivation at a minimum of three weekly visits , with further visits if required . RESULTS : There were no differences between the control and treatment groups in preterm birth ( 9.3 % compared with 9.7 % , odds ratio [ OR ] 1.05 , 95 % confidence interval [ CI 0.7–1.58 ] , P=.81 ) , birth weight ( 3,450 compared with 3,410 g , P=.12 ) , preeclampsia ( 4.1 % compared with 3.4 % , OR 0.82 , 95 % CI 0.44–1.56 , P=.55 ) , or other obstetric endpoints . There were four unexplained stillbirths in the control group and no pregnancy losses in the treated group ( P=.12 ) . Measures of fetal and neonatal well-being were similar in the two groups , including abnormalities in fetal heart rate recordings ( P=.26 ) , umbilical artery flow studies ( P=.96 ) , and umbilical artery blood gas values ( P=.37 ) . The periodontal treatment was highly successful in improving health of the gums ( P<.01 ) . CONCLUSION : The evidence provided by the present study does not support the hypothesis that treatment of periodontal disease during pregnancy in this population prevents preterm birth , fetal growth restriction , or preeclampsia . Periodontal treatment was not hazardous to the women or their pregnancies . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00133926 . LEVEL OF EVIDENCE : BACKGROUND There is convincing evidence to suggest that infections affecting the mother during pregnancy may produce alterations in the normal cytokine- and hormone-regulated gestation , which could result in preterm labor , premature rupture of membranes , and preterm birth ( PTB ) . Studies in the late 1990s associated periodontitis with preterm low birth weight ( PLBW ) deliveries , and this may have similar pathogenic mechanisms as other maternal infections . This study determined the effect of non-surgical periodontal therapy on pregnancy outcome . METHODS A total of 200 pregnant women with periodontitis were r and omly assigned to treatment and control groups . Detailed data about previous and current pregnancies were obtained . All women received a full-mouth periodontal examination , including oral hygiene index-simplified , bleeding index , and clinical attachment level . The women in the treatment group received non-surgical periodontal therapy during the gestational period , and those in the control group received periodontal treatment after delivery . Periodontal therapy included plaque control instructions and scaling and root planing performed under local anesthesia . The outcome measures assessed were gestational age and birth weight of the infant . PTB was recorded when delivery occurred at < 37 weeks of gestation , and low birth weight ( LBW ) was recorded when the infant weighed<2,500 g. RESULTS There were 53 PTBs in the treatment group and 68 PTBs in the control group . Twenty-six LBW infants were recorded in the treatment group , and 48 LBW infants were noted in the control group . The mean gestational ages were 33.8+/-2.8 weeks and 32.7+/-2.8 weeks in the treatment and control groups , respectively . The difference was statistically significant at P<0.006 . The mean birth weight was 2,565.3+/-331.2 g in the treatment group and 2,459.6+/-380.7 g in the control group , with the difference being statistically significant at P<0.044 . A multiple regression model showed a significant effect of periodontal treatment on birth outcomes . CONCLUSIONS Non-surgical periodontal therapy can reduce the risk for preterm births in mothers who are affected by periodontitis . Additional multicentered , r and omized , controlled clinical trials are required to confirm this link between periodontitis and PLBW BACKGROUND Previous case-control and prospect i ve studies have shown an association between the presence of periodontitis and the risk of preterm birth ( PTB ) . The goal of this pilot trial was to determine the feasibility of conducting a trial to determine whether treatment of periodontitis reduces the risk of spontaneous preterm birth ( SPTB ) . METHODS Three hundred sixty-six ( 366 ) women with periodontitis between 21 and 25 weeks ' gestation were recruited and r and omized to one of three treatment groups with stratification on the following two factors : 1 ) previous SPTB at < 35 weeks and 2 ) body mass index < 19.8 or bacterial vaginosis as assessed by Gram stain . The treatment groups consisted of : 1 ) dental prophylaxis plus placebo capsule ; 2 ) scaling and root planing ( SRP ) plus placebo capsule ; and 3 ) SRP plus metronidazole capsule ( 250 mg t.i.d . for one week ) . An additional group of 723 pregnant women meeting the same criteria for periodontitis and enrolled in a prospect i ve study served as an untreated reference group . RESULTS The rate of PTB at < 35 weeks was 4.9 % in the prophylaxis group , compared to 3.3 % in the SRP plus metronidazole group and 0.8 % in the SRP plus placebo group ( P = 0.75 and 0.12 , respectively ) . The rate of PTB at < 35 weeks was 6.3 % in the reference group . CONCLUSIONS This trial indicates that performing SRP in pregnant women with periodontitis may reduce PTB in this population . Adjunctive metronidazole therapy did not improve pregnancy outcome . Larger trials will be needed to achieve statistical significance , especially at less than 35 weeks gestational age t d p reterm birth is one of the most complicated and challenging research issues in perinatal medicine . Despite decades f scientific inquiry , the preterm birth rate has remained contant or increased annually in the United States . Nearly 12 % of ll deliveries occur at 37 weeks of gestation . Spontaneous reterm birth is a complex and heterogeneous public health roblem with multiple risk factors . Some of these risk factors re social ( such as maternal race/ethnicity and poverty ) , and ome are individual ( such as underweight , tobacco use , and aternal infection ) . Many of these risk factors occur in comination , which complicates preventive strategies . Periodontal disease is an infectious stimulus that has been ssociated with preterm birth . Periodontal disease is a Gramegative anaerobic infection of the mouth that occurs in 40 % f pregnant women . Infection and subsequent inflammation f the gingival and local support attachments of the teeth can esult in tissue , bone , and , ultimately , tooth loss . This destrucive process involves both direct tissue damage from plaque acterial products and indirect damage through bacterial stimlation of local and systemic inflammatory and immune reponses . In a recent meta analysis of the association between aternal periodontal disease and preterm birth , Vergnes and ixou examined 17 studies and reported a pooled estimate dds ratio for preterm birth of 2.83 ( 95 % confidence interval CI ] , 1.95– 4.10 ; P .0001 ) . Polyzos et al conducted a met analysis of r and omized clinical trials to determine whether eriodontal treatment during pregnancy reduced preterm irth . After examination of 7 trials that included 2663 patients 1491 patients were assigned r and omly to periodontal treatent and 1172 patients were assigned to no treatment ) , they ound that periodontal treatment during pregnancy result ed in ignificantly lower preterm birth ( odds ratio , 0.55 ; 95 % CI , .35– 0.86 ; P .008 ) . Although these data support a relationship between materal periodontal disease and preterm birth , several studies |
12,254 | 27,062,438 | StO2 more rapidly identifies occult shock in human patients compared to traditional methods , which can lead to earlier intervention in these patients .
VETERINARY DATA SYNTHESIS Veterinary studies involving tissue oxygen monitoring are limited , but the technology may have utility for identification of hemorrhagic shock earlier than changes in base excess , blood lactate concentration , or other traditional perfusion parameters .
CONCLUSION Tissue oxygen monitoring is most commonly performed utilizing a noninvasive , portable monitor , which provides real-time , continuous , repeatable StO2 measurements .
A decline in StO2 is an early indicator of shock in both human and veterinary patients .
Low StO2 values in human patients are associated with increased morbidity , mortality , and length of hospitalization , as well as the development of multiple organ system dysfunction and surgical site infections | " HUMAN DATA SYNTHESIS Tissue oxygen monitors have been evaluated in a wide variety of human clinical applications including trauma and triage , surgery , sepsis , and septic shock , and early goal -directed therapy . | Introduction Near-infrared spectroscopy ( NIRS ) noninvasively measures peripheral tissue oxygen saturation ( StO2 ) . NIRS may be utilized along with a vascular occlusion test , in which limb blood flow is temporarily occluded and released , to quantify a tissue bed 's rate of oxygen exchange during ischemia and recovery . The objective of this study was to test the hypothesis that NIRS-derived StO2 measures ( StO2 initial , StO2 occlusion and StO2 recovery ) identify patients who are in shock and at increased risk of organ dysfunction ( Sequential Organ Failure Assessment ( SOFA ) score ≥ 2 at 24 hours ) and dying in the hospital . Methods This prospect i ve , observational study comprised a convenience sample of three cohorts of adult patients ( age > 17 years ) at three urban university emergency departments : ( 1 ) a septic shock cohort ( systolic blood pressure < 90 after fluid challenge ; the " SHOCK " cohort , n = 58 ) , ( 2 ) a sepsis without shock cohort ( the " SEPSIS " cohort , n = 60 ) and emergency department patients without infection ( n = 50 ) . We measured the StO2 initial , StO2 occlusion and StO2 recovery slopes for all patients . Outcomes were sepsis syndrome severity , organ dysfunction ( SOFA score at 24 hours ) and in-hospital mortality . Results Among the 168 patients enrolled , mean initial StO2 was lower in the SHOCK cohort than in the SEPSIS cohort ( 76 % vs 81 % ) , with an impaired occlusion slope ( -10.2 and 5.2%/minute vs -13.1 and 4.4%/minute ) and an impaired recovery slope ( 2.4 and 1.6%/second vs 3.9 and 1.7%/second ) ( P < 0.001 for all ) . The recovery slope was well-correlated with SOFA score at 24 hours ( -0.35 ; P < 0.001 ) , with a promising area under the curve ( AUC ) for mortality of 0.81 . The occlusion slope correlation with SOFA score at 24 hours was 0.21 ( P < 0.02 ) , with a fair mortality AUC of 0.70 . The initial StO2 was significantly but less strongly correlated with SOFA score at 24 hours ( -0.18 ; P < 0.04 ) , with a poor mortality AUC of 0.56 . Conclusions NIRS measurements for the StO2 initial , StO2 occlusion and StO2 recovery slope were abnormal in patients with septic shock compared to sepsis patients . The recovery slope was most strongly associated with organ dysfunction and mortality . Further validation is warranted . Trial registration Introduction The aim of this study was to evaluate the effects of red blood cell ( RBC ) transfusions on muscle tissue oxygenation , oxygen metabolism and microvascular reactivity in critically ill patients using near-infrared spectroscopy ( NIRS ) technology . Methods This prospect i ve , observational study included 44 consecutive patients hospitalized in the 31-bed , medical-surgical intensive care unit of a university hospital with anemia requiring red blood cell transfusion . Thenar tissue oxygen saturation ( StO2 ) and muscle tissue hemoglobin index ( THI ) were measured using a tissue spectrometer ( InSpectra ™ Model 325 ; Hutchinson Technology Inc. , Hutchinson , MN , USA ) . A vaso-occlusive test was performed before and 1 hour after RBC transfusion by rapid inflation of a pneumatic cuff around the upper arm . The following variables were recorded : THI , the StO2 desaturation slope during the occlusion ( % /minute ) and the StO2 upslope of the reperfusion phase following the ischemic period ( % /second ) . Muscle oxygen consumption ( NIR VO2 ; arbitrary units ) was calculated as the product of the inverse StO2 desaturation slope and the mean THI over the first minute of arterial occlusion . Results Blood transfusion result ed in increases in hemoglobin ( from 7.1 ( 6.7 to 7.7 ) to 8.4 ( 7.1 to 9 ) g/dl ; P < 0.01 ) and in oxygen delivery ( from 306 ( 259 to 337 ) to 356 ( 332 to 422 ) ml/minute/m2 ; P < 0.001 ) . However , systemic VO2 was unchanged . RBC transfusion did not globally affect NIRS-derived variables , but there was considerable interindividual variation . Changes in the StO2 upslope of the reperfusion phase after transfusion were negatively correlated with baseline StO2 upslope of the reperfusion phase ( r2 = 0.42 ; P < 0.0001 ) . Changes in NIR VO2 after transfusion were also negatively correlated with baseline NIR VO2 ( r2 = 0.48 ; P = 0.0015 ) . There were no correlations between RBC storage time and changes in StO2 slope or NIR VO2 . Conclusions Muscle tissue oxygenation , oxygen consumption and microvascular reactivity are globally unaltered by RBC transfusion in critically ill patients . However , muscle oxygen consumption and microvascular reactivity can improve following transfusion in patients with alterations of these variables at baseline Introduction The prognostic value of continuous monitoring of tissue oxygen saturation ( StO2 ) during early goal -directed therapy of critically ill patients has not been investigated . We conducted this prospect i ve study to test the hypothesis that the persistence of low StO2 levels following intensive care admission is related to adverse outcome . Methods We followed 22 critically ill patients admitted with increased lactate levels ( > 3 mmol/l ) . Near-infrared spectroscopy ( NIRS ) was used to measure the thenar eminence StO2 and the rate of StO2 increase ( RincStO2 ) after a vascular occlusion test . NIRS dynamic measurements were recorded at intensive care admission and each 2-hour interval during 8 hours of resuscitation . All repeated StO2 measurements were further compared with Sequential Organ Failure Assessment ( SOFA ) , Acute Physiology and Chronic Health Evaluation ( APACHE ) II and hemodynamic physiological variables : heart rate ( HR ) , mean arterial pressure ( MAP ) , central venous oxygen saturation ( ScvO2 ) and parameters of peripheral circulation ( physical examination and peripheral flow index ( PFI ) ) . Results Twelve patients were admitted with low StO2 levels ( StO2 < 70 % ) . The mean scores for SOFA and APACHE II scores were significantly higher in patients who persisted with low StO2 levels ( n = 10 ) than in those who exhibited normal StO2 levels ( n = 12 ) at 8 hours after the resuscitation period ( P < 0.05 ; median ( interquartile range ) : SOFA , 8 ( 7 to 11 ) vs. 5 ( 3 to 8) ; APACHE II , 32(24 to 33 ) vs. 19 ( 15 to 25 ) ) . There was no significant relationship between StO2 and mean global hemodynamic variables ( HR , P = 0.26 ; MAP , P = 0.51 ; ScvO2 , P = 0.11 ) . However , there was a strong association between StO2 with clinical abnormalities of peripheral perfusion ( P = 0.004 ) , PFI ( P = 0.005 ) and RincStO2 ( P = 0.002 ) . The persistence of low StO2 values was associated with a low percentage of lactate decrease ( P < 0.05 ; median ( interquartile range ) : 33 % ( 12 to 43 % ) vs. 43 % ( 30 to 54 % ) ) . Conclusions We found that patients who consistently exhibited low StO2 levels following an initial resuscitation had significantly worse organ failure than did patients with normal StO2 values , and found that StO2 changes had no relationship with global hemodynamic variables Objective : This study aim ed to investigate , in patients with severe sepsis , the correlation between central venous oxygen saturation and tissue oxygen saturation at different levels . Design : Prospect i ve observational study . Setting : General intensive care unit at an academic medical center in France . Patients : Thirty-eight patients with underresuscitated severe sepsis and septic shock on intensive care unit admission . Interventions : None . Measurements and Main Results : During early resuscitation according to the 6-hr bundles of the Surviving Sepsis Campaign guidelines , tissue oxygen saturation was recorded every other hour at the level of the thenar , masseter , and deltoid muscles along with central hemodynamics , arterial lactate concentrations , and central venous oxygen saturation . Over the 6-hr resuscitation period , thenar tissue oxygen saturation was consistently higher than masseter tissue oxygen saturation ( p = .04 ) and deltoid tissue oxygen saturation ( p = .002 ) , and masseter tissue oxygen saturation was consistently higher than deltoid tissue oxygen saturation ( p = .04 ) . Receiver operating characteristic curves analyses showed that masseter tissue oxygen saturation was better predictor of central venous oxygen saturation > 70 % than thenar tissue oxygen saturation ( area under the curve , 0.80 ; 95 % confidence interval 0.71−0.89 vs. 0.67 ; 95 % confidence interval 0.56–0.77 ; p = .02 ) . The crude 28-day mortality was 36.8 % . Receiver operating characteristic curve analysis showed that masseter tissue oxygen saturation ( area under the curve 0.87 ; 0.75−0.98 ) and deltoid tissue oxygen saturation ( area under the curve 0.88 ; 0.77−0.98 ) but not thenar tissue oxygen saturation ( area under the curve 0.66 ; 0.46–0.86 ) or central venous oxygen saturation ( area under the curve 0.56 ; 0.38–0.80 ) were strong predictors of 28-day mortality . Conclusions : This study suggested that in the early 6-hr resuscitation period , masseter tissue oxygen saturation accurately identified patients with severe sepsis and central venous oxygen saturation > 70 % . Both masseter tissue oxygen saturation and deltoid tissue oxygen saturation but not central venous oxygen saturation or thenar tissue oxygen saturation are strong predictors of 28-day mortality BACKGROUND : Tissue oximetry ( StO2 ) plus a vascular occlusion test is a noninvasive technology that targets indices of oxygen uptake and delivery . We hypothesize that prehospital tissue oximetric values and vascular occlusion test response can predict the need for in-hospital lifesaving interventions ( LSI ) . METHODS : We conducted a prospect i ve , blinded observational study to evaluate StO2 slopes to predict the need for LSI . We calculated the DeO2 slope using Pearson 's coefficients of regression ( r2 ) for the first 25 % of descent and the ReO2 slope using the entire recovery interval . The primary outcome was LSI defined as the need for emergent operation or transfusion in the first 24 hours of hospitalization . We created multivariable logistic regression models using covariates of age , sex , vital signs , lactate , and mental status . RESULTS : We assessed StO2 in a convenience sample of 150 trauma patients from April to November of 2009 . In-hospital mortality was 3 % ( 95 % confidence interval [ CI ] , 1.1–7.6 ) ; 31 % ( 95 % CI , 24–39 ) were admitted to the intensive care unit , 6 % ( 95 % CI , 2.8–11.1 ) had an emergent operation , and 10 % ( 95 % CI , 5.7–15.9 ) required transfusion . Decreasing DeO2 was associated with a higher proportion of patients requiring LSI . In the multivariate model , the association between the need for LSI and DeO2 , Glasgow Coma Scale , and age persists . CONCLUSION : Prehospital DeO2 is associated with need for LSI in our trauma population . Further study of DeO2 is warranted to determine whether it can be used as an adjunct triage criterion or an endpoint for resuscitation . LEVEL OF EVIDENCE : III , observational study BACKGROUND In a single-center study published more than a decade ago involving patients presenting to the emergency department with severe sepsis and septic shock , mortality was markedly lower among those who were treated according to a 6-hour protocol of early goal -directed therapy ( EGDT ) , in which intravenous fluids , vasopressors , inotropes , and blood transfusions were adjusted to reach central hemodynamic targets , than among those receiving usual care . We conducted a trial to determine whether these findings were generalizable and whether all aspects of the protocol were necessary . METHODS In 31 emergency departments in the United States , we r and omly assigned patients with septic shock to one of three groups for 6 hours of resuscitation : protocol -based EGDT ; protocol -based st and ard therapy that did not require the placement of a central venous catheter , administration of inotropes , or blood transfusions ; or usual care . The primary end point was 60-day in-hospital mortality . We tested sequentially whether protocol -based care ( EGDT and st and ard-therapy groups combined ) was superior to usual care and whether protocol -based EGDT was superior to protocol -based st and ard therapy . Secondary outcomes included longer-term mortality and the need for organ support . RESULTS We enrolled 1341 patients , of whom 439 were r and omly assigned to protocol -based EGDT , 446 to protocol -based st and ard therapy , and 456 to usual care . Resuscitation strategies differed significantly with respect to the monitoring of central venous pressure and oxygen and the use of intravenous fluids , vasopressors , inotropes , and blood transfusions . By 60 days , there were 92 deaths in the protocol -based EGDT group ( 21.0 % ) , 81 in the protocol -based st and ard-therapy group ( 18.2 % ) , and 86 in the usual-care group ( 18.9 % ) ( relative risk with protocol -based therapy vs. usual care , 1.04 ; 95 % confidence interval [ CI ] , 0.82 to 1.31 ; P=0.83 ; relative risk with protocol -based EGDT vs. protocol -based st and ard therapy , 1.15 ; 95 % CI , 0.88 to 1.51 ; P=0.31 ) . There were no significant differences in 90-day mortality , 1-year mortality , or the need for organ support . CONCLUSIONS In a multicenter trial conducted in the tertiary care setting , protocol -based resuscitation of patients in whom septic shock was diagnosed in the emergency department did not improve outcomes . ( Funded by the National Institute of General Medical Sciences ; ProCESS Clinical Trials.gov number , NCT00510835 . ) BACKGROUND Early goal -directed therapy ( EGDT ) has been endorsed in the guidelines of the Surviving Sepsis Campaign as a key strategy to decrease mortality among patients presenting to the emergency department with septic shock . However , its effectiveness is uncertain . METHODS In this trial conducted at 51 centers ( mostly in Australia or New Zeal and ) , we r and omly assigned patients presenting to the emergency department with early septic shock to receive either EGDT or usual care . The primary outcome was all-cause mortality within 90 days after r and omization . RESULTS Of the 1600 enrolled patients , 796 were assigned to the EGDT group and 804 to the usual-care group . Primary outcome data were available for more than 99 % of the patients . Patients in the EGDT group received a larger mean ( ±SD ) volume of intravenous fluids in the first 6 hours after r and omization than did those in the usual-care group ( 1964±1415 ml vs. 1713±1401 ml ) and were more likely to receive vasopressor infusions ( 66.6 % vs. 57.8 % ) , red-cell transfusions ( 13.6 % vs. 7.0 % ) , and dobutamine ( 15.4 % vs. 2.6 % ) ( P<0.001 for all comparisons ) . At 90 days after r and omization , 147 deaths had occurred in the EGDT group and 150 had occurred in the usual-care group , for rates of death of 18.6 % and 18.8 % , respectively ( absolute risk difference with EGDT vs. usual care , -0.3 percentage points ; 95 % confidence interval , -4.1 to 3.6 ; P=0.90 ) . There was no significant difference in survival time , in-hospital mortality , duration of organ support , or length of hospital stay . CONCLUSIONS In critically ill patients presenting to the emergency department with early septic shock , EGDT did not reduce all-cause mortality at 90 days . ( Funded by the National Health and Medical Research Council of Australia and the Alfred Foundation ; ARISE Clinical Trials.gov number , NCT00975793 . ) The scientific community has agreed upon developing accurate monitoring of tissue perfusion and oxygenation to improve the management of subjects with sepsis . This pilot study aim ed to investigate the feasibility of targeting tissue oxygen saturation ( StO2 ) in addition to the currently recommended resuscitation goals , central venous pressure , mean arterial pressure and central venous oxygen saturation , in patients with severe sepsis or septic shock . A pilot , single-centre , r and omised , non-blinded trial recruited 30 subjects with severe sepsis upon intensive care unit admission at an academic medical centre in France . Subjects were r and omly assigned to a 6 h resuscitation strategy following the Surviving Sepsis Campaign guidelines with ( experimental ) or without ( control ) StO2 . StO2 was measured over several muscles ( masseter , deltoid and pectoral or thenar muscles ) , and a StO2 above 80 % over at least 2 muscles was the therapeutic goal . The primary outcome was evaluated as follows : 7-day mortality or worsening of SOFA score between day 7 and study onset , i.e. , DSOFA > 0 ) . Thirty subjects were included in the study over a period of 40 weeks . Fifteen subjects were included in each group . Monitoring of StO2 over three areas was performed in the experimental group . However , measures over the pectoral muscle provided poor results . At study day 7 , there were 5/15 ( 33.3 % ) subjects who died or had a DSOFA > 0 in the experimental arm and 4/15 ( 26.6 % ) who died or had a DSOFA > 0 in the control arm ( p = 1.00 ) . This pilot study was the first r and omised controlled trial using an algorithm derived from the SSC recommendations , which included StO2 as a treatment goal . However , the protocol showed no clear trend for or against targeting StO2 BACKGROUND Early goal -directed therapy ( EGDT ) is recommended in international guidance for the resuscitation of patients presenting with early septic shock . However , adoption has been limited and uncertainty remains over its clinical effectiveness and cost-effectiveness . OBJECTIVES The primary objective was to estimate the effect of EGDT compared with usual resuscitation on mortality at 90 days following r and omisation and on incremental cost-effectiveness at 1 year . The secondary objectives were to compare EGDT with usual resuscitation for requirement for , and duration of , critical care unit organ support ; length of stay in the emergency department ( ED ) , critical care unit and acute hospital ; health-related quality of life , re source use and costs at 90 days and at 1 year ; all-cause mortality at 28 days , at acute hospital discharge and at 1 year ; and estimated lifetime incremental cost-effectiveness . DESIGN A pragmatic , open , multicentre , parallel-group r and omised controlled trial with an integrated economic evaluation . SETTING Fifty-six NHS hospitals in Engl and . PARTICIPANTS A total of 1260 patients who presented at EDs with septic shock . INTERVENTIONS EGDT ( n = 630 ) or usual resuscitation ( n = 630 ) . Patients were r and omly allocated 1 : 1 . MAIN OUTCOME MEASURES All-cause mortality at 90 days after r and omisation and incremental net benefit ( at £ 20,000 per quality -adjusted life-year ) at 1 year . RESULTS Following withdrawals , data on 1243 ( EGDT , n = 623 ; usual resuscitation , n = 620 ) patients were included in the analysis . By 90 days , 184 ( 29.5 % ) in the EGDT and 181 ( 29.2 % ) patients in the usual-resuscitation group had died [ p = 0.90 ; absolute risk reduction -0.3 % , 95 % confidence interval ( CI ) -5.4 to 4.7 ; relative risk 1.01 , 95 % CI 0.85 to 1.20 ] . Treatment intensity was greater for the EGDT group , indicated by the increased use of intravenous fluids , vasoactive drugs and red blood cell transfusions . Increased treatment intensity was reflected by significantly higher Sequential Organ Failure Assessment scores and more advanced cardiovascular support days in critical care for the EGDT group . At 1 year , the incremental net benefit for EGDT versus usual resuscitation was negative at -£725 ( 95 % CI -£3000 to £ 1550 ) . The probability that EGDT was more cost-effective than usual resuscitation was below 30 % . There were no significant differences in any other secondary outcomes , including health-related quality of life , or adverse events . LIMITATIONS Recruitment was lower at weekends and out of hours . The intervention could not be blinded . CONCLUSIONS There was no significant difference in all-cause mortality at 90 days for EGDT compared with usual resuscitation among adults identified with early septic shock presenting to EDs in Engl and . On average , costs were higher in the EGDT group than in the usual-resuscitation group while quality -adjusted life-years were similar in both groups ; the probability that it is cost-effective is < 30 % . FUTURE WORK The ProMISe ( Protocol ised Management In Sepsis ) trial completes the planned trio of evaluations of EGDT across the USA , Australasia and Engl and ; all have indicated that EGDT is not superior to usual resuscitation . Recognising that each of the three individual , large trials has limited power for evaluating potentially important subgroups , the harmonised approach adopted provides the opportunity to conduct an individual patient data meta- analysis , enhancing both knowledge and generalisability . TRIAL REGISTRATION Current Controlled Trials IS RCT N36307479 . FUNDING This project was funded by the National Institute for Health Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 19 , No. 97 . See the NIHR Journals Library website for further project information Objective To vali date thenar oxygen saturation ( StO2 ) measured by near-infrared spectroscopy ( NIRS ) as a noninvasive estimation of central venous saturation ( ScvO2 ) in septic patients . Design Prospect i ve observational study . Setting A 26-bed medical – surgical intensive care unit at a university-affiliated hospital . Patients Patients consecutively admitted to the ICU in the early phase of severe sepsis and septic shock , after normalization of blood pressure with fluids and /or vasoactive drugs . Measurements We recorded demographic data , severity score , hemodynamic data , and blood lactate , as well as ScvO2 , and StO2 measured simultaneously on inclusion . Patients were divided into two groups according to ScvO2 values : group A , with ScvO2 < 70 % , and group B , with ScvO2 ≥ 70 % . Results Forty patients were studied . StO2 was significantly lower in group A than in group B ( 74.7 ± 13.0 vs. 83.3 ± 6.2 , P 0.018 ) . No differences in age , severity score , hemodynamics , vasoactive drugs , or lactate were found between groups . Simultaneously measured ScvO2 and StO2 showed a significant Pearson correlation ( r = 0.39 , P 0.017 ) . For a StO2 value of 75 % , sensitivity was 0.44 , specificity 0.93 , positive predictive value 0.92 , and negative predictive value 0.52 for detecting ScvO2 values lower than 70 % . Conclusions StO2 correlates with ScvO2 in normotensive patients with severe sepsis or septic shock . We propose a StO2 cut-off value of 75 % as a specific , rapid , noninvasive first step for detecting patients with low ScvO2 values . Further studies are necessary to analyze the role of noninvasive StO2 measurement in future resuscitation algorithms Introduction The study objectives were to evaluate septic shock-induced alterations in skeletal muscle hemoglobin oxygenation saturation ( StO2 ) using near-infrared spectroscopy ( NIRS ) and forearm skin blood flow velocity using laser Doppler ( LD ) to determine the relationship of macroperfusion and microperfusion parameters , and to test the relationship of the worst NIRS parameters during the first 24 hours of shock with 28-day prognosis . Methods A prospect i ve , observational study was performed in a 21-bed university hospital surgical intensive care unit . Forty-three septic shock patients with at least another organ failure underwent a 3-minute , upper arm ( brachial artery ) vascular occlusion test ( VOT ) . Microperfusion parameters ( thenar eminence StO2 and forearm LD skin blood flow ) were collected on days 1 , 2 and 3 , before ( baseline StO2 and LD values ) and during the 3-minute VOT with calculation of occlusion and reperfusion slopes for StO2 and LD . Daily Sequential Organ Failure Assessment ( SOFA ) score , macrohemodynamic parameters ( systolic arterial blood pressure , cardiac output ( pulmonary artery catheter or transesophageal Doppler ) , mixed venous oxygen saturation ( pulmonary artery or superior vena cava catheter ) ) and metabolic parameters ( pH , base excess , lactate ) were determined . Results Baseline StO2 ( 82 % ( 75 to 88 ) vs. 89 % ( 85 to 92 ) , P = 0.04 ) and reperfusion slope ( 2.79%/second ( 1.75 to 4.32 ) vs. 9.35%/second ( 8.32 to 11.57 ) , P < 0.0001 ) were lower in septic shock patients than in healthy volunteers . StO2 reperfusion slope correlated with occlusion slope ( P < 0.0001 ) , cardiac output ( P = 0.01 ) and LD reperfusion slope ( P = 0.08 ) , and negatively with lactate level ( P = 0.04 ) . The worst StO2 reperfusion slope during the first day of shock was lower in nonsurvivors than in survivors ( P = 0.003 ) and improved significantly the predictive value of Simplified Acute Physiology Score II and SOFA scores . Conclusions The alteration of StO2 reperfusion slope in septic shock patients compared with healthy volunteers was related with macrohemodynamic , microhemodynamic and metabolic parameters . The addition of the worst value of the day 1 StO2 reperfusion slope improved the outcome prediction of Simplified Acute Physiology Score II and SOFA scores Purpose Thenar eminence tissue oxygen saturation ( StO2 ) was developed to assess organ perfusion . However , mottling , a strong predictor of mortality in septic shock , develops preferentially around the knee . We aim ed to evaluate the prognostic value of StO2 measured around the knee in septic shock patients and compare it to thenar StO2 . Methods This was a prospect i ve observational study in a tertiary teaching hospital . All consecutive patients with septic shock were included . Parameters were recorded when vasopressors were started ( H0 ) and every 6 h during 24 h. Their predictive value was assessed on 14-day mortality . Results Fifty-two patients were included . SOFA score was 11 ( 9–15 ) and SAPS II was 56 ( 40–72 ) . At 6 h after ICU admission ( H6 ) , mean arterial pressure , cardiac index , and central venous pressure were not different between non-survivors and survivors ; but non-survivors had higher arterial lactate level ( 8.8 ± 5.0 vs. 2.2 ± 1.5 mmol/l , P < 0.001 ) , lower urinary output ( 0.22 ± 0.45 vs. 0.70 ± 0.50 ml/kg/h , P < 0.001 ) and ScvO2 ( 62 ± 20 vs. 72 ± 9 % , P = 0.03 ) . At H6 , StO2 was lower in non-survivors ; this difference was not significant for thenar StO2 ( 70 ± 15 vs. 77 ± 12 % , P = 0.10 ) but was very pronounced for knee StO2 ( 39 ± 23 vs. 71 ± 12 % , P < 0.001 ) . At H6 , a low knee StO2 was associated with a higher mottling score ( P < 0.01 ) , a higher lactate level ( P < 0.002 , R2 = 0.2 ) , and a lower urinary output ( P = 0.02 , R2 = 0.12 ) . Conclusion After initial septic shock resuscitation , StO2 measured around the knee is a strong predictive factor of 14-day mortality BACKGROUND Continuous and minimally invasive near-infrared spectroscopy (NIRS)-derived gastric tissue oxygen saturation ( GStO(2 ) ) and muscle tissue oxygen saturation ( MStO(2 ) ) were evaluated in a clinical ly relevant porcine model of hemorrhagic shock and abdominal compartment syndrome ( ACS ) . METHODS Phenobarbital-anesthetized swine underwent pulmonary artery catheter insertion for mixed venous oxygen saturation ( SvO(2 ) ) measurement and midline laparotomy to permit placement of a gastric NIRS probe , a jejunal ( regional carbon dioxide [ PrCO(2 ) ] ) tonometer , superior mesenteric artery ( SMA ) flow probe , and a portal vein oxygen saturation ( SpvO(2 ) ) catheter . A muscle NIRS probe was placed on the front limb . After r and omization , Group 1 underwent hemorrhage and resuscitation . Group 2 had no hemorrhage or resuscitation . ACS was induced by peritoneal fluid infusion in both groups . A significant decrease in SMA flow , SpvO(2 ) , GStO(2 ) , SvO(2 ) , and MStO(2 ) was observed after hemorrhage in Group 1 and with abdominal hypertension in both groups . RESULTS GStO(2 ) significantly correlated with SMA flow ( Group 1 : r(2 ) = 0.90 ; Group 2 : r(2 ) = 0.83 ) and mesenteric oxygen delivery ( mesenteric oxygen delivery , Group 1 : r(2 ) = 0.73 ; Group 2 : r(2 ) = 0.89 ) . MStO(2 ) significantly correlated with SvO(2 ) ( Group 1 : r(2 ) = 0.99 ; Group 2 : r(2 ) = 0.65 ) and systemic oxygen delivery ( SDO2 , Group 1 : r(2 ) = 0.60 ; Group 2 : r(2 ) = 0.88 ) . Tonometer-derived PrCO(2 ) values did not change at any time point in either group . CONCLUSIONS NIRS measurement of GStO(2 ) and MStO(2 ) reflected changes in mesenteric and systemic perfusion respectively during hemorrhage and ACS The purpose of this study is to compare Near Infrared Spectroscopy ( NIRS ) thenar eminence parameters obtained with 2 different devices from the same manufacturer ( InSpectra Models 325 and 650 , Hutchinson Tech , Min USA ) , and 2 different probes ( 15 vs. 25 mm spacing ) , in healthy volunteers ( HV ) and ICU patients . Prospect i ve , observational study in ICU setting . Simultaneous , cross over NIRS inter-device comparison and comparison between different probes ( 25 vs. 15 mm spacing ) were done at baseline and during vascular occlusion tests ( VOTs ) . Forty patients ( 19 septic shock , 21 trauma ) , and 29 HV were included . NIRS inter-device comparison showed similar baseline StO2 values in HV and patients . The VOT result were significantly different for minimal StO2 value reached during VOT ( StO2min ) ( intraclass concordance coefficient ( ICC ) = 0.18 ) , the occlusion slope ( ICC = 0.16 ) and the reperfusion slope ( StO2reperf ) ( ICC = 0.26 ) . The probe comparison was also significantly different for VOT parameters ( StO2min ( ICC = 0.43 ) , occlusion ( ICC = 0.50 ) and StO2reperf ( ICC = 0.48 ) . The low concordance , poor agreement and large bias ( ICC and Bl and & Altman ) observed , were related both to the device used and the probe spacing . StO2 data obtained with NIRS model 650 and 15 mm probe differ from values obtained with the previous device ( 325 and probe spacing 25 or 15 mm ) . This difference is not related to the population tested , but to the device and probe spacing . As a consequence , despite similar trends for variations between HV and patients during VOT , threshold and predictive values for outcome should be revisited with the new device before the acceptance for routine clinical use Introduction Discrepancies of 5 - 24 % between superior vena cava oxygen saturation ( ScvO2 ) and mixed venous oxygen saturation ( SvO2 ) have been reported in patients with severe heart failure . Thenar muscle tissue oxygenation ( StO2 ) measured with near-infrared spectroscopy ( NIRS ) during arterial occlusion testing decreases slower in sepsis/septic shock patients ( lower StO2 deoxygenation rate ) . The StO2 deoxygenation rate is influenced by dobutamine . The aim of this study was to determine the relationship between the StO2 deoxygenation rate and the ScvO2-SvO2 discrepancy in patients with severe left heart failure and additional sepsis/septic shock treated with or without dobutamine . Methods Fifty-two patients with severe left heart failure due to primary heart disease with additional severe sepsis/septic shock were included . SvO2 and ScvO2 were compared to the thenar muscle StO2 before and during arterial occlusion . Results SvO2 correlated significantly with ScvO2 ( Pearson correlation 0.659 , P = 0.001 ) , however , Bl and Altman analysis showed a clinical ly important difference between both variables ( ScvO2-SvO2 mean 72 ± 8 % , ScvO2-SvO2 difference 9.4 ± 7.5 % ) . The ScvO2-SvO2 difference correlated with plasma lactate ( Pearson correlation 0.400 , P = 0.003 ) and the StO2 deoxygenation rate ( Pearson correlation 0.651 , P = 0.001 ) . In the group of patients treated with dobutamine , the ScvO2-SvO2 difference correlated with plasma lactate ( Pearson correlation 0.389 , P = 0.011 ) and the StO2 deoxygenation rate ( Pearson correlation 0.777 , P = 0.0001 ) . Conclusions In patients with severe heart failure with additional severe sepsis/septic shock the ScvO2-SvO2 discrepancy presents a clinical problem . In these patients the skeletal muscle StO2 deoxygenation rate is inversely proportional to the difference between ScvO2 and SvO2 ; dobutamine does not influence this relationship . When using ScvO2 as a treatment goal , the NIRS measurement may prove to be a useful non-invasive diagnostic test to uncover patients with a normal ScvO2 but potentially an abnormally low SvO2.Trial Registration NCT00384644 Clinical Trials . Gov Introduction Adequate volume expansion ( VE ) in patients with evidence of hypoperfusion should be aim ed not only at achieving an increase in stroke volume ( SV ) and cardiac index ( CI ) but also at improved tissue perfusion and oxygenation . Our aim in this study was to assess the dynamic changes in muscle tissue oxygen saturation ( StO2 ) during hypovolaemia and in response to VE . Methods We conducted a prospect i ve study of 42 fluid challenges in patients undergoing major abdominal surgery with evidence of hypovolaemia , defined as pulse pressure variation ( PPV ) > 13 % and SV variation ( SVV ) > 12 % . CI , SV , SVV ( FloTrac/Vigileo ) and PPV were measured before and after VE . Fluid responsiveness was defined as an increase of SV > 15 % after a 500-mL colloid infusion over 15 minutes . In all patients , the muscle StO2 and its changes during a st and ardised vascular occlusion test were analysed using a near-infrared spectroscopy device after anaesthesia induction ( which defined the baseline state ) and before and after each VE . Results No patients were preload-responsive after anaesthesia induction . Twenty-nine of forty-two fluid challenges ( 69 % ) were positive for VE , with a statistically significant ( P < 0.001 ) difference in SV changes between positive and negative responses to VE . There was a statistically significant difference in PPV and SVV values before VE in the positive and negative fluid responses [ PPV : 16 % ( 15 % to 18 % ) vs. 14 % ( 13 % to 15 % ) , P = 0.001 ; and SVV : 14 % ( 13 % to 16 % ) vs. 16 % ( 15 % to 16 % ) , P = 0.03 or positive and negative fluid responses , respectively ] . Data are presented as medians and 25th and 75th percentiles Before VE there was no significant difference in StO2 values relative to baseline [ 86 % ( 78 % to 88 % ) vs. 84 % ( 77 % to 91 % ) , P = 0.83 ] , without a significant difference ( P = 0.36 ) between positive and negative fluid challenges . Hypovolaemia was associated with a significant reduction ( P = 0.004 ) in StO2 recovery slope , with a significant difference ( P = 0.02 ) between positive and negative fluid challenges . The VE-induced increase in the StO2 recovery slope was 62 ± 49 % ( P < 0.001 ) for positive fluid challenges and 26 ± 34 % ( P = 0.04 ) for negative fluid challenges . Conclusions Hypovolaemia significantly affects the muscle StO2 recovery slope . Restoring effective intravascular volume with fluid loading significantly improves the StO2 recovery slope , despite apparently ineffective changes in systemic haemodynamics BACKGROUND Severely bleeding trauma patients requiring massive transfusion ( MT ) often experience poor outcomes . Our purpose was to determine the potential role of near infrared spectrometry derived tissue hemoglobin oxygen saturation ( StO2 ) monitoring in early prediction of MT , and in the identification of those MT patients who will have poor outcomes . METHODS Data from a prospect i ve multi-institution StO2 monitoring study were analyzed to determine the current epidemiology of MT ( defined as transfusion volume > /=10 units packed red blood cells in 24 hours of hospitalization ) . Multivariate logistic regression was used to develop prediction models . RESULTS Seven US level I trauma centers ( TC ) enrolled 383 patients . 114 ( 30 % ) required MT . MT progressed rapidly ( 40 % exceeded MT threshold 2 hours after TC arrival , 80 % after 6 hours ) . One third of MT patients died . Two thirds of deaths were due to early exsanguination and two thirds of early exsanguination patients died within 6 hours . One third of the early MT survivors developed multiple organ dysfunction syndrome . MT could be predicted with st and ard , readily available clinical data within 30 minutes and 60 minutes of TC arrival ( area under the receiver operating characteristic curve = 0.78 and 0.80 ) . In patients who required MT , StO2 was the only consistent predictor of poor outcome ( multiple organ dysfunction syndrome or death ) . CONCLUSION MT progresses rapidly to significant morbidity and mortality despite level I TC care . Patients who require MT can be predicted early , and persistent low StO2 identifies those MT patients destined to have poor outcome . The ultimate goal is to identify these high risk patients as early as possible to test new strategies to improve outcome . Further validation studies are needed to analyze appropriate allocation and study appropriate use of damage control interventions Objective To determine changes in the rate of thenar muscles tissue deoxygenation during stagnant ischemia in patients with severe sepsis and septic shock . Design and setting Prospect i ve observational study in the medical ICU of a general hospital . Patients and participants Consecutive patients admitted to ICU with septic shock ( n=6 ) , severe sepsis ( n=6 ) , localized infection ( n=3 ) , and healthy volunteers ( n=15 ) . Interventions Upper limb ischemia was induced by rapid automatic pneumatic cuff inflation around upper arm . Measurements and results Thenar muscle tissue oxygen saturation ( StO2 ) was measured continuously by near-infrared spectroscopy before and during upper limb ischemia . StO2 before intervention was comparable in patients with septic shock , severe sepsis , or localized infection and healthy volunteers ( 89 [ 65 , 92]% vs. 82 [ 72 , 91]% vs. 87 [ 85 , 92]% vs. 83 [ 79 , 93]% , respectively ; p>0.1 ) . The rate of StO2 decrease during stagnant ischemia after initial hemodynamic stabilization was slower in septic shock patients than in those with severe sepsis or localized infection and in controls ( –7.0 [ –3.6 , –11.0 ] % /min vs. –10.4 [ –7.8 , –13.3 ] % /min vs. –19.5 [ –12.3 , –23.3 ] vs. –37.4 [ –27.3 , –56.2 ] % /min , respectively ; p=0.041 ) . At ICU discharge the rate of StO2 decrease did not differ between the septic shock , severe sepsis , and localized infection groups ( –17.0 [ –9.3 , –28.9 ] % /min vs. –19.9 [ –13.3 , –23.6 ] % /min vs. –23.1 [ –20.7 , –26.2 ] % /min , respectively ) , but remained slower than in controls ( p<0.01 ) . The rate of StO2 decrease was correlated with Sequential Organ Failure Assessment ( SOFA ) score ( r=0.739 , p<0.001 ) . Conclusions After hemodynamic stabilization thenar muscle tissue oxygen saturation during stagnant ischemia decreases slower in septic shock patients than in patients with severe sepsis or localized infection and in healthy volunteers . During ICU stay and improvement of sepsis the muscle tissue deoxygenation rate increases in survivors of both septic shock and severe sepsis and was correlated with SOFA score UNLABELLED Vital healthcare re sources are devoted to caring for patients with prolonged hospitalization after routine , moderate-risk surgery . Despite the significant cost , little is known about the overall incidence and pattern of complications in these patients . Four hundred thirty-eight patients undergoing a diverse group of routine , moderate-risk , elective surgical procedures were enrolled into a prospect i ve , blinded , cohort study . Complications were assessed using a postoperative morbidity survey . The main outcome was postoperative complication , defined as either in-hospital death or prolonged postoperative hospitalization ( > 7 days ) . The mortality rate was 1.6 % . Postoperative complications occurred in 118 patients ( 27 % [ 95 % CI 23 - 31 ] ) . Complications frequently observed in these patients included : gastrointestinal 51 % ( 42 - 60 ) , pulmonary 25 % ( 17 - 33 ) , renal 21 % ( 14 - 28 ) , and infectious 13 % ( 7 - 19 ) . Most complications were not directly related to the type/site of surgery . Indices of tissue trauma ( blood loss [ P < 0.001 ] , surgical duration [ P = 0.001 ] ) and tissue perfusion ( arterial base deficit [ P = 0.008 ] , gastric pHi [ P = 0.02 ] ) were the strongest intraoperative predictors of complications . Despite a low mortality rate , we found that complications after routine , moderate-risk , elective surgery are common and involve multiple organ systems . Our 9-point survey can be used by healthcare providers and payers to characterize post-operative morbidity in their respective setting s. IMPLICATION S Little is known about the overall incidence and pattern of complications in patients with prolonged hospitalization after routine , elective surgery . We prospect ively assessed these complications using a novel postoperative morbidity survey . The postoperative morbidity survey can be used in future clinical outcome trials , as well as in routine hospital-based quality assurance BACKGROUND Near-infrared spectroscopy ( NIRS ) can continuously and noninvasively monitor tissue oxygen saturation ( StO2 ) in muscle and may be an indicator of shock severity . Our purpose was to evaluate how well StO2 predicted outcome in high-risk torso trauma patients presenting in shock . METHODS The primary outcome in this prospect i ve study was multiple organ dysfunction syndrome ( MODS ) . StO2 data were obtained upon hospital arrival and for 24 hours along with other known predictors of hypoperfusion and clinical outcomes . Clinicians were blinded to StO2 measurements . RESULTS Seven Level I trauma centers enrolled 383 patients , 50 of whom developed MODS . Minimum StO2 performed similarly to maximum base deficit ( BD ) in discrimination of MODS patients . The sensitivity for both measures ( StO2 cutoff = 75 % ; BD cutoff = 6 mEq/L ) was 78 % , the specificity was 34 % to 39 % , the positive predictive value was 18 % to 20 % and the negative predictive value was 88 % to 91 % . StO2 and BD were also comparable in predicting death . CONCLUSIONS NIRS-derived muscle StO2 measurements perform similarly to BD in identifying poor perfusion and predicting the development of MODS or death after severe torso trauma , yet have the additional advantages of being continuous and noninvasive ObjectiveS epsis is now considered a disease of the microcirculation . Little is known about the various sepsis-induced changes responsible for microvascular dysfunction . We investigated human microvascular function , regulation , oxygenation , and cellular metabolism during subacute septic shock . Design and setting Prospect i ve case-control study in a nine-bed polyvalent surgical ICU of a university hospital . Patients and participants A prospect ively enrolled group of 26 patients ( 13 with septic shock , 13 nonseptic postsurgical patients ) and 15 healthy volunteer controls . Measurements and results The absolute tissue hemoglobin concentrations ( oxygenated hemoglobin and deoxyhemoglobin ) were measured noninvasively in arterioles , capillaries , and venules by phase-modulation near-infrared spectroscopy in the human brachioradial muscle during a series of venous occlusions and an arterial occlusion ( ischemia ) induced by applying a pneumatic cuff . These measurements were used to calculate tissue blood volume , postischemic hemoglobin resaturation time , microvascular compliance , and O2 consumption . Patients with sepsis had significantly higher tissue blood volume values and lower compliance than healthy controls . They also had longer postischemic hemoglobin resaturation times than the other two groups and blunted resaturation curves . O2 consumption was lower in patients with sepsis than in healthy controls . In patients with septic shock cuff-induced ischemia left O2 consumption unchanged , whereas in healthy volunteers it reduced O2 consumption to values almost matching those of patients with septic shock . Conclusions These findings show that septic shock alters microvascular muscle function and regulation . Diminished local VO2 presumably reflects maldistribution and faulty autoregulation of local blood flow Purpose To examine the consequences of administration of norepinephrine on muscle tissue oxygenation in severely hypotensive septic shock patients . Methods This was a prospect i ve observational study conducted in a medical intensive care unit of a university hospital . We included 28 septic shock patients that received early volume resuscitation . All were eligible for receiving norepinephrine because of life-threatening hypotension and low diastolic arterial pressure . Muscle tissue oxygen saturation ( StO2 ) and its changes during a vascular occlusion test were measured at the level of the thenar eminence using a near-infrared spectroscopy ( NIRS ) device . Transpulmonary thermodilution cardiac index ( CI ) and NIRS-derived variables were obtained before and after the mean arterial pressure ( MAP ) was increased by norepinephrine . The baseline StO2 and the vascular occlusion test-derived variables of 17 healthy volunteers were measured and served as controls . Results In healthy volunteers , StO2 ranged between 75 and 90 % and StO2 recovery slopes ranged between 1.5 and 3.4%/s . Administration of norepinephrine , which was associated with an increase in MAP from 54 ± 8 to 77 ± 9 mmHg ( p < 0.05 ) , also induced increases in CI from 3.14 ± 1.03 to 3.61 ± 1.28 L/min/m2 ( p < 0.05 ) , in StO2 from 75 ± 9 to 78 ± 9 % ( p < 0.05 ) and in StO2 recovery slope from 1.0 ± 0.6 to 1.5 ± 0.7%/s ( p < 0.05 ) . Conclusions Norepinephrine administration aim ed at achieving a MAP higher than 65 mmHg in septic shock patients with life-threatening hypotension result ed in improvement of NIRS variables measured at the level of the thenar eminence BACKGROUND A tissue hemoglobin oxygen saturation ( STO2 ) monitor was created to assess the perfusion status of a peripheral muscle bed using near infrared light to directly measure oxygen saturation in the microcirculation . Hypoperfusion has been noted when the STO2 is < 75 % . The use of this technology has not been tested in the prehospital setting . This pilot study was performed to assess the technology 's ease of use in the field and to correlate STO2 readings with patient outcomes . METHODS Hospital-based transport vehicles were equipped with STO2 monitors and personnel were asked to evaluate the functionality of the technology . Initial , average , and minimal STO2 values were collected and compared with data of the trauma registry . RESULTS Forty five of 55 surveys were returned with 100 % reporting ease of use and no reports of interference with monitors or avionics . Monitoring length averaged 16.9 minutes + /- 6.9 minutes . Forty-one patients had complete data sets and five deaths were reported for a mortality rate of 12 % . STO2 endpoints revealed and increased risk of death for every 10 % decrease in STO2 . CONCLUSION The STO2 monitor can easily be used in the prehospital environment . In addition , initial recordings were significantly different between survivors and nonsurvivors with every 10 % decrease in STO2 increasing mortality threefold . This monitor seems to give the prehospital provider a noninvasive tool for assessment of hypoperfusion in the field and may allow for earlier resuscitative efforts to commence BACKGROUND Near-infrared spectroscopy measures the percentage of hemoglobin oxygen saturation in the microcirculation of tissue up to 3 cm below the skin . The purpose of this study was to describe the measurable response of normal tissue oxygenation in the leg after acute trauma with use of this technique . METHODS Twenty-six patients with acute unilateral tibial fractures and twenty-five uninjured volunteer control subjects were enrolled . Near-infrared spectroscopy measurements were obtained for both legs in all four compartments : anterior , lateral , deep posterior , and superficial posterior . The twenty-six injured legs were compared with twenty-five uninjured legs ( r and omly selected ) of the volunteer control group , with the contralateral limb in each patient serving as an internal control . RESULTS The mean tissue oxygenation for each compartment in the injured legs was 69 % ( anterior ) , 70 % ( lateral ) , 74 % ( deep posterior ) , and 70 % ( superficial posterior ) . In the control ( uninjured ) legs , the average tissue oxygenation percentage in each compartment was 54 % , 55 % , 60 % , and 57 % , respectively . Repeated- measures analysis revealed that near-infrared spectroscopy values averaged 15.4 percentage points ( 95 % confidence interval , 12.2 to 18.6 percentage points ) higher for injured legs than for uninjured legs , controlling for the value of the contralateral limb ( p < 0.0001 ) . CONCLUSIONS Tibial fracture produces a predictable increase in tissue oxygenation as measured by near-infrared spectroscopy . The corresponding compartment of the contralateral leg can provide strong utility as an internal control value when evaluating the hyperemic response to injury To compare skeletal muscle microvascular blood flow at rest and during reactive hyperemia in septic patients , a prospect i ve , controlled trial was conducted on 16 patients with severe sepsis and a control group of 10 patients free of infection in the intensive care unit of a university hospital . Systemic hemodynamics , whole-body oxygen transport , and skeletal muscle microvascular blood flow at rest and during reactive hyperemia were measured . Reactive hyperemia was produced by arrest of leg blood flow with a pneumatic cuff ; on completion of the 3 min ischemic phase the occluding cuff was rapidly deflated to 0 . Hemodynamic and oxygen-derived variables were determined invasively . Skeletal muscle microvascular blood flow data were obtained using a laser Doppler flowmetry technique and values expressed in millivolts . Whole-body oxygen delivery in septic patients was increased compared with control subjects . Resting skeletal muscle blood flow was decreased in septic patients compared with control subjects ( 233 + /- 52 versus 394 + /- 93 mV ; p < 0.05 ) . Peak flow during reactive hyperemia was also decreased in septic patients compared with control subjects ( 380 + /- 13 versus 2,033 + /- 853 mV ; p < 0.05 ) . Cyclic variation in blood flow ( vasomotion ) was observed in control subjects but not in septic patients . Skeletal muscle microvascular perfusion is altered in patients with severe sepsis despite normal or elevated whole-body oxygen delivery . These microvascular abnormalities may further compromise tissue nutrient flow and may contribute to the development of organ failure in septic patients BACKGROUND : Cerebral deoxygenation is associated with various adverse systemic outcomes . We hypothesized , by using the brain as an index organ , that interventions to improve cerebral oxygenation would have systemic benefits in cardiac surgical patients . METHODS : Two-hundred coronary artery bypass patients were r and omized to either intraoperative cerebral regional oxygen saturation ( rSO2 ) monitoring with active display and treatment intervention protocol ( intervention , n = 100 ) , or underwent blinded rSO2 monitoring ( control , n = 100 ) . Predefined clinical outcomes were assessed by a blinded observer . RESULTS : Significantly more patients in the control group demonstrated prolonged cerebral desaturation ( P = 0.014 ) and longer duration in the intensive care unit ( P = 0.029 ) versus intervention patients . There was no difference in overall incidence of adverse complications , but significantly more control patients had major organ morbidity or mortality ( death , ventilation > 48 h , stroke , myocardial infa rct ion , return for re-exploration ) versus intervention group patients ( P = 0.048 ) . Patients experiencing major organ morbidity or mortality had lower baseline and mean rSO2 , more cerebral desaturations and longer lengths of stay in the intensive care unit and postoperative hospitalization , than patients without such complications . There was a significant ( r2 = 0.29 ) inverse correlation between intraoperative rSO2 and duration of postoperative hospitalization in patients requiring ≥10 days postoperative length of stay . CONCLUSION : Monitoring cerebral rSO2 in coronary artery bypass patients avoids profound cerebral desaturation and is associated with significantly fewer incidences of major organ dysfunction Objective : To compare data gathered via four different types of vascular occlusion test ( VOT ) by using near-infrared spectroscopy . The data may support a st and ardized method to appropriately measure the postischemic recovery slope , which is currently emphasized as a quantitative marker of the microvascular reserve in septic patients . Design : Prospect i ve study . Setting : Medical intensive care unit of a university hospital . Patients and Measurements : In 20 healthy volunteers and in 20 septic shock patients , we measured muscle tissue oxygen saturation at the thenar eminence by using near-infrared spectroscopy and performed four different vascular occlusion tests in a r and om order . A pneumatic cuff was placed around either the upper arm ( A ) or the forearm ( FA ) . Cuff inflation was maintained either during 3 mins ( VOTA3min and VOTFA3min ) or until muscle tissue oxygen saturation decreased to 40 % ( VOTA40 % and VOTFA40 % ) . Results : In volunteers : 1 ) During VOTA3min and VOTFA3min , the minimal muscle tissue oxygen saturation was significantly higher than 40 % ( 52 % ± 10 % and 54 % ± 6 % , respectively ) , and 2 ) the muscle tissue oxygen saturation recovery slopes were steeper with VOTA40 % and VOTFA40 % than with VOTA3min and VOTFA3min , respectively . Considering the pooled data obtained during VOTA3min and VOTFA3min ( n = 40 ) , recovery slope negatively correlated with minimal muscle tissue oxygen saturation in volunteers ( r2 = .46 , p < .0001 ) as in septic patients ( r2 = .34 , p = .0001 ) . Considering the pooled data obtained during 40 % VOTs , the recovery slope did not correlate with ischemic time in either group . The overlap of recovery slopes between volunteers and septic patients was small for both 40 % VOTs but large for both 3-min occlusion VOTs . Conclusion : The comparison of recovery slopes between volunteers and septic patients and the fact that the recovery slope was influenced by the extent of muscle tissue oxygen saturation decrease during ischemia and not by the ischemic time both support the use of a fixed minimal muscle tissue oxygen saturation target ( 40 % ) over the use of a fixed ischemic time ( 3 mins ) for assessing reactive hyperemia by using near-infrared spectroscopy BACKGROUND Peripheral muscle tissue oxygenation determined noninvasively using near-infrared spectroscopy may help to identify tissue hypoperfusion in septic patients . The aim of this study was to investigate regional oxygen saturation index ( rSO2 ) in the brachioradialis ( forearm ) muscle by comparing measurements in healthy subjects and in intensive care unit ( ICU ) septic shock patients , and determine whether brachioradialis muscle rSO2 is associated with poor outcome in ICU septic shock patients . METHODS We conducted a prospect i ve observational study in healthy volunteers ( n = 50 ) and ICU septic shock patients ( n=19 ) . Brachioradialis ( forearm ) rSO2 measurements in healthy volunteers at rest and in ICU septic shock patients were compared . Pulmonary artery catheter monitoring was used in ICU patients . RESULTS Significant differences in rSO2 were observed between healthy volunteers and ICU septic shock patients at ICU admission ( 68.7±4.9 vs. 55.0±13.0 ; p<0.001 ) . When comparing septic shock survivors and nonsurvivors , significant differences were observed in rSO2 at baseline ( 64.5±8.9 vs. 47.5±10.7 ; p<0.01 ) , 12 hours ( 67.3±9.6 vs. 45.0±14.9 ; p<0.01 ) , and 24 hours ( 65.7±7.0 vs. 50.1±10.3 ; p<0.01 ) . Lactate concentration was lower in survivors than nonsurvivors at 24 hours ( 12.0±7.5 mmol/L vs. 23.2±12.5 mmol/L ; p<0.04 ) . Cardiac index was greater in nonsurvivors than survivors at baseline ( 4.6 + 1.9 L/min/m vs. 3.0 + 0.9 L/min/m ; p<0.05 ) and 12 h ( 3.9 + 0.5 L/min/m vs. 3.1 + 0.3 L/min/m ; p<0.05 ) . CONCLUSIONS We observed that septic shock patients with forearm skeletal muscle rSO2≤60 % throughout first 24 hours after ICU admission had significantly greater mortality rate than patients with forearm skeletal muscle rSO2>60 % throughout this critical time OBJECTIVE To compare tissue oxygen saturation in ovariohysterectomized dogs recovering postoperatively on room air versus nasal oxygen insufflation . DESIGN Prospect i ve clinical study . SETTING University teaching hospital . ANIMALS Twenty dogs undergoing ovariohysterectomy . INTERVENTIONS Dogs were r and omized to breathe either room air or 100 mL/kg/min of nasal oxygen insufflation for 2 hours postoperatively . Tissue oxygen saturation ( StO(2 ) ) was evaluated at 2 mm and 20 mm lateral to the surgical incision , as well as in the inguinal region using a noninvasive tissue oximeter . MEASUREMENTS AND MAIN RESULTS In dogs recovered on nasal oxygen insufflation ( n = 10 ) , tissue oxygen saturation was significantly higher--20 mm from the surgical site ( 88.44 ± 2.50 % , P = 0.02 ) and in the inguinal region ( 83.56 ± 1.91 % , P = 0.032)-- compared to dogs recovered on room air ( n = 10 , 79.11 % ± 2.50 and 77.12 % ± 1.91 , respectively ) . CONCLUSIONS In ovariohysterectomized dogs , oxygen supplementation for 2 hours postoperatively improves tissue oxygen saturation 20 mm adjacent to the linea alba and in the inguinal region . Oxygen supplementation in postoperative dogs is an inexpensive and easily applicable method to improve tissue oxygen saturation BACKGROUND Our recent experimental study showed that peripheral muscle tissue oxygen saturation ( StO2 ) , determined noninvasively by near-infrared spectroscopy ( NIRS ) , was more reliable than systemic hemodynamics or invasive oxygenation variables as an index of traumatic shock . The purpose of this study was to establish the normal range of thenar muscle StO2 in humans and the relationship between shock state and StO2 in trauma patients . METHODS This was a prospect i ve , nonr and omized , observational , descriptive study in normal human volunteers ( n = 707 ) and patients admitted to the resuscitation area of our Level I trauma center ( n = 150 ) . To establish a normal StO2 range , an NIRS probe was applied to the thenar eminence of volunteers ( normals ) . Subsequently , in a group of trauma patients , an NIRS probe was applied to the thenar eminence and data were collected and stored for offline analysis . StO2 monitoring was performed continuously and noninvasively , and values were recorded at 2-minute intervals . Five moribund trauma patients were excluded . Members of our trauma faculty , blinded to StO2 values , classified each patient into one of four groups ( no shock , mild shock , moderate shock , and severe shock ) using conventional physiologic parameters . RESULTS Mean + /- SD thenar StO2 values for each group were as follows : normals , 87 + /- 6 % ( n = 707 ) ; no shock , 83 + /- 10 % ( n = 85 ) ; mild shock , 83 + /- 10 % ( n = 19 ) ; moderate shock , 80 + /- 12 % ( n = 14 ) ; and severe shock , 45 + /- 26 % ( n = 14 ) . The thenar StO2 values clearly discriminated the normals or no shock patients and the patients with severe shock ( p < 0.05 ) . CONCLUSION Decreased thenar muscle tissue oxygen saturation reflects the presence of severe hypoperfusion and near-infrared spectroscopy may be a novel method for rapidly and noninvasively assessing changes in tissue dysoxia BACKGROUND We hypothesized that near-infrared spectroscopy (NIRS)-derived tissue oxygenation saturation ( StO2 ) could assist in identifying shock in casualties arriving to a combat support hospital and predict the need for life-saving interventions ( LSIs ) and blood transfusions . METHODS We performed a prospect i ve observational trial at a single US Army combat support hospital in Iraq from August to December 2007 . Arriving casualties had NIRS-derived StO2 recorded in the emergency department . Minimum ( StO2 min ) and initial 2-minute averaged StO2 and tissue hemoglobin index readings were used as end points . Outcomes measured were requirement for LSIs , any blood transfusion , massive transfusion ( > 10 units in 24 hours ) , and early mortality . The data were subjected to univariate and multivariate logistic regression modeling . RESULTS Of the 147 combat casualties enrolled in the trial , 72 ( 49 % ) required an LSI , 42 ( 29 % ) required blood transfusion , and 10 ( 7 % ) required massive transfusion . On multivariate logistic regression analysis of the whole study group , systolic blood pressure ( SBP ) , international normalized ratio , tissue hemoglobin index , and hematocrit predicted blood transfusion with an area under the curve of 0.90 ( 0.84 - 0.96 ) , with a confidence interval of 95 % . When just the group with an SBP > 90 was analyzed , independent predictors of patients requiring blood transfusion on logistic regression analysis were StO2 min ( odds ratio of 1.35 ) and hematocrit ( odds ratio of 2.66 ) for an area under the curve of 0.84 ( 0.76 - 0.92 ) . CONCLUSIONS NIRS-derived StO2 obtained on arrival predicts the need for blood transfusion in casualties who initially seem to be hemodynamically stable ( SBP > 90 ) . Further study of this technology for use in the resuscitation of trauma patients is warranted BACKGROUND Despite normalization of vital signs , critically injured patients may remain in a state of occult underresuscitation that sets the stage for sepsis , organ failure , and death . A continuous , sensitive , and accurate measure of resuscitation after injury remains elusive . METHODS In this pilot study , we evaluated the ability of two continuous measures of peripheral tissue oxygenation in their ability to detect hypoperfusion : the Licox polarographic tissue oxygen monitor ( PmO2 ) and the InSpectra near-infrared spectrometer ( StO2 ) . We hypothesized that deltoid muscle tissue oxygenation measurements could detect patients in " occult shock " who are at increased risk for post-injury complications . The study was design ed to ( 1 ) define values for PmO2 and StO2 in patients who by all st and ard measures appeared to be clinical ly resuscitated ; ( 2 ) evaluate the relationship between PmO2 , StO2 and other physiologic variables including mean arterial pressure ( MAP ) , lactate and base deficit ( BD ) ; and ( 3 ) examine the relationship between early low tissue oxygen values and the subsequent development of infections and organ dysfunction . Licox probes were inserted into the deltoid muscle of critically injured patients after initial surgical and radiologic interventions , and transcutaneous StO2 monitors were applied over the same muscle bed . PmO2 , StO2 , and st and ard physiologic data were collected continuously using a multimodal bioinformatics system . RESULTS Twenty-eight critically injured patients were enrolled in this study at admission to the intensive care unit ( ICU ) . For patients who appeared to be well resuscitated ( defined as MAP > or = 70 mm Hg , heart rate [ HR ] < or = 110 bpm , BD > or = -2 , and partial pressure of arterial oxygen ( PaO2 ) = 80 and 150 mm Hg ) , the mean PmO2 was 34 + /- 11 mm Hg and StO2 was 63 + /- 27 % . There was a strong relationship between PmO2 and BD ( p < 0.001 ) but no significant relationship between StO2 and BD . The relationship between PmO2 and StO2 was weak but statistically significant . Early low values of both PmO2 and StO2 identified patients at risk for infectious complications or multiple organ failure ( MOF ) . In patients who were well resuscitated by st and ard continuous parameters ( HR and MAP ) , low PmO2 during the first 24 hours after admission ( PmO2 < or = 25 for at least 2 hours ) was strongly associated with the development of infectious complications ( Odds Ratio = 16.5 , 95 % CI 1.49 to 183 , p = 0.02 ) . CONCLUSIONS PmO2 is a responsive , reliable and continuous monitor of changes in base deficit . Initial low values for either PmO2 or StO2 were associated with post-injury complications . PmO2 monitoring may be useful in identifying patients in the state of occult underresuscitation who remain at risk for developing infection and MOF Objectives To determine the derangement of muscle tissue oxygen saturation ( StO2 ) in the early phase of emergency department ( ED ) sepsis management and its relationship to 30-day mortality in patients with severe sepsis or septic shock . Methods A prospect i ve cohort study conducted in the ED of a university hospital . Patients were included if they had a clinical diagnosis of severe sepsis or septic shock . Thenar muscle tissue StO2 on arrival in the ED and its change with usual ED sepsis management was measured using near-infrared spectroscopy . A follow-up measurement was obtained after 24 h of treatment . All patients were followed for 30 days . Results 49 patients were included , of which 24 ( 49 % ) died . There was no difference in mean StO2 on arrival in the ED between survivors and non-survivors ( 72 % vs 72 % ; p=0.97 ) . Following ED treatment the mean StO2 of survivors improved significantly to 78 % ( p<0.05 ) while StO2 remained persistently low in non-survivors ( p=0.94 ) . Persistently low StO2 ( < 75 % ) despite initial resuscitative treatment was associated with a twofold increase in mortality ( RR of death 2.1 % ; 95 % CI 1.2 % to 3.5 % ) . Conclusion Patients with severe sepsis/septic shock have abnormal muscle tissue StO2 upon arrival in the ED . Inability to normalise StO2 with ED sepsis management is associated with a poor outcome . The role of StO2 as an early prognostic and potential therapeutic biomarker in severe sepsis or septic shock warrants further exploration Free flap monitoring is essential to the early detection of compromise thereby increasing the chance of successful salvage surgery . Many alternatives to classical clinical monitoring have been proposed . This study seeks to investigate a relatively new monitoring technology : near infrared spectroscopy ( NIRS ) . Patients were recruited prospect ively to the study from a single center . During the research period , 10 patients underwent reconstruction with a free deep inferior epigastric perforator flap ( DIEP ) . Measurements of flap perfusion were taken using NIRS in the preoperative and intraoperative phases and postoperatively for 72 hours . NIRS showed characteristic changes in all cases which returned to theater for pedicle compromise . In these cases , NIRS identified pedicle compromise prior to clinical identification . There were no false-positives . NIRS accurately identified all compromised flaps in our study . In most cases , there was an evidence of changes in oxygen saturation on NIRS prior to clinical observation . Further research , ideally double blind r and omized control trials with large sample groups would be required to definitively establish NIRS as an ideal flap monitoring modality |
12,255 | 15,942,415 | No effect was found on blood pressure or cholesterol .
Psychological outcome : state anxiety was reduced , trait anxiety was not , depression was reduced .
Cardiac effects : the frequency of occurrence of angina pectoris was reduced , the occurrence of arrhythmia and exercise induced ischaemia were reduced .
Return to work was improved .
Cardiac events occurred less frequently , as well as cardiac deaths .
With the exception of resting heart rate , the effects were small , absent or not measured in studies in which abbreviated relaxation therapy was given .
No difference was found between the effects of full or exp and ed relaxation therapy .
Conclusion Intensive supervised relaxation practice enhances recovery from an ischaemic cardiac event and contributes to secondary prevention . | Aims To establish the effects of relaxation therapy on the recovery from a cardiac ischaemic event and secondary prevention . | OBJECTIVES To examine the effects of progressive muscle relaxation and guided imagery on psychological and physiologic outcomes in adults with cardiovascular disease who were participating in a phase II cardiac rehabilitation program . To examine tension levels , practice patterns , and perceived helpfulness of the intervention reported by subjects . DESIGN Prospect i ve , quasi-experimental , with r and om group assignment within sites . Independent replication and extension of a study by Bohachik ( 1984 ) . SETTING Four midwestern hospital-based phase II cardiac rehabilitation programs . PATIENTS Fifty patients who within the preceding 12 weeks had had acute myocardial infa rct ion or coronary artery bypass surgery or both , studied during 6 weeks of participation in a phase II cardiac rehabilitation program . OUTCOME MEASURES Psychological measures included state and trait anxiety scores on the State-Trait Anxiety Inventory and reported symptoms on the Symptom Checklist-90-Revised . Physiologic measures were resting heart rate and blood pressure . Subjective tension levels before and after home practice , practice patterns , and perceived helpfulness of the intervention were examined . INTERVENTION Individual instruction session in progressive muscle relaxation and guided imagery at the phase II cardiac rehabilitation program , followed by daily home practice with audiotape instructions over a 6-week period . RESULTS No statistical differences at the p < or = 0.05 level were found in state anxiety scores or reported symptoms at study exit . However , reductions in mean subscale scores for interpersonal sensitivity ( t [ 19 ] = 2.11 , p < or = 0.05 ) and depression ( t [ 19 ] = 2.07 , p < or = 0.05 ) by paired t tests were found for the relaxation group ( RG ) . The two groups differed at study exit in resting heart rate ( t [ 42 ] = -2.02 , p < or = 0.05 ) by independent t tests and in systolic blood pressure ( F [ 1,42 ] = 5.13 , p < or = 0.05 ) by analysis of covariance . The RG had a mean resting heart rate 8.6 beats/min lower than that of the control group ( CG ) and also had within-group reductions in mean heart rate ( t [ 19 ] = 2.09 , p < or = 0.05 ) by paired t tests . Contrary to expectation , the CG had a 3.5 mm Hg lower mean systolic blood pressure and within-group reductions in systolic ( t [ 22 ] = 3.02 , p < 0.01 ) and diastolic ( t [ 22 ] = 3.83 , p < 0.01 ) blood pressure by paired t tests . CG subjects had a greater number of dose increases in cardiac medications and fewer dose reductions than did RG subjects , who also had a higher number of dose reductions . RG subjects reported frequent practice of the technique , rated it as helpful , and reported lower subjective tension levels after practice . CONCLUSIONS Findings in this study did not support those of Bohachik ( who reported lowered state anxiety and fewer somatization , interpersonal sensitivity , and depression symptoms ) . More instruction sessions on the relaxation method may have result ed in more positive outcomes . However , the within-group scores for interpersonal sensitivity and depression , the reduction in heart rate , and the receptivity of subjects to this intervention suggest that it may be a feasible and helpful adjunctive therapy for participants in a phase II cardiac rehabilitation program BACKGROUND There have been six r and omized controlled trials of psychological therapy with generalized anxiety disorder ( GAD ) using DSM-III-R and DSM-IV . All have used the Trait version of the Spielberger State-Trait Anxiety Inventory ( STAI-T ) as one of several outcome measures . Each study , however , employed different methods of calculating the clinical significance of outcomes making it difficult to reach a balanced appraisal of the efficacy of psychological treatment . METHODS Raw data on STAI-T scores at pre- , post- and follow-up were obtained for each of the six studies ( total N = 404 ) . Jacobson methodology for defining clinical ly significant change ( criterion c , reliable change index = 8 , cut-off point = 46 ) was used to allocate each patient to one of four outcomes : worse , unchanged , improved and recovered . The proportion of patients in each category was calculated for treatment conditions in each study and also for aggregate data across types of treatment . RESULTS A recovery rate of 40 % was found for the sample as a whole with 12 of the 20 treatment conditions obtaining very modest recovery rates of 30 % or less . Two treatment approaches -- individual cognitive behavioural therapy and applied relaxation -- do relatively well with overall recovery rates at 6-month follow-up of 50 - 60 % . CONCLUSIONS Jacobson methodology , in distinguishing between improvement and recovery on a st and ardized measure of general vulnerability to anxiety , provides a stringent but clinical ly more meaningful evaluation of the efficacy of psychological therapies with GAD than has been available hitherto . Systematic focus on either excessive worry or physiological arousal gives worthwhile results The purpose of this study was to evaluate the effect of stress management training on quality of life , functional capacity , and heart rate variability in elderly patients with New York Heart Association class I-III congestive heart failure ( CHF ) . While substantial research exists on stress management training for patients with coronary heart disease , there are few data on the value of psychosocial training on patients with CHF . Thirty-three multiethnic patients ( mean age , 66+/-9 years ) were assigned through incomplete r and omization to one of two treatment groups or a wait-listed control group . The 14 participants who completed the treatment attended eight training sessions during a 10-week period . The training consisted of 75-minute sessions adapted from the Freeze-Frame stress management program developed by the Institute of HeartMath . Subjects were assessed at baseline and again at the completion of the training . Depression , stress management , optimism , anxiety , emotional distress , and functional capacity were evaluated , as well as heart rate variability . Significant improvements ( p<0.05 ) were noted in perceived stress , emotional distress , 6-minute walk , and depression , and positive trends were noted in each of the other psychosocial measures . The 24-hour heart rate variability showed no significant changes in autonomic tone . The authors noted that CHF patients were willing study participants and their emotional coping and functional capacity were enhanced . This program offers a simple and cost-effective way to augment medical management of CHF . Given the incompleteness of CHF medical management and the exploding interest in complementary medical intervention , it seems imperative that further work in psychosocial treatment be undertaken One hundred fifty-six myocardial infa rct ion patients were r and omly assigned to either exercise plus relaxation and breathing therapy ( treatment A , n = 76 ) or to exercise training only ( treatment B , n = 80 ) . Effects on exercise testing showed a more pronounced training bradycardia and a remarkable improvement in ST abnormalities in treatment A ( p less than 0.005 ) . A model was developed to integrate the various exercise parameters into a single measure for training benefit . Approximately half the patients showed a training success , with a more positive and less negative outcome in treatment A ( p = 0.09 ) . The odds for failure were 0.25 for treatment A and 0.51 for treatment B ( odds ratio : 2.04 ; 95 % confidence interval , 0.94 to 4.6 ) . Thus the risk of failure was reduced by half when relaxation was added to exercise training . These results indicate that exercise training is not successful in all MI patients and that relaxation therapy enhances training benefit The objective of this study was to assess the impact of group-based stress management training on emotional well-being , functional status , social activity and chest pain in cardiac patients , within a r and omized controlled trial . Fifty acute myocardial infa rct ion and 50 coronary artery bypass patients were r and omized to experimental ( 27 myocardial infa rct ion and 23 coronary artery bypass ) and control ( 23 myocardial infa rct ion and 27 coronary artery bypass ) groups 3 months after infa rct ion or surgery . Experimental patients underwent a 10-week relaxation-based stress management programme , while the controls received normal care . Following assessment at the end of the treatment period , controls were offered the stress management programme . Follow-up data were collected 6 months post-treatment from both groups . Significantly greater improvements in emotional well-being as assessed on the Hospital Anxiety and Depression scale ( P < 0.005 ) and the Psychological General Well-being Index ( P < 0.001 ) were found in the experimental than control groups , and improvements were maintained at 6 month follow-up . Greater improvements were also recorded in experimental than control groups in activities of daily living ( P < 0.005 ) , satisfaction with health ( P < 0.025 ) , reports from spouses or relatives of patients ' emotional state ( P < 0.001 ) , and in disruption due to chest pain ( P < 0.001 ) . Similar responses to stress management were observed in myocardial infa rct ion and coronary artery bypass patients . When controls underwent treatment , they too showed significant reductions in anxiety and depression , but no changes in social or functional status . We conclude that stress management training may lead to improvements in the quality of life of myocardial infa rct ion and coronary artery bypass patients . Such programmes might usefully be made available even to patients who have participated in formal rehabilitation The authors report on the influence of autogenous training on blood pressure at rest and under stress conditions in patients with coronary heart disease following coronary bypass operation . We investigated the influence of autogenous training on the microcirculation and the left ventricular ejection fraction ( LVEF ) as well . The results showed a significant decrease in blood pressure at rest and also an increase of muscle circulation F and of LVEF OBJECTIVES To determine if cardiorespiratory biofeedback increases heart rate variability ( HRV ) in patients with documented coronary artery disease ( CAD ) . BACKGROUND Diminished HRV has been associated with increased cardiac morbidity and mortality . Evidence suggests that various lifestyle changes and pharmacologic therapies can improve HRV . The objective of this study was to determine if biofeedback increases HRV in patients with CAD . METHODS Patients with established CAD ( n = 63 ; mean age , 67 years ) were r and omly assigned to conventional therapy or to 6 biofeedback sessions consisting of abdominal breath training , heart and respiratory physiologic feedback , and daily breathing practice . HRV was measured by the st and ard deviation of normal-to-normal QRS complexes ( SDNN ) at week 1 ( pretreatment ) , week 6 ( after treatment ) , and week 18 ( follow-up ) . RESULTS Baseline characteristics were similar for the treatment and control groups . The SDNN for the biofeedback and control groups did not differ at baseline or at week 6 but were significantly different at week 18 . The biofeedback group showed a significant increase in SDNN from baseline to week 6 ( P < .001 ) and to week 18 ( P = .003 ) . The control subjects had no change from baseline to week 6 ( P = .214 ) and week 18 ( P = .27 ) . CONCLUSIONS Biofeedback increases HRV in patients with CAD and therefore may be an integral tool for improving cardiac morbidity and mortality rates OBJECTIVES Autogenic training ( AT ) is a method of autosuggestion with some potential for reducing anxiety . This study tests whether AT lowers anxiety levels experienced by patients undergoing coronary angioplasty . METHODS Fifty-nine patients were r and omly assigned to receive regular AT or no such therapy as an adjunct to st and ard care for 5 months . The primary outcome measure was State Anxiety at 2 months . Qualitative information was generated by face-to-face interviews . RESULTS State Anxiety showed a significant intergroup difference both at 2 and 5 months . This finding was corroborated by secondary outcome measures , for example , quality of life , and by qualitative information about patients ' experiences . The results do not allow us to determine whether the observed effects are specific to AT or of a nonspecific nature . CONCLUSIONS Our results suggest that AT may have a role in reducing anxiety of patients undergoing coronary angioplasty OBJECTIVE To conduct a feasibility study on stress management for patients with heart disease ; more specifically , to test the availability of patients , determine dropout rates , and investigate the sensitivity to change of a large number of psychologic and biologic stress indexes . DESIGN R and om assignment , two-group clinical trial . SETTING Pacific Northwest university-affiliated teaching hospital . PATIENTS Forty-five patients with heart disease ( mean age 56 years ) , who either had a myocardial infa rct ion or coronary bypass surgery . OUTCOME MEASURES Hostility , subjective distress , resting electrocardiogram , resting blood pressure and blood pressure reactivity to a psychologic stressor , and blood lipid , cortisol , and catecholamine levels . INTERVENTION Patients were r and omly assigned to either ( 1 ) exercise rehabilitation ( ER ) and an 8-week stress management ( SM ) program ( ER + SM ) or ( 2 ) ER only . Although the recruitment rate was satisfactory , 67 % of patients assigned to the control condition and 40 % of the SM subjects were not available for posttesting . RESULTS Computed effect sizes indicated that blood pressure reactivity to a psychologic challenge was reduced after treatment in the ER + SM group but not in ER group . The ER + SM group showed improvement in perceived health status and had clinical ly meaningful reductions in triglyceride levels , whereas the ER group did not . The ER group had a reduction in high-density lipoproteins , whereas the high-density lipoprotein levels of the ER + SM group did not change . CONCLUSIONS Patients r and omly assigned to a control condition may be less willing to participate in time-consuming and invasive posttests than treated patients . Reducing the invasiveness of measurement may increase cost-effectiveness and reduce the dropout rate under controlled conditions . Blood pressure reactivity to a psychologic stress test and changes in serum lipid levels may be sensitive and cost-effective measures to include in future studies of cardiac rehabilitation This study examined the effects of exercise and stress management training on clinical outcomes and medical expenditures over a 5-year follow-up period in 94 male patients with established coronary artery disease ( CAD ) and evidence of ambulatory or mental stress-induced myocardial ischemia . Patients were r and omly assigned to 4 months of aerobic exercise 3 times per week or to a 1.5-hour weekly class on stress management ; patients who lived too far from Duke to participate in the weekly treatments formed the usual care control group . Follow-up was performed at the end of treatment and annually thereafter for 5 years . Stress management was associated with a significant reduction in clinical CAD events relative to usual care over each of the first 2 years of follow-up and after 5 years . Economic analyses revealed that stress management was associated with lower medical costs than usual care and exercise in the first 2 years , and that the cumulative cost over 5 years was also lower for stress management relative to usual care . These results suggest that there may be clinical and economic benefit to offering the type of preventive stress management and exercise interventions provided to patients with myocardial ischemia . Moreover , these findings suggest that the financial benefits that accrue from an appropriately targeted intervention may be substantial and immediate BACKGROUND Previous studies have demonstrated that myocardial ischemia can be elicited by mental stress in the laboratory and during daily life and that ischemia induced by mental stress is associated with an increased risk for future cardiac events in patients with coronary artery disease . OBJECTIVES To examine the extent to which ischemia induced by mental stress can be modified by exercise stress management , and to evaluate the impact of these interventions on clinical outcomes . METHODS One hundred seven patients with coronary artery disease and ischemia documented during mental stress testing or ambulatory electrocardiographic monitoring were r and omly assigned to a 4-month program of exercise or stress management training . Patients living at a distance from the facility formed a nonr and om , usual care comparison group . Myocardial ischemia was reassessed following treatment , and patients were contacted annually for as long as 5 years to document cardiac events , including death , nonfatal myocardial infa rct ion , and cardiac revascularization procedures . RESULTS Twenty-two patients ( 21 % ) experienced at least 1 cardiac event during a mean ( + /- SD ) follow-up period of 38 + /- 17 months . Stress management was associated with a relative risk of 0.26 compared with controls . The relative risk for the exercise group also was lower than that of controls , but the effect did not reach statistical significance . Stress management also was associated with reduced ischemia induced by mental stress and ambulatory ischemia . CONCLUSION These data suggest that behavioral interventions offer additional benefit over and above usual medical care in cardiac patients with evidence of myocardial ischemia BACKGROUND Although psychosocial therapy has been shown to reduce mortality after myocardial infa rct ion , it is unknown whether the benefits of psychosocial therapy on mortality reduction extend to out-of-hospital sudden cardiac arrest , a main cause of cardiovascular mortality . OBJECTIVE Describe efficacy of psychosocial therapy on two-year cardiovascular mortality in sudden cardiac arrest survivors . METHOD Survivors of out-of-hospital ventricular fibrillation or asystole ( N = 129 ) , documented by electrocardiograms from registries of a citywide Medic One unit and two countywide emergency units , were r and omized into a two group , experimental , longitudinal design . The intervention consisted of 11 individual sessions , implementing three components : physiologic relaxation with biofeedback training focused on altering autonomic tone ; cognitive behavioral therapy aim ed at self-management and coping strategies for depression , anxiety , and anger ; and cardiovascular health education . The primary outcome measure was cardiovascular mortality . RESULTS Risk of cardiovascular death was significantly reduced 86 % by psychosocial therapy , p = .03 . Six of the seven cardiovascular deaths in the control group were caused by ventricular arrhythmias . The cardiovascular death in the therapy group was due to stroke . Controlling for depression , previous myocardial infa rct ion , low ejection fraction , decreased heart rate variability , and ventricular ectopic beats had little impact on estimated treatment effect . The risk of all-cause mortality was reduced by 62 % in the therapy group , p = .13 . There were a total of three deaths in the therapy group and eight deaths in the control group . CONCLUSIONS Psychosocial therapy significantly reduced the risk of cardiovascular death in sudden cardiac arrest survivors Restenosis after successful percutaneous coronary angioplasty ( PTCA ) is a major problem because it occurs in 25 % to 35 % of all patients . Because psychological factors , especially anger and vital exhaustion , have been found to increase the risk of new cardiac events after PTCA , a behavioral intervention might contribute to the reduction of the risk of restenosis . To investigate the operational and method ological aspects of a behavioral intervention , and to estimate the effect size of the risk reduction , we did a feasibility study of angioplasty patients who remained exhausted after PTCA . Breathing therapy was used as the main method for intervention . Thirty patients who participated in the intervention program and 65 controls were followed during an average period of 16 and 18 months , respectively . It was observed that the intervention result ed in a significant decrease of the mean exhaustion scores and reduced the risk of a new coronary event ( cardiac death , coronary artery bypass grafting , myocardial infa rct ion , rePTCA , restenosis ) by 50 % ( chi = 2.19 ; p = 0.13 ) . These results indicate that a clinical trial to test the hypothesis that a reduction of vital exhaustion and hostility reduces the risk of a new cardiac event after PTCA , is feasible and merits the efforts required Twenty-one patients with documented coronary artery disease were tested at baseline by exercise tolerance testing , and assigned to either stress reduction using the Transcendental Meditation ( TM ) program or to a wait-list control , After 8 months , the TM group had a 14.7 % increase in exercise tolerance , an 11.7 % increase in maximal workload , an 18 % delay in onset of ST-segment depression , and significant reductions in rate-pressure product at 3 and 6 minutes , and at maximal exercise compared with the control group |
12,256 | 24,105,444 | There were no significant differences between groups for other outcomes including duration of the second stage of labour , or other outcomes related to the well being of mothers and babies .
AUTHORS ' CONCLUSIONS There is clear and important evidence that walking and upright positions in the first stage of labour reduces the duration of labour , the risk of caesarean birth , the need for epidural , and does not seem to be associated with increased intervention or negative effects on mothers ' and babies ' well being . | BACKGROUND It is more common for women in both high- and low-income countries giving birth in health facilities , to labour in bed .
There is no evidence that this is associated with any advantage for women or babies , although it may be more convenient for staff .
Observational studies have suggested that if women lie on their backs during labour this may have adverse effects on uterine contractions and impede progress in labour , and in some women reduce placental blood flow .
OBJECTIVES To assess the effects of encouraging women to assume different upright positions ( including walking , sitting , st and ing and kneeling ) versus recumbent positions ( supine , semi-recumbent and lateral ) for women in the first stage of labour on duration of labour , type of birth and other important outcomes for mothers and babies . | The purpose of this study was to determine whether women in labor report less pain when they are in a vertical ( sitting or st and ing ) position than in a horizontal ( side-lying or supine ) position . Pain scores were obtained from 60 women in early labor ( dilation 2 - 5 cm ) who alternated between the two positions . The results show that about 35 % of women feel less front pain and 50 % feel less back pain when they are in a vertical position than in a horizontal position . The decrease in continuous back pain ( 83 % ) was particularly impressive , but the front and back pains associated with contractions were significantly diminished as well . These results , taken together with those of earlier studies , indicate that many women in early labor have less pain and are generally more comfortable in a vertical than in a horizontal position . Since early labor comprises a substantial proportion of the entire process of labor and delivery , any simple procedure which alleviates pain without danger to mother or child , such as shifting from a horizontal to a vertical position , should be promoted and employed There has been a relatively recent interest in alternative birthing techniques , including increased maternal mobility during labor . This literature review was pursued to evaluate the effect of upright maternal posture and ambulation on the first stage of labor . Although previous review s frequently assume that maternal ambulation speeds labor progress , the data presented in this review are not conclusive as to whether the upright maternal posture or ambulation during the first stage of labor shortens labor length or improves fetal outcome . However , it is clear that ambulation in labor is not harmful either to the mother or fetus . In addition , many investigators have reported that mobility in labor results in greater maternal comfort and ability to tolerate labor and decreased use of anesthesia and analgesia . Thus , acceptance of mobility in labor by patients and staff is generally reported . This information can serve as a guide to clinical management . However , there is a need for further analysis of the effect of maternal ambulation during labor , and specific suggestions for research are presented The cl aim that an upright maternal posture during labour improves the efficiency of the uterus to the benefit of both mother and fetus has been investigated in a r and omised prospect i ve study . 40 patients undergoing induction of labour were allocated to a recumbent group or an upright group . No differences were found between the groups in the length of labour , mode of delivery , requirements of oxytocic and analgesic drugs , or fetal and neonatal condition . Our data do not support calls to change conventional intrapartum nursing attitudes OBJECTIVE Our purpose was to test the hypothesis that the supine versus the lateral position is associated with a greater decrement in cardiac output after epidural analgesia in labor . STUDY DESIGN Twenty-one normal term subjects were r and omized to the left lateral or supine position in early labor . Cardiac output measured by the acetylene rebreathing method , stroke volume , heart rate , mean arterial pressure , and systemic vascular resistance were obtained at 5-minute intervals , beginning before a 500 ml intravenous fluid bolus ( baseline ) and ending 45 minutes after epidural injection . RESULTS Mean baseline supine versus lateral group differences were significant for 21 % lower cardiac output , 21 % lower stroke volume , 19 % higher mean arterial pressure , 50 % higher systemic vascular resistance , and equivalent heart rate . In the supine group fluid bolus result ed in significantly increased cardiac output and stroke volume , decreased mean arterial pressure and systemic vascular resistance , and unchanged heart rate . In the supine group cardiac output and stroke volume decreased significantly after epidural injection . The lateral position group exhibited no hemodynamic alterations after fluid bolus or epidural . CONCLUSIONS In contrast to the lateral position , the supine position is associated with a significant postepidural decrement in cardiac output , not identified by a change in heart rate . This likely reflects an inability to maintain stable preload volume in the supine position BACKGROUND Childbirth is an important life event for which a positive experience is important to many women . METHODS As secondary outcomes from the r and omised controlled Comparative Obstetric Mobile Epidural Trial , various aspects of satisfaction were assessed in women who had one of three types of regional analgesia ( two of which were low-dose techniques and a high-dose control using 0.25 % epidural bupivacaine ) and a comparison group who did not have epidural analgesia , shortly after delivery and 12 months later . RESULTS The predominant finding was satisfaction with spontaneous vaginal delivery whatever the mode of analgesia . The overall immediate and long-term satisfaction was similar for all three neuraxial techniques . Satisfaction with the speed of pain relief and the amount of mobility were significantly greater for the combined spinal-epidural technique compared with the low-dose infusion ( P<0.001 ) . The degree of control felt by women who had combined spinal-epidural analgesia was greater than with the high-dose ( P<0.05 ) . Women in the non-epidural comparison group did not report a greater feeling of control . Among those who delivered spontaneously , more women in the combined spinal-epidural group ( 30 % ) felt in full control compared with the high-dose group ( 17 % ) ( P<0.05 ) . By comparison 22 % in the low-dose infusion group and only 15 % who had no epidural felt in full control . CONCLUSIONS Whilst satisfaction with the experience of childbirth appears intimately related to the attainment of a spontaneous delivery , mobile epidurals enhance women 's feeling of control in labour and are popular for future choice of regional analgesia Telemetry and conventional cardiotocography were compared by monitoring the labor of 60 patients with an uneventful pregnancy and delivery in the 38th-42nd week of pregnancy . 31 patients were monitored by telemetry and 29 by cardiotocography . The patients were matched for age ( + /- 5 years ) , duration of pregnancy ( + /- 7 days ) and parity ( I or II ) . The husb and attended labor and delivery in 42 % of the cases in the telemetry group and in 59 % of the cases in the control group . Induction of labor by amniotomy was performed in 32 % of the cases in the telemetry group and in 24 % of the cases in the cardiotocography group . The patients monitored subjective pain every half hour during the opening phase . The telemetric patients were encouraged to sit or walk during the first stage . No maternal or fetal complications occurred . All infants were born in good condition with APGAR scores greater than or equal to 7 recorded at one and five minutes . There were 4 operative deliveries in the telemetry group and 5 in the control group . Indications for these were maternal or uterine exhaustion with the exception of two control patients where fetal asphyxia was suspected . The duration of the first stage of labor did not differ significantly between the telemetry and the cardiotocography groups . The telemetric patients received less analgesics than the controls but this difference was not significant . In spite of less analgesia in the telemetry group , the secondparas of the telemetry group experienced significantly less ( p less than 0.01 ) labor pain than the controls . In addition , the secondparas of the telemetry group considered the present labor less painful than the previous one significantly more often than the controls . Among the primiparous patients there was no difference in the amount of pain experienced by the patients Our purpose was to study the feasibility and results of encouraging ambulation during the first stage of labor in routine obstetric practice . Six-hundred and thirty low risk mothers with intact membranes were r and omized into an ambulant and a control group . The results in the ambulant group were not better than in the control group . Our study suggests that , in principle ambulation may be beneficial , but that the concomitant changes in practice should be different from those in our study A prospect i ve study of 300 consecutive deliveries has been made to assess the benefits and acceptability of ambulation during spontaneous labour . Ambulation during the first stage occurred in 48 patients with 55 non‐ambulant patients acting as controls . No difference in the length of first or second stage , incidence of fetal distress or mode of delivery was observed . In spite of the lack of apparent advantage to the fetal condition , ambulation was acceptable to both patients and nursing staff and should not be discouraged Objectives To determine whether snoring , sleep position , and other sleep practice s in pregnant women are associated with risk of late stillbirth . Design Prospect i ve population based case-control study . Setting Auckl and , New Zeal and Participants Cases : 155 women with a singleton late stillbirth ( ≥28 weeks ’ gestation ) without congenital abnormality born between July 2006 and June 2009 and booked to deliver in Auckl and . Controls : 310 women with single ongoing pregnancies and gestation matched to that at which the stillbirth occurred . Multivariable logistic regression adjusted for known confounding factors . Main outcome measure Maternal snoring , daytime sleepiness ( measured with the Epworth sleepiness scale ) , and sleep position at the time of going to sleep and on waking ( left side , right side , back , and other ) . Results The prevalence of late stillbirth in this study was 3.09/1000 births . No relation was found between snoring or daytime sleepiness and risk of late stillbirth . However , women who slept on their back or on their right side on the previous night ( before stillbirth or interview ) were more likely to experience a late stillbirth compared with women who slept on their left side ( adjusted odds ratio for back sleeping 2.54 ( 95 % CI 1.04 to 6.18 ) , and for right side sleeping 1.74 ( 0.98 to 3.01 ) ) . The absolute risk of late stillbirth for women who went to sleep on their left was 1.96/1000 and was 3.93/1000 for women who did not go to sleep on their left . Women who got up to go to the toilet once or less on the last night were more likely to experience a late stillbirth compared with women who got up more frequently ( adjusted odds ratio 2.28 ( 1.40 to 3.71 ) ) . Women who regularly slept during the day in the previous month were also more likely to experience a late stillbirth than those who did not ( 2.04 ( 1.26 to 3.27 ) ) . Conclusions This is the first study to report maternal sleep related practice s as risk factors for stillbirth , and these findings require urgent confirmation in further studies An investigation was conducted on the maintenance of control in labor , using a 28-item revised Labor Agentry Scale with an estimated reliability of .98 . Thirty low-risk subjects who had attended prenatal classes were r and omly allocated during labor to either the control group , which received st and ard electronic fetal monitoring , or the experimental group , which received radiotelemetric fetal monitoring . Significant differences ( The purpose of this study was to determine if women who assumed upright positions during the phase of maximum slope would have a shorter phase of maximum slope in their labor and experience more comfort than women who assumed recumbent positions . Forty laboring women were r and omly assigned to either an upright or recumbent position group . Subjects assumed the positions of their assigned group during the phase of maximum slope in their labor ( cervical dilatation from 4 cm to 9 cm ) . Every hour during the phase of maximum slope , each subject was examined vaginally to determine her cervical dilatation and assessed for her level of comfort using the Maternal Comfort Assessment Tool . Women in the upright position group had a significantly shorter phase of maximum slope in labor , but did not significantly differ in comfort level from women in the recumbent group . Newborn Apgar scores were not significantly different between the two groups . Nurses need to be aware that the upright labor positions have the distinct advantages of facilitating efficient uterine contractions and reducing the duration of the phase of maximum slope in labor , with no increase in the discomfort experienced or adverse effect on newborn well-being Background Ambulatory epidural analgesia ( AEA ) is a popular choice for labor analgesia because ambulation reportedly increases maternal comfort , increases the intensity of uterine contractions , avoids inferior vena cava compression , facilitates fetal head descent , and relaxes the pelvic musculature , all of which can shorten labor . However , the preponderance of evidence suggests that ambulation during labor is not associated with these benefits . The purpose of this study is to determine whether ambulation with AEA decreases labor duration from the time of epidural insertion to complete cervical dilatation . Methods In this prospect i ve , r and omized study , 160 nulliparous women with AEA were r and omly assigned to one of two groups : AEA with ambulation and AEA without ambulation . AEA blocks were initiated with 15–20 ml ropivacaine ( 0.07 % ) plus 100 & mgr;g fentanyl , followed by a continuous infusion of 0.07 % ropivacaine plus 2 & mgr;g/ml fentanyl at 15–20 ml/h . Maternal measured variables included ambulation time , time from epidural insertion to complete dilatation , stage II duration , pain Visual Analogue Scale scores , and mode of delivery . APGAR scores were recorded at 1 and 5 min . Results are expressed as mean ± SD or median and analyzed using the t test , chi-square , or the Mann – Whitney test at P ≤ 0.05 . Results The ambulatory group walked 25.0 ± 23.3 min , sat upright 40.3 ± 29.7 min , or both . Time from epidural insertion to complete dilatation was 240.9 ± 146.1 min in the ambulatory group and 211.9 ± 133.9 min in the nonambulatory group ( P = 0.206 ) . Conclusion Ambulatory epidural analgesia with walking or sitting does not shorten labor duration from the time of epidural insertion to complete cervical dilatation BACKGROUND Dense perineal block from epidural analgesia increases the risk of urinary catheterization in labour . Mobile epidurals using low-dose local anaesthetic in combination with opioid preserve maternal mobility and may reduce the risk of bladder dysfunction . We conducted a three-arm r and omized controlled trial to compare high-dose epidural pain relief with two mobile epidural techniques . METHODS A total of 1054 primparous women were r and omized to receive high-dose bupivacaine , epidural analgesia ( Control ) , combined spinal epidural ( CSE ) , or low-dose infusion ( LDI ) . The requirement for urinary catheterization during labour and postpartum was recorded . Both end points were pre-specified secondary trial outcomes . Women were evaluated by postnatal interview , when their bladder function had returned to normal . RESULTS Relative to Control , more women who received mobile epidural techniques maintained the ability to void urine spontaneously at any time ( Control 11 % , CSE 31 % and LDI 32 % ) and throughout labour ( Control 3.7 % , CSE 13 % and LDI 14 % ) , for both mobile techniques P<0.01 . There was no difference in the requirement for catheterization after delivery . Women in the CSE group reported a more rapid return of normal voiding sensation , relative to high-dose Control ( P=0.02 ) . CONCLUSIONS Relative to conventional high-dose block , mobile epidural techniques encourage the retention of normal bladder function and reduce the risk of urinary catheterization in labour We compared breastfeeding initiation and duration in 1054 nulliaparae r and omised to bupivacaine Control epidural , Combined Spinal Epidural or Low Dose Infusion and 351 matched non‐epidural comparisons . Women were interviewed after delivery and completed a postal question naire at 12 months . Regression analysis determined factors which independently predicted breastfeeding initiation . Breastfeeding duration was subjected to Kaplan – Meier analysis . A similar proportion of women in each epidural group initiated breastfeeding . Women with no epidural did not report a higher initiation rate relative to epidural groups and those who received pethidine reported a lower initiation rate than control epidural ( p = 0.002 ) . Older age groups ( p < 0.001 ) and non‐white ethnicity ( p < 0.026 ) were predictive of breastfeeding . Epidural fentanyl dose , delivery mode and trial group were not predictive . Mean duration for breastfeeding was similar across epidural groups ( Control 13.3 , Combined Spinal Epidural 15.5 , Low Dose Infusion 15.0 weeks ) . Our data do not support an effect of epidural fentanyl on breastfeeding initiation Background The authors recently showed that “ mobile ” epidural analgesia , using low-dose local anesthetic-opioid mixtures , reduces the impact of epidural analgesia on instrumental vaginal delivery , relative to a traditional technique . The main prespecified assessment of pain relief efficacy , women 's postpartum estimates of labor pain after epidural insertion , did not differ . The detailed analgesic efficacy and the anesthetic characteristics of the techniques are reported here . Methods A total of 1,054 nulliparous women were r and omized , in labor , to receive boluses of 10 ml 0.25 % bupivacaine ( traditional ) , combined spinal-epidural ( CSE ) analgesia , or low-dose infusion ( LDI ) , the latter groups utilizing 0.1 % bupivacaine with 2 & mgr;g/ml fentanyl . Visual analog scale pain assessment s were collected throughout labor and delivery and 24 h later . Details of the conduct of epidural analgesia , drug utilization , and requirement for anesthesiologist reattendance were recorded . Results A total of 353 women were r and omized to receive traditional epidural analgesia , 351 received CSE , and 350 received LDI . CSE was associated with a more rapid onset of analgesia , lower median visual analog scale pain scores than traditional in the first hour after epidural insertion , and a significant reduction in bupivacaine dose given during labor . Pain scores reported by women receiving LDI were similar to those in the traditional group throughout labor and delivery . Anesthesiologist reattendance was low but greater with each mobile technique . Conclusions Relative to traditional epidural analgesia , LDI is at least as effective and CSE provided better pain relief in the early stages after insertion . The proven efficacy of mobile epidurals and their beneficial impact on delivery mode make them the preferred techniques for epidural pain relief in labor Published reports imply that intrapartum ambulation may improve labor . This suggests the possible efficacy of ambulation in labors requiring augmentation , provided that adequate monitoring surveillance is maintained . Fourteen patients who failed to progress in active-phase labor , and who required augmentation for " inadequate " contractions were r and omized into ambulation ( eight ) and oxytocin ( six ) groups . Internal fetal monitoring was used in all patients for 30 minute baseline and 2 hour study periods , with two-channel telemetry used in ambulating patients . Oxytocin was administered by infusion pump . Study parameters included changes in cervical dilation and station , contraction frequency , intensity and baseline tonus , and uterine activity . Labor progress was slightly but not significantly better in the ambulatory group . A mean increase in uterine activity units ( UAU ) in the ambulatory group was immediate to ranges not reached in the oxytocin group for 2 hours . Increase in Montevideo units was slightly greater in the ambulatory group during the first hour , but was exceeded by the oxytocin group during the second hour . These initial observations seem to indicate that , in terms of labor progress and initial effects on uterine activity , ambulation is as effective as oxytocin for the enhancement of labor and warrants further investigation OBJECTIVE To investigate the effect on correction of occipito-posterior ( OP ) by changing maternal posture during labor . METHODS One hundred normal primigravida with head OP position in the latent phase of labor were r and omly divided into 2 groups : Group A ( n = 50 ) , women were instructed to lay on the same lateral posture with the fetal spine during labor in order to correct the fetal position from OP to occipito anterior ( OA ) ; Group B ( n = 50 ) lay on the opposite side to the fetal spine . The OP position was diagnosed by vaginal examination or B ultrasound , and the course of labor and mode of delivery were observed . RESULTS Thirty-four women delivered vaginally ( 68 % ) in group A , with 27 of them turned to OA position ( 54 % ) ; spontaneously while they were 22 ( 44 % ) and 12 ( 24 % ) in group B respectively , a significant difference was shown ( P < 0.005 ) . The average time interval for the 1st stage was ( 13.5 + /- 6.5 ) hour and ( 17.1 + /- 7.2 ) hour for group A and B respectively , also a significant difference was noted ( P < 0.01 ) . CONCLUSION To instruct women in labor to take the lateral recumbent position with the same side of fetal spine for correcting OP to OA is an effective method . It may increase vaginal deliveries and shorten the first stage of labor , thus reduce dystocia due to OP position . This method is simple and effective , and maybe adopted in most obstetric units Ambulation during labor is becoming more popular , although its impact on the progress of labor and on pain intensity remains unclear . We wondered whether prolonged ambulation with epidural analgesia had a possible effect on duration of labor and pain . In this prospect i ve , r and omized trial , 61 parturients with uncomplicated term pregnancies were allocated to be recumbent ( n = 31 ) or to ambulate ( n = 30 ) . Epidural analgesia was provided with intermittent administrations of 0.08 % bupivacaine-epinephrine plus 1 & mgr;g/mL of sufentanil . Of the 30 women assigned to the ambulatory group , 25 actually walked . Their ambulating time was 64 ± 34 min ( mean ± sd ) , i.e. , 29 % ± 16 % of the first stage . There were no differences between the two groups in the length of labor and in pain visual analog scale scores . However , the ambulatory group received smaller doses of bupivacaine ( 6.4 ± 2.2 mg/h versus 8.4 ± 3.6 mg/h ; P = 0.01 ) and of oxytocin ( 6.0 ± 3.7 mUI/min versus 10.2 ± 8.8 mUI/min ; P < 0.05 ) . A greater ability to void was also found in the ambulatory group ( P < 0.01 ) . Although the duration of labor and pain relief was unchanged , these findings support that ambulation during labor may be advantageous OBJECTIVES Ambulatory epidural analgesia has become a common option for women in labor in France . We tested the hypothesis that a method of epidural analgesia that allowed women to walk had specific advantages regarding mode of delivery , consumption of local anesthetic , oxytocin requirement , and labor duration . METHODS Two hundred and twenty-one women with uncomplicated pregnancies who presented in spontaneous labor between 36 and 42 weeks of gestation or who were scheduled for induced labor were r and omly divided into two groups , ambulatory and non-ambulatory . All were given intermittent epidural injections of 0.1 % ropivacaine with 0.6 microg/ml sufentanil for analgesia during labor ( P<0.05 was considered significant ) . None of the women had previous cesarean delivery . RESULTS There were no significant differences between the two groups in mode of delivery , consumption of local anesthetic , or oxytocin requirement . However , a significant difference was noted in labor duration ( 173.4+/-109.9 min vs. 236.4+/-130.6 min ; P=0.001 ) . CONCLUSIONS Walking with ambulatory labor analgesia shortens labor duration but has no other effect on the progress and outcome of labor Compared to high‐dose epidurals where mobility is impossible , mobile epidurals have been shown to reduce instrumental vaginal delivery rates . The mechanism for this benefit may depend on women walking or adopting upright postures during labour . We investigated maternal motor power and ambulation of 1052 primparous women r and omised to high‐dose epidural ( Control ) , Combined Spinal Epidural ( CSE ) or Low‐Dose Infusion ( LDI ) as a pre‐specified , secondary outcome of the Comparative Obstetric Mobile Epidural Trial . Modified Bromage power scores and the level of mobility a woman actually achieved were recorded each hour after epidural placement during first and second stage , until delivery . Relative to control , significantly more women maintained normal leg power throughout labour in both mobile groups and significantly more women with CSE maintained superior leg power for longer than with LDI . Observational analysis did not demonstrate an association between the level of ambulation a woman actually achieved after epidural placement and delivery mode Summary . Conventional and telemetric monitoring of labour were compared in a r and omized study of 200 patients to assess the effect on the pattern of labour , outcome and attitude of the patients . All the telemetry patients had the option of mobility , but only 45 % elected to get out of bed , and then often only for short periods . No clear physical benefits accrued from voluntary mobility . Ambulant patients who had spontaneous deliveries had a longer second stage and more of their babies were slow to establish regular respiration . Quantitative subjective assessment s of pain , anxiety and comfort were made . Primigravidae with telemetric monitoring who chose to get out of bed had higher pain scores than primigravidae monitored conventionally , but anxiety scores were highest among primigravidae with telemetry who elected to stay in bed . There was a significant bias towards increased anxiety in the lower social classes . Primigravidae gained more reassurance from monitoring than did multigravidae , but there were no differences result ing from whether or not the recording apparatus was within the patient 's view . Multigravidae who had experienced both forms of monitoring preferred telemetry because they felt less restricted and less anxious We compared ambulation with oxytocin in the treatment of protracted labour with a r and omized , controlled trial of 57 patients . Sixty percent of the women in the ambulant group delivered their babies without oxytocin . In the ambulant group , the mean length of the second stage of labour was shorter and the women themselves held relatively positive views on their experiences . In the oxytocin group , on the other h and , the women experienced stronger contractions before pushing and also suffered from more excessively strong contractions . Our trial included too few women to judge which treatment is better for the infant 's health . Nevertheless , the women 's opinions and the quality of their contractions demonstrate that more attention should be paid to ambulation as a treatment for protracted labour Using continuous cardiotocography , the effect of maternal position on fetal heart rate ( FHR ) was studied during extradural analgesia ( EA ) with either 50 or 100 mg of etidocaine without adrenaline for labour and vaginal delivery . Of 70 healthy parturients , 39 were supine and 40 were in the lateral position . FHR was normal in all patients during the control period before EA , and remained normal during EA in 53 . Transient abnormal patterns occurred in 26 patients , 22 ( 56 % ) in the supine group and four ( 10 % ) in the lateral group , a significant difference ( P less than 0.001 ) . The decrease in arterial pressure ( AP ) did not differ between the groups , but the frequency of abnormal FHR associated with a small or moderate decrease in AP ( 30 % or less ) was greater in the supine ( 51 % ) than in the lateral group ( 3 % ) BACKGROUND Among nulliparous women , there appears to be an association between the use of epidural analgesia during labor and an increased risk of dystocia . We tested the hypothesis that combined spinal-epidural analgesia , which permits ambulation during labor , is associated with a lower incidence of dystocia than continuous lumbar epidural analgesia . METHODS Between July 1995 and September 1996 , we r and omly assigned 761 nulliparous women in spontaneous labor at term who requested epidural analgesia to receive either continuous lumbar epidural analgesia or a combination of spinal and epidural analgesia . Among the women who received combined spinal-epidural analgesia , some were discouraged from walking and others were encouraged to walk . Maternal and neonatal outcomes , the incidence of dystocia necessitating cesarean section , and measures of patients ' satisfaction were compared in the two groups . RESULTS There were no significant differences in the overall rate of cesarean section , the incidence of dystocia , the frequency of maternal or fetal complications , the patients ' or nursing staff 's assessment of the adequacy of analgesia , or the degree of overall satisfaction between the two groups . Significantly more women receiving combined spinal-epidural analgesia had pruritus ( P<0.001 ) and requested additional epidural bolus doses of local anesthetic ( P=0.01 ) . For all the women , dystocia necessitating cesarean section was significantly more likely when analgesia was administered with the fetal vertex at a negative station ( odds ratio , 2.5 ; P<0.001 ) or at less than 4 cm of cervical dilatation ( odds ratio , 2.2 ; P<0.001 ) . CONCLUSIONS As compared with continuous lumbar epidural analgesia , the combination of spinal and epidural analgesia is not associated with an overall decrease in the incidence of cesarean delivery Summary : This study was conducted at the Lokmanya Tilak Municipal General Hospital , Bombay , India during the year 1990 . The aim was to compare the routinely used supine position versus ambulation in the first stage and squatting position during the second stage of labour . Our study was comprised of 200 patients both primigravidas and multigravidas ; 100 were kept in the supine position throughout labour and 100 were kept ambulatory in the first stage and adopted the squatting position during the second stage . The study showed a shortening of both stages of labour in the squatting group but the incidence of complications was less in the control group . It was concluded that without proper birthing chairs which can give excellent perineal support , the usual supine position is preferable in our setup A r and omised study of 189 deliveries was conducted to compare performance in the conventional dorsal position with that in a birth chair . There was no significant difference in the length of the second stage of labour , the time spent bearing down , or the need for operative delivery . Overall blood-loss was greater among patients delivered in the chair but more of this group had either an intact perineum or only superficial damage . The condition of the neonates in the two delivery groups was similar BACKGROUND The evaluation of the birth position and its effects on maternal and fetal wellbeing has been a topic of perinatal research over the last decades . The aim of our observational study was to determine the effects of a modified and vertical maternal position on fetal oxygen saturation measured by pulse oximetry . METHODS Fetal oxygen saturation was measured by pulse oximetry in 56 labouring women r and omly and successively adopting the supine position in 96.4 % , the sitting position in 25.0 % , the st and ing position in 14.3 % and the prone position in 12.5 % . The statistical analysis addressed the integrated 10 minutes period of SpO2 registration s before versus after adopting the modified position . Furthermore the mean values and the st and ard deviation ( SD ) for the total registration periods of different birth position was calculated . RESULTS While the supine position induced a reduction in oxygen saturation , sitting and prone position were favorable for fetal oxygenation as compared to horizontal position . DISCUSSION These findings implicate a clinical benefit of the modified birth position This study was design ed to evaluate the relationship between the parturient 's position and her abdominal and lumbar ( continuous and contraction ) pain during the first stage of labor . A homogeneous group of 100 parturients was r and omly assigned to alternately assume the horizontal or the vertical position for 15-min periods . Their pain was measured at 2 - 3 , 4 - 5 , 6 - 7 , and 8 - 9 centimeters dilatation . To avoid " carry over " effect , these positions were preceded by a self-elected posture . Thus , the patient adopted ( a ) a self-elected position , ( b ) recumbent ( or erect ) , ( c ) a self-elected position , ( d ) erect ( or recumbent ) , and so on . Pain intensity was measured by the Argentine Pain Question naire 's Present Pain Intensity and the Huskisson 's visual analogue scale . Only the patients with at least one pain evaluation in both positions using both instruments were included in the study . The setting for the study was the obstetric department of a general hospital for people connected with public education ( professors , teachers , or members of school administrative staffs ) . The analysis revealed that a majority of patients felt less abdominal and lumbar pain , either continuous or due to contractions , during recumbency . The effect was more remarkable when dilation exceeded 5 centimeters and less intense during the first half of the first stage of labor BACKGROUND AND METHODS Walking during labor may reduce patients ' discomfort and improve outcomes . We conducted a r and omized trial of walking during active labor to determine whether it altered the duration of labor or other maternal or fetal outcomes . Women with uncomplicated pregnancies between 36 and 41 weeks ' gestation and in active labor were r and omly assigned either to walking or to no walking ( usual care ) . Pedometers were used to quantify walking , and the time spent walking was recorded . RESULTS Of the 536 women assigned to the walking group , 380 actually walked . Their mean ( + /-SD ) walking time was 56+/-46 minutes . There were no significant differences between the women assigned to the walking group and the 531 women assigned to the usual-care group in the duration of the first stage of labor ( 6.1 hours in both groups , P=0.83 ) , the need for labor augmentation with oxytocin ( 23 percent vs. 26 percent , P=0.25 ) , and the use of analgesia ( 84 percent vs. 86 percent , P=0.59 ) . Similarly , the percentages of women requiring delivery by forceps ( 4 percent vs. 3 percent , P=0.35 ) and cesarean section ( 4 percent vs. 6 percent , P=0.25 ) were not significantly different . These labor and delivery outcomes were unrelated to walking in both nulliparous and parous women . The infants ' outcomes were also similar in the two study groups . CONCLUSIONS Walking neither enhanced nor impaired active labor and was not harmful to the mothers or their infants |
12,257 | 30,157,006 | The review yielded strong evidence for psychoeducation and occupation‐ and cognitive‐based interventions , moderate evidence for skills‐based interventions , and limited evidence for technology‐supported interventions .
NA ; Effective occupational therapy interventions help people with SMI to engage in everyday living activities , leisure , social participation , and rest and sleep | This systematic review evaluates the evidence for the effectiveness of interventions within the scope of occupational therapy to improve and maintain performance and participation for people with serious mental illness . | The majority of clinical trials of cognitive-behavioral therapy ( CBT ) for schizophrenia have used individual therapy to target positive symptoms . Promising results have been found , however , for group CBT interventions and other treatment targets like psychosocial functioning . CBT for functioning in schizophrenia is based on a cognitive model of functional outcome in schizophrenia that incorporates dysfunctional attitudes ( eg , social disinterest , defeatist performance beliefs ) as mediators between neurocognitive impairment and functional outcome . In this report , 18 clinical trials of CBT for schizophrenia that included measures of psychosocial functioning were review ed , and two-thirds showed improvements in functioning in CBT . The cognitive model of functional outcome was also tested by examining the relationship between social disinterest attitudes and functional outcome in 79 people with schizophrenia r and omized to either group cognitive-behavioral social skills training or a goal -focused supportive contact intervention . Consistent with the cognitive model , lower social disinterest attitudes at baseline and greater reduction in social disinterest during group therapy predicted better functional outcome at end of treatment for both groups . However , the groups did not differ significantly with regard to overall change in social disinterest attitudes during treatment , suggesting that nonspecific social interactions during group therapy can lead to changes in social disinterest , regardless of whether these attitudes are directly targeted by cognitive therapy interventions OBJECTIVE This study evaluated the effects of the illness management and recovery program on mental illness and functional outcomes of persons with serious mental illness who were receiving supportive housing services . METHODS A r and omized controlled trial was conducted with 104 persons with serious mental illness who were assigned either to illness management classes for six months or to a waitlist control group , with follow-up assessment s conducted six months posttreatment . Assessment s included self-reports , nonblinded clinical ratings , and blinded interview ratings and included the domains of illness management , symptoms , psychosocial functioning , hospitalizations , and substance abuse and dependence . RESULTS Participants assigned to the program showed significantly greater improvements than the control group in self-reported and clinician ratings of illness management , interview-based ratings of symptoms on the Brief Psychiatric Rating Scale , and interview-based ratings of psychosocial functioning on the abbreviated Quality of Life Scale . Participants in both groups improved in self-ratings of symptom distress and had low rates of hospitalization and substance abuse over the course of the study . CONCLUSIONS The results suggest that the program was effective at improving illness management and functional outcomes for persons with serious mental illness who were receiving supportive housing services OBJECTIVE This study examined the effectiveness of an Internet parenting education and support intervention among mothers with a serious mental illness ( SMI ) . METHODS Sixty mothers diagnosed with a schizophrenia spectrum or mood disorder who had primary /shared custody for a child 18 or younger were enrolled in a r and omized controlled trial ( RCT ) with two conditions . The experimental condition involved participation in the online parental education course and a listserv co-moderated by a parent with a mental illness and a mental health professional . The control condition involved participation in online education healthy lifestyle course . St and ardized measures were used at baseline and 3 months to assess outcomes . Using an intent-to-treat approach , group differences over time were assessed using a two-tailed independent sample t test on all dependent variables , including parental efficacy , skills , coping , support , and stress . RESULTS Participation in an online parenting intervention for mothers with a SMI enhanced parenting and coping skills , and decreased parental stress . No support was found for improved efficacy or support . CONCLUSION This RCT establishes that mothers with a SMI are interested in and capable of receiving online parenting education and support . Findings demonstrate that an online parenting intervention can improve parenting and coping skills and decrease parental stress Objectives : To investigate the effectiveness of a long established intervention , occupational therapy for people with psychotic conditions , and to inform future research design s. Design : A pilot r and omized controlled trial . Setting : Two community mental health teams in a UK city . Participants : Forty-four adults with schizophrenia or other psychotic conditions , and functional problems . Interventions : Twelve months of individualized occupational therapy in community setting s , as an adjunct to usual care and compared to treatment as usual . A two to one r and omization ratio was used in favour of occupational therapy . Outcome measures : Social Functioning Scale , Scale for the Assessment of Negative Symptoms and employment . Results : Both groups ' scores on Social Functioning Scale and Scale for the Assessment of Negative Symptoms showed significant improvement over 12 months . The Social Functioning Scale overall mean difference for occupational therapy was 2.33 , P=0.020 and for treatment as usual was 6.17 , P=0.023 . The Scale for the Assessment of Negative Symptoms total mean difference for occupational therapy was -16.25 , P<0.001 and for treatment as usual was -17.36 , P= 0.011 . There were no differences between the two groups on any of the outcome measures . After 12 months the occupational therapy group showed clinical ly significant improvements that were not apparent in the control group . These were in four subscales of the Social Functioning Scale : relationships , independence performance , independence competence and recreation . Out of 30 people receiving occupational therapy those with a clinical level of negative symptoms reduced from 18 ( 64 % ) to 13 ( 46 % ) , P=0.055 . Conclusion : This pilot study suggested that individualized occupational therapy may contribute to recovery but more focus is recommended on people 's cognitive abilities and employment BAKGROUND To investigate the efficacy of the " Life Adaptation Skills Training ( LAST ) " program for persons with depression . METHODS Sixty-eight subjects with depressive disorder were recruited from psychiatric outpatient clinics in Taipei city and were r and omly assigned to either an intervention group ( N=33 ) , or a control group ( N=35 ) . The intervention group received 24-sessions of the LAST program , as well as phone contact mainly related to support for a total of 24 times . The control group only received phone contact 24 times . The primary outcome measure utilized was the World Health Organization Quality of Life-BREF-Taiwan version . Secondary outcome measures included the Occupational self- assessment , the Mastery scale , the Social support question naire , the Beck anxiety inventory , the Beck depression inventory-II , and the Beck scale for suicide ideation . The mixed-effects linear model was applied to analyze the incremental efficacy of the LAST program , and the partial eta squared ( ηp(2 ) ) was used to examine the within- and between- group effect size . RESULTS The subjects who participated in the LAST program showed significant incremental improvements with moderate to large between-group effect sizes on their level of anxiety ( -5.45±2.34 , p<0.05 ; ηp(2)=0.083 ) and level of suicidal ideation ( -3.09±1.11 , p<0.01 ; ηp(2)=0.157 ) when compared to the control group . The reduction of suicidal ideations had a maintenance effect for three months after the end of intervention ( -3.44±1.09 , p<0.01 ) , with moderate between-group effect sizes ( ηp(2)=0.101 ) . Both groups showed significant improvement on overall QOL , overall health , physical QOL , psychological QOL , level of anxiety , and level of depression . The within-group effect sizes achieved large effects in the intervention group ( ηp(2)=0.328 - 0.544 ) , and were larger than that of the control group . LIMITATIONS A small sample size in the study , a high dropout rate , lower compliance rates for the intervention group , and lacking of true control group . CONCLUSIONS The occupation-based LAST program , which focuses on lifestyle rearrangement and coping skills enhancement , could significantly improve the level of anxiety and suicidal ideations for persons with depression BACKGROUND Social cognition difficulties in schizophrenia are seen as a barrier to recovery . Intervention tackling problems in this domain have the potential to facilitate functioning and recovery . Social Cognition and Interaction Training ( SCIT ) is a manual-based psychological therapy design ed to improve social functioning in schizophrenia . AIMS The aim of this study is to evaluate the feasibility and acceptability of a modified version of SCIT for inpatient forensic wards . The potential benefits of the intervention were also assessed . METHOD This study is a r and omized single blind controlled design , with participants r and omized to receive SCIT ( N = 21 ) or treatment as usual ( TAU ; N = 15 ) . SCIT consisted of 8-week therapy sessions twice per week . Participants were assessed at week 0 and one week after the intervention on measures of social cognition . Feasibility was assessed through group attendance and attrition . Participant acceptability and outcome was evaluated through post-group satisfaction and achievement of social goals . RESULTS The intervention was well received by all participants and the majority reported their confidence improved . The SCIT group showed a significant improvement in facial affect recognition compared to TAU . Almost all participants agreed they had achieved their social goal as a result of the intervention . CONCLUSIONS It is feasible to deliver SCIT in a forensic ward setting ; however , some adaptation to the protocol may need to be considered in order to accommo date for the reduced social contact within forensic wards . Practice of social cognition skills in real life may be necessary to achieve benefits to theory of mind and attributional style Sleep disturbance is a common problem associated with depression , and cognitive-behavioral therapy ( CBT ) is a more common behavioral intervention for sleep problems . The present study compares the effect of a newly developed Chinese Chan-based intervention , namely Dejian mind-body intervention ( DMBI ) , with the CBT on improving sleep problems of patients with depression . Seventy-five participants diagnosed with major depressive disorder were r and omly assigned to receive 10 weekly sessions of CBT or DMBI , or placed on a waitlist . Measurements included ratings by psychiatrists who were blinded to the experimental design , and a st and ardized question naire on sleep quantity and quality was obtained before and after the 10-week intervention . Results indicated that both the CBT and DMBI groups demonstrated significantly reduced sleep onset latency and wake time after sleep onset ( effect size range = 0.46–1.0 , P ≤ 0.05 ) as compared to nonsignificant changes in the waitlist group ( P > 0.1 ) . Furthermore , the DMBI group , but not the CBT or waitlist groups , demonstrated significantly reduced psychiatrist ratings on overall sleep problems ( effect size = 1.0 , P = 0.00 ) and improved total sleep time ( effect size = 0.8 , P = 0.05 ) after treatment . The present findings suggest that a Chinese Chan-based mind-body intervention has positive effects on improving sleep in individuals with depression OBJECTIVE We evaluated the effects of cognitive behavioral therapy for insomnia ( CBT-I ) in in patients with a diagnosis of depression and comorbid insomnia . METHOD This study used a prospect i ve , parallel-group design . The experimental group received CBT-I for no more than 90 min once weekly for 6 weeks and the control group only have health education manuals for insomnia . The following question naires were administered at baseline : the Hamilton Rating Scale for Depression ( HAM-D ) , Dysfunctional Beliefs and Attitudes about Sleep ( DBAS ) , Presleep Arousal Scale ( PSAS ) , Sleep Hygiene Practice ( SHP ) , and Pittsburgh Sleep Quality Index . The question naires were readministered after the completion of the 6-wk CBT-I intervention and 1 month following the completion of CBT-I , to determine the effects of the CBT-I intervention over time . The analysis of Generalized Estimation Equations was identified the difference between the experimental group and the control group by controlling for the variables in BZD dose and propensity score of gender , age , and the scores for the DBAS-16 , PSAS , SHPS , and HAM-D. RESULTS Consequently , the significant difference in the PSQI scores was observed at the 1-month follow-up assessment however , no significant intergroup difference in the PSQI scores was found at the completion of the CBT-I intervention between two groups . CONCLUSIONS As a conclusion , we found that overall sleep quality significantly improved in patients who received CBT-I after we controlled for the BZD dose and propensity score , which suggests that CBT-I may represent a useful clinical strategy for improving sleep quality in patients with depression and comorbid insomnia The aim of this study was to evaluate the impact of a sailing rehabilitation program on the quality of life ( QoL ) in a sample of patients with severe mental disorders . The study adopted a r and omized , crossover , waiting-list controlled design . The participants enrolled in the study were out patients diagnosed with severe chronic mental disorders . The participants ( N=40 ) exposed to rehabilitation with sailing took part in a series of supervised cruises near the gulf of Cagliari , South Sardinia , and showed a statistically significant improvement of their quality of life compared to the control group . This improvement was comparable to the improvement in psychopathologic status and social functioning as shown in a previous report of the same research project . The improvement was maintained at follow-up only during the trial and for a few months later : after 12 months , patients returned to their baseline values and their quality of life showed a worsening trend . This is the first study to show that rehabilitation with sailing may improve the quality of life of people with severe chronic mental disorders . In all likelihood , a program grounded on learning how to manage a sailing vessel - during which patients perform cruises that emphasize the exploration of the marine environment by sailing - might be interesting enough and capture the attention of the patients so as to favour greater effectiveness of st and ard rehabilitation protocol s , but this should be specifically tested Background Current practice guidelines for schizophrenia care recommend that antipsychotic medication is essential for patients ’ long-term maintenance treatment but their non-adherence to this medication is still a main obstacle to relapse prevention . This study evaluated the effects of a motivational-interviewing-based adherence therapy for people with schizophrenia spectrum disorders . Methods This r and omised controlled trial was conducted with 134 out patients with schizophrenia spectrum disorders ; 67 of them received a six-session adherence therapy ( in addition to usual care ) and 67 received usual psychiatric care alone . Participants ’ outcome measures included symptom severity , medication adherence , hospitalisation rates , insight into illness/treatment , and functioning . Results The adherence therapy group reported significantly greater improvements in symptom severity ( p < 0.003 ) , insight into illness/treatment ( p < 0.001 ) , functioning ( p < 0.005 ) , duration of re-hospitalisations ( p < 0.005 ) , and medication adherence ( p < 0.005 ) over 18 months follow-up , when compared with usual care alone . Conclusions Motivational-interviewing-based adherence therapy can be an effective approach to treatment for people with early stage of schizophrenia who poorly adhere to medication regimen . Trial registration Clinical Trials.gov NCT01780116 , registration date January 29 , 2013 Background The benefits of Animal-Assisted Therapy ( AAT ) for humans with mental disorders have been well-documented using cats and dogs , but there is a complete lack of controlled studies using farm animals as therapeutic agents for psychiatric patients . The study was developed in the context of Green care , a concept that involves the use of farm animals , plants , gardens , or the l and scape in recreational or work-related interventions for different target groups of clients in cooperation with health authorities . The present study aim ed at examining effects of a 12-week intervention with farm animals on self-efficacy , coping ability and quality of life among adult psychiatric patients with a variety of psychiatric diagnoses . Methods The study was a r and omized controlled trial and follow-up . Ninety patients ( 59 women and 31 men ) with schizophrenia , affective disorders , anxiety , and personality disorders completed question naires to assess self-efficacy ( Generalized Self-Efficacy Scale ; GSE ) , coping ability ( Coping Strategies Scale ) , and quality of life ( Quality of Life Scale ; QOLS-N ) before , at the end of intervention , and at six months follow-up . Two-thirds of the patients ( N = 60 ) were given interventions ; the remaining served as controls . Results There was significant increase in self-efficacy in the treatment group but not in the control group from before intervention ( SB ) to six months follow-up ( SSMA ) , ( SSMA-SB ; F1,55 = 4.20 , p= 0.05 ) and from end of intervention ( SA ) to follow-up ( SSMA-SA ; F1,55 = 5.6 , p= 0.02 ) . There was significant increase in coping ability within the treatment group between before intervention and follow-up ( SSMA-SB = 2.7 , t = 2.31 , p = 0.03 ) , whereas no changes in quality of life was found . There were no significant changes in any of the variables during the intervention . Conclusion AAT with farm animals may have positive influences on self-efficacy and coping ability among psychiatric patients with long lasting psychiatric symptoms PURPOSE The study aims to assess the impact of personalized in-home nursing care plans on the degree of dependence among adult patients with schizophrenia , and on family burden . DESIGN AND METHODS This is a r and omized controlled study with 94 participants : The experimental group received a personalized in-home nursing care plan . The comparison group got a st and ard care at its mental health center . FINDINGS The pretest-posttest multivariate analysis of covariance revealed statistically significant group differences ( p = .003 ) . The help received the positive activity and the degree of independence in the experimental group improved mainly due to intervention . PRACTICE IMPLICATION S A personalized in-home nursing care plan improves the degree of independence of people diagnosed with schizophrenia living in the community and reduces the burden perceived by the family OBJECTIVE Identifying treatments to improve functioning and reduce negative symptoms in consumers with schizophrenia is of high public health significance . METHOD In this r and omized clinical trial , participants with schizophrenia or schizoaffective disorder ( N = 149 ) were r and omly assigned to cognitive behavioral social skills training ( CBSST ) or an active goal -focused supportive contact ( GFSC ) control condition . CBSST combined cognitive behavior therapy with social skills training and problem-solving training to improve functioning and negative symptoms . GFSC was weekly supportive group therapy focused on setting and achieving functioning goals . Blind raters assessed functioning ( primary outcome : Independent Living Skills Survey [ ILSS ] ) , CBSST skill knowledge , positive and negative symptoms , depression , and defeatist performance attitudes . RESULTS In mixed-effects regression models in intent-to-treat analyses , CBSST skill knowledge , functioning , amotivation/asociality negative symptoms , and defeatist performance attitudes improved significantly more in CBSST relative to GFSC . In both treatment groups , comparable improvements were also found for positive symptoms and a performance-based measure of social competence . CONCLUSIONS The results suggest CBSST is an effective treatment to improve functioning and experiential negative symptoms in consumers with schizophrenia , and both CBSST and supportive group therapy actively focused on setting and achieving functioning goals can improve social competence and reduce positive symptoms BACKGROUND Sleep disturbances are persistent residual symptoms following remission of major depressive disorder ( MDD ) and are associated with an increased risk of MDD recurrence . The purpose of the current study was to examine the effect of exercise augmentation on self-reported sleep quality in participants with non-remitted MDD . Method Participants were r and omized to receive selective serotonin reuptake inhibitor ( SSRI ) augmentation with one of two doses of exercise : 16 kilocalories per kilogram of body weight per week ( KKW ) or 4 KKW for 12 weeks . Depressive symptoms were assessed using the clinician-rated Inventory of Depressive Symptomatology ( IDS-C ) . The four sleep-related items on the IDS-C ( Sleep Onset Insomnia , Mid-Nocturnal Insomnia , Early Morning Insomnia , and Hypersomnia ) were used to assess self-reported sleep quality . RESULTS Significant decreases in total insomnia ( p < 0.0001 ) were observed , along with decreases in sleep onset , mid-nocturnal and early-morning insomnia ( p 's < 0.002 ) . Hypersomnia did not change significantly ( p = 0.38 ) . Changes in total , mid-nocturnal and early-morning insomnia were independent of changes in depressive symptoms . Higher baseline hypersomnia predicted a greater decrease in depression severity following exercise treatment ( p = 0.0057 ) . No significant moderating effect of any baseline sleep on change in depression severity was observed . There were no significant differences between exercise treatment groups on total insomnia or any individual sleep item . CONCLUSIONS Exercise augmentation result ed in improvements in self-reported sleep quality in patients with non-remitted MDD . Given the prevalence of insomnia as a residual symptom following MDD treatment and the associated risk of MDD recurrence , exercise augmentation may have an important role in the treatment of MDD Psychosocial interventions that target social cognition show promise for enhancing the functional outcomes of people with psychotic disorders . This r and omized controlled trial evaluated the efficacy and treatment- outcome specificity of a 24-session Social Cognitive Skills Training ( SCST ) that targets emotional processing , social perception , attributional bias , and mentalizing ( or Theory of Mind ) . Sixty-eight stable out patients with primary psychotic disorders were r and omly assigned to one of four time- and group format-matched treatment conditions : ( 1 ) SCST , ( 2 ) computerized neurocognitive remediation , ( 3 ) st and ard illness management skills training , or ( 4 ) a Hybrid treatment that combined elements of SCST and neurocognitive remediation . The SCST group demonstrated greater improvements over time than comparison groups in the social cognitive domain of emotional processing , including improvement on measures of facial affect perception and emotion management . There were no differential benefits among treatment conditions on neurocognitive or clinical symptom changes over time . Results indicate that a targeted social cognitive intervention led to improvements in social cognition among out patients with psychosis . Findings provide guidance for continued efforts to maximize the benefits of social cognitive interventions OBJECTIVE Social cognition and interaction training ( SCIT ) has shown promise in improving consumers ' social cognition and functioning , in both inpatient and outpatient setting s. This r and omized controlled trial examined the effectiveness of SCIT among persons with serious mental illness living in community setting s in Israel . METHODS Fifty-five participants in social-mentoring services were assigned r and omly to SCIT with social mentoring or to social mentoring only . Emotion recognition , theory of mind , attributional bias , and social functioning were assessed at baseline ( February 2010 ) and about six months later , upon completion of the intervention . RESULTS Interactions between time of measurement and group were significant for theory of mind and social engagement . Emotion recognition by the SCIT group improved significantly , but the time × group interaction for this variable was not significant . CONCLUSIONS This study provides preliminary evidence that SCIT plus social mentoring improves social cognition and functioning among persons with severe mental illness who are living in the community OBJECTIVE Most research on the Illness Management and Recovery ( IMR ) program for people with severe mental illnesses has focused on individuals with stable symptoms living in the community , with less attention to persons being treated in an inpatient setting . We evaluated the feasibility and effects of an IMR program adapted for individuals with schizophrenia who were awaiting discharge into the community . METHOD A r and omized controlled trial was conducted at 2 hospitals in Taiwan to compare the adapted IMR program with treatment as usual ( TAU ) . Ninety-seven individuals with schizophrenia were r and omized to the adapted IMR program or TAU . Four outcome indicators including illness-management knowledge , attitudes toward medication , insight , and symptoms were assessed at baseline , posttreatment , and at a 1-month follow-up following discharge from the hospital . RESULTS Participants in the adapted IMR group showed significantly greater improvements at posttreatment and 1-month follow-up in illness-management knowledge , attitudes toward medication , insight , and negative symptoms on the Brief Psychiatric Rating Scale ( BPRS ) than individuals in the TAU group . There were no significant differences between the 2 groups on other subscales of the BPRS . CONCLUSIONS AND IMPLICATION S FOR PRACTICE This is the first controlled evaluation of a version of the IMR program in an East Asian culture , and the first to evaluate it in an acute care inpatient setting . Our findings support the feasibility and potential benefits of implementing an adapted IMR program , focused on the prevention of relapses and rehospitalizations , during the discharge period of an inpatient treatment stay to prepare individuals to reenter the community OBJECTIVES To determine whether Cognitive Behavioral Social Skills Training ( CBSST ) is an effective psychosocial intervention to improve functioning in older consumers with schizophrenia , and whether defeatist performance attitudes are associated with change in functioning in CBSST . DESIGN An 18-month , single-blind , r and omized controlled trial . SETTING Outpatient clinic at a university-affiliated Veterans Affairs hospital . PARTICIPANTS Veteran and non-veteran consumers with schizophrenia or schizoaffective disorder ( N = 79 ) age 45 - 78 . INTERVENTIONS CBSST was a 36-session , weekly group therapy that combined cognitive behavior therapy with social skills training and problem-solving training to improve functioning . The comparison intervention , goal -focused supportive contact ( GFSC ) , was supportive group therapy focused on achieving functioning goals . MEASUREMENTS Blind raters assessed functioning ( primary outcome : Independent Living Skills Survey ) , CBSST skill mastery , positive and negative symptoms , depression , anxiety , defeatist attitudes , self-esteem , and life satisfaction . RESULTS Functioning trajectories over time were significantly more positive in CBSST than in GFSC , especially for participants with more severe defeatist performance attitudes . Greater improvement in defeatist attitudes was also associated with better functioning in CBSST , but not GFSC . Both treatments showed comparable significant improvements in amotivation , depression , anxiety , positive self-esteem , and life satisfaction . CONCLUSIONS CBSST is an effective treatment to improve functioning in older consumers with schizophrenia , and both CBSST and other supportive goal -focused interventions can reduce symptom distress , increase motivation and self-esteem , and improve life satisfaction . Participants with more severe defeatist performance attitudes may benefit most from cognitive behavioral interventions that target functioning . TRIAL REGISTRY Clinical Trials . Gov # NCT00237796 ( http:// clinical trials . gov/show/NCT00237796 ) Cognitive adaptation training ( CAT ) is a home-based , manualized treatment that utilizes environmental supports to improve target behaviors and functional outcomes in persons with schizophrenia . Although clinical trials have shown CAT to be effective across functional , clinical , and treatment adherence domains , when the intervention is withdrawn clients experience significant declines . The aim of the current study was to test a modified version of CAT , which decreases the duration of intensive CAT intervention while utilizing ongoing case management-supported CAT to maintain the fundamental components of the treatment . Twenty-three people participated in an outcome study of the modified version of CAT , evaluating improvements after 4months of CAT specialist intervention and after an additional 5months of case manager support . Analysis revealed significant improvements in adaptive functioning , psychiatric symptomatology , and goal attainment , which were maintained throughout case management follow-up . This suggests that an intervention that has previously demonstrated good functional outcomes in r and omized trials might sustain its impacts in an abbreviated format with support from existing case managers BACKGROUND AND AIMS Many people with schizophrenia have severe cognitive impairments that hamper their activities . The effect of pharmacological and behavioural interventions on cognitive functioning has been demonstrated , but even after successful intervention considerable impairments can remain . Therefore , we sought for alternative ways to help patients cope with the effects of their cognitive impairments . In the present study , we have evaluated the efficacy of short message service ( SMS ) text messages to compensate for the effects of cognitive impairments in schizophrenia in daily life . DESIGN A waiting list controlled trial was conducted : patients were quasi-r and omly assigned to an A-B-A ( baseline-intervention-follow-up ) condition or an A-A-B-A condition that included an additional 7-week waiting list . The waiting list was included to control for the effect of time on relevant outcome . METHOD Sixty-two people with schizophrenia or related psychotic disorders were included in the study . All patients showed impaired goal -directed behaviour in daily life-situations . Patients were prompted with SMS text messages to improve their everyday functioning . The primary outcome measure was the percentage of goals achieved . RESULTS The overall percentage of goals achieved increased with prompting , while performance dropped to baseline level after withdrawing the prompts . Keeping appointments with mental health workers and carrying out leisure activities increased with prompting , while medication adherence and attendance at training sessions remained unchanged . A majority of the patients enjoyed receiving the SMS text messages . DISCUSSION Prompting can significantly improve achievement of a number of relevant goals . For other goals , combining prompting with interventions that enhance motivation seems indicated OBJECTIVES The efficacy of cognitive behaviour therapies for psychosis ( CBTp ) has been sufficiently established for its inclusion in some national treatment guidelines . However , treatment efficacy does not guarantee effectiveness in routine practice , where clinician expertise and patient mix may be different . Thus , we evaluated the applicability , acceptability and effectiveness of CBTp when offered routinely in a public mental health service . DESIGN A prospect ively recruited representative sample ( N=94 ) of patients with psychotic disorders from a geographic catchment area in Melbourne , Australia , was r and omized to CBTp or treatment as usual . METHOD The CBTp intervention included psychoeducation , positive symptom , and co-morbid problem components . Therapists collaboratively negotiated goals with patients and utilized treatment components from a manual . Intention-to-treat analyses used data at baseline , 9 months and 18 months . RESULTS Working alliance and client satisfaction measures indicated excellent acceptability . Both groups improved to a similar degree on the Positive And Negative Syndrome Scale , with no advantage for the CBTp group . The most frequent CBTp components implemented were co-morbid disorders/personal issues and personalized psychoeducation ; working with persisting symptoms was the main focus in relatively few sessions . CONCLUSIONS The lack of advantage for the CBTp group may be due to : the infrequent focus on positive symptoms ( the most replicated outcome domain for CBTp ) ; the unselected nature of the patients ( rather than those with distressing symptoms or referred by clinicians ) ; or , to insufficient therapist expertise Objective : To investigate the effect of the Boston Psychiatric Rehabilitation ( PR ) Approach on attainment of personal rehabilitation goals , social functioning , empowerment , needs for care , and quality of life in people with severe mental illness ( SMI ) in the Netherl and s. Method : A 24-month , multicentre , r and omized controlled trial was used to compare the results of PR to care as usual ( CAU ) . Patients with SMI were r and omly assigned by a central r and omization centre to PR ( n = 80 ) or CAU ( n = 76 ) . The primary outcome of goal attainment was assessed by independent raters blind to treatment allocation . Measures for secondary outcomes were change in work situation and independent living , the Personal Empowerment Scale , the Camberwell Assessment of Needs , and the World Health Organization Quality of Life assessment . Effects were tested at 12 and 24 months . Data were analyzed according to intention to treat . Covariates were psychiatric centre , psychopathology , number of care contacts , and educational level of the professionals involved . Results : The rate of goal attainment was substantially higher in PR at 24 months ( adjusted risk difference : 21 % , 95 % CI 4 % to 38 % ; number needed to treat [ NNT ] = 5 ) . The approach was also more effective in the area of societal participation ( PR : 21 % adjusted increase , CAU : 0 % adjusted increase ; NNT = 5 ) but not in the other secondary outcome measures . Conclusions : The results suggest that PR is effective in supporting patients with SMI to reach self-formulated rehabilitation goals and in enhancing societal participation , although no effects were found on the measures of functioning , need for care , and quality of life OBJECTIVES In schizophrenia , the ability to adaptively infer the thoughts and feelings of others ( i.e. , social cognition ) is strongly associated with community functioning . Research ers have design ed psychosocial interventions to improve social cognition with the aim of improving downstream social functioning . Social Cognition and Interaction Training ( SCIT ) is one such intervention . Previous research on SCIT has been promising , but has consisted largely of smaller trials with insufficient experimental control . DESIGN R and omized , controlled trial . METHODS The current article reports on a controlled trial of 66 adults with schizophrenia r and omized to receive either SCIT ( n = 33 ) , delivered in weekly group sessions , or treatment as usual ( n = 33 ) for 6 months . Participants completed assessment s of social cognition , social functioning , neurocognition and symptoms at baseline , post-treatment , and 3-month follow-up . RESULTS Primary analyses suggest that SCIT may improve social functioning , negative symptoms , and possibly hostile attributional bias . Post-hoc analyses suggest a dose-response effect . CONCLUSIONS Findings are discussed in the context of continuing to refine and improve social cognitive interventions for schizophrenia . PRACTITIONER POINTS Social cognitive intervention is a feasible and promising approach to improving social functioning among individuals with schizophrenia-spectrum disorders . Dose-response findings suggest that delivering social cognitive interventions with greater frequency may maximize their benefit to patients . Research on social cognitive interventions is still young and effects from well-controlled trials have been inconsistent . It is not yet clear which components of social cognitive training may be the key active ingredients The aim of this study was to determine whether occupational therapy ( OT ) can improve the interpersonal relationships and negative symptoms of hospitalized chronic schizophrenia patients with severe negative symptoms . Subjects were 38 patients with chronic schizophrenia . They were r and omly divided into an OT group and a control group . Patients in the OT group participated in cooking activities once a week for 15 weeks , while patients in the control group did not . During this period , both groups had the usual treatment except for the cooking activities . In interviews , the patient was asked to place a chair toward the interviewer ( a therapist ) . The angle and distance from the interviewer were taken as indicators of an ability to have interpersonal relationships . Negative symptoms were evaluated with the Scale for the Assessment of Negative Symptoms ( SANS ) . Patients who received OT were able to sit at the smaller angle and shorter distance from the interviewer than before OT ( p=0.015 and p=0.013 , respectively ) . The total SANS score was lower after OT than before OT ( p=0.033 ) . In the control group , the distance from the interviewer also decreased during the experimental period ( p=0.040 ) but the seating angle and the SANS scores did not change . The results suggest that OT can help to improve a relationship allowing the patient to face the therapist and that it might improve negative symptoms of schizophrenia BACKGROUND Presently few studies demonstrate improved outcomes in patients with schizophrenia treated in day rehabilitation centres . One reason is the absence of an evidence based protocol for rehabilitation in such centres . Hence further research is required to assess whether such a protocol will improve psychosocial outcomes . AIMS We performed a controlled evaluation study of a protocol based rehabilitation day program ( RDC ) for persons suffering from schizophrenia . METHODS Patients from the experimental group ( N=50 ) were treated within the RDC for a 6 month period . The control group were patients on the waiting list for the RDC . Quality of life ( MANSA ) , social functioning ( OSA ) and self-esteem ( Rosenberg ) were measured before and after the intervention . RESULTS Statistically significant improvement was shown in social functioning measured by OSA ( F(1,96)=33.7 ; p<0.001 ) , quality of life measured by MANSA ( F(1,96)=69.3 ; p<0.001 ) and self esteem measured by Rosenberg scale ( F(1,96)=84.5 ; p<0.001 ) for patients treated in the RDC compared with the control group , conversely , the control group outcomes deteriorated . CONCLUSION An evidence based protocol for rehabilitation within the RDC lead to improved social outcomes and recovery for persons suffering from schizophrenia Achieving social functioning and achieving social competence are two main objectives of psychosocial interventions for people suffering from schizophrenia . The present preliminary study presents a novel approach of social skills training ( SST ) based on the proposals of Kopelowicz et al. ( Kopelowicz , A. , Liberman , R. P. , and Zarate , R. , 2006 . Schizophr . Bull . 32 ( 1 ) : S12 - 23 ) that link the treatment to seven specific target behaviours : social perception , social information processing , responding and sending skills , affiliative skills , interactional skills , and behaviour governed by social norms . Thirty-one stabilised out patients were r and omly assigned to one of two groups , SST ( n=13 ) or treatment-as-usual ( n=18 ) ( TAU ; case management , medication adherence , psychotherapy , leisure engagement , and family support ) and were assessed at baseline in cognitive performance , clinical symptomatology , social cognition , and psychosocial functioning . These outcomes were evaluated across post-treatment and at the 6-month follow-up appointment . SST subjects showed improvements in psychopathology , social discomfort , social cognition ( self-regulation statements during interactions ) , social withdrawal , interpersonal communication , and quality of life compared with the TAU group . At the 6-month follow-up , results were maintained for negative symptoms , social discomfort , and some functioning outcomes . Neuropsychological variables were also examined , as mediators of benefit from skills training . Results support the efficacy of the brief SST for out patients with schizophrenia and show the need to implement empirically supported interventions in mental health services to enhance patients ' social functioning and quality of life OBJECTIVE The effectiveness of Occupational Goal Intervention ( OGI ) in clients with schizophrenia was compared with that of the Frontal Executive Program and a control group . METHOD We used a quasi-experimental design with 18 adult participants ages 20 - 38 who were r and omly assigned to three groups . Testing was performed before treatment , after treatment , and at 6-mo follow-up ( Time 2 ) . Instruments assessed executive functions ( EFs ) and activity and participation . Participants received 18 treatment sessions over a period of 6 - 8 wk . RESULTS We found no significant differences among the groups on pretest-posttest change ; however , we did find significant differences within groups before and after intervention and moderate to high effect sizes . The OGI group showed relative improvement on all measures of EF and activity and participation . Most participants ' achievements were maintained at Time 2 . CONCLUSIONS Results provide initial support for the OGI 's effectiveness for clients with schizophrenia . Further studies are needed to verify these initial findings OBJECTIVE Mindfulness-based cognitive therapy ( MBCT ) has recently been proposed as a treatment option for chronic depression . The cognitive behavioral analysis system of psychotherapy ( CBASP ) is the only approach specifically developed to date for the treatment of chronically depressed patients . The efficacy of MBCT plus treatment-as-usual ( TAU ) , and CBASP ( group version ) plus TAU , was compared to TAU alone in a prospect i ve , bicenter , r and omized controlled trial . METHOD One hundred and six patients with a current DSM-IV defined major depressive episode and persistent depressive symptoms for more than 2 years were r and omized to TAU only ( N = 35 ) , or to TAU with additional 8-week group therapy of either 8 sessions of MBCT ( n = 36 ) or CBASP ( n = 35 ) . The primary outcome measure was the Hamilton Depression Rating Scale ( 24-item HAM-D , Hamilton , 1967 ) at the end of treatment . Secondary outcome measures were the Beck Depression Inventory ( BDI ; Beck , Steer , & Brown , 1996 ) and measures of social functioning and quality of life . RESULTS In the overall sample as well as at 1 treatment site , MBCT was no more effective than TAU in reducing depressive symptoms , although it was significantly superior to TAU at the other treatment site . CBASP was significantly more effective than TAU in reducing depressive symptoms in the overall sample and at both treatment sites . Both treatments had only small to medium effects on social functioning and quality of life . CONCLUSIONS Further studies should inquire whether the superiority of CBASP in this trial might be explained by the more active , problem-solving , and interpersonal focus of CBASP The aim of this study was to evaluate the effects of animal-assisted activity on self-esteem , control over activities of daily living , and other psycho-physiological aspects among Taiwanese in patients with schizophrenia . Thirty participants were r and omly assigned to either the treatment or control group . A weekly animal-assisted activity program was arranged for patients in the treatment group for 2 months . A question naire assessing self-esteem , self-determination , social support , and psychiatric symptoms was completed the week before and the week after the animal-assisted activity . Compared with the control group , the treatment group showed significant improvement on all measures except for social support and negative psychiatric symptoms . The results of this study showed that animal-assisted activity can promote significant improvements in many clinical aspects among in patients with schizophrenia . Therefore , animal-assisted activity should be integrated into the treatment of institutionalized patients with schizophrenia Rehabilitation programs integrating cognitive remediation ( CR ) and psychosocial rehabilitation are often implemented as they seem to yield greater improvements in functional outcome than st and alone treatment approaches . Mechanisms underlying synergistic effects of combining CR with psychosocial interventions are not fully understood . Disentangling the relative contribution of each component of integrated programs might improve underst and ing of underlying mechanisms . In the present study we compared the efficacy of two components of our rehabilitation program [ the Neurocognitive Individualized Training ( NIT ) and the Social Skills Individualized Training ( SSIT ) ] . Seventy-two patients with schizophrenia or schizoaffective disorder were r and omly assigned to one of two treatment groups . Changes in cognitive , psychopathological and real-world functioning indices after 6 and 12 months were compared between the two groups . After both 6 and 12 months , NIT produced an improvement of attention , verbal memory and perseverative aspects of executive functioning , while SSIT produced a worsening of visuo-spatial memory and attention and no significant effect on the other cognitive domains . As to the real-world functioning , NIT produced a significant improvement of interpersonal relationships , while SSIT yielded a significant improvement of QLS instrumental role subscale . According to our findings , cognitive training is more effective than social skills training on several cognitive domains and indices of real-world functioning relevant to subject 's relationships with other people . Integrated approaches might target different areas of functional impairment but should be planned carefully and individually to fully exploit the synergistic potential OBJECTIVE To test cognitive-behavioral therapy for insomnia ( CBT-I ) in patients who not only receive psychiatric treatment in a outpatient psychiatry clinic but also continue to experience chronic insomnia despite receiving pharmacological treatment for sleep . CBT-I included an optional module for discontinuing hypnotic medications . METHOD Patients were r and omized to 5 sessions of individual CBT-I ( n = 13 ) or treatment as usual ( n = 10 ) . Sleep parameters were assessed using sleep diaries at pre- and posttreatment . Question naires measuring depression , anxiety , and health-related quality of life were also administered . RESULTS CBT-I was associated with significant improvement in sleep , with 46 % obtaining normal global sleep ratings after treatment . However , no changes in secondary outcomes ( depression , anxiety , quality of life ) were obtained and no patients elected to discontinue their hypnotic medications . CONCLUSIONS Patients with complex , chronic psychiatric conditions can obtain sleep improvements with CBT-I beyond those obtained with pharmacotherapy alone ; however , sleep interventions alone may not have the same effect on mental health outcomes in sample s with more severe and chronic psychiatric symptoms and dependency on hypnotic medications We examined the short-term efficacy of two treatments using environmental supports ( e.g. signs , alarms , pill containers , and checklists ) to improve target behaviors in individuals with schizophrenia . 120 participants were r and omized into one of the following three treatment groups : 1 ) Cognitive Adaptation Training ( CAT ; a manual-driven set of environmental supports customized to individual cognitive impairments and behaviors , and established and maintained in participants ' homes on weekly visits ; 2 ) Generic Environmental Supports ( GES ; a generic set of supports given to patients at a routine clinic visit and replaced on a monthly basis ) ; and 3 ) treatment as usual ( TAU ; st and ard follow-up provided by a community mental health center ) . Global level of functional outcome and target behaviors , including orientation , grooming and hygiene , and medication adherence , were assessed at baseline and 3 months . Results of an analysis of covariance indicated that patients in both CAT and GES had better scores on global functional outcome at 3 months than those in TAU . Results of Chi Square analyses indicated that patients in CAT were more likely to improve on target behaviors , including orientation , hygiene , and medication adherence , than those in GES . Irrespective of treatment group , individuals who were high utilizers of environmental supports were more likely to improve on target behaviors than individuals who were low utilizers of supports OBJECTIVE The Helping Older People Experience Success ( HOPES ) program was developed to improve psychosocial functioning and reduce long-term medical burden in older people with severe mental illness ( SMI ) living in the community . HOPES includes 1 year of intensive skills training and health management , followed by a 1-year maintenance phase . METHOD To evaluate effects of HOPES on social skills and psychosocial functioning , we conducted a r and omized controlled trial with 183 older adults with SMI ( 58 % schizophrenia spectrum ) age 50 and older at 3 sites who were assigned to HOPES or treatment as usual with blinded follow-up assessment s at baseline and 1- and 2-year follow-up . RESULTS Retention in the HOPES program was high ( 80 % ) . Intent-to-treat analyses showed significant improvements for older adults assigned to HOPES compared to treatment as usual in performance measures of social skill , psychosocial and community functioning , negative symptoms , and self-efficacy , with effect sizes in the moderate ( .37-.63 ) range . Exploratory analyses indicated that men improved more than women in the HOPES program , whereas benefit from the program was not related to psychiatric diagnosis , age , or baseline levels of cognitive functioning , psychosocial functioning , or social skill . CONCLUSIONS The results support the feasibility of engaging older adults with SMI in the HOPES program , an intensive psychiatric rehabilitation intervention that incorporates skills training and medical case management , and improves psychosocial functioning in this population . Further research is needed to better underst and gender differences in benefit from the HOPES program OBJECTIVE The purpose of the study was to rigorously test Illness Management and Recovery ( IMR ) against an active control group in a sample that included veterans . METHODS A total of 118 participants with schizophrenia spectrum disorders , 56 of whom were veterans , were recruited from a Department of Veterans Affairs medical center and a community mental health center in the same city and were r and omly assigned to an IMR group ( N=60 ) or a weekly problem-solving group intervention ( N=58 ) . Groups met weekly for nine months . Blinded assessment s were conducted at baseline , nine months , and 18 months on measures of symptoms , functioning , illness self-management , medication adherence , subjective recovery experiences , and service utilization . RESULTS No significant differences were found between IMR and problem-solving groups . Participants in both groups improved significantly over time in symptom severity , illness management , and quality of life and had fewer emergency department visits . Participation rates in both interventions were low . Only 28 % of consumers assigned to IMR and 17 % of those assigned to the problem-solving group participated in more than half the scheduled groups , and 23 % and 34 % , respectively , attended no sessions . CONCLUSIONS This is the first r and omized controlled trial of IMR to report negative findings . Given the inclusion of an active control group and the low participation rates , further research is needed to underst and factors affecting IMR effectiveness . Increased attention may need to be paid to facilitate more active participation in IMR , such as individual follow-up with consumers and the integration of IMR with ongoing treatment Cognitive remediation improves cognition in patients with schizophrenia , but its effect on other relevant factors such as negative symptoms and functional outcome has not been extensively studied . In this hospital-based study , 84 in patients with chronic schizophrenia were recruited from Alava Hospital ( Spain ) . All of the subjects underwent a baseline and a 3-month assessment that examined neurocognition , clinical symptoms , insight , and functional outcome according to the Global Assessment of Functioning ( GAF ) scale and Disability Assessment Schedule from World Health Organization ( DAS-WHO ) . In addition to receiving st and ard treatment , patients were r and omly assigned either to receive neuropsychological rehabilitation ( REHACOP ) or to a control group . REHACOP is an integrative program that taps all basic cognitive functions . The program included experts ' latest suggestions about positive feedback and activities of daily living in the patients ' environment . The REHACOP group showed significantly greater improvements at 3 months in the areas of neurocognition , negative symptoms , disorganization , and emotional distress compared with the control group ( Cohen 's effect size for these changes ranged from d = 0.47 for emotional distress to d = 0.58 for disorganization symptoms ) . The REHACOP group also improved significantly in both the GAF ( d = 0.61 ) and DAS-WHO total scores ( d = 0.57 ) . Specifically , the patients showed significant improvement in vocational outcomes ( d = 0.47 ) , family contact ( d = 0.50 ) , and social competence ( d = 0.56 ) . In conclusion , neuropsychological rehabilitation may be useful for the reduction of negative symptoms and functional disability in schizophrenia . These findings support the integration of neuropsychological rehabilitation into st and ard treatment programs for patients with schizophrenia OBJECTIVE This report describes 1- , 2- , and 3-year outcomes of a combined psychosocial skills training and preventive healthcare intervention ( Helping Older People Experience Success [ HOPES ] ) for older persons with serious mental illness . METHODS A r and omized controlled trial compared HOPES with treatment as usual ( TAU ) for 183 older adults ( age ≥ 50 years [ mean age : 60.2 ] ) with serious mental illness ( 28 % schizophrenia , 28 % schizoaffective disorder , 20 % bipolar disorder , 24 % major depression ) from two community mental health centers in Boston , Massachusetts , and one in Nashua , New Hampshire . HOPES comprised 12 months of weekly skills training classes , twice-monthly community practice trips , and monthly nurse preventive healthcare visits , followed by a 1-year maintenance phase of monthly sessions . Blinded evaluations of functioning , symptoms , and service use were conducted at baseline and at a 1-year ( end of the intensive phase ) , 2-year ( end of the maintenance phase ) , and 3-year ( 12 months after the intervention ) follow-up . RESULTS HOPES compared with TAU was associated with improved community living skills and functioning , greater self-efficacy , lower overall psychiatric and negative symptoms , greater acquisition of preventive healthcare ( more frequent eye exams , visual acuity , hearing tests , mammograms , and Pap smears ) , and nearly twice the rate of completed advance directives . No differences were found for medical severity , number of medical conditions , subjective health status , or acute service use at the 3-year follow-up . CONCLUSION Skills training and nurse facilitated preventive healthcare for older adults with serious mental illness was associated with sustained long-term improvement in functioning , symptoms , self-efficacy , preventive healthcare screening , and advance care planning |
12,258 | 30,375,188 | There was no convincing evidence for satisfactory pain relief by acetaminophen alone or in combination with strong opioids .
We found substantial evidence of moderate quality for a satisfactory pain relief in cancer by non-steroidal anti-inflammatory drugs ( NSAIDs ) , flupirtine , and dipyrone compared with placebo or other analgesics .
There was no evidence for a superiority of one specific non-opioid .
There was moderate quality of evidence for a similar pain reduction by NSAIDs in the usual dosage range compared with up to 15 mg of morphine or opioids of equianalgesic potency .
The combination of NSAID and step III opioids showed a beneficial effect , without a decreased tolerability .
There is scarce evidence concerning the combination of NSAIDs with weak opioids .
Non-steroidal anti-inflammatory drugs , flupirtine , and dipyrone can be recommended for the treatment of cancer pain either alone or in combination with strong opioids .
The use of acetaminophen in the palliative setting can not be recommended .
There is a lack of evidence regarding pain treatment by non-opioids in specific cancer entities | Non-opioid analgesics are widely used for pain relief in palliative medicine .
However , there is a lack of evidence -based recommendations addressing the efficacy , tolerability , and safety of non-opioids in this field .
A comprehensive systematic review and meta- analysis on current evidence can provide a basis for sound recommendations in clinical practice .
There are no r and omized-controlled studies on the use of non-opioids in a wide range of end-stage diseases except for cancer . | Background Persistent pain is a challenging clinical problem after breast cancer treatment . After surgery , inflammatory pain and nociceptive input from nerve injury induce central sensitization which may play a role in the genesis of persistent pain . Using quantitative sensory testing , we tested the hypothesis that adding COX-2 inhibition to st and ard treatment reduces hyperalgesia after breast cancer surgery . A secondary hypothesis was that patients developing persistent pain would exhibit more postoperative hyperalgesia . Methods 138 women scheduled for lumpectomy/mastectomy under general anesthesia with paravertebral block were r and omized to COX-2 inhibition ( 2x40 mg parecoxib on day of surgery , thereafter 2x200 mg celecoxib/day until day five ) or placebo . Preoperatively and 1 , 5 , 15 days and 1 , 3 , 6 , 12 months postoperatively , we determined electric and pressure pain tolerance thresholds in dermatomes C6/T4/L1 and a 100 mm VAS score for pain . We calculated the sum of pain tolerance thresholds and analyzed change in these versus preoperatively using mixed models analysis with factor medication . To assess hyperalgesia in persistent pain patients we performed an additional analysis on patients reporting VAS>30 at 12 months . Results 48 COX-2 inhibition and 46 placebo patients were analyzed in a modified intention to treat analysis . Contrary to our primary hypothesis , change in the sum of tolerance thresholds in the COX-2 inhibition group was not different versus placebo . COX-2 inhibition had an effect on pain on movement at postoperative day 5 ( p<0.01 ) . Consistent with our secondary hypothesis , change in sum of pressure pain tolerance thresholds in 11 patients that developed persistent pain was negative versus patients without pain ( p<0.01 ) from day 5 to 1 year postoperatively . Conclusions Perioperative COX-2 inhibition has limited value in preventing sensitization and persistent pain after breast cancer surgery . Central sensitization may play a role in the genesis of persistent postsurgical pain In a clinical double-blind study , the analgesic efficacy and the side-effects of nimesulide ( Aulin , CAS 51803 - 78 - 2 ) and naproxen administered to 68 patients affected by advanced cancer pain were compared . Patients were treated with non-steroidal anti-inflammatory drugs according to the first step of the pharmacological analgesic scale of the WHO . The dose administered was 200 mg b.i.d . ( every 12 h ) for nimesulide and 500 mg b.i.d . ( every 12 h ) for naproxen . From this study the analgesic effect and the tolerability of the two drugs appeared to be similar . Both drugs result ed to be effective with a low incidence of adverse events that may be related to their use The analgesic efficacy of ketorolac tromethamine was compared to placebo in 126 patients suffering moderate or severe chronic pain due to cancer in a double-blind parallel r and omized study . Ketorolac was administered intramuscularly in doses of 10 , 30 or 90 mg . Pain intensity and pain relief were assessed for 6 hours by scoring st and ard verbal scales and an overall assessment of the medication was given by the patients and the observer on completion of the study . Each dose of ketorolac was statistically superior to placebo for the sum of pain intensity difference ( SPID ) but no difference was seen between the three ketorolac regimens . When the ketorolac groups are combined , there was a significantly better pain relief as compared to placebo . The global evaluation scores were also statistically superior in the ketorolac groups combined than in the placebo group . A total of 15 patients reported minor adverse events , 10 being after ketorolac doses . This study shows that single intramuscular doses of ketorolac of 10 mg and above are effective in the relief of cancer pain , and are associated with a low incidence of side-effects Objectives This study aims to evaluate the efficacy of methadone as substitute for morphine and to investigate if the addition of acetaminophen could reduce the time to attain an equianalgesic dose of methadone and /or to improve the level of pain control in oncologic patients . Patients and methods Fifty patients on stable doses of morphine for 1 week were switched to methadone using a “ stop – start ” strategy and r and omized in a double-blind fashion to receive either acetaminophen ( 750 mg PO every 6 hours ) or placebo for a 7-day period . We collected data regarding level of pain , side effects , and quality of life . Results Substitution of morphine for methadone result ed in a significant reduction in constipation ( p < 0.001 ) and xerostomia ( p = 0.03 ) . There was also an improvement in the numeric pain scale ( p = 0.03 ) as well as a significant improvement in the functional level and symptomatology according to the QLQ-C30 question naire . Addition of acetaminophen did not improve pain control or reduce the time of stabilization of analgesia once methadone was introduced . At the end of the study , most patients ( 70.8 % , p = 0.001 ) preferred methadone to morphine . Conclusions Early switching from morphine to methadone was a safe and efficient strategy for the reduction of side effects and improvement of analgesia , allowing for a comfortable dosing regimen . In this scenario , the association with acetaminophen did not improve pain control or reduce the time to achieve an equianalgesic dose of methadone Benzydamine hydrochloride rinse reduced pain associated with radiation mucositis when it was used during the course of radiation therapy . Fewer patients using benzydamine rinse required systemic analgesics . All patients using benzydamine tolerated the rinse well and continued with regular rinsing throughout the course of radiation therapy . Benzydamine hydrochloride is currently undergoing clinical trials in the United States for application for approval from the Food and Drug Administration The role of non-steroidal anti-inflammatory drugs ( NSAIDs ) in cancer pain has been well established in the treatment of mild pain and in association with opioids in the treatment of moderate to severe pain . The aim of this study was to verify the effects of NSAIDs on morphine escalation in advanced cancer patients with pain followed-up at home and to assess the pharmacoeconomic implication s. A prospect i ve r and omised controlled study was carried out in 156 consecutive advanced cancer patients with pain followed-up at home in the period December 1999-December 2000 . In this group of patients , 47 were selected with pain progression after 1 week of opioid stabilisation . Patients were r and omly assigned to one of two groups : group ' O ' patients were treated with continuing opioid escalation according to their clinical needs ; group ' OK ' received ketorolac 60 mg/daily orally ( p.o . ) in three doses and then continued opioid escalation according to their clinical situation . Performance status , doses of morphine before and after starting treatment , mean weekly pain intensity ( assessed by means of a numerical scale from 0 to 10 ) , mean weekly symptoms intensity , adverse effects and pain mechanisms were recorded . Moreover , drug costs per day in both groups were calculated . Patients who received ketorolac in addition to morphine showed a better analgesia after a week in comparison to the group treated with morphine only ( P=0.005 ) . Thereafter , morphine escalation was slower and the maximum morphine dose was lower in the group treated with ketorolac . The incidence and the severity of gastric discomfort was more evident in patients treated with ketorolac , while constipation was significantly increased in patients who received morphine only . Drug costs per day were similar in both groups ; statistical differences were observed in patients who started on lower morphine doses ( < 100 mg/daily ) in the two groups ( 4.3 in the ketorolac-morphine group versus 3.4 in the morphine group ; P=0.012 ) . The use of NSAIDs reduces the need for an opioid dose escalation or allows the use of lower doses . Their use is associated with a more intense gastric discomfort , but results in less opioid-related constipation . The eventual additive cost for NSAIDs therapy is negligible , especially in patients taking high doses of morphine In a controlled double blind study of analgesics for the pain of gastrointestinal cancer , aspirin ( 650 mg ) was significantly more effective than placebo and superior to orally used codeine sulfate ( 60 mg ) . The effectiveness of aspirin was not specific for carcinoma of the pancreas , however , because the same pattern of pain relief was found in colonic carcinoma Introduction Adjunct nonopioid analgesics may improve pain control in patients with cancer needing morphine or its derivates . Dypirone is a cheap nonopioid analgesic widely used in many countries . Objective The objective of the study was to evaluate , whenever morphine was started , if associating dipyrone with it would improve pain control and if this effect was time dependent . Material s and methods This is a double-blind placebo-controlled r and omized crossover study . Thirty-four ambulatory cancer patients experiencing cancer-related pain for which oral morphine was to be started at the dose of 10 mg orally ( PO ) every 4 h were r and omized to take either dipyrone 500 mg PO every 6 h or placebo . After 48 h , patients would be switched from dipyrone to placebo and vice versa . Pain was the primary outcome and was measured using a visual analogue scale before starting medications , at 48 and 96 h. Results We r and omized 16 patients to start with placebo ( group 1 ) and 18 with dipyrone ( group 2 ) . Pain scores for groups 1 and 2 were at baseline : 7.31 ± 0.29 vs 6.88 ± 0.28 ( p = 0.3 ) , at 48 h : 7.06 ± 0.32 vs 5.5 ± 0.31 ( p = 0.001 ) , and at 96 h : 3.18 ± 0.39 vs 1.94 ± 0.37 ( p = 0.03 ) . Both groups had significant improvements in pain scores after introducing dipyrone ( p < 0.001 , for both ) . Main toxicities were nausea , vomiting , epigastric pain , and myalgias . Twenty-eight patients chose dipyrone , four placebo , and two were indifferent . Conclusions We conclude that dipyrone adds significantly to the analgesic effect of morphine and , when given at the time of starting morphine , results in better pain scores even after dipyrone is discontinued Objective The present study aim ed to examine the effectiveness of intravenous administration of paracetamol added to morphine in the control of cancer pain and its possible contribution as reduction of opioid consumption and opioid-related side effects . Material s and methods A total of 43 patients with chronic cancer pain without neuropathic origin aged between 18 and 76 years and receiving step 2 treatment according to the World Health Organization analgesic ladder were included . Patients were r and omized to receive intravenous administration of saline ( control ) or 1 g of paracetamol on top of morphine . Visual analog scale ( VAS ) , patient rating index ( PRI ) , Eastern Cooperative Oncology Group ( ECOG ) status , patient satisfaction , and safety were evaluated . Main results Both treatments result ed in improved VAS and PRI scores compared to baseline . However , groups did not differ in terms of VAS and PRI scores , morphine consumption , side-effect frequencies , laboratory values , ECOG status , and patient satisfaction . Conclusions Although safe and there are signals for a true analgesic efficacy , our results failed to confirm any benefits of add-on treatment with intravenous administration of paracetamol . However , the study was underpowered , and future studies in this important area need to be wary of background noise and the risk of a type II error As professionals , we want to use the best treatments ; as patients , we want to be given them . Knowing whether an intervention works ( or does not work ) is fundamental to clinical decision making . However , clinical decision making involves more than simply taking published results of research directly to the bedside . Physicians need to consider how similar their patients are to those in the published studies , to take the values and preferences of their patients into account , and to consider their own experience with a given test or treatment . Evidence from clinical research is becoming increasingly important in medical- practice decisions as more and better evidence is published . But when is the evidence strong enough to justify changing a practice ? Individual studies that involve only small numbers of patients may have results that are distorted by the r and om play of chance and thus lead to less than optimal decisions . As is clear from other papers in this series , systematic review s identify , critically appraise , and review all the relevant studies on a clinical question and are more likely to give a valid answer . They use explicit methods and quality st and ards to reduce bias . Their results are the closest we can come to reaching the truth given our current state of knowledge . The questions about an intervention that a systematic review should answer are the following : 1 . Does it work ? 2 . If it works , how well does it work in general and compared with placebo , no treatment , or other interventions that are currently in use ? 3 . Is it safe ? 4 . Will it be safe and effective for my patients ? Whereas the critical appraisal and qualitative synthesis provided by review articles can be interpreted directly , the numerical products of quantitative review s can be more difficult to underst and and apply in daily clinical practice . This paper provides guidance on how to interpret the numerical and statistical results of systematic review s , translate these results into more underst and able terms , and apply them directly to individual patients . Many of these principles can also be used to interpret the numerical results of individual clinical studies . They are particularly relevant to systematic review s , however , because such review s contain more information than do primary studies and often exert greater influence than do individual studies . Making Sense of the Numerical Results of Clinical Studies Although the results of clinical studies can be expressed in intuitively meaningful ways , such results do not always easily translate into clinical decision making . For example , results are frequently expressed in terms of risk , which is an expression of the frequency of a given outcome . ( Risks are probabilities , which can vary between 0.0 and 1.0 . A probability of 0.0 means that the event will never happen , and a probability of 1.0 means that it always happens . ) Consider a hypothetical study of the recurrence of migraine headaches in a control group receiving placebo and a treatment group receiving a new antimigraine preparation , drug M ( a secondary prevention trial ) . Suppose that at the end of the trial , migraines recurred in 30 % of the control group ( the risk for recurrence was 0.30 ) but in only 5 % of the drug M group ( risk of 0.05 ) ( Table 1 ) . Table 1 . Numerical Expression of Hypothetical Clinical Trial Results The outcomes of the study are clear enough for the two groups when they are examined separately . But clinicians and patients are more interested in the comparative results , that is , the outcome in one group relative to the outcome in the other group . This overall ( comparative ) result can be expressed in various ways . For example , the relative risk , which is the risk in the treatment group relative to that in the control group , is simply the ratio of the risks in the two groups . In other words , relative risk is the risk in the treatment group divided by that in the control group , 0.05 0.30 , or 0.17 . The comparison can also be expressed as the reduction in relative risk , which is the ratio between the decrease in risk ( in the treatment group ) and the risk in the control group , 0.25 0.30 , or 0.83 ( Table 1 ) . ( The relative risk reduction can also be calculated as 1 relative risk ) . Although the clinical meaning of relative risk ( and relative risk reduction ) is reasonably clear , relative risk has the distinct disadvantage that a given value ( for example , 0.17 ) is the same whether the risk with treatment decreases from 0.80 to 0.14 , from 0.30 to 0.05 , from 0.001 to 0.00017 , and so forth . The clinical implication s of these changes clearly differ from one another enormously and depend on the specific disease and intervention . An important alternate expression of comparative results , therefore , is the absolute risk reduction . Absolute risk reduction is determined by subtracting the risk in one group from the risk in the other ( for example , the risk in the treatment group is subtracted from the risk in the placebo group ) . In the case of our migraine study , the absolute risk reduction would be 0.30 0.05 , which equals 0.25 , or 25 percentage points . In contrast , for a study in which the risk decreased from 0.001 to 0.00017 , the absolute risk reduction would be only 0.00083 , or 0.083 percentage points , which is a trivial change in comparison ( Table 1 ) . This arithmetic emphasizes the difficulty of expressing the results of clinical studies in meaningful ways . Relative risk and relative risk reduction clearly give a quantitative sense of the effects of an intervention in proportional terms but provide no clue about the size of an effect on an absolute scale . In contrast , although it tells less about proportional effects , absolute risk says a great deal about whether an effect is likely to be clinical ly meaningful . Despite this benefit , even absolute risk is problematic because it is a dimensionless , abstract number ; that is , it lacks a direct connection with the clinical situation in which the patient and physician exist . However , another way of expressing clinical research results can provide that clinical link : the number needed to treat ( NNT ) . Number Needed To Treat The NNT for a given therapy is simply the reciprocal of the absolute risk reduction for that treatment [ 1 , 2 ] . In the case of our hypothetical migraine study ( in which risk decreased from 0.30 without treatment with drug M to 0.05 with treatment with drug M , for a relative risk of 0.17 , a relative risk reduction of 0.83 , and an absolute risk reduction of 0.25 ) , the NNT would be 1 0.25 , or 4 . In concrete clinical terms , an NNT of 4 means that you would need to treat four patients with drug M to prevent migraine from recurring in one patient . To emphasize the difference between the concepts embodied in NNT and relative risk , recall the various situations mentioned above , in all of which the relative risk was 0.17 but in which the absolute risk decreased from 0.80 to 0.14 in one case and from 0.001 to 0.00017 in another . Note that the corresponding NNTs in these two other cases are 1.5 and 1204 , respectively : that is , you would need to treat 1.5 and 1204 patients to obtain a therapeutic result in these two situations compared with 4 patients with drug M ( Table 1 ) . The NNT can be calculated easily and kept as a single numerical reminder of the effectiveness ( or , as we will see , the potential for harm ) of a particular therapy . As we suggested , the NNT has the crucial advantage of direct applicability to clinical practice because it shows the effort that is required to achieve a particular therapeutic target . The NNT has the additional advantage that it can be applied to any beneficial outcome or any adverse event ( when it becomes the number needed to harm [ NNH ] ) . The concept of NNT always refers to a comparison group ( in which patients receive placebo , no treatment , or some other treatment ) , a particular treatment outcome , and a defined period of treatment . In other words , the NNT is the number of patients that you will need to treat with drug or treatment A to achieve an improvement in outcome compared with drug or treatment B for a treatment period of C weeks ( or other unit of time ) . To be fully specified , NNT and NNH must always specify the comparator , the therapeutic outcome , and the duration of treatment that is necessary to achieve the outcome . Important Qualities of the Number Needed To Treat The NNT is treatment specific . It describes the difference between treatment and control in achieving a particular clinical outcome . Table 2 shows NNTs from a selection of systematic review s and large r and omized , controlled trials . Table 2 . Numbers Needed To Treat from Systematic Review s and R and omized , Controlled Trials A very small NNT ( that is , one that approaches 1 ) means that a favorable outcome occurs in nearly every patient who receives the treatment and in few patients in a comparison group . Although NNTs close to 1 are theoretically possible , they are almost never found in practice . However , small NNTs do occur in some therapeutic trials , such as those comparing antibiotics with placebo in the eradication of Helicobacter pylori infection or those examining the use of insecticide for head lice ( Table 2 ) . An NNT of 2 or 3 indicates that a treatment is quite effective . In contrast , such prophylactic interventions as adding aspirin to streptokinase to reduce 5-week vascular mortality rates after myocardial infa rct ion may have NNTs as high as 20 to 40 and still be considered clinical ly effective . Limitations of the Number Needed To Treat Although NNTs are powerful instruments for interpreting clinical effects , they also have important limitations . First , an NNT is generally expressed as a single number , which is known as its point estimate . As with all experimental measurements , however , the true value of the NNT can be higher or lower than the point estimate determined through clinical studies . The 95 % CIs of the NNT are useful in this regard because they provide an indication that In a single-dose , a double-blind crossover study in 40 patients with chronic pain due to advanced cancer , zomepirac sodium ( Zomax ) , a new , single-entity , non-narcotic analgesic , was compared to oxycodone with APC ( Percodan ) and placebo . Both a verbal and a curvilinear visual analog scale were used in the study , and the results obtained were comparable . Zomepirac sodium , 100 mg , provided analgesia equal to oxycodone with APC in all assessment s of pain intensity and pain relief . The analgesic activity of zomepirac sodium was apparent by 1 hour , reached a peak between 3 and 4 hours after administration , and lasted at least 6 hours . Zomepirac sodium , 100 mg , appears to be an acceptable alternative to narcotic combinations such as oxycodone with APC in the management of moderate to severe cancer pain . The visual analog scale presented appears to be useful in the evaluation of analgesic efficacy and appears to be acceptable as an alternative to the more conventional verbal scale In a double-blind , r and omised and parallel clinical trial , two oral doses of dipyrone ( 1 and 2 g ) administered every 8 h were compared with 10 mg of oral morphine given every 4 h for the relief of chronic cancer pain . A total of 121 patients with cancer pain without gastric involvement participated in a 7-day treatment course and were allocated to receive either dipyrone 1 g ( n = 41 ) , dipyrone 2 g ( n = 38 ) or morphine ( n = 42 ) . Drug efficacy was analysed according to the degree of pain relief using a 100-mm visual analogue scale , and the number of patients who decided to increase the dose of the analgesic drug on day 4 . The analgesic effect of dipyrone , 2 g every 8 h , was similar to that of morphine . The efficacy of both schedules was significantly greater than that of dipyrone , 1 g every 8 h. Dipyrone at either 1 or 2 g doses tended to be better tolerated than morphine , although the differences were not statistically significant With a subjective response technique the analgetic activity of two non-steroidal anti-inflammatory agents which greatly differ in kinetics is compared . The double-blind cross-over trial was carried out in 18 patients of both sexes suffering from pain due to malignant tumours who received single doses of 200 mg indoprofen and 250 mg naproxen p.o . Both compounds were efficacious and there was no difference in the duration of their activity in spite of the great difference between their half-lives STUDY DESIGN In a multicentric double-blind trial , flupirtine was compared with tramadol in the treatment of cancer pain . METHODS Over a period of four weeks , 4 ( -6 ) capsules containing either 100 mg flupirtine ( n = 35 ) or 50 mg tramadol ( n = 36 ) were taken daily in accordance with a fixed time schedule . Severity of pain was scored on a weekly basis using a five-stage verbal scale . RESULTS Initially comparable in the two groups , pain was more markedly reduced after four weeks of treatment with flupirtine than after tramadol , the need for additional analgesic drugs also being less in the flupirtine group . The final general assessment by the attending doctors of the results achieved was " good " to " very good " in 63 % of the patients on flupirtine , and in 46 % of those on tramadol . Undesired effects were observed in 6 % of the flupirtine patients and in 19 % of those taking tramadol OBJECTIVE To compare the effectiveness of intravenous patient-controlled ( i.v.-PCA ) ketorolac to i.v.-PCA morphine in the treatment of postoperative pain in cancer patients . DESIGN In a double-blind , prospect i ve , r and omized trial , patients received either morphine in 1 mg/ml concentration or ketorolac 5 mg/ml for postoperative pain control . On arrival to the postanesthesia care unit ( PACU ) , the patients received 2 ml of medication every 5 min , until satisfactory analgesia was achieved . If pain persisted after 20 ml of study drug had been administered , 0.1 mg/kg morphine was given i.m . On discharge from the PACU , the patients were placed on an i.v.-PCA pump . All patients received a basal infusion of 1 ml/h with a 1-ml on-dem and bolus and a lockout interval of 10 min . Patients were offered 0.1 mg/kg morphine IM every 6 h , which they could refuse . SETTING University Cancer Center . PATIENTS Seventy patients scheduled for abdominal or truncal cancer operations . MAIN OUTCOME MEASURES Visual analog pain scores ( VAPS ) and Visual analog sedation scores ( VASS ) were used to measure the quality of pain control achieved either with ketorolac or morphine . The incidence of side effects was documented . RESULTS The VAPS were comparable between the groups . Patients in the ketorolac group requested more supplemental i.m . morphine . However , the total morphine dose and incidence of side effects was significantly higher in patients receiving i.v.-PCA morphine . CONCLUSIONS These results indicate that ketorolac supplemented with small doses of morphine is associated with a lower incidence of nausea , vomiting , and pruritus compared to morphine alone . This combination should be considered where immunosuppression from operation and administration of morphine is undesirable The efficacy of diflunisal in cancer pain was evaluated and compared with dipyrone . Diflunisal was given at the dosage of 500 mg perorally twice a day , and dipyrone was given at the dosage of 500 mg perorally three times a day . Duration of each treatment was 7 days ; after a 12-hour wash-out period , patients were given the other drug for another 7 days . A total of 50 patients were enrolled in the study . Pain intensity was assessed by 10-point visual analog scale ( VAS ) . Patients who had a VAS score higher than 5 were included . A total of 47 patients were evaluable . Initial VAS score was a mean of 8.57+/-1.33 . Diflunisal reduced the pain score by a mean of 4.65+/-3.10 , whereas dipyrone reduced the pain score by a mean of 3.25 < or = 2.85 ( p < 0.001 ) . Patients were also analyzed in three subgroups according to the presence of nonmetastatic , metastatic , and bone metastatic diseases . In each of these subgroups , diflunisal reduced the pain score more than dipyrone ; however , the difference was statistically significant only in patients who had bone metastasis . Adverse reactions were rare and acceptable with both drugs . Diflusinal is superior to dipyrone at this dosage and schedule in the treatment of moderate to severe cancer pain The analgesic effects of single oral doses of ketoprofen 100 and 300 mg , the combination of aspirin 650 mg plus codeine 60 mg , and placebo were compared under double-blind conditions in 160 hospitalized patients with cancer pain . At baseline and at 30 minutes and hourly for 6 hours after treatment , patients evaluated their pain intensity and pain relief . The 100 mg ketoprofen dose was significantly ( P less than 0.05 ) superior to placebo for all 14 derived efficacy parameters ; the 300 mg dose was significantly superior to placebo in all assessment s except derived onset of relief . Aspirin plus codeine was significantly ( P less than 0.05 ) superior to placebo for nine of the 14 assessment s. No statistically significant differences were observed among active treatments for any of the 14 derived parameters . The number of patients with a " good " response was greatest in the ketoprofen 100 mg group ( 55 % ) ; the numbers of good responders in the aspirin plus codeine ( 37.5 % ) and the ketoprofen 300 mg ( 30 % ) groups were comparable . The three active treatment groups were not significantly different from each other for patient response . The numbers of patients requiring rescue analgesic were significantly ( P less than 0.05 ) lower for both ketoprofen groups , but not for the aspirin plus codeine group , as compared with the placebo group . Twenty-three percent of the 160 patients reported adverse experiences , but there were no significant differences between the treatment groups in the number or type of experience . These results show that ketoprofen is as effective and well tolerated as aspirin plus codeine in relieving cancer pain Objetives The purpose of this study was to compare the analgesic efficacy and tolerability of opioids hydrocodone and tramadol in the relief of cancer pain . Methods One hundred and eighteen patients with chronic cancer pain participated in a double-blind , r and omized controlled trial . Sixty-two patients received hydrocodone and 56 patients received tramadol . Results Hydrocodone/acetaminophen was effective in relieving pain in 56.5 % of the patients at the starting dose of 25 mg/2500 mg/d . An additional 14.5 % of the patients responded to a double dose , and the remaining 29 % of patients did not experience any pain relief from hydrocodone administration . One dose of tramadol at 200 mg/d produced pain relief in 62 % of the patients and alleviated pain in another 11 % of patients at a dose of 400 mg/d , and remaining 27 % of patients did not experience pain relief from tramadol . No significant statistical difference in the analgesic efficacy of tramadol clorhydrate and hydrocodone/acetaminophen was found . The groups differed significantly in the incidence of side effects like nausea ( P=0.03 ; relative risk ( RR ) , 1.69 ; confidence interval ( IC ) 95 % , 1.03 - 2.77 ) , vomiting ( P=0.02 ; RR , 2.21 ; IC 95 % , 1.14 - 4.32 ) , dizziness ( P=0.03 ; RR , 2.12 ; IC 95 % , 1.17 - 3.86 ) , loss of appetite ( P=0.02 ; RR , 3.27 ; IC 95 % , 1.12 - 9.55 ) and weakness ( P=0.019 ; RR , 7.75 ; IC 95 % , 0.98 - 61.05 ) . Conclusions There was no superior analgesic efficacy with the administration of hydrocodone/acetaminophen when compared to patients receiving tramadol in the relief of cancer pain . Tramadol produced more mild side effects than hydrocodone To determine whether informed consent in a therapeutic trial modifies the analgesic effect of naproxen and placebo , we conducted a prospect i ve , r and omised , single dose , placebo-controlled trial . Patients were r and omly selected to receive or not information concerning the study . All patients included were then given a single dose of naproxen and placebo according to a crossover , double-blind design . Forty-nine patients with mild or moderate cancer pain which did not need narcotic analgesics entered the study . Twenty-five received both treatments without any information and constituted the uninformed group . Twenty-four had a complete information about the trial ; six refused to participate . The 18 others constituted the informed-consent group . Visual analogue scales of pain before and 30 , 60 , 120 and 180 min after the intake of naproxen and placebo were recorded . As an analgesic , naproxen was more effective than placebo in both groups of patients ( p = 0.001 ) . For naproxen as well as for placebo , the analgesic effect was better in the informed-consent group compared to the uninformed group ( p = 0.012 ) . The difference in therapeutic activity between naproxen and placebo was moderately higher in the uninformed patients ( p = 0.08 ) . We concluded that , in contrast with parallel studies , giving information in a crossover , placebo-controlled trial may increase the apparent efficacy of both the tested agent and the placebo , and decrease the perceived difference the two Abstract Background : Ketorolac is a parenteral nonsteroidal antiinflammatory drug ( NSAID ) . Two features have limited its clinical utility : tendency to elicit kidney failure and inability to produce complete analgesia . Because most NSAIDs are weak acids ( pKa 3–5 ) and become concentrated in acidic tissues , such as injured and inflamed tissues , we hypothesized that local administration may enhance its analgesic efficacy while lowering the potential for systemic complications . Methods : We conducted a r and omized , placebo-controlled study of 60 group I – III ( American Society of Anesthesiology criteria ) mastectomy patients , 20 in each group . Near the end of surgery and every 6 h postoperatively , 20 ml of the study solution containing normal saline with or without 30 mg of ketorolac were administered simultaneously either via a Jackson-Pratt drain or intravenously in a double-blind fashion . The quality of pain control , the amount and character of the drain fluid , incidence of nausea and vomiting , length of stay in the postoperative care unit , and amount of morphine used for treatment of breakthrough pain were recorded . Results : Intraoperative administration of ketorolac result ed in better quality of pain control in the immediate postoperative period regardless of route of administration . The incidence of nausea was significantly higher in the placebo group , and drain output in the ketorolac groups did not exceed the output in the placebo group . Conclusion : Analgesic of the locally administered ketorolac is equally effective to the efficacy of ketorolac administered intravenously Little attention has been accorded to the terminal course and end-of-life care of patients after dialysis discontinuation . This prospect i ve cohort observational study involves six dialysis clinics in the United States and two clinics in Canada . Data were collected on 131 patients who were undergoing maintenance dialysis and died after treatment discontinuation . Seventy-nine of the patients ( 60 % ) were prospect ively studied until their deaths . Caregivers and families provided information about the symptoms and treatment provided in the final 24 hours of life , and structured interviews were conducted at the time of stopping dialysis with patients and families . The patient population was primarily white ( 73 % ) , elderly ( 70 + /- 1.2 years ) , and diabetic ( 46 % ) . Three quarters of the subjects had between three and seven comorbid conditions . Pain and agitation were the most common symptoms during the last day of life . Terminal treatment was generally considered to be satisfactory , and most people had good deaths . Although dialysis prolongs life , the integration of palliative medicine into dialysis programs offers opportunities to improve the quality of end-of-life care , especially for those patients who elect to stop treatment . Recommendations include making advance care planning an expectation at all clinics and using quality -of-dying measures to establish benchmarks for the provision of terminal care Objectives According to international guidelines , nonsteroidal anti-inflammatory drugs ( NSAIDs ) and opioids are the cornerstone drugs for cancer pain . In clinical practice , severe cancer pain often requires 3 step analgesics and alternative routes of administration , thus NSAIDs are usually ab and oned . Our aim was to evaluate feasibility , safety , and efficacy of ketoprofen combined with opioids in long-term continuous subcutaneous infusion ( CSI ) for cancer pain in a prospect i ve observational open-label pilot study . Methods Ketoprofen was added to morphine CSI in 172 consecutive patients ( study group , SG ) . Concomitantly , 48 received opioids CSI without ketoprofen for contraindication to NSAIDs ( control group , CG ) . CSI was delivered through a single-use elastomeric pump refilled weekly . Safety was evaluated according to the number of adverse events and their severity . The measures of efficacy were pain relief ( NRS , Numerical Rating Scale ) , percentage of patients that needed to increase morphine dosage , and median relative increase between weeks 2 and 4 . Results Toxicity typically attributable to NSAIDs were recorded in 4.1 % of patients after 3 months of treatment and the combination of NSAIDs and corticosteroids seems not to influence the risk of gastrointestinal adverse effects . The local side effects related to the CSI regimen were negligible in both the groups . By the fourth week , pain was well controlled ( NRS 0 to 2 ) in 80 % of patients receiving ketoprofen compared with 46 % of patients without ketoprofen ( P<0.01 . ) Moreover , the percentage of patients needing to increase the morphine dosage ( 40.5 % vs. 68.7 % P<0.01 ) and the relative dose increase ( 12 % vs. 25 % P<0.005 ) were significantly lower in the SG . Conclusions Ketoprofen CSI in combination with opioids is a feasible , safe , and effective approach to cancer pain A scheduled regimen of oral narcotic analgesics was compared with a regimen of oral narcotic analgesics plus ibuprofen for analgesic efficacy in patients with cancer . Ten patients with metastatic cancer were r and omly assigned to receive either ibuprofen 400 mg or a look-alike placebo four times daily in addition to each patient 's existing regimen of scheduled oral narcotics . A two-period changeover study design was used . The 24-hour narcotic intake equated to injectable morphine was computed for each patient at baseline and during the nine study days . A visual analogue scale was used to evaluate pain relief , nausea , mood depression , daytime drowsiness and nighttime sleeplessness . The analgesic efficacy of the narcotic-ibuprofen combination was significantly greater than the analgesic efficacy of the narcotic-placebo combination . Eight patients demonstrated a positive treatment effect with added ibuprofen ; the overall improvement in analgesia averaged 39.1 % in these patients . There was no significant increase from baseline in the incidence of nausea , mood depression , daytime drowsiness or nighttime sleeplessness . At the doses used in this study , a treatment regimen of oral narcotic analgesics plus ibuprofen was more effective than oral narcotics alone in relieving pain associated with cancer It is uncertain whether there exists a nociceptive component in malignant nerve pain responsive to NSAIDs and opioids . 20 patients with malignant nerve pain were r and omly assigned to treatment with naproxen 1500 mg versus slow-release morphine 60 mg daily during 1 week , followed by cross-over medication during the second week in a double-blind , double-dummy protocol . In the 16 evaluable patients , a significant ( P < 0.05 ) reduction of 26 % ( S.E. + /- 7.9 ) in pain intensity was reached at day 7 , compared to baseline pain . At day 7 , significant pain relief of 32 % ( P < 0.05 ) was observed in the naproxen group , but not in the morphine group ( 21 % , P = 0.14 ) . Patients using morphine needed approximately twice as much paracetamol rescue than patients using naproxen . Additional pain relief could be observed in 4/9 patients with cross-over medication . These data support the concept of a nociceptive component in malignant nerve pain responding to NSAIDs and opioids , and favour the combination of both an anti-inflammatory drug and an opioid for symptomatic pain relief Single doses of indoprofen ( 400 mg , i.v . ) , morphine hydrochloride ( 10 mg , i.m . ) , and placebo were given to 12 women with moderate to severe tumor pain , mainly due to bone involvement , according to a Latin square design . Analgesic response , along with serum prolactin ( PRL ) and growth hormone ( GH ) levels , were measured after each treatment under double-blind conditions . Indoprofen and morphine were not significantly different as regards pain relief , but both were significantly more effective than placebo . Unlike morphine , however , indoprofen did not raise PRL . GH levels did not change following any treatment . In a second study indoprofen ( 400 mg , i.v . , three times daily for 7 days ) did not modify the PRL response to thyrotropin-releasing hormone nor serum GH levels . On the basis of the above findings it is suggested that indoprofen may be a safe alternative to opiates for relief of moderate to severe pain in women with breast tumors suspected of being prolactin-dependent WHAT IS KNOWN AND OBJECTIVE Bone-cancer pain is a common and refractory cancer pain . Opioids , on their own , do not control this type of pain well enough , and co-analgesics are necessary . METHODS Patients with bone metastasis-related pain at Numeric Rating Scale ≥4 were enrolled to this r and omized placebo-controlled trial . They had also received morphine or transdermal fentanyl patches for at least 1 week . During the 3-day efficacy phase , patients received placebo or 1 - 3 tablets of oxycodone/paracetamol ( 5/325 mg ) , four times daily for 3 days . All patients kept a daily pain diary . The primary endpoint was the Pain Intensity Difference ( PID ) . Secondary endpoints were cases of breakthrough pain and rescue morphine consumption . Additional analyses included the Short Form-6 Dimensions ( SF-6D ) quality -of-life scale and a general impression ( GI ) of patient satisfaction with treatment at the end of the phase . RESULTS AND DISCUSSION Of the 246 patients in the intent-to-treat set , 89·4 % completed the 3-day efficacy phase . PIDs were 0·9 and 0·3 in the oxycodone/paracetamol and placebo groups respectively , on day 1 ( P < 0·001 ) , and 1·5 and 0·3 respectively on day 3 ( P < 0·001 ) . Thirty-eight patients in the treatment group , and 58 in the placebo group , suffered breakthrough pain on day 3 ( P < 0·001 ) . The SF-6D score decreased to 21·2 ± 2·5 in the oxycodone/paracetamol group at the end of the phase ( P = 0·001 ) . In the oxycodone/paracetamol group , 67 % rated GI as good , very good , or excellent . WHAT IS NEW AND CONCLUSION Patients with bone-cancer pain , already on opioids , obtain clinical ly important , additional pain-control , with regular oxycodone/paracetamol dosing Ketorolac tromethamine administered intramuscularly ( i.m . ) 10 mg 6-hourly was compared with morphine 10 mg i.m . 6-hourly in a r and omised , double-blind , cross-over trial for its analgesic efficacy and safety in 51 patients with moderate to severe cancer pain . There was no overall significant difference between the analgesic effect of the two treatments . 57 % of ketorolac- and 74 % of morphine-treated patients changed their analgesic . Among these , significantly more patients stopped ketorolac than morphine due to pain ( p=0.007 ) whilst more patients discontinued morphine than ketorolac because of adverse effects ( p=0.001 ) , predominantly emesis . Only one patient ( 2 % ) stopped ketorolac because of intolerance . Ketorolac shows promise as an effective and well tolerated analgesic for cancer pain and merits further study The efficacy and tolerability of acetylsalicylic acid , paracetamol , diclofenac , ibuprofen , indomethacin , pirprofen , sulindac , naproxen and suprofen were compared in the treatment of cancer pain . In a double-blind , within-patient r and omized study , each drug was given for 1 week to eight patients and for another week to a further eight patients . A total of 65 patients were effectively treated ; only 48 completed week 1 and 41 completed week 2 . Naproxen , diclofenac and indomethacin were highly effective in pain relief ( tested by means of a 100 mm visual analogue scale ) and were relatively well tolerated . It is concluded that these non-steroidal anti-inflammatory drugs can be considered as first choice in the treatment of cancer pain Thirty-six patients suffering from severe pain due to bone involvement from cancer participated in an analgesic study that compared single doses of ketoprofen 100 or 400 mg iv or injectable acetylsalicylic acid 1 g. A double-blind , balanced incomplete block design was adopted , in which each patient received two of the three test treatments , with an interval of 24 hours . Ketoprofen 400 mg proved significantly superior to 100 mg of the same drug , and was superior to 1 g of the acetylsalicylic acid derivative in the patients ' assessment of the overall response . This was expressed by a visual analog scale and preferences . No adverse reaction was observed with any treatment In a r and omized single-blind study carried out simultaneously in five Departments for Pain Therapy and Palliative Care , the analgesic efficacy and side effects of oral ketorolac ( ketorolac tromethamine , Tora-Dol , CAS 74103 - 07 - 4 ) and diclofenac sodium were compared in a population of 100 advanced cancer patients suffering from somatic and /or visceral pain . The treatment was carried out in agreement with the first step of the WHO pharmacological strategy in cancer pain . The administered dosage was 10 mg every 6 h for ketorolac and 50 mg every 8 h for diclofenac sodium . The study showed the efficacy of both drugs in cancer pain . A greater number of keterolac patients could pass to the second WHO step later than diclofenac patients . As to the tolerability , both drugs turned out to be similar , except for " sleepiness " , which was four times more frequent ( p < 0.05 ) in the diclofenac group A r and omized double-blind trial was performed to evaluate the efficacy of a new non-steroidal anti-inflammatory analgesic drug , ketorolac , in the treatment of cancer pain compared with the opioid pentazocine . A total of 40 patients with moderate to severe cancer pain were studied , 20 patients being treated with 10 mg ketorolac given orally every 6 h and 20 receiving 50 mg pentazocine given orally every 6 h for up to 7 days . A reduction in the severity of the pain was recorded in both treatment groups with no significant difference in efficacy being found between the two therapies , although withdrawals due to adverse reactions were significantly less in the ketorolac-treated group ( P < 0.005 ) . It is concluded that ketorolac may be a useful and more acceptable alternative to opioids in the treatment of cancer pain This r and omized double-blind crossover study compares the narcotic methadone alone with methadone in combination with the peripherally acting , antiprostagl and in agent ibuprofen ( Motrin , Upjohn ) in 28 patients with moderate to severe cancer-related pain , who were already using a narcotic for pain relief . Results show that the addition of 600 mg of ibuprofen to either 2.5 or 5 mg of methadone significantly increased analgesia , without concomitantly increasing side effects or euphoria CONTEXT The adjunctive use of paracetamol ( acetaminophen ) with strong opioids has become entrenched practice in palliative care pain management , despite little evidence to support its use . OBJECTIVE The study aim was to investigate potential analgesic benefits of 4 g of paracetamol daily for palliative cancer patients requiring high-dose opioids . METHODS Thirty-one patients , using at least 200 mg of oral morphine equivalent daily , were recruited to a prospect i ve , double-blinded , r and omized , crossover trial . Patients received usual medications plus 4 g of paracetamol or placebo for five days each in r and om order . Primary outcome , effect on pain , was assessed using daily diaries , including a numerical rating scale ( NRS ) from zero ( no pain ) to 10 ( unbearable ) and recording numbers of breakthrough analgesics . Secondary outcomes -nausea , vomiting , cognitive impairment , constipation , and overall well-being -- were assessed using the NRS . Data from the last four days of each treatment were analyzed . Patients also indicated in which part of the study their pain was better controlled . RESULTS Twenty-two patients , requiring a median dose of 255 mg of oral morphine equivalent daily , completed the trial . There were no significant order or treatment-by-order interaction effects for any variable ; paired t-tests were conducted to investigate change in mean levels on outcome variables with placebo vs. paracetamol . For none of the variables was there a statistically significant difference when assessed with placebo compared with paracetamol . No change approached clinical ly significant levels , with a mean difference in rated pain of 0.16 , and mean difference of 0.42 for a number of breakthrough medications . Fifteen patients were undecided whether paracetamol improved pain . CONCLUSIONS These data do not support the common practice of adding regular paracetamol daily as an adjunct to high-dose opioids for pain control in cancer patients receiving palliative care Thirty subjects with chronic moderate to severe pain who were receiving oxycodone/acetaminophen ( oxy/APAP ) for analgesia were initially evaluated for at least 7 days for oxy/APAP requirements for pain control . Each subject then received , in a r and omized double‐blind fashion , either 600 mg ibuprofen or placebo for an additional 7 days while hospitalized . Oxy/APAP usage was recorded daily along with efficacy and toxicity parameters . Overall global evaluations were also recorded on completion of the study . Comparison of mean differences before and after treatment with ibuprofen or placebo indicated a marked decrease in oxy/APAP use with ibuprofen ( p < 0.01 ) and a slight increase in use in the placebo group . Reduction in oxy/APAP usage occurred within 24 hours and maximized at 5 days . Overall global scores showed a marked preference for the ibuprofen combination over placebo ( p < 0.01 ) . Daily pain intensity ( p < 0.05 ) and pain relief scores ( p < 0.05 ) also improved with the addition of ibuprofen . This study indicates that ibuprofen is efficacious in the management of chronic cancer pain , result ing in both enhanced analgesia and a reduction in concomitant narcotic use This study investigated the opioid-sparing effect of diclofenac using patient-controlled analgesia with oral methadone . Fifteen patients with advanced cancer participated . After achieving adequate analgesia with regular dosing of oral methadone ( T1 ) , patient-controlled analgesia with methadone was administered for 3 days ( T2 ) . Intramuscular diclofenac 75 mg twice daily was then added to this regimen for 3 days ( T3 ) . Compared to T2 values , methadone dose was significantly reduced at T2 and T2 , and pain report ( recorded on a visual analogue scale ) was significantly reduced at T3 . A reduction in methadone plasma concentration was also observed at T2 and T3 , although it did not attain statistical significance . Significant decreases in the intensity of several symptoms other than pain were also found at T2 and T3 . Diclofenac appears to have a relevant opioid-sparing effect when using patient-controlled analgesia with oral methadone AIM To compare the analgesic efficacy and toxicity of the nonsteroidal anti-inflammatory analgesic drug , ketorolac ( Toradol , Recordati spa , Milan ) 10 mg p.o . ( t.i.d . ) with diclofenac ( Voltaren , Novartis Farma , Origglo , VA ) 50 mg p.o . ( t.i.d . ) in cancer patients with moderate to severe chronic pain . METHODS AND STUDY DESIGN The study was a multicenter r and omized double-blind cross-over trial . Each treatment lasted 7 days , after which the patients crossed over to the other drug . Pain intensity was evaluated by the visual analogue scale ( VAS ) after the first dose and by the 5-point verbal rating scale ( VRS ) by the patient and by the physician following the 7-day treatment . RESULTS AND CONCLUSIONS A total of 138 advanced cancer patients were enrolled in the study . Overall 251 single-dose administrations ( 117 cross-over observations ) and 257 multiple treatments ( 127 cross-over experiments ) were assessable . After a single administration of ketorolac and diclofenac , no significant difference could be observed in analgesic activity , as indicated by the area under the pain-intensity time curve ( AUC0 - 8 ) , in the maximum efficacy , or the duration of efficacy of the two drugs . The Westlake confidence intervals of the AUC0 - 8 ratio ( ketorolac : diclofenac ) ( 1.07 ; 90 % CI , 0.94 - 1.19 ) , of the maximum efficacy ratio ( 1.03 ; 90 % CI , 0.92 - 1.14 ) , and the duration of efficacy ratio ( 1.05 ; 90 % CI , 0.97 - 1.11 ) showed the bioequivalence of the two drugs . Satisfactory pain relief was reported for multiple 7-day treatments , with no significant differences between the two therapies : according to the physician 's evaluation , in 93/128 ( 73 % ; 95 % CI , 65 - 80 % ) ketorolac treatments and 91/129 ( 71 % ; 95 % CI , 63 - 78 % ) diclofenac treatments ; according to the patient 's evaluation , in 83/128 cases ( 65 % ; 95 % CI , 57 - 73 % ) after ketorolac and in 74/129 cases ( 57 % ; 95 % CI , 49 - 66 % ) after diclofenac . Adverse symptoms were acceptable with both drugs . Interestingly , a pronounced sequence effect was found : gastric disturbances after ketorolac were observed mainly ( 10 out of 15 observed events ) when the drug was given to patients pretreated with diclofenac PURPOSE To determine whether adding regular acetaminophen ( paracetamol ) could improve pain and well-being in people with advanced cancer and pain despite strong opioids . PATIENTS AND METHODS Participants took acetaminophen for 48 hours and placebo for 48 hours . The order ( acetaminophen or placebo first ) was r and omly allocated . Pain was the primary outcome . Preferences , number of opioid breakthrough doses , overall well-being , nausea and vomiting , drowsiness , constipation , and cold sweats were secondary outcomes . Patients rated themselves daily with visual analog scales ( VAS ) and a verbal numeric scale ( VNS ) for pain , all scaled from 0 to 10 . RESULTS Thirty patients completed the trial . The oral opioid was morphine in 23 patients and hydromorphone in seven patients . The median daily opioid dose in oral morphine equivalents was 200 mg ( range , 20 to 2,100 mg ) . Nonsteroidal anti-inflammatory drugs , corticosteroids , or both were used by 16 patients . Pain and overall well-being were better for patients receiving acetaminophen than for those receiving placebo . The mean difference was 0.4 ( 95 % CI , 0.1 to 0.8 ; P = .03 ) in VNS for pain , 0.6 ( 95 % CI , -0.1 to 1.3 ; P = .09 ) in VAS for pain , and 0.7 ( 95 % CI , 0.0 to 1.4 ; P = .05 ) in VAS for overall well-being . More patients preferred the period they took acetaminophen ( n = 14 ) than the period they took placebo ( n = 8) , but many had no preference ( n = 8) . There were no differences in the other outcomes . CONCLUSION Acetaminophen improved pain and well-being without major side effects in patients with cancer and persistent pain despite a strong opioid regimen . Its addition is worth considering in all such patients OBJECTIVE The objective of this study was to compare the effectiveness of combination hydrocodone 7.5 mg and ibuprofen 200 mg with that of combination codeine 30 mg and acetaminophen 300 mg for the treatment of chronic pain . BACKGROUND Hydrocodone 7.5 mg with ibuprofen 200 mg is the only approved fixed-dose combination analgesic containing an opioid and ibuprofen . METHODS In this r and omized , parallel-group , double-blind , repeated-dose , active-comparator , 4-week , multicenter study , 469 patients were r and omly assigned to receive a 1-tablet ( n = 156 ) or 2-tablet ( n = 153 ) dose of combination hydrocodone 7.5 mg and ibuprofen 200 mg ( HI1 and HI2 , respectively ) or a 2-tablet dose of combination codeine 30 mg and acetaminophen 300 mg ( CA , n = 160 ) , the active comparator , every 6 to 8 hours as needed for pain . Efficacy was measured through pain relief scores , number of daily doses of study medication , number of daily doses of supplemental analgesics , number of patients who discontinued therapy due to an unsatisfactory analgesic response , and global assessment scores . RESULTS Of the 469 patients , 255 ( 54.4 % ) were female and 214 ( 45.6 % ) were male . The mean age was 51.1 years . Types of chronic pain included back ( 214 ; 45.6 % ) , arthritic ( 145 ; 30.9 % ) , other musculoskeletal ( 65 ; 13.9 % ) , cancer ( 6 ; 1.3 % ) , diabetic neuropathic ( 3 ; 0.6 % ) , postherpetic neuralgic ( 5 ; 1.1 % ) , other neurologic ( 21 ; 4.5 % ) , and other unclassified chronic pain ( 10 ; 2.1 % ) . During the 48 hours prior to the study , 351 ( 74.8 % ) patients had been treated with opioid or opioid-nonopioid combination analgesics . The overall mean daily pain relief score was significantly greater in the HI2 group ( 2.25+/-0.89 ) than in the HI1 group ( 1.98+/-0.87 ) ( P = 0.003 ) or the CA group ( 1.85+/-0.96 ) ( P < 0.001 ) . The overall mean number of daily doses of study medication was significantly less in the HI2 group ( 2.94+/-0.99 ) than in the HI1 group ( 3.23+/-0.76 ) ( P = 0.036 ) or the CA group ( 3.26+/-0.75 ) ( P = 0.014 ) . The overall mean number of daily doses of supplemental analgesics was significantly less in the HI2 group ( 0.24+/-0.49 ) than in the HI1 group ( 0.34+/-0.58 ) ( P = 0.021 ) or CA group ( 0.49+/-0.85 ) ( P = 0.010 ) . The number of patients who discontinued treatment due to an unsatisfactory analgesic response was significantly less in the HI2 group ( 2 ; 1.3 % ) than in the CA group ( 12 ; 7.5 % ) ( P = 0.008 ) . HI2 was more effective than HI1 and CA as measured by pain relief scores for week 1 ( P < 0.001 vs HI1 and CA ) , week 2 ( P < 0.001 vs HI1 and CA ) , and week 3 ( P = 0.008 vs HI1 and P < 0.001 vs CA ) ; daily doses of study medication for week 1 ( P = 0.019 vs HI1 and P = 0.011 vs CA ) ; daily doses of supplemental analgesics for week 1 ( P = 0.010 vs HI1 and CA ) ; and global assessment scores for week 1 ( P = 0.018 vs HI1 and P < 0.001 vs CA ) , week 2 ( P = 0.005 vs HI1 and P < 0.001 vs CA ) , and week 4 ( P = 0.013 vs HI1 and P = 0.023 vs CA ) . There were no significant differences between HI1 and CA in any efficacy variable . There were no significant differences in the number of patients experiencing adverse events in the HI2 ( 127 ; 83 % ) , HI1 ( 124 ; 79.5 % ) , and CA ( 129 ; 80.6 % ) groups . However , the mean number of patients who discontinued treatment due to adverse events was significantly greater in the HI2 group ( 40 ; 26.1 % ) than in the HI1 group ( 23 ; 14.7 % ) ( P = 0.013 ) . CONCLUSIONS The results of this study suggest that 2-tablet doses of combination hydrocodone 7.5 mg and ibuprofen 200 mg may be more effective than either 1-tablet doses of this combination or 2-tablet doses of combination codeine 30 mg and acetaminophen 300 mg . Moreover , 1-tablet doses of combination hydrocodone 7.5 mg and ibuprofen 200 mg may be as effective as 2-tablet doses of combination codeine 30 mg and acetaminophen 300 mg Seventy-five patients with moderate to severe cancer pain were r and omly assigned in a double-blind fashion to receive first-dose ketorolac tromethamine 10 mg orally , acetaminophen 600 mg plus codeine 60 mg orally , or placebo , followed by subsequent doses of ketorolac or acetaminophen plus codeine four times daily for 7 days . Patient characteristics were similar among the treatment groups . The first-dose observation documented that both ketorolac and acetaminophen plus codeine produced an equivalent reduction in cancer pain and were superior to placebo as measured by pain intensity differences and pain relief . Multidose comparison documented a small but statistically significant advantage in mean daily pain relief favoring acetaminophen plus codeine , although there were no differences in mean daily ratings of overall effects for either study medication . Adverse symptoms were acceptable with both ketorolac and acetaminophen plus codeine . We conclude that ketorolac has significant analgesic activity in patients with cancer pain , although its precise role in the treatment regimen of these patients remains undefined In a multicentric , interindividual , double-blind study , the analgesic action , duration of effect , tolerability and side effects of the new combination preparation , Combaren ( diclofenac-Na 50 mg+codeine phosphate 50 mg ) , were compared with those of diclofenac-Na 50 mg ( Voltaren 50 ) in 184 patients with severe tumor-related pain . The results show that Combaren is a highly effective preparation for the treatment of severe tumor pain . The combination of diclofenac-Na with codeine phosphate leads to a clear , statistically significant , augmentation of the effectiveness of additionally used analgesics on pain severity , and the general effectiveness of the combination is more positively assessed that that of monotherapy with diclofenac ( also effective ) . In the staged approach to the treatment of malignancy-related pain in which the aim is to provide continuous , preventive analgesia rather than ad hoc treatment of newly developing or worsening pain , this combination preparation will presumably find a permanent place in stage I/II of the generally accepted staged pain-treatment scheme Summary 64 patients with pain associated with advanced cancer were treated with either nimesulide or diclofenac as initial analgesia . Patients were r and omly allocated to 1 of 4 treatment groups : oral nimesulide 300 mg/day ; oral diclofenac 150 mg/day ; rectal nimesulide 400 mg/day ; and rectal diclofenac 200 mg/day . After 1 week of treatment , both drugs provided an adequate degree of pain relief and allowed an increase in sleep duration . There were no significant differences in efficacy between the drugs or routes of administration . Fewer side effects were observed with nimesulide , giving this agent a better therapeutic index than the reference compound In a double‐blind study , indoprofen was superior to placebo in decreasing pain in patients with primary and metastatic cancer and with neuralgia . A single oral dose of 200 mg was more active than a 100‐mg dose . The preferences of patients proved to be a more sensitive parameter in this study than scores of pain intensity , pain relief , and other related measurements ( SPID , TOTPAR , and Peak PID ) In a double-blind clinical trial the analgesic efficacy and safety of ethyl-N-(2-amino-6-[4-fluorophenyl-methylamino ] pyridin-3-yl)carbamate ( flupirtine , design ated trademark : Katadolon ) as 100-mg capsules were compared to pentazocine capsules 50 mg in 52 patients with severe to very severe cancer pain . The duration of treatment was up to one week , the daily dose up to 6 capsules . The analgesic effect was assessed by a 4-point verbal rating scale . In both drug groups was no difference between the baseline pain intensity . Moreover , also the dosage ( number of capsules/day ) was similar in both groups . Final evaluation demonstrated that flupirtine was significantly more effective than pentazocine in reducing pain . The incidence of side-effects was similar in both treatment groups , flupirtine , however , caused less intensive and less clinical ly relevant adverse reactions . In conclusion the results indicate that flupirtine is a potent and well tolerated analgesic in the treatment of cancer pain This double-blind , placebo controlled study compared the analgesic efficacy of piroxicam with acetylsalicylic acid ( ASA ) in patients having continuous pain with advanced head and neck cancers . They were r and omly divided into two groups of 25 patients each ; 36 of these 50 patients completed the study . After four days of treatment , there was a significant reduction in a modified numerical rating scale ( NRS ) of pain in the piroxicam group as well as in the ASA group . There was a concomitant increase in the hours of sleep in the piroxicam group and in the ASA group . The decrease in NRS and the increase in sleeping hours was not statistically significantly different between the two groups . Patients receiving piroxicam had a low incidence of upper gastrointestinal side-effects compared with those receiving ASA . The results of this study suggest that piroxicam can be used as first line treatment in place of ASA in patients with head and neck cancers suffering from moderate to severe pain . The advantages are less frequent dosing , better patient compliance and few side-effects Summary The effectiveness of diclofenac 50 mg t.i.d . as additive treatment to parenteral patient-controlled administration therapy ( PCAT ) with morphine in cancer pain has been investigated in a double-blind study . In the fifteen patients who completed the study , morphine i.v . was titrated to optimal pain relief over 5 days . The mean total morphine consumption was significantly reduced during diclofenac administration ( 82.8 mg morphine per day ) compared to placebo ( 95.0 mg morphine per day ) . The reduction in mean morphine consumption during active treatment with diclofenac was independent of the initial dose of self-titrated morphine . Pain , self-assessed according to VAS , tended to be lower during the diclofenac period , although the difference did not reach statistical significance . No adverse events were recorded among the 15 patients who completed the study .The present findings show that a non-steroidal anti-inflammatory agent , such as diclofenac , has a morphine-sparing effect in morphine-treated patients with cancer pain A double-blind study of analgesic drug combinations was conducted , involving 100 patients with pain due to cancer . The combinations of 650 mg of aspirin plus either 65 mg of codeine , 9.76 mg of oxycodone , or 25 mg of pentazocine hydrochloride each produced significantly greater pain relief than aspirin alone . Side effects for a single dose of these effective combinations were essentially equal and clinical ly tolerable . The combinations of 650 mg of aspirin plus either 65 mg of caffeine , 32 mg of pentobarbital sodium , 25 mg of promazine hydrochloride , 75 mg of ethoheptazine citrate , or 100 mg of propoxyphene napsylate did not show significant advantage in analgesic effect over aspirin alone . ( JAMA 229:55 - 59 , 1974 The analgesic efficacy of naproxen ( 500 mg / 12 h ) and aspirin ( 600 mg / 4 h ) in 28 patients with advanced malignant disease was assessed in a r and omized , double-blind , cross-over study of two weeks ’ duration . Efficacy was assessed using severity of pain ( linear analogue self- assessment ) , pain score ( McGill Pain Question naire ) , pain severity , and time of onset of pain relief . Both analgesics provided equal , highly effective relief of pain . It is concluded that naproxen is a useful addition to the analgesics available for patients with advanced malignant disease and has the advantage of 12-h rather than 4-h dosage In a single-blind r and om study , simultaneously carried out by five Pain Therapy and Palliative Care Centres , the analgesic power and side-effects of sodium naproxen ( CAS 26159 - 34 - 2 ) and sodium diclofenac ( CAS 15307 - 86 - 5 ) by mouth were compared in a group of 100 advanced cancer patients . The patients complained of somatic and /or visceral pain and were treated with non-steroid anti-inflammatories as required . The dose administered amounted to 550 mg every 12 h for sodium naproxen and to 100 mg every 12 h for sodium diclofenac . The study stressed the similar analgesic effect of the two drugs -- pain intensity and duration decreased by half in the first week of treatment-- and a comparatively low morbidity rate Evaluation of the analgesic activity of indoprofen was carried out in patients with cancer pain under double‐blind conditions and compared with aspirin and placebo . A r and omized experimental design was followed . Single oral doses were given of the test drug ( 100 and 200 mg ) , aspirin ( 600 and 1,000 mg ) , and placebo . For measuring analgesia , 5‐point pain intensity and pain relief semiquantitative scales were used . Potency ratio between drugs was calculated on SPID ( sum of pain intensity differences ) and TOTPAR ( total pain relief ) and result ed in 10.3 by combination of estimates . In a group of only 24 patients , the data supported the following conclusions : indoprofen at 100 and 200 mg single doses is effective in relieving cancer pain ; it displays a dose‐related analgesic effect comparable to that of aspirin with only one‐tenth the dose |
12,259 | 30,810,255 | Optical fluorescence imaging demonstrated positive results , with higher sensitivity scores , increased lesion detection and visualisation than comprehensive oral examination alone in the clinical evaluation of oral squamous cell carcinoma and oral potentially malignant disorders . | OBJECTIVES This study aim ed to systematic ally review the efficacy of direct optical fluorescence imaging as an adjunct to comprehensive oral examination in the clinical evaluation , risk assessment and surgical management of oral cancer and potentially malignant disorders . | BACKGROUND The clinical oral examination ( COE ) is the criterion st and ard for the initial detection of oral lesions that harbor dysplasia or oral squamous cell carcinoma ( OSCC ) at an early stage when they are most treatable . The authors conducted a systematic review to assess the effectiveness of the COE in predicting histologic diagnosis of dysplasia or OSCC . METHODS The authors conducted automated search es of PubMed , Web of Knowledge , and the Cochrane Library from 1966 through 2010 for r and omized controlled trials and observational studies that included the terms " oral mucosal lesion screening " and " oral lesions . " They determined the quality ( sensitivity , specificity , positive predictive value , negative predictive value and diagnostic odds ratio ) of selected studies by using the Quality Assessment of Diagnostic Accuracy Studies tool . RESULTS The overall diagnostic odds ratio was 6.1 ( 95 % confidence interval , 2.1 - 17.6 ) ; therefore , the COE was considered to have poor overall performance as a diagnostic method for predicting dysplasia and OSCC . CLINICAL IMPLICATION S On the basis of the available literature , the authors determined that a COE of mucosal lesions generally is not predictive of histologic diagnosis . The fact that OSCCs often are diagnosed at an advanced stage of disease indicates the need for improving the COE and for developing adjuncts to help detect and diagnose oral mucosal lesions BACKGROUND The aim of this prospect i ve study was to evaluate the efficacy of a new form of autofluorescence imaging and tissue reflectance spectroscopy ( Identafi , DentalEZ ) in examining patients with oral mucosal lesions . METHODS The authors examined 88 patients with 231 oral mucosal lesions by conventional oral examination ( COE ) using white-light illumination and ×2.5 magnification loupes , followed by examination using Identafi . The authors noted fluorescence visualization loss , the presence of blanching , and diffuseness of vasculature . They performed incisional biopsies to provide definitive histopathologic diagnosis . RESULTS Identafi 's white light produced lesion visibility and border distinctness equivalent to COE . Identafi 's violet light displayed a sensitivity of 12.5 % and specificity of 85.4 % for detection of oral epithelial dysplasia ( OED ) . The authors noted visible vasculature using the green-amber light in 40.9 % of lesions . CONCLUSIONS Identafi 's intraoral white light provided detailed visualization of oral mucosal lesions comparable with examination using an extraoral white-light source with magnification . A high level of clinical experience is required to interpret the results of autofluorescence examination as the violet light displayed low sensitivity for detection of OED . The green-amber light provided additional clinical information in relation to underlying vasculature and inflammation of lesions . PRACTICAL IMPLICATION S Examination using Identafi can provide clinicians with more clinical data than a st and ard COE with yellow inc and escent light , but the clinical and optical findings should be interpreted as a whole and not in isolation . Clinicians should use the light features of Identafi in a sequential and differential manner The prognosis for patients with oral squamous cell carcinoma remains poor despite advances in multimodal treatment concepts . Early diagnosis and treatment is the key to improved patient survival . A device ( VELscope ) that uses autofluorescence technology , allowing direct fluorescence visualization of the oral cavity , might be a useful tool for oral cancer detection or as an adjunct to st and ard clinical examination . A total of 289 patients with oral premalignant lesions were r and omly divided into two groups for clinical examination of precancerous oral lesions . In group 1 , 166 patients were examined conventionally with white light , and in group 2 , 123 patients were examined with the autofluorescence visualization device ( VELscope ) in addition to the white light examination . Biopsies were obtained from all suspicious areas identified in both examination groups ( n=52 ) . In the first step , baseline characteristics of the two groups ( only white light vs. white light and VELscope ) were compared to exclude selection bias . In the second step , for the group examined with white light and VELscope ( 123 patients ) , the diagnostic strategies were compared with regard to sensitivity and specificity using biopsy as the gold st and ard . The results showed that using the VELscope leads to higher sensitivity ( 100 % instead of 17 % ) , but to lower specificity ( 74 % instead of 97 % ) . Thus , we can conclude that the VELscope is a useful new diagnostic device for detection of oral cancer diseases The survival of patients with oral cancer is decreased by locoregional recurrence after an initial multimodal treatment . In order to identify lesions in the oral cavity for a possible recurrence , clinical evaluation as well as MRI or CT scanning is advised . The evaluation of mucosa lesions is hampered by changes related to radio- and chemotherapy as well as reconstruction with tissue flaps . Several techniques for easier identification of tissue abnormalities in the oral cavity have been advocated as adjuncts in order to facilitate identification . Especially methods using altered tissue fluorescence have gained much interest during the last decade . The aim of our prospect i ve study was to evaluate fluorescence properties of undiagnosed mucosa lesions with the VELscope device in patients with multimodal treated oral cancer prior to histological confirmation . In total , 41 patients with a history of oral squamous cell carcinomas ( OSCC ) ( 19 females and 22 males ) with undiagnosed mucosa lesions where included in the study . After clinical evaluation , examination and documentation using the VELscope ® device were performed . Then , an incisional biopsy was performed . An autofluorescence loss indicating a malignant or dysplastic mucosa condition could be detected in six patients ( 14.6 % ) ; however , only one OSCC and one SIN revealed a complete autofluorescence loss . In four patients , OSCC was present in lesions with retained autofluorescence . Sensitivity and specificity for the VELscope ® examination to identify malignant oral lesions by autofluorescence were 33.3 and 88.6 % , respectively . The positive and negative predictive values were 33.3 and 88.6 % , respectively . No statistical correlation between gender and lesion appearance versus autofluorescence loss could be detected . In contrast to mucosa lesions in patients with no prior treatment , the autofluorescence evaluation with the VELscope reveals no additional information in our analysis . Accordingly , invasive biopsies as gold st and ard are still needed to get sufficient evidence regarding potential malignancy in patients after multimodal treatment for oral cancer BACKGROUND An expert panel convened by the American Dental Association ( ADA ) Council on Scientific Affairs and the Center for Evidence -Based Dentistry conducted a systematic review and formulated clinical recommendations to inform primary care clinicians about the potential use of adjuncts as triage tools for the evaluation of lesions , including potentially malignant disorders ( PMDs ) , in the oral cavity . TYPES OF STUDIES REVIEW ED This is an up date of the ADA 's 2010 recommendations on the early diagnosis of PMDs and oral squamous cell carcinoma . The authors conducted a systematic search of the literature in MEDLINE and Embase via Ovid and the Cochrane Central Register of Controlled Trials to identify r and omized controlled trials and diagnostic test accuracy studies . The authors used the Grading of Recommendations Assessment , Development and Evaluation approach to assess the certainty in the evidence and to move from the evidence to the decisions . RESULTS The panel formulated 1 good practice statement and 6 clinical recommendations that concluded that no available adjuncts demonstrated sufficient diagnostic test accuracy to support their routine use as triage tools during the evaluation of lesions in the oral cavity . For patients seeking care for suspicious lesions , immediate performance of a biopsy or referral to a specialist remains the single most important recommendation for clinical practice . In exceptional cases , when patients decline a biopsy or live in rural areas with limited access to care , the panel suggested that cytologic testing may be used to initiate the diagnostic process until a biopsy can be performed ( conditional recommendation , low- quality evidence ) . CONCLUSIONS AND PRACTICAL IMPLICATION S The authors urge clinicians to remain alert and take diligent action when they identify a PMD . The authors emphasize the need for counseling because patients may delay diagnosis because of anxiety and denial OBJECTIVE AND STUDY DESIGN Several noninvasive adjunctive methods have been proposed for identification of potentially malignant mucosa lesions . The VELscope is an optical device for detecting spatial changes in mucosa autofluorescence caused by premalignant lesions in conjunction with an intraoral exam . The aim of our prospect i ve study was to correlate loss of autofluorescence from undiagnosed mucosa lesions with histology . RESULTS In total 64 patients considered at risk for squamous cell carcinoma ( 20 had previous OSCC ) were included in the study . Regions with fluorescence visualization loss were considered as malignant or dysplastic . All patients underwent biopsy after VELscope examination . In 22 patients ( 34.4 % ) a loss of autofluorescence indicating a squamous intraepithelial neoplasia ( SIN ) or malignant mucosal lesion was detected . The sensitivity of identification of malignant and dysplastic areas with the VELscope was 100 % and the specificity was 80.8 % , respectively , compared with histology as gold st and ard . The positive predictive value was 54.5 % and the negative predictive value was 100 % respectively . CONCLUSION Evaluation of autofluorescence imaging with VELscope can assist in the identification of malignant and potentially malignant oral lesions from normal mucosa in high-risk patients but does not help discriminating benign lesions from malignant or premalignant mucosal conditions BACKGROUND To analyze the efficacy of fluorescence visualization in early detection of oral early neoplastic processes when used by an inexperienced and an adept oral examiner . METHODS A dental student and an expert professional in oral diagnosis examined 15 r and omly selected patients using conventional oral examination and fluorescence visualization search ing for early signs of epithelial dysplasia and oral potentially malignant disorders . Patients detected with oral lesions in any of examinations were su bmi tted to incisional biopsy for definitive diagnosis . RESULTS Taking histopathologic analysis as Gold St and ard , sensitivity , specificity , positive and negative predictive values and accuracy of inexperienced examiner for detecting both epithelium dysplasia and oral potentially malignant disorders increased when using fluorescence visualization compared to conventional white light examination , matching the same values found for expert professional in oral diagnosis . Furthermore , it was possible to observe discrete increase in the efficacy of expert professional 's examination when using fluorescence visualization . CONCLUSION This study indicates fluorescence visualization is capable of improve inexperienced professionals ' efficacy for early detecting oral lesions more prone to be dysplastic and oral potentially malignant disorders Objective . Although approved by the US Food and Drug Administration for clinical use , the utility of h and held tissue reflectance and autofluorescence devices for screening head and neck cancer patients is poorly defined . There is limited published evidence regarding the efficacy of these devices . The authors investigated the sensitivity and specificity of these modalities compared with st and ard examination . Study Design . Prospect i ve , cross-sectional analysis . Setting . Tertiary care medical center . Subjects and Methods . Patients who were treated previously for head and neck cancer ( n = 88 ) between 2009 and 2010 were included . Patients were screened using white light visualization ( st and ard of care ) and compared with tissue reflectance and autofluorescence visualization . Screening results were compared with biopsy or long-term follow-up . Results . Autofluorescence visualization had a specificity of 81 % and a sensitivity of 50 % for detecting oral cavity cancer , whereas white light visualization had a specificity of 98 % and a sensitivity of 50 % . Tissue reflectance visualization had low sensitivity ( 0 % ) and good specificity ( 86 % ) . The power of this study was insufficient to compare the positive and negative predictive values of st and ard white light examination ( 50 % and 98 % , respectively ) to tissue autofluorescence ( 11 % and 97 % ) or reflectance ( 0 % and 95 % ) . In addition , stratification by previous radiation therapy found no statistically significant difference in screening results . Conclusion . St and ard clinical lighting has a higher specificity than tissue reflectance and autofluorescence visualization for detection of disease in patients with a history of head and neck cancer . This study does not support the added costs associated with these devices OBJECTIVE To determine the usefulness of the VELscope in detecting malignant and premalignant oral cavity lesions . STUDY DESIGN Prospect i ve clinical study . SETTING Head and neck oncology clinic at an academic tertiary care centre . SUBJECTS AND METHODS Eighty-five patients with a history of smoking , alcohol use , and /or head and neck cancer were recruited into the study . The VELscope was used to examine patients ' oral cavities after a clinical examination . Biopsies were then taken from suspicious areas . RESULTS Of the 85 patients included in the study , 33 underwent biopsies prompted by a clinical examination , the VELscope , or both . Biopsy results that showed invasive malignancy or dysplasias were considered positive . Five positive biopsies for premalignant lesions were detected only by the VELscope and were not visible on clinical examination . On the other h and , only one positive biopsy for a premalignant lesion was detected by the clinical examination only and not seen on the VELscope . Seven positive biopsies were detected by both methods . This indicates that the diagnostic yield from a regular examination was 47 % ( 95 % CI 23 - 72 ) and that the diagnostic yield from the addition of the VELscope was an additional 31 % ( 95 % CI 11 - 59 ) . Sensitivity and specificity for the VELscope were 92 % and 77 % , respectively . CONCLUSION The Velscope may add sensitivity to the clinical examination and be a useful adjunct in high-risk patients |
12,260 | 31,437,211 | Here we provide initial synthesis ed quantitative evidence of the effectiveness of behavioural interventions for treating sleep problems in children with ASD . | BACKGROUND Autism spectrum disorders ( ASD ) are a set of neurodevelopmental disorders characterised by behavioural , communication and social impairments .
The prevalence of sleep disturbances in children with ASD is 40 - 80 % , with significant effects on quality of life for the children and carers .
This systematic review aim ed to synthesis e evidence of the effects of behavioural interventions to improve sleep among children with ASD .
CONCLUSIONS There are very few high quality r and omised controlled trials in this area . | Although melatonin and cognitive-behavioural therapy have shown efficacy in treating sleep disorders in children with autism spectrum disorders , little is known about their relative or combined efficacy . One hundred and sixty children with autism spectrum disorders , aged 4 - 10 years , suffering from sleep onset insomnia and impaired sleep maintenance , were assigned r and omly to either ( 1 ) combination of controlled-release melatonin and cognitive-behavioural therapy ; ( 2 ) controlled-release melatonin ; ( 3 ) four sessions of cognitive-behavioural therapy ; or ( 4 ) placebo drug treatment condition for 12 weeks in a 1 : 1 : 1 : 1 ratio . Children were studied at baseline and after 12 weeks of treatment . Treatment response was assessed with 1-week actigraphic monitoring , sleep diary and sleep question naire . Main outcome measures , derived actigraphically , were sleep latency , total sleep time , wake after sleep onset and number of awakenings . The active treatment groups all result ed in improvements across all outcome measures , with moderate-to-large effect sizes from baseline to a 12-week assessment . Melatonin treatment was mainly effective in reducing insomnia symptoms , while cognitive-behavioural therapy had a light positive impact mainly on sleep latency , suggesting that some behavioural aspects might play a role in determining initial insomnia . The combination treatment group showed a trend to outperform other active treatment groups , with fewer dropouts and a greater proportion of treatment responders achieving clinical ly significant changes ( 63.38 % normative sleep efficiency criterion of > 85 % and 84.62 % , sleep onset latency < 30 min ) . This study demonstrates that adding behavioural intervention to melatonin treatment seems to result in a better treatment response , at least in the short term OBJECTIVE Sleep difficulties are common reasons why parents seek medical intervention in children with autism spectrum disorders ( ASDs ) . We determined whether a pamphlet alone could be used by parents to help their child ’s insomnia . METHODS Thirty-six children with ASD , ages 2 to 10 years , were enrolled . All had prolonged sleep latency confirmed by actigraphy showing a mean sleep latency of 30 minutes or more . Parents were r and omly assigned to receive the sleep education pamphlet or no intervention . Children wore an actigraphy device to record baseline sleep parameters , with the primary outcome variable being change in sleep latency . Actigraphy data were collected a second time 2 weeks after the parent received the r and omization assignment and analyzed by using Student ’s t test . Parents were also asked a series of questions to gather information about the pamphlet and its usefulness . RESULTS Although participants r and omized to the 2 arms did not differ statistically in age , gender , socioeconomic status , total Children ’s Sleep Habits Question naire score , or actigraphy parameters , some differences may be large enough to affect results . Mean change in sleep-onset latency did not differ between the r and omized groups ( pamphlet versus no pamphlet ) . Parents commented that the pamphlet contained good information , but indicated that it would have been more useful to be given specific examples of how to take the information and put it into practice . CONCLUSIONS A sleep education pamphlet did not appear to improve sleep latency in children with ASDs Objective : Sleep problems are common in children with autism spectrum disorders ( ASD ) and ADHD and impact adversely on child and parent well-being . The study evaluated the efficacy of a brief behavioral sleep intervention in children with comorbid ADHD – ASD . Method : A sub sample of children with ADHD – ASD ( n = 61 ; 5 - 13 years ; 89 % male ) participating in the Sleeping Sound With ADHD study were included in the current investigation . The sub sample comprised of 28 children r and omized to the sleep intervention group , while 33 were r and omized to usual clinical care . The intervention consisted of two clinical consultations and a follow-up phone call covering sleep hygiene and st and ardized behavioral strategies . Results : Children with ADHD – ASD who received the intervention had large improvements in sleep problems and moderate improvements in child behavioral functioning 3 and 6 months post-r and omization . Conclusion : These findings suggest that a brief behavioral sleep intervention can improve sleep problems in children with ADHD – ASD OBJECTIVES A large percentage of children with autism spectrum disorders ( ASD ) have bedtime and sleep disturbances . However , the treatment of these disturbances has been understudied . The purpose of our study was to develop a manualized behavioral parent training ( BPT ) program for parents of young children with ASD and sleep disturbances and to test the feasibility , fidelity , and initial efficacy of the treatment in a small r and omized controlled trial ( RCT ) . PARTICIPANTS AND METHODS Parents of a sample of 40 young children diagnosed with ASD with an average age of 3.5years were enrolled in our study . Participants were r and omized to either the BPT program group or a comparison group who were given nonsleep-related parent education . Each participant was individually administered a 5-session program delivered over the 8-week study . Outcome measures of feasibility , fidelity , and efficacy were collected at weeks 4 and 8 after the baseline time point . Children 's sleep was assessed by parent report and objective ly by actigraphy . RESULTS Of the 20 participants in each group , data were available for 15 participants r and omized to BPT and 18 participants r and omized to the comparison condition . Results supported the feasibility of the manualized parent training program and the comparison program . Treatment fidelity was high for both groups . The BPT program group significantly improved more than the comparison group based on the primary sleep outcome of parent report . There were no objective changes in sleep detected by actigraphy . CONCLUSIONS Our study is one of few RCTs of a BPT program to specifically target sleep disturbances in a well-characterized sample of young children with ASD and to demonstrate the feasibility of the approach . Initial efficacy favored the BPT program over the comparison group and suggested that this manualized parent training approach is worthy of further examination of the efficacy within a larger RCT |
12,261 | 28,233,406 | The presence of global contractile reserve at baseline , as assessed by dobutamine stress echocardiography , is associated with a higher chance of CRT response in patients with heart failure | AIM To perform a meta- analysis and systematic review of published data to assess the relationship between contractile reserve and response to cardiac resynchronization therapy ( CRT ) in patients with heart failure . | BACKGROUND Recently concluded multicenter studies have shown that none of an array of echocardiographic indicators of ventricular dyssynchrony have enough sensitivity and specificity for predicting response to cardiac resynchronization therapy ( CRT ) . Inotropic contractile reserve ( ICR ) on dobutamine stress echocardiography can differentiate viable myocardium from scar and is a predictor of improvement in regional and global left ventricular function in patients with cardiomyopathy . Its role in patients undergoing CRT is unknown . The aim of this study was to evaluate the role of ICR in predicting response to CRT in patients with markedly remodeled left ventricles . METHODS Fifty-four patients ( mean age , 69±11 years ; 63 % men ) referred for clinical ly indicated CRT were evaluated . All patients underwent low-dose dobutamine stress echocardiography to assess for ICR , defined as an improvement in contractility in more than five of 16 left ventricular segments . RESULTS During a mean follow-up period of 206±167 days , 31 patients ( 57 % ) were responders , as defined by a 5-point increase in ejection fraction after CRT . The presence of ICR was a stronger predictor of response to CRT ( area under the curve , 0.94 ; χ2=39.0 ; P<.0001 ) compared with dyssynchrony ( area under the curve , 0.74 ; χ2=10.07 ; P=.002 ) . It was a significant predictor of response ( odds ratio , 2.84 ; 95 % confidence interval , 1.59 to 5.09 ; P<.0001 ) , even after controlling for the other predictors , and provided incremental prognostic value beyond that provided by QRS duration and dyssynchrony ( increase in area under the curve from 0.47 to 0.75 to 0.93 ; P=.030 and P=.008 ) . CONCLUSIONS In patients referred for CRT , ICR was a stronger predictor of response and provided incremental value beyond that of current known predictors of response to CRT ( dyssynchrony and QRS duration ) . Dobutamine stress echocardiography may have an important role in identifying CRT responders , and further multicenter studies are needed to confirm this AIMS Contradicting reports have been published regarding the relation between a dobutamine-induced increase in either cardiac dyssynchrony or left-ventricular ejection fraction ( LVEF ) and the response to cardiac resynchronization therapy ( CRT ) . Using apical rocking ( ApRock ) as surrogate dyssynchrony parameter , we investigated the dobutamine stress echocardiography (DSE)-induced changes in left-ventricular ( LV ) dyssynchrony and LVEF and their potential pathophysiological interdependence . METHODS AND RESULTS Fifty-eight guideline -selected CRT c and i date s were prospect ively enrolled for low-dose DSE . Dyssynchrony was quantified by the amplitude of ApRock . An LVEF increase during stress of > 5 % was regarded significant . Scar burden was assessed by magnetic resonance imaging . Mean follow-up after CRT implantation was 41 ± 13 months for the occurrence of cardiac death . ApRock during DSE predicted CRT response ( AUC 0.88 , 95 % CI 0.77 - 0.99 , P < 0.001 ) and correlated inversely with changes in EF ( r = -0.6 , P < 0.001 ) . Left-ventricular ejection fraction changes during DSE were not associated with CRT response ( P = 0.082 ) . Linear regression analysis revealed an inverse association of LVEF changes during DSE with both , total scar burden ( B = -2.67 , 95CI -3.77 to -1.56 , P < 0.001 ) and the DSE-induced change in ApRock amplitude ( B = -1.23 , 95 % CI -1.53 to -0.94 , P < 0.001 ) . Kaplan-Meier analysis revealed that DSE-induced increase in ApRock , but not LVEF , was associated with improved long-term survival . CONCLUSION During low-dose DSE in CRT c and i date s with baseline dyssynchrony , myocardial contractile reserve predominantly results in more dyssynchrony , but less in an increase in LVEF . Dyssynchrony at baseline and its dobutamine-induced changes are predictive of both response and long-term survival following CRT Background — Data from single-center studies suggest that echocardiographic parameters of mechanical dyssynchrony may improve patient selection for cardiac resynchronization therapy ( CRT ) . In a prospect i ve , multicenter setting , the Predictors of Response to CRT ( PROSPECT ) study tested the performance of these parameters to predict CRT response . Methods and Results — Fifty-three centers in Europe , Hong Kong , and the United States enrolled 498 patients with st and ard CRT indications ( New York Heart Association class III or IV heart failure , left ventricular ejection fraction ≤35 % , QRS ≥130 ms , stable medical regimen ) . Twelve echocardiographic parameters of dyssynchrony , based on both conventional and tissue Doppler – based methods , were evaluated after site training in acquisition methods and blinded core laboratory analysis . Indicators of positive CRT response were improved clinical composite score and ≥15 % reduction in left ventricular end-systolic volume at 6 months . Clinical composite score was improved in 69 % of 426 patients , whereas left ventricular end-systolic volume decreased ≥15 % in 56 % of 286 patients with paired data . The ability of the 12 echocardiographic parameters to predict clinical composite score response varied widely , with sensitivity ranging from 6 % to 74 % and specificity ranging from 35 % to 91 % ; for predicting left ventricular end-systolic volume response , sensitivity ranged from 9 % to 77 % and specificity from 31 % to 93 % . For all the parameters , the area under the receiver-operating characteristics curve for positive clinical or volume response to CRT was ≤0.62 . There was large variability in the analysis of the dyssynchrony parameters . Conclusion — Given the modest sensitivity and specificity in this multicenter setting despite training and central analysis , no single echocardiographic measure of dyssynchrony may be recommended to improve patient selection for CRT beyond current guidelines . Efforts aim ed at reducing variability arising from technical and interpretative factors may improve the predictive power of these echocardiographic parameters in a broad clinical setting OBJECTIVE To underst and whether patients with post-ischemic dilated cardiomyopathy and myocardial viability ( MV ) could benefit from cardiac resynchronization therapy ( CRT ) in terms of clinical , echocardiographic and neuro- hormonal parameters compared to patients without MV . METHODS One hundred and four consecutive patients were enrolled in a prospect i ve observational cohort study . Using dobutamine stress echocardiography , 2 groups were identified : group A of 51 patients with MV and group B of 53 patients without MV . All patients were implanted with biventricular pacing devices combined with an internal cardioverter-defibrillator . Clinical , echocardiographic and neuro-hormonal parameters were evaluated at baseline and at six month follow-up . Analysis of variance for repeated measures on each variable suggestive of remodeling was performed . We considered responder every patient with : decrease of > 15 % in left ventricular volumes and /or improvement in left ventricular ejection fraction of > 5 % in addition to NYHA class improvement . RESULTS All the variables improved in both groups ( time effect ) . Comparing the two groups ( group effect ) , the following variables were significantly better in group A : N-terminal pro-B-type natriuretic peptide ( p=0.02 ) , NYHA class ( p=0.003 ) , reverse remodeling ( RR ) ( p=0.007 ) , dP/dt ( p=0.005 ) , left ventricular ejection fraction ( p=0.009 ) , 3rd sound ( p=0.01 ) , and left ventricular end-systolic volume after the first week ( p=0.035 ) . RR occurred at the first week after CRT only in Group A and was maintained for all the time of this study . The maximum difference of the decrease of left ventricular volumes between the two groups occurred after the first week ( p<0.001 ) . CONCLUSION Patients with MV responded better than patients without MV with a significant improvement after the first week from CRT BACKGROUND The clinical response to biventricular pacing is unpredictable , especially in patients with ischemic cardiomyopathy . OBJECTIVES The purpose of this study was to prospect ively examine the relationship between the extent of myocardial viability and the response to cardiac resynchronization therapy . METHODS Twenty-one patients with ischemic left ventricular ( LV ) dysfunction ( left ventricular ejection fraction [ LVEF ] 21 + /- 5 % ) , New York Heart Association ( NYHA ) functional class III-IV , and QRS > 120 ms received biventricular devices . Myocardial viability was assessed by myocardial contrast echocardiography , and a perfusion score index ( PSI ) was calculated from summed segmental perfusion scores . LV performance was assessed by echocardiography on the day after implantation and at 6 months . RESULTS PSI was closely correlated with acute improvement in LVEF ( P = .003 , r = 0.65 ) , stroke volume ( P = .02 , r = 0.54 ) , and end-systolic volume ( P = .05 , r = -0.49 ) . PSI also correlated with early diastolic LV relaxation ( E ' , P < .05 , r = 0.50 ) and global myocardial performance or Tei index ( P = .003 , r = 0.63 ) . By multiple linear regression analysis , PSI provided incremental predictive value to the degree of dyssynchrony , measured by tissue Doppler imaging , for predicting improvement in LVEF . At 6 months , PSI remained positively correlated with improvement in ventricular performance and with reduction in LV end-diastolic dimension ( P = .003 , r = -0.68 ) . PSI also influenced the clinical variables of NYHA class , 6-minute walk distance , quality -of-life score , and number of hospitalizations for heart failure . CONCLUSION In patients with ischemic cardiomyopathy , the extent of myocardial viability predicts acute and long-term improvement in LV performance , exercise tolerance , and reduction in LV end-diastolic dimension with biventricular pacing A substantial proportion of patients who meet the current guidelines for cardiac resynchronization therapy ( CRT ) fail to respond to this pacing modality . Although appropriate patient selection and left ventricular ( LV ) lead location have been ascribed as determinants of CRT response , the interaction among contractile reserve , dynamics of dyssynchrony , and lead location is not well understood . The present study prospect ively evaluated the effect of contractile reserve and dobutamine-induced changes in LV synchrony , in relation to the LV lead location , as predictors of the response to CRT . In the present study , 31 patients were prospect ively evaluated and underwent low-dose dobutamine echocardiography . The dobutamine-induced increase in ejection fraction ( contractile reserve [ CR ] ) was measured , and the most mechanically delayed segment was identified to classify patients into 2 groups . Group 1 had a CR of > 20 % and a LV lead position concordant with the mechanically delayed segment . Group 2 included the remaining patients ( i.e. , low CR , discordant LV lead position , or both ) . Patients in group 1 were significantly more likely to have an echocardiographic response at 6 months ( 80 % of group 1 vs 29 % of group 2 , p = 0.018 ) and had an improved 2-year heart failure hospitalization-free survival rate ( 90 % in group 1 vs 33 % in group 2 , p = 0.006 ) . In conclusion , low-dose dobutamine echocardiography provides information that can help to predict responders to CRT . The response rates and heart failure hospitalization-free survival were improved in those patients with a CR > 20 % and an LV lead tip concordant with the most delayed mechanical segment BACKGROUND Cardiac resynchronization therapy ( CRT ) is effective in selected patients with heart failure ( HF ) . Nevertheless , the nonresponder rate remains high . The low-dose dobutamine stress-echo ( DSE ) test detects the presence of left ventricular ( LV ) contractile reserve ( LVCR ) in HF patients of any etiology and may be useful in predicting response to resynchronization . OBJECTIVE The purpose of this study was to present the results of the LODO-CRT trial , which evaluated whether LVCR presence at baseline increases the chances of response to CRT . METHODS LODO-CRT is a multicenter prospect i ve study that enrolled CRT c and i date s according to guidelines . LVCR presence was defined as an LV ejection fraction increase > 5 units during DSE test . CRT response is assessed at 6-month follow-up as an LV end-systolic volume reduction ≥10 % . RESULTS Two hundred seventy-one patients were enrolled . The DSE test was feasible without complications in 99 % of patients . Nine patients died from noncardiac disease , and 31 presented inadequate data . Two hundred thirty-one patients were included in the analysis . Mean patient age was 67 ± 10 years ; 95 % were in New York Heart Association class III , and 42 % had HF of ischemic etiology . Mean QRS and LV ejection fraction were 147 ± 25 ms and 27 % ± 6 % , respectively . LVCR presence was found in 185 subjects ( 80 % ) . At follow-up , 170 ( 74 % ) patients responded to CRT , 145/185 in the group with LVCR ( 78 % ) and 25/46 ( 54 % ) in the group without LVCR . Difference in responder proportion to CRT was 24 % ( P < .001 ) . Reported test sensitivity is 85 % . CONCLUSION The DSE test in CRT c and i date s is safe and feasible . LVCR presence at baseline increases the chances of response to CRT BACKGROUND The presence of viable myocardium may predict response to cardiac resynchronization therapy ( CRT ) . The aim of this study is to evaluate in patients with left ventricular ( LV ) dyssynchrony whether response to CRT is related to myocardial viability in the region of the pacing lead . METHODS Forty-nine consecutive patients with advanced heart failure , LV ejection fraction < 35 % , QRS duration > 120 ms and intraventricular asynchronism > or = 50 ms were included . Dobutamine stress echocardiography was performed within the week before CRT implantation . Resting echocardiography was performed 6 months after CRT implantation . Viability in the region of LV pacing lead was defined as the presence of viability in two contiguous segments . Response to CRT was defined by evidence of reverse LV remodeling ( > or = 15 % reduction in LV end-systolic volume ) . RESULTS Thirty-one patients ( 63 % ) were identified as responders at follow-up . The average of viable segments was 5.9 + /- 2 in responders and 3.2 + /- 3 in nonresponders ( P = 0.0003 ) . Viability in the region of the pacing lead had a sensitivity of 94 % , a specificity of 67 % , a positive predictive value of 83 % , and a negative predictive value of 86 % for the prediction of response to CRT . CONCLUSIONS In patients with LV dyssynchrony , reverse remodeling after CRT requires viability in the region of the pacing lead . This simple method using echocardiography dobutamine for the evaluation of local viability ( i.e. , viability in two contiguous segments ) may be useful to the clinician in choosing the best LV lead positioning AIM Left ventricular ( LV ) lead position at the latest mechanically activated non-scarred myocardial LV region confers improved response to cardiac resynchronization therapy ( CRT ) . We conducted a double-blind , r and omized controlled trial to evaluate the clinical benefit of multimodality imaging-guided LV lead placement in CRT . METHODS AND RESULTS Patients were allocated ( 1:1 ) to imaging-guided LV lead placement using cardiac computed tomography ( CT ) venography , 99 m Technetium myocardial perfusion imaging , and speckle-tracking echocardiography radial strain to target the optimal coronary sinus ( CS ) branch closest to the non-scarred myocardial segment with latest mechanical activation ( imaging group , n = 89 ) or to routine LV lead implantation in a posterolateral region with late electrical activation ( control group , n = 93 ) . The primary endpoint was clinical non-response to CRT [ ≥1 of the following after 6 months : ( 1 ) death , ( 2 ) heart failure hospitalization , or ( 3 ) no improvement in New York Heart Association class and < 10 % increase in 6-min walk distance ] . Secondary outcomes included LV remodelling and the combination of all-cause mortality and hospitalization owing to heart failure during 1.8 ± 0.9 years . Analysis was intention-to-treat . In the imaging group , fewer patients reached the primary endpoint ( 26 % vs. 42 % , P = 0.02 ) . More patients in the imaging group had the LV lead placed in the optimal CS branch ( 83 % vs. 65 % , P = 0.01 ) . There were no between-group differences in reverse LV remodelling or the combined endpoint of death or hospitalizations for heart failure . CONCLUSIONS Multimodality imaging-guided LV lead placement towards the CS branch closest to latest mechanically activated non-scarred myocardial LV segment reduces the proportion of clinical non-responders to CRT . Larger long-term multicentre studies are needed |
12,262 | 22,940,882 | Antifibrinolytics are effective in reducing blood loss and transfusion requirements in major pediatric surgery .
TXA and EACA also appear to have reasonable side-effect profiles . | A systematic review aim ed to evaluate the efficacy and safety of aprotinin , epsilon-aminocaproic acid ( EACA ) , and tranexamic acid ( TXA ) in reducing perioperative blood loss , risk for transfusion , and total perioperative transfusion volume in major pediatric surgery . | Pediatric patients who undergo posterior spinal fusion surgery to correct scoliosis often require multiple blood transfusions . Tranexamic acid is a synthetic antifibrinolytic drug that reduces transfusion requirements in cardiac surgery and total knee arthroplasty . We evaluated the efficacy of prophylactic tranexamic acid to reduce perioperative blood transfusion requirements in a prospect i ve , double-blinded , placebo control study . Forty patients , 9–18 yr of age , were r and omized to either tranexamic acid ( initial dose of 10 mg/kg and infusion of 1 mg · kg−1 · h−1 ) or placebo ( isotonic saline ) . Perioperative management was st and ardized . A uniform transfusion threshold for noncell saved red blood cells was 7.0 g/dL. The total amount of blood transfused in the perioperative period was significantly reduced in the Tranexamic group ( P = 0.045 ) . No thrombotic complications were detected in either group . The administration of prophylactic tranexamic acid in patients with scoliosis undergoing posterior spinal fusion surgery has the potential to reduce perioperative blood transfusion requirements Background : Previous studies have noted that the use of antifibrinolytic medications can help reduce blood loss and transfusion requirements during cardiac , total joint arthroplasty , and spine surgery . Tranexamic acid ( TXA ) has been investigated in these patient groups but consensus with respect to the dosing regimen has not been achieved , especially in the pediatric scoliosis literature . The purpose of this study was to compare the effects of 2 TXA dosing regimens on reducing transfusion requirements . Methods : A retrospective chart review was performed on all idiopathic scoliosis patients undergoing posterior spinal instrumentation and fusion from 2005 to 2006 to determine total perioperative transfusion requirements . Transfusion requirements for those patients receiving either a low ( 10 mg/kg loading , 1 mg/kg/h infusion ) or high ( 20 mg/kg loading , 10 mg/kg/h infusion ) dose of TXA were compared . Results : High-dose TXA ( n = 11 ) showed a trend toward a reduction in transfusion requirements compared with the low dose ( n = 15 ) for idiopathic scoliosis patients undergoing posterior only instrumentation and fusion ( 687.9 ± 778.1 mL vs 1372.6 ± 1077.3 mL ; P = 0.07 ; 95 % confidence interval for the mean difference , −66.3 mL to 1435.7 mL ) . Although substantial , this difference was underpowered to show a difference . Conclusions : The use of the higher dose of TXA result ed in a 50 % reduction in transfusion requirements for idiopathic scoliosis patients . Given previous studies , there appears to be a dose-response effect . A prospect i ve dose-ranging study is now required to determine the optimal dose for pediatric patients with idiopathic scoliosis . Level of Evidence : III , retrospective cohort study Background : Excessive bleeding often occurs during pediatric scoliosis surgery and is attributed to numerous factors , including accelerated fibrinolysis . The authors hypothesized that administration of tranexamic acid would reduce bleeding and transfusion requirements during scoliosis surgery . Methods : Forty-four patients scheduled to undergo elective spinal fusion were r and omly assigned to receive either 100 mg/kg tranexamic acid before incision followed by an infusion of 10 mg · kg−1 · h−1 during surgery ( tranexamic acid group ) or 0.9 % saline ( placebo group ) . General anesthesia was administered according to a st and ard protocol . Blood loss , transfusion requirements , coagulation parameters , and complications were assessed . Results : In the tranexamic acid group , blood loss was reduced by 41 % compared with placebo ( 1,230 ± 535 vs. 2,085 ± 1,188 ml ; P < 0.01 ) . The amount of blood transfused did not differ between groups ( 615 ± 460 vs. 940 ± 718 ml ; P = 0.08 ) . Administration of tranexamic acid was a multivariate predictor of blood loss , as was American Society of Anesthesiologists physical status and preoperative platelet count . No apparent adverse drug effects occurred in any patient . Conclusion : Intraoperative administration of tranexamic acid significantly reduces blood loss during spinal surgery in children with scoliosis BACKGROUND Aprotinin and epsilon aminocaproic acid are antifibrinolytic agents used to reduce postoperative blood loss after cardiopulmonary bypass . We compared low dose aprotinin with epsilon aminocaproic acid and a combination of the two agents to reduce postoperative blood loss in infants with congenital cyanotic heart disease undergoing corrective surgical procedures . METHODS This prospect i ve study was conducted r and omly on 300 children . Group I ( n = 80 ) acted as the control and did not receive either of the study drugs . Group II ( n = 100 ) received low dose aprotinin , group III ( n = 60 ) received epsilon aminocaproic acid , and group IV ( n = 60 ) received a combination of the two antifibrinolytic agents . RESULTS The control group had the longest time for sternal closure , maximum blood loss at 24 hours , and greatest requirements for packed red blood cells and platelets . Fibrinogen levels were significantly lower , and levels of fibrin breakdown products were significantly higher compared with the groups given either or both of the antifibrinolytics . CONCLUSIONS Epsilon aminocaproic acid is as efficacious as low dose aprotinin in reducing postoperative blood loss and packed red blood cell and platelet requirements in children with congenital cyanotic heart disease . The combination of the two was slightly more effective UNLABELLED In this prospect i ve cohort study of 548 children undergoing open-heart surgery , we evaluated demographic and perioperative factors to identify variables associated with perioperative blood loss and blood product transfusions . Using multivariate analysis , younger patient age was found to be the variable most significantly associated with bleeding and transfusions . Higher preoperative hematocrit , complex surgery , lower platelet count during cardiopulmonary bypass ( CPB ) , and longer duration of deep hypothermic circulatory arrest were also significantly associated with bleeding and transfusion . Excessive postoperative chest tube ( CT ) drainage was associated with intraoperative bleeding . Independently associated variables accounted for 76 % of the variability in CT output measured after 2 h in intensive care . Patients were subdivided into children aged < or = 1 yr ( infants ) and children > 1 yr ; infants bled more intraoperatively ( P<0.005 ) ; had greater cumulative CT output at 2 , 6 , 12 , and 24 h ( P<0.0001 ) ; and received more blood products ( P<0.0001 ) . Factors associated with bleeding and transfusions varied with patient age . Lower body core temperature during CPB was highly associated with blood loss and transfusions in infants , whereas resternotomy , preoperative congestive heart failure , and prolonged duration of CPB were significant factors associated with bleeding and transfusions in children > 1 yr old . IMPLICATION S Knowledge of the factors associated with blood loss and blood product transfusions can help to identify children at risk of excessive bleeding after open-heart surgery Background : Surgical correction of craniosynostosis in children is associated with substantial intraoperative bleeding . Tranexamic acid ( TXA ) decreases intraoperative blood loss during cardiac or orthopedic surgery in children . We hypothesized that intraoperative TXA would reduce blood transfusion relative to placebo in patients pretreated with erythropoietin . Methods : Forty consecutive children , American Society of Anesthesiologists status 1 or 2 , scheduled to undergo surgical correction of craniosynostosis were r and omly assigned to receive either intravenous TXA or saline , 0.9 % , intraoperatively . All children received preoperative erythropoietin ( 600 U/kg once a week for 3 weeks before surgery ) . Perioperative blood loss , number and volume of transfusions , percentage of children who underwent transfusion , and side effects were noted after surgery and at the end of the study . Surgeon satisfaction and cost of treatment were also recorded . Results : There was no significant difference between groups in demographic or surgical data . In the TXA group , the volume of packed erythrocytes transfused was significantly reduced by 85 % ( from 11 to 1.6 ml/kg ) intraoperatively and by 57 % ( from 16.6 to 7.2 ml/kg ) throughout the study period ( P < 0.05 ) . Compared with the placebo group , the percentage of children requiring blood transfusion was lower in the TXA group during surgery ( 9 [ 45 % ] of 20 vs. 2 [ 11 % ] of 19 children ; P < 0.05 ) and during the whole study period ( 14 [ 70 % ] of 20 vs. 7 [ 37 % ] of 19 ; P < 0.05 ) . Preoperative and postoperative hematologic parameters were comparable in both groups . There were no adverse events . Conclusion : In children undergoing surgical correction of craniosynostosis and pretreated with erythropoietin , intraoperative TXA reduces the transfusion requirement Study Design . A retrospective study of the effectiveness of Amicar ( epsilon aminocaproic acid ) . Objective . Evaluate the effectiveness of Amicar in decreasing perioperative blood loss and transfusion requirements in same-day anterior ( ASF ) and posterior spinal fusion ( PSF ) with segmental spinal instrumentation ( SSI ) for idiopathic scoliosis . Summary of Background Data . Preliminary prospect i ve , prospect i ve r and omized double-blind , and fibrinogen studies have demonstrated Amicar to be effective in decreasing perioperative blood loss in patients with idiopathic scoliosis undergoing PSF with SSI . Increased fibrinogen secretion is a possible explanation . Methods . There were 73 consecutive patients divided into 3 study groups based on the administration of Amicar : Group 1 ( n = 16 ) , no Amicar ; Group 2 ( n = 18 ) , Amicar for the PSF with SSI only ; and Group 3 ( n = 39 ) , Amicar for both ASF and PSF with SSI . All patients were managed using the same general anesthesia technique , intraoperative procedure , postoperative care path , and indications for transfusion ( hemoglobin < 7g/dL ) . Total perioperative blood loss ( estimated intraoperative blood loss for both procedures and measured postoperative chest tube and PSF wound suction drainage ) and total transfusion requirements between groups were compared using one-way ANOVA . Results . There were statistically significant decreases in mean estimated intraoperative PSF with SSI , total perioperative blood loss , and transfusion requirements in the 2 Amicar groups . However , Amicar had no significant effect on estimated intraoperative ASF blood loss , chest tube drainage , or PSF wound suction drainage . Total perioperative blood loss and transfusion requirements ( cell saver , autologous , directed , and allogeneic blood ) were : 3442.8 ± 1344.0 mL and 1537.1 ± 905.1 mL in Group 1 ; 2089.8 ± 684.0 mL and 485.2 ± 349.8 mL in Group 2 ; and 2184.1 ± 1163.7 mL and 531.5 ± 510.5 mL in Group 3 . There were no Amicar related complications . Conclusion . Amicar was highly effective in decreasing total perioperative blood loss and transfusion requirements in same-day ASF and PSF with SSI for idiopathic scoliosis . It results in less preoperative autologous blood donation , perioperative blood transfusion , costs , and potential transfusion-related complications . It was mosteffective in decreasing intraoperative estimated PSF with SSI blood loss . It had no significant effect during the ASF , postoperative chest tube , or PSF wound suction drainage . We now recommend that it be used for the PSF with SSI procedure only We performed a prospect i ve , r and omized , placebo-controlled , double-blind trial to assess the efficacy of aprotinin in 61 children ( median age 3.7 yr ) undergoing reoperative open heart surgery ( OHS ) . Three demographically similar groups were studied : large-dose aprotinin ( ALD ) , small-dose aprotinin ( ASD ) , and placebo ( P ) . Over the first 24 postoperative hours fewer patients in the aprotinin groups received packed red cells ( ALD , 53 % ; ASD , 89 % ; and P , 95 % ; P = 0.001 ) , platelets ( ALD , 32 % ; ASD , 50 % ; and P , 65 % ; P = 0.04 ) , and fresh frozen plasma ( ALD , 16 % ; ASD , 17 % ; and P , 60 % ; P = 0.003 ) than placebo patients . Most importantly , aprotinin patients had fewer exposures to banked blood components ( ALD , median 1 U ; and ASD , median 2 U ) than P ( median 6 U ; P = 0.001 ) , with no difference in overall complication rate . Use of aprotinin was associated with a savings in the patient charges for blood components , operating room time , and duration of hospitalization . In conclusion , aprotinin decreased the number of units of banked blood components used during the first 24 postoperative hours in reoperative pediatric OHS . Aprotinin thus decreases the risks associated with exposure to banked blood components and reduces hospital charges . ( Anesth Analg 1996;83:1193 - 9 BACKGROUND Children with cyanotic heart disease undergoing cardiac surgery in which cardiopulmonary bypass is used are at increased risk of postoperative bleeding . In this study , the authors investigated the possibility of reducing postoperative blood loss by using aprotinin and tranexamic acid alone or a combination of these two agents . METHODS In a prospect i ve , r and omized , blind study , 100 children undergoing cardiac surgery were investigated . In group 1 ( n = 25 ) patients acted as the control and did not receive either study drugs . In group 2 ( n = 25 ) patients received aprotinin ( 30.000 KIU.kg(-1 ) after induction of anesthesia , 30.000 KIU.kg(-1 ) in the pump prime and 30.000 KIU.kg(-1 ) after weaning from bypass ) . In group 3 ( n = 25 ) patients received tranexamic acid ( 100 mg.kg(-1 ) after induction of anesthesia , 100 mg.kg(-1 ) in the pump prime and 100 mg.kg(-1 ) after weaning from bypass ) . In group 4 ( n = 25 ) patients received a combination of the two agents in the same manner . Total blood loss and transfusion requirements during the period from protamine administration until 24 h after admission to the intensive care unit were recorded . In addition , hemoglobin , platelet counts and coagulation studies were recorded . RESULTS Postoperative blood loss was significantly higher in the control group ( group 1 ) compared with children in other groups who were treated with aprotinin , tranexamic acid or a combination of the two agents ( groups 2 , 3 and 4 ) during the first 24 h after admission to cardiac intensive care unit ( 40 + /- 18 ml.kg(-1).24 h(-1 ) , aprotinin ; 35 + /- 16 ml.kg(-1).24 h(-1 ) , tranexamic acid ; 34 + /- 19 ml.kg(-1).24 h(-1 ) , combination ; 35 + /- 15 ml.kg(-1).24 h(-1 ) ) . The total transfusion requirements were also significantly less in the all treatment groups . Time taken for sternal closure was longer in the control group ( 68 + /- 11 min ) compared with treatment groups 2 , 3 and 4 , respectively ( 40 + /- 18 , 42 + /- 11 , 42 + /- 13 min , P < 0.05 ) . The coagulation parameters were not found to be significantly different between the three groups . CONCLUSIONS Our results suggested that both agents were effective to reduce postoperative blood loss and transfusion requirements in patients with cyanotic congenital heart disease . However , the combination of aprotinin and tranexamic acid did not seem more effective than either of the two drugs alone BACKGROUND Though multiple studies have affirmed the effectiveness of aprotinin in reducing blood loss in adult cardiac surgery , the possible benefit in pediatric cardiac surgery is controversial . METHODS In a double-blind , r and omized , and placebo-controlled study , the efficacy of aprotinin in attenuating the hemostatic and inflammatory activation during cardiopulmonary bypass in 60 patients weighing less than 10 kg was investigated . Secondary endpoints were the influence of aprotinin on the reduction of blood loss and allogeneic blood requirement , as well as postoperative oxygenation and length of mechanical ventilation . Aprotinin was administered in a high-dose of 3 x 10(4 ) KIU/kg plus a bolus of 5 x 10(5 ) KIU ( not weight adjusted ) added to the pump prime . RESULTS Aprotinin plasma concentration at the end of cardiopulmonary bypass ( CPB ) was with 184 + /- 45 KIU/mL , within the targeted range of 200 KIU/mL. Coagulation and fibrinolysis were suppressed ( F1.2 1 hour after CPB : 5.35 + /- 2.9 nmol/L vs 14.5 + /- 23.1 nmol/L ; D-dimer 1 hour after CPB : 0.63 + /- 0.6 ng/mL vs 2.3 + /- 3.1 ng/mL ; p < 0.05 ) , inflammatory markers ( interleukin [IL]-6 , IL-8 , IL-10 ) increased over time without significant differences between the groups , and only complement C3a activation was significantly attenuated at the end of CPB in the aprotinin group . Chest tube drainage was significantly reduced ( 24 hours : median 13.5 [ IQR 12.2 ] mL/kg vs 19.4 [ 8.2 ] mL/kg ; p < 0.05 ) . All patients received one unit of packed cells to prime the heart lung machine . A second unit was needed significantly less often in the aprotinin group ( 13 % vs 47 % ; p < 0.05 ) . Postoperative oxygenation ( pO2/FIO2 172 [ IQR 128 ] mm Hg vs 127 [ 74 ] ; p < 0.05 ) improved , and the time on ventilator was shorter in the aprotinin group ( median 45 hours [ IQR 94 ] vs 101 [ IQR 74 ] ; p < 0.05 ) . No side effects were attributable to the use of aprotinin . CONCLUSIONS High-dose aprotinin effectively attenuated hemostatic activation and reduced blood loss and transfusion requirement in pediatric cardiac surgery . Postoperative ventilation was also shortened in the aprotinin group BACKGROUND Antifibrinolytic agents are commonly used during cardiac surgery to minimize bleeding and to reduce exposure to blood products . We sought to determine whether aprotinin was superior to either tranexamic acid or aminocaproic acid in decreasing massive postoperative bleeding and other clinical ly important consequences . METHODS In this multicenter , blinded trial , we r and omly assigned 2331 high-risk cardiac surgical patients to one of three groups : 781 received aprotinin , 770 received tranexamic acid , and 780 received aminocaproic acid . The primary outcome was massive postoperative bleeding . Secondary outcomes included death from any cause at 30 days . RESULTS The trial was terminated early because of a higher rate of death in patients receiving aprotinin . A total of 74 patients ( 9.5 % ) in the aprotinin group had massive bleeding , as compared with 93 ( 12.1 % ) in the tranexamic acid group and 94 ( 12.1 % ) in the aminocaproic acid group ( relative risk in the aprotinin group for both comparisons , 0.79 ; 95 % confidence interval [ CI ] , 0.59 to 1.05 ) . At 30 days , the rate of death from any cause was 6.0 % in the aprotinin group , as compared with 3.9 % in the tranexamic acid group ( relative risk , 1.55 ; 95 % CI , 0.99 to 2.42 ) and 4.0 % in the aminocaproic acid group ( relative risk , 1.52 ; 95 % CI , 0.98 to 2.36 ) . The relative risk of death in the aprotinin group , as compared with that in both groups receiving lysine analogues , was 1.53 ( 95 % CI , 1.06 to 2.22 ) . CONCLUSIONS Despite the possibility of a modest reduction in the risk of massive bleeding , the strong and consistent negative mortality trend associated with aprotinin , as compared with the lysine analogues , precludes its use in high-risk cardiac surgery . ( Current Controlled Trials number , IS RCT N15166455 [ controlled-trials.com ] . ) BACKGROUND Neonates undergoing open-heart surgery are especially at risk for massive bleeding and pronounced inflammation . The efficacy of aprotinin , a serine protease inhibitor , at ameliorating these adverse effects of cardiopulmonary bypass has not been clearly demonstrated in neonates . METHODS Term neonates were enrolled and r and omly assigned in a blinded fashion to receive saline ( group P , placebo ) or high-dose aprotinin ( group A ) . Intraoperative management was st and ardized : surgeon , anesthesia , cardiopulmonary bypass and hemostasis therapy . Patients were admitted postoperatively to a pediatric cardiac intensive care unit . Primary outcome measure of efficacy was duration of the postoperative mechanical ventilation . Secondary outcome measures were total volume and units of blood products transfused intraoperatively and for 24 h after surgery , duration of chest tube in situ , and intensive care and hospital stays after surgery . RESULTS Twenty-six neonates were enrolled ; 13 received aprotinin and 13 received placebo . The study was halted prematurely because of US Food and Drug Administration 's concerns about aprotinin 's safety . Baseline patient , surgery and cardiopulmonary bypass characteristics were similar between groups . No outcome variables differed between groups ( P > 0.05 ) . Duration of postoperative ventilation was 115 + /- 139 h ( group A ) ; 126 + /- 82 h ( group P ) ; P = 0.29 , and total blood product exposure was 8.2 + /- 2.6 U ( group A ) ; 8.8 + /- 1.4 U ( group P ) ; P = 0.1 . Postoperative blood creatinine values did not differ between groups . In-hospital mortality rate was 4 % . CONCLUSIONS Aprotinin was not shown to be efficacious in neonates undergoing open-heart surgery . It is unclear whether adult aprotinin safety data are relevant to neonates undergoing open-heart surgery Thirty children undergoing surgical repair for congenital heart defects were r and omly selected for a double-blind study on the anti-hemorrhagic and blood-saving properties of aprotinin . The treatment group comprised 14 patients who received aprotinin 7 mg/kg of body weight until the end of perfusion . The placebo group ( n = 16 ) received an infusion of the corresponding volumes of saline . Patients treated with aprotinin bled less during the operation ( 12.6 ml/kg versus 18.1 ml/kg , p = 0.25 ) and in the first 24 postoperative hours ( chest drainage 12.1 ml/kg versus 17.7 ml/kg , p = 0.07 ) . Hemoglobin loss into chest drainage was reduced in the treated group by half ( 0.66 versus 1.21 gm in 24 hours , p = 0.07 ) . Fewer blood donors were needed during hospitalization by patients receiving aprotinin ( 1.07 versus 2.75 donors per patient , p = 0.04 ) . Postoperative transfusion was unnecessary in 64.2 % of patients receiving aprotinin compared with only 25 % of the placebo group ( p = 0.03 ) . Aprotinin increased diuresis significantly during perfusion ( 4.3 ml/kg versus 1.0 ml/kg , p = 0.005 ) . Other parameters are evaluated , and considerations are made regarding adequacy of the dosage regimen . The drug seems to be safe and easy to h and le in children We have studied the efficacy of epsilon aminocaproic acid in reducing postoperative blood loss in infants and children with congenital cyanotic cardiac anomalies undergoing corrective operative procedures . This prospect i ve study was carried out on 170 infants and children r and omly divided into two equal groups . Group A acted as the control group and received normal saline as placebo while group B patients received epsilon aminocaproic acid ( 100 mg/kg body wt ) intravenously slowly soon after anaesthetic induction followed by 100 mg/kg in the cardiopulmonary bypass pump at the time of starting of cardiopulmonary bypass and 100 mg/kg after weaning from bypass over a period of 3 h. In group A the time for sternal closure after separation from bypass and administration of protamine was 75.18 + /- 5.5 min and in group B 50.7 + /- 5.2 , ( P < 0.001 ) . Blood loss at 24 h in group A was 42.6 + /- 6.9 ml/kg/24 h and in group B 23.7 + /- 5.8 ml/kg/24 h , ( P < 0.001 ) . The need for packed red cells in group A was 21.8 + /- 7.1 ml/kg/24 h and in group B 10.7 + /- 7.8 ml/kg/24 h , ( P < 0.001 ) . The need for platelet concentrate in group A was 22.0 + /- 6.7 ml/kg/24 h and group B 6.2 + /- 3.2 ml/kg/24 h , ( P < 0.001 ) . Fibrin degradation products ( split ) in group A was 8.2 + /- 0.8 micrograms/ml , and group B 3.8 + /- 1.3 micrograms/ml , ( P < 0.001 ) . Reexploration rate was also considerably reduced in group B , 5 of 85 ( 6 % ) compared to group A , 13 of 85 ( 15 % ) , ( P < 0.001 ) . It was found that epsilon aminocaproic acid is effective in reducing postoperative blood loss , packed red cells and plasma product requirements in paediatric patients undergoing corrective surgical procedures for congenital cyanotic heart diseases We have investigated hemostatic parameters including platelet activation in 56 pediatric patients with or without cyanosis undergoing cardiopulmonary bypass ( CPB ) and cardiac surgery to repair congenital defects . Patients were participants in a study assessing the effects of tranexamic acid on surgery-related blood loss . Parameters monitored included blood loss , prothrombin F1.2 , thrombin-antithrombin complexes , t-PA , PAI-1 , plasminogen , fibrin D-dimer , and plasma factor XIII . Additionally , flow cytometry monitored platelet degranulation ( P-selectin or CD63 ) , as well as surface-bound fibrinogen , von Willebr and factor and factor XIIIa . Cyanotic patients had evidence of supranormal coagulation activation as both fibrin D-dimer and PAI-1 levels were elevated prior to surgery . While the extent of expression of P-selectin or CD63 was not informative , platelet-associated factor XIIIa was elevated in cyanotic patients at baseline . In both patient groups , CPB altered platelet activation state and coagulation status irrespective of the use of tranexamic acid OBJECTIVE This study compared the efficacy of aminocaproic acid and tranexamic acid in reducing postoperative blood loss , as well as blood and blood product requirements in children with cyanotic congenital heart disease . DESIGN A prospect i ve r and omized study . SETTING Cardiac center of a tertiary care , referral hospital . PARTICIPANTS One hundred fifty children in the age group of 2 months to 14.5 years with cyanotic congenital heart disease undergoing corrective surgery on cardiopulmonary bypass ( CPB ) . INTERVENTIONS Patients were r and omized into 3 groups . Group A was given aminocaproic acid in a dose of 100 mg/kg after anesthetic induction , 100 mg/kg on CPB and 100 mg/kg after protamine . Group T was given tranexamic acid , 10 mg/kg , after anesthetic induction , 10 mg/kg on CPB , and 10 mg/kg after protamine . Group C was the control group . MAIN RESULT Control group had the longest sternal closure time , maximum blood loss at 24 hours , and maximum requirements of blood and blood products . Among the 2 groups given antifibrinolytics , there was no significant difference in postoperative blood loss , blood and product requirement , and reexploration rates . CONCLUSION Aminocaproic acid and tranexamic acid are equally effective in reducing postoperative blood loss , as well as blood and blood product requirements in children with cyanotic heart disease undergoing corrective surgery as compared with the control group Aprotinin is a proteinase inhibitor with antifibrinolytic properties that has found widespread application during cardiac surgical procedures due to its ability to decrease blood loss and transfusion requirements . Recently it has been used by orthopedic surgeons in hip replacement and other major surgeries except for scoliosis surgery , which is known to be associated with major blood loss . To evaluate the effect of aprotinin in reducing blood loss during spinal fusion surgery for idiopathic scoliosis , a double-blind r and omized prospect i ve clinical study was performed . Forty-three patients with idiopathic scoliosis underwent spinal fusion and instrumentation and were divided r and omly into two groups . Fifteen patients received aprotinin , whereas 28 patients received placebo . The aprotinin group had less blood loss than the placebo group . The transfusion requirement was less in the aprotinin group than the placebo group . Although the difference was not significant statistically , the benefit of aprotinin in reducing blood loss in spinal surgery for idiopathic scoliosis was consistent BACKGROUND Aprotinin consistently reduces blood loss and transfusion requirements in adults during and after cardiac surgical procedures , but its effectiveness in children is debated . We evaluated the hemostatic and economic effects of aprotinin in children undergoing reoperative cardiac procedures with cardiopulmonary bypass . METHODS Control , low-dose aprotinin , and high-dose aprotinin groups were established with 15 children per group . Platelet counts , fibrinogen levels , and thromboelastographic values at baseline and after protamine sulfate administration , number of blood product transfusions , and 6-hour and 24-hour chest tube drainage were used to evaluate the effects of aprotinin on postbypass coagulopathies . Time needed for skin closure after protamine administration and lengths of stay in the intensive care unit and the hospital were recorded prospect ively to determine the economic impact of aprotinin . RESULTS Coagulation tests performed after protamine administration rarely demonstrated fibrinolysis but did show significant decreases in platelet and fibrinogen levels and function . The thromboelastographic variables indicated a preservation of platelet function by aprotinin . Decreased blood product transfusions , shortened skin closure times , and shortened duration s of intensive care unit and hospital stays were found in the aprotinin groups , most significantly in the high-dose group with a subsequent average reduction of nearly $ 3,000 in patient charges . CONCLUSIONS In children undergoing reoperative cardiac surgical procedures , aprotinin is effective in attenuating postbypass coagulopathies , decreasing blood product exposure , improving clinical outcome , and reducing patient charges BACKGROUND The use of aprotinin in children undergoing cardiopulmonary bypass is controversial . We hypothesized that aprotinin would reduce blood product use and operative closure time in selected pediatric patients . METHODS For a 6-month period starting in October 1999 , consecutive cardiopulmonary bypass patients 6 months of age or less ( n = 18 ) or having a repeat sternotomy ( n = 18 ) received aprotinin . Similar consecutive patients from the preceding 6 months served as controls ( n = 35 and 41 , respectively ) . Data extracted from medical records included preoperative clinical characteristics , operative and postoperative procedures , and total blood product use . RESULTS Patients in the aprotinin and control groups were well matched with regard to preoperative and intraoperative variables . Patients 6 months of age or less who received aprotinin required less operative closure time when compared with controls ( median , 93 vs 127 minutes , p = 0.004 ) , and trended toward requiring fewer red blood cell unit exposures ( median , three vs five exposures , p = 0.07 ) . Patients undergoing repeat sternotomy who received aprotinin required less operative closure time when compared with controls ( mean , 126 vs 159 minutes , p = 0.007 ) , fewer red blood cell unit exposures ( median three vs four exposures , p = 0.002 ) , and fewer fresh-frozen plasma unit exposures ( median , zero vs one exposure , p = 0.007 ) . CONCLUSIONS Aprotinin reduced operative closure time and blood product exposure in pediatric patients undergoing cardiopulmonary bypass who were 6 months of age or less or underwent a repeat sternotomy BACKGROUND The benefits and the current indications of aprotinin in congenital operations are not well defined . At present there are only a few studies available that have investigated a small number of patients in several heterogeneous groups of malformations . METHODS We investigated efficacy and safety of aprotinin in three groups of children < 15 kg , presenting with isolated ventricular septum defect ( n = 60 ) , tetralogy of Fallot ( n = 52 ) , and transposition of the great arteries ( n = 56 ) . Low-dose aprotinin regimen A1 ( 500,000 KIU in pump prime only ) and high-dose aprotinin A2 ( 50,000 KIU/kg during induction of anesthesia , 50,000 KIU/kg in pump prime , and 20,000 KIU/h continuous infusion ) were compared to a control group A0 ( without aprotinin ) regarding perioperative blood loss , transfusion requirements , and effects on the coagulation system . RESULTS The most common coagulation tests of aprotinin-treated patients and the platelet numbers were comparable with those of control patients preoperatively and 15 minutes after protamine administration . A significant dose-dependent reduction in fibrin-fibrinogen split products was observed at the end of cardiopulmonary bypass in the majority of aprotinin-treated patients with transposition . In patients with ventricular septum defect and Fallot , no significant difference in blood loss and transfusion requirements could be observed between patients with or without aprotinin and no difference was observed between low- and high-dose regimen . In transposition of the great arteries , high-dose aprotinin led to significant reduction of blood loss ( p = 0.02 ) and postoperative blood transfusion ( p = 0.003 ) . Severe side effects as a result of administration of aprotinin were not observed . CONCLUSIONS High-dose aprotinin reduces blood loss and transfusion requirement only in complex congenital cardiac operations ; therefore aprotinin can not be recommended as a blood conservation agent in routine pediatric operations Reduction of blood transfusions in patients with neuromuscular scoliosis can decrease potential complications such as immune suppression , infection , hemolytic reaction and viral transmission . Aprotinin ( Trasylol ® , Bayer ) , an antifibrinolytic , has proven to be effective in reducing blood loss in cardiac and liver surgery , but little data exists in patients undergoing spinal fusion for neuromuscular scoliosis . The purpose of this study was to evaluate the safety and efficacy of aprotinin in pediatric neuromuscular scoliosis patients undergoing spinal fusion . The medical records of all patients undergoing initial spinal fusions for neuromuscular scoliosis between January 1999 and March 2003 were review ed to determine demographic data , perioperative data , wound drainage and number of transfusion required . Cases were compared to a matched group of historical controls . We had 14 patients in the aprotinin group and 17 in the control group . Total blood loss in the aprotinin group was significantly lower compared to the control group ( 715 vs. 2,110 ml ; P = 0.007 ) . Significantly less blood loss occurred in the aprotinin group when blood loss per kilogram was evaluated as well ( 23 vs. 60 ml/kg , respectively ; P = 0.002 ) . Intra-operative packed red blood cell ( PRBC ) transfusions were also significantly lower in the aprotinin group ( 1.25 vs. 3.16 units ; P = 0.001 ) . No clinical evidence of anaphylaxis , deep vein thrombosis ( DVT ) or renal failure was observed in the aprotinin group . After considering the price of drug therapy , operating room time , and the cost of blood products , the use of aprotinin saved an average of $ 8,577 per patient . In our series , the use of aprotinin result ed in decreased blood loss and a decreased rate of transfusions in children with neuromuscular scoliosis undergoing extensive spinal fusion . At out institution , the use of aprotinin is safe and cost effective for patients with neuromuscular scoliosis BACKGROUND Perioperative aprotinin decreases postoperative blood loss in adults undergoing cardiac operations , but its role is less clear in children . Therefore , a trial of aprotinin in pediatric cardiac operations was conducted to study the efficacy of its use in children . METHODS Forty-two patients were r and omly assigned to receive either high-dose aprotinin or placebo . Aprotinin efficacy was assessed using time from protamine administration to skin closure , postoperative blood loss and hemoglobin loss , and postoperative transfusion requirements . Measures of fibrinolysis ( fibrin degradation product titers ) and platelet preservation ( beta-thromboglobulin levels ) were also assessed . RESULTS There were no statistically significant differences between groups in any of the blood loss or transfusion parameters . Fibrin degradation product levels , measured 4 hours postoperatively , had increased significantly for control patients , but remained unchanged for the aprotinin group ( p < 0.02 ) . beta-Thromboglobulin levels increased more rapidly during cardiopulmonary bypass in the control group ( p = 0.03 ) . CONCLUSIONS Aprotinin appears to provide no clinical benefit in routine pediatric cardiac operations . A reduction in fibrinolysis , with perhaps an early preservation of platelet structure , is seen in the aprotinin group Study Design . A prospect i ve study evaluating the efficacy of & egr;-aminocaproic acid ( EACA ) in decreasing perioperative blood loss in idiopathic scoliosis . Objectives . To compare the perioperative blood loss and need for blood replacement in two groups of patients undergoing surgery for idiopathic scoliosis . One group received intraoperative EACA ; the other did not and served as controls . Summary of Background Data . Excessive blood loss increases the operative time , risk for blood product disease transmission , postoperative complications , and costs associated with posterior spinal fusion and instrumentation . EACA is an antifibrinolytic agent that has been shown to be effective in reducing perioperative blood loss during pediatric cardiothoracic surgical procedures . We hypothesized that it would also be effective in lowering blood loss during posterior spinal fusion for idiopathic scoliosis . Methods . We compared the perioperative blood loss of 28 consecutive pediatric patients with idiopathic scoliosis who underwent posterior spinal fusion and received intraoperative EACA with 31 consecutive patients who did not receive this medication and served as a control group . Results . The patients in both groups were similar . Patients in the EACA group demonstrated statistically significant decreases in total estimated perioperative blood loss and the need for autologous blood transfusion . The patients in the EACA group had no intraoperative or postoperative complications related to the use of this medication . Conclusions . Based on these preliminary findings , we believe that EACA is helpful in decreasing blood loss in patients undergoing posterior spinal fusion and instrumentation , and may decrease the number of autologous units needed to maintain safe perioperative hemoglobin levels , thereby improving safety and lowering cost associated with scoliosis surgery BACKGROUND Processing of pericardial shed blood with a cell-saving device was cl aim ed to prevent lipid microembolization and to protect from neurocognitive dysfunction after cardiopulmonary bypass . The present study tested the hypothesis that processing of pericardial shed blood with a cell-saving device during cardiopulmonary bypass would significantly decrease serum levels of protein S100B , and improve brain oxygen saturation and neurologic outcome , all markers of brain injury in elderly patients . METHODS Forty patients , 65 years of age and older , undergoing coronary artery bypass graft with cardiopulmonary bypass , were prospect ively r and omly assigned to processing of pericardial shed blood with a cell-saving device or to conventional use of a st and ard closed venous reservoir where cardiotomy blood was collected and reinfused through the arterial circuit ( control group ) . Serum in S100B was measured 30 minutes , 4 hours , 24 hours , and 48 hours after surgery . Near-infrared spectroscopy monitoring was performed during the procedure and the National Institutes of Health stroke scale was measured before surgery and at the time of discharge of the hospital . RESULTS Patients in the cell-saving device group averaged 72 + /- 3 years of age and underwent 3.1 + /- 0.7 coronary artery grafts with a mean of 62 + /- 20 minutes of cardiopulmonary bypass time . Patients in the control group averaged 75 + /- 4 years of age ( p = 0.03 ) and underwent 3.3 + /- 0.6 coronary artery grafts ( p = 0.49 ) with a mean of 75 + /- 25 minutes of cardiopulmonary bypass time ( p = 0.12 ) . The quantity of blood administered from the cell-saving device averaged 281 + /- 162 mL per patient . Serum protein S100B levels averaged 0.06 + /- 0.03 before surgery and 0.51 + /- 0.23 microg/L 30 minutes after surgery in the cell-saving device patients compared with 0.076 + /- 0.04 before surgery ( p = 0.32 ) and 1.48 + /- 0.66 ( p < 0.0001 ) in the control patients . The near-infrared spectroscopy baseline mean value of left and right cortical region was 58 % + /- 12 % and 55 % + /- 7 % in the cell-saving device group versus 59 % + /- 7 % and 53 % + /- 6 % in the control group ( p = 0.67 and 0.36 ) , and no difference occurred over time in each group . The National Institutes of Health stroke score before and after surgery was similar in the two groups . There was one cerebrovascular complication in the control group ( 1 of 20 , 5 % ) after surgery . CONCLUSIONS The difference between the two groups occurred 30 minutes after surgery , at which time serum levels of protein S100B were significantly higher in the control group compared with cell-saving device patients . Although use of the cell-saving device was not associated with higher brain oxygen saturation nor changes in the National Institutes of Health stroke score , it is associated with lesser release of nonspecific markers of brain injury in elderly patients BACKGROUND & OBJECTIVES Antifibrinolytic agents are used commonly in adult cardiac surgery to reduce postoperative blood loss . Paucity of literature on the use of a newer antifibrinolytic agent tranexamic acid ( TA ) in children undergoing cardiac surgery promoted us to conduct this study in children with cyanotic heart disease . METHODS One hundred and twenty consecutive children with cyanotic heart disease were r and omised into two groups . Control ( group A ) ( n=24 ) given no drug while the study ( group B , n=96 ) group was given tranexamic acid 10 mg/kg each after anaesthetic induction , on bypass and after protamine at the end of bypass . Postoperatively , total mediastinal chest tube drainage and blood and blood product usage at 24 h were recorded . Tests of coagulation including activated clotting time , fibrinogen , fibrin degradation products and platelet count were performed at 6 h postoperatively . RESULTS The two groups were comparable in terms of demographic characteristics such as age , sex , weight , operations performed , and preoperative haematocrit . Postoperatively , group B , had a significantly ( P<0.05 ) lower blood loss , blood and blood product usage , re-exploration rate compared to the control group . There was preservation of fibrinogen and lower levels of fibrin degradation products in group B. INTERPRETATION & CONCLUSION Tranexamine acid was highly effective in reducing post-operative blood loss , blood and blood product usage in children with congenital cyanotic heart disease undergoing corrective surgery Children undergoing cardiac operations in which cardiopulmonary bypass is used are at risk of significant postoperative blood loss . The acquired coagulopathy is complex but is thought to be due , in part , to excessive fibrinolysis . We examined the possibility of reducing postoperative blood loss in children by using the antifibrinolytic drug tranexamic acid . Using a prospect i ve , r and omized , double-blind study design , we administered a single dose of tranexamic acid ( 50 mg/kg intravenously ) or saline placebo , before skin incision , in 88 children undergoing cardiac operations . Post-operative blood loss and fluid replacement were recorded for the next 24 hours . In addition , hemoglobin , platelet counts , and coagulation measures were recorded every 6 hours . When all patients were examined , there was no significant difference in postoperative blood loss between the treated and placebo groups ( 21.2 + /- 12 ml/kg per 24 hours , tranexamic acid , vs 27.2 + /- 20.3 mls/kg per 24 hours , placebo ) . However , when the children with cyanosis were analyzed separately , there was a highly significant difference in blood loss between the groups during the first 6 hours ( 11.2 + /- 3.7 ml/kg per 6 hours , tranexamic acid , vs 27.2 + /- 11.4 mls/kg per 6 hours , placebo ; p < 0.002 ) , as well as the overall 24 hour study period ( 23.7 + /- 7.5 mls/kg per 24 hours , tranexamic acid , vs 48.9 + /- 27.6 mls/kg per 24 hours , placebo ; p < 0.02 ) . Also significantly less blood and blood products were administered to the treated cyanosed group . Tranexamic acid produced a significant reduction in postoperative blood loss and blood product requirements in children with cyanosis undergoing heart operations . The drug had no effect in children without cyanosis or those requiring a second thoracotomy OBJECT This prospect i ve , r and omized , placebo-controlled , double-blind trial was undertaken to assess the efficacy of aprotinin in reducing the need for blood transfusions in 39 children undergoing reconstructive craniofacial surgery . METHODS Two demographically similar groups -- a total of 39 patients with a mean age of 1.2 + /- 1.2 years -- were studied . The efficacy of aprotinin ( 240 mg/m2 administered intravenously over 20 minutes , followed by infusions of 56 mg/m2/hr ) was compared with that of an equal infusion of 0.9 % saline ( placebo ) . Patients in the aprotinin group received less blood per kilogram of body weight than patients in the placebo group ( 32 + /- 25 ml/kg compared with 52 + /- 34 m/kg , respectively ; p = 0.04 ) . Those patients in whom aprotinin was administered experienced less change in their hematocrit levels during surgery ( aprotinin -33 + /- 13 % compared with placebo -44 + /- 9 % , p = 0.01 ) . Each patient underwent a transfusion as per study protocol , and there was no significant change in hematocrit levels from the beginning to the end of surgery . The surgical faculty judged blood loss in patients in the aprotinin group to be significantly less than usual ( p = 0.03 ) . The use of aprotinin was also associated with reduced blood transfusion requirements during the first 3 postoperative days ( p = 0.03 ) . There was no adverse event reported in either the aprotinin or placebo group . CONCLUSIONS Aprotinin decreased blood transfusion requirements in pediatric patients undergoing craniofacial reconstruction , thereby reducing the risks associated with exposure to banked blood components The antifibrinolytic drug , tranexamic acid , decreases blood loss in adult patients undergoing cardiac surgery . However , its efficacy has not been extensively studied in children . Using a prospect i ve , r and omized , double-blind study design , we examined 41 children undergoing repeat sternotomy for repair of congenital heart defects . After induction of anesthesia and prior to skin incision , patients received either tranexamic acid ( 100 mg/kg , followed by 10 mg [ centered dot ] kg-1 [ centered dot ] h-1 ) or saline placebo . At the onset of cardiopulmonary bypass , a second bolus of tranexamic acid ( 100 mg/kg ) or placebo was administered . Total blood loss and transfusion requirements during the period from protamine administration until 24 h after admission to the intensive care unit were recorded . Children who were treated with tranexamic acid had 24 % less total blood loss ( 26 + /- 7 vs 34 + /- 17 mL/kg ) compared with children who received placebo ( univariate analysis P = 0.03 and multivariate analysis P < 0.01 ) . Additionally , the total transfusion requirements , total donor unit exposure , and financial cost of blood components were less in the tranexamic acid group . In conclusion , tranexamic acid can reduce perioperative blood loss in children undergoing repeat cardiac surgery . ( Anesth Analg 1997;84:990 - 6 Study Design . A prospect i ve blinded , r and omized controlled study compared the effect of a perioperative infusion of aprotinin versus placebo during long segment spinal fusions in children . Objectives . To determine whether aprotinin decreases blood loss and transfusion requirements in pediatric patients with spinal deformities undergoing posterior spinal fusions of seven or greater segments . Summary of Background Data . Blood loss is a major cause of morbidity during long segment spinal fusion . Several preoperative and intraoperative techniques are currently used to reduce blood loss and transfusion requirements . Aprotinin , an antifibrinolytic and anti-inflammatory agent , has been used to decrease blood loss in cardiac surgical patients . We design ed a prospect i ve , r and omized , and blinded controlled study to evaluate aprotinin ’s efficacy in reducing bleeding during pediatric spine surgery . Methods . After obtaining informed written consent , we studied 44 children and adolescents who were anticipated to be at higher risk for major blood loss during posterior spinal fusion . Children were r and omly assigned to receive high dose aprotinin or placebo infusion during the perioperative period . Patients were assessed for blood loss , transfusion requirements , days in the intensive care unit , and days in hospital . Results . Demographics in the two groups of patients were similar . The study demonstrated a significant reduction in estimated blood loss ( aprotinin 545 cc , placebo 930 cc ) and transfusion requirements ( aprotinin 1.1 U , placebo 2.2 U ) . The duration of intensive care unit admission was similar in the two groups , as was the time until discharge . Conclusions . This r and omized , blinded study suggests that aprotinin significantly decreased blood loss and transfusion requirements in pediatric and adolescent scoliosis surgical patients at increased risk for intraoperative bleeding Study Design . A prospect i ve , r and omized , double-blind Institutional Review Board-approved study evaluating the efficacy of Amicar ( epsilon aminocaproic acid ) , an antifibrinolytic agent , in decreasing perioperative blood loss in idiopathic scoliosis . Objectives . To compare the perioperative ( intraoperative and postoperative ) blood loss and the need for autologous and homologous blood replacement in two groups of essentially identical patients undergoing a posterior spinal fusion for idiopathic scoliosis . Summary of Background Data . Reducing perioperative blood loss and the need for transfusion in patients undergoing spinal surgery is important to orthopedic surgeons . Recently , there has been interest in pharmacologic agents , particularly Amicar and Aprotinin , to assist in decreasing perioperative blood loss . In 2001 , in a preliminary study , we demonstrated that Amicar appeared to be effective in reducing perioperative blood loss in patients with idiopathic scoliosis undergoing a posterior spinal fusion and segmental spinal instrumentation . This was a study of 28 consecutive patients receiving Amicar compared to a historical control group of the 31 previous consecutive patients with the same study criteria . The current study was performed to confirm our preliminary findings . Methods . We analyzed the perioperative blood loss of 36 patients with idiopathic scoliosis who were blindly r and omized by the operating room pharmacy into an Amicar and control group . The criteria to be included in the study was the same as the preliminary study : diagnosis of idiopathic scoliosis , age at surgery 11 to 18 years , posterior spinal fusion and segmental spinal instrumentation only , autogenous iliac crest bone graft or homologous cancellous bone graft , and a signed agreement to participate in the study . The patients in both groups had the same anesthetic technique , intraoperative procedure , instrumentation , postoperative management , and st and ardized indications for transfusions . Results . Before surgery , the patients in both groups were essentially identical . The distribution of patients and their results was not known until the completion of the study . Patients in the Amicar group demonstrated a statistically significant decrease in perioperative blood loss and the need for autologous blood transfusion . Interestingly , this decrease was predominantly in the postoperative suction drainage . This may be due to elevated fibrinogen levels induced by Amicar . The patients taking Amicar had no intraoperative or postoperative thromboembolic complications . Conclusions . The results of this study confirmed that the use of intraoperative Amicar is a safe , effective , and inexpensive method to significantly reduce perioperative blood loss in patients with idiopathic scoliosis undergoing posterior spinal fusion and segmental spinal instrumentation . The results have allowed us to reduce our recommendation for perioperative autologous blood donation , thereby further decreasing costs Study Design . A retrospective case-control study . Objective . Evaluate the effectiveness of Amicar in decreasing perioperative blood loss in patients with neuromuscular scoliosis undergoing posterior spinal fusion ( PSF ) and segmental spinal instrumentation ( SSI ) . Summary of Background Data . Previously , a preliminary prospect i ve ; prospect i ve r and omized double-blind ; same-day anterior and posterior spinal fusion ; and fibrinogen studies have demonstrated Amicar to be effective in decreasing total perioperative blood loss and transfusion requirements in surgery for idiopathic scoliosis . Increased fibrinogen secretion is a possible explanation . We are now analyzing its effectiveness in neuromuscular scoliosis . Methods . Amicar was administered at 100 mg/kg over 15 minute not to exceed 5 g after anesthesia induction . Maintenance is 10 mg/kg/h until wound closure . There were 2 study groups : group 1 ( n = 34 ) , no Amicar and group 2 ( n = 62 ) who received Amicar . The majority of patients in both groups had cerebral palsy . Total perioperative blood loss was determined from the estimated intraoperative blood loss and measured postoperative suction drainage . Total perioperative blood loss and transfusion requirements ( cell saver and allogeneic ) were compared using & khgr;2 or Fisher exact test . Results . There was statistically less estimated intraoperative blood loss , total perioperative blood loss , and transfusion requirements in group 2 . Postoperative suction drainage was also less but did not reach statistical significance . In group 1 , estimated intraoperative blood loss , measured postoperative suction drainage , and total perioperative blood loss were 2194 ± 1626 mL , 903 ± 547 mL , and 3055 ± 1852 mL , whereas in group 2 , it was 1125 ± 715 mL , 695 ± 489 mL , and 1805 ± 940 mL. Transfusion requirements were 1548 ± 962 mL in group 1 but only 660 ± 589 mL in group 2 ( P < 0.0001 ) . Amicar was equally effective in all diagnoses . There were no complications related to the use of Amicar . Conclusion . Amicar was highly effective in decreasing perioperative blood loss and transfusion requirements in patients with neuromuscular scoliosis undergoing PSF and SSI . It was most effective in decreasing estimated intraoperative blood loss . This results in decreased transfusion requirements , costs , and potential transfusion-related complications |
12,263 | 26,854,816 | Costs were lower for ESD/HAH than UC .
ESD/HAH is safe in selected patients with an AE COPD . | A systematic review and meta- analysis was performed to assess the safety , efficacy and cost of Early Supported Discharge ( ESD ) and Hospital at Home ( HAH ) compared to Usual Care ( UC ) for patients with acute exacerbation of COPD ( AE COPD ) . | BACKGROUND A r and omised trial was performed on patients presenting to hospital with an exacerbation of chronic obstructive pulmonary disease ( COPD ) to compare outcomes in those managed at home with support with those admitted to hospital in the st and ard manner . METHODS Over an 18 month period all patients presenting to the Royal Infirmary of Edinburgh on weekdays ( n=718 ) with a diagnosis of an exacerbation of COPD were assessed for inclusion in the trial . Patients with impaired level of consciousness , acute confusion , acute changes on radiography , or an arterial pH of < 7.35 or with other serious medical or social reasons for admission were excluded . Patients r and omised to home support were discharged with an appropriate treatment package ( antibiotics , corticosteroids , nebulised bronchodilators and , if necessary , home oxygen ) . They were visited by a nurse the following day and thereafter at intervals of 2 - 3 days until recovery when they were discharged from follow up . Parallel observations were made on patients allocated to normal hospital admission up to the point of discharge . Patients in both groups were assessed at home eight weeks after the initial assessment . RESULTS Among weekday patients 353 ( 50 % ) were considered obligatory admissions , 140 ( 19 % ) were admitted because of co-morbidity , 17 ( 2 % ) because of poor social circumstances , and 24 ( 3 % ) did not consent to the trial . The remaining 184 ( 26 % ) were r and omised ( 2:1 ) either to home support or to a st and ard hospital admission . The median time to discharge was 7 days for the home support group and 5 days for the admitted group ( p<0.01 ) ; 25 % of the home support group and 34 % of the admitted group were readmitted before the final assessment at eight weeks ( p>0.05 ) . There were no significant differences between the groups in attendances by GPs and carers or in health status measured eight weeks after the initial assessment . Satisfaction with the service was good . The mean total health service cost per patient was estimated as 877 pounds sterling for the home support group and 1753 pounds sterling for the admitted group . CONCLUSIONS This study shows that home supported discharge is a well tolerated , safe , and economic alternative to hospital admission for a proportion of patients referred to hospital for admission for an exacerbation of COPD The aim of the present prospect i ve multicentric study was to develop a simple rule for the prediction of poor outcome in patients presenting to emergency departments with initially non-life threatening-chronic obstructive pulmonary disease ( COPD ) exacerbations in a real-life setting . All patients with an acute exacerbation of COPD visiting the emergency departments of 103 hospitals during a 3-month period were included , except those who immediately required intensive care unit admission and /or ventilatory support . The data collected included patient characteristics , in-hospital outcomes ( mortality and length of stay ) and mode of discharge ( unsupported or need for post-hospital assistance ) . The in-hospital mortality rate was 7.4 % ( 59 out of 794 ) . Independent prognostic factors were age , number of clinical signs of severity ( among cyanosis , impaired neurological status , lower limb oedema , asterixis and use of accessory inspiratory or expiratory muscles ) and dyspnoea grade in the stable state . The need for post-hospital support was also predicted by female sex . In order to construct and vali date a prediction score for mortality based on these items , patients were r and omly allocated to a derivation and a validation cohort . The prediction score showed good discrimination , with a c-statistic of 0.79 in the derivation cohort and 0.83 in the validation cohort . Thus simple purely clinical factors can reliably predict the risk of death and requirement for post-hospital support in an initially non-life threatening-acute exacerbation of chronic obstructive pulmonary disease . Their use needs to be prospect ively vali date Background Exacerbations of Chronic Obstructive Pulmonary Disease ( COPD ) are the main cause for hospitalisation . These hospitalisations result in a high pressure on hospital beds and high health care costs . Because of the increasing prevalence of COPD this will only become worse . Hospital at home is one of the alternatives that has been proved to be a safe alternative for hospitalisation in COPD . Most schemes are early assisted discharge schemes with specialised respiratory nurses providing care at home . Whether this type of service is cost-effective depends on the setting in which it is delivered and the way in which it is organised . Methods / Design GO AHEAD ( Assessment Of Going Home under Early Assisted Discharge ) is a 3-months , r and omised controlled , multi-centre clinical trial . Patients admitted to hospital for a COPD exacerbation are either discharged on the fourth day of admission and further treated at home , or receive usual inpatient hospital care . Home treatment is supervised by general nurses . Primary outcome is the effectiveness and cost effectiveness of an early assisted discharge intervention in comparison with usual inpatient hospital care for patients hospitalised with a COPD exacerbation . Secondary outcomes include effects on quality of life , primary informal caregiver burden and patient and primary caregiver satisfaction . Additionally , a discrete choice experiment is performed to provide insight in patient and informal caregiver preferences for different treatment characteristics . Measurements are performed on the first day of admission and 3 days , 7 days , 1 month and 3 months thereafter . Ethical approval has been obtained and the study has been registered . Discussion This article describes the study protocol of the GO AHEAD study . Early assisted discharge could be an effective and cost-effective method to reduce length of hospital stay in the Netherl and s which is beneficial for patients and society . If effectiveness and cost-effectiveness can be proven , implementation in the Dutch health care system should be considered . Trial registration Netherl and s Trial Register NTR1129 BACKGROUND We have previously reported the use of a hospital based respiratory nurse service ( Acute Respiratory Assessment Service , ARAS ) to support home treatment of patients with exacerbations of chronic obstructive pulmonary disease ( COPD ) . A controlled trial was undertaken to compare early discharge with home treatment supported by respiratory nurses with conventional hospital management of patients admitted with exacerbations of COPD . METHODS Patients with COPD admitted as emergencies were identified the next working day . They were eligible for inclusion in the study if the differential diagnosis included an exacerbation of COPD , but were excluded if other medical conditions or acidotic respiratory failure required inpatient investigation or management . Of 360 patients review ed , 209 were being assessed for other active medical problems and were excluded , 33 potential participants were already involved in research studies and so were ineligible , and 37 did not wish to participate in the study . Eighty one patients were r and omised to receive conventional inpatient care ( n=40 ) or to planned early discharge the next working day ( n=41 ) . Those discharged early continued treatment at home under the supervision of specialist respiratory nurses . Outcome measures were readmission , additional hospital days , and deaths within 60 days of initial admission . Process measures included number of visits , duration of follow up by the respiratory nurse , and additional treatment provided to support early discharge . RESULTS On an intention to treat basis , a policy of early discharge reduced inpatient stay from a mean of 6.1 ( range 1–13 ) days with conventional management to 3.2 ( 1–16 ) days with an early discharge policy . Twelve patients ( 30 % conventional management , 29.3 % early discharge ) were readmitted in each group giving a mean difference in readmission of 0.7 % ( 95 % CI of the difference –19.2 to 20.6 ) . In the conventional management group readmitted patients spent a mean of 8.75 additional days in hospital compared with 7.83 days in the early discharge group , giving a mean difference of 0.92 days ( 95 % CI of the difference –6.5 to 8.3 ) . There were two deaths ( 5 % ) in the conventional management group and one ( 2.4 % ) in the early discharge group , a mean difference of 2.6 % ( 95 % CI of the difference –5.7 to 10.8 ) . CONCLUSIONS Patients with acute exacerbations of COPD uncomplicated by acidotic respiratory failure or other medical problems can be discharged home earlier than is current practice with support by visiting respiratory nurses . No difference was found in the subsequent need for readmission It was postulated that home hospitalisation ( HH ) of selected chronic obstructive pulmonary disease ( COPD ) exacerbations admitted at the emergency room ( ER ) could facilitate a better outcome than conventional hospitalisation . To this end , 222 COPD patients ( 3.2 % female ; 71±10 yrs ( mean±sd ) ) were r and omly assigned to HH ( n=121 ) or conventional care ( n=101 ) . During HH , integrated care was delivered by a specialised nurse with the patient 's free-phone access to the nurse ensured for an 8‐week follow-up period . Mortality ( HH : 4.1 % ; controls : 6.9 % ) and hospital readmissions ( HH : 0.24±0.57 ; controls : 0.38±0.70 ) were similar in both groups . However , at the end of the follow-up period , HH patients showed : 1 ) a lower rate of ER visits ( 0.13±0.43 versus 0.31±0.62 ) ; and 2 ) a noticeable improvement of quality of life ( Δ St George 's Respiratory Question naire ( SGRQ ) , −6.9 versus −2.4 ) . Furthermore , a higher percentage of patients had a better knowledge of the disease ( 58 % versus 27 % ) , a better self-management of their condition ( 81 % versus 48 % ) , and the patient 's satisfaction was greater . The average overall direct cost per HH patient was 62 % of the costs of conventional care , essentially due to fewer days of inpatient hospitalisation ( 1.7±2.3 versus 4.2±4.1 days ) . A comprehensive home care intervention in selected chronic obstructive pulmonary disease exacerbations appears as cost effective . The home hospitalisation intervention generates better outcomes at lower costs than conventional care Objectives To determine the effectiveness of early assisted discharge for chronic obstructive pulmonary disease ( COPD ) exacerbations , with home care provided by generic community nurses , compared with usual hospital care . Design Prospect i ve , r and omised controlled and multicentre trial with 3-month follow-up . Setting Five hospitals and three home care organisations in the Netherl and s. Participants Patients admitted to the hospital with an exacerbation of COPD . Patients with no or limited improvement of respiratory symptoms and patients with severe unstable comorbidities , social problems or those unable to visit the toilet independently were excluded . Intervention Early discharge from hospital after 3 days inpatient treatment . Home visits by generic community nurses . Primary outcome measure was change in health status measured by the Clinical COPD Question naire ( CCQ ) . Treatment failures , readmissions , mortality and change in generic health-related quality of life ( HRQL ) were secondary outcome measures . Results 139 patients were r and omised . No difference between groups was found in change in CCQ score at day 7 ( difference in mean change 0.29 ( 95 % CI −0.03 to 0.61 ) ) or at 3 months ( difference in mean change 0.04 ( 95 % CI –0.40 to 0.49 ) ) . No difference was found in secondary outcomes . At day 7 there was a significant difference in change in generic HRQL , favouring usual hospital care . Conclusions While patients ’ disease-specific health status after 7-day treatment tended to be somewhat better in the usual hospital care group , the difference was small and not clinical ly relevant or statistically significant . After 3 months , the difference had disappeared . A significant difference in generic HRQL at the end of the treatment had disappeared after 3 months and there was no difference in treatment failures , readmissions or mortality . Early assisted discharge with community nursing is feasible and an alternative to usual hospital care for selected patients with an acute COPD exacerbation . Trial registration : Netherl and sTrialRegister NTR 1129 BACKGROUND The study was conducted to investigate the safety of " hospital at home " versus hospital care . MATERIAL S AND METHODS It was a prospect i ve r and omised controlled trial . Patients with an exacerbation of chronic obstructive pulmonary disease ( COPD ) were included and r and omised to supported discharge ( n = 22 ) or to conventional in-patient care ( n = 22 ) . Outcome measures were readmissions , complications , mortality within 60 days of initial admission . RESULTS 390 patients ( COPD ) were admitted and 44 patients ( 12 % ) were included in the study . In the home treatment period 2 patients ( 9 % ) were readmitted . One patient ( 4.5 % ) died 2 weeks after discharge from the home treatment . In the follow-up period 3 patients in the home treated group were readmitted 7 times ( 31.8 % ) , and 7 patients in the conventional in-patient group were readmitted 9 times ( 40.9 % ) . There were 14 complications ( 63.6 % ) in the home treated group and 15 complications ( 68.3 % ) in the conventional in-patient group . The length of hospital stays in the supported discharged group were shorter ( 1.3 ( std = 0.5 ) versus 3.7 ( std = 2.8 ) days , p = 0.002 ) . After discharge a respiratory nurse visited supported discharged patients at home during 5.1 days ( min . 2 days , max . 13 days ) with 2.6 visits per patient ( min . 1 , max 6 visits ) . CONCLUSION This study shows that home supported discharge is a well tolerated , safe and economic alternative to hospital admission for a proportion of patients referred to hospital for admission for COPD Abstract Objectives : To compare “ hospital at home ” and hospital care as an inpatient in acute exacerbations of chronic obstructive pulmonary disease . Design : Prospect i ve r and omised controlled trial with three months ' follow up . Setting : University teaching hospital offering secondary care service to 350 000 patients . Patients : Selected patients with an exacerbation of chronic obstructive pulmonary disease where hospital admission had been recommended after medical assessment . Interventions : Nurse administered home care was provided as an alternative to inpatient admission . Main outcome measures : Readmission rates at two weeks and three months , changes in forced expiratory volume in one second ( FEV1 ) from baseline at these times and mortality . Results : 583 patients with chronic obstructive pulmonary disease referred for admission were assessed . 192 met the criteria for home care , and 42 refused to enter the trial . 100 were r and omised to home care and 50 to hospital care . On admission , FEV1 after use of a bronchodilator was 36.1 % ( 95 % confidence interval 2.4 % to 69.8 % ) predicted in home care and 35.1 % ( 6.3 % to 63.9 % ) predicted in hospital care . No significant difference was found in FEV1 after use of a bronchodilator at two weeks ( 42.6 % , 3.4 % to 81.8 % versus 42.1 % , 5.1 % to 79.1 % ) or three months ( 41.5 % , 8.2 % to 74.8 % versus 41.9 % , 6.2 % to 77.6 % ) between the groups . 37 % of patients receiving home care and 34 % receiving hospital care were readmitted at three months . No significant difference was found in mortality between the groups at three months ( 9 % versus 8 % ) . Conclusions : Hospital at home care is a practical alternative to emergency admission in selected patients with exacerbations of chronic obstructive pulmonary disease This trial compared the cost of an integrated home-based care model with traditional inpatient care for acute chronic obstructive pulmonary disease ( COPD ) . 25 patients with acute COPD were r and omised to either home or hospital management following request for hospital admission . The acute care at home group costs per separation ( $ 745 , CI95 % $ 595-$895 , n = 13 ) were significantly lower ( p < 0.01 ) than the hospital group ( $ 2543 , CI95 % $ 1766-$3321 , n = 12 ) . There was an improvement in lung function in the hospital-managed group at the Outpatient Department review , decreased anxiety in the Emergency Department in the home-managed group and equal patient satisfaction with care delivery . Acute care at home schemes can substitute for usual hospital care for some patients without adverse effects , and potentially release re sources . A funding model that allows adequate re source delivery to the community will be needed if there is a move to devolve acute care to community providers Background : Patients with an acute exacerbation of chronic obstructive pulmonary disease ( COPD ) were r and omised to either hospital at home ( HaH ) or inpatient management , and patient and carer preferred site of management and satisfaction with care received in the two arms was determined . Methods : Emergency admissions with an acute exacerbation of COPD were r and omised to inpatient care or HaH care . After discharge an independent observer administered a question naire to both patients and carers on the preferred site of care and scored satisfaction with the care received . Results : Of 60 patients recruited , 30 were r and omised to receive HaH care . Retrospective patient preference for HaH care was 96.3 % in the domiciliary arm and 59.3 % in the conventional arm ; carer preference figures were 85.7 % and 42.9 % , respectively . There was a higher preference for domiciliary care by both patients and carers in the HaH arm than in the inpatient arm ( p=0.001 and p=0.01 , respectively ) . Patients recorded equal satisfaction with care in the two arms ( 88.1 % in the conventional arm , 91.7 % in the domiciliary arm ) ; carer scores were 91.3 % and 91.9 % , respectively . Conclusions : The results of this study show that both patients and carers were significantly more likely to prefer domiciliary care if they were in the HaH arm . Since patients had to be willing to be looked after at home , both patients ' and carers ' perceptions of the benefits of HaH care were reinforced by their experience . HaH care of acute exacerbations of COPD is the preferred option in suitable patients OBJECTIVES Hospital admissions for exacerbations of chronic obstructive pulmonary disease are the main cost drivers of the disease . An alternative is to treat suitable patients at home instead of in the hospital . This article reports on the cost-effectiveness and cost-utility of early assisted discharge in The Netherl and s. METHODS In the multicenter r and omized controlled Assessment of GOing Home under Early Assisted Discharge trial ( n = 139 ) , one group received 7 days of inpatient hospital treatment ( HOSP ) and one group was discharged after 3 days and treated at home by community nurses for 4 days . Health care re source use , productivity losses , and informal care were recorded in cost question naires . Microcosting was performed for inpatient day costs . RESULTS Seven days after admission , mean change from baseline Clinical Chronic Obstructive Pulmonary Disease Question naire score was better for HOSP , but not statistically significantly : 0.29 ( 95 % confidence interval [CI]-0.04 to 0.61 ) . The difference in the probability of having a clinical ly relevant improvement was significant in favor of HOSP : 19.0%-point ( 95 % CI 0.5%-36.3 % ) . After 3 months of follow-up , differences in effectiveness had almost disappeared . The difference in quality -adjusted life-years was 0.0054 ( 95 % CI-0.021 to 0.0095 ) . From a health care perspective , early assisted discharge was cost saving:-€244 ( treatment phase , 95 % CI-€315 to-€168 ) and -€168 ( 3 months , 95 % CI-€1253 to € 922 ) . Societal perspective:-€65 ( treatment phase , 95 % CI-€152 to € 25 ) and € 908 ( 3 months , 95 % CI-€553 to € 2296 ) . The savings per quality -adjusted life-year lost were € 31,111 from a health care perspective . From a societal perspective , HOSP was dominant . CONCLUSIONS No clear evidence was found to conclude that either treatment was more effective or less costly |
12,264 | 20,515,769 | However , currently no definitive evidence of an association between increased IMT and cognitive impairment can be established . | The conversion rate of cognitive impairment to Alzheimer 's disease is 1 to 25 % per year .
Early detection of cognitive impairment will thus become a major concern , particularly when pharmacological intervention for preventing or delaying conversion will prove effective .
If simple carotid artery intima media thickness ( IMT ) measurements were to predict cognitive impairment , IMT could become one of the detection tools , as it is inexpensive , reliable and non-invasive . | BACKGROUND Subjects with a mild cognitive impairment ( MCI ) have a memory impairment beyond that expected for age and education yet are not demented . These subjects are becoming the focus of many prediction studies and early intervention trials . OBJECTIVE To characterize clinical ly subjects with MCI cross-sectionally and longitudinally . DESIGN A prospect i ve , longitudinal inception cohort . SETTING General community clinic . PARTICIPANTS A sample of 76 consecutively evaluated subjects with MCI were compared with 234 healthy control subjects and 106 patients with mild Alzheimer disease ( AD ) , all from a community setting as part of the Mayo Clinic Alzheimer 's Disease Center/Alzheimer 's Disease Patient Registry , Rochester , Minn. MAIN OUTCOME MEASURES The 3 groups of individuals were compared on demographic factors and measures of cognitive function including the Mini-Mental State Examination , Wechsler Adult Intelligence Scale-Revised , Wechsler Memory Scale-Revised , Dementia Rating Scale , Free and Cued Selective Reminding Test , and Auditory Verbal Learning Test . Clinical classifications of dementia and AD were determined according to the Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer 's Disease and Related Disorders Association criteria , respectively . RESULTS The primary distinction between control subjects and subjects with MCI was in the area of memory , while other cognitive functions were comparable . However , when the subjects with MCI were compared with the patients with very mild AD , memory performance was similar , but patients with AD were more impaired in other cognitive domains as well . Longitudinal performance demonstrated that the subjects with MCI declined at a rate greater than that of the controls but less rapidly than the patients with mild AD . CONCLUSIONS Patients who meet the criteria for MCI can be differentiated from healthy control subjects and those with very mild AD . They appear to constitute a clinical entity that can be characterized for treatment interventions Intima-media thickness ( IMT ) is increasingly used as a surrogate end point of vascular outcomes in clinical trials aim ed at determining the success of interventions that lower risk factors for atherosclerosis and associated diseases ( stroke , myocardial infa rct ion and peripheral artery diseases ) . The necessity to promote further criteria to distinguish early atherosclerotic plaque formation from thickening of IMT and to st and ardize IMT measurements is expressed through this up date d consensus . Plaque is defined as a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50 % of the surrounding IMT value or demonstrates a thickness > 1.5 mm as measured from the media-adventitia interface to the intima-lumen interface . St and ard use of IMT measurements is based on physics , technical and disease-related principles as well as agreements on how to perform , interpret and document study results . Harmonization of carotid image acquisition and analysis is needed for the comparison of the IMT results obtained from epidemiological and interventional studies around the world . The consensus concludes that there is no need to ‘ treat IMT values ’ nor to monitor IMT values in individual patients apart from exceptions named , which emphasize that inside r and omized clinical trials should be performed . Although IMT has been suggested to represent an important risk marker , according to the current evidence it does not fulfill the characteristics of an accepted risk factor . St and ardized methods recommended in this consensus statement will foster homogenous data collection and analysis . This will help to improve the power of r and omized clinical trials incorporating IMT measurements and to facilitate the merging of large data bases for meta-analyses A , Delecluse C et al. Habitual level of physical activity and muscle fatigue of the elbow flexor muscles in older men . L et al. Lower extremity performance is associated with daily life physical activity in individuals with and without peripheral arterial disease . Muscle strength in the triceps surae and objective ly measured customary walking activity in men and women over 65 years of age . A short physical performance battery assessing lower extremity function : association with self-reported disability and prediction of mortality and nursing home admission . The association between physical function and lifestyle activity and exercise in the health , aging and body composition study . Effect of exercise on ease in performing activities of daily living and instrumental activities of daily living from age 70 to 77 : the Jerusalem longitudinal study . Rennie KL et al. Validity and repeatability of a simple index derived from the short physical activity question naire used in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) study . SIR — The Folstein Mini-Mental State Examination ( MMSE ) , developed in 1975 as a bedside test of cognitive function , has been extensively used in clinical practice and research and is widely accepted as a clinical tool for diagnosing and monitoring dementia [ 1 ] . Despite its low sensitivity and specificity ( 0.56 and 0.73 , respectively , in one recent study ) [ 2 ] , comparable tools , including the Modified MMSE of Teng and Chui [ 3 ] have not received such widespread acceptance . It contains 11 questions that test orientation , registration , attention , calculation , recall , language and visuospatial functioning , with a maximum score of 30 . It takes minutes to administer and is practical for routine clinical use . Most questions are administered verbally . Hearing loss reduces performance on the verbal parts of the examination even in cognitively intact patients , with potential diagnostic error and alteration of management [ 4 ] . This is of concern , as hearing impairment affects over one-fourth of people over 65 years of age , and half of those over 75 years in most industrialised nations [ 5 ] . Uhlmann [ 6 ] tested 71 Alzheimer 's disease subjects with varying levels of hearing , using both written and st and ard versions of the MMSE . Paradoxically , they found that hearing-impaired subjects scored higher in the st and ard than the written version , while subjects with normal hearing performed better using the written version , although these findings were not statistically significant . We ( M.M. ) developed a written version of the MMSE , found it clinical ly useful , and report here an evaluation of its performance in a hospital-based population Background : The cognitive continuum in the elderly population can be conceptually divided into those who are functioning normally ( control subjects ) , those with a mild cognitive impairment ( MCI ) , and those with probable AD . Objectives : To test the hypothesis that the annualized rates of hippocampal atrophy differ as a function of both baseline and change in clinical group membership ( control , MCI , or AD ) . Methods : The authors identified 129 subjects from the Mayo Clinic AD Research Center/AD Patient Registry who met established criteria for normal control subjects , MCI , or probable AD , both at entry and at the time of a subsequent clinical follow-up evaluation 3 ± 1 years later . Each subject underwent an MRI examination of the head at the time of the initial assessment and at follow-up clinical assessment ; the annualized percentage change in hippocampal volume was computed . Subjects who were classified as controls or patients with MCI at baseline could either remain cognitively stable or could decline to a lower functioning group over the period of observation . Results : The annualized rates of hippocampal volume loss for each of the three initial clinical groups decreased progressively in the following order : AD > MC > control . Within the control and MCI groups , those who declined had a significantly greater rate of volume loss than those who remained clinical ly stable . The mean annualized rates of hippocampal atrophy by follow-up clinical group were : control-stable 1.73 % , control-decliner 2.81 % , MCI-stable 2.55 % , MCI-decliner 3.69 % , AD 3.5 % . Conclusion : Rates of hippocampal atrophy match both baseline cognitive status and the change in cognitive status over time in elderly persons who lie along the cognitive continuum from normal to MCI to AD Cerebral white matter lesions ( WML ) seen on magnetic resonance imaging scans are associated with cardiovascular disease and vascular risk factors . To assess the association between WML and atherosclerosis , we studied 111 people , aged 65 to 85 years , r and omly sample d , and stratified by age and sex , from participants in the Rotterdam Study . Cerebral T2-weighted magnetic resonance images in the axial plane were obtained for all subjects . Carotid atherosclerosis was ultrasonographically assessed by the presence of stenosis , measurement of intima to media wall thickness ( IMT ) , and the presence of atherosclerotic plaques . A possible or definite myocardial infa rct ion on an electrocardiogram was used as an indicator of coronary atherosclerosis . The ankle to arm systolic blood pressure ratio ( ABI ) was determined , and peripheral arterial disease was defined as an ABI lower than 0.90 in at least one side . Carotid atherosclerosis was significantly more pronounced in people with WML . The difference in common carotid IMT was 0.13 mm ( 95 % confidence interval [ CI ] 0.04 - 0.21 ) , whereas the odds ratio of WML associated with plaques in the carotid bifurcation was 3.9 . The degree of internal carotid artery stenosis was not , however , associated with WML . The mean ABI was significantly lower in people with WML than in those without lesions with a difference of -0.11 ( 95 % CI -0.21 to -0.01 ) . The odds ratio of WML associated with peripheral arterial disease and a possible or definite myocardial infa rct ion was 2.4 and 3.1 , respectively . We conclude that atherosclerosis , indicated by increased common carotid IMT , carotid plaques , and a lower ABI , is related to WML To evaluate the association between common carotid intima-media thickness and noninvasively assessed atherosclerosis elsewhere in the carotid artery , we used data from the Rotterdam Study , a single-center population -based , prospect i ve follow-up study among 7983 subjects aged 55 years or older . Baseline measurements included ultrasonographic evaluation of the vessel wall characteristics of the carotid arteries , that is , assessment of the presence of atherosclerotic lesions , measurement of common carotid intima-media thickness , and determination of the presence of hemodynamically significant stenosis . The present analysis is based on data obtained from the first 1000 participants . The results were adjusted for age and gender . An increase of 1 st and ard deviation in common carotid intima-media thickness ( 0.19 mm ) doubled the risk of plaques in the carotid bifurcation : odds ratio 2.0 ( 95 % confidence interval ( CI ) : 1.6 , 2.4 ) . For hemodynamically significant stenosis of the right internal carotid artery ( > or = 50 % ) , a 1.4 ( 95 % CI : 1.0 , 2.0 ) increased risk was found . The risk of atherosclerotic plaques in the bifurcation in subjects with an intima-media thickness above 0.89 mm ( upper quintile ) relative to those with an intima-media thickness below 0.63 mm ( lowest quintile ) was 6.0 ( 95 % CI : 3.5 , 10.2 ) . For internal carotid artery stenosis , a relative risk of 2.8 ( 95 % CI 0.5 , 15.7 ) was found . The findings of the present study provide evidence that increased common carotid intima-media thickness indicates atherosclerosis at other sites of the carotid artery . This study lends support to the view that noninvasively assessed increased intima-media thickness of the distal common carotid artery is an indicator of generalized atherosclerosis Stroke is considered the second most common cause of dementia , but the magnitude of the risk posed by stroke has not been fully clarified . The aim of this study was to determine the long-term risk of developing dementia after stroke onset in a hospitalized cohort . We prospect ively examined 185 nondemented patients aged ≥60 years hospitalized with ischemic stroke and 241 age-matched nondemented controls without stroke from the same community using neurologic , neuropsychological , and functional assessment s given annually . Using criteria modified from the DSM-III-R , we diagnosed incident dementia based on the annual examination findings . We used life-table methods to estimate incidence in the two groups , Kaplan-Meier analysis to determine the proportion surviving without dementia , and Cox proportional-hazards analysis to compute the relative risk ( RR ) of dementia after 1 to 4 years of follow-up . The incidence of dementia was 8.4 per 100 person-years in the stroke group and 1.3 per 100 person-years in the control group . After 52 months of follow-up , the cumulative proportion ( ±SE ) surviving without dementia was 66.3 ± 5.5 % for stroke and 90.3 ± 4.3 % for control subjects . The RR of dementia associated with stroke compared with controls was 5.5 ( 95 % CI , 2.5 to 11.1 ) after adjusting for demographic factors . Older age at stroke onset and fewer years of education were significant covariates , but sex and race were not . A low score on the Mini-Mental State Examination at baseline was a significant predictor when added to this model . We conclude that ischemic stroke in elderly persons increases the long-term risk of developing dementia by approximately five-fold compared with those without stroke . Age , education , and baseline intellectual function contribute independently to that risk The agreement between neuropsychologists identifying cognitive impairment ( CI ) in older adults was examined , as were factors influencing the classification process . Twenty four neuropsychologists in 18 study centers classified cases with or without CI after review ing neuropsychological findings and other relevant information . All cases were participants in the third wave of the Canadian Study of Health and Aging , a study of CI in later life . For 117 r and omly selected cases , a second neuropsychologist review ed the same material and reclassified the cases . Cases given the same ( concordant ) or different ( discordant ) classifications were compared with respect to patient and rater characteristics . The inter-rater agreement was moderate ( 77.7 % agreement , kappa = .49 ) . On all measures of cognitive functioning , the concordant group without impairment obtained a higher mean score than the discordant group , and the discordant group obtained a higher mean score than the concordant group with impairment . For 5 out of 8 cognitive measures , the concordant group with impairment differed from the concordant group without impairment and the discordant group , but the latter two groups did not differ significantly . The findings are comparable to others in the field and highlight the need for neuropsychologists to further clarify procedures for identifying subtle , or mild , forms of cognitive impairment BACKGROUND AND PURPOSE The goal of the present study was to examine a series of putative risk factors of poststroke dementia ( PSD ) , especially those factors usually associated with cerebrovascular disease and degenerative dementia , in a series of 251 consecutive unselected stroke patients . METHODS A st and ard protocol was prospect ively applied at admission and 3 months after stroke ; this protocol included clinical , functional , and cognitive assessment s , hemogram and serum biochemistry , ECG and CT exams , apolipoprotein E and angiotensin-converting enzyme genotype , and neuropsychological examination . After a neuropsychological examination and an interview with a relative , the following diagnostic criteria were used : the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV for dementia after stroke , DSM-III-R for previous dementia and dementia stage , and Association Internationale pour la Recherche et l'Enseignement en Neurologie ( NINDS-AIREN ) for vascular dementia . RESULTS Seventy-five cases ( 30 % ) demonstrated dementia at 3-month follow up ; 25 of them ( 10 % ) had demonstrated dementia before the stroke . Dementia was unrelated to type ( ischemic/hemorrhagic ) or location of stroke , vascular factors ( hypertension , diabetes , ischemic heart disease , or hypercholesterolemia ) , apolipoprotein E or angiotensin-converting enzyme genotype , and serum homocysteine . Age ( odds ratio [ OR ] 1.1 , 95 % CI 1.03 to 1.2 ) , previous nephropathy ( OR 6.1 , 95 % CI 1.5 to 24.3 ) , atrial fibrillation ( OR 4.4 , 95 % CI 1 . 4 to 13.9 ) , low Canadian Neurological Scale score at discharge ( OR 0 . 5 , 95 % CI 0.4 to 0.6 ) , and previous mental decline assessed by the shortened Spanish version of the Informant Question naire on Cognitive Decline in the Elderly ( SS-IQCODE ; OR 1.2 , 95 % CI 1.1 to 1 . 4 ) were the correlates of dementia in logistic regression analyses . The same risks factors were found when cases with previous dementia and with hemorrhagic stroke were excluded . CONCLUSIONS Dementia is frequent after ischemic or hemorrhagic stroke . Age , nephropathy , atrial fibrillation , previous mental decline , and stroke severity independently contribute to the risk Background : The Honolulu Heart Program ( HHP ) is a prospect i ve study of heart disease and stroke that has accumulated risk factor data on a cohort of 8,006 Japanese American men since the study began in 1965 . A recent examination of the cohort identified all patients with vascular dementia ( VaD ) using the criteria of the California Alzheimer ’s Disease Diagnostic and Treatment Center . Objective : To characterize patients with VaD by stroke subtype and to investigate risk factors for VaD in a cohort of Japanese American men , aged 71 to 93 , living in Hawaii and participating in the HHP . Methods : Sixty-eight men with VaD were compared with 3,335 men without dementia or stroke ( NSND ) . Men with VaD were also compared with 106 men with stroke who were not demented ( SND ) . C and i date risk factors were measured prospect ively . Results : Of the 68 men with VaD there were 34 ( 50 % ) whose VaD was attributed to small vessel infa rcts , 16 ( 23 % ) whose VaD was related to large vessel infa rcts , and 11 ( 16 % ) with both large and small vessel infa rcts . The remainder could not be classified . In a multivariate logistic regression model for VaD compared with NSND containing variables found to be associated with VaD in a univariate analysis , age ( odds ratio [ OR ] 1.19 , 95 % confidence interval [ CI ] 1.13 to 1.27 ) , coronary heart disease ( OR 2.50 , 95 % CI 1.35 to 4.62 ) , and 1-hour postpr and ial glucose ( OR 1.41 , 95 % CI 1.06 to 1.88 ) remained significantly predictive of VaD , whereas preference for a Western diet ( OR 0.54 , 95 % CI 0.30 to 0.98 ) as opposed to an Oriental or mixed diet and use of supplementary vitamin E ( OR 0.32 , 95 % CI 0.12 to 0.82 ) were protective . A similar model for the comparison of men with VaD and SND revealed age ( OR 1.24 , 95 % CI 1.14 to 1.35 ) was predictive of VaD , whereas preference for a Western diet ( OR 0.43 , 95 % CI 0.22 to 0.86 ) was protective . Conclusions : The most common stroke subtype associated with VaD was lacunar stroke . Age and traditional vascular risk factors are important contributors to the development of VaD in late life . The antioxidant vitamin E and presently unknown factors related to a Western diet as opposed to an Oriental diet may be protective against developing Objective : This study investigated the relationship between serum levels of two neurotrophic factors , insulin-like growth factor-1 ( IGF-1 ) and hepatocyte growth factor ( HGF ) , and carotid atherosclerosis and cognitive function in the elderly . Methods : Serum levels of IGF-1 and HGF , carotid artery intima-media thickness ( IMT ) , and Mini-Mental State Examination ( MMSE ) scores were determined in 60 subjects over 65 years old ( 35 patients with vascular dementia and 25 without dementia ) . Results : In all subjects IGF-1 levels showed a significant positive correlation with the MMSE score ( r = 0.262 , p = 0.0427 ) and a negative correlation with the IMT ( r = –0.284 , p = 0.0277 ) and the HGF level ( r = –0.422 , p = 0.0007 ) . HGF levels were significantly correlated with IMT ( r = 0.259 , p = 0.0455 ) and lipoprotein(a ) levels ( r = 0.279 , p = 0.0372 ) . Mean MMSE scores and IGF-1 levels were significantly lower in patients with vascular dementia than in the non-demented controls . Mean IMT and the frequency of atherosclerotic plaque in the carotid arteries as well as the serum levels of HGF , LDL cholesterol , lipoprotein(a ) and lipid peroxides were significantly increased in the demented patients compared with the non-demented controls . Conclusion : A decrease of IGF-1 along with an increase of HGF may reflect an underlying biological process that influences cognitive decline as well as carotid atherosclerosis in the elderly |
12,265 | 15,932,647 | These exemplary studies indicate CAM therapies that may be considered cost-effective compared to usual care for various conditions : acupuncture for migraine , manual therapy for neck pain , spa therapy for Parkinson 's , self-administered stress management for cancer patients undergoing chemotherapy , pre- and post-operative oral nutritional supplementation for lower gastrointestinal tract surgery , biofeedback for patients with " functional " disorders ( eg , irritable bowel syndrome ) , and guided imagery , relaxation therapy , and potassium-rich diet for cardiac patients . | Background Out-of-pocket expenditures of over $ 34 billion per year in the US are an apparent testament to a widely held belief that complementary and alternative medicine ( CAM ) therapies have benefits that outweigh their costs .
However , regardless of public opinion , there is often little more than anecdotal evidence on the health and economic implication s of CAM therapies .
The objectives of this study are to present an overview of economic evaluation and to exp and upon a previous review to examine the current scope and quality of CAM economic evaluations . | Abstract This single-blind r and omised clinical trial compared osteopathic manipulative treatment with chemonucleolysis ( used as a control of known efficacy ) for symptomatic lumbar disc herniation . Forty patients with sciatica due to this diagnosis ( confirmed by imaging ) were treated either by chemonucleolysis or manipulation . Outcomes ( leg pain , back pain and self-reported disability ) were measured at 2 weeks , 6 weeks and 12 months . The mean values for all outcomes improved in both groups . By 12 months , there was no statistically significant difference in outcome between the treatments , but manipulation produced a statistically significant greater improvement for back pain and disability in the first few weeks . A similar number from both groups required additional orthopaedic intervention ; there were no serious complications . Crude cost analysis suggested an overall financial advantage from manipulation . Because osteopathic manipulation produced a 12-month outcome that was equivalent to chemonucleolysis , it can be considered as an option for the treatment of symptomatic lumbar disc herniation , at least in the absence of clear indications for surgery . Further study into the value of manipulation at a more acute stage is warranted BACKGROUND Shock-absorbing and biomechanic shoe orthoses are frequently used in the prevention and treatment of back and lower extremity problems . One review concludes that the former is clinical ly effective in relation to prevention , whereas the latter has been tested in only 1 r and omized clinical trial , concluding that stress fractures could be prevented . OBJECTIVES To investigate if biomechanic shoe orthoses can prevent problems in the back and lower extremities and if reducing the number of days off-duty because of back or lower extremity problems is possible . DESIGN Prospect i ve , r and omized , controlled intervention trial . STUDY SUBJECTS One female and 145 male military conscripts ( aged 18 to 24 years ) , representing 25 % of all new conscripts in a Danish regiment . METHOD Health data were collected by question naires at initiation of the study and 3 months later . Custom-made biomechanic shoe orthoses to be worn in military boots were provided to all in the study group during the 3-month intervention period . No intervention was provided for the control group . Differences between the 2 groups were tested with the chi-square test , and statistical significance was accepted at P < .05 . Risk ratio ( RR ) , risk difference ( ARR ) , numbers needed to prevent ( NNP ) , and cost per successfully prevented case were calculated . OUTCOME VARIABLES Outcome variables included self-reported back and /or lower extremity problems ; specific problems in the back or knees or shin splints , Achilles tendonitis , sprained ankle , or other problems in the lower extremity ; number of subjects with at least 1 day off-duty because of back or lower extremity problems and total number of days off-duty within the first 3 months of military service because of back or lower extremity problems . RESULTS Results were significantly better in an actual-use analysis in the intervention group for total number of subjects with back or lower extremity problems ( RR 0.7 , ARR 19 % , NNP 5 , cost 98 US dollars ) ; number of subjects with shin splints ( RR 0.2 , ARR 19 % , NNP 5 , cost 101 US dollars ) ; number of off-duty days because of back or lower extremity problems ( RR 0.6 , ARR < 1 % , NNP 200 , cost 3750 US dollars ) . In an intention-to-treat analysis , a significant difference was found for only number of subjects with shin splints ( RR 0.3 , ARR 18 % , NNP 6 cost 105 US dollars ) , whereas a worst-case analysis revealed no significant differences between the study groups . CONCLUSIONS This study shows that it may be possible to prevent certain musculoskeletal problems in the back or lower extremities among military conscripts by using custom-made biomechanic shoe orthoses . However , because care-seeking for lower extremity problems is rare , using this method of prevention in military conscripts would be too costly . We also noted that the choice of statistical approach determined the outcome OBJECTIVES This level II outcome study was conducted to examine the efficacy and toxicity of a diagnostic and treatment protocol using electrodermal screening ( EDS ) in allergy/sensitivity patients . METHODS Ninety-six patients with a diagnosis of allergy or sensitivity entered the study between 1994 and 1998 ; 90 participants completed the study . All participants followed the same protocol , and all interactions were with a single clinician at a single site . The Allergy Symptom Severity Index ( ASSI ) was developed to record symptomatic information . EDS - conductance measurement 1/ ( - of specific acupuncture points was used as an objective endpoint ( indicator of outcome ) and for identification of antigens , according to Voll criteria . All measurements were taken before and after treatment , and EDS was carried out at all treatment sessions . Outcome criteria suggesting efficacy were reduction in ASSI score , reduction in number of items testing positive , and normalization of conductance measurements . A statistical analysis of the outcomes was performed using the student 's paired t-test . RESULTS There was a statistically significant change in pre- and post-treatment measurements of the ASSI . The conductance measurements normalized and the number of items testing positive decreased compared to pre-treatment testing . In addition to these parameters , 87.2 percent of subjects rated efficacy as good to excellent , and less than one-percent rated the outcome as poor . The outcome demonstrated longevity , meaning that people who had their post-treatment evaluation up to three years after primary treatment were still showing minimal ASSI scores , with no additional treatment . The treatment appeared to work equally well across age groups and gender . Forty-eight percent of participants had an aggravation of symptoms after treatment , lasting an average of 10 hours , with reactions described as mild to moderate . Average cost of the desensitization protocol ( all costs included ) was $ 822.16 . CONCLUSIONS This protocol demonstrated efficacy without serious toxicity and no long-term adverse effects . It is natural , non-invasive , and does not require long periods of avoidance of offending foods or environmental stimuli . The desensitization protocol is a low-cost , effective therapy for the treatment of patients suffering from symptoms of allergy/sensitivity disease Postoperative oral nutritional supplementation has been shown to be of clinical benefit . This study examined the clinical effects and cost of administration of oral supplements both before and after surgery BACKGROUND Re source -based relative value scales ( RBRVS ) have become a st and ard method for identifying costs and determining reimbursement for physician services . Development of RBRVS systems and methods are review ed , and the RBRVS concept of physician " work " is defined . OBJECTIVE Results of work and time inputs from chiropractic physicians are compared with those reported by osteopathic and medical specialties . Last , implication s for reimbursement of chiropractic fee services are discussed . METHODS Total work , intraservice work , and time inputs for clinical vignettes reported by chiropractic , osteopathic , and medical physicians are compared . Data for chiropractic work and time reports were drawn from a national r and om sample of chiropractors conducted as part of a 1997 workers ' compensation chiropractic fee schedule development project . Medical and osteopathic inputs were drawn from RBRVS research conducted at Harvard University under a federal contract reported in 1990 . Both data sets used the same or similar clinical vignettes and similar methods . Comparisons of work and time inputs are made for clinical vignettes to assess whether work reported by chiropractors is of similar magnitude and variability as work reported by other specialties . RESULTS Chiropractic inputs for vignettes related to evaluation and management services are similar to those reported by medical specialists and osteopathic physicians . The range of variation between chiropractic work input and other specialties is of similar magnitude to that within other specialties . Chiropractors report greater work input for radiologic interpretation and lower work input for manipulation services . CONCLUSIONS Chiropractors seem to perform similar total " work " for evaluation and management services as other specialties . No basis exists for excluding chiropractors from using evaluation and management codes for reimbursement purpose s on grounds of dissimilar physician time or work estimates . Greater work input by chiropractors in radiology interpretation may be related to a greater importance placed on findings in care planning . Consistently higher reports for osteopathic work input on manipulation are likely attributable to differences in reference vignettes used in the respective population s. Research with a common reference vignette used for manipulation providers is recommended , as is development of a single generic approach to coding for manipulation services Purpose . To determine whether practice of the Transcendental Meditation ( TM ) technique can affect medical expenses . Design . The evaluation was a quasi experimental , longitudinal , cost-minimization study . Setting . Province of Quebec , Canada . Subjects . This study involved 1418 Quebec health insurance enrollees who practice d the TM technique compared with 1418 subjects who were r and omly selected from enrollees of the same age , sex , and region . TM subjects had chosen to begin the technique prior to learning about and choosing to enter the study . Measures . This 14-year , pre- and postintervention study retrospectively assessed government payments to physicians for treating the TM and comparison groups . Other medical expense data for individuals were unavailable . Data were inflation-adjusted . For each subject , least squares regression slopes were calculated to estimate pre- and postintervention annual rates of change in payments . We compared the groups ' means and 1 % , 5 % , and 10 % trimmed means ( robust estimators ) of the slopes . Results . Before starting meditation , the yearly rate of increase in payments between groups was not significantly different ( p > .17 ) . After commencing meditation , the TM group 's mean payments declined 1 % to 2 % annually . The comparison group 's payments increased up to 11 . 73 % annually over 6 years . There was a 13 . 78 % mean annual difference ( p = .0017 ) . Conclusions . The results suggest that the TM technique reduced payments to physicians between 5 % and 13 % annually relative to comparison subjects over 6 years . R and omized studies are recommended OBJECTIVES To measure the marginal costs of providing complementary medicine services ( mostly homoeopathy ) in outpatient clinics for patients with rheumatoid arthritis ( RA ) and to illustrate how parameters to which the cost of complementary medicine may be sensitive can be identified . DESIGN Retrospective , observational costing study . SETTING The outpatient clinic of the Royal London Homoeopathic Hospital . SUBJECTS R and om sample of 89 patients from the 427 ( RA ) patients attending outpatient clinics from April 1995 to March 1996 . MAIN OUTCOME MEASURES The marginal costs incurred by the hospital of treating 89 patients attending outpatient clinics and the relative contribution of the different re sources to the total costs . RESULTS The total costs of treating 89 patients were 7,124 Pounds of which 543 Pounds was assumed to be fixed and the remainder variable . The marginal costs of treating additional patients , starting from zero patients treated , are presented . Consultation time ( doctors and dietician ) contributed to 29 % of the total costs , non-conventional drugs contributed to 22 % of the total costs . CONCLUSIONS Underst and ing the marginal costs of providing complementary care to RA patients will inform the debate over whether these therapies are likely to be cost-effective . In addition , those who would like to explore the practicalities of establishing a service involving complementary medicine will gain an underst and ing of the likely provider costs . The cost of complementary medicine appears to be most sensitive to the time spent with the patient by the doctor Abstract Objective : To evaluate the cost effectiveness of physiotherapy , manual therapy , and care by a general practitioner for patients with neck pain . Design : Economic evaluation alongside a r and omised controlled trial . Setting : Primary care . Participants : 183 patients with neck pain for at least two weeks recruited by 42 general practitioners and r and omly allocated to manual therapy ( n=60 , spinal mobilisation ) , physiotherapy ( n=59 , mainly exercise ) , or general practitioner care ( n=64 , counselling , education , and drugs ) . Main outcome measures : Clinical outcomes were perceived recovery , intensity of pain , functional disability , and quality of life . Direct and indirect costs were measured by means of cost diaries that were kept by patients for one year . Differences in mean costs between groups , cost effectiveness , and cost utility ratios were evaluated by applying non-parametric bootstrapping techniques . Results : The manual therapy group showed a faster improvement than the physiotherapy group and the general practitioner care group up to 26 weeks , but differences were negligible by follow up at 52 weeks . The total costs of manual therapy ( € 447 ; £ 273 ; $ 402 ) were around one third of the costs of physiotherapy ( € 1297 ) and general practitioner care ( € 1379 ) . These differences were significant : P<0.01 for manual therapy versus physiotherapy and manual therapy versus general practitioner care and P=0.55 for general practitioner care versus physiotherapy . The cost effectiveness ratios and the cost utility ratios showed that manual therapy was less costly and more effective than physiotherapy or general practitioner care . Conclusions : Manual therapy ( spinal mobilisation ) is more effective and less costly for treating neck pain than physiotherapy or care by a general practitioner . What is already known on this topic The cost of treating neck pain is considerable Many conservative interventions are available , such as prescription drugs , yet their cost effectiveness has not been evaluated No r and omised trials of conservative treatment for neck pain have so far included an economic evaluation What this study adds Manual therapy is more effective and less costly than physiotherapy or care by a general practitioner for treating neck pain Patients undergoing manual therapy recovered more quickly than those undergoing the other HYPOTHESIS Perioperatively administered enteral immunonutrition will improve early postoperative morbidity and cost-effectiveness after gastrointestinal tract surgery . DESIGN A prospect i ve , r and omized , double-blind , multicenter clinical trial . SETTING Surgical departments in German university and teaching hospitals . PATIENTS One hundred fifty-four patients with upper gastrointestinal tract malignant neoplasms who were eligible for analysis . INTERVENTION Preoperatively , patients received 5 days of oral immunonutrition ( an arginine- , RNA- , and omega3 fatty acid-supplemented diet ) or an isoenergetic control diet ( 1 L/d ) . Early postoperative enteral feeding with immunonutrition or an isoenergetic , isonitrogenous control diet using a catheter jejunostomy was performed for 10 days . MAIN OUTCOME MEASURES Postoperative infectious complications , their treatment costs , and cost-effectiveness of immunonutrition were analyzed . Plasma levels of the fatty acids eicosapentaenoic acid and docosahexaenoic acid were measured . RESULTS In the immunonutrition group , significantly fewer infectious complication events occurred ( 14 vs 27 ; P = .05 ) . The number of patients with complications was significantly lower in the supplemented diet group after postoperative day 3 ( 7 vs 16 ; P = .04 ) . The treatment costs of complications in the supplemented diet group were suggestively lower than in the control diet group ( DM 75172 vs DM 204273 ) . Cost-effectiveness was DM 1503 in the experimental group vs DM 3587 in the control group , where DM denotes deutsche mark ( German currency ) . CONCLUSION The perioperative administration of an enteral immunonutrition significantly ( P = .05 ) decreased the early occurrence of postoperative infections and reduced substantially the treatment costs of the complications after major upper gastrointestinal tract surgery CONTEXT A prior national survey documented the high prevalence and costs of alternative medicine use in the United States in 1990 . OBJECTIVE To document trends in alternative medicine use in the United States between 1990 and 1997 . DESIGN Nationally representative r and om household telephone surveys using comparable key questions were conducted in 1991 and 1997 measuring utilization in 1990 and 1997 , respectively . PARTICIPANTS A total of 1539 adults in 1991 and 2055 in 1997 . MAIN OUTCOMES MEASURES Prevalence , estimated costs , and disclosure of alternative therapies to physicians . RESULTS Use of at least 1 of 16 alternative therapies during the previous year increased from 33.8 % in 1990 to 42.1 % in 1997 ( P < or = .001 ) . The therapies increasing the most included herbal medicine , massage , megavitamins , self-help groups , folk remedies , energy healing , and homeopathy . The probability of users visiting an alternative medicine practitioner increased from 36.3 % to 46.3 % ( P = .002 ) . In both surveys alternative therapies were used most frequently for chronic conditions , including back problems , anxiety , depression , and headaches . There was no significant change in disclosure rates between the 2 survey years ; 39.8 % of alternative therapies were disclosed to physicians in 1990 vs 38.5 % in 1997 . The percentage of users paying entirely out-of-pocket for services provided by alternative medicine practitioners did not change significantly between 1990 ( 64.0 % ) and 1997 ( 58.3 % ) ( P=.36 ) . Extrapolations to the US population suggest a 47.3 % increase in total visits to alternative medicine practitioners , from 427 million in 1990 to 629 million in 1997 , thereby exceeding total visits to all US primary care physicians . An estimated 15 million adults in 1997 took prescription medications concurrently with herbal remedies and /or high-dose vitamins ( 18.4 % of all prescription users ) . Estimated expenditures for alternative medicine professional services increased 45.2 % between 1990 and 1997 and were conservatively estimated at $ 21.2 billion in 1997 , with at least $ 12.2 billion paid out-of-pocket . This exceeds the 1997 out-of-pocket expenditures for all US hospitalizations . Total 1997 out-of-pocket expenditures relating to alternative therapies were conservatively estimated at $ 27.0 billion , which is comparable with the projected 1997 out-of-pocket expenditures for all US physician services . CONCLUSIONS Alternative medicine use and expenditures increased substantially between 1990 and 1997 , attributable primarily to an increase in the proportion of the population seeking alternative therapies , rather than increased visits per patient CONTEXT Visit length is an important component of physician payment systems . As use and insurance coverage of complementary and alternative medicine ( CAM ) increases , equitable reimbursement strategies for CAM providers will be needed . Little information is available about the time CAM providers spend with patients . OBJECTIVE To describe the length of visit and determinants of visit time to chiropractors and acupuncturists . DESIGN Survey of CAM practitioners that collected information on providers ( e.g. , socio-demographics , practice patterns , training ) and professional visit encounters ( e.g. , patient demographics , payment source , problem acuity , visit length , procedures performed ) . SUBJECTS R and om sample of 130 licensed chiropractors and 133 licensed acupuncturists surveyed in 1998 - 1999 , each from one Western and one Northeastern US state . MEASURES Patient , provider , and visit factors associated with visit duration were analyzed using weighted linear regression . RESULTS Data were available on 2550 chiropractic and 2561 acupuncture visits . Mean chiropractic visit length was 21.5 minutes ( SE = 0.8 ) . Mean acupuncture visit length was 56.6 minutes ( SE = 0.7 ) In both professions , new patient visits took longer , while visits for wellness or chronic problems were shorter . Preventive counseling by the chiropractor increased visit time , as did use of manual ( vs. instrument ) spinal manipulation , soft tissue techniques and physiotherapeutics . Acupuncture visits were shorter when specialized needling techniques ( e.g. auricular or scalp acupuncture ) were used , and longer with other adjunctive Asian therapies ( e.g. , cupping or magnets ) . Self-paid acupuncture visits were longer , as were visits with acupuncturists who had less practice experience or fewer years of training . CONCLUSIONS For both chiropractic and acupuncture , certain visit factors , provider characteristics , and procedures increase visit length , many of which parallel those observed in conventional medical setting s. Thus , a similar time-based payment scheme may be a reasonable starting point for developing methods for reimbursing CAM providers This study was carried out in 120 patients affected by migraine without aura , treated in 4 public health centers and r and omly divided into acupuncture group ( AG ) and conventional drug therapy group ( CDTG ) . The evaluation of clinical results was made 6 and 12 months after the beginning of treatment and was worked out as well according to socio-medical parameters . Acupuncture was applied to the following points : Touwei ( ST 8) , Xuanlu ( GB 5 ) , Fengchi ( GB 20 ) , Dazhui ( GV 14 ) , Lieque ( LU 7 ) , treated with the reducing method . In AG , the figure scoring the entity and frequency of migraine attacks drops from 9,823 before treatment to 1,990 6 months after and 1,590 12 months after ; while in CDTG , it drops from 8,405 before treatment to 3,927 6 months after and 3,084 12 months after . In AG , the total absence from work amounted to 1,120 working days/year , with a total cost ( private + social costs ) of 186,677,000 Italian liras . In CDTG , the absence from work amounted to 1,404 working days/year , with a total cost of 266,614,000 Italian liras . If we consider that in Italy the patients affected by migraine without aura are around 800,000 , and that acupuncture therapy is able to save 1,332,000 Italian liras on the total average cost supported for every single patient , the application of acupuncture in the treatment of migraine without aura would allow a saving of the health expenses in Italy of over 1,000 billion liras Abstract Objective To evaluate the cost effectiveness of acupuncture in the management of chronic headache . Design Cost effectiveness analysis of a r and omised controlled trial . Setting General practice s in Engl and and Wales . Participants 401 patients with chronic headache , predominantly migraine . Interventions Patients were r and omly allocated to receive up to 12 acupuncture treatments over three months from appropriately trained physiotherapists , or to usual care alone . Main outcome measure Incremental cost per quality adjusted life year ( QALY ) gained . Results Total costs during the one year period of the study were on average higher for the acupuncture group ( £ 403 ; $ 768;€598 ) than for controls ( £ 217 ) because of the acupuncture practitioners ' costs . The mean health gain from acupuncture during the one year of the trial was 0.021 quality adjusted life years ( QALYs ) , leading to a base case estimate of £ 9180 per QALY gained . This result was robust to sensitivity analysis . Cost per QALY dropped substantially when the analysis incorporated likely QALY differences for the years after the trial . Conclusions Acupuncture for chronic headache improves health related quality of life at a small additional cost ; it is relatively cost effective compared with a number of other interventions provided by the NHS OBJECTIVE ischaemic lower-extremity ulcers in the diabetic population are a source of major concern because of the associated high risk of limb-threatening complications . The aim of this study was to evaluate the role of hyperbaric oxygen in the management of these ulcers . METHOD eighteen diabetic patients with ischaemic , non-healing lower-extremity ulcers were recruited in a double-blind study . Patients were r and omly assigned either to receive 100 % oxygen ( treatment group ) or air ( control group ) , at 2.4 atmospheres of absolute pressure for 90 min daily ( total of 30 treatments ) . RESULTS healing with complete epithelialisation was achieved in five out of eight ulcers in the treatment group compared to one out of eight ulcers in the control group . The median decrease of the wound areas in the treatment group was 100 % and in the control group was 52 % ( p=0.027 ) . Cost-effectiveness analysis has shown that despite the extra cost involved in using hyperbaric oxygen , there was a potential saving in the total cost of treatment for each patient during the study . CONCLUSION hyperbaric oxygen enhanced the healing of ischaemic , non-healing diabetic leg ulcers and may be used as a valuable adjunct to conventional therapy when reconstructive surgery is not possible The effectiveness of spa therapy in the management of patients with Parkinson 's disease ( PD ) has never been evaluated . This is assessed in this pilot study . A prospect i ve , r and omized , cross-over , controlled study was conducted in 31 PD patients who underwent a 20-week spa period , including spa therapy for 3 weeks , and a 20-week non-spa period . Effectiveness was assessed using quality of life scales ( PDQ-39 and SF-36 ) , motor scale ( UPDRS ) and psychological question naire ( GHQ-28 ) , at baseline and at 4 ( T4 ) and at 20 weeks ( T20 ) . Direct medical costs ( radiological and laboratory tests , physician fees , drug therapy , and ancillary care ) were recorded over each 20-week period . At T4 , spa therapy improved significantly several dimensions of PDQ-39 and SF-36 , part IV of the UPDRS , and GHQ-28 . At T20 , no difference in any parameter was found . The mean direct medical cost over 20 weeks ( euro;1,328 + /- 167 ; pound 776 + /- 97 per patient ) in the spa period was slightly but significantly reduced in comparison with that of the non-spa period ( euro;1380 + /- 523 ; pound 807 + /- 306 per patient ) . This cost-effectiveness analysis suggests that spa therapy is more effective and less expensive than conventional treatment alone and could be beneficial in the management of PD More data are needed providing strong evidence that nutrition services are cost-effective . Economic evaluations , such as cost-effectiveness analyses , are excellent practice -based research projects . We conducted a cost-effectiveness analysis in a clinical setting to compare the cost-effectiveness of lipid-lowering medications plus diet therapy ( medication + diet ) with diet therapy alone ( diet alone ) for treating patients with hypercholesterolemia . Twenty-five adults with hypercholesterolemia ( 13 receiving medication + diet , 12 receiving diet alone ) either participated in an 8-week , home-based , step 1 intervention or were counseled about diet and lifestyle by their care provider . Diet , cost , and laboratory data were collected at baseline , at 9 months , and at 19 months after participation in the intervention ( follow-up ) . Cost per unit change in outcome was evaluated for each group . The diet-alone group made only small changes in dietary intake , changes that were smaller in magnitude than those made by the medication + diet group . Nevertheless , at 9 months , costs per unit change in total serum cholesterol level and low-density lipoprotein cholesterol ( LDL-C ) level were approximately $ 24 and $ 83 less , respectively , for the diet-alone group . At follow-up , however , the cost per unit change in LDL-C level was approximately $ 17 less for the medication + diet group , which can be explained by the medication + diet group 's greater decrease in LDL-C level . The following elements should be considered when conducting a cost-effectiveness analysis of medical nutrition therapy : effectiveness of the nutrition intervention , adequate sample size , confounding variables , compliance with diet and drug therapy , direct and indirect costs of care , and follow-up evaluation Acupuncture treatment and control group interventions in parallel-group r and omised trials of acupuncture are not always precisely reported . In an attempt to improve st and ards , an international group of experienced acupuncturists and research ers devised a set of recommendations , design ating them STRICTA : ST and ards for Reporting Interventions in Controlled Trials of Acupuncture . In a further consensus-building round , the editors of several journals helped redraft the recommendations . These follow the Consoli date d St and ards for Reporting Trials ( CONSORT ) format , acting as an extension of the CONSORT guidelines for the specific requirements of acupuncture studies . Participating journals are publishing the STRICTA recommendations and requesting prospect i ve authors to adhere to them when preparing reports for publication . Other journals are invited to adopt these recommendations . The intended outcome is that interventions in controlled trials of acupuncture will be more adequately reported , thereby facilitating an improvement in critical appraisal , analysis and replication of trials PURPOSE Professionally administered psychosocial interventions have been shown to improve the quality of life of cancer patients undergoing chemotherapy . The present study sought to improve access to psychosocial interventions during chemotherapy treatment by evaluating the efficacy and costs of a patient self-administered form of stress management training that requires limited professional time or experience to deliver . PATIENTS AND METHODS Four hundred eleven patients about to start chemotherapy were r and omly assigned to receive usual psychosocial care only , a professionally administered form of stress management training , or a patient self-administered form of stress management training . Quality -of-life assessment s were conducted before r and omization and before the second , third , and fourth treatment cycles . Intervention costs were estimated from both payer and societal perspectives . RESULTS Compared with patients who received usual care only , patients receiving the self-administered intervention reported significantly ( P < or = .05 ) better physical functioning , greater vitality , fewer role limitations because of emotional problems , and better mental health . In contrast , patients who received the professionally administered intervention fared no better in terms of quality of life than patients receiving usual care only . Costs of the self-administered intervention were estimated to be 66 % ( from a payer perspective ) to 68 % ( from a societal perspective ) less than the average costs of professionally administered psychosocial interventions for patients starting chemotherapy . CONCLUSION Evidence regarding the efficacy and favorable costs of self-administered stress management training suggests that this intervention has the potential to greatly improve patient access to psychosocial intervention during chemotherapy treatment BACKGROUND Because the value of popular forms of alternative care for chronic back pain remains uncertain , we compared the effectiveness of acupuncture , therapeutic massage , and self-care education for persistent back pain . METHODS We r and omized 262 patients aged 20 to 70 years who had persistent back pain to receive Traditional Chinese Medical acupuncture ( n = 94 ) , therapeutic massage ( n = 78 ) , or self-care educational material s ( n = 90 ) . Up to 10 massage or acupuncture visits were permitted over 10 weeks . Symptoms ( 0 - 10 scale ) and dysfunction ( 0 - 23 scale ) were assessed by telephone interviewers masked to treatment group . Follow-up was available for 95 % of patients after 4 , 10 , and 52 weeks , and none withdrew for adverse effects . RESULTS Treatment groups were compared after adjustment for prer and omization covariates using an intent-to-treat analysis . At 10 weeks , massage was superior to self-care on the symptom scale ( 3.41 vs 4.71 , respectively ; P = .01 ) and the disability scale ( 5.88 vs 8.92 , respectively ; P<.001 ) . Massage was also superior to acupuncture on the disability scale ( 5.89 vs 8.25 , respectively ; P = .01 ) . After 1 year , massage was not better than self-care but was better than acupuncture ( symptom scale : 3.08 vs 4.74 , respectively ; P = .002 ; dysfunction scale : 6.29 vs 8.21 , respectively ; P = .05 ) . The massage group used the least medications ( P<.05 ) and had the lowest costs of subsequent care . CONCLUSIONS Therapeutic massage was effective for persistent low back pain , apparently providing long-lasting benefits . Traditional Chinese Medical acupuncture was relatively ineffective . Massage might be an effective alternative to conventional medical care for persistent back pain OBJECTIVES To assess the feasibility of endocrine cervical surgery under hypnoanesthesia as a valuable , safe , efficient , and economic alternative to general anesthesia . METHODS Between April 1994 and June 1997 , 197 thyroidectomies and 21 cervical explorations for hyperparathyroidism were performed under hypnoanesthesia ( HYP ) using Erikson 's method . Operative data and postoperative course of this initial series were compared to a contemporary population of patients ( n = 119 ) clinical ly similar except that they declined HYP or were judged unsuitable for it , and who were therefore operated on under general anesthesia ( GA ) . RESULTS The surgeons all reported better operating conditions for cervicotomy using HYP . Conversion from hypnosis to GA was needed in two cases ( 1 % ) . All patients having HYP reported a pleasant experience and , keeping in mind that the GA group is not a r and omly assigned control group , both had significantly less postoperative pain and analgesic use . Hospital stay was also significantly shorter , providing a substantial reduction in the costs of medical care . The postoperative convalescence was significantly improved after HYP and a full return to social or professional activity was significantly quicker . CONCLUSION From this study , we conclude that HYP is an effective technique for providing relief of intraoperative and postoperative pain in endocrine cervical surgery . The technique results in high patient satisfaction and better surgical convalescence . This technique can therefore be used in most well-chosen patients and reduces the socioeconomic impact of hospitalization PURPOSE To determine , from a societal perspective , the effectiveness and cost effectiveness of concentrated cranberry tablets , versus cranberry juice , versus placebo used as prophylaxis against lower urinary tract infection ( UTI ) in adult women . MATERIAL S AND METHODS One hundred fifty sexually active women aged 21 through 72 years were r and omized for one year to one of three groups of prophylaxis : placebo juice + placebo tablets versus placebo juice + cranberry tablets , versus cranberry juice + placebo tablets . Tablets were taken twice daily , juice 250 ml three times daily . Outcome measures were : ( 1 ) a > 50 % decrease in symptomatic UTI 's per year ( symptoms + > or= 100 000 single organisms/ml ) and ( 2 ) a > 50 % decrease in annual antibiotic consumption . Cost effectiveness was calculated as dollar cost per urinary tract infection prevented . Stochastic tree decision analytic modeling was used to identify specific clinical scenarios for cost savings . RESULTS Both cranberry juice and cranberry tablets statistically significantly decreased the number of patients experiencing at least 1 symptomatic UTI/year ( to 20 % and 18 % respectively ) compared with placebo ( to 32 % ) ( p<0.05 ) . The mean annual cost of prophylaxis was $ 624 and $ 1400 for cranberry tablets and juice respectively . Cost savings were greatest when patients experienced > 2 symptomatic UTI 's per year ( assuming 3 days antibiotic coverage ) and had > 2 days of missed work or required protective undergarments for urgency incontinence . Total antibiotic consumption was less annually in both treatment groups compared with placebo . Cost effectiveness ratios demonstrated cranberry tablets were twice as cost effective as organic juice for prevention . CONCLUSIONS Cranberry tablets provided the most cost-effective prevention for UTI OBJECTIVE To assess dietary costs during a family-based pediatric obesity intervention . DESIGN Families were r and omized to one of two groups . Dietary and cost data were collected from a parent or child using three 24-hour recalls : at baseline , 6 months , and 12 months . SUBJECTS Thirty-one families with an obese 8- to 12-year-old child entered treatment , with complete dietary data provided from 20 families . INTERVENTION The 20-week behavior modification intervention emphasized increasing diet nutrient-density . Families attended group and individual sessions or group sessions . MAIN OUTCOME MEASURES Energy intake ; percent of energy from protein , fat , and carbohydrate ; servings and percent servings from food groups classified by nutrient density ; and daily food costs . STATISTICAL ANALYSES PERFORMED Mixed analyses of variance , with group as the between-subject factor , and time as the within-subject factor . RESULTS No significant effect of group was found in any analyses . Significant decreases in percent overweight were observed at 6 and 12 months for children ( -10.0+/-8.7 and -8.0+/-10.3 , respectively ) ( mean+/-st and ard deviation ) and parents ( -6.7+/-10.3 and -5.3+/-14.1 ) . Energy intake for parents and children combined significantly decreased from baseline ( 1,881+/-462 ) to 6 months ( 1,412+/-284 ) , and 1 year ( 1,338+/-444 ) . Servings from low-nutrient-dense foods significantly decreased from baseline ( 34.7+/-16.2 ) to 6 months ( 16.0+/-8.6 ) and 1 year ( 18.6+/-9.2 ) , causing a significant increase in diet nutrient density . Dietary cost did not change at 6 months , but significantly decreased from baseline to 1 year ( $ 6.77+/-2.41 to $ 5.04+/-1.80 ) . Cost per 1,000 kcal did not significantly change . APPLICATIONS/ CONCLUSIONS Adopting a lower-energy , nutrient-dense diet did not increase dietary costs over time . Consequently , cost should not be a barrier in the adoption of a healthful diet From a societal perspective long-term clinical trials or follow-up studies should preferably not only include an evaluation of the health effect for the patient , but also an economic evaluation . In order to yield comprehensive medical and nonmedical re source use data , we at least partly depend on respondents ' recall for collecting these costing data . A patient cost diary was developed in order to estimate total re source use , expenses , and lost production due to illness and treatment . We applied the cost diary in two r and omized clinical trials evaluating the cost-effectiveness of behavioral rehabilitation in 205 fibromyalgia and chronic low back pain patients . The use of the diary was evaluated , study ing the feasibility , the influence of the period of data collection on the results , and some aspects of validity . Eighty-five percent of the patients completed at least one diary and in total 68 % of the diaries were returned . Although the results for the three alternative periods of data collection ( keeping the diary 1 week every month , 2 weeks every 2 months , or a full year ) were not significantly different , they were only moderately correlated . Finally , self-reported specialist care contacts were generally in agreement with data from an insurance company . However , for physiotherapy contacts there were differences between the self-reported and insurance data . This study shows how the cost diary might be used successfully in cost-effectiveness studies In a prospect i ve study of the efficacy of the ketogenic diet in children with severe , refractory epilepsy , data were collected on medication changes over 1 year . Cost reductions in medications were calculated over the first year and estimated for a second year . Fifty-seven percent of the children stayed on the diet for 1 year , and 74 % of these children had their number of medications reduced . Forty-eight percent of children who stayed on the diet were on no medications at 12 months follow-up . Daily medication costs were reduced by nearly 70 % . ( J Child Neurol 1999;14:469 - 471 ) OBJECTIVES For people with dyspepsia who are receiving orthodox general practice care , what is the effect on outcome and on NHS costs of adding treatment by a choice of acupuncture or homeopathy ? This paper describes and reflects upon a pilot study with user involvement . DESIGN A r and omised pilot study . Patients chose between acupuncture and homeopathy and were then r and omised to this preference or to the control group of normal GP care . SETTING AND PARTICIPANTS Sixty people with dyspepsia ( > /=2 weeks ) presenting in one UK general practice were recruited in consultations and by letter to those on repeat prescriptions . There were few exclusion criteria . The homeopath and the acupuncturist treated the patient individually according to their normal practice for up to 6 months . After the trial there was a focus group for participants . OUTCOME MEASURES SF-36 health survey , Measure Yourself Medical Outcome Profile ( MYMOP ) , and General Well-being Index ( GWBI ) . Counts of prescriptions , consultations and referrals from practice computer records . RESULTS No trend or significant difference between the groups for clinical outcome or NHS costs . Major costs for the 6 months , mean ( S.D. ) cost per patient , were general practitioner consultations pound 8 ( 18 ) , prescriptions pound 64 ( 73 ) , acupuncture pound 175 ( 52 ) , homeopathy pound 105 ( 33 ) . Participants gave insights and suggestions which will inform the full trial design . CONCLUSIONS Reflection on the pilot study data and experience by participants , treating practitioners and research ers led to modifications in the design and a sample size calculation . How to demonstrate individual responses to treatment remains a problem BACKGROUND Cardiac surgery patients are commonly treated with diuretics , which can result in hypokalemia requiring potassium supplementation . OBJECTIVE Our objective was to determine whether cardiac surgery patients receiving therapy with potassium-wasting diuretics can safely and beneficially maintain serum potassium levels by eating potassium-rich foods . DESIGN A prospect ively r and omized trial of diet vs medication supplementation of potassium was undertaken . Patients who were to undergo cardiac surgery and who would be receiving therapy with oral furosemide postoperatively were eligible for the study . Forty-eight patients were enrolled in the trial , and 38 patients completed the study . Patients received either potassium-rich foods ( diet ) or potassium chloride pills ( medication ) . RESULTS There was no significant difference in mean ( + /- SD ) serum potassium concentrations between groups preoperatively ( 4.25 + /- 0.30 vs 4.29 + /- 0.33 mEq/L , respectively ) , on postoperative day 3 ( 4.23 + /- 0.40 vs 4.27 + /- 0.40 mEq/L , respectively ) , or postoperative day 4 ( 4.23 + /- 0.48 vs 4.24 + /- 0.33 mEq/L , respectively ) for the diet and medication groups . Length of stay was significantly lower in the diet group ( 5.0 + /- 0.9 vs 6.3 + /- 2.2 days , respectively ) . When asked their preferences for method of supplementation , 79 % of patients preferred the diet method . CONCLUSIONS Cardiac surgery patients receiving therapy with diuretics can maintain serum potassium levels at clinical ly adequate concentrations by eating potassium-rich foods . Length of stay was significantly reduced . This method of potassium supplementation demonstrates the potential for reduced costs and increased patient satisfaction PURPOSE To compare the cost of st and ard intravenous conscious sedation with that of sedation with adjunct self-hypnotic relaxation during outpatient interventional radiologic procedures . MATERIAL S AND METHODS Data were review ed from a prospect i ve r and omized study in which patients undergoing vascular and renal interventional procedures underwent either st and ard sedation ( n = 79 ) or sedation with adjunct hypnosis ( n = 82 ) . These data were used to construct a decision analysis model to compare the cost of st and ard sedation with the cost of sedation with adjunct hypnosis . Multiple sensitivity analyses were performed to assess the applicability of these results to other institutions with different cost structures with respect to the following variables : cost of the hypnosis provider , cost of room time for interventional radiologic procedure , hours of observation after the procedure , and frequency and cost of complications associated with over- or undersedation . RESULTS According to data from this experience , the cost associated with st and ard sedation during a procedure was $ 638 , compared with $ 300 for sedation with adjunct hypnosis , which result ed in a savings of $ 338 per case with hypnosis . Although hypnosis was known to reduce room time , hypnosis remained more cost-effective even if it added an additional 58.2 minutes to the room time . CONCLUSION Use of adjunct hypnosis with sedation reduces cost during interventional radiologic procedures Whilst significant advances have been made in persuading clinical research ers of the value of conducting economic evaluation alongside clinical trials , a number of problems remain . The most fundamental is the fact that economic principles are almost entirely ignored in the traditional approach to trial design . For example , in the selection of an optimal sample size no consideration is given to the marginal costs or benefits of sample information . In the traditional approach this can lead to either unbounded or arbitrary sample sizes . This paper presents a decision-analytic approach to trial design which takes explicit account of the costs of sampling , the benefits of sample information and the decision rules of cost-effectiveness analysis . It also provides a consistent framework for setting priorities in research funding and establishes a set of screens ( or hurdles ) to evaluate the potential cost-effectiveness of research proposals . The framework permits research priority setting based explicitly on the budget constraint faced by clinical practitioners and on the information available prior to prospect i ve research . It demonstrates the link between the value of clinical research and the budgetary restrictions on service provision , and it provides practical tools to establish the optimal allocation of re sources between areas of clinical research or between service provision and research We sought to determine whether an intervention labeled “ biofeedback ” could be implemented with patients who were diagnosed with “ functional ” disorders ( Irritable Bowel Syndrome , Fibromyagia/Chronic Fatigue Syndrome , Myofascial Pain , Anxiety with somatic features , or Noncardiac Chest Pain ) , in a primary care setting , and whether cost savings through lowered utilization of medical services would be realized . Seventy patients were initially r and omized into a treatment group or comparison group based on willingness to participate . Ultimately , 19 patients completed treatment and 30 were followed through usual treatment as a comparison . Treatment patients completed symptom diaries while working with a biofeedback therapist in the primary care facility . Both group 's medical expenses were tracked for 6 months prior to and 6 months after the treatment time interval . Patients in the treatment group lowered symptom frequency and severity significantly . Medical costs were differentially reduced in this group such that all costs were $ 72 less in the treatment group and $ 9 in the comparison for the 6 months following the treatment time period . ( p < .001 ) . Unfortunately , a large group of assigned treatment patients did not start or complete treatment . These patients had high initial costs and went up even higher post . No comparable group could be found among the controls , limiting any inference regarding cost/benefit . Biofeedback based interventions for “ functional ” disorders can be easily integrated into primary care setting s , can reduce symptoms , and may be able to reduce overall medical costs in this group of patients known as heavy utilizers OBJECTIVE To compare the 1-year costs for patients treated for acute and chronic ambulatory low back pain by medical physicians and chiropractors . STUDY DESIGN Prospect i ve , practice -based observational study undertaken in 13 general medical practice s and 51 chiropractic community-based clinics . PATIENTS AND METHODS Of 2872 study patients , 2263 had complete 1-year records of services . Service data , collected from billing records , chart audits , and provider question naires , were assigned relative value units that were converted into 1995 dollar costs . Prescription drug costs for medical patients were included . Patient data on health status , pain and disability , and socioeconomic characteristics were obtained from self-administered question naires . RESULTS The direct office costs of treating both chiropractic and medical patients over a 1-year period were relatively small . Forty-three percent of chiropractic patients and 57 % of medical patients incurred costs of less than $ 100 . However , the mean costs associated with chiropractic patients ( $ 214 ) were significantly higher than those for medical patients ( $ 123 ) , especially when compared with medical patients who were not referred for further treatment or evaluation ( $ 103 ) . Chiropractic patients had somewhat lower baseline levels of pain and disability than nonreferred medical patients , but the 2 groups were relatively similar on most patient characteristics . There also were no statistically significant differences in the improvements in pain and disability between these 2 groups of patients . CONCLUSION The results of this study indicate that patients treated in chiropractic clinics incur higher costs over a 1-year period , but have about the same degree of relief as nonreferred patients treated in medical clinics The growing use of unsubstantiated complementary and alternative medicine therapies by people in the United States1 along with its increasing coverage by third party payers2 encouraged Congress to create the National Center for Complementary and Alternative Medicine ( NCCAM ) at the National Institutes of Health . The centre 's mission is “ to explore complementary and alternative healing practice s in the context of rigorous science ; to educate and training CAM research ers ; and to disseminate authoritative information to the public and professionals.”3 To complete this mission , NCCAM supports publicly relevant and scientifically rigorous research to identify those complementary and alternative medicine practice s that are safe and effective . The centre 's re sources , although generous ( $ 68.3 m ( £ 46 m ) for fiscal year 2000 ) , are not sufficient to study all complementary and alternative medicine practice s. NCCAM therefore developed criteria to help prioritise the many possible research opportunities ( box ) . As part of the evaluation process , NCCAM seeks advice from its national advisory council , complementary and alternative medicine and conventional clinicians , members of the scientific research community , the public , sister federal agencies , and other stakeholders . # # # # Summary points Many early clinical trials investigating complementary and alternative medicine have had serious flaws Clinical investigations of complementary and alternative medicine are made difficult by factors such as use of complex , individualised treatments and lack of st and ardisation of herbal medicines Other problems include difficulties in accruing , r and omising , and retaining patients and in identifying appropriate placebo interventions Despite these complexities , rigorously design ed clinical trials are possible , including pragmatic studies of complete complementary and alternative medicine systems Strong commitment is required from the research community to provide information about complementary and alternative medicines to the public and health professionals Staff at the centre are often asked why limited re sources are being spent on research that is perceived as replicating previously published work , especially when other western countries have Study Design . A cohort of 114 primary care patients were studied for 1 year before and 1 year after a r and omized clinical trial . Objectives . To explore the therapy use , societal costs , and quality of life of patients with prolonged back pain . To compare the effects of physiotherapy , bone setting , and light exercise therapy on these measures . Summary of Background Data . Analyses of back pain have mostly focused on the minority of patients who cause high costs and a heavy burden on national economies . The majority with low costs have aroused less interest . The patient ’s choice of therapy , especially alternative medicine , has seldom been evaluated despite the increasing popularity of alternative therapies . Methods . Data were collected from the Social Insurance Institution files , patient records , and question naires : the Nottingham Health Profile ( NHP ) . Results . One year before enrollment a third of the patients had consulted primary care . Half of them had had some therapy : mainly massage , physiotherapy , naprapathy , or bone setting . One third of the direct costs were spent on complementary therapies and another third on rehabilitation . Sick leaves accounted for 55 % of the total costs ( US$ 1029 ) . The mean total costs slightly increased after the r and omized therapies ( US$ 1306 ) . The costs of ambulatory care , with the study therapies included , were similar , whereas physiotherapy seemed the cheapest ( US$ 621 ) and bone setting the most expensive ( US$ 2072 ) alternative in view of the total costs . More NHP subscales were improved by physiotherapy and bone setting than by exercise . Conclusions . A third of the direct back pain costs were spent on complementary therapies . The use of health care services and absenteeism tended to decrease after a course of physiotherapy . Physiotherapy and bone setting seemed able to improve the quality of life of patients with prolonged back pain Loss of body cell mass , the active functioning tissue of the body , commonly occurs in patients with human immunodeficiency virus ( HIV ) infection , and the extent of wasting is related to the length of survival . We evaluated the anabolic role of the amino acid L-glutamine ( GLN ) and antioxidants in a double-blind , placebo-controlled trial in 26 patients with > 5 % weight loss since disease onset . Subjects received GLN-antioxidants ( 40 g/d ) in divided doses or glycine ( 40 g/d ) as the placebo for 12 wk . Throughout the study , the subjects were seen weekly by a nutritionist , and body weight , bioelectric impedance assessment , and nutritional counseling were performed . Twenty-one subjects completed the study , and the groups were well matched . The 5 patients excluded from analysis all met a priori exclusion criteria . Over 3 mo , the GLN-antioxidant group gained 2.2 kg in body weight ( 3.2 % ) , whereas the control group gained 0.3 kg ( 0.4 % , P = 0.04 for difference between groups ) . The GLN-antioxidant group gained 1.8 kg in body cell mass , whereas the control group gained 0.4 kg ( P = 0.007 ) . Intracellular water increased in the GLN-antioxidant group but not in the control group . In conclusion , GLN-antioxidant nutrient supplementation can increase body weight , body cell mass , and intracellular water when compared with placebo supplementation . GLN-antioxidant supplementation provides a highly cost-effective therapy for the rehabilitation of HIV+ patients with weight loss Study Design . A cluster r and omized , controlled trial was performed . Objectives . To assess the clinical effectiveness and cost – effectiveness of adding patients ’ referral to neuroreflexotherapy intervention to the usual management of subacute and chronic low back pain in routine general practice . Summary of Background Data . Neuroreflexotherapy consists of the temporary implantation of epidermal devices in trigger points in the back and referred tender points in the ear . The efficacy of this procedure for treating subacute and chronic low back pain has been demonstrated in previous r and omized , double-blind , controlled clinical trials . Methods . Twenty-one primary care physicians working in seven primary care centers of the Spanish National Health Service in Palma de Mallorca , Spain , were r and omly assigned to the intervention group ( n = 11 ) or the control group ( n = 10 ) . The physicians recruited patients who had low back pain that had lasted for 14 or more days despite drug treatment and who did not meet criteria for surgery . The 45 patients recruited by physicians from the control group were treated according to the st and ard protocol , whereas the 59 patients recruited by physicians from the intervention group were , in addition , referred to neuroreflexotherapy intervention . The analysis of variables was performed taking into account that physicians , not patients , were r and omly assigned . Results . Patients underwent clinical evaluations at baseline and 15 , 60 , and 365 days later . At baseline , median intensity of pain was higher in patients undergoing neuroreflexotherapy than in control patients ( visual analogue scale , 6.07 ; range , 4.67–8.80 vs. 5.15 , range 4.11–8.00 ) and median duration of pain was also higher ( 48.1 , range 28.4–211.1 vs. 17.5 , range 15.0–91.5 days ) . At the last follow-up visit , patients treated with neuroreflexotherapy showed greater improvement than did control patients in low back pain ( visual analogue scale , 5.5 ; range , 3.7–8.8 vs. 1.9 ; range , −1.2–3.0;P < 0.001 ) ; referred pain ( visual analogue scale , 3.6 ; range , 2.7–7.3 vs. 0.6 ; range , −1.5–2.0;P = 0.001 ) ; and disability ( Rol and –Morris scale , 8.7 ; range , 2.0–13.3 vs. 2.0 ; range , −1.5–6.7;P = 0.007 ) . Moreover , neuroreflexotherapy intervention was associated with a significantly ( P < 0.035 ) lower number of consultations to private or public specialists , fewer indications of radiographs by primary care physicians , lower cost of drug treatment , and less duration of sick leave throughout the follow-up period . There were also differences in favor of neuroreflexotherapy intervention in the cost – effectiveness ratio for pain , disability , and quality of life that persisted in the most optimistic , the most conservative , and the average ( break-even case ) assumptions . Conclusions . Referral to neuroreflexotherapy intervention improves the effectiveness and cost – effectiveness of the management of nonspecific low back pain BACKGROUND Evidence suggests that breathing and relaxation therapy may influence cardiac events in persons after acute myocardial infa rct ion ( MI ) . The authors studied the effects of breathing and relaxation therapy on rates of cardiac events and cost effectiveness in past MI patients . METHODS Patients ( n = 156 ) were chosen r and omly to receive either exercise training plus relaxation therapy ( relaxation group ; n = 76 ) or exercise training only ( control group ; n = 80 ) . The occurrence of major cardiac events and cardiac rehospitalizations in the two treatment groups was compared . RESULTS At 5-year follow-up , 12 cardiac deaths had occurred , 5 in the relaxation group and 7 in the control group , reinfa rct ion occurred in 10 and 12 patients , and cardiac surgery was performed in 2 and 11 , respectively . In total , 15 ( 20 % ) and 26 ( 33 % ) patients , respectively , experienced at least one cardiac event ( odds ratio [ OR ] for the relaxation group : 0.55 , 95 % confidence interval [ CI ] 0.29 - 1.05 ; adjusted for risk factors OR 0.52 , 95 % CI 0.28 - 0.99 ) . Regarding all cardiac rehospitalizations , in the relaxation group , 30 patients ( 39 % ) had experienced 52 cardiac events , for which the patients were hospitalized for a total of 476 days . In the control group , 38 patients ( 48 % ) had experienced 78 cardiac events ( OR 0.72 ; 95 % CI 0.38 - 1.36 ) , comprising 719 days of hospitalization . The total number of hospitalizations was reduced by 31 % as a result of relaxation instruction . CONCLUSIONS In the long-term , the disease course after myocardial infa rct ion is influenced favorably by giving relaxation therapy in addition to cardiac rehabilitation . The extra costs of the therapy are compensated by a decrease in hospitalization for cardiac problems OBJECTIVE To evaluate the cost effectiveness and cost utility of a 3-week course of combined spa therapy and exercise therapy in addition to st and ard treatment consisting of antiinflammatory drugs and weekly group physical therapy in ankylosing spondylitis ( AS ) patients . METHODS A total of 120 Dutch out patients with AS were r and omly allocated into 3 groups of 40 patients each . Group 1 was treated in a spa resort in Bad Hofgastein , Austria ; group 2 in a spa resort in Arcen , The Netherl and s. The control group stayed at home and continued their usual activities and st and ard treatment during the intervention weeks . After the intervention , all patients followed weekly group physical therapy . The total study period was 40 weeks . Effectiveness of the intervention was assessed by functional ability using the Bath Ankylosing Spondylitis Function Index ( BASFI ) . Utilities were measured with the EuroQoL ( EQ-5D(utility ) ) . A time-integrated summary score defined the clinical effects ( BASFI-area under the curve [ AUC ] ) and utilities ( EQ-5D(utility)-AUC ) over time . Both direct ( health care and non-health care ) and indirect costs were included . Re source utilization and absence from work were registered weekly by the patients in a diary . All costs were calculated from a societal perspective . RESULTS A total of 111 patients completed the diary . The between-group difference for the BASFI-AUC was 1.0 ( 95 % confidence interval [ 95 % CI ] 0.4 - 1.6 ; P = 0.001 ) for group 1 versus controls , and 0.6 ( 95 % CI 0.1 - 1.1 ; P = 0.020 ) for group 2 versus controls . The between-group difference for EQ-5D(utility)-AUC was 0.17 ( 95 % CI 0.09 - 0.25 ; P < 0.001 ) for group 1 versus controls , and 0.08 ( 95 % CI 0.00 - 0.15 ; P = 0.04 ) for group 2 versus controls . The mean total costs per patient ( including costs for spa therapy ) in Euros ( euro ; ) during the study period were euro;3,023 for group 1 , euro;3,240 for group 2 , and euro;1,754 for the control group . The incremental cost-effectiveness ratio per unit effect gained in functional ability ( 0 - 10 scale ) was euro;1,269 ( 95 % CI 497 - 3,316 ) for group 1 , and euro;2,477 ( 95 % CI 601 - 12,098 ) for group 2 . The costs per quality -adjusted life year gained were euro;7,465 ( 95 % CI 3,294 - 14,686 ) for group 1 , and euro;18,575 ( 95 % CI 3,678 - 114,257 ) for group 2 . CONCLUSION Combined spa-exercise therapy besides st and ard treatment with drugs and weekly group physical therapy is more effective and shows favorable cost-effectiveness and cost-utility ratios compared with st and ard treatment alone in patients with AS CONTEXT Women are seeking alternatives to medications and surgeryfor the treatment of uterine fibroids ; therefore , it is important to know whether these therapies work and are cost-effective . OBJECTIVE To report on the treatment of women with uterine fibroids using a suite of nonpharmacological and nonsurgical therapies and to compare this alternative treatment to a matched sample of similar women using st and ard medical approaches . DESIGN Matched comparison to st and ard-of-care control group . SETTING Academic family practice department and clinic , including a center for complementary and alternative medicine . PARTICIPANTS Thirty-seven menstruating women , aged 24 to 45 years , with palpable uterine fibroids , and their matched controls , who were enrolled in conventional treatment . INTERVENTION The treatment program consisted of weekly traditional Chinese medicine , body therapy ( somatic therapy , bodywork ) , and guided imagery . Treatment lasted as long as 6 months . MAIN OUTCOME MEASURES Changes in fibroid size , changes in bothersome symptoms , and patient satisfaction . RESULTS Fibroids shrank or stopped growing in 22 patients among the treatment group and 3 among the comparison group ( P < .01 ) . Cost of care averaged $ 3800 per patient in the treatment group and was significantly greater than costs for the comparison group for the study period . Bothersome symptoms of fibroids responded equally well to pharmacological or nonpharmacological therapies . All measures of patient satisfaction were significantly higher among the treatment group compared to those receiving conventional care . CONCLUSIONS As reported previously in the Chinese medical literature , alternatives exist to pharmacological and surgical methods for treating uterine fibroids , though they are not inexpensive An open , non-r and omised , study ( postmarketing surveillance ) was carried out on three groups of patients aged 18 to 80 presenting over an 18 month period with acute exacerbations of low back pain . The objective was to assess the possible economic impact of including a regular dose of proprietary willow bark extract ( Assalix ) in the treatment provided . A first group of 115 patients , presenting to 3 general practitioners in the first 3 months , was prescribed a daily dose of extract containing 120 mg of salicin ( group W120 ) . They also had access , if necessary , to the range of conventional treatments allowed for in the general practitioners ' budgets . A second group of 112 patients presenting to the same general practitioners over the next 15 months , was prescribed extract equivalent to 240 mg salicin per day ( group W240 ) . A third " control " or " comparator " group of 224 patients , presenting to 3 orthopedists ( specialists in physical medicine ) over the whole 18 month period , received only the conventional therapeutic options allowed in the orthopedists ' budgets ( Group C ) . In the group C patients , the exacerbations had been shorter but the pain had been more intense as judged by Arhus Index and Total Pain Index . After 4 weeks of treatment , about 40 % of group W240 patients were free of pain whether or not they had to resort to supplementary treatments . In group W120 as a whole , about 19 % of patients were pain-free at 4 weeks , but only 8 % of those who did not resort to supplementary treatment . In group C , 18 % of patients were painfree . These findings were reflected reasonably well in the changes in the Arhus Index and Total Pain Index , and the findings in group W240 were consistent with those in a previous r and omised controlled trial . Multivariable modelling to examine for possible confounding effects tended to identify membership of group W240 as an independent explanator of better pain relief than membership of group C. Though the measures of effect tended to be similar in group W120 as a whole and group C , the avoidance of more expensive conventional treatments in group W120 meant that the average cost per patient of treatment was reduced by about 35 - 50 % ( health service and private costings respectively ) . The better pain relief in group W240 was accompanied by an even smaller reliance on supplementary conventional treatments than in group W120 but the extra savings on these were outweighed by the extra cost of the additional Assalix so that the average cost per patient was reduced by 14 - 40 % of the costs in group C. The possibility is discussed that , if orthopedists had relied more on regular full dosing with NSAIDs , they might have increased the effectiveness and reduced the cost of their treatment , though with the possibility of more side effects . Substituting established NSAIDs with COX-2 inhibitors might reduce the side effects , but at greater cost than with the Assalix BACKGROUND This research was conducted to evaluate the effect of enterally administered glutamine ( gln ) dipeptide on metabolic , gastrointestinal , and outcome parameters after severe burn injury . METHODS Forty thermally injured patients with total body surface burns ranging between 50 % and 80 % , and third-degree burns ranging between 20 % and 40 % and without respiratory injuries , were r and omized into a prospect i ve , double-blind , controlled clinical trial . One group received gln-enriched enteral nutrition and the other group received the st and ard enteral formulation . Tube feedings were initiated on postburn day 1 ( PBD + 1 ) , and isocaloric and isonitrogenous feedings were administered to both groups until PBD + 12 . The gln was given as the dipeptide of alanyl-gln ( Ajinomoto , Tokyo , Japan ) , which provided 0.35 g gln/kg body weight/d . Plasma amino acid profiles , serum endotoxin concentrations , and the lactulose/mannitol absorption ratio ( which reflects gut permeability ) were measured at specific times throughout the clinical course . Wound healing at day 30 was assessed , and length of hospital stay and total costs were determined at discharge . RESULTS The 2 groups were similar in terms of age and extent of injury . Plasma gln concentrations were approximately 300 umol/L in both groups on PBD + 1 and remained low in the control group ( 399 + /- 40 umol/L , mean + /- SD ) but increased toward normal in the supplemented group to 591 + /- 74 ( p = .048 ) . Lactulose/mannitol ratios were increased above normal on POD + 1 ( control , 0.221 + /- 0.169 ; gln , 0.268 + /- 0.202 ; not significant ) , reflecting increased intestinal permeability after burn injury . On POD + 3 , the ratio in the gln group was lower than control ( 0.025 + /- 0.008 versus 0.049 + /- 0.016 ; p = .0001 ) , and both groups returned toward normal ratios with time . Endotoxin levels on PBD + 1 were elevated in both groups ( control , 0.089 + /- 0.023 EU/mL ; gln , 0.103 + /- 0.037 EU/mL ; NS ) but decreased significantly on PBD + 3 in the patients receiving gln . Hospital stay was significantly shorter in the gln group than controls ( 67 + /- 4 days versus 73 + /- 6 ; p = .026 ) . On day 30 , wound healing was 86 % + /- 2 % complete in the gln group compared with 72 % + /- 3 % in controls ( p = .041 ) . Total cost of hospitalization was 62794 + /- 6178 RMB ( dollar 7593 + /- 747 US dollars ) in the gln group and 68996 + /- 8620RMB ( dollar 8343 + /- 1042 , p = .031 ) in controls , although the cost of the enteral nutrition was higher in the gln-supplemented patients . CONCLUSION Enteral gln supplementation using a commercially available dipeptide supported plasma gln levels , improved gut permeability , and initially decreased plasma endotoxin levels in severely thermally injured patients . These alterations were associated with a reduction in the length of hospitalization and lower costs The conventional antibiotic treatment of acute otitis media ( AOM ) faces a number of problems , including antibiotic resistance . Homeopathy has been shown to be capable of treating AOM successfully . As AOM has a high rate of spontaneous resolution , a trial to prove any treatment-effect has to demonstrate very fast resolution of symptoms . The purpose of this study was to find out how many children with AOM are relieved of pain within 12 h after the beginning of homeopathic treatment , making additional measures unnecessary . Two hundred and thirty children with AOM received a first individualized homeopathic medicine in the paediatric office . If pain-reduction was not sufficient after 6 h , a second ( different ) homeopathic medicine was given . After a further 6 h , children who had not reached pain control were started on antibiotics . Pain control was achieved in 39 % of the patients after 6 h , another 33 % after 12 h. This resolution rate is 2.4 times faster than in placebo controls . There were no complications observed in the study group , and compared to conventional treatment the approach was 14 % cheaper |
12,266 | 9,135,299 | The effect of propofol on PONV was dependent mainly on the method of administration , time of measurement and range of control event rates .
In all other situations the difference between propofol and control may have reached statistical significance but was of doubtful clinical relevance . | null | null |
12,267 | 29,213,895 | Conclusion Phototest has good diagnostic accuracy for dementia and cognitive impairment .
It is brief , simple and can be used in illiterate persons .
This makes it suitable for use in primary care setting s and /or in subjects with low educational level | The recently developed Phototest is a simple , easy and very brief test for detecting cognitive impairment or dementia .
Objective To evaluate the diagnostic accuracy of the Phototest for detecting cognitive impairment or dementia . | Background Illiteracy , a universal problem , limits the utilization of the most widely used short cognitive tests . Our objective was to assess and compare the effectiveness and cost for cognitive impairment ( CI ) and dementia ( DEM ) screening of three short cognitive tests applicable to illiterates . Methods Phase III diagnostic test evaluation study was performed during one year in four Primary Care centers , prospect ively including individuals with suspicion of CI or DEM . All underwent the Eurotest , Memory Alteration Test ( M@T ) , and Phototest , applied in a balanced manner . Clinical , functional , and cognitive studies were independently performed in a blinded fashion in a Cognitive Behavioral Neurology Unit , and the gold st and ard diagnosis was established by consensus of expert neurologists on the basis of these results . Effectiveness of tests was assessed as the proportion of correct diagnoses ( diagnostic accuracy [ DA ] ) and the kappa index of concordance ( k ) with respect to gold st and ard diagnoses . Costs were based on public prices at the time and hospital accounts . Results The study included 139 individuals : 47 with DEM , 36 with CI , and 56 without CI . No significant differences in effectiveness were found among the tests . For DEM screening : Eurotest ( k = 0.71 [ 0.59–0.83 ] , DA = 0.87 [ 0.80–0.92 ] ) , M@T ( k = 0.72 [ 0.60–0.84 ] , DA = 0.87 [ 0.80–0.92 ] ) , Phototest ( k = 0.70 [ 0.57–0.82 ] , DA = 0.86 [ 0.79–0.91 ] ) . For CI screening : Eurotest ( k = 0.67 [ 0.55–0.79 ] ; DA = 0.83 [ 0.76–0.89 ] ) , M@T ( k = 0.52 [ 0.37–0.67 ] ; DA = 0.80 [ 0.72–0.86 ] ) , Phototest ( k = 0.59 [ 0.46–0.72 ] ; DA = 0.79 [ 0.71–0.86 ] ) . There were no differences in the cost of DEM screening , but the cost of CI screening was significantly higher with M@T ( 330.7±177.1 € , mean±sd ) than with Eurotest ( 294.1±195.0 € ) or Phototest ( 296.0±196.5 € ) . Application time was shorter with Phototest ( 2.8±0.8 min ) than with Eurotest ( 7.1±1.8 min ) or M@T ( 6.8±2.2 min ) . Conclusions Eurotest , M@T , and Phototest are equally effective . Eurotest and Phototest are both less expensive options but Phototest is the most efficient , requiring the shortest application time INTRODUCTION The changeover to the new currency has meant that the Money test , a screening test for dementia with a number of advantages over those currently available , is now of no use . AIMS Our aim was to perform a preliminary evaluation of the Eurotest , which is a version of the Money test adapted to the new currency system . SUBJECTS AND METHODS DESIGN phase I , diagnostic evaluation ( convenience sampling ; pre-test prevalence 50 % ) . SUBJECTS > 65 years with no sensory deficit ; 30 with mild dementia and 30 without dementia . METHOD evaluation of socio-demographic variables and of mini-mental performance ( MMSE ) , Pfeiffer 's test ( SPMSQ ) , the seven-minute test ( 7MT ) and Eurotest . Statistical study : comparison between groups using t test and chi squared , depending on the variables ; determination of diagnostically useful parameters and ROC curves , with their respective 95 % confidence intervals ; linear regression study with a step by step strategy . RESULTS The groups did not differ as regards age , sex , level of schooling , degree of literacy , employment and knowledge of money systems . The Eurotest has a sensitivity of 0.93 ( 0.76 - 0.99 ) and a specificity of 0.87 ( 0.68 - 0.96 ) , which is similar to that of the MMSE and the 7MT . The Eurotest ( 6.77 + /- 1.65 min ) takes less time than the 7MT ( 8.87 + /- 1.81 min ) and is not modified by the subject 's clinical situation . The level of schooling does not affect the results of the Eurotest . CONCLUSIONS The Eurotest is simple , quick , valid , useful and is unaffected by the level of schooling , which are features that make it a valid alternative to the tests currently available Background To assess and compare the effectiveness and costs of Phototest , Mini Mental State Examination ( MMSE ) , and Memory Impairment Screen ( MIS ) to screen for dementia ( DEM ) and cognitive impairment ( CI ) . Methods A phase III study was conducted over one year in consecutive patients with suspicion of CI or DEM at four Primary Care ( PC ) centers . After undergoing all screening tests at the PC center , participants were extensively evaluated by research ers blinded to screening test results in a Cognitive-Behavioral Neurology Unit ( CBNU ) . The gold st and ard diagnosis was established by consensus of expert neurologists . Effectiveness was assessed by the proportion of correct diagnoses ( diagnostic accuracy [ DA ] ) and by the kappa index of concordance between test results and gold st and ard diagnoses . Costs were based on public prices and hospital accounts . Results The study included 140 subjects ( 48 with DEM , 37 with CI without DEM , and 55 without CI ) . The MIS could not be applied to 23 illiterate subjects ( 16.4 % ) . For DEM , the maximum effectiveness of the MMSE was obtained with different cutoff points as a function of educational level [ k = 0.31 ( 95 % Confidence interval [ 95%CI ] , 0.19 - 0.43 ) , DA = 0.60 ( 95%CI , 0.52 - 0.68 ) ] , and that of the MIS with a cutoff of 3/4 [ k = 0.63 ( 95%CI , 0.48 - 0.78 ) , DA = 0.83 ( 95%CI , 0.80 - 0.92 ) ] . Effectiveness of the Phototest [ k = 0.71 ( 95%CI , 0.59 - 0.83 ) , DA = 0.87 ( 95%CI , 0.80 - 0.92 ) ] was similar to that of the MIS and higher than that of the MMSE . Costs were higher with MMSE ( 275.9 ± 193.3 € [ mean ± sd euros ] ) than with Phototest ( 208.2 ± 196.8 € ) or MIS ( 201.3 ± 193.4 € ) , whose costs did not significantly differ . For CI , the effectiveness did not significantly differ between MIS [ k = 0.59 ( 95%CI , 0.45 - 0.74 ) , DA = 0.79 ( 95%CI , 0.64 - 0.97 ) ] and Phototest [ k = 0.58 ( 95%CI , 0.45 - 0.74 ) , DA = 0.78 ( 95%CI , 0.64 - 0.95 ) ] and was lowest for the MMSE [ k = 0.27 ( 95%CI , 0.09 - 0.45 ) , DA = 0.69 ( 95%CI , 0.56 - 0.84 ) ] . Costs were higher for MMSE ( 393.4 ± 121.8 € ) than for Phototest ( 287.0 ± 197.4 € ) or MIS ( 300.1 ± 165.6 € ) , whose costs did not significantly differ . Conclusion MMSE is not an effective instrument in our setting . For both DEM and CI , the Phototest and MIS are more effective and less costly , with no difference between them . However , MIS could not be applied to the appreciable percentage of our population who were illiterate OBJECTIVE Fototest is a short simple test , applicable to illiterate subjects and not influenced by educational level . The purpose of this study is to assess its validity for cognitive impairment ( CI ) and dementia ( DEM ) under routine clinical practice conditions . MATERIAL AND METHODS A cross-sectional , multicentre and naturalistic study conducted in General Neurology clinics . The subjects were , over 60 years old , with a previously established diagnosis of no cognitive impairment ( NoCI ) , cognitive impairment without dementia ( CInoDEM ) , or dementia ( DEM ) . The discriminant validity was assessed using the area under the ROC curve ( AUC ) , sensitivity ( Sn ) , specificity ( Sp ) , and probability coefficients . Partial correlations were calculated , adjusted for age , sex and education level with Eurotest , verbal fluency test ( VFT ) and Global Deterioration Scale ( GDS ) score to evaluate the concurrent and construct validity . RESULTS Nineteen neurologists included a total of 589 subjects : 361 NoCI , 106 CINoDEM and 122 DEM . The discriminant value was better for DEM ( AUC 0.94 ± 0.02 ) than for CI ( 0.86 ± 0.02 ) . For DEM the best cut-off point was 26/27 ( Sn=0.88 [ 95 % CI , 0.93 - 0.97 ] , Sp=0.87 [ 95 % CI , 0.84 - 0.90 ] ) ; and for CI , 28/29 ( Sn=0.71 [ 95 % CI , 0.65 - 0.77 ] , Sp=0.84 [ 95 % CI , 0.80 - 0.88 ] ) . Fototest showed a high and significant correlation with Eurotest ( r=0.70 ± 0.02 ) , VFT ( r=0.68 ± 0.02 ) and the GDS score ( r=-0.77 ± 0.02 ) . CONCLUSION The Fototest showed adequate validity for CI and DEM in general Neurology clinics in an extensive and wide geographical area INTRODUCTION The recently developed Phototest is a simple , easy and very brief ( <3 minutes ) test with theoretical advantages over available dementia screening tests . Our objective was to evaluate its diagnostic accuracy under routine clinical conditions . MATERIAL AND METHODS A phase II cross-sectional validation study of diagnostic tests was performed in a sample of 308 patients referred to a general neurology department and in a group of 70 healthy individuals . The diagnostic accuracy ( DA ) of the Phototest was assessed and compared with that of the Eurotest and a verbal fluency test ( VFT ) in relation to the clinical diagnosis of dementia ( DEM ) and cognitive impairment ( CI ) by calculating the area under the ROC curve ( aROC ) and determining Sensitivity ( Se ) , Specificity ( Sp ) and likelihood ratios . RESULTS The total sample comprised 225 subjects without CI ( NOR ) , 58 with CI and without DEM and 95 with DEM . Phototest results showed a normal distribution in NOR subjects ( 33.4 + /- 3.9 [ mean + /- st and ard desviation ] ) and were not influenced by educational variables . The DA of the Phototest for DEM and CI ( 0.95 + /- 0.01 [ aRO C+/- Se ] ) was similar to that of the Eurotest and higher for both tests than that of the VFT . The cutoff points of 25/26 for DEM ( Se=0.88 [ 0.80 - 0.94 ] , Sp=0.90 [ 0.86- 0.93 ] ) and 28/29 for CI ( Se=0.90 [ 0.84 - 0.94 ] , Sp=0.90 [ 0.83 - 0.93 ] ) maximised the sum of Se and Sp . CONCLUSIONS The Phototest is a very short test of easy application that is applicable to illiterate subjects , uninfluenced by educational variables and useful to identify CI and DEM in routine clinical practice |
12,268 | 10,932,023 | Effectiveness There is some evidence that liquid-based cytological methods offer the following advantages over traditional smear techniques : • a reduction in the proportion of inadequate specimens • an improvement in sensitivity • a possible reduction in specimen interpretation times .
Conclusions From the evidence available , it is likely that the liquid-based cytology technique will reduce the number of false-negative test results , reduce the number of unsatisfactory specimens and may decrease the time needed for examination of specimens by cytologists .
In this review , it became clear that increasing the coverage of the programme , and the use of more effective cervical specimen collection devices are also important ways of reducing the burden of the invasive cervical cancer . | Background Around 4 million women per annum in Engl and have a cervical screening test .
Currently the age-st and ardised incidence of cervical cancer is around 9.3 per 100,000 per annum .
The mortality rate in 1997 was 3.7 per 100,000 per annum .
Liquid-based cytology is a new method of preparing cervical sample s for cytological examination .
Unlike the conventional ‘ smear ’ preparation , it involves making a suspension of cells from the sample and this is used to produce a thin layer of cells on a slide .
The new intervention would thus form part of the process of population screening to reduce cervical cancer .
It is not possible to be certain whether this will reduce the incidence of invasive cancer , but modelling studies have suggested that this would occur . | The authors compared the accuracy of conventionally prepared smears and smears prepared by an automated , fluid-based , thin-layer processing device in the detection of cytologic abnormalities . A total of 3218 patients from five centers took part in this study , in which a single cervical sample was split into a matched pair . The conventional smear was made in the routine fashion ; the remainder of the cells on the sampling device were rinsed into a transport-fixation fluid . A slide was then prepared from the solution using the thin-layer processor . Diagnostic findings identified on the two preparations were compared in a blinded fashion , and a discrepancy resolution procedure was used to eliminate screening differences . Overall , there was a high correlation in the diagnoses of the two methods . For low- grade or more severe disease , the thin-layer method result ed in a 13 % increase in the rate of detection , as compared with the conventional Papanicolaou smear technique OBJECTIVE To obtain preliminary data on the Roche CytoRich thin-layer system for the preparation of gynecologic cytology specimens , derived from a pre clinical startup evaluation of the instrument and comparing the CytoRich method to conventional smears . STUDY DESIGN At six different clinical sites , 286 pairs of conventional and CytoRich slides derived from the same patient sample were compared for the following : final Bethesda classification diagnosis , specimen adequacy and presence of microorganisms . RESULTS The study showed agreement between the methods for an exact Bethesda diagnosis in 78 % and agreement within one Bethesda diagnosis category in 95 % . The CytoRich method diagnosed more cases of squamous intraepithelial lesion ( SIL ) than did the conventional method , and the differences in SIL detection were statistically significant . The CytoRich method identified similar numbers of cases with microorganisms as did the conventional smears , and the CytoRich system improved overall specimen adequacy as compared to the conventional method , with fewer cases of unsatisfactory and less-than-optimal smears . CONCLUSION The CytoRich method may improve the overall sensitivity and specificity of the cervical cytology procedure . Clinical trials to verify these preliminary data are ongoing OBJECTIVE To examine the efficacy of the ThinPrep method , an automated , fluid-based technique for the collection and preparation of exfoliated and aspirated cells in cervical cytology . STUDY DESIGN A total of 251 patients participated . From each patient a sample was obtained by scraping with a wooden spatula , split and prepared with both conventional Papanicolaou and ThinPrep methods . In the ThinPrep processor , epithelial cells were homogenized in a vial of preservative solution and r and omly sample d onto a microscopic slide . From a single vial of sample suspension a series of 10 ThinPrep slides of the same quality were made . All cells were concentrated within an approximately 20-mm-diameter circle in a uniform , thin layer on the ThinPrep slide . RESULTS Twenty-five percent of the screening area , 10 % of the epithelial cells observed and 50 % of the screening time were required to arrive at a final diagnosis as compared with the Papanicolaou smear . Virtually complete concurrence was ascertained between the Papanicolaou and ThinPrep diagnoses , for direct agreement of 95.3 % and agreement within one diagnostic grade of 99.5 % . CONCLUSION An overall improvement was ascertained in the preparation of microscopic slides and the recognition of abnormal cells with the ThinPrep method OBJECTIVE To compare the AutoCyte PREP direct-to-vial procedure to the conventional Pap smear in two large and similar patient groups compiled from the testing experience of three cytology laboratories in Switzerl and and France . STUDY DESIGN R and omly selected , large patient groups were evaluated using either the conventional Pap smear or the AutoCyte PREP direct-to-vial liquid-based preparation . Results were then compared statistically as to disease detection and sample adequacy . RESULTS Specimen adequacy was greatly improved in the group tested with the AutoCyte PREP . PREP also demonstrated a significant reduction in ASCUS and ASCUS : LSIL+ ratios . The three laboratories participating in this review found significantly improved detection of both low and high grade SIL . Routine use of AutoCyte PREP for cervical cytology screening offers substantial improvements in adequacy and disease detection OBJECTIVE To compare the cytologic diagnoses and specimen adequacy of the ThinPrep Pap Test with historical data within a distinct patient population to assess test performance and its impact on clinical practice . STUDY DESIGN A total of 16,314 ThinPrep Pap tests were processed and evaluated at Fletcher Allen Health Care over a seven-month period . A subset of 8,574 tests from a selected provider group ( cohort ) was compared to the historical conventional cervical cytologic smear data from the cohort population for both cytologic diagnoses and specimen adequacy . The cohort consisted of 12 practice groups , including 60 physicians and providers , utilizing the ThinPrep Pap Test as their primary cervical cancer screening sampling technique . Cytologic diagnoses and specimen adequacy were classified using the Bethesda system . RESULTS Using a three-tiered diagnostic system similar to the Cytyc clinical trials ( within normal limits [ WNL ] , atypical squamous cells of undetermined significance [ASCUS]/atypical gl and ular cells of undetermined significance [ AGUS ] and low grade squamous intraepithelial lesion and higher [LSIL]+ ) , the ThinPrep method increased the percentage of cases that could be definitively diagnosed as WNL by 1.71 % , lowered the percentage of ambiguous or borderline cases diagnosed as ASCUS/AGUS by 26.59 % and increased the percentage of cases diagnostic of LSIL+ by 52.15 % in the cohort population . Further subdivision by the Bethesda classification showed that the identification of infectious agents increased 25.51 % and the detection of high grade squamous intraepithelial lesion/carcinoma increased 55.14 % . Concurrently , cases reported as benign cellular changes ( reactive/reparative ) decreased 23.1 % , and the percentage of cases reported as unsatisfactory/"limited by ... " was reduced 52.71 % . Histologic correlation of cases reported as squamous intraepithelial lesion revealed that the percentage of patients with subsequent benign biopsies was reduced by 31.7 % utilizing the ThinPrep technique . Further , the percentage of ThinPrep patients with histologically confirmed cervical intraepithelial neoplasia ( CIN ) 1 and CIN 2/3 increased by 16.3 % and 9.3 % , respectively . CONCLUSION Implementation of the ThinPrep Pap Test result ed in statistically significant improvements in both diagnostic yield and specimen adequacy , as seen by others in clinical trials . Comparison of results to historical data within a cohort population reinforced earlier data and lent further support to the cl aim that the ThinPrep Pap Test is " significantly more effective " than the conventional smear in clinical practice OBJECTIVE To eliminate the disadvantages and inherent bias of split- sample studies by evaluating the relative performance of monolayers and conventional cervical cytologic smears in a single laboratory through evaluation of two large and similar , r and omly derived patient groups from the same geographical and demographically similar population . STUDY DESIGN Two r and omly created large patient groups from the same population were evaluated using conventional microscopic screening . One group was tested using the conventional smear . The other was evaluated using only the new liquid-preservative-based CytoRich preparation ( AutoCyte , Inc. , Elon College , North Carolina , U.S.A. ) with the intended direct-tovial cell collection method . Results were then compared statistically as to disease detection and sample adequacy . RESULTS Age comparisons between the two groups demonstrated equivalency . Specimen adequacy was greatly improved in the group tested with the CytoRich monolayer preparation . The monolayer group also demonstrated a significant reduction in ambiguous atypical squamous cells of undetermined significance /atypical gl and ular cells of undetermined significance diagnoses and a threefold increase in the detection of squamous intraepithelial lesion and cancer . CONCLUSION Routine use of homogeneous monolayer preparations as a total replacement for the conventional smear can be expected to dramatically improve specimen adequacy and sensitivity of the conventional smear alone . Direct-to-vial use of the new monolayer preparation generated significantly better results than those shown in any of the earlier split- sample trials OBJECTIVE To compare the CytoRich system with conventional cervical cytology in a university medical center hospital laboratory . STUDY DESIGN The CytoRich system combines liquid preservation , selective reduction of blood/inflammation , thin-layer preparation and discrete staining . Two thous and thirty-two parallel conventional and CytoRich sample s were examined as part of a multicenter trial of the CytoRich/AutoCyte systems . Same-patient conventional and CytoRich slides were su bmi tted to separate cytotechnologists blindly . The results were compared , and all nonmatching sample pairs were review ed again . A consensus diagnosis was derived for all cases . The initial readings of the CytoRich and conventional smears were compared with each other and with the consensus diagnosis . RESULTS Of the 148 squamous intraepithelial lesions ( SILs ) found by either method , 85 % were found by CytoRich , while only 58.5 % were found by conventional smear . As compared with the consensus diagnosis , CytoRich slides had 86.7 % sensitivity for SIL and 99.1 % specificity , while the conventional slides had 63.6 % sensitivity and 99.7 % specificity . Consensus review result ed in upgrading to SIL in 1.8 % of conventional slides and 1.4 % of CytoRich slides . The biopsy correlation results were similar for the two methods . CONCLUSION The CytoRich system affords excellent cellular presentations and superior sensitivity for SILs when compared to the conventional technique OBJECTIVE To assess specimen adequacy of the ThinPrep slide preparation method in routine use . STUDY DESIGN Two studies , a feasibility study of 299 women and a clinical study of 499 women , were conducted . A broom-type collection device was used and rinsed directly into Pre-servCyt vials . Slides were prepared with the ThinPrep 2000 device , screened and classified according to the Bethesda System . The proportion of ThinPrep slides described as " Satisfactory But Limited By : No Endocervical Component ( SBLB : No ECC ) " was then compared to the proportion of SBLB : No ECC slides found on conventional smears in a previously conducted clinical trial of over 7,000 patients . RESULTS For the feasibility study the proportion of ThinPrep slides described as SBLB : No ECC was 9.36 % as compared to the clinical trial combined rate of 9.4 % for conventional smears . For the clinical study , 4.96 % of ThinPrep slides were SBLB : No ECC as compared to the 4.4 % SBLB : No ECC rate for conventional smears from the same clinical trial . The proportions were statistically equivalent for both studies . CONCLUSION It is expected that the rate of representing endocervical component will be maintained when the ThinPrep preparation method is used routinely in place of the conventional cytologic smear method Several studies have examined the role of tests for human papillomavirus ( HPV ) in screening for cervical cancer but as yet the relevance is unclear . We looked at HPV testing for types 16 , 18 , 31 , and 33 on material taken at the time of a cervical smear in 2009 eligible women having routine screening . Women with any degree of dyskaryosis or high levels of one of these HPV types were referred for colposcopy . 44 % of the cervical intraepithelial neoplasia ( CIN ) lesions of grade 2/3 detected had negative cytology and were found only by HPV testing . A further 22 % of the CIN 2/3 lesions were positive for HPV but showed only borderline or mild cytological changes . The positive predictive value of HPV testing was 42 % , which was similar to that for moderate dyskaryosis . HPV types 16 and 31 were more sensitive and specific for CIN 2/3 than were types 18 or 33 . However , 25 % of the CIN 2/3 lesions were not detected by these four HPV tests . We suggest that HPV testing could usefully augment but not replace conventional cytology . These results should stimulate a much larger r and omised trial to assess the impact of these improved CIN 2/3 detection rates on the subsequent incidence of invasive cancer Objective To compare the cytologic diagnoses and specimen adequacy of a fluid-based , thin-layer preparation and conventional Papanicolaou tests . Methods A total of 7360 women from six separate sites — three screening centers and three hospitals — participated in split- sample /matched-pair , double-masked clinical trials . A conventional Papanicolaou test was performed , after which residual material on the sampling device was rinsed into a fluid preservative from which a thin-layer slide ( ThinPrep ) was prepared using the ThinPrep 2000 automated slide processor ( Cytyc Corp. , Boxborough , MA ) . Conventional and ThinPrep slides were read independently . Cytologic diagnoses and specimen adequacy were classified using the Bethesda system . Results For the three screening centers , 65 % more diagnoses of low- grade squamous intraepithelial lesions and higher were made on the ThinPrep slides ( P < .001 ) ; for the three hospital centers , 6 % more of these diagnoses were made with the ThinPrep method ( P = .294 ) . Comparison of specimen adequacy showed a significant increase in satisfactory specimens and a reduction in the number of “ satisfactory but limited by ” specimens using the ThinPrep method ( P < .001 ) . Conclusion The fluid-based , ThinPrep method of sample preparation result ed in a statistically significant increase in cytologic diagnosis of cervical cancer precursors and in specimen adequacy compared with the conventional Papanicolaou testing method To evaluate the sensitivity and suitability of ThinPrep , a new slide preparation technique , 2026 paired cervical cytology slides were examined . After conventional Papanicolaou smears were prepared , the sampling instruments were rinsed in a fluid fixative . ThinPrep slides were then prepared in the laboratory from the surplus cells in the fixative . Compared with the Pap smears , ThinPrep slides were easier and quicker to screen , were inconclusive less often , and had similar rates for detecting abnormalities and infection . There were more unsatisfactory ThinPrep slides and more ThinPrep slides lacked endocervical cells . Both of these shortcomings were found to be linked to the choice of sampling implements . This study , in which a variety of sampling instruments was used , fails to confirm some of the previous cl aims made for the new technique Thin-layer ( TL ) technology can improve the detection rate for squamous lesions of the uterine cervix . Studies to date have under-represented high grade lesions and malignancies . The present study utilized a patient population at high risk for such lesions in order to analyze the performance of TL procedures in this group , and in addition , to assess the similarities and differences in morphologic appearances of specimens prepared by the two methods . Conventional ( CS ) and thin-layer smears ( TLS ) were made in parallel from the same specimen . Each slide was examined in a blinded fashion . Diagnoses were compared and morphologic observations made . Two hundred fifty-nine cases were included , of which 32 ( 12 % ) were high grade dysplasias ( 11 ) or carcinomas ( 21 ) . Thirty five ( 14 % ) were atypical or low grade dysplasias . There was exact correlation between Bethesda classification in 231 cases ( 89 % ) . Of the 21 carcinomas identified , 19 ( 91 % ) were present on each preparation . Two cases of endometrial adenocarcinoma were missed on unsatisfactory or negative TLS . One case of squamous cell carcinoma was called high grade squamous intraepithelial lesion ( HGSIL ) on TLS while the CS was unsatisfactory . Three cases called atypical gl and ular cells ( AGCUS ) on TLS , and negative on CS , showed HGSIL ( 1 ) or no lesion ( 2 ) on follow-up . Morphologic features of low grade lesions were virtually identical on both preparations . Distinct features were noted on TLS in the high grade lesions . These included smaller appearing nuclear areas , less distinct nuclear chromatin , thicker three-dimensional groupings , and more isolated cells . Such findings were most pronounced in the gl and ular lesions . With training and experience , these features were easily identified in TL preparations , further documenting the utility of this procedure for use in routine practice The diagnoses of 1,000 pairs of conventional Papanicolaou ( Pap ) smears and ThinPrep preparations were compared . Cervical cells were collected using an Ayre spatula and endocervical brush . The conventional smear was made first , the collection devices were rinsed into PreservCyt solution , and the slides were prepared using the ThinPrep Processor . The diagnoses of the paired smears agreed in 988 of the 1,000 cases ( 98.8 % ) , including 949 negatives , 28 atypicals , 9 low grade squamous intraepithelial lesions ( LGSIL ) , and 2 high grade squamous intraepithelial lesions ( HGSIL ) . Five cases where LGSIL or HGSIL was found on the ThinPrep slide were negative or atypical on the conventional smear . No conventional smear abnormalities were missed on the ThinPrep slide . Although not statistically significant , this difference indicates that the ThinPrep method gives a better diagnosis of abnormalities than the conventional method . The ThinPrep method was acceptable to participating physicians and ThinPreps were easier and faster to screen than conventional smears In this paper a mathematical model is developed to determine the probability that a truly negative cervical cytologic smear will be correctly identified by a system of screening policies that uses one or more cytotechnologists to independently and sequentially prescreen such smears for the detection of cervical cancer . This is an extension of previous work that modeled the probability of detecting a truly positive smear under the same set of policies . In this system any positive reading by a cytotechnologist causes a slide to be rescreened by a pathologist , and if all cytotechnologists declare a slide to be negative , the slide is placed in a pool for r and om selection of slides to be rescreened by the pathologist . The policy of single screening by a cytotechnologist , with subsequent 10 % rescreening of the negative slides , as suggested by the Clinical Laboratory Improvement Amendments of 1988 , is thus embedded in the policies that are modeled . In addition , a cost model is developed that takes into account the cost of screening a slide by a cytotechnologist , of rescreening a slide by a pathologist , of a false-positive reading and of a false-negative reading . This cost model can be used to determine which policy is optimal for the parameters that pertain to a specific situation . Examples are presented to illustrate the use of the cost model . The results of a computer simulation model are also presented to vali date the mathematical results and to display the variability of total cost Whilst significant advances have been made in persuading clinical research ers of the value of conducting economic evaluation alongside clinical trials , a number of problems remain . The most fundamental is the fact that economic principles are almost entirely ignored in the traditional approach to trial design . For example , in the selection of an optimal sample size no consideration is given to the marginal costs or benefits of sample information . In the traditional approach this can lead to either unbounded or arbitrary sample sizes . This paper presents a decision-analytic approach to trial design which takes explicit account of the costs of sampling , the benefits of sample information and the decision rules of cost-effectiveness analysis . It also provides a consistent framework for setting priorities in research funding and establishes a set of screens ( or hurdles ) to evaluate the potential cost-effectiveness of research proposals . The framework permits research priority setting based explicitly on the budget constraint faced by clinical practitioners and on the information available prior to prospect i ve research . It demonstrates the link between the value of clinical research and the budgetary restrictions on service provision , and it provides practical tools to establish the optimal allocation of re sources between areas of clinical research or between service provision and research Combining medical decision theory and epidemiologic information , the authors have devel oped a strategy to assess diagnostic technologies . For any patient , patient utilities with new diagnostic information are compared with the preferred fallback action absent that diagnostic information . After determination of whether the expected value of diagnostic information ( EVDI ) justifies its cost , the method adds across the eligible population to determine whether the global EVDI justifies the technology 's deployment , employing a screen ( Hurdle 1 ) that assumes that the diagnostic device has perfect accuracy . This preliminary evaluation relies on published data on treatment efficacy , population probabilities of illness , etc . , but not on new clinical trials . If the technology is not sufficiently cost-effective , even with this optimistic assumption , the strategy recommends against its use . Otherwise , the next step is Hurdle II , in which the critical clinical studies , identified by the decision-theory model , are undertaken . These commonly include measuring the actual diagnostic accuracy of a device , with which the cost-effectiveness is recalculated . These studies in general do not require r and omized controlled trials . Key words : technology assessment ; decision theory ; diagnostic information . ( Med Decis Making 8:279 - 289 , 1988 The objective of this study was to compare the sensitivity of a new test method with the smear method for detection of neoplasia of the uterine cervix . The new procedure , the ThinPrep process , is an automated , fluid-based technique for the collection and preparation of exfoliated and aspirated cytologic specimens . A single sample from each patient was split and prepared both with the smear and test methods . The diagnostic results from the two slides were compared in this blind study . Among a total of 2,655 patients , diagnoses concurred in 92 % of cases and were within one diagnostic level of each other 98 % of the time . The ThinPrep method facilitated the detection of more low- grade lesions ( P less than .001 , McNemar 's test ) . In addition , the test method decreased the number of ambiguous interpretations . The ThinPrep method appears to improve the cervical cytologic smear quality by the harvest of a r and om and reproducible sample , with a reduction in artifacts . The new method improves the sensitivity of the cervical cytologic screening test OBJECTIVE To evaluate the ThinPrep Pap test as an adjunct to the conventional Pap smear . DESIGN AND SETTING Prospect ively collected cervical sample s were split for independent screening at a large specialised private gynaecological pathology practice in Sydney . MAIN OUTCOME MEASURES Detection of additional significant abnormalities ( cervical intraepithelial neoplasia 1 , or more severe ) ; changed management recommendations from " repeat smear in 12 months " or " ... six months " to " colposcopy " , a reduction in unsatisfactory reports . RESULTS 35,560 paired ( split- sample ) conventional and ThinPrep slides were prepared . Significant abnormalities were detected in 724 conventional smears ( 2 % ) . Additional significant abnormalities were found in 85 ThinPrep slides whose corresponding conventional smear was negative or unsatisfactory even after review , representing a 12 % increase in the detection of significant abnormalities . As a result of the addition of ThinPrep , management recommendations were changed from " repeat smear in 12 months " or " ... six months " to " colposcopy " for 89 of 1669 women whose conventional Pap smears showed minor non-specific changes or papillomavirus . There were 1258 conventional smears ( 3.5 % ) that were unsatisfactory compared with 235 ThinPrep slides ( 0.7 % ) ; for only 74 sample s ( 0.2 % ) were both slides unsatisfactory . CONCLUSIONS The addition of the ThinPrep Pap test improves detection and clinical management of cervical abnormalities , and reduces the number of unsatisfactory sample s which would otherwise require repeat tests OBJECTIVE To compare the quality and sensitivity of CytoRich slides with conventional cytologic smears and to evaluate the benefits of using this technology as an add-on procedure . STUDY DESIGN The study design consisted of non-r and omized , paired cervical sample s. The subjects were 2,125 Sydney women who were routine patients of 13 gynecologists and 8 general practitioners and had cytologic smears taken between January and June 1995 . All smears were taken using the Cervex brush . After preparing the conventional cytologic smear slide , the head of the sample r was detached and placed in a vial of fluid fixative . Paired slides were then prepared in the laboratory from the cells in the fluid fixative , using the CytoRich processing machine . The CytoRich and conventional cytologic smear slides were compared for quality , ease of screening , presence of endocervical cells , recognition of infections , and detection of squamous and gl and ular abnormalities . RESULTS CytoRich slides were of much better quality , were easier to screen , had substantially fewer unsatisfactory results ( 0.3 % vs. 2.6 % ) but lacked endocervical cells more often ( 16.1 % vs. 10.6 % ) . As regards abnormalities , the CytoRich slides showed fewer abnormalities , particularly in the low grade category . However , as a result of screening the paired CytoRich slide , some additional abnormalities were detected and a number of abnormalities reported on the conventional slide were reclassified ( some to higher grade s but more to negative ) . CONCLUSION As an add-on technology , the CytoRich process has much to offer , in particular in the virtual elimination of unsatisfactory smears and in helping to resolve the difficult dichotomy between normal and low grade categories . Examining additional cellular material on a CytoRich slide enhances the sensitivity and accuracy of the combined results The aim of the study was to assess the ability of the CytoRich System to prepare optimal gynaecological smears for diagnosis . The diagnostic results obtained from evaluating 1,325 matched slide-pairs , prepared using conventional methods and thin-layer technology , were compared . Cytological material for study was obtained using the combined spatula-cytobrush sampling technique . An assessment of the pitfalls associated with the interpretation of these smears was also undertaken . Diagnostic agreement was achieved in 1,272 of the 1,325 matched slide-pairs ( 96.0 % ) , and these included 1,172 negative , 50 atypical , 24 low- grade squamous intraepithelial lesion ( LSIL ) , 24 high- grade SIL ( HSIL ) , and two malignancies . A total of 1,309 cases showed the same diagnosis within one diagnostic grade for an agreement of 98.8 % . Evaluation of the 53 discordant diagnoses revealed that the conventional smear identified a significantly greater number of abnormal smears than the CytoRich technique ( P < .001 ) . It is suspected that the use of the combined spatula-cytobrush sampling technique did not provide adequate residual specimen for CytoRich after conventional smear preparation . This limitation is evidence d by the fact that the CytoRich preparations showed a lower yield of endocervical cells ( P < .001 ) and infectious organisms ( P < .001 ) than was demonstrated on conventional smears . Despite a number of diagnostic pitfalls associated with the interpretation of thin-layer smears , these preparations were easier and faster to screen and showed well-preserved and evenly distributed cells . Thin-layer smears were also characterised by a marked reduction in thick cell groups , air drying artifact , and obscuring inflammation and blood . The results confirm the limitation of the combined spatula-cytobrush technique in these types of comparative studies OBJECTIVE To evaluate and compare histologic diagnosis of squamous intraepithelial neoplasia and cancer of the cervix with cytologic diagnosis using the conventional Pap smear versus the AutoCyte PREP liquid-based , thin-layer preparation . STUDY DESIGN Two r and omly selected , large patient groups from the same population were studied using two different cervical cytology preparation techniques . Cytologic results were compared to histologic diagnosis to estimate the relative sensitivities and specificities of the preparations . RESULTS AutoCyte 's liquid-based , thin-layer preparation method demonstrated improved agreement with histologic diagnosis as compared to the conventional Pap smear . This result supported the previously reported finding that use of this thin-layer method reduced atypical squamous cells of undetermined significance cases and substantially increased the detection of squamous intraepithelial lesions ( SILs ) . CONCLUSION Our cytohistologic correlation for conventional Pap smears and the AutoCyte PREP liquid-based preparations demonstrate that the increased rate of both low and high grade SILs on AutoCyte PREP reflects real detection as opposed to overdiagnosis OBJECTIVE To evaluate the use of the ThinPrep method to reduce rates of unsatisfactory Papanicolaou ( Pap ) smears in women in remote communities . DESIGN Prospect ively collected sample s were split and screened conventionally and by ThinPrep at the Queensl and Cytology Service . PATIENTS Three hundred women having cervical smears taken by a Mobile Women 's Health Service nurse or at the antenatal and sexual health clinics of a remote north Queensl and community . MAIN OUTCOME MEASURE Number of Pap smears reported as unsatisfactory for evaluation and requiring a repeat smear request . RESULTS 17.3 % of conventionally prepared smears were technically unsatisfactory , compared with 6.3 % prepared with ThinPrep . The overall rate of unsatisfactory smears was only 4.3 % when both ThinPrep and conventional smears were assessed for a combined report . CONCLUSION A significant reduction in the proportion of unsatisfactory Pap smears is possible with the ThinPrep method . Targeted use of ThinPrep in communities with high rates of unsatisfactory smears may prove cost-effective Methods are proposed for the analysis of the natural history of disease from screening data when it can not be assumed that untreated pre clinical disease always progresses to clinical disease . The methodology is based on a two-stage model for pre clinical disease in which stage 1 lesions may or may not progress to stage 2 , but all stage 2 lesions progress to clinical disease . The focus is on joint estimation of the total pre clinical duration and the sensitivity of the screening test . A partial likelihood is proposed for the analysis of prospect ively collected screening data , and an analogous conditional likelihood is proposed for retrospective data . Some special cases for the joint sojourn distribution of the two stages are considered , including the independent model and limiting models where the duration of stage 2 is short relative to stage 1 . The methods are applied to a case-control study of cervical cancer screening in Northeast Scotl and |
12,269 | 15,106,229 | REVIEW ERS ' CONCLUSIONS IVIG , thymosin and TIAOJINING may have positive effects on prevention of nosocomial or unspecified infection with no obvious serious adverse events in children with nephrotic syndrome .
However the method ological quality of all trials was poor , the sample sizes small and all studies were from China , and thus there is no strong evidence on the effectiveness of these interventions | BACKGROUND Infection is one of the most common complications and still remains a significant cause of morbidity and occasionally mortality in patients , especially children with nephrotic syndrome .
Many different prophylactic interventions have been used or recommended for reducing the risks of infection in nephrotic syndrome in clinical practice .
Whether the existing evidence is scientifically rigorous and which prophylactic intervention can be recommended for routine use based on the current evidence is still unknown .
OBJECTIVES To assess the benefits and harms of any prophylactic interventions for reducing the risk of infection in children and adults with nephrotic syndrome . | OBJECTIVE To determine whether clinical trials originating in certain countries always have positive results . DATA SOURCES Abstract s of trials from Medline ( January 1966-June 1995 ) . STUDY SELECTION Two separate studies were conducted . The first included trials in which the clinical outcome of a group of subjects receiving acupuncture was compared to that of a group receiving placebo , no treatment , or a nonacupuncture intervention . In the second study , r and omized or controlled trials of interventions other than acupuncture that were published in China , Japan , Russia/USSR , or Taiwan were compared to those published in Engl and . DATA EXTRACTION Blinded review ers determined inclusion and outcome and separately classified each trial by country of origin . DATA SYNTHESIS In the study of acupuncture trials , 252 of 1085 abstract s met the inclusion criteria . Research conducted in certain countries was uniformly favorable to acupuncture ; all trials originating in China , Japan , Hong Kong , and Taiwan were positive , as were 10 out of 11 of those published in Russia/USSR . In studies that examined interventions other than acupuncture , 405 of 1100 abstract s met the inclusion criteria . Of trials published in Engl and , 75 % gave the test treatment as superior to control . The results for China , Japan , Russia/USSR , and Taiwan were 99 % , 89 % , 97 % , and 95 % , respectively . No trial published in China or Russia/USSR found a test treatment to be ineffective . CONCLUSIONS Some countries publish unusually high proportions of positive results . Publication bias is a possible explanation . Research ers undertaking systematic review s should consider carefully how to manage data from these countries Abstract Varicella , or chickenpox , is very communicable and has been shown to be transmitted to nearly 90 % of household contacts . Severe varicella infections with fatal complications have been noted in children receiving corticosteroids despite the administration of varicella-zoster immune globulin ( VZIG ) . The use of post-exposure acyclovir prophylaxis in immunocompetent children exposed to a household contact with varicella has been shown to decrease the transmission rate of varicella significantly . We studied the safety and efficacy of acyclovir prophylaxis as an adjunctive preventive measure in 8 children ( 10 separate exposures ) receiving corticosteroids for renal disease . Four children ( 6 separate exposures ) served as controls . No adverse reactions were reported with the acyclovir prophylaxis . The maximum change between pre- and study serum creatinine levels was 0.1 mg/dl . None of the 8 patients who received acyclovir prophylaxis developed chickenpox . One of these 8 patients developed humoral immunity to varicella despite the absence of clinical infection . One of 4 patients who received VZIG prophylaxis alone developed chickenpox . These data support the use of acyclovir prophylaxis as an adjunctive measure to VZIG for the prevention of potentially serious varicella infection in children receiving steroids BACKGROUND Respiratory tract infections are among the most common diseases both in adults and children . METHODS This multicentre study , was carried out in 212 patients ( 118 adults with chronic respiratory diseases and 94 children with recurrent respiratory infections ) at six Italian study centres . It was performed to establish the efficacy of Lantigen B for the prevention of bacterial complications and /or reduction of associated symptoms . Lantigen B is an oral product based on bacterial lysates of six different inactivated strains commonly involved in respiratory tract infections . RESULTS The results of prophylactic treatment with Lantigen B in the population investigated were as follows : - the mean incidence of recurrence in the pediatric patients over the 6-month observation period of the study was 1.643 in the placebo group and 1.211 in the Lantigen B group ( a relative reduction of 35.7 % ) ; - the mean incidence of recurrence in the adult patients over the 6-month observation period of the study was 0.73 in the placebo group and 0.56 in the Lantigen B group ( a relative reduction of 30.4 % ) . The improvement in other important parameters , such as the number of days with a high temperature , cough , and catarrh in the children and objective clinical findings at the lymph nodes of the neck , chest , and pharyngotonsillar region in the adults , provides further evidence of the efficacy of Lantigen B. CONCLUSIONS This study demonstrates Lantigen B 's effectiveness in the prevention of bacterial complications and suggests that it can be used in patients who are particularly at risk of infection ( children , the elderly , diabetics , and immunocompromised patients ) or those in whom an infection might aggravate a clinical picture that is already inherently complicated ( diabetics again , but also patients with heart , kidney , or liver disease ) Infection has been recognized as an important cause of morbidity and mortality in children with nephrotic syndrome . However , the incidence and severity of infection and the mechanisms responsible for the increased susceptibility to infection are still unclear in adults . We studied 86 consecutive adult patients with nephrotic syndrome but no diabetic nephropathy . Risk factors for infection were evaluated by logistic regression analysis . Infections were found in 16 patients ( 19 % ) , of whom six died of infection and two developed end-stage renal failure associated with infection . The relative risk for bacterial infection among patients with serum immunoglobulin G ( IgG ) levels below 600 mg/dL was 6.74 compared with that for patients with serum IgG levels over 600 mg/dL ( 95 % confidence interval , 1.22 to 36.32 ; P = 0.029 ) . In patients with serum creatinine levels over 2.0 mg/dL , the relative risk of bacterial infection was 5.31 compared with patients with serum creatinine levels below 2.0 mg/dL ( 95 % confidence interval , 1.08 to 26.09 ; P = 0.040 ) . Intravenous immunoglobulin ( 10 to 15 g ) was administered prospect ively every 4 weeks to 18 patients with serum IgG levels below 600 mg/dL until serum IgG levels increased to over 600 mg/dL. Administration of immunoglobulin result ed in a decreased rate of bacterial infections to a level equal to that in patients with endogenous levels over 600 mg/dL. These data indicate that hypogammaglobulinemia and renal insufficiency are independent risk factors for bacterial infection in adult patients with nephrotic syndrome . The effects of intravenous immunoglobulin suggest that maintenance of serum IgG levels over 600 mg/dL may reduce the risk of infection Abstract Renal-biopsy specimens from Nigerian children with the nephrotic syndrome were studied by fluorescence microscopy after staining with fluorescein isothiocyanate-labelled antibodies against human immunoglobulins and complement ( β-1-C ) . In all patients bound immunoglobulin and complement were observed , characteristically in the form of granular deposits along the glomerular capillary walls . Electron microscopy showed deposition of immune complexes along the epithelial side of the glomerular basement membrane , and reactive changes in epithelial and endothelial cells . Antibody eluted from the kidney of one patient gave precipitates with preparations containing Plasmodium malariœ antigens , but no reaction with P. falciparum or normal kidney antigens . Immune complexes containing P. malariœ antigen are thought to play a causal role in the aetiology of the nephrotic syndrome of African children Children with sickle cell anemia have an increased susceptibility to bacterial infections , especially to those caused by Streptococcus pneumoniae . We therefore conducted a multicenter , r and omized , double-blind , placebo-controlled clinical trial to test whether the regular , daily administration of oral penicillin would reduce the incidence of documented septicemia due to S.pneumoniae in children with sickle cell anemia who were under the age of three years at the time of entry . The children were r and omly assigned to receive either 125 mg of penicillin V potassium ( 105 children ) or placebo ( 110 children ) twice daily . The trial was terminated 8 months early , after an average of 15 months of follow-up , when an 84 percent reduction in the incidence of infection was observed in the group treated with penicillin , as compared with the group given placebo ( 13 of 110 patients vs. 2 of 105 ; P = 0.0025 ) , with no deaths from pneumococcal septicemia occurring in the penicillin group but three deaths from the infection occurring in the placebo group . On the basis of these results , we conclude that children should be screened in the neonatal period for sickle cell hemoglobinopathy and that those with sickle cell anemia should receive prophylactic therapy with oral penicillin by four months of age to decrease the morbidity and mortality associated with pneumococcal septicemia OBJECTIVE To evaluate the safety and immunogenicity of varicella vaccine in children with nephrotic syndrome , including those taking low-dose , alternate-day prednisone . STUDY DESIGN Prospect i ve , open-label , multicenter clinical trial of varicella vaccine in a 2-dose regimen in US and Canadian children ( 12 months to < 18 years ) with nephrotic syndrome . Varicella Zoster Virus ( VZV ) antibody levels were measured after the first and second vaccine dose and yearly for 2 years . Patients were monitored for adverse reactions to vaccine , exposure to varicella , dermatomal zoster , and chickenpox . RESULTS Twenty-nine children , mean age 4.9 ( SD 1.9 ) years , 45 % receiving every-other-day steroids , received 2 vaccine doses . All patients seroconverted and had VZV antibody levels considered protective against breakthrough varicella ( > or=5 gpELISA units ) after 2 doses . At 2-year follow-up , all patients retained detectable antibody , and 91 % ( 21 of 23 ) had levels > or=5 gpELISA units . There were no adverse events associated with vaccination . CONCLUSIONS Varicella vaccine was generally well tolerated and highly immunogenic in children with nephrotic syndrome , including those on low-dose , alternate-day prednisone In order to study the preventive efficiency of IVIgG on nosocomial infection(NI ) , 54 cases of the children with nephrotic syndrome(NS ) were r and omly divided into 2 groups , test group(n = 22 ) and control group(n = 32 ) . Routine treatment was adopted to all cases . Besides the routine treatment , the test group was injected with IVIgG(100 - 300 mg.kg-1.d-1 ) for 2 - 3 days . The results showed that the NI rate of test group ( 13.6 % ) was significantly lower than that of the control(46.88 % ) ( P < 0.05 ) , and the hospital days of the test group(27.33 + /- 15.51 ) d was significantly shorter than that of the control(64.50 + /- 18.52 ) d ( P < 0.05 ) . These suggest that IVIgG , as one of the ways to prevent NI , can improve the immune state and effectively prevent the NI in the children with NS |
12,270 | 24,919,719 | There was no clear evidence of an improvement in pressure ulcer healing from the nutritional supplements evaluated in any of these individual studies .
There is currently no clear evidence of a benefit associated with nutritional interventions for either the prevention or treatment of pressure ulcers . | BACKGROUND Pressure ulcers affect approximately 10 % of people in hospitals and older people are at highest risk .
A correlation between inadequate nutritional intake and the development of pressure ulcers has been suggested by several studies , but the results have been inconsistent .
OBJECTIVES To evaluate the effects of enteral and parenteral nutrition on the prevention and treatment of pressure ulcers . | BACKGROUND Pressure ulcers are an important source of morbidity and suffering for patients and a formidable burden on caregivers . OBJECTIVES To assess the impact of a feeding formula enriched with fish oil on healing of preexisting pressure ulcers and serum levels of C-reactive protein in critical care patients . METHODS Adult patients with pressure ulcers grade II or higher were r and omly allocated to receive either a formula enriched with fish oil or an isocaloric control formula . Wound healing was assessed by using the Pressure Ulcer Scale for Healing tool on days 7 , 14 , and 28 . Blood levels of C-reactive protein were measured on days 0 , 7 , and 14 . RESULTS Baseline demographics did not differ between the study ( n = 20 ) and the control ( n = 20 ) groups . The mean score on the ulcer healing tool increased significantly ( P = .02 ) from day 0 to day 28 in the control group ( from 9.25 [ SD , 2.12 ] to 10.75 [ SD , 3.41 ] ) compared with the study group ( from 9.10 [ SD , 2.84 ] to 9.40 [ SD , 3.72 ] ) . Mean levels of C-reactive protein decreased significantly ( P= .02 ) from day 0 to day 14 in the study group ( from 191 [ SD , 104.4 ] mg/L to 111.7 [ SD , 97.8 ] mg/L ) compared with the control group ( from 145 [ SD , 90 ] mg/L to 139 [ SD , 62 ] mg/L ) . CONCLUSION Administration of a feeding formula enriched with fish oil was associated with decreased progression of pressure ulcers and a decrease in blood concentrations of C-reactive protein BACKGROUND & AIMS Nutrients putatively implicated in pressure ulcer healing were evaluated in a clinical setting . METHODS Sixteen in patients with a stage 2 , 3 or 4 pressure ulcer r and omised to receive daily a st and ard hospital diet ; a st and ard diet plus two high-protein/energy supplements ; or a st and ard diet plus two high-protein/energy supplements containing additional arginine ( 9 g ) , vitamin C ( 500 mg ) and zinc ( 30 mg ) . Nutritional status measurements ( dietary , anthropometric and biochemical ) and pressure ulcer size and severity ( by PUSH tool ; Pressure Ulcer Scale for Healing ; 0=completely healed , 17=greatest severity ) were measured weekly for 3 weeks . RESULTS Patients ' age and BMI ranges were 37 - 92 years and 16.4 - 28.1 k g/m2 ) respectively . Baseline PUSH scores were similar between groups ( 8.7+/-0.5 ) . Only patients receiving additional arginine , vitamin C and zinc demonstrated a clinical ly significant improvement in pressure ulcer healing ( 9.4+/-1.2 vs. 2.6+/-0.6 ; baseline and week 3 , respectively ; P<0.01 ) . All patient groups presented with low serum albumin and zinc and elevated C-reactive protein . There were no significant changes in biochemical markers , oral dietary intake or weight in any group . CONCLUSIONS In this small set of patients , supplementary arginine , vitamin C and zinc significantly improved the rate of pressure ulcer healing . The results need to be confirmed in a larger study Measuring progress toward healing is fundamental to the management of pressure ulcers . A method to assess progress of an individual ulcer over time is lacking . Given the limitations of currently available instruments and the need for a precise and practical method of monitoring healing in clinical practice , the National Pressure Ulcer Advisory Panel initiated the development of a new tool for measuring pressure ulcer healing . The key elements in developing an instrument include simplicity of use in clinical setting s , validity for measuring whether ulcers are improving or worsening , and sensitivity to changes in the ulcer between observations . A new tool incorporating surface area , exu date amount , and surface appearance is proposed . Content validity , correlation validity , prospect i ve validity , and sensitivity to change can be met by the proposed Pressure Ulcer Scale for Healing instrument AIMS To investigate whether a nutritional intervention in older women and men with femoral neck fracture had an effect on postoperative complications during hospitalization and on nutritional status at a four-month follow-up . METHODS The design was a r and omized controlled trial . The present study sample consisted of 157 patients aged 70 years and above with femoral neck fracture . The nutritional intervention included , among other things , a nutritional journal to detect nutrition deficiencies and protein-enriched meals for at least four days postoperatively . Further , at least two nutritional and protein drinks were served each day during the whole hospitalization and other factors that would influence the patient 's nutrition were also considered and dealt with . Postoperative complications were registered and patients were assessed using the Mini Nutritional Assessment ( MNA ) scale , including body mass index ( BMI ) , on admission and at a four-month follow-up . RESULTS Malnutrition was common and low MNA scores were associated with postoperative complications such as delirium and decubitus ulcers . There were significantly fewer days of delirium in the intervention group , seven patients in the intervention group developed decubitus ulcers vs. 14 patients in the control group and the total length of hospitalization was shorter . There were no detectable significant improvements regarding nutritional parameters between the intervention and the control group at the four-month follow-up but men improved their mean BMI , body weight and MNA scores in both the intervention and the control groups while women deteriorated in both groups . CONCLUSIONS Malnutrition was common among older people with hip fractures admitted to hospital . The nutritional intervention might have contributed to the patients suffering fewer days with delirium , fewer decubitus ulcers and shorter hospitalization but did not improve the long-term nutritional status , at least not in women . RELEVANCE TO CLINICAL PRACTICE This nutritional intervention , which was included in a multifactorial multidisciplinary intervention , is inexpensive and relatively easy to implement . It has significant effects on complications but no long-term effect on nutritional parameters , at least not in women UNLABELLED Bedsores prevention is part of the specific role of the nurse , as defined namely in the order 84 - 869 of the 17 . July 1984 . The analysis of the risk factors for the appearance of bedsores shows that immobilization , reduction of mobility linked to vigilance disorders and the urinary and faecal incontinence are major elements which justify protocol s of well defined local cares . More recently , the role of undernutrition was highlighted but the recommendations lack accuracy . The proteino-energizing undernutrition is frequent among the elderly patients in hospital , reaching 60 % of all the patients in the department of acute affections . The association of a constituted bedsore and of clinical and /or biological scars of protein-energizing undernutrition is demonstrated and justifies a re-feeding of the patients suffering from bedsores . On the other h and , although a bad nutrition state seems to favour the appearance of a bedsore , it is not proved that the nutrition intensification associating the diagnosis of an under-nutrition and the starting of an adapted re-feeding ( with enriched food or assistance ) decreases the actual incidence of the bedsores . A prospect i ve , multicentered , r and omized survey was therefore proposed . Its aim was to study the Influence of Nutrition in the Bedsores Prevention among the Elderly Patients in hospitals , suffering from acute affections . This research follows upon the preventions audits of bedsores and the nutrition protocol started up in a department of geriatrics intern medicine in the Regional Center of Geriatrics of Bordeaux . CONCLUSION Two results must be retained in this nursing survey . It gave the possibility of calling into question the professional experience of the nursing teams which participated to the research and to up date their knowledge in the field of the bedsores prevention . They could thus be acquainted with the existence of the grids which evaluate the risk of bedsore , the dependence or even the nutrition supply and to assess the interest for improving the cares quality . On the other h and , we highlighted the possibility of increasing the energy and protein supply by a distribution of enriched food supplements . Moreover , this action has had a beneficial influence in the bedsores prevention among the old people Pressure sores are a frequent problem , especially in elderly patients . Nutritional status may influence the incidence , progression and severity of pressure sores , data , however , are contradictory ( 1 ) . The purpose of this study was to determine the effect of supplemental feeding on the nutritional status and the development and severity of pressure sores . The effect of supplemental feeding overnight ( tube + ) on patients with a fracture of the hip and a high pressure-sore risk score , was studied in a r and omized clinical trial . The control group ( tube - ) had no supplemental feeding . After informed consent , 140 patients were r and omized , and 129 of these took part in the trial ( 62 tube + , and 67 tube - ) . Protein and energy intake , haemoglobin , serum albumin , total serum protein and pressure-sore grade were measured at admission and after 1 and 2 weeks . Of the 62 patients r and omized for tube feeding ( tube + ) , only 25 tolerated their tube for more than 1 week and 16 for 2 weeks . Nevertheless , energy and protein intake was significantly higher in the tube + group ( P < 0.001 ) . This , however , did not significantly influence total serum protein , serum albumin and development and severity of pressure sores after 1 and 2 weeks . Comparison of the actually tube fed group ( n=25 at 1 week , n = 16 at 2 weeks ) and the control group showed a 2 - 3 times higher protein and energy intake ( P < 0.0001 ) , and a significantly higher total serum protein and serum albumin after 1 and 2 weeks in the actually tube fed group ( all P < 0.001 ) . Pressure-sore development and severity were not significantly influenced in the actually tube fed group . We conclude that we were not able to show a significant decrease in development and severity of pressure sores , because the nasogastric tube for supplemental feeding was not well tolerated in this patient group . Nevertheless , tube feeding overnight does result in a significant higher protein and energy intake , and has a significant effect on nutritional status in the actually tube-fed group . Other means of supplemental feeding will have to be used in order to answer the question of whether supplemental feeding can decrease development and severity of pressure sores 59 elderly patients ( mean age 82 ) with femoral neck fractures were r and omised into two groups . 27 patients received daily an oral nutrition supplement ( 250 ml , 20 g protein , 254 kcal ) for a mean of 32 days ; 32 patients acted as controls . On admission most patients had nutritional deficiencies . Despite being offered adequate quantities , nutritional requirements were not met during the hospital stay . Clinical outcome was significantly better in the supplemented group ( 56 % favourable course vs 13 % in controls ) during the stay in the convalescent hospital . The rates of complications and deaths were also significantly lower in supplemented patients ( 44 % vs 87 % ) . 6 months after the fracture the rates of complications and mortality were significantly lower in supplemented patients ( 40 % vs 74 % ) . The median duration of hospital stay was significantly shorter in the supplemented group ( 24 vs 40 days ) . Thus the clinical outcome of elderly patients with femoral neck fracture can be improved by once daily dietary oral supplementation Objectives : To identify independent predictors for development of pressure ulcers in hospitalized patients and to develop a simple prediction rule for pressure ulcer development . Design : The Prevention and Pressure Ulcer Risk Score Evaluation ( prePURSE ) study is a prospect i ve cohort study in which patients are followed up once a week until pressure ulcer occurrence , discharge from hospital , or length of stay over 12 weeks . Data were collected between January 1999 and June 2000 . Setting : Two large hospitals in the Netherl and s. Participants : Adult patients admitted to the surgical , internal , neurological and geriatric wards for more than 5 days were eligible . A consecutive sample of 1536 patients was visited , 1431 ( 93 % ) of whom agreed to participate . Complete follow up data were available for 1229 ( 80 % ) patients . Main outcome measures : Occurrence of a pressure ulcer grade 2 or worse during admission to hospital . Results : Independent predictors of pressure ulcers were age , weight at admission , abnormal appearance of the skin , friction and shear , and planned surgery in coming week . The area under the curve of the final prediction rule was 0.70 after bootstrapping . At a cut off score of 20 , 42 % of the patient weeks were identified as at risk for pressure ulcer development , thus correctly identifying 70 % of the patient weeks in which a pressure ulcer occurred . Conclusion : A simple clinical prediction rule based on five patient characteristics may help to identify patients at increased risk for pressure ulcer development and in need of preventive measures Protein energy malnutrition is an important determinant of clinical outcome in older patients after hip fracture , but the effectiveness of nutritional support programs in routine clinical practice is controversial . We performed a prospect i ve , r and omized , controlled clinical trial to determine if nutritional supplementation decreased fracture-related complications in a selection of otherwise healthy patients with hip fractures . Patients were r and omized to intervention or control groups . The control group ( n = 40 ) was given ordinary hospital food and beverage . The intervention group ( n = 40 ) also was administered a 1000 kcal daily intravenous supplement for 3 days , followed by a 400 kcal oral nutritional supplement for 7 days . We recorded daily fluid and energy intake during the first 10 days of hospitalization and fracture-related complications up to 4 months . The total fluid and energy intake in the intervention group neared optimal levels . The control group received 54 % and 64 % of optimal energy and fluid intake , respectively . The risk of fracture- related complications was greater in the control group ( 70 % ) than in the intervention group ( 15 % ) . Four patients in the control group died within 120 days postoperatively . The comprehensive balanced nutrition supplement result ed in lower complication rates and mortality at 120 days postoperatively . Level of Evidence : Therapeutic Level I. See the Guidelines for Authors for a complete description of levels of evidence The predictive validity of the Braden Scale and the timing of assessment for optimal prediction of pressure sore development ( PS ) were studied in a nursing home population . Subjects ( N = 102 ) over age 19 , free of PS and admitted within the previous 72 hr , were r and omly selected from consecutive admissions to a skilled nursing facility . Subjects were assessed for risk and skin condition every 48 to 72 hr for 4 weeks . Twenty-eight subjects ( 27.5 % ) developed a PS . A cut score of 18 used at the observation prior to the first recorded PS maximized prediction , producing a sensitivity of 79 % , a specificity of 74 % , a 54 % predictive value of a positive test , 90 % predictive value of a negative test , and 75 % correct classification rate OBJECTIVE : To compare Pressure Ulcer Scale for Healing ( PUSH ) scores at 8 weeks in long-term-care residents with pressure ulcers who were given st and ard care plus a concentrated , fortified , collagen protein hydrolysate supplement vs. residents who were given st and ard care plus placebo . DESIGN : R and omized , prospect i ve , controlled , multicenter trial at 23 long-term-care facilities in 4 states . SUBJECTS : A total of 89 residents with Stage II , III , or IV pressure ulcers were entered into the trial ; 71 residents completed the study . INTERVENTION : Residents were r and omized to receive st and ard care plus a concentrated , fortified , collagen protein hydrolysate supplement ( n = 56 ) or st and ard care plus placebo ( n = 33 ) 3 times daily for 8 weeks . Wound healing was assessed biweekly using the PUSH tool , version 3.0 . This tool categorizes pressure ulcers by surface area , exu date , and type of wound tissue . PRIMARY OUTCOME MEASURE : Change in PUSH tool scores in each group at 8 weeks . RESULTS : After 8 weeks of treatment , residents who received st and ard care plus the concentrated , fortified , collagen protein hydrolysate supplement had significantly better PUSH tool scores compared with those who received st and ard care plus placebo ( 3.55 ± 4.66 vs 3.22 ± 4.11 , respectively ; P < .05 ) . CONCLUSION : By week 8 , PUSH tool scores-a measurement of pressure ulcer healing-showed approximately twice the rate of pressure ulcer healing in the treatment group compared with the control group . A concentrated , fortified , collagen protein hydrolysate supplement may be of benefit to residents of long-term-care facilities who have pressure ulcers OBJECTIVE We investigated the potential of a high-protein , arginine- and micronutrient-enriched oral nutritional supplement ( ONS ) to improve healing of pressure ulcers in non-malnourished patients who would usually not be considered for extra nutritional support . METHODS Forty-three non-malnourished subjects with stage III or IV pressure ulcers were included in a multicountry , r and omized , controlled , double-blind , parallel group trial . They were offered 200 mL of the specific ONS or a non-caloric control product three times per day , in addition to their regular diet and st and ard wound care , for a maximum of 8 wk . Results were compared with repeated- measures mixed models ( RMMM ) , analysis of variance , or Fisher 's exact tests for categorical parameters . RESULTS Supplementation with the specific ONS accelerated pressure ulcer healing , indicated by a significantly different decrease in ulcer size compared with the control , over the period of 8 wk ( P < or= 0.016 , RMMM ) . The decrease in severity score ( Pressure Ulcer Scale for Healing ) in the supplemented group differed significantly ( P < or= 0.033 , RMMM ) from the control . Moreover , significantly fewer dressings were required per week in the ONS group compared with the control ( P < or= 0.045 , RMMM ) and less time was spent per week on changing the dressings ( P < or= 0.022 , RMMM ) . At the end of the study , blood vitamin C levels had significantly increased in the ONS group compared with the control ( P = 0.015 , analysis of variance ) . CONCLUSION Specific nutritional supplementation accelerated healing of pressure ulcers and decreased wound care intensity in non-malnourished patients , which is likely to decrease overall costs of pressure ulcer treatment Abstract Objective : To evaluate whether risk assessment scales can be used to identify patients who are likely to get pressure ulcers . Design : Prospect i ve cohort study . Setting : Two large hospitals in the Netherl and s. Participants : 1229 patients admitted to the surgical , internal , neurological , or geriatric wards between January 1999 and June 2000 . Main outcome measure : Occurrence of a pressure ulcer of grade 2 or worse while in hospital . Results : 135 patients developed pressure ulcers during four weeks after admission . The weekly incidence of patients with pressure ulcers was 6.2 % ( 95 % confidence interval 5.2 % to 7.2 % ) . The area under the receiver operating characteristic curve was 0.56 ( 0.51 to 0.61 ) for the Norton scale , 0.55 ( 0.49 to 0.60 ) for the Braden scale , and 0.61 ( 0.56 to 0.66 ) for the Waterlow scale ; the areas for the sub population , excluding patients who received preventive measures without developing pressure ulcers and excluding surgical patients , were 0.71 ( 0.65 to 0.77 ) , 0.71(0.64 to 0.78 ) , and 0.68 ( 0.61 to 0.74 ) , respectively . In this sub population , using the recommended cut-off points , the positive predictive value was 7.0 % for the Norton , 7.8 % for the Braden , and 5.3 % for the Waterlow scale . Conclusion : Although risk assessment scales predict the occurrence of pressure ulcers to some extent , routine use of these scales leads to inefficient use of preventive measures . An accurate risk assessment scale based on prospect ively gathered data should be developed The objective of this study was to assess the effects of ascorbic acid supplementation , 500 mg twice daily in the treatment of pressure ulcers as an adjunct to st and ardized treatment . The design consisted of a multicenter blinded r and omized trial . The control group received 10 mg of ascorbic acid twice daily . Patients from 11 nursing homes and 1 hospital participated . Main outcome measures included wound survival , healing rates of wound surfaces , and clinimetric changes over 12 weeks . Eighty-eight patients were r and omized . Intention-to-treat analysis showed that the wound closure probability per unit time ( i.e. , the closure rate ) was not higher in the intervention group than in the control group ( Cox hazard ratio of 0.78 [ 90 % precision interval , 0.44 - 1.39 ] ) . Mean absolute healing rates were 0.21 and 0.27 cm2/week in the intervention and control group , respectively ( PI of the adjusted difference : -0.17 to 0.13 ) . Relative healing rates and healing velocities did not show favorable results of ascorbic acid supplementation , either . A panel scored slides of the ulcers with a report mark between 1 ( bad ) and 10 ( excellent ) . The improvement was 0.45 and 0.72 points per week in the intervention and control group , respectively ( PI of the adjusted difference : -0.50 to 0.20 ) . With another clinimetric index we could not show any differences , either . These data do not support the idea that ascorbic acid supplementation ( 500 vs. 10 mg twice daily ) speeds up the healing of pressure ulcers BACKGROUND & AIMS Strategies to treat malnutrition lack practicability in the hospital setting . The present study aim ed at developing and evaluating a routinely manageable concept for an improved nutritional care of malnourished in-hospital patients . METHODS A r and omized controlled intervention study was conducted . 132 risk patients defined by Nutritional Risk Screening 2002 , were r and omized to individualised nutrition support ( intervention group [ n = 66 ] ) or st and ard hospital care ( control group [ n = 66 ] ) . Body weight , plasma vitamin levels , quality of life , complications , antibiotic therapies , readmissions and mortality were assessed . RESULTS Nutrition interventions led to higher intakes ( mean [ st and ard deviation ] ) in energy ( 1553 [ 341 ] kcal vs. 1115 [ 381 ] kcal , p < 0.001 ) and protein ( 65.4 [ 16.4 ] g vs. 43.9 [ 17.2 ] g , p < 0.001 ) . Intervention patients ( n = 66 ) kept their body weight in comparison to control patients ( n = 66 ; 0.0 [ 2.9 ] kg vs. -1.4 [ 3.2 ] kg , p = 0.008 ) . Positive effects on plasma ascorbic acid level ( 46.7 [ 26.7 ] μmol/l vs. 34.1 [ 24.2 ] μmol/l , p = 0.010 ) , SF-36 function summary scale ( 37 [ 11 ] % vs. 32 [ 9 ] % , p = 0.030 ) , number of complications ( 4/66 vs. 13/66 , p = 0.035 ) , antibiotic therapies ( 1/66 vs. 8/66 , p = 0.033 ) and readmissions ( 17/64 vs. 28/61 , p = 0.027 ) were recorded . CONCLUSIONS Malnourished patients profit from nutrition support regarding nutrition status and quality of life . They have fewer complications , need fewer antibiotics and are less often re-hospitalised The present study was design ed to evaluate to the effect of dietary supplements on clinical outcome and nutritional status in a large group of geriatric patients ( n = 501 ) . The patients were r and omised into an experimental group which received nutritional supplementation ( 400 kcal ) as well as a st and ard hospital diet , and a control group on hospital diet alone . The nutritional state was measured on admission and after 8 and 26 weeks by anthropometry , serum protein analysis and a delayed hypersensitivity skin test . Protein energy malnutrition was defined as the presence of three or more abnormal parameters . 28.5 % of patients showed evidence of malnutrition on admission . Hospitalisation itself result ed in a gradual deterioration in nutritional status . Nutritional supplementation generally improved nutritional state . Among those patients who were well nourished on admission , and subsequently receiving dietary supplementation , 8.3 % fulfilled malnutrition criteria after 26 weeks , while 21.1 % were considered malnourished in the control group ( p < 0.05 ) . The improvement observed in transport proteins was probably related to nutritional support and not just to the reversal of inflammation . In the initially well nourished group of more than 300 patients , the mortality rate was 8.6 % in those given nutritional support compared to 18.6 % in the control group ( p < 0.02 ) BACKGROUND Undernutrition is common in hospital patients with stroke , can develop or worsen in hospital , and is associated with poor outcomes . We aim ed to establish whether routine oral nutritional supplements improve outcome after stroke . METHODS The FOOD trials are a family of three pragmatic , multicentre , r and omised controlled trials . We measured the outcomes of stroke patients who could swallow and who were r and omly allocated normal hospital diet or normal hospital diet plus oral nutritional supplements until hospital discharge . The primary outcome was death or poor outcome ( modified Rankin scale [ MRS ] grade 3 - 5 ) , 6 months after enrollment , measured unaware of treatment allocation . Analysis was by intention to treat . FINDINGS Between Nov 1 , 1996 , and July 31 , 2003 , 4023 patients were enrolled by 125 hospitals in 15 countries . Only 314 ( 8 % ) patients were judged to be undernourished at baseline . Vital status and MRS at the end of the trial were known for 4012 and 4004 patients , respectively . Supplemented diet was associated with an absolute reduction in risk of death of 0.7 % ( 95 % CI -1.4 to 2.7 ) and an increased risk of death or poor outcome of 0.7 % ( -2.3 to 3.8 ) . INTERPRETATION We could not confirm the anticipated 4 % absolute benefit for death or poor outcome from routine oral nutritional supplements for mainly well nourished stroke patients in hospital . Our results would be compatible with a 1 % or 2 % absolute benefit or harm from oral supplements . These results do not support a policy of routine oral supplementation after stroke PURPOSE To estimate the annual incidence , cumulative probability of presumed urinary tract infection ( UTI ) by age , and the social costs . METHODS Analysis of a r and om digit dialing survey of 2000 women in the United States . RESULTS 10.8 percent ( 95 % CI : 9.4 , 12.1 % ) of women aged 18 and older reported at least one presumed UTI during the past 12 months , with the majority of the cases occurring among women with a history of two or more UTI episodes in their life . We estimate that by age 24 , one-third of women will have at least one physician-diagnosed UTI that was treated with prescription medication . Overall , an estimated 11.3 million women in the United States had at least one presumed UTI treated with antibiotics in 1995 . We estimate the annual cost of UTI cases with prescriptions to be $ 1.6 billion in 1995 . If the costs occurring after 1995 are discounted at 5 % annually , the total cost over 20 years has a present value of $ 25.5 billion . CONCLUSION If a vaccine were developed that would prevent either initial or recurrent UTI the net benefits to society would be substantial , even at a developmental cost of one billion dollars BACKGROUND & AIMS Malnutrition is a risk factor for development of pressure ulcers ( PU ) . Nutritional supplementation may thus reduce the incidence of PU . We investigated the effect of nutritional supplementation on incidence of PU in hip-fracture patients at risk of developing PU . METHODS Hip-fracture patients ( n=103 ) were included in this double-blind , r and omised , placebo-controlled trial . They received 400 ml daily of a supplement enriched with protein , arginine , zinc and antioxidants ( n=51 ) or a non-caloric , water-based placebo supplement ( n=52 ) . Presence and stage of PU were assessed daily for 28 days or until discharge ( median : 10 days during supplementation ) . RESULTS Incidence of PU was not different between supplement ( 55 % ) and placebo ( 59 % ) , but incidence of PU stage II showed a 9 % difference ( difference : 0.091 ; 95 % CI : 0.07 - 0.25 ) between supplement ( 18 % ) and placebo ( 28 % ) . Of patients developing PU 57 % developed it by the second day . Time of onset ( days ) showed a trend ( P=0.090 ) towards later onset of PU with supplement ( 3.6+/-0.9 ) than placebo ( 1.6+/-0.9 ) . CONCLUSIONS Hip-fracture patients develop PU at an early stage . Nutritional supplementation may not prevent PU at this stage , but contributes possibly to a delayed onset and progression of PU . Nutritional supplementation may be more effective if initiated earlier OBJECTIVE To investigate if a lower dose of arginine in the form of an oral nutritional supplement can show similar benefit in the healing rate of pressure ulcers compared with the current evidence for 9 g of arginine . METHOD Twenty-three in patients with category II , III or IV pressure ulcers were r and omised to receive daily , for 3 weeks , the st and ard hospital diet plus 4.5 or 9 g arginine in the form of a commercial supplement . Pressure ulcer size and severity was measured weekly ( by PUSH tool ; pressure ulcer scale for healing ; 0= completely healed , 17= greatest severity ) . Nutritional status was determined by Subjective Global Assessment . RESULTS There were no significant differences in patients ' age , gender , BMI , haemoglobin levels , albumin levels and diagnosis of diabetes between treatment groups . There was a significant decrease in pressure ulcer severity over time ( p < 0.001 ) , with no evidence of a difference in healing rate between the two arginine dosages ( p=0.991 ) . Based on expected healing time , patients in both treatment groups were estimated to achieve an almost 2-fold improvement compared with the historical control group . Patients categorised as malnourished showed clinical ly significant impaired healing rates compared with well nourished patients ( p=0.057 ) , although this was unaffected by arginine dosage ( p=0.727 ) . CONCLUSION Similar clinical benefits in healing of pressure ulcers can be achieved with a lower dosage of arginine , which can translate into improved concordance and significant cost-savings for both the health-care facilities and for patients INTRODUCTION The prevalence of hyponutrition in hospitalized patients in our setting is 53 % . The therapeutic approach is controversial . OBJECTIVES To determine whether an early nutritional intervention in hospitalized patients by means of oral nutritional support can improve their prognosis regarding decreased morbimortality and hospital stay . MATERIAL AND METHODS R and omized prospect i ve study comprised by a treatment group and a control group of malnourished patients hospitalized at the Internal Medicine and Respiratory Medicine Departments . The nutritional diagnosis was made by using the Subjective Global Assessment . Groups B and C were assigned to receive the hospital diet according to their needs and pathology ( control group ) and the treatment group also received a st and ard nutritional supplement . We recorded the development of infections , pressure ulcers , hospitalization days , mortality , and weight . RESULTS We performed more than 1,700 Subjective Global Assessment s. Five hundred and thirty seven patients ( 264 treated and 273 controls ) were followed-up until hospital discharge or death . We did not find statistically significant differences in mortality , hospital stay , or occurrence of complications between the treatment group and the control group . The treatment group presented statistically significant weight increase as compared with the control group . CONCLUSIONS We could not demonstrate benefits when using the oral nutritional supplement in terms of mortality , hospital stay , infectious complications , or pressure ulcers . The significant weight increase in the treatment group allowed us concluding that the supplement effectively treated hyponutrition in this group . This new clinical status implies a better prognosis , as it has already been shown . However , this could not be observed by means of the study parameters . Long-term studies are required to determine for how long this nutritional improvement can be sustained , implying a better prognosis in the long run The purpose of this study was to identify prospect ively risk factors for pressure sores and to compare these results with a cross-sectional analysis in the same population . Medical records on all admissions to a chronic care hospital over a 13-month period were review ed . Data on potential risk factors were abstract ed from the initial history , physical examination , nursing assessment , and laboratory studies . Pressure sore status on admission and at three weeks was determined from a st and ardized from completed on all patients with a score . The cross-sectional analysis was performed by comparing patients with and without a pressure sore at the time of admission . The cohort analysis used patients initially without a pressure sore and monitored for a new sore at three weeks . Factors associated with pressure sores on univariate testing were entered into a stepwise logistic regression model . One hundred of the 301 admissions presented with a pressure sore . Factors significantly associated with the presence of a sore were altered level of consciousness ( OR = 4.1 ) , bed- or chair-bound ( OR = 2.4 ) , impaired nutritional intake ( OR = 1.9 ) , and hypoalbuminemia ( OR = 1.8 for 10 mg/mL decrease ) . Of the 185 patients without a pressure sore , 20 ( 10.8 % ) developed a sore . Factors significantly associated with the development of a new pressure sore were a history of cerebrovascular accident ( OR = 5.0 ) , bed- or chair-bound ( OR = 3.8 ) , and impaired nutritional intake ( OR = 2.8 ) . Neither urinary nor fecal incontinence , nor the presence of hypoalbuminemia , was associated with sore development . We have prospect ively identified risk factors for pressure sores . ( ABSTRACT TRUNCATED AT 250 WORDS Prevention of pressure ulcers is fundamental to safe care of nursing home residents yet the role of hydration in pressure ulcer prevention has not been systematic ally examined . This r and omized clinical trial was undertaken to determine whether administration of supplemental fluid to nursing home residents at risk for pressure ulcers would enhance collagen deposition , increase estimated total body water , augment subcutaneous tissue oxygenation , and was safe . After a baseline period , 64 subjects were r and omized to receive the fluid volume prescribed or additional fluid ( prescribed plus 10 mL/kg ) for 5 days . Participants ' potential to heal as measured with hydroxyproline was low at baseline and did not increase significantly during treatment when additional fluid was systematic ally provided . Fluid intake increased significantly during treatment . Estimates of total body water and subcutaneous oxygen did not increase , indicating hydration was not improved . Supplemental fluid did not result in overhydration as measured by clinical parameters . Further work is needed to examine the relationship between fluid intake and hydration in nursing home residents as well as the role of hydration in pressure ulcer prevention The aims of the study were to investigate the relationship between nutritional state and the development of pressure sores and to test the hypothesis that supplementary nutritional support might prevent pressure sore development and improve healing . Newly admitted long-term care patients hospitalised for more than 3 weeks were included and r and omised into an experimental and a control group . The nutritional state was evaluated using serum protein analyses , anthropometry and the delayed hypersensitivity skin test . Further , the patients ' condition was assessed weekly using a modified Norton scale . The experimental group received extra nutritional support . Significantly more patients with protein-energy malnutrition had , or developed , pressure sores . Regression analyses indicated albumin , mobility , activity and food intake as predictors for pressure sores . Patients who received extra nutritional support tended to develop fewer pressure sores and to heal existing pressure sores to a greater extent than the control group , although this did not reach statistical significance Objective Pressure ulcers affect predominantly the elderly and nutritional status is a known risk factor . Guidelines on pressure ulcers provide recommendation on nutritional management . Ornithine alpha-ketoglutarate ( OKG ) is an adjuvant treatment in undernourished elderly patients or in patients with hypercatabolism states . It is a precursor of different amino-acids which play a role in the process of healing . The objective of the study is to determine the efficacy of OKG on pressure ulcer area reduction after six weeks of treatment . Design Multi-centre , international , r and omized , comparative , double blind , parallel groups , placebo-controlled study . Participants 160 patients ( ITT population ) aged over 60 years with a heel pressure ulcer at stage II or III.Intervention Patients received OKG ( n=85 ) or placebo ( n=75 ) once a day for 6 weeks . Measurements Ulcer area was measured each week , using a tracer . The primary endpoint was the percentage reduction of the surface at the final visit : [ ( Wound areatn — Wound areat0)/(Wound areat0 ) ] . Results At inclusion , ulcer area distribution deviated from normal distribution ( median ulcer area OKG 6.6cm2 , placebo 3.9 cm2 , p=0.044 , Mann-Whitney test ) . As healing is strongly related to baseline ulcer area , the abnormal distribution was a major bias . Therefore it was decided to perform the analysis on 2 sub-groups of patients according to the mean ulcer area , i.e. above or below 8cm2 . The mean wound area reduction for baseline area ≤ 8 cm2 are −59 . 5 ± 71.4 % and −54.0 ± 69.0 % for the OKG group and placebo groups respectively ( p=0.477 , Mann-Whitney test ) . In the group with baseline pressure ulcer area > 8 cm2 no between group differences on either parameter was detected . When closure rate is considered , a significant difference in favor of OKG group is observed ( − 0.07 cm2/day in the OKG group and − 0.04 cm2/day in the placebo groups respectively p=0.007 , Mann-Whitney test ) . Thirty serious adverse events were reported in 28 patients ( 15 allocated to OKG and 13 to placebo ) . None of them was considered treatment related . Conclusion This clinical trial supports a potential benefit of OKG 10 g daily in the subgroup of patients with pressure ulcers ≤ 8 cm2 surface area in elderly population when associated with debridement together with wound management according to pressure ulcer guidelines . However this study highlights method ological difficulties to perform clinical trials in old-old patients that may affect the robustness of the results for this type of study BACKGROUND Immune function declines with age , increasing risk for infection and delaying wound healing . Arginine enhances immune function and healing of st and ardized wounds in healthy elderly persons . The purpose of this study was to determine what level of arginine supplementation was orally and metabolically tolerated and effective in enhancing immune function in elderly persons with pressure ulcers . METHODS Residents with one or more pressure ulcers were recruited from two local nursing homes . Subjects were r and omized to receive 0 g ( n = 10 ; age , 82 + /- 3 years ) , 8.5 g ( n = 11 ; 81 + /- 3 years ) , or 17 g ( n = 11 ; 87 + /- 2 years ) of supplemental arginine each day for 4 weeks . Oral tolerance , ie , absence of nausea , vomiting , abdominal distention , or diarrhea , was assessed daily . Metabolic tolerance was assessed weekly by evaluating serum electrolytes . Lymphocyte proliferation to phytohemagglutinin and interleukin 2 production were measured at baseline and after 4 weeks of supplementation as indicators of immune function . RESULTS Supplemental arginine significantly increased plasma arginine levels and was orally and metabolically tolerated with no complaints of abdominal distress or no clinical ly relevant changes in electrolyte levels among groups . Lymphocyte proliferation and interleukin 2 production were significantly different between nursing homes . When data from nursing homes were considered individually , arginine supplementation did not enhance the proliferative response . In subjects from nursing home 2 only , there was a 38 % and 75 % decrease ( p < .05 ) in lymphocyte proliferation with 8.5 and 17 g of supplemental arginine , respectively . Interleukin 2 production was no different among supplementation groups . CONCLUSIONS Pharmacologic doses of arginine were well tolerated but did not enhance lymphocyte proliferation or interleukin 2 production in nursing home residents with pressure ulcers . CLINICAL RELEVANCY : Enteral formulas supplemented with pharmacologic levels of arginine are frequently administered to elderly persons . This study demonstrates that the very old can tolerate these nitrogen loads if baseline renal function is normal and fluid intake is encouraged . Further research needs to be completed investigating the effect of arginine supplementation on immune function in this population before recommending arginine use The purpose of this study was to assess the effect of nutritional supplementation on dietary intake and on pressure ulcer development in critically ill older patients . The multi-center trial involved 19 wards stratified according to specialty and recruitment for critically ill older patients ; 9 wards were r and omly selected for nutritional intervention ( nutritional intervention group ) , consisting of the daily distribution of two oral supplements , with each supplement containg 200 kcal , for 15 d. Pressure ulcer incidence was prospect ively recorded for grade s I ( erythema ) , II ( superficial broken skin ) , and III ( subcutaneous lesion ) for 15 d. Nutritional intake was monitored by using estimates in units of quarters vali date d by comparison with weight measurement . There were 672 subjects older than 65 y , and 295 were in the nutritional intervention group versus 377 in the control group . The patients were similar for age , sex ratio , and C-reactive protein . In comparison with the control group , the nutritional intervention group included more patients with stroke , heart failure , and dyspnea and fewer with antecedent falls , delirium , lower limb fractures , and digestive disease . The nutritional intervention group had a lower risk of pressure ulcers according to the Norton score but was less dependent ( Kuntzman score ) and had a lower serum albumin level . During the trial , energy and protein intakes were higher in the nutritional intervention group ( day 2 : 1081 + /- 595 kcal versus 957 + /- 530 kcal , P = 0.006 ; 45.9 + /- 27.8 g protein versus 38.3 + /- 23.8 g protein in the control group , P < 0.001 ) . At 15 d , the cumulative incidence of pressure ulcers was 40.6 % in the nutritional intervention group versus 47.2 % in the control group . The proportion of grade I cases relative to the total number of cases was 90 % . Multivariate analysis , taking into account all diagnoses , potential risk factors , and the intra-ward correlation , indicated that the independent risk factors of developing a pressure ulcer during this period were : serum albumin level at baseline , for 1 g/L decrease : 1.05 ( 95 % confidence interval : 1.02 to 1.07 , P < 0.001 ) ; Kuntzmann score at baseline , for 1-point increase : 1.22 ( 0.32 to 4.58 , P = 0.003 ) ; lower limb fracture : 2.68 ( 1.75 to 4.11 , P < 0.001 ) ; Norton score < 10 versus > 14 : 1.28 ( 1.01 to 1.62 , P = 0.04 ) ; and belonging to the control group : 1.57 ( 1.03 to 2.38 , P = 0.04 ) . In conclusion , it was possible to increase the dietary intake of critically ill elderly subjects by systematic use of oral supplements . This intervention was associated with a decreased risk of pressure ulcer incidence To derive a brief bedside pressure ulcer prediction tool for patients admitted to acute care hospitals , we conducted a prospect i ve study of first pressure ulcer incidence among 1,190 consecutive patients hospitalized in selected wards of a Swiss teaching hospital . Baseline predictors included patient age and items from the Norton and Braden ulcer prediction scales . During follow-up , 170 patients developed new pressure ulcers . The predictive ability of baseline assessment s decayed over time . Occurrence of first pressure ulcer in the 5 days after admission ( 129 events ) was best predicted by patient age ( 5 levels ) , mobility ( 3 levels ) , mental status ( 3 levels ) , and friction/shear ( 3 levels ) . The Fragmment score ( sum of friction , age , mobility , mental status ) was linearly related to pressure ulcer risk , and its area under the receiver operating characteristic curve ( 0.80 ) was higher than for the Norton ( 0.74 ; P = 0.006 ) and Braden ( 0.74 ; P = 0.004 ) scores . This brief pressure ulcer prediction scale performed well in an acute care setting . Use of this scale may facilitate the implementation of pressure ulcer prevention interventions A preliminary study was conducted on 80 patients with all stages of pressure ulcers to ascertain the seven-day effect on healing of four treatments : 1 ) consistent wound care , 2 ) carefully controlled nutritional support , 3 ) both consistent wound care and carefully controlled nutritional support , and 4 ) st and ard hospital treatment . Formal analysis confirmed that differences observed in the sample characteristics of treatment groups did not influence outcomes . There were no group differences in healing as shown by three indicators : 1 ) improvement in the ulcer stage , 2 ) decrease in ulcer size , and 3 ) a dichotomous clinical rating of improvement . In all groups a normal transferrin was correlated with improvement in stage and size of ulcers . This suggests a nutritional role in wound healing OBJECTIVE To determine the effect of dietary protein on healing of pressure ulcers in malnourished patients . DESIGN Nutritional intervention trial with the non-r and omized assignment of patients by pressure ulcer stage and bed type . SETTING Long-term care facility . PATIENTS Twenty-eight malnourished patients ( age = 72 + /- 18 years , mean + /- SD ) with a total of 33 truncal pressure ulcers . Nine patients had stage II ulcers , eight had stage III ulcers , and 16 had stage IV ulcers . METHODS Patients received liquid nutritional formulas as tubefeedings or meal supplements containing either 24 % protein ( 61 g protein/L ; n = 15 ) or 14 % protein ( 37 g protein/L ; n = 13 ) for 8 weeks . RESULTS There was a significant decrease in total truncal pressure ulcer surface area of the 15 patients in the 24 % protein group ( -4.2 + /- 7.1 cm2 , P < 0.02 ) , but not in the 13 patients in the 14 % protein group ( -2.1 + /- 11.5 cm2 , P = NS ) . The change in total ulcer area correlated with both dietary protein intake per kg body weight ( rs = -0.50 , P < 0.01 ) and caloric intake per kg body weight ( rs = -0.41 , P < 0.03 ) . The decrease in stage IV ulcer area in eight patients in the 24 % protein group ( -7.6 + /- 5.8 cm2 , P < 0.02 ) was significantly greater ( P < 0.05 ) than in eight patients in the 14 % protein group ( -3.2 + /- 16.4 , P = NS ) . In these 16 patients , the decrease in ulcer size also correlated with dietary protein intake per kg body weight ( rs = -0.63 , P < 0.01 ) . CONCLUSION High protein diets may improve the healing of pressure ulcers in malnourished nursing home patients The objective of this study was to evaluate the effects of nutrition intervention on nutritional states and healing of pressure ulcers by st and ardizing or unified factors including nursing , care and treatment in a multicenter open r and omized trial . Tube-fed patients with Stage III-IV pressure ulcers were selected . The control group ( 30 patients ) received the same nutrition management as before participating in this trial , whereas the intervention group ( 30 patients ) was given calories in the range of Basal Energy Expenditure ( BEE ) × 1.1 × 1.3 to 1.5 . The intervention period was 12 weeks . The efficacy and safety were evaluated based on the nutritional states and the sizes of ulcers ( length × width ) , and on the incidence of adverse events related to the study , respectively . The calories administered to the control and intervention groups were 29.1 ± 4.9 and 37.9 ± 6.5 kcal/kg/day , respectively . Significant interactions between the presence or absence of the intervention and the intervention period were noted for nutritional states ( p<0.001 for body weight , p<0.05 for prealbumin ) . Similarly , the size of ulcers differed significantly between subjects in the intervention group and in the control group ( p<0.001 ) . The results suggest that nutrition intervention could directly enhance the healing process in pressure ulcer patients Many valid and reliable tools and techniques are available for wound measurement . However , few prospect i ve clinical studies assessing these instruments have been conducted . A prospect i ve , method ological study was conducted between September 2006 and November 2007 to evaluate use of the Pressure Ulcer Scale for Healing ( PUSH ) version 3 in patients with one or more pressure ulcer . A convenience sample of 72 persons ( mean age 66.9 + /- 12.8 years ) with 86 pressure ulcers ( 49 % Stage II , 47 % Stage III , and 4 % Stage IV ) was recruited and assessed weekly until healing , transfer , patient death , or end of study for a maximum of 8 weeks . Most ulcers ( 77 % ) were in the sacral area and 56 % had been present for 1 month or longer . Repeated measures analysis revealed that PUSH total scores decreased significantly ( P < 0.001 ) over the 8-week study , with significant differences in PUSH total scores between healed and unhealed ulcers each week , starting on week 1 . The total PUSH score as well as the length x width item in the tool accurately differentiated between healed and nonhealed ulcers . Although the PUSH tool is practical , easy-to-use , and generally sensitive to change , some modifications would improve its value -- ie , a wound size/depth subscale . Additional studies to help clinicians more accurately evaluate the effectiveness of their interventions , including studies to determine whether wound measurements alone may suffice to monitor healing , are needed OBJECTIVES To investigate whether a disease-specific nutritional approach is more beneficial than a st and ard dietary approach to the healing of pressure ulcers ( PUs ) in institutionalized elderly patients . DESIGN Twelve-week follow-up r and omized controlled trial ( RCT ) . SETTING Four long-term care facilities in the province of Como , Italy . PARTICIPANTS Twenty-eight elderly subjects with Stage II , III , and IV PUs of recent onset ( < 1-month history ) . INTERVENTION All 28 patients received 30 kcal/kg per day nutritional support ; of these , 15 received st and ard nutrition ( hospital diet or st and ard enteral formula ; 16 % calories from protein ) , whereas 13 were administered a disease-specific nutrition treatment consisting of the st and ard diet plus a 400-mL oral supplement or specific enteral formula enriched with protein ( 20 % of the total calories ) , arginine , zinc , and vitamin C ( P<.001 for all nutrients vs control ) . MEASUREMENTS Ulcer healing was evaluated using the Pressure Ulcer Scale for Healing ( PUSH ; 0=complete healing , 17=greatest severity ) tool and area measurement ( mm(2 ) and % ) . RESULTS The sample d groups were well matched for age , sex , nutritional status , oral intake , type of feeding , and ulcer severity . After 12 weeks , both groups showed significant improvement ( P<.001 ) . The treatment produced a higher rate of healing , the PUSH score revealing a significant difference at Week 12 ( -6.1+/-2.7 vs -3.3+/-2.4 ; P<.05 ) and the reduction in ulcer surface area significantly higher in the treated patients already by Week 8 ( -1,140.9+/-669.2 mm(2 ) vs -571.7+/-391.3 mm(2 ) ; P<.05 and approximately 57 % vs approximately 33 % ; P<.02 ) . CONCLUSION The rate of PU healing appears to accelerate when a nutrition formula enriched with protein , arginine , zinc , and vitamin C is administered , making such a formula preferable to a st and ardized one , but the present data require further confirmation by high- quality RCTs conducted on a larger scale |
12,271 | 17,443,624 | Another study found that patients on APD had significantly more time for work , family and social activities .
AUTHORS ' CONCLUSIONS APD has not been shown to have significant advantages over CAPD in terms of important clinical outcomes .
APD may however be considered advantageous in select group of patients such as in the younger PD population and those in employment or education due to its psychosocial advantages . | BACKGROUND Peritoneal dialysis ( PD ) can be performed either manually as in continuous ambulatory peritoneal dialysis ( CAPD ) or using mechanical devices as in automated PD ( APD ) .
APD has been considered to have several advantages over CAPD such as reduced incidence of peritonitis , mechanical complications and greater psychosocial acceptability .
OBJECTIVES To assess the comparative efficacy of CAPD and APD in patients who are dialysed for end-stage renal disease ( ESRD ) . | Residual renal function ( RRF ) in end-stage renal disease is clinical ly important as it contributes to adequacy of dialysis , quality of life , and mortality . This study was conducted to determine the predictors of RRF loss in a national r and om sample of patients initiating hemodialysis and peritoneal dialysis . The study controlled for baseline variables and included major predictors . The end point was loss of RRF , defined as a urine volume < 200 ml/24 h at approximately 1 yr of follow-up . The adjusted odds ratios ( AOR ) and P values associated with each of the demographic , clinical , laboratory , and treatment parameters were estimated using an " adjusted " univariate analysis . Significant variables ( P < 0.05 ) were included in a multivariate logistic regression model . Predictors of RRF loss were female gender ( AOR = 1.45 ; P < 0.001 ) , non-white race ( AOR = 1.57 ; P = < 0.001 ) , prior history of diabetes ( AOR = 1.82 ; P = 0.006 ) , prior history of congestive heart failure ( AOR = 1.32 ; P = 0.03 ) , and time to follow-up ( AOR = 1.06 per month ; P = 0.03 ) . Patients treated with peritoneal dialysis had a 65 % lower risk of RRF loss than those on hemodialysis ( AOR = 0.35 ; P < 0.001 ) . Higher serum calcium ( AOR = 0.81 per mg/dl ; P = 0.05 ) , use of an angiotensin-converting enzyme inhibitor ( AOR = 0.68 ; P < 0.001 ) . and use of a calcium channel blocker ( AOR = 0.77 ; P = 0.01 ) were independently associated with decreased risk of RRF loss . The observations of demographic groups at risk and potentially modifiable factors and therapies have generated testable hypotheses regarding therapies that may preserve RRF among end-stage renal disease patients Objective The goals for maintenance dialysis treatment are to improve patient survival , reduce patient morbidity , and improve patient quality of life . This is the first r and omized prospect i ve study comparing automated peritoneal dialysis ( APD ) and continuous ambulatory peritoneal dialysis ( CAPD ) treatment with respect to quality of life and clinical outcomes in relation to therapy costs . Design A prospect i ve , r and omized multicenter study . Setting Three Danish CAPD units . Patients Thirty-four adequately dialyzed patients with high or high-average peritoneal transport characteristics were included in the study . Twenty-five patients completed the study . Interventions After r and omization , 17 patients were allocated to APD treatment and 17 patients to CAPD treatment for a period of 6 months . Medical and biochemical parameters were evaluated at monthly controls in the CAPD units . Quality -of-life parameters were assessed at baseline and after 6 months by the self-administered short-form SF-36 generic health survey question naire supplemented with disease- and treatment-specific questions . Therapy costs were compared by evaluating dialysis-related expenses . Main Outcome Measures Quality -of-life parameters , dialysis-related complications , dialysis-related expenses . Results The quality -of-life studies showed that significantly more time for work , family , and social activities was available to patients on APD compared to those on CAPD ( p < 0.001 ) . Although the difference was not significant , there was a tendency for less physical and emotional discomfort caused by dialysis fluid in the APD group . Sleep problems , on the other h and , tended to be more marked in the APD group . Any positive effect of APD compared to CAPD on dialysis-related hospital days or complication rates could not be confirmed . With larger patient sample s , it is possible , however , that a significant difference might have been achieved . The running costs for APD treatment were US $ 75 per day and for CAPD treatment US $ 61 per day . Conclusion If APD treatment can help to keep selected patients vocationally or socially active , paying the extra cost seems reasonable Both CAPD-Y and CCPD have been reported to reduce the high peritonitis rate of conventional CAPD . As peritonitis was the major complication of CAPD in our centre , both modifications were introduced in 1987 . Initially , treatment modalities were allocated to patients based on their ( doctor 's ) preference . A remarkable difference in peritonitis rate was encountered between patients on CCPD and those on CAPD-Y ( 0.6 vs 1.2 episodes a year ) . As patient selection and doctor 's preference might have contributed to this hopeful result , a prospect i ve study was started . From January 1988 on , all new patients were at r and om assigned to CAPD-Y or CCPD in order to study the incidence of peritonitis in relation to the treatment modality . Up till November 1 , 1990 , 26 patients enrolled in the CAPD-Y group ( follow-up of 292 patient months ) , and 30 patients in the CCPD group ( follow-up of 337 patient months ) . This ongoing study reveals that CCPD patients remained peritonitis free significantly longer than those on CAPD-Y ( quartile time to first peritonitis greater than 12 vs 3 months , p less than 0.05 ) , and had a significantly lower peritonitis incidence ( median time to second peritonitis 18 vs 6 months , p = 0.016 ) . In conclusion , in an unselected patient population CCPD was accompanied with a significant lower peritonitis incidence than Several centers have reported a lower rate of peritonitis among adult patients on continuous cyclic peritoneal dialysis ( CCPD ) as compared to those undergoing continuous ambulatory peritoneal dialysis ( CAPD ) . Preliminary results of our ongoing prospect i ve r and omized study comparing CAPD-Y with CCPD also suggest a lower peritonitis incidence among CCPD-treated patients . To investigate whether the two dialysis regimens could result in differences in local host defense , we studied peritoneal macrophage ( PMO ) function and effluent opsonic activity in eight patients established on CAPD-Y matched with eight chronic CCPD patients . Since short and long dwell times are inherent to both dialysis modalities , and we previously found that dwell time has an impact on PMO function and effluent opsonic activity , patients were studied after both a short ( 4 hr ) and a long ( 15 hr ) dwell time . In both groups PMO phagocytic capacity increased significantly with dwell time ( 39 + /- 3.3 % at 4 hr vs. 58 + /- 4.2 % at 15 hr in CAPD patients , and 40 + /- 3.9 vs. 72 + /- 3.3 % in CCPD patients ; P less than 0.01 ) , as did PMO peak chemiluminescence response ( 31 + /- 4.9 vs. 77 + /- 7.2 counts.min-1/10(4 ) cells in CAPD , and 22 + /- 3.9 vs. 109 + /- 21.2 counts.min-1/10(4 ) cells in CCPD ; P less than 0.01 ) and effluent opsonic activity ( 41 + /- 7.6 vs. 73 + /- 5.8 % in CAPD and 39 + /- 6.2 vs. 70 + /- 5.9 % in CCPD ; P less than 0.01 ) . However , no significant difference was found in either variable between CAPD and CCPD patients when dwell times were equal . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Fluid and sodium removal rates may not be equivalent in patients undergoing automated peritoneal dialysis ( APD ) and continuous ambulatory peritoneal dialysis ( CAPD ) . This may influence compared cardiovascular outcomes in both groups . METHODS The authors compared prospect ively the time courses of ultrafiltration , sodium removal , and residual renal function ( RRF ) in a group of incident patients treated with CAPD ( n = 53 ) or APD ( n = 51 ) for at least 1 year ( mean follow-up , 28.9 months ; range , 13 to 62 ) . The authors analyzed potential effects of these factors on blood pressure ( BP ) control and cardiovascular morbidity and mortality . RESULTS Ultrafiltration and sodium removal rates were consistently lower in APD patients ( mean differences , 236 mL/d ; P = 0.012 , and 36 mmol/d ; P = 0.018 , respectively , end of first year ) . Moreover , univariate and multivariate analysis indicated that APD therapy results in a moderate , but significantly faster decline of RRF than CAPD therapy . Analysis of clinical outcomes showed that CAPD ( versus APD ) therapy or higher ultrafiltration or sodium removal rates were associated with a better time course of systolic , but not diastolic , BP . We were unable to identify PD modality , ultrafiltration , or sodium removal rates as independent predictors of cardiovascular morbidity and mortality . CONCLUSION Ultrafiltration and sodium removal rates are consistently lower in incident APD patients than in their counterparts undergoing CAPD . Moreover , RRF declines faster during APD than during CAPD therapy , although this difference may be partially counteracted by a detrimental effect of ultrafiltration on RRF . Aside from a better control of systolic BP in CAPD patients , these differences do not portend significant cardiovascular consequences during the first years of PD therapy Objectives To compare sodium removal in continuous ambulatory peritoneal dialysis ( CAPD ) and automated peritoneal dialysis ( APD ) patients , and to identify the main factors that modify Na removal in clinical practice in these patients . Design Study in three steps . Cross-sectional observational ( Study A ) , and longitudinal interventional ( Studies B and C ) . Patients and Methods First ( Study A ) we carried out a cross-sectional survey of Na removal in 63 patients on CAPD and 78 patients on APD . Second ( Study B ) , we studied Na removal in 32 patients before and after changing from CAPD to APD therapy . Finally ( Study C ) , we analyzed the impact on Na removal of introducing icodextrin for the long dwell in 16 patients undergoing CAPD or APD . Results In Study A , total Na removal averaged 210 mmol/day for CAPD patients and 91 mmol/day for APD patients ( p < 0.001 ) ; Na removal was < 100 mmol/day in 7.1 % of CAPD patients and 56.4 % of APD patients . Multivariate analysis identified ultrafiltration [ B = 125 mmol/day , 95 % confidence interval ( CI ) 110 , 140 ] , CAPD therapy ( B = 60 mmol/day , 95%CI 37 , 83 ) , and residual diuresis ( B = 51 mmol/L , 95%CI 34 , 69 ) as independent predictors of Na removal ( adjusted r2 = 0.76 ) . For APD patients , longer nocturnal dwell times and performing a supplementary diurnal exchange were also independently associated with higher Na removal rates . In Study B , Na removal decreased from 192 to 92 mmol/day ( median ) after the change to APD ( p = 0.02 ) . In Study C , peritoneal Na removal increased from 98 to 148 mmol/day ( median ) ( p = 0.04 ) after introducing icodextrin . Conclusions St and ard APD schedules are frequently associated with poor Na removal rates . For any degree of ultrafiltration , Na removal is better in CAPD than in APD . Icodextrin , supplementary diurnal exchanges , and longer nocturnal dwell times improve Na removal in APD . Sodium removal can be estimated from ultrafiltration in patients on CAPD , but must be specifically monitored in patients on APD An increasing number of patients are prescribed a continuous-cycling regimen because st and ard manual peritoneal-dialysis exchanges alone are not sufficient in achieving adequate dialysis as defined by the Dialysis Outcome Quality Initiative . Consequently , the number of patients on continuous-cycler therapy is increasing . There is controversy as to whether there are differences in the development of peritonitis between patients maintained on manual therapy and those on continuous cycling therapy . As a result , we retrospectively review ed the charts of all cycler peritoneal dialysis ( CPD ) patients maintained on either manual peritoneal dialysis ( Baxter UltraBag ; Group I ) or continuous cycler peritoneal dialysis ( Baxter HomeChoice Cycler ; Group II ) between 1 June 1994 and 31 December 1996 . A total of 239 patients were in Group I and 106 in Group II . Both groups were similar in age , race , gender , and presence of diabetes mellitus , coronary artery disease , peripheral vascular disease , and gastrointestinal disease . There was no difference in the overall rate of peritonitis between the two groups of patients [ 1 episode in 10.4 patient-months ( Group I ) vs. 1 in 10.0 patient-months ( Group II ) ; -0.01843 to 0.02619 ] . The rates of Staphylococcus aureus peritonitis [ 1 episode in 48.5 patient-months ( Group I ) vs. 1 in 141.8 patient months ( Group II ) ; -0.06152 to -1.1689 ] ; polymicrobial peritonitis [ 1 episode in 278.8 patient-months ( Group I ) vs. 1 in 1134 patient months ( Group II ) : -0.0079 to -0.0478 ] , and fungal peritonitis ( 1 episode in 202.7 patient-months ( Group I ) vs. no episodes ( Group II ) ; 0.00202 to 0.00785 ] were significantly lower among patients maintained on the Baxter HomeChoice Cycler . The rate of gram-negative peritonitis was higher among patients maintained on the Baxter HomeChoice Cycler , but this difference was not statistically significant [ 1 episode in 82.6 patient-months ( Group I ) vs. 1 episode in 45.4 patient months ( Group II ) ; 0.4723 to -0.0248 ] . We conclude that individual rates of peritonitis were different for patients maintained on either manual or continuous CPD therapy , while the overall rate of peritonitis was found to be similar for both groups of patients . The finding that there may be a difference with the gram-negative peritonitis rate is important since gram-negative peritonitis has been shown to have a more severe outcome in terms of morbidity , mortality , and patient dropout from CPD therapy . A larger , r and omized , multicenter study comparing the rates of gram-positive , gram-negative , fungal , and polymicrobial peritonitis is warranted The objective of this study was to evaluate the association of peritoneal membrane transport with technique and patient survival . In the Canada-USA prospect i ve cohort study of adequacy of continuous ambulatory peritoneal dialysis ( CAPD ) , a peritoneal equilibrium test ( PET ) was performed approximately 1 mo after initiation of dialysis ; patients were defined as high ( H ) , high average ( HA ) , low average ( LA ) , and low ( L ) transporters . The Cox proportional hazards method evaluated the association of technique and patient survival with independent variables ( demographic and clinical variables , nutrition , adequacy , and transport status ) . Among 606 patients evaluated by PET , there were 41 L , 192 LA , 280 HA , and 93 H. The 2-yr technique survival probabilities were 94 , 76 , 72 , and 68 % for L , LA , HA , and H , respectively ( P = 0.04 ) . The 2-yr patient survival probabilities were 91 , 80 , 72 , and 71 % for L , LA , HA , and H , respectively ( P = 0.11 ) . The 2-yr probabilities of both patient and technique survival were 86 , 61 , 52 , and 48 % for L , LA , HA , and H , respectively ( P = 0.006 ) . The relative risk of either technique failure or death , compared to L , was 2.54 for LA , 3.39 for HA , and 4.00 for H. The mean drain volumes ( liters ) in the PET were 2.53 , 2.45 , 2.33 , and 2.16 for L , LA , HA , and H , respectively ( P < 0.001 ) . After 1 mo CAPD treatment , the mean 24-h drain volumes ( liters ) were 9.38 , 8.93 , 8.59 , and 8.22 for L , LA , HA , and H , respectively ( P < 0.001 ) ; the mean 24-h peritoneal albumin losses ( g ) were 3.1 , 3.9 , 4.3 , and 5.6 for L , LA , HA , and H , respectively ( P < 0.001 ) . The mean serum albumin values ( g/L ) were 37.8 , 36.2 , 33.8 , and 32.8 for L , LA , HA , and H , respectively ( P < 0.001 ) . Among CAPD patients , higher peritoneal transport is associated with increased risk of either technique failure or death . The decreased drain volume , increased albumin loss , and decreased serum albumin concentration suggest volume overload and malnutrition as mechanisms . Use of nocturnal cycling peritoneal dialysis should be considered in H and HA transporters BACKGROUND A prospect i ve sequential study on continuous ambulatory peritoneal dialysis ( CAPD ) and three techniques of automated peritoneal dialysis ( APD ) was conducted to assess peritoneal clearances , the influence of peritoneal permeability on nocturnal APD clearances and the suitability of the peritoneal equilibration test ( PET ) for predicting clearances on APD . METHODS After performing a PET , a series of clinical , biochemical and dialysis adequacy markers were evaluated after 2 months on CAPD , continuous cycling peritoneal dialysis ( CCPD ) and tidal volume peritoneal dialysis ( TPD ) with 50 % and 25 % tidal volumes . Forty five patients participated and 33 completed the study . RESULTS Serum urea and creatinine decreased significantly whereas haemoglobin and glucose increased . Mean peritoneal urea clearance ( 1/week ) was 55.40+/-8.76 on CAPD , 74.82+/-12.62 on CCPD , 69.20+/-14.63 on TPD ( tidal 50 % ) and 66.89+/-13.23 on TPD ( tidal 25 % ) ; mean creatinine clearance ( 1/week/1.73 m2 ) was 42.80 + /- 9.95 , 52.19 + /- 11.11 , 51.31 + /- 13.3 and 49.17 + /- 11.83 , respectively . Both clearances were significantly lower on CAPD than on APD ( P<0.001 ) . CCPD was the automated technique that provided the best nocturnal urea clearance ( P<0.01 ) . Nocturnal creatinine clearance did not show significant differences between CCPD and TPD ( tidal 50 % ) , being better with both techniques than with TPD ( tidal 25 % ) . There were statistically significant differences between nocturnal dialysate to plasma ( D/P ) ratios and those corresponding to the nearest times in the PET . The urea D/P ratio at 180 min and the creatinine D/P ratio at 240 min of the PET were the parameters that better estimated nocturnal clearances on APD . CONCLUSIONS This study confirms that TPD does not improve the results of CCPD . Significant differences between D/P ratios during actual nocturnal cycles and PETs were observed Objective To compare the incidence of peritonitis and exit-site infection in an ample group of patients undergoing continuous ambulatory peritoneal dialysis ( CAPD ) and automated peritoneal dialysis in a single center during a 10-year period . Design Nonr and omized , prospect i ve study . Setting Public , tertiary care hospital providing peritoneal dialysis care to a population of ( approximately ) 750 000 people . Patients We studied 213 patients on CAPD and 115 on automated peritoneal dialysis ( APD ) starting therapy between January 1989 and August 1998 , with a minimum follow-up of 3 months . Main Outcome Measures Using a multivariate approach , we compared the incidence , clinical course , and outcome of peritonitis and exit-site infections in both groups , controlling for other risk factors for the complications studied . Results The incidence of peritonitis was higher in CAPD than in APD ( adjusted difference 0.20 episodes/ patient/year , 95 % confidence interval 0.08 – 0.32 ) . There was a trend for CAPD patients to present earlier with peritonitis than APD patients , yet the incidence of and survival to the first exit-site infection were similar in both groups . The etiologic spectrum of infections displayed minor differences between groups . Automated PD patients were more frequently hospitalized for peritonitis , but otherwise , the complications and outcome of peritonitis and exit-site infections did not differ significantly between patients on CAPD and those on APD . Conclusions Automated PD is associated with a lower incidence of peritonitis than is CAPD , while exit-site infection is similarly incident under both modes of therapy . The etiologic spectrum , complications , and outcome of peritonitis and exit-site infection do not differ markedly between CAPD and APD . Prevention of peritonitis should be included among the generic advantages of APD over CAPD Decline in residual renal function in CAPD patients often leads to reduced overall solute clearances . Inadequate dialysis has been linked to malnutrition and increased morbidity and mortality rates . Achieving dialysis adequacy targets is often difficult by the conventional method of increasing CAPD exchange volumes . In comparison , substantial increases in solute clearances can be achieved with the use of automated peritoneal dialysis with large fill volumes and an extra daytime exchange In tidal peritoneal dialysis ( TPD ) only a part of the infused dialysate is drained with each exchange , leaving a residual volume on top of which fresh fluid is cycled . As the persistent presence of a buffered intraperitoneal reserve volume might favour peritoneal macrophage ( PMO ) function , PMO obtained from eight patients during a 3-h continuous cyclic peritoneal dialysis ( CCPD ) or TPD session were studied in a r and omized cross-over trial . PMO were studied for uptake of E. coli ( complement-dependent ) and S. epidermidis ( antibody-dependent ) , as well as for their killing capacity and peak chemiluminescence response . In addition , dialysate was sample d during both treatment sessions and studied for pH , osmolality , and effect on the viability of donor phagocytes and mesothelial cells . TPD-derived PMO were significantly better able to phagocytose E. coli than CCPD-PMO ( 48 + /- 8 versus 33 + /- 6 % uptake , P < 0.05 ) , whereas the other tested functional capacities revealed no significant difference between TPD- and CCPD-PMO . During TPD dialysate pH ranged from 6 to 7 as compared to a pH range from 5 to 7 in CCPD . The presence of a residual dialysate volume result ed in less wash-out of cells and opsonins early in the treatment , and to some extent blunted the noxious effects of fresh dialysis solutions . Overall , however , tidal PD appeared to have no advantage over CCPD regarding preservation of peritoneal defences The European APD Outcome Study ( EAPOS ) is a 2-yr , prospect i ve , multicenter study of the feasibility and clinical outcomes of automated peritoneal dialysis ( APD ) in anuric patients . A total of 177 patients were enrolled with a median age of 54 yr ( range , 21 to 91 yr ) . Previous median total time on dialysis was 38 mo ( range , 1.6 to 259 mo ) , and 36 % of patients had previously been on hemodialysis for > 90 d. Diabetes and cardiovascular disease were present in 17 % and 46 % of patients , respectively . The APD prescription was adjusted at physician discretion to aim for creatinine clearance ( Ccrea ) > /=60 L/wk per 1.73 m(2 ) and ultrafiltration ( UF ) > /=750 ml/24 h during the first 6 mo . Baseline solute transport status ( D/P ) was determined by peritoneal equilibration test . At 1 yr , 78 % and 74 % achieved Ccrea and UF targets , respectively ; median drained dialysate volume was 16.2 L/24 h with 50 % of patients using icodextrin . Baseline D/P was not related to UF achieved at 1 yr . At 2 yr , patient survival was 78 % and technique survival was 62 % . Baseline predictors of poor survival were age ( > 65 yr ; P = 0.006 ) , nutritional status ( Subjective Global Assessment grade C ; P = 0.009 ) , diabetic status ( P = 0.008 ) , and UF ( < 750 ml/24 h ; P = 0.047 ) . Time-averaged analyses showed that age , Subjective Global Assessment grade C and diabetic status predicted patient survival with UF the next most significant variable ( risk ratio , 0.5/L per d ; P = 0.097 ) . Baseline Ccrea , time-averaged Ccrea , and baseline D/P had no effect on patient or technique survival . This study shows that anuric patients can successfully use APD . Baseline UF , not Ccrea or membrane permeability , is associated with patient survival Objective To determine whether gender , race , diabetes , peritoneal dialysis ( PD ) modality , and comorbid conditions influence loss of residual renal function ( RRF ) . Design Retrospective study of incident PD patients , using data base of prospect ively collected demographic , laboratory , and clearance data . Setting Peritoneal Dialysis Registry of the University of Pittsburgh Medical Center . Patients The study included 184 continuous ambulatory PD and automated PD patients who had at least two 24-hour urine collection s for glomerular filtration rate ( GRF ) between April 1991 and March 2000 . 836 urine collection s were analyzed . Outcome Measures Loss of RRF was defined as the slope of the decline in GFR as measured by the average of creatinine and urea clearances in 24-hour urine collection s. Stepwise forward regression was used to identify demographic and laboratory factors associated with loss of GFR . Spearman correlations were used to assess the significance of associations . Results The median rate of decline of renal function was –0.17 mL/minute/month . Gender , race , diabetes , automated PD , peritoneal equilibration test , protein equivalent of nonprotein nitrogen appearance normalized to body surface area , and serum albumin did not predict loss of RRF . Cardiac disease was the only variable affecting decline of RRF ( p = 0.045 ) . Conclusion Modality of PD and patient demographic factors do not contribute to the rate at which RRF is lost in incident PD patients . Additional study of the factors contributing to the decline and maintenance of RRF is needed Peritoneal dialysis has been used to treat chronic renal failure since 1962 [ 1 ] , but it was not until the introduction of continuous ambulatory peritoneal dialysis by Popovich and associates [ 2 ] in 1976 that peritoneal dialysis was recognized as an important treatment for end-stage renal failure . However , since the inception of continuous ambulatory peritoneal dialysis as a renal replacement therapy , peritonitis has been its most frequent and limiting complication . Peritonitis may strike these patients repeatedly . It leads to considerable morbidity , and may require a change to hemodialysis therapy [ 3 - 5 ] . Continuous cyclic peritoneal dialysis was developed as an alternative to continuous ambulatory peritoneal dialysis for patients who were incapable of or unwilling to perform manual dialysate exchanges [ 6 ] . Whereas in continuous ambulatory peritoneal dialysis fluid is instilled manually ( by gravity ) into the peritoneal cavity through a permanent catheter and drained after a dwelling period of several hours , continuous cyclic peritoneal dialysis incorporates a cycler that automatically provides short nocturnal dialysate exchanges and a long diurnal exchange that is cycler-free . Investigators who did an uncontrolled study cl aim ed that continuous cyclic peritoneal dialysis was superior to continuous ambulatory peritoneal dialysis [ 7 ] . Since its introduction in 1981 , substantially lower infection rates have been reported with continuous cyclic peritoneal dialysis than with continuous ambulatory peritoneal dialysis [ 7 - 12 ] . However , lower infection rates have not been found universally [ 13 - 16 ] . Moreover , continuous cyclic peritoneal dialysis has only been used with a small number of selected patients . Further , these early reports compared continuous cyclic peritoneal dialysis with conventional continuous ambulatory peritoneal dialysis , whereas the recent introduction of various Y-set ambulatory dialysis systems has result ed in a universal reduction in peritonitis rates [ 17 - 22 ] . If continuous cyclic peritoneal dialysis is at least as effective as continuous ambulatory peritoneal dialysis and if it can decrease the dropout rate from peritoneal dialysis to hemodialysis , then continuous cyclic peritoneal dialysis may offer a treatment option that does not increase overall costs because continuous cyclic peritoneal dialysis , although more costly than continuous ambulatory peritoneal dialysis , is less expensive than hemodialysis . Because no prospect i ve study has compared continuous ambulatory peritoneal dialysis with a Y-connector and continuous cyclic peritoneal dialysis , we began such a study in 1988 . Our goals were to determine the treatment outcomes of new patients with end-stage renal failure r and omly assigned to receive continuous ambulatory peritoneal dialysis with a Y-connector or continuous cyclic peritoneal dialysis . Methods Patients All new patients with end-stage renal failure entering the dialysis program of the Free University Hospital from January 1988 until August 1991 were directed to peritoneal dialysis . Patients were r and omly assigned to receive either continuous ambulatory peritoneal dialysis with a Y-connector or continuous cyclic peritoneal dialysis after stratification for age and sex . After the patients were given information about the treatment methods , the goals of the study , and the need for r and omization , a physician who was not involved in dialysis patient care and who was objective about the treatment methods being studied assigned the patients to the two treatment plans . Absolute contraindications to peritoneal dialysis ( such as previous serious abdominal inflammation with adhesions and ostomies including colostomies , ileostomies , and nephrostomies ) were the only criteria for exclusion . St and ardized training for home peritoneal dialysis ( on an outpatient basis ) usually began within 2 weeks after insertion of the peritoneal catheter . Comorbid factors at the start of dialysis were registered using a predetermined list . To determine outcome in relation to treatment , we followed patients prospect ively for these end points : blood pressure , body weight , ultrafiltration ( calculated daily from the difference between inflow and outflow volumes ) , routine laboratory assessment s , neurologic variables ( nerve conduction velocities , which were measured every 6 months ) , Karnofsky score ( a measure of patients ' performance status , using a scale from 0 [ death ] to 100 [ normal , no complaints , no evidence of disease ] ) , complications , and hospital admissions . We calculated peritoneal and residual renal clearances of urea and creatinine every 6 months by measuring these solutes in the 24-hour dialysate and urine , respectively ; as well as simultaneous serum concentrations . In addition , we estimated KT/V urea by dividing peritoneal urea clearance ( KT ) by the distribution volume of urea ( Vurea ) , as previously described [ 23 ] . We considered urea volume of distribution and total body water synonymous and calculated them from body surface area [ 24 ] . The minimum target weekly KT/Vurea measurement was 2.1 . We modified the dialysis prescription to achieve the desired KT/V by changing either the fill volume per cycle or the number of exchanges , depending on the individual peritoneal permeability characteristics . We defined exit site infection as pericatheter erythema , discharge , tenderness , or any combination of these symptoms . We based diagnosis of peritonitis on the presence of two of the following findings : abdominal signs or symptoms ; a dialysate leukocyte count 108/L , 50 % or more granulocytes in the differentiation , or both ; and presence of microorganisms using Gram stain or dialysate cultures . We defined relapse as a recurrence of cloudy effluent within 15 days after antibiotic treatment and culture of the same organism or no growth . We considered definite change in mode of dialysis as transfer to another method of dialysis for more than 1 month ; this included renal transplant . We defined hospital admission as inpatient care for any reason once patients had begun dialysis at home . All data were collected every 6 to 8 weeks from the time of catheter insertion . Follow-up was discontinued on 1 August 1992 or earlier in cases of definitive change of treatment ( including transplant ) , death , or recovery of renal function . No patients were transferred to other renal units . The Ethical and Research Committee of the Free University Hospital approved the study and all patients gave informed consent . Data Analysis Data are expressed as mean SD . We compared biochemical results for the two groups using the Wilcoxon rank-sum test . To compare changes over time between the two groups , we used analysis of variance for repeated measures . However , because the size of the study sample decreased with time as a result of patient dropout , we based the means SD as observed at the start of follow-up and at 6 , 12 , 18 , and 24 months on different subsets of patients . Therefore , we replaced observed means SD by so-called predicted means and st and ard deviations according to the method of Little and Rubin [ 25 ] . To compare duration of antibiotic therapy and hospitalization , we computed an average duration for each patient separately and compared these averages for the groups using the Wilcoxon rank-sum test . We estimated patient and technique survival curves and time to first and time to second peritonitis curves using the Kaplan-Meier method [ 26 ] . We used the generalized Wilcoxon test to compare curves of the two groups [ 27 ] . To compare average rates of peritonitis , hospital admission , and catheter removal , we computed the respective rate for each patient separately . We compared these rates for the two groups using a weighted t-test and duration s of follow-up as weights [ 28 ] . All null hypotheses were tested for two sides at the 0.05 significance level . Results Patients From January 1988 until 1 August 1991 , 98 previously untreated patients with end-stage renal failure entered our dialysis program , and 97 were r and omly assigned to two dialysis programs . One patient refused to participate because he spent winters in an area with frequent interruptions in electric service . Thus , no new patients had absolute contraindications for peritoneal dialysis . Fifty patients were allocated to receive continuous ambulatory peritoneal dialysis with a Y-connector and 47 , to receive continuous cyclic peritoneal dialysis . Before starting dialysis , seven patients who were to receive continuous ambulatory peritoneal dialysis with a Y-connector dropped out because of death ( n = 3 ) , renal transplant ( n = 1 ) , hydrothorax ( n = 1 ) , and , despite informed consent , a preference for hemodialysis ( n = 2 ) . Six patients who were to receive continuous cyclic peritoneal dialysis dropped out because of death ( n = 3 ) , renal transplant ( n = 2 ) , and inadequate housing ( n = 1 ) . Two patients receiving continuous ambulatory peritoneal dialysis with a Y-connector regained sufficient residual renal function after r and omization and did not depend on dialysis before 1 August 1992 . Thus , we scheduled 41 patients to receive continuous ambulatory peritoneal dialysis with a Y-connector and 41 patients to receive continuous cyclic peritoneal dialysis . Patient characteristics , including cause of end-stage renal failure , are listed in Table 1 . Comorbid factors present at the start of therapy ( cerebrovascular or cardiovascular disease , diabetes , dyslipidemia , chronic respiratory disorders , multisystem disease , and malignancy ) were distributed equally among the two groups . All patients receiving continuous ambulatory peritoneal dialysis used the Y set without disinfectant and performed three to five daily 2-L exchanges . Patients receiving continuous cyclic peritoneal dialysis were trained to use an automated cycler ( PAC-X , Baxter , Deerfield , Illinois ) that provided four or five nocturnal cycles and one diurnal cycle ( 2-L fill volume per cycle ) . The median duration of training was 8 days for continuous BACKGROUND The Peritoneal Dialysis- Clinical Performance Measures Project ( PD-CPM ) characterizes peritoneal dialysis within the U.S. Current survey results are reported and compared to those of previous years . METHODS Prevalence data from r and om national sample s of adult peritoneal dialysis ( PD ) patients participating in the United States End-Stage Renal Disease ( ESRD ) program have been collected annually since 1995 . RESULTS In 1995 , 79 % of the respondents used continuous ambulatory peritoneal dialysis ( CAPD ) rather than automated peritoneal dialysis ( APD ) . The mean hematocrit ( Hct ) of PD patients was 32 % and only 66 % of individuals had a measurement of dialysis adequacy reported . The mean weekly Kt/Vurea ( wKt/V ) and weekly creatinine clearance ( wCCr ) reported for CAPD patients in 1995 were 1.9 and 67 L/1.73 m2/week , respectively . In 2000 the median age of PD patients was 55 years and 63 % were white . The leading cause of ESRD was diabetes mellitus ( 34 % ) and 54 % of adult PD patients performed some form of APD rather than CAPD . Age , sex , size , hematocrit , peritoneal permeability , dialysis adequacy , residual renal function and nutritional indices did not differ between APD and CAPD patients . The mean hemoglobin ( Hb ) for the 2000 PD-CPM population was 11.6 + /- 1.4 g/dL ( mean + /- 1 SD ) and 11 % of patients had an average Hb below 10 g/dL. The average serum albumin was 3.5 + /- 0.5 g/dL by the bromcresol green method and 56 % of subjects had an average serum albumin equal to or above 3.5 g/dL ( or 3.2 g/dL by bromcresol purple ) . In 2000 85 % of patients had a dialysis adequacy measurement reported and the mean calculated wKt/V and wCCr were 2.3 + /- 0.6 and 72.7 + /- 24.9 liters/1.73 m2/week for CAPD patients and 2.3 + /- 0.6 and 71.6 + /- 25.1 L/1.73 m2/week for APD patients . PD subjects had a mean body weight of 76 + /- 19 kg and body mass index ( BMI ) of 27.5 + /- 6.4 kg/m2 . The protein equivalent of nitrogen appearance ( nPNA ) of these patients was 0.95 + /- 0.31 g/kg/day , their normalized creatinine appearance rate ( nCAR ) equaled 17 + /- 6.5 mg/kg/day , result ing in a percent lean body mass ( % LBM ) of 64 + /- 17 % of actual body weight . Serum albumin correlated in a positive fashion with BMI , nPNA , nCAR and % LBM , but not with wCCr . CONCLUSIONS The majority of indicator variables monitored by the PD-CPM have improved since 1995 . PD patients have higher hemoglobins and a greater proportion of patients meet the criteria for adequate dialysis . Serum albumin values , however , remain marginal and unchanged over the five-year project . Furthermore , serum albumin values fail to correlate with the intensity of renal replacement therapy and are not strongly correlated with alternative estimates of nutritional status Objective To determine the effect of peritoneal dialysis modalities such as nightly intermittent peritoneal dialysis ( NIPD ) , continuous cyclic peritoneal dialysis ( CCPD ) , and continuous ambulatory peritoneal dialysis ( CAPD ) on residual renal function . Design A six-month prospect i ve , nonr and omized comparison study . Setting Outpatient CAPD unit of a university hospital . Participants Eighteen end-stage renal disease patients treated by peritoneal dialysis ( 8 by NIPD , 5 by CCPD , and 5 by CAPD ) . Interventions Sample s from the total dialysate , blood , and 24hour urine collection were obtained monthly . Measurements Urea , creatinine , and beta2-microglobulin concentrations were measured . Renal and peritoneal clearances of each substance and KT/V urea were calculated . Residual renal function ( RRF ) was estimated by renal creatinine clearance ( RCcr ) . Results No significant differences in age , sex , and primary renal disease among the three groups were noted . In all groups , anemic and hypertensive states were controlled identically , and mean weekly total ( renal + peritoneal ) KT/V urea ( over 2.1/wk ) and total creatinine clearance ( over 60 L/wk/1.73 m2 ) were maintained during the whole experimental period . Starting mean RCcr was near 4.0 mL/min/1.73 m2 in all groups . Thereafter , a rapid and significant decline in RRF was demonstrated on NIPD and CCPD . The declining rates of RCcr values at 6 months after starting NIPD and CCPD were -0.29 and -0.34 mL/min/month , respectively , which were much greater than those of CAPD ( + 0.01 mL/min/month ) . Conclusion Because of a possibly characteristic progressive loss of RRF in automated peritoneal dialysis ( APD ) , strict regular assessment of RRF should be performed from the start of APD |
12,272 | 17,636,396 | HER2/neu overexpression and /or amplification was associated with greater efficacy of the anthracycline or taxane regimen .
Conclusions Current evidence supports the conclusion that the benefit of both anthracycline-based and taxane-based adjuvant chemotherapy is associated on HER2/neu status , with patients with HER2/neu-positive cancers benefiting more from these therapies than those with HER2/neu-negative cancers | Background Amplification and /or overexpression of the HER2/neu gene is associated with a poor prognosis in breast cancer .
Many studies have suggested that this gene may be associated with the relative efficacy of chemotherapy and endocrine therapy options . | BACKGROUND Amplification of the human epidermal growth factor receptor type 2 ( HER2 , also called HER2/neu ) gene and overexpression of its product in breast-cancer cells may be associated with responsiveness to anthracycline-containing chemotherapy regimens . METHODS In the r and omized , controlled Mammary.5 trial , we studied 639 formalin-fixed paraffin-embedded specimens obtained from 710 premenopausal women with node-positive breast cancer who had received either cyclophosphamide , epirubicin , and fluorouracil ( CEF ) or cyclophosphamide , methotrexate , and fluorouracil ( CMF ) as adjuvant chemotherapy . HER2 amplification or overexpression was evaluated with the use of fluorescence in situ hybridization , immunohistochemical analysis , and polymerase-chain-reaction analysis . RESULTS Amplification of HER2 was associated with a poor prognosis regardless of the type of treatment . In patients whose tumors showed amplification of HER2 , CEF was superior to CMF when assessed on the basis of relapse-free survival ( hazard ratio , 0.52 ; 95 percent confidence interval , 0.34 to 0.80 ; P=0.003 ) and overall survival ( hazard ratio , 0.65 ; 95 percent confidence interval , 0.42 to 1.02 ; P=0.06 ) . For women whose tumors lacked amplification of HER2 , CEF did not improve relapse-free survival ( hazard ratio for relapse , 0.91 ; 95 percent confidence interval , 0.71 to 1.18 ; P=0.49 ) or overall survival ( hazard ratio for death , 1.06 ; 95 percent confidence interval , 0.83 to 1.44 ; P=0.68 ) . The adjusted hazard ratio for the interaction between treatment and HER2 amplification was 1.96 for relapse-free survival ( 95 percent confidence interval , 1.15 to 3.36 ; P=0.01 ) and 2.04 for overall survival ( 95 percent confidence interval , 1.14 to 3.65 ; P=0.02 ) . CONCLUSIONS Amplification of HER2 in breast-cancer cells is associated with clinical responsiveness to anthracycline-containing chemotherapy . ( cancer.gov number , NCI-V90 - 0027 . ) BACKGROUND The use of high-dose adjuvant chemotherapy for high-risk primary breast cancer is controversial . We studied its efficacy in patients with 4 to 9 or 10 or more tumor-positive axillary lymph nodes . METHODS Patients younger than 56 years of age who had undergone surgery for breast cancer and who had no distant metastases were eligible if they had at least four tumor-positive axillary lymph nodes . Patients in the conventional-dose group received fluorouracil , epirubicin , and cyclophosphamide ( FEC ) every three weeks for five courses , followed by radiotherapy and tamoxifen . The high-dose treatment was identical , except that high-dose chemotherapy ( 6 g of cyclophosphamide per square meter of body-surface area , 480 mg of thiotepa per square meter , and 1600 mg of carboplatin per square meter ) with autologous peripheral-blood hematopoietic progenitor-cell transplantation replaced the fifth course of FEC . RESULTS Of the 885 patients , 442 were assigned to the high-dose group and 443 to the conventional-dose group . After a median follow-up of 57 months , the actuarial 5-year relapse-free survival rates were 59 percent in the conventional-dose group and 65 percent in the high-dose group ( hazard ratio for relapse in the high-dose group , 0.83 ; 95 percent confidence interval , 0.66 to 1.03 ; P=0.09 ) . In the group with 10 or more positive nodes , the relapse-free survival rates were 51 percent in the conventional-dose group and 61 percent in the high-dose group ( P=0.05 by the log-rank test ; hazard ratio for relapse , 0.71 ; 95 percent confidence interval , 0.50 to 1.00 ) . CONCLUSIONS High-dose alkylating therapy improves relapse-free survival among patients with stage II or III breast cancer and 10 or more positive axillary lymph nodes . This benefit may be confined to patients with HER-2/neu-negative tumors PURPOSE In 1992 , the Early Breast Cancer Trialists ' Collaborative Group reported that a meta- analysis of six r and omized trials in European and North American women begun from 1948 to 1972 demonstrated disease-free and overall survival benefit from adjuvant ovarian ablation . Approximately 350,000 new cases of breast cancer are diagnosed annually in premenopausal Asian women who have lower levels of estrogen than western women . PATIENTS AND METHODS From 1993 to 1999 , we recruited 709 premenopausal women with operable breast cancer ( 652 from Vietnam , 47 from China ) to a r and omized clinical trial of adjuvant oophorectomy and tamoxifen ( 20 mg orally every day ) for 5 years or observation and this combined hormonal treatment on recurrence . At later date s estrogen- and progesterone-receptor protein assays by immunohistochemistry were performed for 470 of the cases ( 66 % ) . RESULTS Treatment arms were well balanced . With a median follow-up of 3.6 years , there have been 84 events and 69 deaths in the adjuvant treatment group and 127 events and 91 deaths in the observation group , with 5-year disease-free survival rates of 75 % and 58 % ( P = .0003 unadjusted ; P = .0075 adjusted ) , and overall survival rates of 78 % and 70 % ( P = .041 unadjusted ) for the adjuvant and observation groups , respectively . Only patients with hormone receptor-positive tumors benefited from the adjuvant treatment . In Vietnam , for women unselected for hormone receptor status , a cost-effectiveness analysis suggests that this intervention costs $ 350 per year of life saved . CONCLUSION Vietnamese and Chinese women with hormone receptor-positive operable breast cancer benefit from adjuvant treatment with surgical oophorectomy and tamoxifen The aim of this study was to test the hypothesis of Goldie and Coldman that the use of non-cross-resistant regimens of chemotherapy could lead to maximal anti-tumour effect . We compared st and ard CMF ( cyclophosphamide , methotrexate , fluorouracil ) with alternating CMF/EV ( epirubicin , vincristine ) in the adjuvant therapy of early breast cancer . Stage II premenopausal node-positive or post-menopausal node-positive oestrogen receptor-negative and stage III breast cancer patients were eligible for the study . From January 1985 to December 1990 , 220 patients were r and omised ( 115 to CMF and 105 to CMF/EV ) . Toxicity was mild ; neurotoxicity , vomiting and hair loss were more frequent in the CMF/EV group , while permanent amenorrhoea , diarrhoea , stomach ache and minor infections occurred more often in the CMF arm . At a follow-up of 48 months , 113 patients ( 51.4 % ) had had recurrence ( 62 on CMF and 51 on CMF/EV ) and 54 ( 24.5 % ) had died ( 30 on CMF and 24 on CMF/EV ) . There was no significant difference in disease-free and overall survival between the two arms . After adjusting for menopausal status and stage , the relative risk ( RR ) of recurrence for CMF/EV patients was 0.93 ( 95 % CL 0.64 - 1.35 ) , while the RR of death was 0.85 ( 95 % CL 0.49 - 1.47 ) . In conclusion , the Goldie-Coldman model of alternating therapy is not confirmed in this trial of adjuvant therapy of early breast cancer , although in view of its design a difference of less than 20 % in 3 year disease-free survival could not be excluded The National Surgical Adjuvant Breast and Bowel Project ( NSABP ) implemented protocol B-15 to compare 2 months of Adriamycin ( doxorubicin ; Adria Laboratories , Columbus , OH ) and cyclophosphamide ( AC ) with 6 months of conventional cyclophosphamide , methotrexate , and fluorouracil ( CMF ) in patients with breast cancer nonresponsive to tamoxifen ( TAM , T ) . A second aim was to determine whether AC followed in 6 months by intravenous ( IV ) CMF was more effective than AC without reinduction therapy . Through 3 years of follow-up , findings from 2,194 patients indicate no significant difference in disease-free survival ( DFS , P = .5 ) , distant disease-free survival ( DDFS , P = .5 ) or survival ( S , P = .8 ) among the three groups . Since the outcome from AC and CMF was almost identical , the issue arises concerning which regimen is more appropriate for the treatment of breast cancer patients . AC seems preferable since , following total mastectomy , AC was completed on day 63 versus day 154 for conventional CMF ; patients visited health professionals three times as often for conventional CMF as for AC ; women on AC received therapy on each of 4 days versus on each of 84 days for conventional CMF ; and nausea-control medication was given for about 84 days to conventional CMF patients versus for about 12 days to patients on AC . The difference in the amount of alopecia between the two treatment groups was less than anticipated . While alopecia was almost universally observed following AC therapy , 71 % of the CMF patients also had hair loss and , in 41 % , the loss was greater than 50 % . This study and NSABP B-16 , which evaluates the worth of AC therapy in TAM-responsive patients , indicate the merit of 2 months of AC therapy for all positive-node breast cancer patients BACKGROUND Overexpression of the erbB-2 protein by breast cancer cells has been suggested to be a predictor of response to doxorubicin . A retrospective study was design ed to test this hypothesis . METHODS In National Surgical Adjuvant Breast and Bowel Project protocol B-11 , patients with axillary lymph node-positive , hormone receptor-negative breast cancer were r and omly assigned to receive either L-phenylalanine mustard plus 5-fluorouracil ( PF ) or a combination of L-phenylalanine mustard , 5-fluorouracil , and doxorubicin ( PAF ) . Tumor cell expression of erbB-2 was determined by immunohistochemistry for 638 of 682 eligible patients . Statistical analyses were performed to test for interaction between treatment and erbB-2 status ( positive versus negative ) with respect to disease-free survival ( DFS ) , survival , recurrence-free survival ( RFS ) , and distant disease-free survival ( DDFS ) . Reported P values are two-sided . RESULTS Overexpression of erbB-2 ( i.e. , positive immunohistochemical staining ) was observed in 239 ( 37.5 % ) of the 638 tumors studied . Overexpression was associated with tumor size ( P=.02 ) , lack of estrogen receptors ( P=.008 ) , and the number of positive lymph nodes ( P=.0001 ) . After a mean time on study of 13.5 years , the clinical benefit from doxorubicin ( PAF versus PF ) was statistically significant for patients with erbB-2-positive tumors -- DFS : relative risk of failure (RR)=0.60 ( 95 % confidence interval [CI]=0.44 - 0.83 ) , P=.001 ; survival : RR=0.66 ( 95 % CI=0.47 - 0.92 ) , P = .01 ; RFS : RR=0.58 ( 95 % CI=0.42 - 0.82 ) , P=.002 ; DDFS : RR=0.61 ( 95 % CI=0.44 - 0.85 ) , P=.003 . However , it was not significant for patients with erbB-2-negative tumors-DFS : RR=0.96 ( 95 % CI=0.75 - 1.23 ) , P=.74 ; survival : RR = 0.90 ( 95 % CI=0.69 - 1.19 ) , P=.47 ; RFS : RR=0.88 ( 95 % CI=0.67 - 1.16 ) , P=.37 ; DDFS : RR=1.03 ( 95 % CI=0.79 - 1.35 ) , P=.84 . Interaction between doxorubicin treatment and erbB-2 overexpression was statistically significant for DFS ( P=.02 ) and DDFS ( P=.02 ) but not for survival ( P= .15 ) or RFS ( P=.06 ) . CONCLUSIONS These data support the hypothesis of a preferential benefit from doxorubicin in patients with erbB-2-positive breast cancer PURPOSE To determine the relative efficacy of an intensive cyclophosphamide , epirubicin , and fluorouracil ( CEF ) adjuvant chemotherapy regimen compared with cyclophosphamide , methotrexate , and fluorouracil ( CMF ) in node-positive breast cancer . PATIENTS AND METHODS Premenopausal women with node-positive breast cancer were r and omly allocated to receive either cyclophosphamide 100 mg/m2 orally days 1 through 14 ; methotrexate 40 mg/m2 intravenously ( i.v . ) days 1 and 8 ; and fluorouracil 600 mg/m2 i.v . days 1 and 8 or cyclophosphomide 75 mg/m2 orally days 1 through 14 ; epirubicin 60 mg/m2 i.v . days 1 and 8 ; and fluorouracil 500 mg/m2 i.v . days 1 and 8 . Each cycle was administered monthly for 6 months . Patients administered CEF received antibiotic prophylaxis with cotrimoxazole two tablets twice a day for the duration of chemotherapy . RESULTS The median follow-up was 59 months . One hundred sixty-nine of the 359 CMF patients developed recurrence compared with 132 of the 351 CEF patients . The corresponding 5-year relapse-free survival rates were 53 % and 63 % , respectively ( P = .009 ) . One hundred seven CMF patients died compared with 85 CEF patients . The corresponding 5-year actuarial survival rates were 70 % and 77 % , respectively ( P = .03 ) . The rate of hospitalization for febrile neutropenia was 1.1 % in the CMF group compared with 8.5 % in the CEF group . There was one case of congestive heart failure in a patient who received CMF compared with none in the CEF group . Acute leukemia occurred in five patients in the CEF group . CONCLUSION The results of this trial show the superiority of CEF over CMF in terms of both disease-free and overall survival in premenopausal women with axillary node-positive breast cancer BACKGROUND We present the combined results of two trials that compared adjuvant chemotherapy with or without concurrent trastuzumab in women with surgically removed HER2-positive breast cancer . METHODS The National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide followed by paclitaxel every 3 weeks ( group 1 ) with the same regimen plus 52 weeks of trastuzumab beginning with the first dose of paclitaxel ( group 2 ) . The North Central Cancer Treatment Group trial N9831 compared three regimens : doxorubicin and cyclophosphamide followed by weekly paclitaxel ( group A ) , the same regimen followed by 52 weeks of trastuzumab after paclitaxel ( group B ) , and the same regimen plus 52 weeks of trastuzumab initiated concomitantly with paclitaxel ( group C ) . The studies were amended to include a joint analysis comparing groups 1 and A ( the control group ) with groups 2 and C ( the trastuzumab group ) . Group B was excluded because trastuzumab was not given concurrently with paclitaxel . RESULTS By March 15 , 2005 , 394 events ( recurrent , second primary cancer , or death before recurrence ) had been reported , triggering the first scheduled interim analysis . Of these , 133 were in the trastuzumab group and 261 in the control group ( hazard ratio , 0.48 ; P<0.0001 ) . This result crossed the early stopping boundary . The absolute difference in disease-free survival between the trastuzumab group and the control group was 12 percent at three years . Trastuzumab therapy was associated with a 33 percent reduction in the risk of death ( P=0.015 ) . The three-year cumulative incidence of class III or IV congestive heart failure or death from cardiac causes in the trastuzumab group was 4.1 percent in trial B-31 and 2.9 percent in trial N9831 . CONCLUSIONS Trastuzumab combined with paclitaxel after doxorubicin and cyclophosphamide improves outcomes among women with surgically removed HER2-positive breast cancer . ( Clinical Trials.gov numbers , NCT00004067 and NCT00005970 . Abstract Purpose . To evaluate the predictive value of HER-2 in a population of advanced breast cancer patients r and omly treated either with single-agent doxorubicin ( A ) or with single-agent docetaxel ( T ) . Experimental design . Patients from this study participated in a phase III clinical trial in which doxorubicin or docetaxel was administered for advanced disease . HER-2 was evaluated by IHC . In all positive cases , FISH was used to confirm the HER-2 positive status . The different cohorts of patients identified by HER-2 were examined to assess a possible relationship between HER-2 status and treatment effect . Results . Tumor sample s were available for 176 of the 326 patients entered in the clinical trial ( 54 % ) . HER-2 positivity was observed in 20 % of the study population . A statistically significant interaction was found between response rates to the study drugs and HER-2 status , with HER-2 positive patients deriving the highest benefit from the use of T ( odds ratio for HER-2 positive patients treated with T = 3.12 ( 95 % CI 1.11–8.80 ) , p= 0.03 ) . The interaction between HER-2 and response rates to A and T was also confirmed by a multivariate analysis . No statistically significant interaction was found between HER-2 and drugs efficacy evaluated in terms of time to progression and overall survival , although in the HER-2 negative cohort A was at least as effective as T in term of overall survival . Conclusions . These results suggest that in HER-2 positive breast cancer patients docetaxel might be more active than doxorubicin , while in HER-2 negative patients doxorubicin might be at least as effective as docetaxel . Although the present results can not have an impact on current practice , they allow us to formulate the hypothesis that HER-2 positive breast cancer is a heterogeneous disease with regard to sensitivity to anthracyclines and taxanes , and that this might be dependent upon other molecular markers including the p-53 and topoisomerase II alpha genes . This hypothesis is currently being tested prospect ively in two different ‘ bench to bed-side ’ clinical trials BACKGROUND We have previously reported that high expression of the erbB-2 gene ( also known as HER-2/neu and ERBB2 ) in breast cancer is associated with patient response to dose-intensive treatment with cyclophosphamide , doxorubicin ( Adriamycin ) , and 5-flurouracil ( CAF ) on the basis of short-term follow-up of 397 patients ( set A ) with axillary lymph node-positive tumors who were enrolled in Cancer and Leukemia Group B ( CALGB ) protocol 8541 . METHODS To vali date those findings , we conducted immunohistochemical analyses of erbB-2 and p53 protein expression in an additional cohort of 595 patients ( set B ) from CALGB 8541 , as well as a molecular analysis of erbB-2 gene amplification in tumors from all patients ( sets A and B ) . Marker data were compared with clinical , histologic , treatment , and outcome data . RESULTS Up date d analyses of data from set A ( median follow-up , 10.4 years ) showed an even stronger interaction between erbB-2 expression and CAF dose , by use of either immunohistochemical or molecular data . A similar interaction between erbB-2 expression and CAF dose was observed in all 992 patients , analyzed as a single group . However , for set B alone ( median follow-up , 8.2 years ) , results varied with the method of statistical analysis . By use of a proportional hazards model , the erbB-2 expression-CAF dose interaction was not significant for all patients . However , in the subgroups of patients r and omly assigned to the high- or the moderate-dose arms , significance was achieved . When patient data were adjusted for differences by use of a prognostic index ( to balance an apparent failure of r and omization in the low-dose arm ) , the erbB-2 expression-CAF dose interaction was significant in all patients from the validation set B as well . An interaction was also observed between p53 immunopositivity and CAF dose . CONCLUSIONS The hypothesis that patients whose breast tumors exhibit high erbB-2 expression benefit from dose-intensive CAF should be further vali date d before clinical implementation . Interactions between erbB-2 expression , p53 expression , and CAF dose underscore the complexities of predictive markers where multiple interactions may confound the outcome Breast cancer patients with c-erbB-2-positive tumours seem to benefit from anthracycline-based adjuvant chemotherapy . The predictive value of c-erbB-2 for taxane sensitivity is not yet clear . The purpose of this study was to assess whether c-erbB-2 expression is associated with clinical sensitivity to docetaxel ( T ) or sequential methotrexate and 5-fluorouracil ( MF ) . A total of 283 patients with metastatic breast cancer were initially enrolled in a r and omised multicentre trial comparing docetaxel with sequential MF in advanced breast cancer . Paraffin-embedded blocks of the primary tumour were available for 131 patients ( 46 % ) . c-erbB-2 status was determined by immunohistochemistry using a polyclonal antibody to the c-erbB-2 protein . C-erbB-2 expression was scored in a semi-quantitative fashion using a 0 to 3 + scale . Staining scores 2 + or greater were considered positive . Response evaluation was performed according to World Health Organization ( WHO ) recommendations . Overall 54 ( 42 % ) patients had c-erbB-2-positive tumours . There was no association between treatment outcome and c-erbB-2 overexpression . The overall response rates ( RR ) ( n=128 ) among c-erbB-2-negative and -positive patients were 35 and 44 % , respectively ( P=0.359 ) . In the MF arm ( n=62 ) , the RR was somewhat higher in the c-erbB-2 overexpressors ( 33 % versus 18 % , P=0.18 ) . In the docetaxel arm the RRs were very similar , regardless of the c-erbB-2 expression ( 53 % versus 53 % ) . While several studies have suggested a prognostic and putative predictive significance of c-erbB-2 overexpression in early breast cancer , the significance of c-erbB-2 expression as a predictive factor for response to various cytotoxic treatments in advanced breast cancer is still controversial . In this study , c-erbB-2 expression could not predict response to either MF or T. Thus , tumours over-expressing c-erbB-2 are not uniformly more sensitive to taxanes and c-erbB-2 expression can not yet be applied clinical ly as a predictive factor for response in advanced breast cancer PURPOSE The purpose of this study is to evaluate HER-2 and topoisomerase IIalpha ( topo IIalpha ) as c and i date s for predicting the activity of anthracyclines in the adjuvant treatment of breast cancer patients . EXPERIMENTAL DESIGN In this study , we evaluated HER-2 and topo IIalpha gene aberrations by fluorescence in situ hybridization in a series of 430 primary breast cancer sample s. Sample s came from node-positive breast cancer patients r and omly treated either with one of two anthracycline-based regimens [ full-dose epirubicin-cyclophosphamide ( HEC ) and moderate-dose epirubicin-cyclophosphamide ( EC ) ] or with cyclophosphamide , methotrexate , and 5-fluorouracil ( CMF ) in the context of a Phase III adjuvant therapy trial . Event-free survival comparisons were performed between the three study arms in the subgroups of HER-2-amplified and nonamplified tumors . An explorative analysis was also performed to evaluate the predictive value of topo IIalpha in the cohort of HER-2-amplified patients . RESULTS HER-2 amplification was observed in 73 of the 354 evaluable sample s ( 21 % ) , whereas topo IIalpha amplification was found in 23 of the 61 evaluable HER-2-amplified tumors ( 38 % ) . The three event-free survival comparisons were CMF versus HEC , CMF versus EC , and EC versus HEC . Hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) were as follows : ( a ) CMF versus HEC , HR = 1.42 for HER-2-amplified tumors ( 95 % CI , 0.54 - 3.76 ; P = 0.48 ) and 0.84 for HER-2-nonamplified tumors ( 95 % CI , 0.49 - 1.44 ; P = 0.53 ) ; ( b ) CMF versus EC , HR = 1.65 for HER-2-amplified tumors ( 95 % CI , 0.66 - 4.13 ; P = 0.29 ) and 0.66 for HER-2-nonamplified tumors ( 95 % CI , 0.39 - 1.10 ; P = 0.11 ) ; and ( c ) EC versus HEC , HR = 0.93 for HER-2-amplified tumors ( 95 % CI , 0.31 - 2.77 , P = 0.90 ) and 1.33 for HER-2-nonamplified tumors ( 95 % CI , 0.82 - 2.14 ; P = 0.25 ) . Observed HRs suggest that the anthracycline-based therapy could be more effective than CMF in the subgroup of HER-2-amplified patients , whereas treatments could be equally active in the HER-2-nonamplified cohort . topo IIalpha evaluation suggests that the superiority of anthracyclines over CMF in HER-2-amplified patients could be confined to the subgroup of topo IIalpha-amplified tumors . CONCLUSIONS HER-2 could have a predictive value for the activity of anthracycline-based regimens in the adjuvant therapy of breast cancer patients . The predictive value of HER-2 would most likely be related to the concomitant amplification of the topo IIalpha gene BACKGROUND We compared docetaxel plus doxorubicin and cyclophosphamide ( TAC ) with fluorouracil plus doxorubicin and cyclophosphamide ( FAC ) as adjuvant chemotherapy for operable node-positive breast cancer . METHODS We r and omly assigned 1491 women with axillary node-positive breast cancer to six cycles of treatment with either TAC or FAC as adjuvant chemotherapy after surgery . The primary end point was disease-free survival . RESULTS At a median follow-up of 55 months , the estimated rates of disease-free survival at five years were 75 percent among the 745 patients r and omly assigned to receive TAC and 68 percent among the 746 r and omly assigned to receive FAC , representing a 28 percent reduction in the risk of relapse ( P=0.001 ) in the TAC group . The estimated rates of overall survival at five years were 87 percent and 81 percent , respectively . Treatment with TAC result ed in a 30 percent reduction in the risk of death ( P=0.008 ) . The incidence of grade 3 or 4 neutropenia was 65.5 percent in the TAC group and 49.3 percent in the FAC group ( P<0.001 ) ; rates of febrile neutropenia were 24.7 percent and 2.5 percent , respectively ( P<0.001 ) . Grade 3 or 4 infections occurred in 3.9 percent of the patients who received TAC and 2.2 percent of those who received FAC ( P=0.05 ) ; no deaths occurred as a result of infection . Two patients in each group died during treatment . Congestive heart failure and acute myeloid leukemia occurred in less than 2 percent of the patients in each group . Quality -of-life scores decreased during chemotherapy but returned to baseline levels after treatment . CONCLUSIONS Adjuvant chemotherapy with TAC , as compared with FAC , significantly improves the rates of disease-free and overall survival among women with operable node-positive breast cancer PURPOSE Human epidermal growth factor receptor 2 ( HER2 ) overexpression was found to predict a good response in breast carcinoma patients treated with doxorubicin ( Adriamycin [ ADM ] ) . Evidence from our recent study indicates that node-positive patients respond to cyclophosphamide , methotrexate , and fluorouracil ( CMF ) regardless of HER2 status . We address the issue of whether therapy regimens including CMF and ADM versus CMF alone have the same therapeutic effect in patients with HER2 + and HER2- tumors in terms of relapse-free survival ( RFS ) and overall survival ( OS ) . METHODS Archival specimens of the primary tumors from 506 patients in a prospect i ve clinical trial were stained with the anti-HER2 monoclonal antibody CB11 . Originally , patients were r and omly allocated to receive either 12 courses of intravenous CMF or eight courses of the same regimen followed by four cycles of ADM . RFS and OS were analyzed by a Cox model taking into account treatment , HER2 status , and the interaction between treatment and HER2 status , adjusting for the effect of other known clinical and biopathologic factors . RESULTS Analysis of survival rates indicates a possible differential effect of treatment in the patients grouped according to HER2 status . Improved RFS and OS were observed in the HER2 + subgroup after treatment with CMF plus ADM versus CMF alone . With a median follow-up of 15 years , the hazard ratio ( HR ) for RFS was 0.83 in HER2 + tumors and 1.22 in HER2- tumors . The effect of treatment was more evident on OS in HER2 + patients ( HR = 0.61 ; CI , 0.32 to 1.16 ) than in HER2- patients ( HR = 1.26 ) . CONCLUSION Our data indicate that adding ADM to CMF might be beneficial for patients with HER2 + tumors PURPOSE The aim of the study was to evaluate the predictive value of HER2 and topoisomerase IIalpha gene ( TOP2A ) for the efficacy of epirubicin in the adjuvant setting of breast cancer patients . PATIENTS AND METHODS In the Danish Breast Cancer Cooperative Group trial 89D , 980 pre- and postmenopausal primary patients were r and omly allocated to either CMF ( cyclophosphamide , methotrexate , and fluorouracil ; n = 500 ) or CEF ( cyclophosphamide , epirubicin , and fluorouracil ; n = 480 ) times 9 , between January 1990 and November 1999 . Tumor tissue was retrospectively identified from 805 patients and was analyzed for HER2-positivity and for TOP2A-amplifications and deletions . RESULTS HER2-positivity was found in 33 % of the 805 investigated tumors and was not a predictive marker for epirubicin sensitivity . TOP2A changes were identified in 23 % of the 773 investigated tumors : 12 % had TOP2A amplifications and 11 % had TOP2A deletions . We found that patients with TOP2A amplification had an increased recurrence-free ( RFS ; hazard ratio [ HR ] , 0.43 ; 95 % CI , 0.24 to 0.78 ) and overall survival ( OS ; HR , 0.57 ; 95 % CI , 0.29 to 1.13 ) , respectively if treated with CEF compared with CMF , and that patients with TOP2A deletions had an almost identical hazard ratio ( RFS : HR , 0.63 ; 95 % CI , 0.36 to 1.11 ; OS : HR , 0.56 ; 95 % CI , 0.30 to 1.04 ) . This is in contrast to patients with a normal TOP2A genotype for whom similar outcome was observed in both treatment arms ( RFS : HR , 0.90 ; 95 % CI , 0.70 to 1.17 ; OS : HR , 0.88 ; 95 % CI , 0.66 to 1.17 ) . CONCLUSION TOP2A amplification- and possibly deletion-seems to be predictive markers for the effect of adjuvant epirubicin containing therapy in primary breast cancer , but a final conclusion has to await a confirmative study or a meta- analysis PURPOSE Vascular endothelial growth factor A ( VEGF-A ) and vascular endothelial growth factor receptor 2 ( VEGFR2 ) are often coexpressed in breast cancer , and potentially affect cellular pathways and key proteins such as the estrogen receptor ( ER ) targeted by endocrine treatment . We therefore explored the association between adjuvant tamoxifen treatment in breast cancer and expression of VEGF-A and VEGFR2 , as well as human epidermal growth factor receptor 2 ( HER2 ) , which represents a c and i date gene product involved in tamoxifen resistance . PATIENTS AND METHODS Immunohistochemical expression of tumor-specific VEGF-A , VEGFR2 , and HER2 was evaluated in tumor specimens from premenopausal breast cancer patients r and omly assigned to 2 years of tamoxifen or no treatment ( n = 564 ) , with 14 years of follow-up . Hormone receptor status was determined in 96 % of the tumors . RESULTS VEGF-A , VEGFR2 , and HER2 were assessable in 460 , 472 , and 428 of the tumors , respectively . In patients with ER-positive and VEGFR2-low tumors , adjuvant tamoxifen significantly increased recurrence-free survival ( RFS ; [ HR ] hazard ratio for RFS , 0.53 ; P = .001 ) . In contrast , tamoxifen treatment had no effect in patients with VEGFR2-high tumors ( HR for RFS , 2.44 ; P = .2 ) . When multivariate interaction analyses were used , this difference in treatment efficacy relative to VEGFR2 expression status was statistically significant for both ER-positive ( P = .04 ) plus ER-positive and progesterone receptor-positive tumors . We found no significant difference in tamoxifen treatment effects in relation to VEGF-A or HER2 status . CONCLUSION Tumor-specific expression of VEGFR2 was associated with an impaired tamoxifen effect in hormone receptor-positive premenopausal breast cancer . Tamoxifen in combination with VEGFR2 inhibitors might be a novel treatment approach for VEGFR2-expressing breast cancer , and such a treatment might restore the tamoxifen response PURPOSE To compare a full-dose epirubicin-cyclophosphamide ( HEC ) regimen with classical cyclophosphamide , methotrexate , and fluorouracil ( CMF ) therapy and with a moderate-dose epirubicin-cyclophosphamide regimen ( EC ) in the adjuvant therapy of node-positive breast cancer . PATIENTS AND METHODS Node-positive breast cancer patients who were aged 70 years or younger were r and omly allocated to one of the following treatments : CMF for six cycles ( oral cyclophosphamide ) ; EC for eight cycles ( epirubicin 60 mg/m(2 ) , cyclophosphamide 500 mg/m(2 ) ; day 1 every 3 weeks ) ; and HEC for eight cycles ( epirubicin 100 mg/m(2 ) , cyclophosphamide 830 mg/m(2 ) ; day 1 every 3 weeks ) . RESULTS Two hundred fifty-five , 267 , and 255 eligible patients were treated with CMF , EC , and HEC , respectively . Patient characteristics were well balanced among the three arms . One and three cases of congestive heart failure were reported in the EC and HEC arms , respectively . Three cases of acute myeloid leukemia were reported in the HEC arm . After 4 years of median follow-up , no statistically significant differences were observed between HEC and CMF ( event-free survival [ EFS ] : hazards ratio [ HR ] = 0.96 , 95 % confidence interval [ CI ] , 0.70 to 1.31 , P = .80 ; distant-EFS : HR = 0.97 , 95 % CI , 0.70 to 1.34 , P = .87 ; overall survival [ OS ] : HR = 0.97 , 95 % CI , 0.65 to 1.44 , P = .87 ) . HEC is more effective than EC ( EFS : HR = 0.73 , 95 % CI , 0.54 to 0.99 , P = .04 ; distant-EFS : HR = 0.75 , 95 % CI , 0.55 to 1.02 , P = .06 ; OS HR = 0.69 , 95 % CI , 0.47 to 1.00 , P = .05 ) . CONCLUSION This three-arm study does not show an advantage in favor of an adequately dosed epirubicin-based regimen over classical CMF in the adjuvant therapy of node-positive pre- and postmenopausal women with breast cancer . Moreover , this study confirms that there is a dose-response curve for epirubicin in breast cancer adjuvant therapy 572 Background : We previously reported the preliminary pathological response data of a phase III trial comparing a weekly dose-dense approach ( PET ) to a st and ard epirubicin-paclitaxel q3wk combination , in LABC pts . ( ASCO 2004 ; abstr.511 ) . In the present abstract , we report the final data on response and PFS , and a subgroup analysis according to the hormone-receptor , and HER2/neu status . METHODS Overall , 200 patients with stage IIIB disease were r and omised to receive either 12 weekly cycles of cisplatin 30 mg/m2 , epirubicin 50 mg/m2 , and paclitaxel 120 mg/m2 ( PET ) plus granulocyte-colony stimulating factor support , or 4 cycles of epirubicin 90 mg/m2 + paclitaxel 175 mg/m2 ( ET ) every 3 weeks . RESULTS Overall , a pCR in both breast and axilla occurred in 16 ( 16 % ) PET patients and in 6 ( 6 % ) ET patients ( P=0.02 ) . The higher activity of PET was evident only in ER negative ( 27.5 % vs 5.4 % ; P=0.026 ) , and in HER/neu 3 + ( 31 % vs 5 % ; P=0.037 ) tumours . The 2 arms yielded similar pCR rate in ER positive ( PET/ET=7.5%/7.1 % ) and HER/neu negative ( PET/ET=10%/6 % ) patients . At a 45 months median follow-up , 78 patients showed a progression or relapse ( PET= 32 vs ET= 46 ) . The 5-year Failure-free survival rates in PET/ET arms were : Total = 27%/21 % ; ER+= 26%/23 % ; ER- = 25%/9 % ; HER2+=.18%/11 % ; HER2- = 29%/25 % . CONCLUSIONS The PET weekly regimen is superior to ET in terms of pCR rate in LABC patients . The advantage of such an aggressive approach is limited to ER negative and HER2 positive pts . A large r and omised trial comparing weekly PET to a st and ard regimen in ER- LABC pts . , with FFS as the main end-point , is highly recommendable . No significant financial relationships to disclose Summary Purpose To assess the prognostic and predictive significance of HER-2 overexpression and high expression of VEGF in high-risk patients with breast cancer treated with dose – dense sequential chemotherapy . Patients and methods From June 1997 until November 2000 , 595 patients were r and omized to three cycles of epirubicin ( E ) 110 mg/m2 followed by three cycles of paclitaxel ( T ) 250 mg/m2 followed by three cycles of “ intensified ” CMF ( cyclophosphamide 840 mg/m2 , methotrexate 47 mg/m2 and fluorouracil 840 mg/m2 ) or to four cycles of E , followed by four cycles of CMF . HER-2 was assessed by immunohistochemistry ( IHC ) in 394 patients , and by fluorescence in situ hybridization ( FISH ) in cases scored as 2 + by IHC . VEGF was evaluated in 323 patients by IHC . Results HER-2 overexpression was detected in 123 patients ( 31 % ) and high expression of VEGF in 233 ( 72 % ) . The rate of HER-2 overexpression was significantly higher in patients with positive VEGF staining ( 35 % vs. 21 % , p=0.02 ) . Overexpression of HER-2 was significantly associated with negative hormonal status , high histologic grade and larger tumors . HER-2 overexpression was a significant negative predictor of DFS ( p=0.002 ) , but not of OS . Adjusting for HER-2 overexpression , DFS and OS did not significantly differ between treatment groups . Positive VEGF staining was not associated with receptor status , number of positive nodes , grade , tumor size , incidence of relapse or death . Conclusions For both treatments , HER-2 overexpression was a significant negative prognostic factor for DFS but not for OS , while high expression of VEGF was not significantly associated to either DFS or OS . No predictive ability of HER-2 status or VEGF overexpression for T treatment was evident 510 Background : CALGB 9344 showed 4 cycles of paclitaxel ( T ) after 4 cycles of doxorubicin/cyclophosphamide ( AC ) improved disease-free ( DFS ) and overall survival ( OS ) compared to 4 cycles of AC . Higher dose of A had no benefit ( Henderson JCO ' 03 ) . Prior studies suggest HER2 is associated with benefit from st and ard vs low dose of C&A ( Dressler JCO ' 05 ) . We hypothesized that HER2 might predict benefit from higher dose of A or from T , and that HER2 might refine the observed negative interaction of T with estrogen receptor ( ER ) . METHODS 3121 node + women in CALGB 9344 received 4 q3wk cycles of AC ( A : 60 , 75 , or 90 mg/m2 ) and then 4 cycles of T ( 175 mg/m2 q3wk ) or no T. Blocks were collected from ∼2800 subjects . 2 sets of 750 patients each were r and omly selected from these cases : Set 1 to develop hypotheses ; Set 2 for validation . Tissue specimens were available from 643 ( set1 ) and 679 ( set2 ) cases ( 20 % & 22 % total enrolled in 9344 respectively ) . HER2 was evaluated by FISH and by IHC ( by antibody cb11 and by Herceptest ) . Statistical analyses used Cox proportional hazards models , including interaction terms , and Kaplan-Meier estimates for comparing 5-yr DFS by treatment group . RESULTS In Set 1 , all 3 assays suggested that T improved DFS for HER2 + but not for HER2- . For this single set the interaction was not statistically significant . There appeared to be an interaction of HER2 , T and ER . IHC using cb11 was applied to Set 2 , revealing nearly identical results . In the two sets combined ( n=1322 ) , the interaction between HER2 and T was statistically significant ( p=0.013 ) . The 3-way interaction of HER2 , ER and T was hypothesis-generating and not tested statistically . Differences in 5-yr DFS rates ( 95 % CI ) for T vs. no T by HER2 and ER ( both sets combined ) There was no interaction between HER2 and dose of A. CONCLUSIONS These results suggest that the benefit of adding T to AC is greater for HER2 + tumors , even if ER+ , while T was of no apparent benefit in the ER+ , HER2- group . Further validation is needed from remaining cases in 9344 and from other trials involving T. [ Table : see text ] [ Table : see text ] BACKGROUND Tamoxifen , taken for five years , is the st and ard adjuvant treatment for postmenopausal women with primary , estrogen-receptor-positive breast cancer . Despite this treatment , however , some patients have a relapse . METHODS We conducted a double-blind , r and omized trial to test whether , after two to three years of tamoxifen therapy , switching to exemestane was more effective than continuing tamoxifen therapy for the remainder of the five years of treatment . The primary end point was disease-free survival . RESULTS Of the 4742 patients enrolled , 2362 were r and omly assigned to switch to exemestane , and 2380 to continue to receive tamoxifen . After a median follow-up of 30.6 months , 449 first events ( local or metastatic recurrence , contralateral breast cancer , or death ) were reported--183 in the exemestane group and 266 in the tamoxifen group . The unadjusted hazard ratio in the exemestane group as compared with the tamoxifen group was 0.68 ( 95 percent confidence interval , 0.56 to 0.82 ; P<0.001 by the log-rank test ) , representing a 32 percent reduction in risk and corresponding to an absolute benefit in terms of disease-free survival of 4.7 percent ( 95 percent confidence interval , 2.6 to 6.8 ) at three years after r and omization . Overall survival was not significantly different in the two groups , with 93 deaths occurring in the exemestane group and 106 in the tamoxifen group . Severe toxic effects of exemestane were rare . Contralateral breast cancer occurred in 20 patients in the tamoxifen group and 9 in the exemestane group ( P=0.04 ) . CONCLUSIONS Exemestane therapy after two to three years of tamoxifen therapy significantly improved disease-free survival as compared with the st and ard five years of tamoxifen treatment PURPOSE Tamoxifen ( TAM ) is increasingly administered to new early breast cancer patients . Because it is not devoid of toxic effects , we studied factors potentially predictive of its efficacy . EXPERIMENTAL DESIGN From 1978 to 1983 , 433 patients were enrolled in the GUN r and omized trial : 206 were assigned to TAM versus 227 controls ( no-TAM ) . Premenopausal patients with axillary lymph node involvement ( 60 TAM versus 65 no-TAM ) also received nine CMF cycles . Eight biological markers were retrospectively assayed for most patients : estrogen ; progesterone ; prolactin receptors ( PrlRs ) ; microvessel count ( MVC ) ; S-phase fraction ; tumor ploidy ; epidermal growth factor receptor ( EGFR ) ; and HER2 . We performed a multivariate test of the TAM/covariate interactions to establish whether these variables predicted for TAM efficacy . Estimates of the TAM effect were expressed as hazard ratio ( HR ) of death of TAM over no-TAM patients with 95 % confidence intervals ( 95 % CIs ) . RESULTS At a median follow-up of 15 years , PrlRs , MVC , S-phase fraction , ploidy , and EGFR did not influence TAM efficacy . Differently , HER2 had an overall significant predictive effect : HR = 0.59 ( 95 % CI : 0.40 - 0.87 ) in HER2-negative subjects versus HR = 1.09 ( 95 % CI : 0.63 - 1.87 ) in HER2-positive subjects ( interaction test : P = 0.04 ) . The predictive effect of HER2 was also evident in the subgroup of patients with steroid receptor-positive tumors ( HER2 positive : HR = 1.33 , 95 % CI : 0.70 - 2.51 ; HER2 negative : HR = 0.73 , 95 % CI : 0.47 - 1.14 ) . CONCLUSIONS With the statistical power of the present r and omized trial , S-phase , ploidy , EGFR , PrlR , and MVC do not seem to predict for TAM efficacy . Conversely , our data support the hypothesis that tumors overexpressing HER2 might not benefit from adjuvant TAM The aim of this study was to compare the efficacy and tolerability of docetaxel to methotrexate and 5-fluorouracil in advanced breast cancer after anthracycline failure . A r and omised multicentre trial was conducted in 283 patients with advanced breast cancer who had failed previous anthracycline treatment . Docetaxel at a dose of 100 mg/m2 every 3 weeks ( n = 143 ) was compared with sequential methotrexate and 5-fluorouracil ( MF ; n = 139 ) given at day 1 and 8 every 3 weeks at dosages of 200 mg/ m2 and 600 mg/m2 , respectively . After progression , crossover to the alternative treatment group was recommended . There was a significantly higher overall response rate in the docetaxel 42 % ( CR 8 % + PR 34 % ) than in the MF arm 21 % ( CR 3 % + PR 18 % ) ( P < 0.001 ) . The median time to progression ( TTP ) was 6.3 months in the docetaxel arm and 3.0 months in the MF arm ( P < 0.001 ) . Docetaxel also had a significantly higher response rate of 27 % following crossover compared with MF ( 12 % ) . Significantly more side-effects ( leucopenia , infections , neuropathy , oedema , asthenia , skin , nail changes , alopecia ) were seen in the docetaxel than in the MF group . However , grade 3 and 4 side-effects were infrequent with both drugs , with the exception of fatigue , alopecia and infections . Median overall survival ( OS ) including crossover phase was 10.4 months in the docetaxel and 11.1 months in the MF arm ( P = 0.79 ) . Based on the response rate and the primary endpoint of TTP , docetaxel is superior to sequential methotrexate and 5-fluorouracil in advanced breast cancer after anthracycline failure BACKGROUND A r and omized , double-blind , multicenter study was conducted to compare the anti-tumor activity of letrozole vs. tamoxifen in postmenopausal women with ER and /or PgR positive primary untreated breast cancer . PATIENTS AND METHODS Three hundred thirty-seven postmenopausal women with ER and /or PgR positive primary untreated breast cancer were r and omly assigned once daily treatment with either letrozole 2.5 mg or tamoxifen 20 mg for four months . At baseline none of the patients were considered to be c and i date s for breast-conserving surgery ( BCS ) and 14 % of the patients were considered inoperable . The primary endpoint was to compare overall objective response ( CR + PR ) determined by clinical palpation . Secondary endpoints included overall objective response on ultrasound and mammography and the number of patients who qualified for BCS . RESULTS Overall objective response rate ( clinical palpation ) was statistically significantly superior in the letrozole group , 55 % compared to tamoxifen , 36 % ( P < 0.001 ) . Secondary endpoints of ultrasound response , 35 % vs. 25 % ( P = 0.042 ) , mammographic response , 34 % vs. 16 % ( P < 0.001 ) , and BCS , 45 % vs. 35 % ( P = 0.022 ) between the letrozole and tamoxifen groups , respectively , showed letrozole to be significantly superior . Both treatments were well tolerated . CONCLUSIONS This study shows that letrozole is more effective than tamoxifen as preoperative therapy in postmenopausal patients with ER and /or PgR positive primary untreated breast cancer and is at least as well tolerated PURPOSE Expression of ErbB-1 and ErbB-2 ( epidermal growth factor receptor and HER2/neu ) in breast cancer may cause tamoxifen resistance , but not all studies concur . Additionally , the relationship between ErbB-1 and ErbB-2 expression and response to selective aromatase inhibitors is unknown . A neoadjuvant study for primary breast cancer that r and omized treatment between letrozole and tamoxifen provided a context within which these issues could be addressed prospect ively . PATIENTS AND METHODS Postmenopausal patients with estrogen- and /or progesterone receptor-positive ( ER+ and /or PgR+ ) primary breast cancer ineligible for breast-conserving surgery were r and omly assigned to 4 months of neoadjuvant letrozole 2.5 mg daily or tamoxifen 20 mg daily in a double-blinded study . Immunohistochemistry ( IHC ) for ER and PgR was conducted on pretreatment biopsies and assessed by the Allred score . ErbB-1 and ErbB-2 IHC were assessed by intensity and completeness of membranous staining according to published criteria . RESULTS For study biopsy-confirmed ER+ and /or PgR+ cases that received letrozole , 60 % responded and 48 % underwent successful breast-conserving surgery . The response to tamoxifen was inferior ( 41 % , P = .004 ) , and fewer patients underwent breast conservation ( 36 % , P = .036 ) . Differences in response rates between letrozole and tamoxifen were most marked for tumors that were positive for ErbB-1 and /or ErbB-2 and ER ( 88 % v 21 % , P = .0004 ) . CONCLUSION ER+ , ErbB-1 + , and /or ErbB-2 + primary breast cancer responded well to letrozole , but responses to tamoxifen were infrequent . This suggests that ErbB-1 and ErbB-2 signaling through ER is lig and -dependent and that the growth-promoting effects of these receptor tyrosine kinases on ER+ breast cancer can be inhibited by potent estrogen deprivation therapy The efficacy of trastuzumab for metastases coupled with the relatively poor prognosis of patients with node-positive , HER2-positive breast cancer has led to the evaluation of trastuzumab as an adjuvant therapy . A prospect i ve , r and omized , three-arm , phase III trial is being conducted by the Breast Intergroup ( N9831 ) for women with primary , operable , histologically confirmed , node-positive breast carcinoma that strongly overexpresses ( 3 + ) HER2 protein and /or displays HER2/neu gene amplification , as determined by local laboratory testing . The protocol requires confirmatory central testing of HER2 status using the HercepTest immunohistochemistry and the Vysis PathVysion fluorescence in situ hybridization ( FISH ) assays . Tumor specimens from the first 119 patients enrolled in N9831 were central ly tested ; 74 % were found to be HercepTest 3 + and 66 % were found to have HER2 gene amplification . Only six of nine ( 67 % ) of the specimens su bmi tted by local laboratories as FISH positive could be confirmed by central assays . The concordance for central HercepTest and central FISH assays was 92 % . The poor concordance ( 74 % ) between local and central testing for HER2 status has led to modifications in the eligibility criteria for N9831 BACKGROUND High-dose chemotherapy in the adjuvant treatment of breast cancer has been ab and oned by many . PATIENTS AND METHODS 885 patients with stage III primary breast cancer and four or more axillary lymph node metastases were r and omised to receive either five courses of FEC ( fluorouracil , epirubicin and cyclophosphamide ) followed by radiation therapy and tamoxifen , or the same treatment but with high-dose alkylating chemotherapy ( cyclophosphamide , thiotepa and carboplatin ) replacing the fifth course of FEC . Of these patients , 621 had HER2/neu-negative disease , as determined by immunohistochemistry and chromogenic in situ hybridisation . RESULTS At a median follow-up of 84 months , a trend for a better relapse-free survival was observed in the high-dose arm : ( hazard ratio ( HR ) 0.84 , P = 0.076 , two-sided ) . The 621 patients with HER2/neu-negative disease benefited from high-dose therapy , while patients with HER2/neu-positive disease did not ( test for interaction , P = 0.006 ) . There was a marked relapse-free survival benefit for patients with HER2/neu-negative disease ( 71.5 % versus 59.1 % , 5 years after r and omisation ; HR 0.68 , P = 0.002 ) and also a survival benefit ( 78.2 % versus 71.0 % at 5 years ; HR 0.72 , P = 0.02 ) . CONCLUSIONS The findings from this subgroup analysis provide additional evidence that HER2/neu-positive breast cancer is relatively resistant to alkylating agents . For HER2/neu-negative tumours , however , high-dose chemotherapy should remain the subject of clinical studies BACKGROUND The predictive role of HER-2 in node-positive breast cancer patients receiving CMF or an anthracycline-based adjuvant therapy remains unclear . In addition , topo-isomerase II alpha ( topo IIalpha ) , as the cellular target of anthracyclines , might have value as a predictive marker . PATIENTS AND METHODS Four hundred eighty-one archival primary tumor sample s were collected among 777 patients entered into a multicenter phase III trial comparing classical CMF with epirubicin cyclophosphamide ( HEC ) as adjuvant therapy of node-positive breast cancer . HER-2 was evaluated by immunohistochemistry ( IHC ) using different antibodies ( Abs ) . Topo IIalpha was evaluated by IHC using the Ab KiS 1 . In each subgroup of patients identified by HER-2 and topo IIalpha , adjusted hazard ratios for event-free survival ( EFS ) and the corresponding 95 % confidence intervals have been calculated for the different study comparisons . An interaction test has been performed to investigate the role of HER-2 and topo IIalpha as predictive markers . RESULTS When HER-2 was evaluated by CB-11 and 4D5 mAbs , the EFS adjusted hazard ratios ( HR ) for the main study comparison HEC vs. CMF were : HER-2 positive : 0.33 ( 95 % confidence interval ( 95 % CI ) : 0.09 1.27 , P = 0.08 ) , HER-2 negative : 1.16 ( 95 % , CI : 0.71 - 1.90 , P = 0.56 ) ; the P-value for the interaction test was 0.10 . When HER-2 was evaluated by TAB-250 + pAbl Abs , the adjusted HR for the same comparison were : HER-2 positive : 1.06 ( 95 % CI : 0.45 - 2.52 , P = 0.90 ) , HER-2 negative : 0.99 ( 95 % CI : 0.58 - 1.68 , P = 0.97 ) ; the P-value for the interaction test was 0.84 . With regard to topo IIalpha , the adjusted HR for the EFS comparison HEC vs. CMF were : topo IIalpha positive : 0.66 ( 95 % CI : 0.32 - 1.36 , P = 0.25 ) , topo IIalpha negative : 1.26 ( 95 % CI : 0.63 - 2.50 , P = 0.51 ) ; the P-value for the interaction test was 0.13 . CONCLUSIONS This study suggests that in node-positive breast cancer patients r and omly treated with CMF or an epirubicin-based regimen , the predictive value of HER-2 may vary according to the Abs used in the immunohistochemistry assay . In addition , the study supports the concept that topo IIalpha might be involved in the determination of tumor responsiveness to an anthracycline-based adjuvant therapy BACKGROUND Trastuzumab , a recombinant monoclonal antibody against HER2 , has clinical activity in advanced breast cancer that overexpresses HER2 . We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy . METHODS This international , multicenter , r and omized trial compared one or two years of trastuzumab given every three weeks with observation in patients with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy and at least four cycles of neoadjuvant or adjuvant chemotherapy . RESULTS Data were available for 1694 women r and omly assigned to two years of treatment with trastuzumab , 1694 women assigned to one year of trastuzumab , and 1693 women assigned to observation . We report here the results only of treatment with trastuzumab for one year or observation . At the first planned interim analysis ( median follow-up of one year ) , 347 events ( recurrence of breast cancer , contralateral breast cancer , second nonbreast malignant disease , or death ) were observed : 127 events in the trastuzumab group and 220 in the observation group . The unadjusted hazard ratio for an event in the trastuzumab group , as compared with the observation group , was 0.54 ( 95 percent confidence interval , 0.43 to 0.67 ; P<0.0001 by the log-rank test , crossing the interim analysis boundary ) , representing an absolute benefit in terms of disease-free survival at two years of 8.4 percentage points . Overall survival in the two groups was not significantly different ( 29 deaths with trastuzumab vs. 37 with observation ) . Severe cardiotoxicity developed in 0.5 percent of the women who were treated with trastuzumab . CONCLUSIONS One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer . ( Clinical Trials.gov number , NCT00045032 . BACKGROUND Most women with oestrogen receptor ( ER ) positive primary breast cancer receive adjuvant tamoxifen after surgery . The measurement of tumour biomarkers should allow better selection of patients for such treatment or for therapies such as aromatase inhibitors . PATIENTS AND METHODS Histopathological blocks of primary breast cancer patients who had been r and omized to receive 2-years tamoxifen or no adjuvant therapy in two mature r and omised clinical trials were retrieved . Immunohistochemical staining for ER , progesterone receptor ( PgR ) , HER2 and epidermal growth factor receptor ( EGFR ) was undertaken . The primary endpoint was relapse free survival . RESULTS 813 patients were included in the study . Benefit from tamoxifen was seen in ER-positive patients [ Relative risk ( rr ) 0.77 , ci 0.63 - 0.93 ] . ER-negative patients also showed a strong trend to benefit from tamoxifen ( rr 0.73 , ci 0.52 - 1.02 ) which was largely confined to the PgR-positive group . Amongst the ER-positive group , PgR-positive and PgR-negative patients showed similar benefit ( rr 0.81 ; ci 0.65 - 1.02 and 0.70 ; ci 0.49 - 0.99 , respectively ) . Patients positive for HER2 did not benefit significantly ( rr 1.14 ; ci 0.75 - 1.73 ) but this group was small . CONCLUSIONS Measurement of PgR status in ER-negative patients defines a group of patients that benefit from tamoxifen but would be excluded from tamoxifen therapy on the basis of ER status alone . The data are consistent with HER2 positive tumours being resistant to tamoxifen A r and omised controlled trial of tamoxifen as a single adjuvant agent after mastectomy for early breast cancer , reported on at an average follow-up of almost 2 years in 1983 , has now been followed up to a maximum of 6 years . 1285 patients aged 75 or less were entered into the trial . Premenopausal women with positive axillary nodes and postmenopausal women with both positive and negative axillary nodes were r and omised to receive either tamoxifen 10 mg twice daily for two years or to the untreated control group with systemic therapy reserved until the time of relapse . 46 % of the trial population had primary tumour specimens assayed for oestradiol receptor ( ER ) content . There has been a highly significant prolongation of the disease-free interval in the tamoxifen-treated group followed by a highly significant reduction in death rate , with 45 ( 34 % ) fewer deaths observed in the treated group than in the control group . This benefit appeared to be independent of menopausal , nodal , or ER status PURPOSE The Immediate Preoperative Anastrozole , Tamoxifen , or Combined With Tamoxifen ( IMPACT ) trial was design ed to test the hypothesis that the clinical and /or biologic effects of neoadjuvant tamoxifen compared with anastrozole and with the combination of tamoxifen and anastrozole before surgery in postmenopausal women with estrogen receptor ( ER ) -positive , invasive , nonmetastatic breast cancer might predict for outcome in the Arimidex , Tamoxifen Alone or in Combination ( ATAC ) adjuvant therapy trial . PATIENTS AND METHODS Postmenopausal women with ER-positive , invasive , nonmetastatic , and operable or locally advanced potentially operable breast cancer were r and omly assigned to neoadjuvant tamoxifen ( 20 mg daily ) , anastrozole ( 1 mg daily ) , or a combination of tamoxifen and anastrozole for 3 months . The tumor objective response ( OR ) was assessed by both caliper and ultrasound . Comparisons were also made of clinical response with ultrasound response , actual and feasible surgery with feasible surgery at baseline , OR in human epidermal growth factor receptor 2 (HER2)-positive cancers , and tolerability . RESULTS There were no significant differences in OR in the intent-to-treat population between patients receiving tamoxifen , anastrozole , or the combination . In patients who were assessed as requiring mastectomy at baseline ( n = 124 ) , 44 % of patients received breast-conserving surgery ( BCS ) after anastrozole compared with 31 % of patients after tamoxifen ( P = .23 ) ; this difference became significant for patients who were deemed feasible for BCS by their surgeon ( 46 % v 22 % , respectively ; P = .03 ) . The OR for patients with HER2-positive cancer ( n = 34 ) was 58 % for anastrozole compared with 22 % for tamoxifen ( P = .18 ) . All treatments were well tolerated . CONCLUSION Neoadjuvant anastrozole is as effective and well tolerated as tamoxifen in ER-positive operable breast cancer in postmenopausal women , but the hypothesis that clinical outcome might predict for long-term outcome in adjuvant therapy was not fulfilled We compared a relatively short regimen of monochemotherapy with epirubicin versus polychemotherapy with CMF ( cyclophosphamide , methotrexate , 5-fluorouracil ) as adjuvant treatment for stage I and II breast cancer patients . 348 patients with oestrogen receptor negative ( ER- ) node negative and ER- or ER+ node-positive with < 10 nodes were accrued . CMF was given intravenously ( i.v . ) on days 1 and 8 , every 4 weeks , for six courses ; epirubicin was given weekly for 4 months . Postmenopausal patients received tamoxifen for 3 years . The primary endpoints were overall survival ( OS ) , relapse-free survival ( RFS ) and event-free survival ( EFS ) . Outcome evaluation was performed both in eligible patients and in all r and omised patients according to the intention-to-treat principle . 8 r and omised patients were considered ineligible . At a median follow-up of 8 years , there was no difference in OS ( Hazard Ratio (HR)=1.11 , 95 % Confidence Interval ( CI ) : 0.77 - 1.61 , P=0.58 ) , EFS ( HR=1.14 , 95 % CI : 0.78 - 1.64 , P=0.48 ) , and RFS ( HR=1.14 , 95 % CI : 0.8 - 1.64 , P=0.48 ) between the two arms for all of the patients . At 8 years , the RFS percentages ( + /-St and ard Error ( S.E. ) ) were 65.4 % ( + /-4 % ) in the CMF arm and 62.7 % ( + /-4 % ) in the epirubicin arm ; for EFS these were 64.2 % ( + /-4 % ) for CMF and 60.8 % ( + /-4 % ) for epirubicin , respectively . A significant difference in RFS ( P=0.015 ) was observed in patients with 4 - 9 positive nodes in favour of the CMF arm . Toxicity in the two arms was superimposable except for more frequent grade 3 alopecia in the epirubicin-treated patients ( P=0.001 ) . Overall , at a median follow-up of 8 years , there were no differences between the two arms in terms of OS , EFS and RFS AIM We aim ed to study the importance of erbB2 status in early stage postmenopausal breast cancer for patients who participated in a trial of five vs. two years of adjuvant tamoxifen . PATIENTS AND METHODS We analysed the erbB2 status of the tumours from 577 patients participating in the trial , either by a DNA amplification assay ( n = 181 ) or by measurement of the protein level with flow cytometry ( n = 396 ) . RESULTS ErbB2 was overexpressed or gene amplified in 102 of the patients ( 18 % ) . Overall , erbB2-positive patients had a significantly lower recurrence-free probability than others , 62 % at five years as compared to 83 % , and showed a significantly decreased breast cancer survival rate ( P = 0.0007 ) . ErbB2 status was significantly associated with recurrence and death in Cox multivariate analysis , adjusting for nodal status , tumour size and estrogen receptor status . The relative risk of recurrence ( RR ) for five vs. two years of tamoxifen was analysed in relation to erbB2 status for patients still disease-free two years after surgery . Whereas erbB2-negative patients showed significant benefit from prolonged treatment ( RR = 0.62 , 95 % confidence interval ( 95 % CI ) : 0.42 - 0.93 ) , no benefit was evident for erbB2-positive patients ( RR = 1.1 , 95 % CI : 0.41 - 3.2 ) . When the same analysis was restricted to ER-positive patients a similar difference in relative hazard was obtained but the difference was not strictly significant ( P = 0.065 ) . CONCLUSIONS For early stage breast cancer patients treated with adjuvant tamoxifen , overexpression of erbB2 is an independent marker of poor prognosis . The results suggest that overexpression decreases the benefit from prolonged tamoxifen treatment PURPOSE Studies evaluating the relationship of HER-2/neu breast tumor status and response to adjuvant endocrine therapy have reached conflicting conclusions about resistance of HER-2/neu-positive tumors to this treatment . We studied 282 patients participating in a r and omized controlled trial of adjuvant oophorectomy and tamoxifen or observation who had estrogen receptor-positive tumors and whose tumors were evaluated for HER-2/neu overexpression by immunohistochemistry . PATIENTS AND METHODS Univariate and multivariate Cox proportional hazards regression models and Kaplan-Meier disease-free and overall survival estimate methods were used . RESULTS HER-2/neu overexpression was a negative prognostic factor for overall survival . In univariate analyses , in HER-2/neu-positive patients , the hazard ratio ( HR ) for disease-free survival ( DFS ) with adjuvant endocrine therapy was 0.37 ( 95 % confidence interval [ CI ] , 0.26 to 0.89 ) ; for HER-2/neu-negative patients , the corresponding HR for DFS was 0.48 ( 95 % CI , 0.31 to 0.71 ) . The overall survival ( OS ) data were HR=0.26 ( 95 % CI , 0.07 to 0.92 ) and HR=0.68 ( 95 % CI , 0.32 to 1.42 ) for HER-2/neu-positive and HER-2/neu-negative patients , respectively . In multivariate models , the P values for tests of interaction of HER-2/neu status and response to adjuvant endocrine therapy were 0.18 and 0.07 for DFS and OS , respectively . Kaplan-Meier DFS and OS curves and 3-year DFS estimates were consistent in showing greater benefit to the HER-2/neu-positive subgroup given adjuvant treatment . CONCLUSION HER-2/neu overexpression does not adversely and may favorably influence response to adjuvant oophorectomy and tamoxifen treatment in patients with estrogen receptor-positive tumors PURPOSE To determine the effect of elevated serum HER-2/neu on the response of metastatic breast cancer patients to an aromatase inhibitor versus an antiestrogen . PATIENTS AND METHODS Five hundred sixty-two estrogen receptor-positive metastatic breast cancer patients were r and omized to first-line hormone therapy with either letrozole or tamoxifen . An automated enzyme-linked immunosorbent assay was used to detect serum HER-2/neu . RESULTS For patients with normal serum HER-2/neu ( 70.5 % ) , objective response rate ( ORR ; 39 % in letrozole-treated patients v 26 % in tamoxifen-treated patients ; P = .008 ) , clinical benefit ( CB ; 57 % v 45 % ; P = .016 ) , time to progression ( TTP ; median , 12.2 v 8.5 months ; P = .0019 ) , and time to treatment failure ( TTF ; median , 11.6 v 6.2 months ; P = .0066 ) were significantly better in patients treated with letrozole . In the elevated HER-2/neu group ( 29.5 % ) , there was no significant difference in ORR ( 17 % in letrozole-treated patients v 13 % in tamoxifen-treated patients ; P = .45 ) or CB ( 33 % v 26 % ; P = .31 ) , but there was a strong trend in favor of a longer TTP with letrozole ( median , 6.1 v 3.3 months ; P = .0596 ) and a significantly longer TTF with letrozole ( median , 6.0 v 3.2 months ; P = .0418 ) . Multivariate analysis revealed that elevated serum HER-2/neu was a negative predictor for ORR and TTP . CONCLUSION Patients with normal serum HER-2/neu receiving letrozole demonstrated a significantly greater ORR and CB and longer TTP and TTF than patients receiving tamoxifen . Although in patients with elevated serum HER-2/neu there was no significant difference between letrozole and tamoxifen in ORR or CB , there was a strong trend favoring longer TTP and significantly longer TTF with letrozole Despite numerous reports of findings obtained following the use of doxorubicin ( Adriamycin [ A ] ; Adria Laboratories , Columbus , OH ) for the postoperative treatment of patients with primary breast cancer and positive axillary nodes , no clear consensus exists regarding its worth when used in that setting . In June 1981 , the National Surgical Adjuvant Breast and Bowel Project ( NSABP ) implemented two r and omized clinical trials aim ed at evaluating the worth of doxorubicin when administered in conjunction with melphalan ( L-PAM ) and fluorouracil ( 5-FU ) ( PF ) . A prior NSABP study identified cohorts of patients who did or did not benefit from tamoxifen ( TAM , T ) when used with chemotherapy . That information was employed in the design of the present studies . Women considered responsive to TAM ( 1,106 ) were r and omized between PFT and PAFT , and those nonresponsive to TAM ( 707 ) were r and omized between PF and PAF . Findings through 6 years of follow-up ( mean duration of potential time on study , 64 months and 63 months , respectively ) indicate that non-TAM-responsive patients who received PAF had a significantly better disease-free survival ( DFS ) ( P = .003 ) and survival ( P = .05 ) than did those receiving PF . By contrast , there was no significant difference in DFS ( P = .6 ) or survival ( P = .7 ) between PFT- and PAFT-treated patients . No disparity in the amount of drug received , whether related to the median amount or to dose-intensity , is present to account for the difference in findings between the studies . Aside from alopecia and emesis , the toxicity from the doxorubicin-containing regimens was similar to those in which doxorubicin was omitted . Cardiomyopathy was not a significant finding ; there were no deaths from cardiac toxicity . The incidence of arterial and venous complications in patients receiving TAM was less than reported by others PURPOSE Few studies have examined the possible importance of biologic prognostic factors in breast cancer connected with differentiation and growth in predicting response to a specific adjuvant treatment . HER2 , epidermal growth factor receptor ( EGFR ) , and p53 have all been suggested as possible markers of tamoxifen resistance . The aim of this study was to investigate interactions between adjuvant treatment with tamoxifen and the content of EGFR , HER2 , and p53 in steroid receptor-positive patients . PATIENTS AND METHODS A total of 1,716 high-risk postmenopausal breast cancer patients were r and omly assigned to treatment with tamoxifen ( 868 women ) or to observation ( 848 women ) in a prospect i ve trial ( Danish Breast Cancer Cooperative Group 's 77c protocol ) . The content of the steroid receptors and expression of p53 , EGFR , and HER2 were determined by immunohistochemical analysis of paraffin-embedded tissue . The length of follow-up was 10 years . The end point for this analysis was disease-free survival . RESULTS Multivariate analysis demonstrated no increased risk of recurrence after treatment with tamoxifen for HER2- , EGFR- , and p53-positive , high-risk , steroid receptor-positive patients . Patients with steroid receptor-positive tumors and positive immunohistochemical staining for HER2 , EGFR or p53 benefited from treatment with tamoxifen for 1 year , although the latter variable contained independent prognostic information by itself . CONCLUSION With the statistical power of the present r and omized study , we did not find support for the hypothesis that HER2/EGFR or p53 status predicts benefit from tamoxifen treatment in estrogen receptor-positive patients with early-stage breast cancer . Thus , neither HER2 , EGFR , nor p53 overexpression/accumulation should be used as a contraindication for giving tamoxifen The role of high-dose chemotherapy in the adjuvant treatment of high-dose breast cancer has not been established . Results have been reported from six r and omized studies with a symmetrical study design ( Table (Table1).1 ) . All show a lower relapse rate in the high-dose arm , but in only one study was this result statistically significant . Table 1 R and omized studies evaluating the role of high-dose chemotherapy in high-risk breast cancer Methods Patients below 56 years of age who had undergone surgery for stage II or III breast cancer were eligible if they had at least four tumor-positive axillary lymph nodes . Patients in the conventional dose ( CD ) arm received five courses of FEC ( fluorouracil 500 mg/m2 , epirubicin 90 mg/m2 and cyclophosphamide 500 mg/m2 ; every 3 weeks ) followed by radiation therapy and tamoxifen . The high-dose ( HD ) arm was identical , except that high-dose chemotherapy ( CTC [ cyclophosphamide 6 g/m2 , thiotepa 480 mg/m2 and carboplatin 1600 mg/m2 ] ) with peripheral blood progenitor cell reinfusion was given instead of the fifth FEC course |
12,273 | 16,856,105 | The combination of antipsychotics and antidepressants may be effective in treating negative symptoms of schizophrenia , but the amount of information is currently too limited to allow any firm conclusions . | BACKGROUND Negative symptoms are common in people with schizophrenia and are often difficult to treat with antipsychotic drugs .
Treatment often involves the use of various add-on medications such as antidepressants .
OBJECTIVES To review the effects of the combination of antipsychotic and antidepressant drug treatment for management of negative symptoms in schizophrenia and schizophrenia-like psychoses . | 19.552 R.P. is 2-Dimethylsulphamoyl-10 - 3(4(2-palmitoyloxyethyl ) piperidino-(1 ) ) propyl phenothiazine . It is the palmitic ester of 19.366 R.P. with rhe proposed generic name of pipotiazine . The substances were developed by the Rh6ne-Poulenc laboratories . Pipotiazine has neuroleptic properties , pharmacological studies and clinical trials indicating an effect in many ways resembling that of thioproperazine . The palmitic ester was developed in a search for a suitable depot preparation with a long duration of action . Pilot trials indicated a potent neuroleptic effect and marked depot properties . The pilot trials suggested that it might be sufficient to give injections of 19.552 R.P. at intervals of 4 weeks . A depot preparation with such a duration of action would have important advantages in the long-term treatment of chronic psychoses . I t could provide a very suitable pivot around which the necessary after-care of discharged patients could be organized , and in the hospital it could represent an effective and convenient way of administering the necessary neuroleptic treatment . With this background it w-as decided to try 19.552 R.P. in Opd01 Sykehus , a regional mental hospital in Norway . The trial aim ed to answer the following questions 1 . Twenty-one schizophrenic or schizoaffective patients with histories of cannabis abuse and operationally-defined syndromes of post-psychotic depression completed a double-blind trial of adjunctive imipramine added to their on-going medication regimen of fluphenazine decanoate and benztropine . 2 . The imipramine-treated patients had superior global outcome . 3 . Subscales suggested that specific improvement occurred in imipramine-treated patients in the domain of depression-like features . 4 . Psychotic symptomatology was not found to be exacerbated by the imipramine Undertaken in the context of a controlled drug trial involving newly admitted psychiatric hospital patients , this study compared the effectiveness of a " Doctor 's Choice " ( DC ) method of administering psychotropic drugs versus an experimentally determined treatment regimen employing r and om assignment and double-bline procedures . The 32-day drug trial sought to determine the comparative effectiveness of thioridazine-placebo , thioridazine-chlordiazepoxide , and thioridazine-imipramine , with the daily dosage of openly administered thioridazine ranging from 100 to 900 mg and dosages for chlordiazepoxide and imipramine , administered in a double-blind fashion , fixed at daily dosages of 30 and 75 mg , respectively . DC medication , consisting of a choice ( by a research physician ) of any of the three experimental medications determined on the basis of judged clinical need , was added as a fourth treatment category for present purpose s. Criteria of effectiveness included st and arized psychiatric rating scales and global measures of imporvement completed by research team members and ward physicians . Outcome results for the DC group compared to those for a single control group made up of individuals matched with DC patients on the basis of drug assignment indicated an essentially similar clinical effectiveness under both DC and control treatment conditions . Generalization of the finding was limited by the fact that the main treatment effect , attributable to thioridazine , overshadowed the more subtle action of the ancillary drugs Two drug trials in schizoaffective patients are reported . Nineteen " schizomanic " patients were treated for one month , on a double blind basis , with chlorpromazine or lithium and 41 " schizodepressive " patients with amitriptyline , chlorpromazine or both . In the schizodepressive patients there was a trend to a better response to chlorpromazine , but drug response generally was poor , only 20 per cent of patients recovering within the month . In the schizomanic patients lithium seemed as effective as chlorpromazine , which supports the view that these patients were suffering from a variant of mania BACKGROUND Schizophrenic patients have high rates of cigarette smoking compared with the general population . We compared sustained-release ( SR ) bupropion with placebo for smoking cessation in patients with schizophrenic disorders . We also examined how antipsychotic class predicts smoking cessation outcomes with bupropion . METHODS Thirty-two subjects meeting DSM-IV criteria for schizophrenia or schizoaffective disorder and nicotine dependence were r and omized to bupropion SR ( BUP , 300 mg/day ) or placebo ( PLA ) . Outcomes included treatment retention , smoking abstinence rates , expired breath carbon monoxide ( CO ) levels , psychotic symptoms , and medication side effects . RESULTS Bupropion significantly increased trial endpoint 7-day point prevalence smoking abstinence rates compared with placebo [ BUP , 8/16 ( 50.0 % ) , PLA , 2/16 ( 12.5 % ) ; chi(2 ) = 5.24 , df = 1 , p < .05 ] , and reduced CO levels during the trial [ Medication x Time interaction ; Z = 3.09 , p < .01 ] . Positive schizophrenia symptoms were not altered by BUP , but negative symptoms were significantly reduced . Atypical antipsychotic drug treatment enhanced smoking cessation responses to BUP . Major side effects were dry mouth , gastrointestinal symptoms , headache , and insomnia . CONCLUSIONS Our results suggest that 1 ) BUP enhances smoking abstinence rates compared with PLA in nicotine-dependent schizophrenic smokers ; 2 ) BUP is well-tolerated and safe for use in these patients ; and 3 ) atypical antipsychotics may enhance smoking cessation outcomes with BUP The relative efficacy of 4 tranquilizers was investigated in 66 chronic schizophrenics who had been hospitalized for 10.01 years ( mean ) . The role of adding an anti-depressant was also studied . Following a 4 week placebo period , high dosage tranquilizers were given for 16 weeks and amitriptyline was added for the following 16 weeks . Statistical analyses of the various change measures revealed that patients worsened significantly on placebo , all 4 tranquilizers were significantly better than placebo for symptom reduction and maximum improvement was attained within 16 weeks of tranquilizer administration . No significant differences in efficacy were observed among the 4 tranquilizers and addition of amitriptyline did not confer any additional therapeutic advantage The negative symptoms of schizophrenia remain a major clinical challenge . Reboxetine is an antidepressant whose major mechanism of action is as a noradrenergic reuptake inhibitor . This study was a 6-week r and omized placebo-controlled trial of reboxetine or placebo add on to haloperidol 5 mg in the treatment of 30 patients with DSM-IV schizophrenia . The trial failed to demonstrate any significant difference between the placebo and reboxetine groups on any of the outcome measures . This trial does not suggest that increased noradreneregic drive mediated by reuptake inhibition in patients taking dopamine antagonists is of therapeutic value in schizophrenia The beneficial effect of atypical antipsychotic drugs ( APDs ) in treatment-resistant schizophrenia patients has been attributed , mostly , to their relatively high serotonergic (5-HT)2 to dopaminergic (D)2 receptor blockade ratio . We hypothesized that a combination of typical APDs ( D2 antagonists ) and mianserin , a potent 5-HT2 antagonist , might also exert superior efficacy in this population . Eighteen in patients with treatment-resistant schizophrenia who had an acute psychotic exacerbation of the disorder received , in a double-blind design , 30 mg/day mianserin ( n = 9 ) or placebo ( n = 9 ) in conjunction with typical neuroleptics [ haloperidol ( n = 9 ) or perphenazine ( n = 9 ) ] . Clinical status was evaluated before , during , and at the end of 6 weeks of combined treatment with the Brief Psychiatric Rating Scale ( BPRS ) , Scale for the Assessment of Positive Symptoms ( SAPS ) , Scale for the Assessment of Negative Symptoms and Hamilton Rating Scale for Depression . The typical APD/mianserin group exhibited significantly greater improvement in total BPRS scores ( 17.6 % versus 5.5%;P = 0.03 ) and a trend towards greater improvement in SAPS scores ( 35.3 % versus 13.0%;P = 0.07 ) . Our study indicates that patients with chronic treatment-resistant schizophrenia who have an acute psychotic exacerbation ( ‘ acute-on-chronic ’ ) may benefit from the addition of a potent 5-HT2 blocker , such as mianserin , to typical antipsychotics . Our findings may further emphasize the contribution of enhanced 5-HT2 blockade to the ‘ atypicality ’ of the atypical APDs and to their greater efficacy in alleviating symptoms of chronic treatment-resistant schizophrenia & NA ; The efficacy and safety of adding fluvoxamine to antipsychotic treatment in schizophrenic patients with mixed positive and negative symptoms was examined . Fifty‐three patients selected for persistent negative and positive symptoms who were receiving antipsychotic treatment were r and omly allocated to additional fluvoxamine ( 50‐100 mg / day ) or placebo in a double‐blind manner . Fluvoxamine was associated with significant improvement in negative symptoms ( Scale for the Assessment of Negative Symptoms ) compared to placebo . The combination was well tolerated . Fluvoxamine augmentation of antipsychotics is safe in chronic schizophrenic patients with mixed positive and negative symptoms and may ameliorate negative symptoms in such patients Following a 2-week placebo lead-in , schizophrenic patients were r and omly assigned to fluoxetine 20 mg/day or placebo added to depot neuroleptic for a 6-week , double blind trial . All patients had received a stable dose of depot neuroleptic for at least 6 months and did not meet criteria for depression . Serum sample s were obtained at baseline and at weeks 4 and 6 . Scores on the negative symptom subscale of the Brief Psychiatric Rating Scale ( BPRS ) were significantly lower at week 6 , controlling for baseline scores , in patients receiving fluoxetine ( n=20 ) compared to patients receiving placebo ( n=21 ) . Measures of psychosis , depression , global functioning and extrapyramidal symptoms ( EPS ) did not differ between groups at week 6 . Fluoxetine administration was associated with a mean 65 % increase in serum fluphenazine concentrations in 15 patients and a mean 20 % increase in serum haloperidol concentrations in three patients . The change in negative symptoms at week 6 did not correlate with serum concentrations of fluoxetine or norfluoxetine , but did inversely correlate withS-norfluoxetine , an active stereoisomer of fluoxetine . For these chronically ill patients , fluoxetine significantly improved negative symptoms and did not worsen EPS , despite causing substantial elevation in serum concentrations of neuroleptics Four patients with chronic schizophrenia were treated with a combination of fluvoxamine , haloperidol , and benztropine . The combination significantly impaired performance on tests of delayed recall memory and attentional function . Haloperidol concentrations in serum were monitored in three patients and were robustly elevated by fluvoxamine Forty-six schizophrenic or schizoaffective patients with operationally defined episodes of postpsychotic depression were assessed for previous histories of substance abuse . Thirty-five percent had histories of previous cannabis ( marijuana ) abuse . Additionally , 13 % had also abused cocaine , 13 % amphetamines , 11 % hallucinogens , 4 % sedatives , and 2 % opiates . Patients with histories of substance abuse were younger and showed higher index ratings on a subscale of endogenous depressive features . These findings are considered in the context of a possible self-medication hypothesis of substance abuse . A history of substance abuse did not appear to be a contraindication to a therapeutic trial of adjunctive imipramine ( Ciba Geigy Corp. , Summit , NJ ) for postpsychotic depression Eighty-seven predominantly withdrawn chronic male schizophrenics were r and omly assigned to one of three treatment groups . After a two-week course of placebo administration treatment was started with matching tablets containing either amitriptyline 25 mg.+perphenazine 4 mg . , perphenazine 4 mg . , or placebo . For the first five weeks of the trial the dose was one tablet t.i.d . , and for the second five weeks , 2 tablets t.i.d . Neither the nursing staff nor the doctors concerned knew which tablets were which . Wing Scale Form A ( completed by two psychiatrists independently ) and Form B ( filled in by a senior nurse ) yielded very similar results , rating the effectiveness of the three treatments as amitriptyline/perphenazine > perphenazine > Analysis of variance of overall improvement and of individual symptoms revealed that differences between doctors ' assessment s were insignificant . Patients taking amitriptyline/perphenazine showed a significant weight gain . Regular blood examination revealed no abnormalities . The withdrawn , inert hospitalized male schizophrenic constitutes a difficult problem to many workers in the psychiatric field . The encouraging fact emerged from this clinical trial that symptoms such as flattening and incongruity of affect , sometimes made worse by long-term administration of tranquilizing drugs , could effectively be relieved , bringing a hope that rehabilitation may perhaps be possible in some seemingly hopeless cases 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 In a double-blind placebo , controlled clinical study , lasting 12 weeks , 48 male and 48 female ambulatory schizophrenic patients were r and omly assigned to one of four treatments : placebo ; amitriptyline hydrochloride , 125 mg/day ; perphenazine , 20 mg/day ; or amitriptyline-perphenazine , 20 mg/day . Treatment groups contained an equal number of male and female patients . Perphenazine alone or in combination was substantially more effective in reducing psychopathological disorder than was the placebo , but there was no evidence to indicate the superiority of the amitriptyline-perphenazine combination over perphenazine alone . Amitriptyline alone was not substantially better than placebo and could not be considered an efficacious medication for the maintenance treatment of these patients . Less response to treatment was made by patients with longer-term records of prior hospitalization OBJECTIVE Since olanzapine-induced weight gain may be attributable to the antagonistic activity of olanzapine at the serotonin-2C receptor , the authors hypothesized that it might be attenuated by addition of the selective serotonin reuptake inhibitor fluoxetine . METHOD First-episode hospitalized schizophrenia patients ( N=30 ) were r and omly assigned in an 8-week double-blind study of olanzapine , 10 mg/day , coadministered with either fluoxetine , 20 mg/day ( N=15 ) , or placebo ( N=15 ) . RESULTS The group receiving olanzapine plus fluoxetine showed significantly less improvement in positive and disorganized symptom dimensions than the group receiving olanzapine plus placebo . The two groups demonstrated similar and substantial gradual weight gains . CONCLUSIONS These results suggest that fluoxetine coadministration is clinical ly ineffective and can not attenuate olanzapine-induced weight gain The effectiveness of selective serotonin reuptake inhibitors for depression in remitted schizophrenia has not been clearly demonstrated . A r and omized , double-blind , prospect i ve placebo-controlled study was performed of 48 subjects meeting DSM-IV criteria for both schizophrenia in remission and for a major depressive episode . Twenty-seven patients were r and omized to placebo and 21 to sertraline . All subjects had a 1-week anticholinergic phase before r and omization . The treatment duration was 6 weeks . Sertraline was started at 50 mg/day ; this could be increased to 100 mg after 4 weeks for an inadequate response . There were no statistically significant differences in symptoms between the two groups at r and omization . There were no differences in outcome between treatment groups . In both groups , between 40 % and 50 % of subjects showed a 50 % reduction in depression score . This study does not provide support for the efficacy of sertraline in the treatment of depression in remitted schizophrenia . The small sample size limits the strength of the conclusions that can be drawn from this study . The study design called for a sample size of 96 on the basis of an expected placebo response rate of 30 % . Recruitment for the study was difficult because of the placebo design . The placebo response was 50 % . Clinicians and patients underestimate the strength of the placebo response and may overestimate the risk of participating in such a study . Testing the efficacy of widely accepted but poorly evaluated treatments should be a research priority . Future studies require a larger sample size and longer duration of treatment The purpose of this study was to investigate the effect of adding sustained-release ( SR ) bupropion to cognitive behavioral therapy ( CBT ) on smoking behavior and stability of psychiatric symptoms in patients with schizophrenia . We conducted a 3-month , double-blind , placebo-controlled trial of bupropion SR , 150 mg/day , added to a concurrent CBT program with 3-month follow-up in 19 stable out patients with schizophrenia who wanted to quit smoking . Eighteen subjects completed the trial . Bupropion treatment was associated with significantly greater reduction in smoking , as measured by self-report verified by expired-air carbon monoxide ( 6/9 subjects , 66 % ) , than placebo ( 1/9 subjects , 11 % ) during the 3-month active treatment period and the 3-month follow-up period . One subject in the bupropion group ( 11 % ) and no subjects in the placebo group achieved sustained tobacco abstinence for the 6-month trial . Bupropion treatment was associated with improvement in negative symptoms and greater stability of psychotic and depressive symptoms , compared with placebo , during the quit attempt . Subjects in the bupropion group experienced significant weight loss , compared with those on placebo during the smoking cessation attempt . These data suggest that bupropion SR , 150 mg/day , combined with CBT , may facilitate smoking reduction in patients with schizophrenia while stabilizing psychiatric symptoms during a quit attempt Despite the availability of atypical antipsychotics , the treatment of negative symptoms in schizophrenia remains a challenge . This study was design ed to confirm the positive effect observed in our pilot study with paroxetine as augmentation to antipsychotics in the treatment of negative symptoms in chronic schizophrenia . Twenty-nine patients with chronic schizophrenia , as defined by DSM-IV , who scored at least 20 points on the negative subscale of the Positive and Negative Syndrome Scale ( PANSS ) were r and omized for treatment with 30 mg paroxetine or placebo in a double-blind , placebo-controlled study for 12 weeks . Ratings included the PANSS , the Hamilton Rating Scale for Depression ( HAM-D ) and scales for extrapyramidal side-effects . An intention-to-treat analysis was based on the 25 patients who were available for at least one follow-up assessment . The last observation carried forward principle was applied . The mean score of the negative subscale of the PANSS decreased in both groups . Using an analysis of covariance , there was a significant treatment effect with paroxetine compared to placebo with respect to negative symptoms ( –4.53 ; 95 % confidence interval −9.054 to −0.015 ) . The mean HAM-D scores remained almost constant . The study suggests the efficacy of paroxetine with respect to the treatment of negative symptoms in chronic schizophrenia THE DEVELOPMENT of effective Psychopharmacological agents confronted the psychiatric profession with the inadequacy of its diagnostic system for the provision of rational indications and contraindications for drug therapy . Within each st and ard diagnostic group there are wide variations in drug-induced behavioral reactions . Therefore , clinical treatment with psychotropic agents has been governed by rule of thumb modified by trial and error . This paper will emphasize the utility of psychiatric diagnosis when appropriately modified for prediction of treatment outcome . The issue of the prediction of drug effect is one of considerable practical and theoretical importance . It is difficult to arrive at generally valid conclusions predictive of drug effect from clinical empiricism because of spontaneous remissions , uncontrolled fluctuations of life circumstance , and the meager abilities of many psychiatric patients to describe objective ly their level of cognitive , affective , and social functioning . Most systematic attempts to predict As an expansion of work examining the usefulness of adjunctive imipramine added to fluphenazine decanoate and benztropine in the treatment of post-psychotic depression , a previously successful and informative protocol was extended to a larger and more heterogeneous cohort of clinic and day-treatment patients . Although the benefit of the adjunctive antidepressant strategy was still observable in the total sample , as calculated by the prospect ively intended data analysis , the findings were weaker than those obtained for the initial cohort . Owing to the possibility that differences between the later and earlier cohorts might account for the muted nature of the benefit , a post-hoc analysis was undertaken . This revealed that the later cohort was sicker in general and more psychotic in particular . The later cohort was also treated with lower doses of neuroleptic medication while remaining out of hospital longer , consistent with more recent treatment trends . It was also possible that the later cohort was subtly selected for more refractoriness of depression , since treatment of post-psychotic depression with adjunctive antidepressants had become more commonplace , and patients responding to this in general practice would not have gone on to be referred to the study . Thus a benefit from adjunctive antidepressant medication persists , but more remains to be learned about its character and likelihood in specific situations Summary It is proposed that the increased dopamine function suggested by the dopamine hypothesis of schizophrenia is a dopaminergic postsynaptic receptor supersensitivity result ing from a dopamine deficiency . In support of this , three double-blind controlled studies conducted on drugs which alter brain dopaminergic activity in a manner different from that of classic neuroleptics are reported . 1 ) α-methyldopa-neuroleptic interaction proved efficacious for schizophrenic positive symptoms but only on a short-term basis . 2 ) Rubidium improved negative symptoms rapidly , and in contrast has a late onset of action on positive symptoms of schizophrenia . 3 ) Tryptophan-benserazide was efficacious in controlling both negative and positive symptoms of schizophrenia ( although less so than chlorpromazine ) . It is concluded that currently accepted modes of pharmacological therapy ( classical neuroleptics ) are in the short-term controlling the dopamine supersensitivity secondary to a deficiency , but contributing in the long-term to increase the dopamine deficiency , and so exacerbate the supersensitivity . More effective forms of treatment may involve the use of agents which alter dopamine activity without inducing dopamine supersensitivity The objective of the present study was to evaluate the efficacy of mianserin and trazodone as antidepressants wish serotonin 2 antagonist properties on negative symptoms and tardive dyskinesia in elderly patients with chronic schizophrenia . In this double-blind , placebo-controlled study the dose of each drug was increased gradually , from,20 mg/day mianserin to 60 nig/day , and from 50 mg/day trazodone to 200 mg/day . Symptoms were assessed using ( he Brief Psychiatric Rating Scale , the Scale for Assessment of Negative Symptoms and the Abnormal Involuntary Movement Scale even week for 5 weeks . A total of Mi patients ( 23 men and IS women ) completed the trial . Mianserin ( n = 13 ) and trazodone ( n= 12 ) did not alter the Brief Psychiatric Rating Scale positive symptom factor oven the 5 weeks . In the mianserin group , the Scale for Assessment of Negative Symptom'- ; total score decreased significantly after 5 weeks . Scores of ‘ affective flattening and blunting ’ and ‘ alogia ’ scores on the Scale for Assessment of Negative Symptoms decreased significantly in both treatment groups . In the trazodone group , the decrease in the Abnormal involuntary Movement Scale total score was statistically significant at weeks 2 and 3 , Results indicate that serotonergic antidepressants , when used in conjunction with neuroleptics . are safe and effective for treating negative symptoms in elderly patients with chronic schizophrenia . Results also indicated a possible beneficial effect of trazodone in treating tardive dyskinesia Summary Analyses of clinical drug effects have largely been derived from univariate rating scale or global improvement scale data . In general , global improvement scales have proved more sensitive and clinical ly useful than univariate scales . Another approach , presented here , is to use qualitative outcome categories to which patients are assigned on the basis of the configuration of multiple changes . Such a systematic qualitative outcome typology is presented as used in an experimental study of 309 non-chronic voluntary psychiatric patients who , regardless of symptomatology or diagnosis , were r and omly assigned to placebo , imipramine or chlorpromazine-procyclidine , in a fixed dosage double-blind study .This outcome typology is compared with a global improvement scale and related to diagnosis . In general , the drug outcome categorization was equal or superior to the global improvement scale in detecting the differences between drugs and placebo . Furthermore , by utilizing the author 's diagnostic schema , as well as the qualitative outcome typology , the prediction of specific drug induced qualitative outcomes by diagnosis was demonstrated BACKGROUND Although recent studies have documented the benefit of adjunctive antidepressant medication for the short-term treatment of certain patients with operationally defined syndromes of postpsychotic depression , the value of maintenance adjunctive antidepressant treatment in this circumstance has not been properly established . METHODS This study examined 24 schizophrenic or schizoaffective patients with postpsychotic depression or negative symptoms . These patients had all been benefited over the short term by the addition of adjunctive imipramine hydrochloride to their ongoing fluphenazine decanoate/benztropine mesylate regimens , and this adjunctive treatment had been successfully continued for 6 months . In a r and omized double-blind protocol , treatment with adjunctive imipramine hydrochloride ( mean , 233 + /- 72 mg/d ) was then either maintained or tapered to placebo for an ensuing 1-year trial , while treatment with fluphenazine and benztropine continued . RESULTS Significantly more patients who received placebo substitution relapsed into depression ( P < .001 ) . Patients who received placebo substitution were also more likely to experience relapses into psychosis ( P < .02 ) . CONCLUSIONS These results support the clinical value of maintenance adjunctive imipramine therapy among initially responsive patients with postpsychotic depressions OBJECTIVE The authors examined the efficacy of fluoxetine augmentation of clozapine treatment response in schizophrenic out patients who , despite adequate treatment with clozapine , continued to exhibit persistent positive or negative symptoms . METHOD Thirty-three patients completed on 8-week , double-blind , parallel-groups comparison of adjunctive fluoxetine and placebo . RESULTS There were no significant differences in positive , negative , depressive , or obsessive-compulsive symptoms between patients given adjunctive fluoxetine or placebo . CONCLUSIONS These results suggest that fluoxetine is not effective in augmenting clozapine treatment response The objective of this study was to compare the efficacy and reliability of sertraline versus imipramine in the treatment of postpsychotic depressive disorder of schizophrenia . The diagnosis was based on DSM-IV research criteria . The Sympson-Angus Scale and SANS were performed in order to discriminate between depressive symptoms , the extrapyramidal side-effects of neuroleptics and the negative symptoms of schizophrenia . A 10-day placebo treatment period was applied to eliminate the possible influence of the placebo effect . The degree of severity of depression was determined using the Hamilton Depression Scale and the Clinical Global Impression Scale . The patients were r and omly divided into two subgroups , each consisting of 20 people , who were given either 50 mg/day sertraline or 150 mg/day imipramine , and their progress was followed for 5 weeks . The diagnosis and treatment results were evaluated using the double-blind method . In conclusion , although both drugs were found to be effective , sertraline was found to be more advantageous than imipramine in terms of rapid onset of action ; frequency , severity and duration of side-effects , and relapse risk of schizophrenia The aim of this double‐blind cross‐over study was to investigate whether treatment with the selective serotonin reuptake inhibitor , citalopram reduces aggressiveness in chronically violent schizophrenic in patients . Initially 19 patients were enrolled into this double‐blind cross‐over study in which the patients were treated for 24 weeks with placebo and 24 weeks with citalopram ( 20–60 mg/day ) as a supplement to their previous neuroleptic medication . Fourteen patients completed the entire study , but sufficient data on 15 patients could be used in the end – point analysis of efficacy . Psychiatric assessment s ( Brief Psychiatric Rating Scale , Clinical Global Impression Scale for Severity of Illness , Social Dysfunction and Aggression Scale and the Global Aggression Scale ) and side effects ( UKU Side Effect Scale ) were recorded at baseline and 4 times during both periods . Aggressive incidents ( Staff Observation Aggression Scale ) were recorded throughout the study . During citalopram treatment , the frequency of aggressive incidents was significantly lower and the mental state did not deteriorate . Patients either experienced no side effects or else side effects were equally mild during both periods OBJECTIVE Since increased norepinephrine availability may account for the weight-reducing effect of appetite suppressants , the authors hypothesized that the addition of the selective norepinephrine reuptake inhibitor reboxetine may prevent or attenuate olanzapine-induced weight gain . METHOD Twenty-six patients hospitalized for first-episode DSM-IV schizophrenic disorder participated in the study . In addition to 6 weeks of treatment with olanzapine , 10 mg/day , patients were r and omly allocated in a double-blind design to receive either reboxetine , 4 mg/day , ( N=13 ) or placebo ( N=13 ) . RESULTS Ten patients in each group completed the 6-week trial . Patients given olanzapine and reboxetine demonstrated a significantly lower increase in body weight ( mean=2.5 kg , SD=2.7 ) than those given olanzapine and placebo ( mean=5.5 kg , SD=3.1 ) . Significantly fewer patients in the olanzapine/reboxetine group ( N=2 of 10 ) than in the olanzapine/placebo group ( N=7 of 10 ) gained at least 7 % of their initial weight , the cutoff for clinical ly significant weight gain . The addition of reboxetine to olanzapine treatment was safe and well tolerated by the patients . A between-group difference in the reduction of Hamilton depression scale scores was seen that favored the olanzapine/reboxetine group ( mean difference=-3.1 , SD=1.25 ) . CONCLUSIONS The selective norepinephrine reuptake inhibitor reboxetine may reduce olanzapine-induced weight gain in schizophrenia patients , and activation of the adrenergic system may attenuate weight gain induced by atypical antipsychotic agents Summary Trifluperidol , a new butyrophenone compound , was evaluated in chronic schizophrenic women under conditions of a controlled clinical trial . Within this framework significant drug effects associated with the st and ard drug , chlorpromazine , attested to the sensitivity of the experiment , while trifluperidol , the experimental drug , was shown to be an antipsychotic agent at least equally as effective as the st and ard . The placebo group tended to deteriorate on all measures . This trend did not differ significantly from a similar trend in a group of subjects receiving neither placebo nor active treatment . The most likely explanation for this deterioration is thought to be an inadequate preliminary dry-out period , although other influences affecting all subjects adversely can not be ruled out . The demonstration of significant drug : placebo differences was dependent in part upon the presence of the negative change in the placebo group . Failure to include a control group in the present study would have precluded the demonstration of statistically significant drug effects The effect of adjunctive fluoxetine on negative schizophrenic symptoms was evaluated in 34 chronic schizophrenic in- patients on maintenance therapy with neuroleptics . They received r and omly , on a double-blind basis , fluoxetine ( 20 mg/day ) or placebo for 12 weeks . In the fluoxetine group , three patients dropped out because of side effects . Negative symptoms , as measured by change on the Scale for Assessment of Negative Symptoms at the end point compared to baseline values , were significantly improved in fluoxetine-treated patients ( p < 0.001 ) , but not in the placebo group . Fluoxetine treatment did not influence positive schizophrenic symptoms , while it induced a slight , but statistically significant , decrease ( p < 0.05 ) in depressive symptoms , as measured by the Hamilton Rating Scale for Depression . Unwanted effects were more common among patients receiving fluoxetine . These data suggest that the addition of fluoxetine to neuroleptic treatment may be beneficial in some schizophrenic patients with negative symptoms BACKGROUND Depressive symptoms are common in older patients with schizophrenia ; yet , few studies have examined the usefulness of antidepressants in this population . OBJECTIVE We conducted a 10-week single-blind trial of citalopram ( 20 - 40 mg/day ) vs no citalopram augmentation in 19 middle-aged and elderly patients with schizophrenia hospitalized for more than six of the last 12 months . At study -entry , the patients had been on stable doses of antipsychotics for at least two weeks , and had a 17-item Hamilton Depression Rating ( HAM-D ) scale score of 12 or greater . Nine patients were r and omly assigned to citalopram augmentation , and 10 to no augmentation of antipsychotics . RESULTS Patients in both groups improved on positive and negative symptoms , but the citalopram group had significantly greater improvement in HAM-D and Clinical Global Impression Scale scores than the control group . There were no major side effects . CONCLUSION Larger double-blind studies are needed to follow up on these preliminary findings Obsessive-compulsive-related disorders are frequently comorbid with schizophrenia . The existence of obsessive and compulsive symptoms in patients with schizophrenia represents one of the most severe types of psychotic disorders and may predict a poor prognosis in most cases . Previous pilot studies and case reports have shown that the condition of some patients with schizophrenia did not exacerbate and even improved when serotonin reuptake inhibitors ( SSRIs ) were added to their st and ard neuroleptic regimen . The aim of this study was to evaluate the efficacy of a combination treatment of an SSRI ( fluvoxamine ) and st and ard neuroleptics for the treatment of obsessive-compulsive ( OC ) symptomatology in patients with schizophrenia compared with administration of neuroleptics only . Thirty in patients who met DSM-IV criteria for schizophrenia and also had prominent OC symptoms were r and omly divided into two groups . Fourteen patients were treated with conventional neuroleptics and fluvoxamine in doses of 100 to 200 mg/day for 8 weeks . Sixteen patients comprised a control group and received only their previous therapeutic neuroleptic therapy . The patients were assessed using the Yale-Brown Obsessive Compulsive Scale ( Y-BOCS ) , the Positive and Negative Syndrome Scale ( PANSS ) , and the Clinical Global Impression Scale ( CGI ) at baseline and endpoint . Side effects were assessed weekly . The data were analyzed using an analysis of variance . A considerable reduction in PANSS ( 34.3 % ) and Y-BOCS ( 29.4 % ) scores was noted , and CGI scores decreased moderately in both groups . None of the patients showed an acute exacerbation at the end of the study . Side effects were mild and easily tolerated in most patients . This open , r and omized , controlled study reveals that coadministration of fluvoxamine , an SSRI , and neuroleptics in patients with schizophrenia and OC symptoms was associated with specific improvements of these symptoms . Thus , the use of an SSRI in treating a patient with schizophrenia and OC symptomatology may be warranted and safe . Other implication s of the findings , including general safety of the combined pharmacotherapy and the use of new antipsychotic medications , are also discussed The negative symptoms of schizophrenia remain a major clinical challenge . Mirtazapine is an antidepressant with antagonist properties at 5-HT2A , 5-HT3 and alpha 2 receptors as well as indirect 5-HT1a agonist effects . Many of these pharmacological actions have clinical or pre clinical evidence of efficacy in schizophrenia . This study was a 6-week r and omized placebo-controlled trial of mirtzepine or placebo add on to haloperidol 5 mg in the treatment of 30 patients with DSM-IV schizophrenia . The primary finding of the trial was a 42 % reduction in Positive and Negative Syndrome Scale ( PANSS ) negative symptom scores in the mirtazapine group compared to placebo at the end of 6 weeks ( mirtazapine 13.9 , SD 1.56 ; placebo 23.9 , SD 1.56 ; P = 0.000 , F = 20.31 , d.f . = 1 ) . The PANNS total scores , Clinical Global Impression severity and improvement scales in addition showed superiority of mirtazapine over placebo . There was no difference between the groups on the Hamilton depression scale at endpoint , suggesting that the improvement in negative symptoms was not an artifact of mood improvement . These results suggest a potential role for mirtazapine in the negative symptoms of schizophrenia Adjunctive imipramine has been found to be useful in the treatment of a substantial number of patients with syndromally defined post-psychotic depressions . This paper examines the clinical effects of the combined anticholinergic activity of imipramine , when added to ongoing fluphenazine decanoate/benztropine treatment , in such patients . Little additional anticholinergic impact of the imipramine was observable beyond that already attributable to the benztropine , and no significant relationships were found between a clinical measure of peripheral anticholinergic activity and either global clinical outcome or antidepressive efficacy . This paper also reports on the concentrations of imipramine and its metabolites in plasma under the conditions of this therapeutic trial . The changes in relative concentrations of imipramine and metabolites with time were consistent with the concept that fluphenazine competes with tricyclic metabolism . The relationship of plasma imipramine and desipramine to clinical improvement in this group of secondary depressions did not parallel previously reported relationships of these antidepressant molecules to clinical outcome in primary depressions In a multicenter , double-blind , parallel group trial , the efficacy of risperidone ( RIS ) was compared with a combination of haloperidol and amitriptyline ( HAL/AMI ) over 6 weeks in patients with coexisting psychotic and depressive symptoms with either a schizoaffective disorder , depressive type , a major depression with psychotic features , or a nonresidual schizophrenia with major depressive symptoms according to DSM-III-R criteria . A total of 123 patients ( 62 RIS ; 61 HAL/AMI ) were included ; the mean daily dosage at endpoint was 6.9 mg RIS versus 9 mg HAL combined with 180 mg AMI . Efficacy results for those 98 patients ( 47 RIS ; 51 HAL/AMI ) who completed at least 3 weeks of double-blind treatment revealed in both treatment groups large reductions in the Positive and Negative Syndrome Scale-derived Brief Psychiatric Rating Scale ( RIS 37 % ; HAL/AMI 51 % ) and the Bech-Rafaelsen Melancholia Scale total scores ( RIS 51 % ; HAL/AMI 70 % ) . The reductions in the Brief Psychiatric Rating Scale and the Bech-Rafaelsen Melancholia Scale scores in the total group were significantly larger in the HAL/AMI group than in the RIS group ( p < 0.01 ) , mostly because of significant differences in the subgroup of patients suffering from depression with psychotic features , whereas treatment differences in the other diagnostic subgroups were not significant . The incidence of extrapyramidal side effects as assessed by the Extrapyramidal Symptom Rating Scale was slightly higher under RIS ( 37 % ) than under HAL/AMI ( 31 % ) . Adverse events were reported by 66 % of RIS and 75 % of HAL/AMI patients . The results of this trial suggest that the therapeutic effect of HAL/AMI is superior to RIS in the total group of patients with combined psychotic and depressive symptoms . However , subgroup differences have to be considered Nineteen male and 21 female psychiatric in patients , aged 15 to 66 , on moderate to high daily doses of chlorpromazine or imipramine , were r and omly subdivided into four groups of 10 patients each . The groups differed in mode of drug administration . Drugs were self-administered with or without instruction , and were also administered in the traditional manner by nurses with or without instruction . Although the overall incidence of drug defaulting ( 24 per cent ) was consistent with previous reports , patients on self-administration schedules revealed greater evidence of drug defaulting than did nurse-medicated patients . Contrary to expectations , instructions by nursing staff apparently undermined rather than supported patients ' attitudes toward and adherence to prescribed medication . Although drugtaking behavior did not change over time , patients showed increasing preference for self-administration . Results are discussed in terms of patient responsibility and the responses of nurses to changes in an important aspect of their traditional role BACKGROUND Serotonin (5-HT):dopamine imbalance may underlie neuroleptic-induced akathisia . AIM To evaluate the efficacy of the 5-HT2 antagonist , mianserin in neuroleptic-induced akathisia . METHODS Thirty neuroleptic-treated patients with schizophrenia were r and omly allocated in a double-blind design to receive either mianserin ( 15 mg/day ) or placebo for five days . Patients were assessed at baseline and on Days 3 and 5 by the Barnes Akathisia Scale ( BARS ) , as well as by other relevant clinical rating scales . RESULTS Compared with the placebo group , the mianserin-treated patients showed a significant reduction in all four BARS subscales by Day 5 , with mean reductions in the BARS global score of 9.9 % and 52.2 % , respectively ( P = 0.006 ) . Response to treatment ( a reduction of at least two points on the BARS global subscale ) , was noted in six patients ( 40 % ) in the mianserin group and only one patient ( 9.1 % ) in the placebo group ( P = 0.04 , log odds ratio 2.23 ) . CONCLUSIONS Mianserin at a low dose may be a promising therapeutic option for patients with acute neuroleptic-induced akathisia Steady-state plasma concentrations of commonly used neuroleptic drugs were measured in 90 schizophrenic patients before and after adding placebo or citalopram ( 40 mg/day ) to their treatment regimen . Plasma concentrations of citalopram and its main metabolite , desmethylcitalopram , were also measured . In addition , patients with exceptionally high neuroleptic levels or an increase in adverse effects during the 12-week study period were evaluated for their debrisoquine/sparteine hydroxylase ( CYP2D6 ) genotype , an enzyme responsible for oxidative metabolism of several neuroleptics and selective serotonin re-uptake inhibitors . There were no significant changes in plasma concentrations of haloperidol , chlorpromazine , zuclopenthixol , levomepromazine , thioridazine or perphenazine during the study . Plasma concentrations of citalopram and desmethylcitalopram were well within the levels reported previously with monotherapy , and remained stable throughout the study . None of the 15 patients analysed for the CYP2D6 genotype was a poor metabolizer . It is concluded that clinical ly important pharmacokinetic drug interactions do not play a crucial role when citalopram is used as an augmentation therapy in neuroleptic-treated schizophrenic patients The author describes a controlled study of an amitriptyline-perphenazine combination given to 58 chronic schizophrenic patients . There was no evidence of the combination 's increased effectiveness over perphenazine used alone . He discusses the possibility of therapeutic incompatibility between perphenazine and amitriptyline at some dosage levels and concludes that there is no evidence that supports using a perphenazine-amitriptyline combination The authors studied 46 patients with the operationally defined syndrome of postpsychotic depression following episodes of schizophrenia or schizoaffective disorder . Half of these patients were also found to satisfy criteria for negative symptoms . The patients with negative symptoms were rated as more severely ill on global measures , but there was only limited evidence that they were more depressed . Nevertheless , in a r and omized double-blind trial of imipramine versus placebo as an adjunct to the fluphenazine decanoate and benztropine regimens of the patients with negative symptoms , the patients who received imipramine seemed to show more improvement A pilot study of a small group of schizophrenic patients manifesting symptoms of a depressive nature was treated in a double-blind study in which viloxazine or a placebo was administered in combination with either chlorpromazine or haloperidol . There appeared to be no difference between the viloxazine-treated group and the placebo-treated group , although the study raised some question as to the adequacies of the dosage utilized since there was an absence of any apparent side effects . In view of these issues concerning the clinical merit of the combination , this obviously requires further investigation There have been no studies specifically examining the efficacy of selective serotonin reuptake inhibitor antidepressants for the symptoms of depression in schizophrenia . This study aim ed to determine the efficacy and safety of sertraline as a treatment for depressive symptoms in patients with stable , chronic schizophrenia . The Beck Depression Inventory ( BDI ) was used as the principal outcome measure and other measures of depressive symptoms as secondary outcome measures . Twenty-six patients were entered into adouble-blind , placebo-controlled , 8-week trial of sertraline and were included in the intent-to-treat ( ITT ) analysis ( 13 in each group ) . Eight patients in the sertraline group and 12 in the placebo group completed at least four weeks in the study and were considered to have had adequate treatment . On the ITT analysis , the mean score on the BDI fell 14.5 % for the sertraline group and 5.6 % for the placebo group ( p > 0.05 ) ; the mean score on the Hamilton Depression Rating Scale ( HDRS ) fell 16.9 % for the sertraline group and 8.3 % for the placebo group ( p > 0.05 ) . When the analysis was repeated for those who had received adequate treatment , the mean BDI score fell by 28 % for the sertraline group and 6 % for the placebo group ( p = 0.1 ) ; the mean HDRS score fell 31 % for the sertraline group and 8.6 % for the placebo group ( p= 0.02 ) . On the Clinical Global Impression-Improvement Scale , 10 of the 13 patients on sertraline improved against four of the 13 in the placebo group ( p = 0.05 ) . Sertraline-treated patients showed a significant improvement on the anxiety/ depression subscale of the BPRS on ITT analysis ( F = 10.1 , p = 0.004 ) . There was no significant effect on negative or positive symptoms . Sertraline was well tolerated . The results suggest that sertraline is useful as a treatment for depressive symptoms in schizophrenia A total of 54 schizophrenic patients , 27 male and 27 female , satisfying study criteria , were r and omly assigned to one of three treatments : placebo ; perphenazine , 20 mg/day ; or the combination of amitriptyline , 125 mg/day , with perphenazine , 20 mg/day . Medication was administered under double-blind conditions for 12 weeks , after which ECGs were taken following an overnight fast and again following a 600-calorie meal . Among patients receiving perphenazine or amitriptyline-perphenazine , there was a statistically significant increase in repolarization abnormally after eating , whereas placebo-treated patients incurred no such increases . This supports the hypothesis that phenothiazine-induced ECG changes may be caused or facilitated by the glucose load . The incidence of increase in repolarization abnormality after the meal was higher among female patients than among male patients . The findings are of practical significance for readings of abnormality in the ECG of phenothiazine-treated patients The effects of citalopram — the most selective serotonin reuptake inhibitor on the market — on psychopathological symptoms were studied in chronic schizophrenic patients on a stable regimen of neuroleptic medication . Out patients suffering from schizophrenic disorder ( DSM‐III‐R ) with Positive and Negative Symptom Scale ( PANSS ) scores higher than 50 were included in a double‐blind placebo‐controlled add‐on study . The daily dose of citalopram was 20 mg in the first week and 40 mg for the remaining period . A total of 90 patients ( 45 patients receiving citalopram and 45 receiving placebo ) completed the 12‐week trial . There were no changes in neuroleptic plasma levels during the trial . There was a significant decrease in total PANNS scores during the trial , although no statistically significant differences between the citalopram group and the placebo group were revealed . The number of responders in terms of severity of illness ( CGI ) was higher and the increase in subjective well‐being ( VAS ) was greater in patients on citalopram than in those receiving placebo . There were no significant differences in the occurrence of side‐effects . It is concluded that , in chronic schizophrenic out‐ patients , citalopram has no clear effect on the psychopathological symptoms ; it may improve the general clinical condition , and it appears to increase the subjective well‐being of these patients . Citalopram appears to be safe when used to treat schizophrenic patients who are receiving concomitant neuroleptic treatment The combination of antidepressants and neuroleptics has been widely recommended and commonly used clinical ly for the schizophrenic patient who becomes depressed . However , the value of the combination for these patients has not been clearly demonstrated . This report presents results of a double-blind , r and omized , placebo-controlled clinical trial design ed to evaluate the combination of perphenazine and amitriptyline hydrochloride with that of perphenazine alone in the treatment of 35 ambulatory chronic schizophrenic patients in whom depressive symptoms developed . Results showed that the addition of amitriptyline to perphenazine , when compared with perphenazine alone , was more effective in reducing symptoms of depression after four months of treatment , but less effective in reducing thought disorder . The study concludes that the value of adding an antidepressant to the usual neuroleptic in the treatment of secondary depression in schizophrenia should be review ed The effects of fluoxetine and imipramine on the pharmacokinetics and nonpsychiatric side effect profile of quetiapine fumarate were investigated in 26 patients with schizophrenia , schizoaffective disorder , or bipolar disorder in a multicenter , twoperiod , multiple-dose , open-label , r and omized trial . Over a 1- to 2-week period , patients were titrated to a 300-mg twice-daily dose of quetiapine . Patients treated for at least 7 days at the target dose entered a combination therapy period , receiving fluoxetine ( 60 mg daily ) or imipramine ( 75 mg twice daily ) for 8 days . Key assessment s included pharmacokinetic analysis of quetiapine , the Udvalg for kliniske undersøgelser ( UKU ) Side Effect Rating Scale , and safety evaluations ( e.g. , adverse events , electrocardiograms , laboratory tests , and vital signs ) . Fluoxetine increased the quetiapine area under the plasma concentration time curve during a 12-hour interval ( + 12 % ) , maximum plasma concentration during the dosing interval ( Cssmax ; + 26 % ) , and minimum plasma concentration at the end of the dosing interval ( + 8 % ) , although it decreased oral clearance ( −11 % ) . The change in Cssmax was statistically although not clinical ly significant . Imipramine did not affect the pharmacokinetics of quetiapine . Overall , scores on the UKU Side Effect Rating Scale improved during combination therapy with either agent , and no statistically significant deterioration was observed for any item . For safety assessment s , the only clinical ly remarkable event was an imipramine-associated complete left bundle branch block in one patient . No unexpected side effects were reported . In conclusion , combination therapy with quetiapine and fluoxetine or imipramine had a minimal effect on quetiapine pharmacokinetics and was well tolerated Although antipsychotic drugs are highly effective in alleviating positive symptoms of schizophrenia they have little impact on the negative symptoms of the illness . These symptoms , including apathy , social withdrawal , blunted affect , and motor retardation present serious obstacles to the successful rehabilitation of chronic schizophrenic patients and have been the focus of renewed interest ( Crow 1980 ; And reasen and Olsen 1982 ) . The " dopamine hypothesis " of schizophrenia , based on a significant correlation between antipsychotic potency of neuroleptic drugs and their propensity to block dopamine receptors ( Seeman et al 1976 ; Snyder 1976 ) is widely accepted , but other neurotransmitters may have a role in the pathogenesis , particularly of negative symptoms . Evidence pointing to serotonergic dysfunction in schizophrenia has accumulated . Increased plasma ( Garelis et al 1975 ; DeLisi et ai 1981 ; Freedman et al 1981 ) and platelet ( Jackman et al 1983 ) serotonin concentrations in chronic schizophrenics including a possible link to cortical atrophy ( DeLisi et al 1981 ) have been reported and our group ( Lerer et al 1988 ) found a blunted prolactin response to fenfluramine challenge in unmedicated chronic schizophrenic patients compared to normal controls . Furthermore , improvement in negative symptoms of schizophrenia has been reported as a result of treatment with serotonin active agents , fenfluramine ( Stahl et al 1985 ) , ritanserin ( Gelders et al 1986 ) and ¢yproheptadine ( Silver et al 1989 ) . Clozapine , which appears to be effective in treatmentresistent positive and negative symptoms of chronic schizophrenia , has a high serotonergic : dopaminergic blocking ratio ( Kant ct al 1988 . Richelson 1984 ) . There is little evidence that antidepressants can ameliorate negative symptoms of schizophrenia , although tricyclic and monoamine oxidase inhibiting ( MAOI ) antidepressants may be useful in schizophrenic patients demonstrating depressive symptoms ( Siris et al 1978 ) . However , the recently developed antidepressants such as fluvoxamine ( Benfield and Ward 1986 ) acting specifically on the serotonergic system may be effective in treating primary negative symptoms of schizophrenia . We report the results of a doubleblind add-on study of fluvoxamine in chronic schizophrenic patients . To our knowledge this is the first such report Recent studies show that obsessive-compulsive symptoms may occur in many patients with schizophrenia and may predict a poor prognosis . Pilot studies have shown that some schizophrenic patients may improve if a serotonin reuptake blocker is added to their neuroleptic . We have performed a pilot , double-blind , crossover study of clomipramine ( CMI ) or placebo , added to maintenance psychotropic medication . Six schizophrenic patients with obsessive-compulsive symptoms were studied in a double-blind CMI versus placebo crossover protocol . The patients met DSM-III-R criteria for chronic schizophrenia , experienced obsessive-compulsive symptoms , and had been previously stabilized on their psychiatric medication . The patients were rated at baseline and longitudinally through the study with the Positive and Negative Symptom Scale for Schizophrenia ( PANSS ) and the Yale Brown Obsessive-Compulsive Scale ( YBOCS ) . An analysis of covariance was used to compare the drug versus placebo effect at the final visit with the baseline rating as a covariate . Ratings on both the YBOCS and the PANSS showed that patients improved significantly more on CMI than on placebo . No patients experienced an exacerbation of psychotic symptoms . Preliminary findings from this double-blind , crossover , pilot study of CMI and placebo , design ed to assess the effect of CMI in the treatment of schizophrenic patients with obsessive symptoms , suggest that CMI is superior to placebo in the treatment of obsessions and compulsions and improves overall schizophrenic symptoms . Further studies with larger sample s and longer follow-up period are necessary to confirm these preliminary findings We conducted a placebo-controlled , r and omized , double-blind , 8-week trial of sertraline added to haloperidol treatment in patients with schizophrenia to evaluate changes in clinical measures and pharmacokinetic interactions with haloperidol . In addition to their haloperidol regimen , 36 in patients with chronic schizophrenia were r and omly assigned to receive capsulized sertraline ( 50 mg/day ; N = 18 ) or identically capsulized placebo ( N = 18 ) for 8 weeks . The results from the Positive and Negative Syndrome Scale ( PANSS ) , Clinical Global Impression ( CGI ) Scale , Simpson-Angus Extrapyramidal Effects ( S-A ) Scale , and plasma concentration levels of haloperidol and reduced haloperidol were examined at baseline and 2 , 4 , 6 , and 8 weeks of treatment . No significant differences between the three PANSS factors ( positive , negative , general psychopathology ) scores , CGI Scale scores , or S-A Scale scores were recorded at any point during sertraline and placebo treatment . Neither plasma haloperidol or reduced haloperidol concentrations was changed significantly at any point during the sertraline and placebo treatments . In this study , the addition of sertraline 50 mg to the treatment regimen of in patients did not differ significantly from the placebo effect on positive and negative symptoms and extrapyramidal side effects . The results further indicate that the pharmacokinetics of haloperidol are seemingly unaffected by sertraline Fifty-eight actively psychotic in patients who initially met criteria for long-st and ing schizophrenia and subsequently met Research Diagnostic Criteria for a current episode of schizoaffective disorder ( mainly schizophrenic ) with a depressive syndrome , and who scored at least 30 ( mean = 55 , SEM = 1.6 ) on the Brief Psychiatric Rating Scale and 17 ( mean = 23 , SEM = 0.7 ) on the Hamilton Rating Scale for Depression , were treated for 5 weeks with haloperidol hydrochloride and benztropine . Haloperidol and benztropine treatment was continued , while those patients who consistently scored greater than 17 on the Hamilton Rating Scale for Depression were r and omly assigned to the following double-blind treatment groups for 4 weeks : adjunctive amitriptyline hydrochloride , desipramine hydrochloride , or placebo . Adjunctive desipramine or amitriptyline showed no significant therapeutic advantage , when compared with haloperidol and placebo , on the Brief Psychiatric Rating Scale or the Hamilton Rating Scale for Depression . After 4 weeks of combine therapy , patients receiving adjunctive amitriptyline or desipramine , as compared with those receiving adjunctive placebo , tended to score higher on the Brief Psychiatric Rating Scale hallucinatory behavior item and on the thinking disturbance factor than patients receiving placebo . These results suggest that adjunctive antidepressants are not indicated for the treatment of depressive symptoms in actively psychotic schizophrenic in patients . Adjunctive antidepressants may retard the rate of resolution of psychosis in this population There is increasing evidence suggesting that symptoms of depression and anxiety may also be associated with serotonergic dysfunction in schizophrenic patients . The effect of the adjuvant selective serotonin reuptake inhibitor citalopram was assessed regarding the symptom dimensions of schizophrenia measured with the Positive and Negative Syndrome Scale ( PANSS ) and with the Hamilton Rating Scale for Depression ( HRSD ) . Citalopram alleviated symptoms of the depression/anxiety dimension of the PANSS , but not the symptoms of the four other PANSS domains or depressive symptoms measured with the HRSD . The results support the hypothesis of a serotonergic dimension in schizophrenia There is considerable evidence that adding selective serotonin reuptake inhibitor ( SSRI ) antidepressants to antipsychotic treatment improves negative symptoms of schizophrenia . This augmentation effect may be due to " nonspecific " antidepressant action or be specifically related to action on the serotonergic system . This study examined the serotonergic specificity of SSRI augmentation by comparing an SSRI antidepressant with a comparably effective antidepressant acting via the noradrenergic system . Consenting patients having chronic schizophrenia with prominent negative symptoms were studied . Either fluvoxamine or maprotiline was added to their regular antipsychotic treatment in a double-blind manner for 6 weeks . Patients were assessed using the Brief Psychiatric Rating Scale , the Scale for the Assessment of Negative Symptoms , the Scale for the Assessment of Positive Symptoms , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , and the Neurological Rating Scale for Extrapyramidal Side Effects . Twenty-five patients completed the study . Negative symptoms improved significantly in the fluvoxamine group , but not in the maprotiline group . MADRS scores , which were low , did not change significantly in either group . Positive symptoms were not affected by either treatment . It is concluded that the mechanism by which fluvoxamine augmentation improves negative symptoms involves the serotonergic system and is distinct from its antidepressant action Seventeen out of 20 inactive and emotionally withdrawn schizophrenic patients under long‐term neuroleptic treatment completed a double‐blind cross‐over investigation of the possible activating effect of maprotiline , a relatively specific noradrenaline‐reuptake inhibitor , compared with that of placebo . Each treatment phase lasted 8 weeks . No significant differences with respect to either the level of activity of schizophrenic symptoms were found between maprotiline ( mean dose 138 mg/day ) and placebo . Maprotiline provoked a slight psychotic exacerbation in one patient and sedation in another , four patients developed orthostatic hypotension , and two patients had an epileptic seizure . In the light of this and other studies , it must be concluded that antidepressant drugs do not represent any therapeutic advance in the treatment of inactive schizophrenic patients receiving neuroleptics The efficacy of adjunctive imipramine hydrochloride treatment for syndromally defined postpsychotic depression was assessed in a six-week , double-blind , placebo-controlled study . All patients had been diagnosed as having schizophrenia or schizoaffective disorder , all were receiving stable doses of fluphenazine decanoate , and all had received benztropine mesylate in an attempt to rule out neuroleptic-induced akinesia . Patients r and omized to imipramine therapy fared significantly better in terms of their global improvement and in terms of individual symptoms that are components of the depression syndrome . There were no significant differences in outcome psychosis ratings or side effects . This study indicates the existence of an identifiable syndrome of secondary depression in this patient group that is likely to respond favorably to treatment with adjunctive imipramine 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 Under double‐blind conditions , increasing amounts of perphenazine , or a perphenazine‐amitriptyline combination , were given to chronic schizophrenic patients already receiving “ optimal ” therapeutic dosages of perphenazine . Slight behavioral improvement was obtained in both groups , but a significantly smaller amount of extrapyramidal side effects was noted in the group receiving the combination . A double‐blind crossover study was used , which eliminated any order effect . The implication s of these findings for therapy are briefly discussed BACKGROUND Prominent and persistent anxiety , depression , and /or negative features characterize a substantial minority of recovered or residually psychotic schizophrenic out patients and contribute to poor outcome . Because extrapyramidal side effects of typical neuroleptic medications often resemble such features , we first systematic ally studied the contribution of extrapyramidal side effects to these problems and their treatment . For patients who remained distressed , controlled trials of supplemental thymoleptics were undertaken . METHODS In trial 1 , 92 distressed ( depressed and /or anxious ) patients and 36 patients in a defect state ( patients with negative symptoms ) participated in a double-blind , intramuscular challenge that compared central ly acting benztropine mesylate with peripherally acting glycopyrrolate . In trial 2 , 57 distressed patients and 22 patients in a defect state were r and omly assigned to a double-blind , neuroleptic medication dose-reduction group . In trial 3 , 57 chronically distressed patients who were maintained on a low dose of fluphenazine decanoate were r and omly assigned to a supplemental desipramine hydrochloride , lithium carbonate , or placebo group under double-blind conditions for 12 weeks . RESULTS For patients who were already maintained on antiparkinsonian medication , impaired affect was not resolved by additional benztropine . Only distressed patients with a family history of severe mental disorder ( often affective ) showed improvement with neuroleptic medication dose reduction . Patients in the defect-state group reported less dysphoria on a reduced neuroleptic medication dose , but negative symptoms persisted . Desipramine improved diverse aspects of mood and residual psychoticism , possibly as a prophylaxis against minor affective exacerbations . Depression improved in women only . Lithium positively affected multiple indexes of anxiety and anxious depression . CONCLUSION Most often , persistent affective impairments are neither resistant extrapyramidal side effects nor characterological traits . Thymoleptics improve the nonphasic , chronic types of anxiety and depression in contrast to the acute , episodic forms , for which little support can be found in the literature In two studies , the relationship among depressive symptoms , depression , and psychotropic drugs was examined . In the first study , imipramine hydrochloride was administered in low and high dosages to chronic schizophrenic patients with prominent apathy and anergy , viz , symptoms of depression . Stimulating properties ( improvement in areas of motor retardation and emotional withdrawal , worsening in tension ) were noted . Not all patients displayed signs of stimulation ; no suppression of the stimulative effect occurred with high dosages . The hypothesis that thiothixene might have a stimulative effect at low dosages in the above patients was not supported . In the second study , thiothixene was compared with amitriptyline hydrochloride in the treatment of 40 patients who had been diagnosed as suffering from endogenous depression . Global ratings and rating scales favored amitriptyline . These results suggest that antidepressants are the treatment of choice in the diagnosis of depression , but they are probably contraindicated in symptoms of depression Fourteen schizophrenic or schizoaffective patients , who had had operationalized syndromes of post psychotic depression or negative symptoms unresponsive to adjunctive benztropine but responsive to adjunctive imipramine , completed a double-blind maintenance treatment trial of adjunctive imipramine vs. placebo . All patients were maintained on st and ing doses of fluphenazine decanoate and benztropine throughout . All six patients tapered to placebo relapsed into their depression-like , negative symptom state , whereas only 2 of 8 patients maintained on imipramine had such a course ( p = .009 , favoring imipramine maintenance ) . No patients maintained on imipramine relapsed into psychosis . These results suggest the advisability of maintaining adjunctive imipramine treatment , in conjunction with appropriate neuroleptic and antiparkinsonian regimens , in stable , syndromally defined , postpsychotic depressed or negative symptom patients initially responsive to adjunctive imipramine |
12,274 | 28,453,189 | The recommendations were based on three systematic review s. Substantive changes were made to the guideline recommendations including the inclusion of palonosetron to the 5-HT3 antagonists recommended for children receiving highly emetogenic chemotherapy ( HEC ) and the recommendation of aprepitant for children 6 months of age or older receiving HEC . | null | null |
12,275 | 25,203,081 | The presence of asthma or asthma symptom(recurrentwheezing ) , significantly increases the risk ofSCD-relatedmorbidity4 and mortality.5 - 7However , the guideline doesnotprovide anyapproach to screen and treat asthma orasthma-like symptoms . | In this issueof JAMA , Yawn and colleagues1publish themuchanticipatedNationalHeart , Lung , and Blood Institute ( NHLBI ) guideline for the management of sickle cell disease ( SCD ) in the United States .
The last SCD guideline sponsored by the NHLBI was published a decadeago .
Thechallengesassociatedwithdeveloping guidelines for individualswithanuncommondisease areunique and formidable becauseof the relianceon evidence other than clinical trials , inparticularexpert opinion .
Given the importance of evidence -derived guidelines , particularly formanagementof anuncommondisease , adherence to rigorous methodology iscritical for their credibility .
The InstituteofMedicine (IOM)published guidelines 2 toaddress the most importantcomponentsofany guideline thatwill allowfor primary care clinicians , specialists , and payers to have confidence in its content . | Allogeneic marrow transplantation can cure sickle cell disease ; however , HLA-matched donors are difficult to find , and the toxicities of myeloablative conditioning are prohibitive for most adults with this disease . We developed a nonmyeloablative bone marrow transplantation platform using related , including HLA-haploidentical , donors for patients with sickle cell disease . The regimen consisted of antithymocyte globulin , fludarabine , cyclophosphamide , and total body irradiation , and graft-versus-host disease prophylaxis with posttransplantation high-dose cyclophosphamide , mycophenolate mofetil , and tacrolimus or sirolimus . After screening 19 patients , we transplanted 17 , 14 from HLA-haploidentical and 3 from HLA-matched related donors . Eleven patients engrafted durably . With a median follow-up of 711 days ( minimal follow up 224 days ) , 10 patients are asymptomatic , and 6 patients are off immunosupression . Only 1 patient developed skin-only acute graft-versus-host disease that resolved without any therapy ; no mortality was seen . Nonmyeloablative conditioning with posttransplantation high-dose cyclophosphamide exp and s the donor pool , making marrow transplantation feasible for most patients with sickle cell disease , and is associated with a low risk of complications , even with haploidentical related donors . Graft failure , 43 % in haploidentical pairs , remains a major obstacle but may be acceptable in a fraction of patients if the majority can be cured without serious toxicities BACKGROUND The use of inhaled glucocorticoids for persistent asthma causes a temporary reduction in growth velocity in prepubertal children . The result ing decrease in attained height 1 to 4 years after the initiation of inhaled glucocorticoids is thought not to decrease attained adult height . METHODS We measured adult height in 943 of 1041 participants ( 90.6 % ) in the Childhood Asthma Management Program ; adult height was determined at a mean ( ±SD ) age of 24.9±2.7 years . Starting at the age of 5 to 13 years , the participants had been r and omly assigned to receive 400 μg of budesonide , 16 mg of nedocromil , or placebo daily for 4 to 6 years . We calculated differences in adult height for each active treatment group , as compared with placebo , using multiple linear regression with adjustment for demographic characteristics , asthma features , and height at trial entry . RESULTS Mean adult height was 1.2 cm lower ( 95 % confidence interval [ CI ] , -1.9 to -0.5 ) in the budesonide group than in the placebo group ( P=0.001 ) and was 0.2 cm lower ( 95 % CI , -0.9 to 0.5 ) in the nedocromil group than in the placebo group ( P=0.61 ) . A larger daily dose of inhaled glucocorticoid in the first 2 years was associated with a lower adult height ( -0.1 cm for each microgram per kilogram of body weight ) ( P=0.007 ) . The reduction in adult height in the budesonide group as compared with the placebo group was similar to that seen after 2 years of treatment ( -1.3 cm ; 95 % CI , -1.7 to -0.9 ) . During the first 2 years , decreased growth velocity in the budesonide group occurred primarily in prepubertal participants . CONCLUSIONS The initial decrease in attained height associated with the use of inhaled glucocorticoids in prepubertal children persisted as a reduction in adult height , although the decrease was not progressive or cumulative . ( Funded by the National Heart , Lung , and Blood Institute and the National Center for Research Re sources ; CAMP Clinical Trials.gov number , NCT00000575 . ) IMPORTANCE Myeloablative allogeneic hematopoietic stem cell transplantation ( HSCT ) is curative for children with severe sickle cell disease , but toxicity may be prohibitive for adults . Nonmyeloablative transplantation has been attempted with degrees of preparative regimen intensity , but graft rejection and graft-vs-host disease remain significant . OBJECTIVE To determine the efficacy , safety , and outcome on end-organ function with this low-intensity regimen for sickle cell phenotype with or without thalassemia . DESIGN , SETTING , AND PARTICIPANTS From July 16 , 2004 , to October 25 , 2013 , 30 patients aged 16 - 65 years with severe disease enrolled in this nonmyeloablative transplant study , consisting of alemtuzumab ( 1 mg/kg in divided doses ) , total-body irradiation ( 300 cGy ) , sirolimus , and infusion of unmanipulated filgrastim mobilized peripheral blood stem cells ( 5.5 - 31.7 × 10(6 ) cells/kg ) from human leukocyte antigen-matched siblings . MAIN OUTCOMES AND MEASURES The primary end point was treatment success at 1 year after the transplant , defined as a full donor-type hemoglobin for patients with sickle cell disease and transfusion independence for patients with thalassemia . The secondary end points were the level of donor leukocyte chimerism ; incidence of acute and chronic graft-vs-host disease ; and sickle cell-thalassemia disease-free survival , immunologic recovery , and changes in organ function , assessed by annual brain imaging , pulmonary function , echocardiographic image , and laboratory testing . RESULTS Twenty-nine patients survived a median 3.4 years ( range , 1 - 8.6 ) , with no nonrelapse mortality . One patient died from intracranial bleeding after relapse . As of October 25 , 2013 , 26 patients ( 87 % ) had long-term stable donor engraftment without acute or chronic graft-vs-host disease . The mean donor T-cell level was 48 % ( 95 % CI , 34%-62 % ) ; the myeloid chimerism levels , 86 % ( 95 % CI , 70%-100 % ) . Fifteen engrafted patients discontinued immunosuppression medication with continued stable donor chimerism and no graft-vs-host disease . The normalized hemoglobin and resolution of hemolysis among engrafted patients were accompanied by stabilization in brain imaging , a reduction of echocardiographic estimates of pulmonary pressure , and allowed for phlebotomy to reduce hepatic iron . The mean annual hospitalization rate was 3.23 ( 95 % CI , 1.83 - 4.63 ) the year before , 0.63 ( 95 % CI , 0.26 - 1.01 ) the first year after , 0.19 ( 95 % CI , 0 - 0.45 ) the second year after , and 0.11 ( 95 % CI , 0.04 - 0.19 ) the third year after transplant . For patients taking long-term narcotics , the mean use per week was 639 mg ( 95 % CI , 220 - 1058 ) of intravenous morphine-equivalent dose the week of their transplants and 140 mg ( 95 % CI , 56 - 225 ) 6 months after transplant . There were 38 serious adverse events : pain and related management , infections , abdominal events , and sirolimus related toxic effects . CONCLUSIONS AND RELEVANCE Among 30 patients with sickle cell phenotype with or without thalassemia who underwent nonmyeloablative allogeneic HSCT , the rate of stable mixed-donor chimerism was high and allowed for complete replacement with circulating donor red blood cells among engrafted participants . Further accrual and follow-up are required to assess longer-term clinical outcomes , adverse events , and transplant tolerance . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00061568 Prior studies of asthma in children with sickle cell disease ( SCD ) were based on reports of a doctor‐diagnosis of asthma with limited description of asthma features . Doctor‐diagnoses of asthma may represent asthma or wheezing unrelated to asthma . Objectives of this study were to determine if asthma characteristics are present in adults with a doctor‐diagnosis of asthma and /or wheezing , and to examine the relationship between doctor‐diagnosis of asthma , wheezing and SCD morbidity . This was an observational cohort study of 114 adults with SCD who completed respiratory symptom question naires and had serum IgE measurements . A subset of 79 participants completed pulmonary function testing . Survival analysis was based on a mean prospect i ve follow‐up of 28 months and data were censored at the time of death or loss to follow‐up . Adults reporting a doctor‐diagnosis of asthma ( N = 34 ) were more likely to have features of asthma including wheeze , eczema , family history of asthma , and an elevated IgE level ( all P < 0.05 ) . However , there was no difference in pain or ACS rate , lung function , or risk of death between adults with and without a doctor‐diagnosis of asthma . In contrast , adults who reported recurrent , severe episodes of wheezing ( N = 34 ) , regardless of asthma , had twice the rates of pain and ACS , decreased lung function and increased risk of death compared with adults without recurrent , severe wheezing . Asthma features were not associated with recurrent , severe wheezing . Our data suggest that wheezing in SCD may occur independently of asthma and is a marker of disease severity . Am . J. Hematol . 2011 . © 2011 Wiley‐Liss , Pain and acute chest syndrome ( ACS ) episodes are 2 of the most common causes of hospitalization in children with sickle cell anemia ( SCA ) . However , very few potentially modifiable risk factors for either condition have been identified . In this prospect i ve infant cohort study , we tested the hypothesis that asthma is associated with an increased incidence rate of pain and ACS episodes . An infant cohort was composed of 291 African American children with hemoglobin SS enrolled in the Cooperative Study for Sickle Cell Disease before age 6 months and followed beyond age 5 years . Asthma was defined by a physician diagnosis , an acute asthma event , or use of prescription asthma medications . The incidence rates of ACS and painful episodes were compared for children with and without asthma . A clinical diagnosis of asthma was made in 17 % of the cohort . Asthma was associated with more frequent ACS episodes ( 0.39 vs 0.20 events per patient year , P < .001 ) and painful episodes ( 1.39 vs 0.47 events per patient year , P < .001 ) . In conclusion , in children with SCA , asthma is associated with an increased incidence of sickle cell disease-related morbidity , including ACS and painful episodes An analysis of a prospect i ve cohort of individuals with sickle cell anemia ( SCA ) , enrolled from birth through adulthood , was conducted to determine if asthma is a risk factor for death in SCA . All-cause mortality was determined for participants after adjusting for known risk factors for death in SCA . The study included 1,963 individuals who were followed for 18,495 patient-years . After controlling for established risk factors , individuals with SCA and asthma had a more than two-fold higher risk of mortality ( hazard ratio 2.36 , 95 % CI 1.21 to 4.62 , p=0.01 ) . To summarize , asthma is a risk factor for death in SCA |
12,276 | 29,885,258 | Low psychological distress at baseline and non evidence -based interventions were the main factors identified for low effectiveness . | OBJECTIVE The aims of this meta- analysis were to estimate the overall effect size ( ES ) of psychological interventions on anxiety in patients with cancer and extract sample and intervention characteristics that influence effectiveness . | OBJECTIVE To evaluate the efficacy of an interactive self-help workbook in reducing distress , and improving quality of life ( QOL ) and coping for women recently diagnosed with breast cancer . DESIGN R and omised controlled trial comparing the use of the workbook and that of an information booklet . PARTICIPANTS AND SETTING 49 women with Stage 0 to II breast cancer diagnosed in the previous month and recruited from 1 February 2007 to 1 February 2008 , in two urban Australian public hospitals . MAIN OUTCOME MEASURES The primary outcome measures were depression , anxiety , and posttraumatic stress . Secondary outcomes included QOL , body image , and the coping styles helplessness/hopelessness , cognitive avoidance and anxious preoccupation . RESULTS After controlling for baseline levels , interactions at 3-month follow-up showed that participants in the workbook group had significantly lower levels of posttraumatic stress ( F[1,89 ] = 7.01 ; P = 0.01 ) , helplessness/hopelessness ( F [ 1,89 ] = 4.75 ; P = 0.03 ) , and cognitive avoidance ( F [ 1,89 ] = 4.95 ; P = 0.03 ) than those in the control ( information booklet ) group . However , women in the workbook group had significantly poorer body image than those in the control group ( F [ 1,89 ] = 6.43 ; P = 0.01 ) . At 6 months , only the body image interaction remained significant ( F [ 1,93 ] = 7.44 ; P = 0.01 ) . CONCLUSION These results suggest that a self-help workbook can be an effective , short-term intervention for improving posttraumatic stress , cognitive avoidance , and certain depressive symptoms in women recently diagnosed with breast cancer . However , issues related to body image need to be dealt with differently . TRIAL REGISTRATION Australian New Zeal and Clinical Trials Background The p value obtained from a significance test provides no information about the magnitude or importance of the underlying phenomenon . Therefore , additional reporting of effect size is often recommended . Effect sizes are theoretically independent from sample size . Yet this may not hold true empirically : non-independence could indicate publication bias . Methods We investigate whether effect size is independent from sample size in psychological research . We r and omly sample d 1,000 psychological articles from all areas of psychological research . We extracted p values , effect sizes , and sample sizes of all empirical papers , and calculated the correlation between effect size and sample size , and investigated the distribution of p values . Results We found a negative correlation of r = −.45 [ 95 % CI : −.53 ; −.35 ] between effect size and sample size . In addition , we found an inordinately high number of p values just passing the boundary of significance . Additional data showed that neither implicit nor explicit power analysis could account for this pattern of findings . Conclusion The negative correlation between effect size and sample s size , and the biased distribution of p values indicate pervasive publication bias in the entire field of psychology Melanoma accounts for > 79 % of skin cancer‐related deaths , although it accounts for only 4 % of skin cancer incidence . Given the potential for lethality , it is likely that patients with melanoma may experience significant emotional distress . The current study was design ed to determine the effect of a cognitive‐behavioral intervention on distress and health‐related quality of life ( HRQOL ) in patients with melanoma who had medium‐to‐high distress OBJECTIVE The aim is to evaluate the effectiveness of a manualized 12-week supportive-expressive group therapy program among primary breast cancer patients treated in community setting s , to determine whether highly distressed patients were most likely to benefit and whether therapist 's training or experience was related to outcome . METHOD Three hundred and fifty-three women within one year of diagnosis with primary breast cancer were r and omly assigned to receive supportive-expressive group therapy or to an education control condition . Participants were recruited from two academic centers and nine oncology practice s , which were members of NCI 's Community Clinical Oncology Program ( CCOP ) and were followed over 2 years . RESULTS A 2x2x19 analysis of variance was conducted with main effects of treatment condition , cohort , and baseline distress and their interactions . There was no main effect for treatment condition after removing one subject with an extreme score . Highly distressed women did not derive a greater benefit from treatment . Therapist training and psychotherapy experience were not associated with a treatment effect . CONCLUSIONS This study provides no evidence of reduction in distress as the result of a brief supportive-expressive intervention for women with primary breast cancer . Future studies might productively focus on women with higher initial levels of distress BACKGROUND As cancer mortality rates improve in Singapore , there is an increasing need to improve the transition to posttreatment survivorship care . This study aim ed to evaluate the effectiveness of a psychoeducation group ( PEG ) intervention program compared with usual care to reduce distress for physical symptom and psychological aspects in Asian breast cancer survivors who have completed adjuvant chemotherapy . METHODS This was a r and omized , controlled trial comprising 72 Asian early stage breast cancer survivors who were r and omized into the PEG ( n = 34 ) or the control ( n = 38 ) arm . The participants in the PEG arm underwent a weekly multidisciplinary PEG program delivered in a group format over 3 weeks coupled with cultural adaptation . Both arms were assessed at baseline and 2 months after intervention using the Rotterdam Symptom Checklist , Beck Anxiety Inventory , and EORTC QLQ-C30 . A satisfaction question naire was also conducted among those survivors who have participated in the PEG program . Effective sizes were calculated using Cohen d. RESULTS The mean age ± SD of all participants was 53.0 ± 8.9 years , with the majority being Chinese ( 84.7 % ) and Malay ( 6.9 % ) , and clinical characteristics were well balanced in both arms . Compared to the control arm , the PEG arm showed a significantly greater reduction in physical symptom distress ( d = 0.76 , P = .01 ) and fatigue ( d = 0.49 , P = .04 ) . The 82.4 % of the participants in the intervention group responded to the satisfaction question naire , and the majority ( 92.9 % ) agreed that the overall duration of the PEG intervention program was appropriate . CONCLUSIONS A culturally adapted PEG program was effective in reducing physical symptom distress in Asian breast cancer survivors . ( Clinical Trials.gov : NCT02600299 ) Background Web and mobile technologies appear to hold promise for delivering evidence -informed and evidence -based intervention to cancer survivors and others living with trauma and other psychological concerns . Health-space.net was developed as a comprehensive online social networking and coping skills training program for cancer survivors living with distress . Purpose The purpose of this study was to evaluate the effects of a 12-week social networking intervention on distress , depression , anxiety , vigor , and fatigue in cancer survivors reporting high levels of cancer-related distress . Methods We recruited 347 participants from a local cancer registry and internet , and all were r and omized to either a 12-week waiting list control group or to immediate access to the intervention . Intervention participants received secure access to the study website , which provided extensive social networking capabilities and coping skills training exercises facilitated by a professional facilitator . Results Across time , the prevalence of clinical ly significant depression symptoms declined from 67 to 34 % in both conditions . The health-space.net intervention had greater declines in fatigue than the waitlist control group , but the intervention did not improve outcomes for depression , trauma-related anxiety symptoms , or overall mood disturbance . For those with more severe levels of anxiety at baseline , greater engagement with the intervention was associated with higher levels of symptom reduction over time . Conclusions The intervention result ed in small but significant effects on fatigue but not other primary or secondary outcomes . Results suggest that this social networking intervention may be most effective for those who have distress that is not associated with high levels of anxiety symptoms or very poor overall psychological functioning . Trial Registration NumberThe trial was registered with the Clinical Trials.gov data base ( Clinical Trials.gov # NCT01976949 ) OBJECTIVE To compare in a multicenter r and omized controlled trial the benefits in terms of anxiety regulation of a 15-session single-component group intervention ( SGI ) based on support with those of a 15-session multiple-component structured manualized group intervention ( MGI ) combining support with cognitive-behavioral and hypnosis components . METHODS Patients with nonmetastatic breast cancer were r and omly assigned at the beginning of the survivorship period to the SGI ( n = 83 ) or MGI ( n = 87 ) . Anxiety regulation was assessed , before and after group interventions , through an anxiety regulation task design ed to assess their ability to regulate anxiety psychologically ( anxiety levels ) and physiologically ( heart rates ) . Question naires were used to assess psychological distress , everyday anxiety regulation , and fear of recurrence . Group allocation was computer generated and concealed till baseline completion . RESULTS Compared with patients in the SGI group ( n = 77 ) , patients attending the MGI group ( n = 82 ) showed significantly reduced anxiety after a self-relaxation exercise ( P = .006 ) and after exposure to anxiety triggers ( P = .013 ) and reduced heart rates at different time points throughout the task ( P = .001 to P = .047 ) . The MGI participants also reported better everyday anxiety regulation ( P = .005 ) , greater use of fear of recurrence-related coping strategies ( P = .022 ) , and greater reduction in fear of recurrence-related psychological distress ( P = .017 ) compared with the SGI group . CONCLUSIONS This study shows that an MGI combining support with cognitive-behavioral techniques and hypnosis is more effective than an SGI based only on support in improving anxiety regulation in patients with breast cancer To compare the effectiveness of individual support , group rehabilitation and a combination of the two in improving health-related quality of life ( HRQOL ) and psychological well-being in cancer patients during 24 months after diagnosis , as compared with st and ard care ( SC ) . Furthermore , to compare the study sample and a r and om sample of the Swedish population with regard to HRQOL . A total of 481 consecutive patients , newly diagnosed with cancer , were r and omly assigned to one of the four alternatives . Data on HRQOL and psychological well-being were collected at baseline and after 3 , 6 , 12 and 24 months . The interventions did not improve HRQOL or psychological well-being , as compared with SC . At 3 months , the study sample reported an HRQOL comparable with the normal population . Many cancer patients are able to manage their cancer-related concerns with the support available from SC . However , it is reasonable to assume that the findings suffer from a lack of data from especially vulnerable patients and a possible Hawthorne effect . It can not be concluded that cancer patients have no need for additional psychosocial interventions . Future projects should include screening and target interventions for those at risk for significant and prolonged psychological distress BACKGROUND The aim of this study was to assess the efficacy of meaning-centered group psychotherapy for cancer survivors ( MCGP-CS ) to improve personal meaning , compared with supportive group psychotherapy ( SGP ) and care as usual ( CAU ) . METHOD A total of 170 cancer survivors were r and omly assigned to one of the three study arms : MCGP-CS ( n = 57 ) ; SGP ( n = 56 ) ; CAU ( n = 57 ) . The primary outcome measure was the Personal Meaning Profile ( PMP ; total score ) . Secondary outcome measures were subscales of the PMP , psychological well-being ( Scales of Psychological Well-being ; SPWB ) , post-traumatic growth ( Posttraumatic Growth Inventory ) , Mental Adjustment to Cancer ( MAC ) , optimism ( Life Orientation Test-Revised ) , hopelessness ( Beck 's Hopelessness Scale ) , psychological distress ( anxiety and depression , Hospital Anxiety and Depression Scale ; HADS ) and quality of life ( European Organization for Research and Treatment of Cancer Quality of Life Question naire ; EORTC QLQ-C30 ) . Outcome measures were assessed before r and omization , post-intervention , and after 3 and 6 months of follow-up ( FU ) . RESULTS Linear mixed model analyses ( intention-to-treat ) showed significant differences between MCGP-CS , SGP and CAU on the total PMP score , and on (sub)scales of the PMP , SPWB , MAC and HADS . Post-hoc analyses showed significantly stronger treatment effects of MCGP-CS compared with CAU on personal meaning ( d = 0.81 ) , goal -orientedness ( d = 1.07 ) , positive relations ( d = 0.59 ) , purpose in life ( d = 0.69 ) ; fighting spirit ( d = 0.61 ) ( post-intervention ) and helpless/hopeless ( d = -0.87 ) ( 3 months FU ) ; and distress ( d = -0.6 ) and depression ( d = -0.38 ) ( 6 months FU ) . Significantly stronger effects of MCGP-CS compared with SGP were found on personal growth ( d = 0.57 ) ( 3 months FU ) and environmental mastery ( d = 0.66 ) ( 6 months FU ) . CONCLUSIONS MCGP-CS is an effective intervention for cancer survivors to improve personal meaning , psychological well-being and mental adjustment to cancer in the short term , and to reduce psychological distress in the long run INTRODUCTION Gaining regular insight into the nature and severity of distress by a psychosocial nurse coupled with referral to psychosocial and /or paramedical healthcare provider(s ) is an experimental supportive care approach . We sought to examine the effects of this approach on quality of life ( QoL ) , patient 's mood and satisfaction , end-of-life care and survival in patients with lung cancer . METHODS Patients with newly diagnosed or recurrent lung cancer starting systemic therapy were r and omly assigned to receive usual care or the experimental approach . Patients were followed up at 1 , 7 , 13 and 25 weeks after r and omisation with the EORTC-QLQ-C30 , the European Quality of Life-5D , the Hospital Anxiety and Depression Scale and the Patient Satisfaction Question naire-III . Primary outcome was the mean change in the EORTC-QLQ-C30 global QoL-score between 1 and 25 weeks . RESULTS A total of 223 patients were r and omised of whom 111 ( 50 % ) completed all four assessment s ( 44 % in the usual care group versus 55 % in the experimental group ) . No significant difference was found in the mean change global QoL-score ( -2.4 , 95 % CI : 12.1 - 7.2 ; P = 0.61 ) , nor in the other patient-reported outcomes . Fewer patients in the experimental group received chemotherapy shortly before the end-of-life , and median survival was comparable ( 10.3 versus 10.1 months , P = 0.62 ) . Of the 112 dropouts , 33 died and 79 discontinued participation for other reasons . CONCLUSIONS This supportive care approach neither improved QoL nor other patient-reported outcomes in patients with lung cancer . However , it reduced the use of chemotherapy shortly before the end of life . Possibly , ( late ) side effects of systemic therapy may have obscured effects of our intervention on QoL. CLINICAL TRIAL REGISTRATION NTR3540 In a prospect i ve , r and omized study , an individual psychosocial support intervention performed by specially trained oncology nurses , or psychologists , were compared with st and ard care . Consecutive primary breast cancer patients about to start adjuvant therapy ( n = 179 ) were included . Data were supplied by the question naires European Organisation for Research and Treatment of Cancer Quality of Life Study Group Core Quality of life question naire with 30 questions ( EORTC QLQ-C30 ) and Breast Cancer Module with 23 questions ( BR23 ) , the Hospital Anxiety and Depression Scale , Spielberger 's State-Trait Anxiety Inventory , and the Impact of Event Scale before r and omization and 1 , 3 , and 6 months later . Patient files provided data on utilization of psychosocial support offered in routine care . Global quality of life/health status , nausea and vomiting , and systemic therapy side effects were the subscales showing significant Group by Time interactions , favoring the interventions . Intervention groups improved statistically significantly more than the st and ard care group regarding insomnia , dyspnea , and financial difficulties . Nurse patients experienced less intrusion compared with the st and ard care group . All groups showed statistically and clinical ly significant improvements with time on several subscales . The intervention groups , however , improved to a greater extent . Fewer patients in the intervention groups used psychosocial hospital support compared with the st and ard care group . In conclusion , psychosocial support by specially trained nurses using techniques derived from cognitive behavioral therapy is beneficial for breast cancer patients and may be a realistic alternative in routine cancer care Background Many patients with cancer experience depression and anxiety , and an associated decrease in quality of life ( QOL ) during radiation therapy ( RT ) . The main objective of the study was to determine the benefits of psychosocial interventions for cancer patients who received RT . Methods Patients with cancer ( n = 178 ) who agreed to participate in the study were r and omized to the intervention arm ( n = 89 ) or the control arm ( n = 89 ) . Patients in the intervention group received psychosocial care during RT , whereas the control group received RT only . The benefits of the intervention were evaluated using the Zung Self-rating Depression Scale ( SDS ) to measure depression , the Self-rating Anxiety Scale ( SAS ) to assess anxiety , and the European Organization for Research and Treatment of Cancer Quality of Life Question naire-Core 30 ( EORTC QLQ-C30 ) to survey health-related QOL . The association between intervention and survival was also assessed . Results Patients r and omly assigned to the intervention arm showed significant improvements on symptoms of depression ( p < 0.05 ) and anxiety ( p < 0.05 ) , health-related QOL ( p < 0.05 ) ( i.e. better global health status , and physical and emotional functioning , and less insomnia ) when compared with controls . In the subset analysis , female patients , those that received high dose irradiation , and those that underwent adjuvant chemotherapy could benefit more from psychosocial intervention . There was no difference between the two groups in disease-free survival ( DFS ) ( 2-year DFS 79.8 % in the intervention arm and 76.4 % in the control arm ; p = 0.527 ) and overall survival ( OS ) ( 2-year OS 83.1 % in the intervention arm and 84.3 % in the control arm ; p = 0.925 ) Conclusions Psychosocial intervention is a cost-effective approach that can improve a patient ’s mood and QOL both during and after RT . However , the intervention was not found to reduce the risk of cancer recurrence and death . Trial registration To reduce the risk of adjustment problems for breast cancer patients in mainl and China , we examined the efficacy of a multidiscipline mentor-based program , Be Resilient to Breast Cancer ( BRBC ) , delivered after breast surgery to ( a ) increase protective factors of social support , hope for the future , etc . ; ( b ) decrease risk factors of Physical and Emotional Distress ; and ( c ) increase outcomes of Resilience , Transcendence and Quality of Life ( QOL ) . A multisite r and omized controlled trial was conducted at 6 specialist cancer hospitals . 101 and 103 breast cancer patients were allocated to intervention group ( IG ) and control group ( CG ) , respectively , and 112 general females ( without breast cancer ) were allocated to the norm group ( NG ) . Participants completed measures that were related to latent variables derived from the Resilience Model for Breast Cancer ( RM-BC ) at baseline ( T1 ) , 2 months ( T2 ) , 6 months ( T3 ) , and 12 months ( T4 ) after intervention . At T2 , the IG reported significantly lower Depression ( ES = 0.65,P = 0.0019 ) and Illness Uncertainty ( ES = 0.57 , P = 0.004 ) , better Hope ( ES = 0.81 , P < 0.001 ) and QOL ( ES = 0.60 , P = 0.002 ) than did the CG . At T3 , the IG reported significantly lower Anxiety ( ES = 0.74 , P < 0.001 ) , better Social Support ( ES = 0.51,P = 0.009 ) , Transcendence ( ES = 0.87 , P < 0.001 ) , and Resilience ( ES = 0.83 , P < 0.001 ) compared with the CG . At T4 , the IG reported better Resilience though not significant ( P = 0.085 ) and better Transcendence ( P = 0.0243 ) than did the NG . The BRBC intervention improves the positive health outcomes and decreases the risk factors of illness-related distress of breast cancer patients during the high-risk cancer treatment ABSTRACT Background : Anxiety among patients after surgery can affect their physiological and psychological well-being . The aim of this study was to investigate and compare the effects of Benson ’s relaxation and rhythmic breathing techniques on postoperative anxiety in c and i date s for the mastectomy surgery . Methods : This r and omized controlled clinical trial study was conducted with ninety patients in 2013 . The patients were hospitalized for the mastectomy surgery in three surgical wards in a teaching hospital , Tehran , Iran . They were r and omly assigned into three groups : Benson ’s relaxation including the cognitive relaxation technique type , rhythmic breathing including the somatic relaxation technique type and control groups . According to the Davidson and Schwartz multi-process theory , the Benson ’s relaxation and the rhythmic breathing techniques have cognitive and somatic effects , respectively . One day before the surgery , the patients in the intervention groups were trained regarding relaxation and breathing techniques and were asked to perform the techniques under the supervision of the research er in the night before the surgery . The cognitive somatic anxiety question naire was used to measure anxiety before the intervention and half an hour after recovery of consciousness after the surgery . Descriptive and inferential statistics were used for data analysis via the SPSS v.21 software . Results : There were no statistically significant differences between the groups in terms of demographic characteristics . The application of both techniques reduced the level of patients ’ anxiety after the surgery . The patients in the Benson ’s relaxation technique group reported only the relief of somatic anxiety . However , the breathing technique patients reported a reduction in both cognitive and somatic anxiety . Conclusion : The Benson ’s relaxation and rhythmic breathing techniques can reduce postoperative anxiety in patients after the mastectomy surgery . Trial Registration Number : I RCT Abstract Objective : To determine the efficacy of adjuvant psychological therapy in patients with testicular cancer and to compare the characteristics and psychosocial outcomes of men who agreed to participate with those who declined to participate in a r and omised trial of psychological intervention . Design : Newly diagnosed patients were asked to participate in a r and omised trial of psychological support compared with st and ard medical care . Participants and non- participants completed self assessment question naires at baseline and at 2 , 4 and 12 months . Setting : Testicular Tumour Unit of the Royal Marsden Hospital . Subjects : 73 of 184 ( 40 % ) eligible patients agreed to enter the r and omised trial ( participants ) and 81 ( 44 % ) declined to participate but agreed to complete further assessment s ( non- participants ) . 30 patients wanted no further contact with the research ers . Outcome measures : Hospital anxiety and depression scale , psychosocial adjustment to illness scale , Rotterdam symptom checklist , mental adjustment to cancer scale . Only scores on the hospital anxiety and depression scale are reported for evaluating treatment efficacy . Results : 111 of 184 ( 60 % ) eligible men declined to participate in the trial . Patients with stage I disease were most likely to refuse to participate . A patient was less likely to participate if he had low volume disease and was receiving no further treatment . Likelihood of participation was associated with stage of disease and with type of primary treatment ( P<0.001 for heterogeneity ) . Patients with early stage disease ( P<0.001 ) and fewer physical symptoms ( P<0.001 ) were less likely to participate . Psychosocial factors associated with participation included anxious preoccupation regarding disease ( P=0.01 ) . There were no differences in outcome between participants and non- participants during follow up . Patients seemed to gain little benefit from adjuvant psychological therapy . At 2 months change from baseline favoured the treated group in the anxiety subscale ( mean difference between groups −1.41 ( 95 % confidence interval −2.86 to 0.03 ) ) . This was not sustained when adjusted for factors related to the disease . By 12 months change from baseline seemed to favour the control group ( mean difference between groups 1.66 ( −0.18 to 3.50 ) ) . Conclusions : Patients with testicular cancer seem to have considerable coping abilities . Those who declined to participate in the trial differed from those who participated . Those who agreed to participate may comprise the clinical group who perceive a need for psychological support . No evidence was found to indicate a need for routinely offering adjuvant psychological therapy . Key messages Counselling for patients with cancer is widely advocated , although its effectiveness has not been fully evaluated No study of patients with cancer has evaluated a psychological intervention in young men or in a group of patients with a disease with an excellent prognosis Most patients with testicular cancer declined to participate in this r and omised trial of adjuvant psychological therapy , and those who participated had more psychosocial dysfunction No evidence of benefit was observed after treatment with adjuvant psychological therapy in this group of patients There were no consistently significant differences in psychosocial outcome over one year between those who agreed to participate and those who declined to OBJECTIVE To evaluate Telephone-Delivered Cognitive Behavioural Therapy ( T-CBT ) compared to CBT face to face treatment as usual ( TAU-CBT ) , in cancer patients with high psychological needs , in terms of mental health and coping . METHOD A prospect i ve r and omised equivalence trial with Patient Reported Outcome ( PRO 's ) , measured pre- and post-therapy including ; Hospital Anxiety and Depression Scale ( HADS ) , Mental Adjustment to Cancer Scale : Helpless/Hopeless subscale only ( MAC H/H ) , Checklist of Cancer Concerns ( CLCC ) and the Cancer Coping Question naire ( CCQ ) . A study -specific Service Evaluation Question naire ( SEQ ) was include . RESULTS Assessment of change scores , in n = 118 r and omised patients referred for psychological care , indicate significant improvements ( P < 0.01 or greater ) for both therapy groups pre- and post-therapy in HADS anxiety , depression and total scores and cancer concerns ( CLCC ) . Overall , for the groups combined , there is a significant shift towards reduction of CCQ stress ( P = 0.028 ) and worry ( P = 0.003 ) post-therapy when compared to baseline levels . Median number of therapy sessions was four . For cancer coping ( CCQ ) and for Mental Adjustment to Cancer ( MAC ) there were significant change scores only for Positive Focus and Helpless/hopeless scores respectively , in the TAU-CBT group . Although equivalence was not observed , the data demonstrate that T-CBT was non-inferior to TAU-CBT . CONCLUSIONS Delivery of CBT to patients with clinician identified high need can be offered according to patient choice without loss of mental health benefit . Both TAU-CBT and T-CBT are effective at reducing mental health problems on the specific outcome measures BACKGROUND Cognitive behaviour therapy ( CBT ) has been shown to reduce psychological morbidity in people with cancer , but no r and omized controlled trial ( RCT ) exists in palliative care . We aim ed to determine whether home care nurses could be taught to deliver basic cognitive behavioural techniques and so reduce symptoms of anxiety and depression . METHOD Clinical nurse specialists ( CNSs ) at St Christopher 's Hospice were r and omly allocated to receive training in CBT or continue their usual practice . At the end of the trial , nurses were rated on the Cognitive Therapy First Aid Rating Scale ( CTFARS ) for CBT competence . Home care patients who scored as possible cases on the Hospital Anxiety and Depression Scale ( HADS ) entered the trial . Participants received home care nursing visits . Assessment s were carried out at baseline , 6 , 10 and 16 weeks . RESULTS Eight nurses received CBT training and seven continued practice as usual . The mean CTFARS scores were 35.9 for the CBT nurses and 19.0 for the controls ( p=0.02 ) . A total of 328 patients ( 54 % ) were possible cases and 80 entered the trial ; most of those excluded were too ill to participate . There was an interaction between group and time : individuals receiving CBT had lower anxiety scores over time [ coefficient -0.20 , 95 % confidence interval ( CI ) -0.35 to -0.05 , p=0.01 ] . No effect of the training was found for depression . CONCLUSIONS It is possible to conduct a r and omized trial of psychological interventions in palliative care but there is considerable attrition from physical morbidity and mortality . Nurses can learn to integrate basic CBT methods into their clinical practice . This training may be associated with better outcomes for symptoms of anxiety AIM This paper is a report of a study to describe the efficacy of cognitive behavioural therapy for insomnia on fatigue , mood and quality of life in breast cancer survivors . BACKGROUND Women who receive primary treatment for breast cancer often complain of insomnia . Rarely evaluated in insomnia intervention studies is the effect of cognitive behavioural treatment on the psychosocial outcomes of fatigue , mood and quality of life . METHOD Data were collected between December 2002 and March 2004 with 72 women who were at least 3 months post-completion of primary treatment without current evidence of disease . Women were r and omly assigned to either the cognitive behavioural therapy for insomnia group , which received stimulus control instructions , sleep restriction therapy and sleep education and hygiene , or the component control group which received sleep education and hygiene only . The 10-week study consisted of 2 weeks of pre-treatment , 6 weeks of treatment and 2 weeks of post-treatment . Fatigue , mood and quality of life were measured at pre- and post-treatment . FINDINGS Women receiving cognitive behavioural therapy for insomnia had significant improvements in fatigue , trait anxiety , depression and quality of life . The component control group also had statistically significant increases in quality of life , with a trend suggestive of lower depression at post-treatment . CONCLUSION Globally , as the number of survivors in this population continues to grow , it is imperative that nurses continue testing interventions that may positively affect quality of life and the commonly experienced symptoms of fatigue , anxiety and depression BACKGROUND The aim of this study was to evaluate the short-term effectiveness of the web-based computer-tailored intervention Kanker Nazorg Wijzer ( Cancer Aftercare Guide ) . The intervention aims to support cancer survivors with managing psychosocial and lifestyle-related issues . In this study , the impact on quality of life , anxiety , depression , and fatigue were evaluated . METHODS Cancer survivors were recruited through 21 Dutch hospitals ( November 2013-June 2014 ) . Outcome measures included quality of life ( European Organization for Research and Treatment of Cancer Quality of Life Question naire-C30 ) , anxiety and depression ( Hospital Anxiety and Depression Scale ) , and fatigue ( Checklist Individual Strength ) . In a r and omized controlled trial with an intervention group ( n = 231 ) and a waiting list control group ( n = 231 ) , the short-term effectiveness was evaluated through multilevel linear regression analyses , controlling for selective dropout , baseline differences , and several demographic and disease-related characteristics . RESULTS In total , 188 participants of the intervention group and 221 of the control group completed the 6-month measurement ( dropout = 11.5 % ) . The intervention was effective in reducing depression ( B = -0.63 , p = 0.007 , f2 = 0.019 , d = 0.21 ) and fatigue ( B = -4.36 , p = 0.020 , f2 = 0.013 , d = 0.21 ) . In addition , effects were found for emotional ( B = 3.47 , p = 0.022 , f2 = 0.013 , d = 0.15 ) and social functioning ( B = 3.95 , p = 0.011 , f2 = 0.017 , d = 0.15 ) , although this evidence was less strong . There were indications that the effects of fatigue and social functioning were influenced by module use . CONCLUSIONS While effect sizes were small , they can be considered as clinical ly relevant . With the Cancer Aftercare Guide being an effective , low-intensive , and easy accessible intervention , it could serve as a first step in stepped care for needs assessment and initial support for psychosocial problems that are present after cancer treatment . Copyright © 2016 John Wiley & Sons , PURPOSE This r and omized clinical trial tests the hypothesis that a psychological intervention can reduce emotional distress , improve health behaviors and dose-intensity , and enhance immune responses . PATIENTS AND METHODS We studied 227 women who were surgically treated for regional breast cancer . Before adjuvant therapy , women completed interviews and question naires assessing emotional distress , social adjustment , and health behaviors . A 60-mL blood sample was drawn for immune assays . Patients were r and omly assigned to either the intervention group or assessment only group . The intervention was conducted in small patient groups , with one session per week for 4 months . The sessions included strategies to reduce stress , improve mood , alter health behaviors , and maintain adherence to cancer treatment and care . Re assessment occurred after completion of the intervention . RESULTS As predicted , patients receiving the intervention showed significant lowering of anxiety , improvements in perceived social support , improved dietary habits , and reduction in smoking ( all P < .05 ) . Analyses of adjuvant chemotherapy dose-intensity revealed significantly more variability ( ie , more dispersion in the dose-intensity values ) for the assessment arm ( P < .05 ) . Immune responses for the intervention patients paralleled their psychological and behavioral improvements . T-cell proliferation in response to phytohemagglutinin and concanavalin A remained stable or increased for the Intervention patients , whereas both responses declined for Assessment patients ; this effect was replicated across three concentrations for each assay ( all P < .01 ) . CONCLUSION These data show a convergence of significant psychological , health behavior , and biologic effects after a psychological intervention for cancer patients BACKGROUND We conducted a r and omised , controlled trial of cognitive-existential group therapy ( CEGT ) for women with early stage breast cancer receiving adjuvant chemotherapy with the aim of improving mood and mental attitude to cancer . METHODS Women were r and omised to 20 sessions of weekly group therapy plus 3 relaxation classes or to a control arm receiving 3 relaxation classes . Assessment s , independently done at baseline , 6 and 12 months , included a structured psychiatric interview and vali date d question naires covering mood , attitudes to cancer , family relationships , and satisfaction with therapy . RESULTS Three hundred and three of 491 ( 62 % ) eligible patients participated over 3 years . Distress was high pre-intervention : 10 % were diagnosed as suffering from major depression , 27 % from minor depression and 9 % from anxiety disorders . On an intention-to-treat analysis , there was a trend for those receiving group therapy ( n=154 ) to have reduced anxiety ( p=0.05 , 2-sided ) compared to controls ( n=149 ) . Women in group therapy also showed a trend towards improved family functioning compared to controls ( p=0.07 , 2-sided ) . The women in the groups reported greater satisfaction with their therapy ( p<0.001 , 2-sided ) , appreciating the support and citing better coping , self-growth and increased knowledge about cancer and its treatment . They valued the CEGT therapy . Overall effect size for the group intervention was small ( d=0.25 ) , with cancer recurrence having a deleterious effect in three of the 19 therapy groups . Psychologists as a discipline achieved a moderate mean effect size ( d=0.52 ) . CONCLUSION CEGT is a useful adjuvant psychological therapy for women with early stage breast cancer . Interaction effects between group members and therapists are relevant to outcome . Group-as-a-whole effects are powerful , but the training and experience of the therapist is especially critical to an efficacious outcome PURPOSE The r and omized study aim ed to determine the efficacy of psychological intervention consisting of relaxation and guided imagery to reduce anxiety and depression in gynecologic and breast cancer patients undergoing brachytherapy during hospitalization . METHODS AND MATERIAL S Sixty-six patients programmed to receive brachytherapy in two hospitals in Barcelona ( Spain ) were included in this study . The patients were r and omly allocated to either the study group ( n=32 ) or the control group ( n=34 ) . Patients in both groups received training regarding brachytherapy , but only study group patients received training in relaxation and guided imagery . After collection of sociodemographic data , all patients were given a set of question naires on anxiety and depression : the Hospital Anxiety and Depression Scale ( HADS ) , and on quality of life : Cuestionario de Calidad de Vida QL-CA-AFex ( CCV ) , prior to , during and after brachytherapy . RESULTS The study group demonstrated a statistically significant reduction in anxiety ( p=0.008 ) , depression ( p=0.03 ) and body discomfort ( p=0.04 ) compared with the control group . CONCLUSIONS The use of relaxation techniques and guided imagery is effective in reducing the levels of anxiety , depression and body discomfort in patients who must remain isolated while undergoing brachytherapy . This simple and inexpensive intervention enhances the psychological wellness in patients undergoing brachytherapy . State : This study has passed Ethical Committee review Background Breathlessness , cough and fatigue are distressing symptoms for patients with lung cancer . There is evidence that these three symptoms form a discreet symptom cluster . This study aim ed to feasibly test a new non-pharmacological intervention for the management of the Respiratory Distress Symptom Cluster ( breathlessness-cough-fatigue ) in lung cancer . Method This was a multi-centre , r and omised controlled non-blinded parallel group feasibility trial . Eligible patients ( patients with primary lung cancer and ‘ bothered ’ by at least two of the three cluster symptoms ) received usual care plus a multicomponent intervention delivered over two intervention training sessions and a follow-up telephone call or usual care only . Follow-up was for 12 weeks , and end-points included six numerical rating scales for breathlessness severity , Dyspnoea-12 , Manchester Cough in Lung Cancer scale , FACIT-Fatigue scale , Hospital Anxiety and Depression scale , Lung Cancer Symptom Scale and the EQ-5D-3L , collected at baseline , week 4 and week 12 . Results One hundred seven patients were r and omised over 8 months ; however , six were removed from further analysis due to protocol violations ( intervention group n = 50 and control group n = 51 ) . Of the ineligible patients ( n = 608 ) , 29 % reported either not experiencing two or more symptoms or not being ‘ bothered ’ by at least two symptoms . There was 29 % drop-out by week 4 , and by week 12 , a further two patients in the control group were lost to follow-up . A sample size calculation indicated that 122 patients per arm would be needed to detect a clinical ly important difference in the main outcome for breathlessness , cough and fatigue . Conclusions The study has provided evidence of the feasibility and acceptability of a new intervention in the lung cancer population and warrants a fully powered trial before we reach any conclusions . The follow-on trial will test the hypothesis that the intervention improves symptom cluster of breathlessness , cough and fatigue better than usual care alone . Full economic evaluation will be conducted in the main trial PURPOSE Survivors of cervical cancer experience quality -of-life ( QOL ) disruptions that persist years after treatment . This study examines the effect of a psychosocial telephone counseling ( PTC ) intervention on QOL domains and associations with biomarkers . PATIENTS AND METHODS We conducted a r and omized clinical trial in survivors of cervical cancer , who were ≥ 9 and less than 30 months from diagnosis ( n = 204 ) , to compare PTC to usual care ( UC ) . PTC included five weekly sessions and a 1-month booster . Patient-reported outcomes ( PROs ) and biospecimens were collected at baseline and 4 and 9 months after enrollment . Changes in PROs over time and associations with longitudinal change in cytokines as categorical variables were analyzed using multivariable analysis of variance for repeated measures . RESULTS Participant mean age was 43 years ; 40 % of women were Hispanic , and 51 % were non-Hispanic white . Adjusting for age and baseline scores , participants receiving PTC had significantly improved depression and improved gynecologic and cancer-specific concerns at 4 months compared with UC participants ( all P < .05 ) ; significant differences in gynecologic and cancer-specific concerns ( P < .05 ) were sustained at 9 months . Longitudinal change in overall QOL and anxiety did not reach statistical significance . Participants with decreasing interleukin ( IL ) -4 , IL-5 , IL-10 , and IL-13 had significantly greater improvement in QOL than those with increasing cytokine levels . CONCLUSION This trial confirms that PTC benefits mood and QOL cancer-specific and gynecologic concerns for a multiethnic underserved population of survivors of cancer . The improvement in PROs with decreases in T-helper type 2 and counter-regulatory cytokines supports a potential biobehavioral pathway relevant to cancer survivorship Background Radiotherapy for localised prostate cancer has many known and distressing side effects . The efficacy of group interventions for reducing psychological morbidity is lacking . This study investigated the relative benefits of a group nurse-led intervention on psychological morbidity , unmet needs , treatment-related concerns and prostate cancer-specific quality of life in men receiving curative intent radiotherapy for prostate cancer . Methods This phase III , two-arm cluster r and omised controlled trial included 331 men ( consent rate : 72 % ; attrition : 5 % ) r and omised to the intervention ( n = 166 ) or usual care ( n = 165 ) . The intervention comprised four group and one individual consultation all delivered by specialist uro-oncology nurses . Primary outcomes were anxious and depressive symptoms as assessed by the Hospital Anxiety and Depression Scale . Unmet needs were assessed with the Supportive Care Needs Survey-SF34 Revised , treatment-related concerns with the Cancer Treatment Scale and quality of life with the Exp and ed Prostate Cancer Index −26 . Assessment s occurred before , at the end of and 6 months post-radiotherapy . Primary outcome analysis was by intention-to-treat and performed by fitting a linear mixed model to each outcome separately using all observed data . Results Mixed models analysis indicated that group consultations had a significant beneficial effect on one of two primary endpoints , depressive symptoms ( p = 0.009 ) , and one of twelve secondary endpoints , procedural concerns related to cancer treatment ( p = 0.049 ) . Group consultations did not have a significant beneficial effect on generalised anxiety , unmet needs and prostate cancer-specific quality of life . Conclusions Compared with individual consultations offered as part of usual care , the intervention provides a means of delivering patient education and is associated with modest reductions in depressive symptoms and procedural concerns . Future work should seek to confirm the clinical feasibility and cost-effectiveness of group interventions .Trial registration Australian and New Zeal and Clinical Trials Registry ANZCTRN012606000184572 . 1 March 2006 OBJECTIVE This study evaluated the psychological effects of a pre-surgical stress management training ( SMT ) in cancer patients . METHODS Stress management training comprised four sessions in total : on 5 days and 1 day pre-surgery and on 2 days and 1 month post-surgery . Patients also received audio CDs with relaxation and coping skills exercises . Patients were r and omly assigned to the SMT ( N = 34 ) or a regular care condition ( N = 36 ) . Depression , anxiety , quality of life , perception of control , fatigue , pain , sleep problems , and surgery-related somatic symptoms were measured at Day 6 and Day 1 pre-surgery , and Day 2 , 5 , 30 and 90 post-surgery . RESULTS Depression and fatigue decreased in the intervention group and increased in the control group , leading to significant group differences at Day 2 ( fatigue ) and Day 5 post-surgery ( fatigue and depression ) . It also appeared that surgery-related symptoms had increased more in the control group 3 months post-surgery than in the SMT group . No intervention effects were observed for anxiety , pain , and sleep problems . CONCLUSION The use of a short psychological intervention is effective in reducing depression and fatigue in the post-surgical period , although the effects are of short duration Abstract Psychological distress contributes to impaired quality of life in hematological cancer patients . Stepped care treatment , in which patients start with the least intensive treatment most likely to work and only receive more intensive interventions if needed , could improve distress . We aim ed to evaluate the outcome of stepped care treatment on psychological distress and physical functioning in patients treated with autologous stem cell transplantation for hematological malignancies . In the present study , we performed a r and omized clinical trial with two treatment arms : stepped care and care as usual . Baseline assessment and r and omization occurred during pre-transplant hospitalization . Stepped care was initiated after 6 weeks , consisting of ( 1 ) watchful waiting , ( 2 ) Internet-based self-help intervention , and ( 3 ) face-to-face counseling/ psychopharmacological treatment/ referral . Follow-up measurements were conducted at 13 , 30 , and 42 weeks after transplantation . Stepped care ( n = 47 ) and care as usual ( n = 48 ) were comparable on baseline characteristics . The uptake of the intervention was low : 24 patients started with step 1 , 23 with step 2 , and none with step 3 . Percentages of distressed patients ranged from 4.1 to 9.7 % . Ten percent of patients received external psychological or psychiatric care . No statistically significant differences were found between stepped care and care as usual on psychological distress or physical functioning in intention to treat analyses , nor in per protocol analyses . The stepped care program was not effective in decreasing psychological distress . The low intervention uptake , probably related to the low levels of psychological distress , offers an explanation for this outcome . Future research should take into account patients ’ specific care needs . Netherl and s Trial Registry identifier : NTR1770 Background : Breast cancer patients frequently experience psychological distress during the chemotherapy period . Objectives : This study aim ed to evaluate the effect of relaxation with guided imagery on patients with breast cancer . Patients and Methods : A two-group , pretest-posttest , quasi-experimental design with a r and omized controlled trial was conducted . Sixty-five breast cancer patients from one medical center in Taiwan were enrolled in the study . These patients were r and omly assigned to the experimental group ( n = 32 ) or to the control group ( n = 33 ) . Both groups received chemotherapy self-care education , but the experimental group also received relaxation with guided imagery training . The training on relaxation with guided imagery was conducted before chemotherapy , and the patients were supplied with a compact disc detailing the performance of relaxation with guided imagery for 20 minutes daily at home for 7 days after chemotherapy . Results : The experimental group showed significant decreases in insomnia ( -0.34 ± 0.83 , P < 0.05 ) , pain ( -0.28 ± 0.58 , P < 0.05 ) , anxiety ( -3.56 ± 2.94 , P < 0.00 ) , and depression ( -2.38 ± 2.70 , P < 0.00 ) between the pretest and the posttest . Comparing the two groups , statistically significant differences were found in the overall symptom distress ( B = 0.11 , P < 0.05 ) , insomnia ( B = 0.50 , P < 0.05 ) , depression ( B = 0.38 , P < 0.05 ) , and numbness in physical symptoms ( B = 0.38 , P < 0.05 ) , as well as in anxiety ( B = 3.08 , P < 0.00 ) and depression ( B = 1.86 , P < 0.00 ) in psychological distress . One week of relaxation with guided imagery can significantly improve the overall symptoms of distress , insomnia , depression , physical symptoms , and anxiety , and can decrease psychological distress . Conclusions : Relaxation with guided imagery had a positive effect on mediating anxiety and depression in breast cancer patients Objective . To test the effectiveness of guided imagery ( GI ) and progressive muscle relaxation ( PMR ) as stress reducing interventions in patients with prostate and breast cancer who undergo chemotherapy . Methods . Patients were r and omly assigned to either the control group or the intervention group ( PMR and GI ) . Patients were observed for a total duration of 3 weeks and assessed with the SAS and BECK-II question naires for anxiety and depression , respectively , in addiotion to two biological markers ( saliva cortisol and saliva amylase ) ( trial registration number : NCT01275872 ) . Results . 256 patients were registered and 236 were r and omly assigned . In total 104 were r and omised to the control group and 104 to the intervention group . Intervention 's mean anxiety score and depression score changes were significantly different compared to the control 's ( b = −29.4 , p < 0.001 ; b = −29.4 , p < 0.001 , resp . ) . Intervention group 's cortisol levels before the intervention ( 0.30 ± 0.25 ) gradually decreased up to week 3 ( 0.16 ± 0.18 ) , whilst the control group 's cortisol levels before the intervention ( 0.21 ± 0.22 ) gradually increased up to week 3 ( 0.44 ± 0.35 ) . The same interaction appears for the Amylase levels ( p < 0.001 ) . Conclusions . The findings showed that patients with prostate and breast cancer undergoing chemotherapy treatment can benefit from PMR and GI sessions to reduce their anxiety and depression Background We examined the effects of psychological and behavioral intervention on health-related quality of life and mental health among patients suffering from differentiated thyroid cancer ( DTC ) treated with postoperative radioactive iodine-131 ( RAI ) . Methods Sixty patients with DTC , undergoing RAI , were r and omly assigned to receive either conventional nursing ( n=30 ) or a 1-year psychological and behavioral intervention based on conventional nursing ( n=30 ) . Health-related quality of life and mental health issues , depression , and anxiety were measured using the Quality of Life Core Question naire , Self-rating Depression Scale , and Self-rating Anxiety Score , respectively . Results After RAI treatment , patients in both groups showed improved functional capacities ( ie , physical , role , cognitive , emotional , and social ) and global quality of life , along with reduced depression and anxiety ( P<0.05 ) . At 1-year follow-up , compared with patients in the routine nursing group , those in the psychological and behavioral intervention group demonstrated greater improvements in functional capacities , global quality of life , and depression and anxiety symptoms ( P<0.05 ) . Conclusion Psychological and behavioral interventions for patients with DTC undergoing RAI facilitated positive outcomes , suggesting that nursing care models that include psychological and behavioral interventions may be a complementary strategy for this patient population Abstract Background . Previous studies have demonstrated that between 20 and 30 % of women treated for breast cancer have measurable signs of anxiety and depression compared with 6 % in a population of healthy women . Depression has been proposed as a predictive factor for recurrence and survival . The aim of the present study was to evaluate if psychosocial support intervention could influence anxiety and depression during the first year after diagnosis . Material and methods . Newly diagnosed breast cancer patients were r and omised between April 2002 and November 2007 and stratified by adjuvant chemotherapy . Of 382 eligible patients , 191 + 191 patients were r and omised to intervention group or control group , respectively . Control patients were subjected to st and ard follow-up routines . The Intervention group had support intervention at the Foundation Lustgården Mälardalen . The rehabilitation lasted one week on a residential basis followed by four days of follow-up two months later . We used the Swedish version of the HAD scale with a cut-off value greater than 10 for clinical symptoms of depression and anxiety . Results . Support group intervention lowered anxiety over time ( p < 0.001 ) but depression was unaffected ( p = 0.610 ) . Conclusion . This prospect i ve r and omised trial of support group intervention in a large homogenous group of breast cancer women showed a statistically significant effect on lowering anxiety over time . No statistically significant effect of intervention could be seen on depression CONTEXT Breathlessness , fatigue , and anxiety are distressing symptoms for patients with advanced lung cancer . Usually managed as isolated symptoms , they often can occur simultaneously . Previous research often has addressed management of discrete symptoms rather than considering them as a cluster , which , in reality , is the situation faced by patients . OBJECTIVES This study aim ed to examine the effectiveness of a psychoeducational intervention ( PEI ) on the symptom cluster of anxiety , breathlessness , and fatigue , compared with usual care . METHODS A pretest/post-test , two-group , r and omized , controlled trial was conducted . Education on symptom management and coaching in the use of progressive muscle relaxation were delivered to patients one week prior to commencing radiotherapy ( RT ) , and repeated three weeks after beginning RT . Symptom data were collected at four time points : prior to the intervention , three weeks , six weeks , and 12 weeks postintervention . RESULTS One hundred forty lung cancer patients receiving palliative RT were recruited from a publicly funded hospital in Hong Kong . Doubly multivariate analysis of variance revealed a significant difference ( time × group interaction effect , P=0.003 ) over time between the PEI and usual care control group on the pattern of change of the symptom cluster . Significant effects on the patterns of changes in breathlessness ( P=0.002 ) , fatigue ( P=0.011 ) , anxiety ( P=0.001 ) , and functional ability ( P=0.000 ) also were found . CONCLUSION PEI is a promising treatment for relieving the symptom cluster and each of the individually assessed symptoms . More effort needs to be directed at study ing impact of interventions on common symptom clusters Background : Limited documentation exists on the effectiveness of psychoeducational group ( PEG ) versus support group ( SG ) interventions among breast cancer patients during primary care . Support group is a component of the hospitals ’ routine breast cancer care . Objective : The aim of this study was to investigate which of these approaches provides the greatest benefits to participants , particularly to women with low optimism ( pessimists ) . The primary outcomes investigated here were anxiety , depression , and mental adjustment to cancer . Methods : A total of 367 women with early-stage breast cancer were r and omized to the PEG or SG intervention starting 1 to 8 weeks after surgery . The PEG intervention included health education , enhancement of problem-solving skills , stress management , and psychological support . Results : Participants in both groups showed improvement over time ; however , no significant differences in emotional distress were found . The PEG participants exhibited more positive attitude at 2 and 6 months ( P < .001 ) and less helplessness/hopelessness ( P = .01 ) at 2 months compared with the SG participants . However , no significant differences were found between the groups at 12 months . Pessimists did not benefit more from attending the PEG than they did from attending the SG . Conclusion : Both groups showed improvement in emotional distress and coping over time . Although the results were limited , the PEG intervention seems to enhance short-term , but not long-term , adaptive coping . Implication s for practice : Psychoeducational group intervention yields benefits during the difficult period when patients receive adjuvant chemotherapy or radiotherapy . Thus , the hospital ’s st and ard group interventions have been changed to include more health education and stress management , but within the same time frame as the original SG Women with breast carcinoma commonly experience psychologic distress following their diagnosis . Women who participate in breast cancer support groups have reported significant reduction in their psychologic distress and pain and improvement in the quality of their lives . Web‐based breast cancer social support groups are widely used , but little is known of their effectiveness . Preliminary evidence suggests that women benefit from their participation in web‐based support groups OBJECTIVE To examine the psychological impact of a referral and telephone intervention , involving information and support , among men with colorectal cancer ( CRC ) and prostate cancer . METHODS 571 newly diagnosed male CRC ( N=182 ) and prostate ( N=389 ) cancer patients were block-r and omised into three arms . In the two intervention arms , the specialist actively referred men to a Cancer Helpline . In Active Referral--4 outcalls , men received calls from the Helpline within 1 week of diagnosis , and at 6 weeks , 3 months and 6 months post-diagnosis . In Active Referral--1 outcall , men received one call within 1 week of diagnosis . In the control arm , Passive Referral , patients were referred to the Helpline , with contact at their initiative . Participants completed scales measuring cancer-specific distress , anxiety and depression at study entry , then 4 , 7 and 12 months post-diagnosis . R and om effects regression models compared rates of change in these outcomes between study arms . RESULTS At the first outcall , over 85 % of participants in both intervention arms discussed treatment management and psychological/emotional issues . Among the Active Referral--4 outcalls arm , over 80 % of participants discussed psychological/emotional issues at each call . Mean changes over time in cancer-specific distress , anxiety and depression were similar between study arms . CONCLUSION Although men were willing to discuss psychosocial issues via the telephone , we found no psychological impact . Further research is required to determine whether the intervention is more effective for patients who do not have psychosocial support or have unmet information needs INTRODUCTION Patients with terminal cancer often experience marked anxiety that is associated with poor quality of life . Although cognitive-behavioral therapy ( CBT ) is an evidence -based treatment for anxiety disorders , the approach needs to be adapted to address realistic concerns related to having cancer , such as worries about disease progression , disability , and death . In this pilot r and omized controlled trial ( clinical trials.gov identifier NCT00706290 ) , we examined the feasibility and potential efficacy of brief CBT to reduce anxiety in patients with terminal cancer . METHODS We adapted CBT by developing treatment modules targeting skills for relaxation , coping with cancer worries , and activity pacing . Adults with incurable malignancies and elevated anxiety based on the Hamilton Anxiety Rating Scale ( HAM-A ) were r and omly assigned to individual CBT or a waitlist control group . Primary outcomes included the number of completed CBT visits and the change in HAM-A scores from baseline to 8-week follow-up per a treatment-blind evaluator . The feasibility criterion was 75 % adherence to the intervention . RESULTS We r and omized 40 patients with terminal cancers to CBT ( n = 20 ) or waitlist control ( n = 20 ) groups ; 70 % completed posttreatment assessment s. Most patients who received CBT ( 80 % ) participated in at least five of the required six therapy sessions . Analysis of covariance models , adjusted for baseline scores , showed that those assigned to CBT had greater improvements in HAM-A scores compared to the control group , with an adjusted mean difference of -5.41 ( 95 % confidence interval : -10.78 to -0.04 ) and a large effect size for the intervention ( Cohen 's d = 0.80 ) . CONCLUSION Providing brief CBT tailored to the concerns of patients with terminal cancer was not only feasible but also led to significant improvements in anxiety BACKGROUND Many women with breast cancer need psychological help to cope more effectively after treatment . Cognitive and behavioural techniques are not yet well established in France . A multi-site r and omized study was conducted to evaluate the effects of a psycho-educational group intervention in this population . METHODS Two hundred and three patients , recruited after primary treatment , were r and omly assigned either to a treatment group ( psycho-educational intervention ) or to a waiting-list control group . The 8-week programme of 2 h sessions comprised of thematic discussion s , information and training in stress management techniques . Evaluation at baseline , after 8 sessions , and 1 month after programme completion , included evaluations using the STAI , POMS , MAC , EORTC QLQ-C30 and EORTC QLQ-BR23 breast module scales . RESULTS We observed a significant reduction in anxiety ( STAI , POMS ) among group participants , a reduction in anger , depression and fatigue ( POMS ) , a significant improvement in vigor and interpersonal relationships ( POMS ) , in emotional and role functioning , in health status and fatigue level ( EORTC QLQ-C30 ) . In contrast , coping strategies ( MAC ) were not significantly different between groups . No group-related negative effects were observed and the global satisfaction levels were very high . CONCLUSION This study demonstrates the feasibility and effectiveness of a psycho-educational intervention , which can accelerate the reduction of those negative affects which are present at the end of treatment . It represents an excellent complement or an alternative to individual psycho-oncologic therapeutic support , widely proposed in France , and should now be tested in groups with other types of cancer and at other disease phases A pilot study was conducted to test the efficacy of a therapeutic group by telephone conference call for women with breast cancer . Sixty-six women with stage I or stage II breast cancer consented to participate in the study . Participants were r and omly assigned to a usual psychosocial care or intervention group , using a permuted block method . Only 2 of 68 patients dropped out of the study , which included 27 % African Americans . Assessment s at 3 time periods ( pretest , immediately after the intervention , and 3 months after the group ended ) included evaluation of quality of life ( QOL ) , mood , and immune function . t tests were performed to determine if differences on important variables existed at pretest . The intervention group had worse QOL and mood scores than did the control group on the pretests . A mixed-model repeated- measures procedure controlling for pretest differences was used to analyze data . A significant Group by Time interaction was found for spiritual well-being and mood . These differences were not in the expected direction . The intervention group showed improvement in QOL and mood during the intervention , but showed decompensation following the intervention . Conversely , the control group demonstrated stable or declining scores . This intervention is feasible and practical for women with breast cancer , especially African American participants . The puzzling results suggest several areas for future research , including a better conceptual fit with outcome measures , increasing dosage , and exploration of the value of emotional expression OBJECTIVE This r and omized controlled trial examines whether a briefer cognitive-behavioural ( CBT ) stress management intervention than the norm can reduce stress and distress and enhance benefit finding in women with breast cancer . It further aims to identify characteristics of those women most likely to benefit from the intervention . DESIGN AND METHOD A r and omized controlled trial was conducted to assess the efficacy of a psychological intervention . Women ( N = 355 ) who had undergone surgery for breast cancer 4 months earlier , the majority of whom were currently undergoing adjuvant therapy , completed question naires assessing global and cancer-specific stress , depression , anxiety , optimism and benefit finding . They were r and omly assigned to a 5-week group cognitive-behavioural stress management ( CBSM ) programme plus st and ard care or st and ard care only . Re assessment occurred post-intervention and 12 months later . RESULTS Analyses of variance revealed that patients who received the intervention showed significant lowering of global stress and anxiety and increased benefit finding compared to controls . These differences , however , were not maintained at 12 months . Effects of the intervention were moderated by stress such that women with high global stress at baseline showed greater reduction in both stress and anxiety . CONCLUSIONS A CBSM intervention , which was briefer than the norm ( 5 weeks vs. 9 - 20 weeks ) , had beneficial effects on adjustment for women with breast cancer and was particularly effective for those with increased global stress . Screening on this basis may facilitate optimal and cost-effective psychological treatment The purpose of this study was to examine the effectiveness of progressive muscle relaxation ( PMR ) in reducing the nausea , vomiting , and anxiety induced by chemotherapy in Japanese patients . Subjects comprised 60 cancer chemotherapy patients who were hospitalized in a cancer center . These subjects were r and omly assigned to either the experimental or control group . In addition to routine nursing care , subjects in the experimental received PMR training , while those in the control received contact with the investigator . Results from this study verified the effectiveness of PMR in reducing total scores used to measure nausea , vomiting , and retching ; subscale scores of nausea ; and subjective feelings of anxiety . The efficacy of PMR to reduce subscale scores of vomiting was not verified , partly due to an extremely low incidence of vomiting PURPOSE The purpose of this study was to determine whether participation in a group psychosocial intervention by patients with breast cancer would result in an improvement in psychological measures and in reduced billings in general medical expenses . DESCRIPTION OF STUDY Eligible women who had completed treatment for stage 0 , I , or II primary breast cancer were prospect ively and r and omly assigned to either the intervention ( n=46 ) or control ( n=43 ) group . Both groups received the usual psychosocial care ; however , the intervention group also participated in six weekly cognitive/behavioral psychosocial meetings . All were assessed on psychiatric symptoms , mood , depression , and coping strategies at four time periods : pre-intervention , post-intervention , 1-year follow-up , and 2-year follow-up . Alberta Healthcare billing records were obtained covering the 2-year follow-up period to determine the amount billed per person over the course of the study . RESULTS Women in the intervention group had less depression , less overall mood disturbance , better overall quality of life , and fewer psychiatric symptoms than those in the control group , beginning immediately post-intervention and remaining so at 2 years post-intervention . Billing in the intervention group was an average of $ 147 less than in the control group , a 23.5 % reduction . CLINICAL IMPLICATION S This is the first study to show that a psychosocial intervention can reduce direct healthcare billings in a sample of patients with cancer . Importantly , these findings help to justify the routine availability of such programs in cancer treatment facilities worldwide PURPOSE Chronic insomnia is highly prevalent in cancer patients . Cognitive-behavioral therapy ( CBT ) is considered the treatment of choice for chronic primary insomnia . However , no r and omized controlled study has been conducted on its efficacy for insomnia secondary to cancer . Using a r and omized controlled design , this study conducted among breast cancer survivors evaluated the effect of CBT on sleep , assessed both subjectively and objective ly , and on hypnotic medication use , psychological distress , and quality of life . PATIENTS AND METHODS Fifty-seven women with insomnia caused or aggravated by breast cancer were r and omly assigned to CBT ( n = 27 ) or a waiting-list control condition ( n = 30 ) . The treatment consisted of eight weekly sessions administered in a group and combined the use of stimulus control , sleep restriction , cognitive therapy , sleep hygiene , and fatigue management . Follow-up evaluations were carried out 3 , 6 , and 12 months after the treatment . RESULTS Participants who received the insomnia treatment had significantly better subjective sleep indices ( daily sleep diary , Insomnia Severity Index ) , a lower frequency of medicated nights , lower levels of depression and anxiety , and greater global quality of life at post-treatment compared with participants of the control group after their waiting period . Results were more equivocal on polysomnographic indices . Therapeutic effects were well maintained up to 12 months after the intervention and generally were clinical ly significant . CONCLUSION This study supports the efficacy of CBT for insomnia secondary to breast cancer PURPOSE To evaluate the effectiveness of psychological intervention in the care of cancer patients and to determine whether routine use of individual psychological therapies is indicated . PATIENTS AND METHODS Patients with newly diagnosed gynecologic malignancies from August 1999 to November 2000 were recruited and r and omly assigned to either a control group receiving routine medical care or to an intervention group receiving individual psychotherapy . A set of fixed-choice , self-report question naires assessing the patients ' psychological status , quality of life , and their perceptions related to the medical consultations was completed at recruitment and then every 3 months for 18 months . Data analysis was performed according to the intention-to-treat principle by fitting the data into a linear mixed-effects model . Multivariable analyses were performed to examine the effects of confounding factors . RESULTS One hundred fifty-five patients participated in the trial . There were no statistically significant differences between the two groups at baseline . There was a trend toward better quality of life and functional status and also improvement of the symptoms over time for both groups . No differences were found between the groups in the scores measured by any of the instruments at baseline and at any time points after the cancer diagnosis . Psychological intervention had no significant effects on the psychosocial parameters . CONCLUSION Routine use of psychological therapies as given in our format has no significant effect on the patients ' quality of life and psychological status The authors report the short-term effects of a clinical trial testing 2 telephone therapies for breast cancer patients . Women ( N = 222 ) with breast cancer were recruited and r and omly assigned to cancer education , emotional expression , or st and ard care . Oncology nurses conducted 6 individual 30-min-therapy phone sessions . Women in the cancer education condition reported greater perceived control than women in the st and ard care condition . No treatment effects were obtained for mood or quality of life . These are the 1st data from a large-scale study testing telephone therapy , and they suggest that such therapies may be ineffective . Explanations for the results include therapy type and delivery , participant characteristics , short- versus long-term results , therapy conent , and whether therapy is necessary for breast cancer patients OBJECTIVES An increasingly important concern for clinicians who care for patients at the end of life is their spiritual well-being and sense of meaning and purpose in life . In response to the need for short-term interventions to address spiritual well-being , we developed Meaning Centered Group Psychotherapy ( MCGP ) to help patients with advanced cancer sustain or enhance a sense of meaning , peace and purpose in their lives , even as they approach the end of life . METHODS Patients with advanced ( stage III or IV ) solid tumor cancers ( N=90 ) were r and omly assigned to either MCGP or a supportive group psychotherapy ( SGP ) . Patients were assessed before and after completing the 8-week intervention , and again 2 months after completion . Outcome assessment included measures of spiritual well-being , meaning , hopelessness , desire for death , optimism/pessimism , anxiety , depression and overall quality of life . RESULTS MCGP result ed in significantly greater improvements in spiritual well-being and a sense of meaning . Treatment gains were even more substantial ( based on effect size estimates ) at the second follow-up assessment . Improvements in anxiety and desire for death were also significant ( and increased over time ) . There was no significant improvement on any of these variables for patients participating in SGP . CONCLUSIONS MCGP appears to be a potentially beneficial intervention for patients ' emotional and spiritual suffering at the end of life . Further research , with larger sample s , is clearly needed to better underst and the potential benefits of this novel intervention Purpose People with a history of melanoma commonly report a fear of cancer recurrence ( FCR ) , yet psychologic support is not routinely offered as part of ongoing melanoma care . This r and omized controlled trial examined the efficacy of a psychoeducational intervention to reduce FCR and improve psychologic adjustment in this patient group compared with usual care . Methods The intervention comprised a newly developed psychoeducational re source and three telephone-based psychotherapeutic sessions over a 1-month period timed in accordance with dermatologic appointments . Participants were r and omly assigned to intervention ( n = 80 ) or usual care ( n = 84 ) . Assessment s were completed at baseline , 1 month , and 6 months after dermatologic appointments . Linear mixed models were used to examine differences between treatment and control groups for patient-reported outcomes , including FCR , anxiety , stress , depression , melanoma-related knowledge , health behaviors , satisfaction with melanoma care , unmet needs , and health-related quality of life . Results At 6 months , the intervention group reported lower FCR severity , trigger , and distress scores than the control group in the baseline-adjusted models ; the between-group mean difference was -1.9 for FCR severity ( 95 % CI , -3.1 to -0.7 ; P = .002 ) , -2.0 for FCR triggers ( 95 % CI , -3.3 to -0.7 ; P = .003 ) , and -0.7 for FCR distress ( 95 % CI , -1.3 to -0.1 ; P = .03 ) . The decrease in FCR severity ( but not triggers or distress ) remained statistically significant after adjustment for other covariates ( P = .04 ) . At 6 months , the intervention group also reported lower stress ( -1.6 ; 95 % CI , -3.1 to -0.2 ; P = .03 ) and improved melanoma-related knowledge ( 1.7 ; 95 % CI , 0.8 to 2.6 ; P < .001 ) compared with the control group . No differences were found between groups for other secondary outcomes . Conclusion This newly developed evidence -based psychoeducational intervention was effective in reducing FCR and stress and increasing melanoma-related knowledge in people at high risk for another melanoma Background : We conducted a r and omised study to investigate whether providing a self-guided Internet support group to cancer patients affected mood disturbance and adjustment to cancer . Methods : Baseline and 1- , 6- and 12-month assessment s were conducted from 2004 to 2006 at a national rehabilitation centre in Denmark . A total of 58 rehabilitation course weeks including 921 survivors of various cancers were r and omly assigned to a control or an intervention group by cluster r and omisation . The intervention was a lecture on the use of the Internet for support and information followed by participation in an Internet support group . Outcome measures included self-reported mood disturbance , adjustment to cancer and self-rated health . Differences in scores were compared between the control group and the intervention group . Results : The effect of the intervention on mood disturbance and adjustment to cancer showed a transient difference at the 6-month follow-up , where the intervention group reported less reduction in anxious preoccupation ( P=0.04 ) , helplessness ( P=0.002 ) , confusion ( P=0.001 ) and depression ( P=0.04 ) . Otherwise no significant effects were observed . Conclusion : We conclude that use of Internet-based support groups in cancer patients still needs to confirm long-lasting psychological effects Goals This study was design ed to assess the effectiveness of progressive muscle relaxation training ( PMRT ) and guided imagery ( GI ) in reducing the anticipatory nausea and vomiting ( ANV ) and postchemotherapy nausea and vomiting ( PNV ) of patients with breast cancer and to measure their effects on the patients ’ quality of life ( QoL ) . Patients and methods Thirty chemotherapy-naive patients with breast cancer were r and omized to the PMRT and GI group and 30 to the control group . Before each of six cycles of adjuvant chemotherapy , each patient was administered a self-report Multiple Affect Adjective Checklist ( MAACL ) , and incidents of ANV and PNV for the first three postchemotherapy days were recorded . All patients were administered the Functional Assessment of Cancer Therapy — Breast ( FACT-B ) at baseline and after 3 and 6 months . Results We found that the PMRT and GI group was significantly less anxious , depressive , and hostile than the control group . We also found that the PMRT and GI group experienced significantly less ANV and PNV and that 6 months after CT , the QoL of the PMRT and GI group was higher than that of the control group . Conclusion These results indicate that PMRT and GI were associated with both the improvements in ANV and PNV and in the QoL of patients with breast cancer Objective . To assess the effects of an 8-week stress management and health promotion program on women undergoing breast cancer chemotherapy treatment . Patients and methods . A total of 61 patients were recruited in 2 cancer centers and were r and omly assigned to the intervention program ( n = 30 ) or control group ( n = 31 ) . The intervention program consisted of different stress management techniques , which were combined with instructions for lifestyle modification . Assessment s were carried out through question naires and measurement of body mass index ( BMI ) at baseline and at the end of the 8-week program . Results . In all , 25 participants completed the intervention program , whereas 28 participants completed the observational control program . The intervention program result ed in a small effect size on internal dimension of Health Locus of Control ( HLC ) and a medium effect size on stress , depression , anxiety , night sleep duration , and chance dimension of HLC . A strong effect size was recorded for BMI and sleep onset latency . Self-rated health , spiritual well-being , and powerful others dimension of HLC were not significantly affected . Additionally , some of the participants reported a reduction in the side effects caused by chemotherapy . Conclusions . The intervention result ed in several benefits for the general health status of patients . Therefore , it should be considered as feasible and potentially beneficial for women undergoing breast cancer chemotherapy . However , it is necessary for this intervention to be tested through a r and omized controlled trial in a larger sample of patients before adopting this program in st and ard cancer care Background Cancer is now becoming a leading cause of death . Chemotherapy is an important treatment for cancer patients . These patients also need consultation during their treatment to improve quality of life and decrease psychological disorders . The objectives of the study were to develop , implement and evaluate the effectiveness of a chemotherapy counseling module by pharmacists among oncology patients on their quality of life and psychological outcomes in Malaysia . Method A single-blind r and omized controlled trial was carried out among 162 oncology patients undergoing chemotherapy from July 2013 to February 2014 in a government hospital with oncology facilities in Malaysia . Participants were r and omized to either the intervention group or the control group . Chemotherapy counseling using the module on ‘ Managing Patients on Chemotherapy ’ by Pharmacists was delivered to the intervention group . The outcome measures were assessed at baseline , first follow-up and second follow-up and third follow-up post-intervention . Chi-square , independent sample s t-test and two-way repeated measures ANOVA were conducted in the course of the data analyses . Results In assessing the impact of the chemotherapy counseling module , the study revealed that the module along with repetitive counseling showed significant improvement of quality of life in the intervention group as compared to the control group with a large effect size in physical health ( p = 0.001 , partial Ƞ2 = 0.66 ) , psychological ( p = 0.001 , partial Ƞ2 = 0.65 ) , social relationships ( p = 0.001 , partial Ƞ2 = 0.30 ) , and environment ( p = 0.001 , partial Ƞ2 = 0.67 ) and decrease in the anxiety ( p = 0.000 ; partial Ƞ2 = 0.23 ) , depression ( p = 0.000 ; partial Ƞ2 = 0.40 ) . Conclusion The module on ‘ Managing Patients on Chemotherapy ’ along with repetitive counseling by pharmacists has been shown to be effective in improving quality of life and decreasing anxiety and depression among oncology patients undergoing chemotherapy . Trial registration numberNational Medical Research Register ( NMRR ) of Malaysia and given a registration number NMRR-12 - 1057 - 12,363 on 21 December 2012 OBJECTIVE To evaluate the mode of delivery of a stress management intervention , in a group or individual setting , on self-reported cancer-related traumatic stress symptoms . A secondary aim was to evaluate a stepped care approach . METHODS All study participants ( n = 425 ) , who were female , newly diagnosed with breast cancer and receiving st and ard oncological care were offered Step I of the stepped care approach , a stress management education ( SME ) . Thereafter , they were screened for cancer-related traumatic stress symptoms , and , if present ( n = 304 ) , were invited to join Step II , a more intense intervention , derived from cognitive behavioral therapy , to which they were r and omized to either a group ( n = 77 ) or individual ( n = 78 ) setting . To assess cancer-related traumatic stress symptoms , participants completed the Impact of Event Scale and the Hospital Anxiety and Depression Scale at the time of inclusion , three-months post- inclusion and approximately 12-months post- inclusion . RESULTS The SME did not significantly decrease any of the cancer-related traumatic stress symptoms . No statistically significant differences were found between the group and the individual setting interventions . However , only 54 % of the participants attended the group setting compared to 91 % for the individual setting . CONCLUSION The mode of delivery had no effect on the cancer-related traumatic stress symptoms ; however , the individual setting was preferred . In future studies , a preference-based RCT design will be recommended for evaluating the different treatment effects OBJECTIVE The objective was to assess the effectiveness of a volunteer-delivered tailored telephone-based intervention in reducing prevalence of unmet supportive care needs , elevated levels of anxiety and depression among people with colorectal cancer over a 9-month period . METHODS There were 653 participants who completed the baseline question naire and were r and omised to usual care ( n = 341 ) or intervention ( n = 306 ) . Three follow-up question naires were completed at 3-monthly intervals ( response rates : 93 % , 87 % , 82 % , respectively ) . All four question naires contained the Supportive Care Needs Survey ( SCNS ) , Hospital Anxiety and Depression Scale ( HADS ) and checklists for colorectal cancer symptoms and use of support services . The intervention consisted of trained volunteers providing emotional support , service referral and information and was delivered after completion of each of the first three question naires . Primary outcomes were prevalence of moderate to high SCNS needs and elevated levels ( scores of 8 + ) of HADS anxiety and depression . RESULTS Over the study period , SCNS needs decreased similarly for both groups , and prevalence of elevated depression did not change for either group . There was a greater reduction in the prevalence of elevated anxiety in the intervention than usual care group ( p < 0.01 ) , with the intervention group decrease mainly occurring between baseline and the first follow-up survey ( p < 0.01 ) . However , the prevalence of elevated anxiety was similar between the two groups at each follow-up point . CONCLUSIONS The intervention had no effect on supportive care needs or depression , although it may be associated with a greater reduction in anxiety . Future research should test the intervention with patients closer to diagnosis BACKGROUND Dignity therapy is a unique , individualised , short-term psychotherapy that was developed for patients ( and their families ) living with life-threatening or life-limiting illness . We investigated whether dignity therapy could mitigate distress or bolster the experience in patients nearing the end of their lives . METHODS Patients ( aged ≥18 years ) with a terminal prognosis ( life expectancy ≤6 months ) who were receiving palliative care in a hospital or community setting ( hospice or home ) in Canada , USA , and Australia were r and omly assigned to dignity therapy , client-centred care , or st and ard palliative care in a 1:1:1 ratio . R and omisation was by use of a computer-generated table of r and om numbers in blocks of 30 . Allocation concealment was by use of opaque sealed envelopes . The primary outcomes --reductions in various dimensions of distress before and after completion of the study --were measured with the Functional Assessment of Chronic Illness Therapy Spiritual Well-Being Scale , Patient Dignity Inventory , Hospital Anxiety and Depression Scale , items from the Structured Interview for Symptoms and Concerns , Quality of Life Scale , and modified Edmonton Symptom Assessment Scale . Secondary outcomes of self-reported end-of-life experiences were assessed in a survey that was undertaken after the completion of the study . Outcomes were assessed by research staff with whom the participant had no previous contact to avoid any possible response bias or contamination . Analyses were done on all patients with available data at baseline and at the end of the study intervention . This study is registered with Clinical Trials.gov , number NCT00133965 . FINDINGS 165 of 441 patients were assigned to dignity therapy , 140 st and ard palliative care , and 136 client-centred care . 108 , 111 , and 107 patients , respectively , were analysed . No significant differences were noted in the distress levels before and after completion of the study in the three groups . For the secondary outcomes , patients reported that dignity therapy was significantly more likely than the other two interventions to have been helpful ( χ(2)=35·50 , df=2 ; p<0·0001 ) , improve quality of life ( χ(2)=14·52 ; p=0·001 ) , increase sense of dignity ( χ(2)=12·66 ; p=0·002 ) , change how their family saw and appreciated them ( χ(2)=33·81 ; p<0·0001 ) , and be helpful to their family ( χ(2)=33·86 ; p<0·0001 ) . Dignity therapy was significantly better than client-centred care in improving spiritual wellbeing ( χ(2)=10·35 ; p=0·006 ) , and was significantly better than st and ard palliative care in terms of lessening sadness or depression ( χ(2)=9·38 ; p=0·009 ) ; significantly more patients who had received dignity therapy reported that the study group had been satisfactory , compared with those who received st and ard palliative care ( χ(2)=29·58 ; p<0·0001 ) . INTERPRETATION Although the ability of dignity therapy to mitigate outright distress , such as depression , desire for death or suicidality , has yet to be proven , its benefits in terms of self-reported end-of-life experiences support its clinical application for patients nearing death . FUNDING National Cancer Institute , National Institutes of Health Background Little is reported in the scientific literature about the modulating effect of anxiety on the coping process before and after surgical treatment for head and neck cancer . Objectives The major purpose of this article is to describe the relationships among preoperative anxiety and use of coping strategies , and postoperative self-care and resocialization behaviors in patients who sustain facial disfigurement/dysfunction with head and neck cancer surgery . Methods Using a prospect i ve descriptive design , 75 ( N = 75 ) adults who were about to sustain facial disfigurement and dysfunction associated with head and neck cancer surgery were entered into the study . The State Trait Anxiety Inventory and the Ways of Coping Question naire were administered to the respondents . The Disfigurement/Dysfunction Scale and Coping Behaviors Score values were calculated by the investigator . Results Self-care and anxiety were significantly correlated on postoperative day 4 ( r = 2.30;p < .05 ) and on postoperative day 5 ( r = 2.35;p < .05 ) . For the 3 days under study , the relationship between total self-care and anxiety became stronger on postoperative day 5 ( r = 2.39;p < .01 ) , indicating that self-care on postoperative day 4 is related to reduced anxiety on postoperative day 5 . In other words , self-care appears to precede reduction in anxiety in this sample . Secondly , there was a negative relationship between self-care and anxiety that increased over the early postoperative period . Conclusions This study prospect ively documents anxiety in surgical head and neck cancer patients . The findings suggest that at a specific point in time ( postoperative day 5 ) , self-care precedes reduction in anxiety , and that this negative relationship increases over time . Additional investigation is now critical in order to describe long-term recovery after surgical treatment for head and neck cancer and to develop appropriate interventions to meet the unique needs of this population Abstract Objective : To evaluate the effect of support from a nurse specialising in breast care and a voluntary support organisation on prevalence of psychological morbidity after surgery for breast cancer . Design : Prospect i ve r and omised study . Setting : Three teaching hospitals in Glasgow with established breast clinics . Subjects : 272 women aged less than 70 years undergoing surgery for breast cancer . Interventions : Patients were r and omly allocated to receive routine care from ward staff , routine care plus support from breast care nurse , routine care plus support from voluntary organisation , or routine care plus support from nurse and organisation . Main outcome measures : Prevalence of psychological morbidity as assessed by self rating scales : 28 item general health question naire and its subscales , and hospital anxiety and depression scale . Measurements were made at first postoperative clinic visit and at three , six , and 12 months after surgery . Results : On each self rating scale , psychological morbidity tended to fall over the 12 month period . For each scale , scores were consistently lower in patients offered support from breast care nurse alone compared with the other groups , which were similar to each other . Differences were significant or nearly so : P values were 0.015 ( 28 item general health question naire ) , 0.027 ( anxiety and insomnia ) , 0.072 ( severe depression ) , 0.053 ( somatic symptoms ) , 0.031 ( social dysfunction ) , 0.093 ( hospital anxiety ) , and 0.003 ( hospital depression ) . Conclusion : Support from breast care nurse can significantly reduce psychological morbidity , as measured by self rating scales , in women undergoing breast cancer surgery . Key messages Key messages The value of different forms of psychological support for breast cancer patients is uncertain We compared effect of four different types of support for patients undergoing surgery for breast cancer : routine care from ward staff , routine care plus support from specialist breast care nurse , routine care plus support from voluntary organisation , or routine care plus support from nurse and organisation Scores of psychological morbidity were consistently lower in patients offered support from breast care nurse alone compared with the other groups , which were similar to each other Psychological support from an experienced breast care nurse can reduce psychological morbidity in patients undergoing surgery for breast To the authors ' knowledge , there had been no evidence for the efficacy of psychosocial intervention among Japanese cancer patients . The objective of this study was to determine the effect of a psychosocial group intervention in reducing psychologic distress and enhancing coping in this population in a r and omized controlled trial BACKGROUND This study aim ed to evaluate the efficacy of stepped care ( SC ) targeting psychological distress in head and neck cancer ( HNC ) and lung cancer ( LC ) patients . PATIENTS AND METHODS Patients with untreated distress [ Hospital Anxiety and Depression Scale ( HADS ; HADS-D > 7 , HADS-A > 7 , or HADS-total > 14 ) ] were r and omized to SC ( n = 75 ) or care-as-usual ( CAU ) ( n = 81 ) . SC consisted of watchful waiting , guided self-help , problem-solving therapy , and psychotherapy and /or psychotropic medication . The primary outcome measure was the HADS ; secondary outcome measures were recovery rate , EORTC QLQ-C30 , QLQ-HN35/QLQ-LC13 , and IN-PATSAT32 . Measures were assessed at baseline , after completion of care , and at 3 , 6 , 9 , and 12 months follow-up . Linear mixed models , t-tests , and effect sizes ( ES ) were used to assess group differences . RESULTS Patients with untreated distress were r and omized to SC ( n = 75 ) or care-as-usual ( CAU ) ( n = 81 ) . The course of psychological distress was better after SC compared with CAU ( HADS-total , P = 0.005 ; HADS-A , P = 0.046 ; HADS-D , P = 0.007 ) . The SC group scored better post-treatment ( HADS-total , ES = 0.56 ; HADS-A , ES = 0.38 ; HADS-D , ES = 0.64 ) and at 9 months follow-up ( HADS-total , ES = 0.42 and HADS-A , ES = 0.40 ) . The recovery rate post-treatment was 55 % after SC compared with 29 % after CAU ( P = 0.002 ) , and 46 % and 37 % at 12 months follow-up ( P = 0.35 ) . Within SC , 28 % recovered after watchful waiting , 34 % after guided self-help , 9 % after problem-solving therapy , and 17 % after psychotherapy and /or psychotropic medication . The effect of SC was stronger for patients with a depressive or anxiety disorder compared with patients without such a disorder ( HADS-total , P = 0.001 ; HADS-A , P = 0.003 ; HADS-D , P = 0.041 ) . CONCLUSIONS SC is effective and speeds up recovery among HNC and LC patients with untreated psychological distress . TRIAL REGISTRATION Netherl and s Trial Register ( NTR1868 ) Objective To examine the effect of counselling and relaxation intervention on psychological symptoms in patients with gynaecological cancer between the post‐operative period and the six‐week review PURPOSE To test the efficacy of meaning-centered group psychotherapy ( MCGP ) to reduce psychological distress and improve spiritual well-being in patients with advanced or terminal cancer . PATIENTS AND METHODS Patients with advanced cancer ( N = 253 ) were r and omly assigned to manualized eight-session interventions of either MCGP or supportive group psychotherapy ( SGP ) . Patients were assessed before and after completing the treatment and 2 months after treatment . The primary outcome measures were spiritual well-being and overall quality of life , with secondary outcome measures assessing depression , hopelessness , desire for hastened death , anxiety , and physical symptom distress . RESULTS Hierarchical linear models that included a priori covariates and only participants who attended ≥ three sessions indicated a significant group × time interaction for most outcome variables . Specifically , patients receiving MCGP showed significantly greater improvement in spiritual well-being and quality of life and significantly greater reductions in depression , hopelessness , desire for hastened death , and physical symptom distress compared with those receiving SGP . No group differences were observed for changes in anxiety . Analyses that included all patients , regardless of whether they attended any treatment sessions ( ie , intent-to-treat analyses ) , and no covariates still showed significant treatment effects ( ie , greater benefit for patients receiving MCGP v SGP ) for quality of life , depression , and hopelessness but not for other outcome variables . CONCLUSION This large r and omized controlled study provides strong support for the efficacy of MCGP as a treatment for psychological and existential or spiritual distress in patients with advanced cancer This study compared the effectiveness of two psychological treatments in a group of 57 patients with various types of cancer attending the Royal Marsden Hospital . Patients referred for psychiatric assessment who met criteria for an abnormal adjustment reaction were r and omly allocated to either 8 weeks of Adjuvant Psychological Therapy ( APT ) , a problem-focused , cognitive behavioural treatment programme , or 8 weeks of a comparison treatment of supportive counselling . At 8 weeks from the baseline assessment , APT had produced a significantly greater change than the counselling intervention on fighting spirit , helplessness , coping with cancer , anxiety , and self-defined problems . At 4 months from baseline , APT had produced a significantly greater change than counselling on fighting spirit , coping with cancer , anxiety and self defined problems . It is concluded that APT produces greater change in anxiety , adjustment to cancer and use of coping strategies than a non-directive , supportive intervention over an 8 week period of treatment . This difference persists at follow up 4 months after baseline assessment Patients with breast cancer who undergo autologous bone marrow/peripheral blood stem cell transplantation ( ABMT ) cope not only with a life-threatening medical treatment , but also with multiple , interrelated symptoms including pain , fatigue , psychological distress , and nausea . The purpose of this study was to determine , in a r and omized controlled clinical trial , whether a comprehensive coping strategy program ( CCSP ) was effective in significantly reducing pain , fatigue , psychological distress , and nausea in patients with breast cancer who underwent ABMT . The CCSP was composed of preparatory information , cognitive restructuring , and relaxation with guided imagery . R and omization placed 52 patients in the CCSP treatment group and 58 patients in the control group . The CCSP was found to be effective in significantly reducing nausea as well as nausea combined with fatigue 7 days after the ABMT when the side effects of treatment were most severe . These results are important given the high incidence of nausea and fatigue in the ABMT population . The CCSP-treated group experienced mild anxiety as compared with the control group who reported moderate anxiety . The greatest effectiveness of CCSP may correspond to the time of the greatest morbidity for patients with breast cancer who have undergone ABM Home visits by health care professionals may constitute a formalized social relationship in which cancer patients can be given emotional and informational support . We aim ed at study ing the effect of home visits on the well-being of colorectal cancer patients . A total of 249 Danish colorectal cancer patients undergoing abdominal surgery were r and omly assigned to a control group or to an intervention group . The intervention group received 10 home visits carried out by a project nurse or a medical doctor during the first 2 years after discharge . Participants were interviewed 3 , 6 , 12 , and 24 months after discharge in order to assess well-being . Using a linear mixed model , we found no overall effect of the intervention on well-being . We recommend that future psychosocial intervention studies include baseline screening for distress and recommend testing the effect of shorter but intensive interventions carried out by trained therapists The diagnosis and treatment of breast cancer are stressful , and stress may be associated with a poorer response to chemotherapy . There is a need , therefore , to develop and evaluate interventions that might enhance quality of life and , possibly , improve treatment response . The effects of relaxation combined with guided imagery ( visualizing host defences destroying tumour cells ) on quality of life and response to primary chemotherapy , to date , have not been adequately evaluated . Ninety-six women with newly diagnosed large or locally advanced breast cancer ( T2 > 4 cm , T3 , T4 , or TxN2 and M0 ) took part in a prospect i ve , r and omized controlled trial . Patients were r and omized following diagnosis to a control condition ( st and ard care ) or to the experimental condition ( st and ard care plus relaxation training and imagery ) . Psychometric tests to evaluate mood and quality of life were carried out before each of the six cycles of chemotherapy and 3 weeks after cycle 6 : tests of personality and coping strategy were carried out prior to cycles one and six . Clinical response to chemotherapy was evaluated after six cycles of chemotherapy using st and ard UICC criteria and pathological response was assessed from the tissue removed at surgery . As hypothesized , patients in the experimental group were more relaxed and easy going during the study ( Mood Rating Scale ) . Quality of life was better in the experimental group ( Global Self- assessment and Rotterdam Symptom Checklist ) . The intervention also reduced emotional suppression ( Courtauld Emotional Control Scale ) . The incidence of clinical ly significant mood disturbance was very low and the incidence in the two groups was similar . Finally , although the groups did not differ for clinical or pathological response to chemotherapy , imagery ratings were correlated with clinical response . These simple , inexpensive and beneficial interventions should be offered to patients wishing to improve quality of life during primary chemotherapy PURPOSE To provide the 4-week prevalence estimates of mental disorders in cancer population s. PATIENTS AND METHODS We enrolled adult patients with cancer from in- and outpatient care facilities , using a proportional stratified r and om sample based on the nationwide cancer incidence in Germany . Patients who scored 9 or above on the Patient Health Question naire ( PHQ-9 ) were administered to the st and ardized computer-assisted Composite International Diagnostic Interview for mental disorders adapted for cancer patients ( CIDI-O ) . A r and om sample of those with a PHQ-9 score that was less than 9 were selected for a CIDI-O. RESULTS A total of 5,889 patients were identified , which led to 4,020 participants ( a 68.3 % response rate ) ; of those , 2,141 patients were interviewed . The 4-week total prevalence for any mental disorder was 31.8 % ( 95 % CI , 29.8 % to 33.8 % ) ; this included any anxiety disorder ( 11.5 % ; 95 % CI , 10.2 % to 12.9 % ) , any adjustment disorder ( 11.1 % ; 95 % CI , 9.7 % to 12.4 % ) , any mood disorder ( 6.5 % ; 95 % CI , 5.5 % to 7.5 % ) , any somatoform/conversion disorder ( 5.3 % ; 95 % CI , 4.3 % to 6.2 % ) , nicotine dependence ( 4.5 % ; 95 % CI , 3.6 % to 5.4 % ) , alcohol abuse/dependence ( 0.3 % ; 95 % CI , 0.1 % to 0.6 % ) , any mental disorder result ing from general medical condition ( 2.3 % ; 95 % CI , 1.7 % to 2.9 % ) , and any eating disorder ( 0 % ) . The highest prevalence for any mental disorder was found in patients with breast cancer ( 41.6 % ; 95 % CI , 36.8 % to 46.4 % ) , followed by patients with head and neck cancer ( 40.8 % ; 95 % CI , 28.5 % to 53.0 % ) . The lowest prevalence was found in patients with pancreatic cancer ( 20.3 % ; 95 % CI , 8.9 % to 31.6 % ) and stomach/esophagus cancers ( 21.2 % ; 95 % CI , 12.8 % to 29.6 % ) . CONCLUSION Our findings provide evidence for the strong need for psycho-oncological interventions BACKGROUND Anxiety and depression are the two most frequent comorbidities of tumour patients . At present , it is unclear to which degree a patient 's psychological condition can be altered during the treatment period and if psycho-oncological support positively affects a patient 's psychological condition . METHODS In a r and om sample analyses , 131 patients beginning inpatient treatment at a hospital specialising in surgical oncology were either classified as ' low-risk ' or ' high-risk ' , according to the HADS . Patients from both categories were then r and omly placed in either a low-threshold ' intervention ' group or an ' observation ' group . Anxiety and depression levels were measured again with the HADS scale prior to the patients discharge from the department of surgical oncology , and at a follow up 12 months after . RESULTS Our findings showed a significant reduction of anxiety and depression in the high-risk patients who had undergone psycho-oncological intervention at the end of inpatient care and even a year after discharge from the hospital . The effects of psychological intervention could be observed in terms of anxiety and depression in the group of high-risk patients during the hospital stay . In the other three groups , no statistically significant changes could be measured . CONCLUSION Cancer patients on a surgical ward benefit from psycho-oncological support especially at an early stage of therapy but also over a long time after discharge from the hospital . The aim of all interventions should be to decrease psychological distress and disorders and thereby improve the quality of life for cancer patients |
12,277 | 31,323,730 | While variation in study protocol , outcome measurement , and effect size reporting precluded further inferential statistical analysis , our review found a sizable number of studies showing improvement in IADL .
Cognitive training may have some benefit in improving IADL function in older adults without major neurocognitive disorder . | There is increasing interest in the effect of non-pharmacological treatments on preserving cognition and function in older adults without major neurocognitive disorder ( dementia ) .
However , its effect on everyday function in terms of instrumental activities of daily living ( IADL ) is unclear .
We conducted a systematic review to examine whether cognitive training , independent of other interventions , can improve IADL function in older adults without major neurocognitive disorder . | INTRODUCTION Cognitive training ( CT ) offers a potential approach for dementia prevention and maintenance of cognitive function in older adults . Online delivery provides a cost-effective means of implementing CT compared with in-person interventions , with the potential of providing an effective public health intervention for risk reduction . METHODS A double-blind 6-month online r and omized controlled trial in adults older than 50 r and omized to General CT , Reasoning CT , or control . The primary outcome was instrumental activities of daily living ( IADL ) in adults older than 60 . Secondary outcomes were reasoning , verbal short-term memory , spatial working memory , verbal learning ( VL ) , and digit vigilance in adults older than 50 . Secondary analyses were performed with a group defined as showing age-associated impairment in reasoning according to baseline scores in this domain . RESULTS A total of 2912 adults older than 60 ( 6742 > 50 ) participated . General and reasoning packages conferred benefit to IADL ( P = .008 , P = .011 ) , reasoning ( P < 0.0001 , P < .0001 ) , and VL ( P = .007 , P = .008 ) at 6 months . Benefit in reasoning was evident from 6 weeks . Other benefits developed over 6 months . Analysis of participants with age-associated impairment also showed the same pattern of benefit . A clear dose-response effect was seen . CONCLUSIONS Online CT confers significant benefit to cognition and function in older adults , with benefit favoring the Reasoning package . Scale of benefit is comparable with in-person training , indicating its potential as a public health intervention . Impact on the group with age-associated impairment indicates a particular sensitivity to this at-risk group , which merits further investigation BACKGROUND Home-based computerised cognitive training ( CCT ) is ineffective at enhancing global cognition , a key marker of cognitive ageing . OBJECTIVES To test the effectiveness of supervised , group-based , multidomain CCT on global cognition in older adults and to characterise the dose-response relationship during and after training . DESIGN A r and omised , double-blind , longitudinal , active-controlled trial . SETTING Community-based training centre in Sydney , Australia Participants : Eighty nondemented community-dwelling older adults ( mean age = 72.1 , 68.8 % females ) with multiple dementia risk factors but no major neuropsychiatric or sensory disorder . Of the 80 participants admitted to the study , 65 completed post-training assessment and 55 were followed up one year after training cessation . INTERVENTIONS Thirty-six group-based sessions over three months of either CCT targeting memory , speed , attention , language and reasoning tasks , or active control training comprising audiovisual educational exercises . MEASUREMENTS Primary outcome was change from baseline in global cognition as defined by a composite score of memory , speed and executive function . Secondary outcome was 15-month change in Bayer Activities of Daily Living from baseline to one year post-training . RESULTS Intention-to-treat analyses revealed significant effects on global cognition in the cognitive training group compared to active control after three weeks of training ( ES = 0.33 , P=.039 ) that increased after 3 months of training ( ES = 0.49 , P=.003 ) and persisted three months after training cessation ( ES = 0.30 , P=0.023 ) . Significant and durable improvements were also noted in memory and processing speed . Dose-response characteristics differed among cognitive domains . Training effects waned gradually but residual gains were noted twelve months post-training . No significant effects on activities of daily living were noted and there were no adverse effects . CONCLUSIONS In older adults with multiple dementia risk factors , group-based CCT is a safe and effective intervention for enhancing overall cognition , memory and processing speed . Dose-response relationships vary for each cognitive domain , vital information for clinical and community implementation and further trial design Introduction Cognitive training improves cognitive performance and delays functional impairment , but its effects on dementia are not known . We examined whether three different types of cognitive training lowered the risk of dementia across 10 years of follow-up relative to control and if greater number of training sessions attended was associated with lower dementia risk . Methods The Advanced Cognitive Training in Vital Elderly ( NCT00298558 ) study was a r and omized controlled trial ( N = 2802 ) among initially healthy older adults , which examined the efficacy of three cognitive training programs ( memory , reasoning , or speed of processing ) relative to a no-contact control condition . Up to 10 training sessions were delivered over 6 weeks with up to four sessions of booster training delivered at 11 months and a second set of up to four booster sessions at 35 months . Outcome assessment s were taken immediately after intervention and at intervals over 10 years . Dementia was defined using a combination of interview- and performance-based methods . Results A total of 260 cases of dementia were identified during the follow-up . Speed training result ed in reduced risk of dementia ( hazard ratio [ HR ] 0.71 , 95 % confidence interval [ CI ] 0.50–0.998 , P = .049 ) compared to control , but memory and reasoning training did not ( HR 0.79 , 95 % CI 0.57–1.11 , P = .177 and HR 0.79 , 95 % CI 0.56–1.10 , P = .163 , respectively ) . Each additional speed training session was associated with a 10 % lower hazard for dementia ( unadjusted HR , 0.90 ; 95 % CI , 0.85–0.95 , P < .001 ) . Discussion Initially , healthy older adults r and omized to speed of processing cognitive training had a 29 % reduction in their risk of dementia after 10 years of follow-up compared to the untreated control group BACKGROUND / OBJECTIVES There is no consensus on the efficacy of cognitive training in persons with mild cognitive impairment ( MCI ) because of the paucity of well- design ed r and omized controlled trials . The objective was to assess the effect of memory training on the cognitive functioning of persons with MCI and its durability and to evaluate whether this effect generalizes to daily life and whether positive effects could be obtained from psychosocial intervention . DESIGN Single-blind r and omized controlled trial . SETTING Research centers of the Institut Universitaire de Gériatrie de Montréal and Institut Universitaire en Santé Mentale de Québec . PARTICIPANTS Older adults meeting criteria for amnestic MCI ( N = 145 ) . INTERVENTION Participants were r and omized to cognitive training , a psychosocial intervention , or a no-contact control condition . Interventions were provided in small groups in eight 2-hour sessions . MEASUREMENT Outcome measures were immediate and delayed composite performance memory scores , psychological health ( depression , anxiety , well-being ) , and generalization effects of the intervention ( strategy use in everyday life , difficulties in complex activities of daily living , memory complaints ) . Testing was administered before training and immediately , 3 months , and 6 months after training . RESULTS Participants in the cognitive training condition improved on the delayed composite memory score and on strategy use in everyday life . Improvement was maintained at the 3- and 6-month follow-up assessment s. Participants in the psychosocial and no-contact conditions did not show any significant improvement . CONCLUSION Cognitive training improves the memory of persons with amnestic MCI . The effect persists over a 6-month period , and learned strategies are used in everyday life . Cognitive training is a valid way to promote cognition in MCI The purpose of the present investigation was to examine the impact of speed of processing training on the cognitive and everyday abilities of older adults with initial processing speed or processing difficulty . Participants were r and omized to either a speed of processing intervention or a social- and computer-contact control group . Results indicate that speed of processing training not only improves processing speed , as indicated by performance on the Useful Field of View test ( UFOV ® ) , but also transfers to certain everyday functions , as indicated by improved performance on Timed Instrumental Activities of Daily Living ( Timed IADL ) . Transfer of speed of processing training to other cognitive domains was not evident . This study provides additional evidence that speed of processing training has the potential to enhance everyday functions that maintain independence and quality of life , particularly when the training is targeted toward individuals who most need it . Further study is needed to learn about the long-term effects of such training in relation to everyday abilities CONTEXT Cognitive function in older adults is related to independent living and need for care . However , few studies have addressed whether improving cognitive functions might have short- or long-term effects on activities related to living independently . OBJECTIVE To evaluate whether 3 cognitive training interventions improve mental abilities and daily functioning in older , independent-living adults . DESIGN R and omized , controlled , single-blind trial with recruitment conducted from March 1998 to October 1999 and 2-year follow-up through December 2001 . SETTING AND PARTICIPANTS Volunteer sample of 2832 persons aged 65 to 94 years recruited from senior housing , community centers , and hospital/clinics in 6 metropolitan areas in the United States . INTERVENTIONS Participants were r and omly assigned to 1 of 4 groups : 10-session group training for memory ( verbal episodic memory ; n = 711 ) , or reasoning ( ability to solve problems that follow a serial pattern ; n = 705 ) , or speed of processing ( visual search and identification ; n = 712 ) ; or a no-contact control group ( n = 704 ) . For the 3 treatment groups , 4-session booster training was offered to a 60 % r and om sample 11 months later . MAIN OUTCOME MEASURES Cognitive function and cognitively dem and ing everyday functioning . RESULTS Thirty participants were incorrectly r and omized and were excluded from the analysis . Each intervention improved the targeted cognitive ability compared with baseline , durable to 2 years ( P<.001 for all ) . Eighty-seven percent of speed- , 74 % of reasoning- , and 26 % of memory-trained participants demonstrated reliable cognitive improvement immediately after the intervention period . Booster training enhanced training gains in speed ( P<.001 ) and reasoning ( P<.001 ) interventions ( speed booster , 92 % ; no booster , 68 % ; reasoning booster , 72 % ; no booster , 49 % ) , which were maintained at 2-year follow-up ( P<.001 for both ) . No training effects on everyday functioning were detected at 2 years . CONCLUSIONS Results support the effectiveness and durability of the cognitive training interventions in improving targeted cognitive abilities . Training effects were of a magnitude equivalent to the amount of decline expected in elderly persons without dementia over 7- to 14-year intervals . Because of minimal functional decline across all groups , longer follow-up is likely required to observe training effects on everyday function We investigated the potential benefits of a novel cognitive-training protocol and an aerobic exercise intervention , both individually and in concert , on older adults ' performances in laboratory simulations of select real-world tasks . The cognitive training focused on a range of cognitive processes , including attentional coordination , prospect i ve memory , and retrospective-memory retrieval , processes that are likely involved in many everyday tasks , and that decline with age . Primary outcome measures were 3 laboratory tasks that simulated everyday activities : Cooking Breakfast , Virtual Week , and Memory for Health Information . Two months of cognitive training improved older adults ' performance on prospect ive-memory tasks embedded in Virtual Week . Cognitive training , either alone or in combination with 6 months of aerobic exercise , did not significantly improve Cooking Breakfast or Memory for Health Information . Although gains in aerobic power were comparable with previous reports , aerobic exercise did not produce improvements for the primary outcome measures . Discussion focuses on the possibility that cognitive-training programs that include explicit strategy instruction and varied practice context s may confer gains to older adults for performance on cognitively challenging everyday tasks OBJECTIVES To determine the effects of cognitive training on cognitive abilities and everyday function over 10 years . DESIGN Ten-year follow-up of a r and omized , controlled single-blind trial ( Advanced Cognitive Training for Independent and Vital Elderly ( ACTIVE ) ) with three intervention groups and a no-contact control group . SETTING Six U.S. cities . PARTICIPANTS A volunteer sample of 2,832 persons ( mean baseline age 73.6 ; 26 % African American ) living independently . INTERVENTION Ten training sessions for memory , reasoning , or speed of processing ; four sessions of booster training 11 and 35 months after initial training . MEASUREMENTS Objective ly measured cognitive abilities and self-reported and performance-based measures of everyday function . RESULTS Participants in each intervention group reported less difficulty with instrumental activities of daily living ( IADLs ) ( memory : effect size = 0.48 , 99 % confidence interval ( CI ) = 0.12 - 0.84 ; reasoning : effect size = 0.38 , 99 % CI = 0.02 - 0.74 ; speed of processing : effect size = 0.36 , 99 % CI = 0.01 - 0.72 ) . At a mean age of 82 , approximately 60 % of trained participants , versus 50 % of controls ( P < .05 ) , were at or above their baseline level of self-reported IADL function at 10 years . The reasoning and speed-of-processing interventions maintained their effects on their targeted cognitive abilities at 10 years ( reasoning : effect size = 0.23 , 99 % CI = 0.09 - 0.38 ; speed of processing : effect size = 0.66 , 99 % CI = 0.43 - 0.88 ) . Memory training effects were no longer maintained for memory performance . Booster training produced additional and durable improvement for the reasoning intervention for reasoning performance ( effect size = 0.21 , 99 % CI = 0.01 - 0.41 ) and the speed-of-processing intervention for speed-of-processing performance ( effect size = 0.62 , 99 % CI = 0.31 - 0.93 ) . CONCLUSION Each Advanced Cognitive Training for Independent and Vital Elderly cognitive intervention result ed in less decline in self-reported IADL compared with the control group . Reasoning and speed , but not memory , training result ed in improved targeted cognitive abilities for 10 years OBJECTIVE the aim of this study was to compare the effects of a functional tasks exercise programme to a cognitive training programme in older adults with mild cognitive impairment . DESIGN a single-blind r and omised control trial with the intervention group compared with an active control group . SETTING out-patient clinic . PARTICIPANTS older adults with mild cognitive impairment ( n = 83 ) aged 60 and older living in the community . METHODS participants were r and omised to either a functional task exercise group ( n = 43 ) or an active cognitive training group ( n = 40 ) for 10 weeks . All outcome measures were undertaken at baseline , post-intervention and 6-month follow-up using Neurobehavioral Cognitive Status Examination , Trail Making Test , Chinese Version Verbal Learning Test , Category Verbal Learning Test , Lawton Instrumental Activities of Daily Living Scale and Problems in Everyday Living Test . RESULTS the functional task exercise group showed significant between-group differences in general cognitive functions , memory , executive function , functional status and everyday problem solving ability . The improvements were sustained over time at 6-month follow-up . CONCLUSION a functional tasks exercise programme is feasible for improving cognitive functions and functional status of older adults with mild cognitive impairment . This may serve as a cost-effective adjunct to the existing interventions for population s with mild cognitive impairment . TRIAL REGISTRATION NUMBER ACTRN12610001025022 Abstract Cognitive decline and dementia represent very important public health problems that impact the ability to maintain social function and independent living . The aim of this study was to investigate the effects of a nonpharmacological intervention consisting of comprehensive cognitive training in elderly people having one of three different cognitive statuses . In all , 321 elderly people with a diagnoses of mild – moderate Alzheimer 's disease ( AD ) , with mild cognitive impairment ( MCI ) and without cognitive decline were r and omly assigned to two groups : experimental group ( EG , who underwent intervention ) and control group ( CG ) , according to a prospect i ve r and omized intervention study . In the three groups , immediately after the end of the intervention , we observed a significant effect on some cognitive and noncognitive outcomes in the EGs . At the end of the intervention , we found an intermediate intervention effect on the Alzheimer 's Disease Assessment Scale ( ADAS ) score of subjects with AD , as well as on functional status , as measured by using the Instrumental Activities of Daily Living scale . A significant intervention effect was also observed on enhancement of auditory verbal short-term memory and subjective memory complaints of subjects with MCI . The group of subjects without cognitive decline obtained a significant intervention effect on subjective complaints outcomes . The obtained results demonstrated that participation in the intervention could improve performance with respect to specific cognitive functions and psychological statuses . The role of healthy lifestyle programs , such as the use of comprehensive interventions , has been shown to be efficient for enhancing memory and other abilities in aged individuals with and without cognitive decline ABSTRACT Objectives : To evaluate the efficacy of a self-administered cognitive training program for improving cognition in normal elderly persons . Method : A multisite , r and omized control , double-blind trial was conducted with 28 experimental participants ( Mage = 70.7 ± 8.89 ) and 28 active controls ( Mage = 74.4 ± 9.39 ) . Treatment conditions : experimental intervention ( EI ) consisted of three modules : ( 1 ) executive functioning , ( 2 ) memory , and ( 3 ) emotion training . Active control ( AC ) consisted of word search es , reading short stories , and answering multiple-choice questions . Treatments were self-administered one hour/five days a week for four weeks . Pre- and post-training neuropsychological outcome measures were utilized as determinants of program success . Results : Compared to the AC group , the EI group displayed significant gains on targeted executive ( p = .002 ) and memory ( p < .001 ) composites , but not the emotion ( p = .105 ) composite . Training-induced benefits were also observed for the EI group on untrained items within global cognition ( BCRS , p = .002 ) and functional abilities ( DAD , p < .001 ; FRS , p = .042 ) . The percentage of participants who showed reliable performance improvements was greater for the EI than AC on executive ( 55.5 % vs. 12.5 % ) , memory ( 55 % vs. 19.5 % ) and functional ( 41 % vs. 7.5 % ) ability . Participant recruitment and compliance rates were enhanced by the involvement of a physician . Conclusion : Results support the efficacy of self-directed cognitive training in reliably improving cognitive and functional abilities in normal older adults . While physicians are critical in enhancing the delivery of regimented treatment , the present study illustrates the potential for self-directed prophylactic training in deterring the development of cognitive decline BACKGROUND Mild cognitive impairment ( MCI ) increases dementia risk with no pharmacologic treatment available . METHODS The Study of Mental and Resistance Training was a r and omized , double-blind , double-sham controlled trial of adults with MCI . Participants were r and omized to 2 supervised interventions : active or sham physical training ( high intensity progressive resistance training vs seated calisthenics ) plus active or sham cognitive training ( computerized , multidomain cognitive training vs watching videos/quizzes ) , 2 - 3 days/week for 6 months with 18-month follow-up . Primary outcomes were global cognitive function ( Alzheimer 's Disease Assessment Scale-cognitive subscale ; ADAS-Cog ) and functional independence ( Bayer Activities of Daily Living ) . Secondary outcomes included executive function , memory , and speed/attention tests , and cognitive domain scores . RESULTS One hundred adults with MCI [ 70.1 ( 6.7 ) years ; 68 % women ] were enrolled and analyzed . Resistance training significantly improved the primary outcome ADAS-Cog ; [ relative effect size ( 95 % confidence interval ) -0.33 ( -0.73 , 0.06 ) ; P < .05 ] at 6 months and executive function ( Wechsler Adult Intelligence Scale Matrices ; P = .016 ) across 18 months . Normal ADAS-Cog scores occurred in 48 % ( 24/49 ) after resistance training vs 27 % ( 14/51 ) without resistance training [ P < .03 ; odds ratio ( 95 % confidence interval ) 3.50 ( 1.18 , 10.48 ) ] . Cognitive training only attenuated decline in Memory Domain at 6 months ( P < .02 ) . Resistance training 18-month benefit was 74 % higher ( P = .02 ) for Executive Domain compared with combined training [ z-score change = 0.42 ( 0.22 , 0.63 ) resistance training vs 0.11 ( -0.60 , 0.28 ) combined ] and 48 % higher ( P < .04 ) for Global Domain [ z-score change = .0.45 ( 0.29 , 0.61 ) resistance training vs 0.23 ( 0.10 , 0.36 ) combined ] . CONCLUSIONS Resistance training significantly improved global cognitive function , with maintenance of executive and global benefits over 18 months BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . With a r and om groups design , the current study examined whether a 10-week cognitive training could improve healthy older adult ’s cognitive functions and everyday problem-solving and whether high ecological validity trainings would have greater positive impact upon everyday problem-solving than low ecological validity trainings . Eighty-six healthy Chinese older adult participants were assigned r and omly to five groups , including one control group receiving no training and four groups receiving low ecological memory training , high ecological memory training , low ecological reasoning training , and high ecological reasoning training , respectively . Participants were measured pre- and posttraining on spatial working memory , numerical working memory , reasoning , and everyday problem-solving . Results of this study showed that cognitive training significantly improved targeted cognitive functions and everyday problem-solving performance in all the intervention groups . However , high ecological cognitive trainings failed to show superior impact upon everyday problem-solving compared with low ecological cognitive trainings |
12,278 | 31,632,640 | Conclusion The available evidence suggests that changes occur in ‘ brain function ’ in response to spinal manipulation but are inconsistent across and - sometimes - within studies .
Conclusion La littérature scientifique suggère que des changements neurophysiologiques surviennent au niveau du cerveau en réponse à la manipulation vertébrale mais , de façon inconsistante .
Ainsi , il est prématuré d’attribuer à la manipulation vertébrale des bénéfices cliniques via un effet sur le cerveau | Background A recent hypothesis purports that spinal manipulation may cause changes at a brain level .
Functional Neurology , a mainly chiropractic approach , promotes the use of spinal manipulation to improve ‘ brain function ’ as if it were a proven construct .
No systematic review has been performed to investigate how well founded this hypothesis is .
Objective To investigate whether spinal manipulation has an effect on ‘ brain function ’ that is associated with any clinical benefits .
It is therefore premature to promote the use of spinal manipulation as a treatment to improve ‘ brain function’.Résumé Introduction Une hypothèse récente propose que la manipulation vertébrale causerait des changements neurophysiologiques au niveau du cerveau .
En Neurologie Fonctionnelle , approche principalement présente en chiropraxie , l’utilisation de la manipulation vertébrale est déjà promue comme capable d’améliorer le fonctionnement du cerveau . | Objectives . Studies have shown decreases in N30 somatosensory evoked potential ( SEP ) peak amplitudes following spinal manipulation ( SM ) of dysfunctional segments in sub clinical pain ( SCP ) population s. This study sought to verify these findings and to investigate underlying brain sources that may be responsible for such changes . Methods . Nineteen SCP volunteers attended two experimental sessions , SM and control in r and om order . SEPs from 62-channel EEG cap were recorded following median nerve stimulation ( 1000 stimuli at 2.3 Hz ) before and after either intervention . Peak-to-peak amplitude and latency analysis was completed for different SEPs peak . Dipolar models of underlying brain sources were built by using the brain electrical source analysis . Two-way repeated measures ANOVA was used to assessed differences in N30 amplitudes , dipole locations , and dipole strengths . Results . SM decreased the N30 amplitude by 16.9 ± 31.3 % ( P = 0.02 ) , while no differences were seen following the control intervention ( P = 0.4 ) . Brain source modeling revealed a 4- source model but only the prefrontal source showed reduced activity by 20.2 ± 12.2 % ( P = 0.03 ) following SM . Conclusion . A single session of spinal manipulation of dysfunctional segments in sub clinical pain patients alters somatosensory processing at the cortical level , particularly within the prefrontal cortex OBJECTIVE The purpose of this study was to determine if high-velocity , low-amplitude spinal manipulation ( SM ) altered the effects of corticospinal excitability on motoneuron activity innervating the paraspinal muscles . In a previous study using transcranial magnetic stimulation ( TMS ) , augmentation of motor-evoked potentials ( MEPs ) from the gastrocnemius muscle after lumbar SM was reported . To date , there is no known report of the effect of SM on paraspinal muscle excitability . METHODS The experimental design was a prospect i ve physiologic evaluation of the effects of SM on corticospinal excitability in asymptomatic subjects . The TMS-induced MEPs were recorded from relaxed lumbar erector spinae muscles of 72 asymptomatic subjects . The MEP amplitudes were evaluated pre-SM and post-SM or conditions involving prethrust positioning and joint loading or control . RESULTS There was a transient increase in MEP amplitudes from the paraspinal muscles as a consequence of lumbar SM ( F([6,414 ] ) = 8.49 ; P < .05 ) without concomitant changes after prethrust positioning and joint loading or in control subjects ( P > .05 ) . These data findings were substantiated by a significant condition x time interaction term ( F([12,414 ] ) = 2.28 ; P < .05 ) . CONCLUSIONS These data suggest that there is a postsynaptic facilitation of alpha motoneurons and /or corticomotoneurons innervating paraspinal muscles as a consequence of SM . It appears that SM may offer unique sensory input to the excitability of the motor system as compared to prethrust positioning and joint loading and control conditions Purpose The primary purpose of this study was to investigate whether a single session of spinal manipulation ( SM ) increases strength and cortical drive in the lower limb ( soleus muscle ) of elite Taekwondo athletes . Methods Soleus-evoked V-waves , H-reflex and maximum voluntary contraction ( MVC ) of the plantar flexors were recorded from 11 elite Taekwondo athletes using a r and omized controlled crossover design . Interventions were either SM or passive movement control . Outcomes were assessed at pre-intervention and at three post-intervention time periods ( immediate post , post 30 min and post 60 min ) . A multifactorial repeated measures ANOVA was conducted to assess within and between group differences . Time and session were used as factors . A post hoc analysis was carried out , when an interactive effect was present . Significance was set at p ≤ 0.05 . Results SM increased MVC force [ F(3,30 ) = 5.95 , p < 0.01 ] , and V-waves [ F(3,30 ) = 4.25 , p = 0.01 ] over time compared to the control intervention . Between group differences were significant for all time periods ( p < 0.05 ) except for the post60 force measurements ( p = 0.07 ) . Conclusion A single session of SM increased muscle strength and corticospinal excitability to ankle plantar flexor muscles in elite Taekwondo athletes . The increased MVC force lasted for 30 min and the corticospinal excitability increase persisted for at least 60 min Significance Functional MRI ( fMRI ) is 25 years old , yet surprisingly its most common statistical methods have not been vali date d using real data . Here , we used resting-state fMRI data from 499 healthy controls to conduct 3 million task group analyses . Using this null data with different experimental design s , we estimate the incidence of significant results . In theory , we should find 5 % false positives ( for a significance threshold of 5 % ) , but instead we found that the most common software packages for fMRI analysis ( SPM , FSL , AFNI ) can result in false-positive rates of up to 70 % . These results question the validity of a number of fMRI studies and may have a large impact on the interpretation of weakly significant neuroimaging results . The most widely used task functional magnetic resonance imaging ( fMRI ) analyses use parametric statistical methods that depend on a variety of assumptions . In this work , we use real resting-state data and a total of 3 million r and om task group analyses to compute empirical familywise error rates for the fMRI software packages SPM , FSL , and AFNI , as well as a nonparametric permutation method . For a nominal familywise error rate of 5 % , the parametric statistical methods are shown to be conservative for voxelwise inference and invalid for clusterwise inference . Our results suggest that the principal cause of the invalid cluster inferences is spatial autocorrelation functions that do not follow the assumed Gaussian shape . By comparison , the nonparametric permutation test is found to produce nominal results for voxelwise as well as clusterwise inference . These findings speak to the need of validating the statistical methods being used in the field of neuroimaging Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials Background This systematic review up date d and extended the " UK evidence report " by Bronfort et al. ( Chiropr Osteopath 18:3 , 2010 ) with respect to conditions/ interventions that received an ' inconclusive ’ or ' negative ’ evidence rating or were not covered in the report . Methods A literature search of more than 10 general medical and specialised data bases was conducted in August 2011 and up date d in March 2013 . Systematic review s , primary comparative studies and qualitative studies of patients with musculoskeletal or non-musculoskeletal conditions treated with manual therapy and reporting clinical outcomes were included . Study quality was assessed using st and ardised instruments , studies were summarised , and the results were compared against the evidence ratings of Bronfort . These were either confirmed , up date d , or new categories not assessed by Bronfort were added . Results 25,539 records were found ; 178 new and additional studies were identified , of which 72 were systematic review s , 96 were r and omised controlled trials , and 10 were non-r and omised primary studies . Most ' inconclusive ’ or ' moderate ’ evidence ratings of the UK evidence report were confirmed . Evidence ratings changed in a positive direction from inconclusive to moderate evidence ratings in only three cases ( manipulation/mobilisation [ with exercise ] for rotator cuff disorder ; spinal mobilisation for cervicogenic headache ; and mobilisation for miscellaneous headache ) . In addition , evidence was identified on a large number of non-musculoskeletal conditions not previously considered ; most of this evidence was rated as inconclusive . Conclusions Overall , there was limited high quality evidence for the effectiveness of manual therapy . Most review ed evidence was of low to moderate quality and inconsistent due to substantial method ological and clinical diversity . Areas requiring further research are highlighted Background In r and omised trials , rather than comparing r and omised groups directly some research ers carry out a significance test comparing a baseline with a final measurement separately in each group . Methods We give several examples where this has been done . We use simulation to demonstrate that the procedure is invalid and also show this algebraically . Results This approach is biased and invalid , producing conclusions which are , potentially , highly misleading . The actual alpha level of this procedure can be as high as 0.50 for two groups and 0.75 for three . Conclusions R and omised groups should be compared directly by two- sample methods and separate tests against baseline are highly misleading OBJECTIVE The aim of the study was to examine the effects of a high-velocity , low-amplitude ( HVLA ) manipulation to the lumbosacral joint on corticospinal excitability , as measured by motor evoked potentials ( MEPs ) using transcranial magnetic stimulation , and spinal reflex excitability , as measured by the Hoffman reflex ( H-reflex ) . METHODS In a r and omized , controlled , crossover design , 14 asymptomatic volunteers ( mean age , 23 ± 5.4 years ; 10 men ; 4 women ) were measured for MEPs and H-reflexes immediately before and after a r and omly allocated intervention . The interventions consisted of HVLA applied bilaterally to the lumbosacral joint and a control intervention . Participants returned a week later , and the same procedures were performed using the other intervention . Data for H-reflex and MEP amplitudes were normalized to the M-wave maximum amplitude and analyzed using 2-way analysis of variance with repeated measures . RESULTS A significant interaction of treatment by time was found for MEP ( F(1,13 ) = 4.87 , P = .04 ) , and post hoc analyses showed that the MEP/M-wave maximum ratio decreased significantly in the HVLA treatment ( P = .02 ; effect size , 0.68 ) . For H-reflex , there was a significant effect of time ( F(1,13 ) = 8.186 , P = .01 ) and treatment and time interaction ( F(1,13 ) = 9.05 , P = .01 ) , with post hoc analyses showing that H-reflexes were significantly reduced after the HVLA manipulation ( P = .004 ; effect size , 0.94 ) . There were no significant changes in MEP latency or silent period duration . CONCLUSION An HVLA manipulation applied to the lumbosacral joint produced a significant decrease in corticospinal and spinal reflex excitability , and no significant change occurred after the control intervention . The changes in H-reflexes were larger than those in MEPs , suggesting a greater degree of inhibition at the level of the spinal cord BACKGROUND The physiologic mechanism by which spinal manipulation may reduce pain and muscular spasm is not fully understood . One such mechanistic theory proposed is that spinal manipulation may intervene in the cycle of pain and spasm by affecting the resting excitability of the motoneuron pool in the spinal cord . Previous data from our laboratory indicate that spinal manipulation leads to attenuation of the excitability of the motor neuron pool when assessed by means of peripheral nerve Ia-afferent stimulation ( Hoffmann reflex ) . OBJECTIVE The purpose of this study was to determine the effects of lumbar spinal manipulation on the excitability of the motor neuron pool as assessed by means of transcranial magnetic stimulation . METHODS Motor-evoked potentials were recorded subsequent to transcranial magnetic stimulation . The motor-evoked potential peak-to-peak amplitudes in the right gastrocnemius muscle of healthy volunteers ( n = 24 ) were measured before and after homolateral L5-S1 spinal manipulation ( experimental group ) or side-posture positioning with no manipulative thrust applied ( control group ) . Immediately after the group-specific procedure , and again at 5 and 10 minutes after the procedure , 10 motor-evoked potential responses were measured at a rate of 0.05 Hz . An optical tracking system ( OptoTRAK , Northern Digital Inc , Waterloo , Canada [ < 0.10 mm root-mean-square ] ) was used to monitor the 3-dimensional ( 3-D ) position and orientation of the transcranial magnetic stimulation coil , in real time , for each trial . RESULTS The amplitudes of the motor-evoked potentials were significantly facilitated from 20 to 60 seconds relative to the prebaseline value after L5-S1 spinal manipulation , without a concomitant change after the positioning ( control ) procedure . CONCLUSIONS When motor neuron pool excitability is measured directly by central corticospinal activation with transcranial magnetic stimulation techniques , a transient but significant facilitation occurs as a consequence of spinal manipulation . Thus , a basic neurophysiologic response to spinal manipulation is central motor facilitation OBJECTIVES To investigate the potential usefulness of a mental rotation paradigm in providing an objective measure of spinal manipulative therapy . To determine if cortical processing , as indicated by response time to a mental rotation reaction-time task , is altered by an upper cervical toggle recoil adjustment . DESIGN Prospect i ve , double-blind , r and omized , controlled trial . SETTING Chiropractic college clinical training facility . PARTICIPANTS Thirty-six chiropractic student volunteers with clinical evidence of upper cervical joint dysfunction . INTERVENTION Participants in the experimental group received a high-velocity , low-amplitude upper cervical adjustment . A non-intervention group was used to control for improvement in the mental rotation task as a result of practice effects . OUTCOME MEASURES Reaction time was measured for r and omly varying angular orientations of an object appearing either as normal or mirror-reversed on a computer screen . RESULTS The average decrease in mental rotation reaction time for the experimental group was 98 ms , a 14.9 % improvement , whereas the average decrease in mental rotation reaction time for the control group was 58 ms , an 8 . 0 improvement . The difference scores after the intervention time were significantly greater for the experimental group compared with the control group , as indicated by a one-tailed , 2- sample , equal variance Student t test , ( P < 05 ) . CONCLUSION The results of this study have demonstrated a significant improvement in a complex reaction-time task after an upper cervical adjustment . These results provide evidence that upper cervical adjustment may affect cortical processing Objective The purpose of this study was to examine whether cerebral activation in response to noxious mechanical stimuli varies with thrust manipulation ( TM ) when compared with sham manipulation ( SM ) as measured by blood oxygenation level – dependent functional magnetic resonance imaging . Methods Twenty‐four volunteers ( 67 % female ) with complaints of acute or subacute mechanical ( nontraumatic ) neck pain satisfied eligibility requirements and agreed to participate . Participants were r and omized to receive TM to the thoracic spine or SM , and then underwent functional magnetic resonance scanning while receiving noxious stimuli before and after TM or SM . An 11‐point numeric pain rating scale was administered pre‐ and postmanipulation for neck pain and to determine perceptions of pain intensity with respect to neck pain and mechanical stimuli . Blood oxygenation level – dependent functional magnetic resonance imaging recorded the cerebral hemodynamic response to the mechanical stimuli . Results Imaging revealed significant group differences , with those individuals in the manipulation group exhibiting increased areas of activation ( postmanipulation ) in the insular and somatosensory cortices and individuals in the sham group exhibiting greater areas of activation in the pre central gyrus , supplementary motor area , and cingulate cortices ( P < .05 ) . However , between‐group differences on the numeric pain rating scale for mechanical stimuli and for self‐reported neck pain were not statistically significant . Conclusions This study provides preliminary level 2b evidence suggesting cortical responses in patients with nontraumatic neck pain may vary between thoracic TM and a sham comparator OBJECTIVE This study sought to investigate the influence of spinal dysfunction and spinal manipulation on the response of the central nervous system to a motor training task . METHODS The dual peripheral nerve stimulation somatosensory evoked potential ( SEP ) ratio technique was used in 11 subjects before and after a 20-minute typing task and again when the typing task was preceded with cervical spine manipulation . Somatosensory evoked potentials were recorded after median and ulnar nerve stimulation at the wrist ( 1 millisecond square wave pulse , 2.47 Hz , 1x motor threshold ) . The SEP ratios were calculated for the N9 , N11 , N13 , P14 - 18 , N20-P25 , and P22-N30 peak complexes from SEP amplitudes obtained from simultaneous median and ulnar ( MU ) stimulation divided by the arithmetic sum of SEPs obtained from individual stimulation of the median ( M ) and ulnar ( U ) nerves . RESULTS There was a significant increase in the MU/M+U ratio for both cortical ( ie , N20-P25 and P22-N30 ) SEP components after the 20-minute repetitive contraction task . This did not occur when the motor training task was preceded with spinal manipulation . Instead , there was a significant decrease in the MU/M+U ratio for the cortical P22-N30 SEP component . The ratio changes appear to be due to changes in the ability to suppress the dual input as concurrent changes in the MU amplitudes were observed . DISCUSSION This study suggests that cervical spine manipulation not only alters cortical integration of dual somatosensory input but also alters the way the central nervous system responds to subsequent motor training tasks . CONCLUSION These findings may help to clarify the mechanisms responsible for the effective relief of pain and restoration of functional ability documented after spinal manipulation and the mechanism involved in the initiation of overuse injuries OBJECTIVE The purpose s of this study were to use functional magnetic resonance imaging to investigate the immediate changes in functional connectivity ( FC ) between brain regions that process and modulate the pain experience after 3 different types of manual therapies ( MT ) and to identify reductions in experimentally induced myalgia and changes in local and remote pressure pain sensitivity . METHODS Twenty-four participants ( 17 men ; mean age ± SD , 21.6 ± 4.2 years ) who completed an exercise-injury protocol to induce low back pain were r and omized into 3 groups : chiropractic spinal manipulation ( n = 6 ) , spinal mobilization ( n = 8) , or therapeutic touch ( n = 10 ) . The primary outcome was the immediate change in FC as measured on functional magnetic resonance imaging between the following brain regions : somatosensory cortex , secondary somatosensory cortex , thalamus , anterior and posterior cingulate cortices , anterior and poster insula , and periaqueductal gray . Secondary outcomes were immediate changes in pain intensity , measured with a 101-point numeric rating scale , and pain sensitivity , measured with a h and held dynamometer . Repeated- measures analysis of variance models and correlation analyses were conducted to examine treatment effects and the relationship between within-person changes across outcome measures . RESULTS Changes in FC were found between several brain regions that were common to all 3 MT interventions . Treatment-dependent changes in FC were also observed between several brain regions . Improvement was seen in pain intensity after all interventions ( P < .05 ) with no difference between groups ( P > .05 ) . There were no observed changes in pain sensitivity , or an association between primary and secondary outcome measures . CONCLUSION These results suggest that MTs ( chiropractic spinal manipulation , spinal mobilization , and therapeutic touch ) have an immediate effect on the FC between brain regions involved in processing and modulating the pain experience . This suggests that neurophysiologic changes after MT may be an underlying mechanism of pain relief |
12,279 | 25,497,683 | In conclusion , TCC practice was beneficial to improve the balance control ability and flexibility of older adults , which may be the reason of preventing falls | BACKGROUND Falls are the main cause of accidental death in the elderly people , which is associated with balance control ability and flexibility of the older adults .
The purpose of this study was to evaluate the effect of TCC on the balance control and flexibility of the older adults . | BACKGROUND recent studies have found that moderate intensity exercise is an effective intervention strategy for preventing falls in older people . However , research is required to determine whether supervised group exercise programmes , conducted in community setting s with at-risk older people referred by their health care practitioner are also effective in improving physical functioning and preventing falls in this group . OBJECTIVES to determine whether participation in a weekly group exercise programme with ancillary home exercises over one year improves balance , muscle strength , reaction time , physical functioning , health status and prevents falls in at-risk community-dwelling older people . METHODS the sample comprised 163 people aged over 65 years identified as at risk of falling using a st and ardised assessment screen by their general practitioner or hospital-based physiotherapist , residing in South Western Sydney , Australia . Subjects were r and omised into either an exercise intervention group or a control group . Physical performance and general health measures were assessed at baseline and repeated 6-months into the trial . Falls were measured over a 12-month follow-up period using monthly postal surveys . RESULTS at baseline both groups were well matched in their physical performance , health and activity levels . The intervention subjects attended a median of 23 exercise classes over the year , and most undertook the home exercise sessions at least weekly . At retest , the exercise group performed significantly better than the controls in three of six balance measures ; postural sway on the floor with eyes open and eyes closed and coordinated stability . The groups did not differ at retest in measures of strength , reaction time and walking speed or on Short-Form 36 , Physical Activity Scale for the Elderly or fear of falling scales . Within the 12-month trial period , the rate of falls in the intervention group was 40 % lower than that of the control group ( IRR=0.60 , 95 % CI 0.36 - 0.99 ) . CONCLUSIONS these findings indicate that participation in a weekly group exercise programme with ancillary home exercises can improve balance and reduce the rate of falling in at-risk community dwelling older people OBJECTIVES To compare the effectiveness of tai chi and low-level exercise in reducing falls in older adults ; to determine whether mobility , balance , and lower limb strength improved and whether higher doses of tai chi result ed in greater effect . DESIGN R and omized controlled trial . SETTING Eleven sites throughout New Zeal and . PARTICIPANTS Six hundred eighty-four community-residing older adults ( mean age 74.5 ; 73 % female ) with at least one falls risk factor . INTERVENTION Tai chi once a week ( TC1 ) ( n = 233 ) ; tai chi twice a week ( TC2 ) ( n = 220 ) , or a low-level exercise program control group ( LLE ) ( n = 231 ) for 20 wks . MEASUREMENTS Number of falls was ascertained according to monthly falls calendars . Mobility ( Timed-Up- and -Go Test ) , balance ( step test ) , and lower limb strength ( chair st and test ) were assessed . RESULTS The adjusted incident rate ratio ( IRR ) for falls was not significantly different between the TC1 and LLE groups ( IRR = 1.05 , 95 % confidence interval ( CI ) = 0.83 - 1.33 , P = .70 ) or between the TC2 and LLE groups ( IRR = 0.88 , 95 % CI = 0.68 - 1.16 , P = .37 ) . Adjusted multilevel mixed-effects Poisson regression showed a significant reduction in logarithmic mean fall rate of -0.050 ( 95 % CI = -0.064 to -0.037 , P < .001 ) per month for all groups . Multilevel fixed-effects analyses indicated improvements in balance ( P < .001 right and left leg ) and lower limb strength ( P < .001 ) but not mobility ( P = .54 ) in all groups over time , with no differences between the groups ( P = .37 ( right leg ) , P = .66 ( left leg ) , P = .21 , and P = .44 , respectively ) . CONCLUSION There was no difference in falls rates between the groups , with falls reducing similarly ( mean falls rate reduction of 58 % ) over the 17-month follow-up period . Strength and balance improved similarly in all groups over time Purpose : To assess some fall-related clinical variables ( balance , gait , fear of falling , functional autonomy , self-actualization and self-efficacy ) that might explain the fact that supervised Tai Chi has a better impact on preventing falls compared to a conventional physiotherapy program . Methods : The participants ( 152 older adults over 65 who were admitted to a geriatric day hospital program ) were r and omly assigned to either a supervised Tai Chi group or the usual physiotherapy . The presence of the clinical variables related to falls was evaluated before the intervention ( T1 ) , immediately after ( T2 ) , and 12 months after the end of the intervention ( T3 ) . Results : Both exercise programs significantly improved fall-related outcomes but only the Tai Chi intervention group decreased the incidence of falls . For both groups , most variables followed the same pattern , i.e. showed significant improvement with the intervention between T1 and T2 , and followed by a statistically significant decrease at the T3 evaluation . However , self-efficacy was the only variable that improved solely with the Tai Chi intervention ( p = 0.001 ) . Conclusions : The impact of supervised Tai Chi on fall prevention can not be explained by a differential effect on balance , gait and fear of falling . It appeared to be related to an increase of general self-efficacy , a phenomenon which is not seen in the conventional physiotherapy program . Implication s for Rehabilitation Each participant received a multidisciplinary intervention with either Tai Chi or physical therapy . Both interventions were associated with improved balance , gait , less fear of falling , improved functional autonomy and greater self actualisation . Only Tai Chi decreased the incidence of falls which appeared to be related to self-efficacy . Tai Chi seems to be a good alternative to physical therapy exercises to prevent falls in frail older people CONTEXT Because Tai Chi ( TC ) is beneficial to elders without cognitive impairment ( CI ) , it also may benefit elders with CI . But elders with CI have generally been excluded from TC studies because many measurement tools require verbal reports that some elders with CI are unable to provide . OBJECTIVES To test the efficacy of a TC program in improving pain and other health outcomes in community-dwelling elders with knee osteoarthritis ( OA ) and CI . METHODS This pilot cluster-r and omized trial was conducted between January 2008 and June 2010 ( Clinical Trials.gov Identifier : NCT01528566 ) . The TC group attended Sun style TC classes , three sessions a week for 20 weeks ; the control group attended classes providing health and cultural information for the same length of time . Measures included the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) pain , physical function and stiffness subscales ; the Get Up and Go test ; the Sit-to-St and test ; and the Mini-Mental State Examination ( MMSE ) , administered at baseline , every four weeks during the intervention and at the end of the study ( post-test ) . RESULTS Eight sites participated in either the TC group ( four sites , 28 participants ) or control group ( four sites , 27 participants ) . The WOMAC pain ( P = 0.006 ) and stiffness scores ( P = 0.010 ) differed significantly between the two groups at post-test , whereas differences between the two groups in the WOMAC physical function score ( P = 0.071 ) and the MMSE ( P = 0.096 ) showed borderline significance at the post-test . WOMAC pain ( P = 0.001 ) , physical function ( P = 0.021 ) , and stiffness ( P ≤ 0.001 ) scores improved significantly more over time in the TC group than in controls . No adverse events were found in either group . CONCLUSION Practicing TC can be efficacious in reducing pain and stiffness in elders with knee OA and CI Balance ability decreases with age , which results in an increased risk of falls for people over age 65 . Tai Chi exercise appears to offer potential benefits in the reduction of falls for the elderly . The purpose of the present study was to examine the effects of extended ( 6- and 12-month ) Tai Chi exercise interventions on balance and selected motor functions for senior citizens . Forty-seven subjects were recruited from two local senior centers . Twenty of them ( M = 71.8 years , SD = 7.1 ) , 11 in the Tai Chi exercise group and 9 in the control group , completed the pre- , mid- and post-tests over 12 months on five selected functional performance tests : static balance , dynamic balance , choice reaction time , heel-rise strength , and ankle flexibility . The Tai Chi group was provided with a one-hour Tai Chi exercise session per week for 12 months ; the control group did not participate in any exercise program . Results showed that static balance improved significantly after a 6-month Tai Chi intervention . Moreover , the Tai Chi group maintained a higher level in the test performance compared with the control group at the end of the 12-month intervention , but there was no significant difference between the two groups . Data suggested that Tai Chi exercise intervention could produce a positive influence on balance control for the elderly over a prolonged period , but not on muscle strength and ankle flexibility |
12,280 | 29,617,153 | Nitrate and nitrite supplementation did not modify CBF or CF . | null | null |
12,281 | 11,533,422 | This study adopts an overview of the magnitude and the nature of clinical quality problems in general practice in three countries . | OBJECTIVES Little is known about the quality of clinical care provided outside the hospital sector , despite the increasingly important role of clinical generalists working in primary care .
In this study we aim ed to summarise published evaluations of the quality of clinical care provided in general practice in the UK , Australia , and New Zeal and . | OBJECTIVE Most data on the prevalence and behaviour of skin cancers is based on hospital studies . The scarcity of community based general practice skin surveys prompted this study . The aim of the survey was to : record the relative frequency of different skin tumours in an Adelaide general practice and compare these with rates published elsewhere . to record clinical accuracy of diagnosis , infection rates and completeness of excision . METHOD Five year prospect i ve study recording age , sex , site of excision and histological diagnosis of 369 skin excisions in a general practice . A sub study recorded clinical diagnostic accuracy , with subsequent histological diagnosis . RESULTS Non-melanotic skin cancer ( NMSC ) accounted for 59.9 % of the total lesions with basal cell carcinomas ( BCCs ) accounting for 30.6 % , squamous cell carcinomas ( SCCs ) 21.7 % , and intra epithelial cancer 7.6 % . The most frequent excision site was head , neck and face . A total of 75 % of SCCs occurred on sun exposed areas , whereas a significant proportion of BCCs occurred on the shoulder and trunk ( 37.1 % ) ; this agrees with recent trends in Australia . Clinical accuracy when compared with histology was 77 % comparing favourably with other published data . CONCLUSION Skin cancer continues to be a major community health issue in Australia in which general practitioners are heavily involved . Due to their expertise and early intervention at a community level , much is being done to reduce this cost in the community . Further research on NMSC trends are needed , especially in general practice A decision support system for the management of oral hypoglycaemic therapy in type II diabetes was evaluated . The ruleset contained therein forms the basis of a prototype computer programme , but in order to assess the robustness of the individual rules , it was decided it was necessary to use a paper-based form of the ruleset . A nurse with no previous experience of managing type II diabetes was trained to use the system and then undertook the exclusive management of half of all new type II diabetics , from a district population of 300,000 , over a 16-month period . General practice s within this area were divided into two groups , study and control , matching for size , geographical area and st and ards of existing diabetes care . Patients ( n = 102 ) from the study group practice s were then assigned to her care . Those patients ( n = 116 ) in the control group of practice s were treated according to their normal procedures . The decision support system for oral hypoglycaemic therapy was based on the following criteria : the current type of treatment ( six levels ) ; current glycaemic control ( HbA1 and FBS)-whether improving , steady or worsening ; and weight-%IBW , whether rising , steady or falling . Each of these parameters was carefully defined on the basis of established practice and clinical experience . Patients after initial education were seen at their usual clinic by the nurse only , on a monthly basis , until satisfactory glycaemic control was established and thereafter review ed 3 monthly . She was also responsible for ensuring the organisation of Diabetes Annual Review procedures . The medical records of the control group patients were examined at the end of the study and data on glycaemic control and Annual Review s extracted . In the study group 98 % patients achieved HbA1 levels within the normal range and all patients had full annual review s performed . The control practice s achieved much poorer degrees of metabolic control ( P < 0.01 ) and completed fewer annual review s. The study group did not demonstrate a significantly increased frequency of clinical hypoglycaemia consequent upon better blood sugar control . No exceptions to the ruleset , as initially defined , were detected . In conclusion , this decision support system was successful at achieving st and ards of diabetes control and care equal to or better than conventional structures of diabetes care . Implementation of such a system , on a simple computer platform , could greatly assist and possibly improve diabetes management in general practice Objective To evaluate whether nurse run clinics in general practice improve secondary prevention in patients with coronary heart disease . Design R and omised controlled trial . Setting A r and om sample of 19 general practice s in northeast Scotl and . Patients 1173 patients ( 685 men and 488 women ) under 80 years with working diagnoses of coronary heart disease , but without terminal illness or dementia and not housebound . Intervention Nurse run clinics promoted medical and lifestyle aspects of secondary prevention and offered regular follow up . Main outcome measures Components of secondary prevention assessed at baseline and one year were : aspirin use ; blood pressure management ; lipid management ; physical activity ; dietary fat ; and smoking status . A cumulative score was generated by counting the number of appropriate components of secondary prevention for each patient . Results There were significant improvements in aspirin management ( odds ratio 3.22 , 95 % confidence interval 2.15 to 4.80 ) , blood pressure management ( 5.32 , 3.01 to 9.41 ) , lipid management ( 3.19 , 2.39 to 4.26 ) , physical activity ( 1.67 , 1.23 to 2.26 ) and diet ( 1.47 , 1.10 to 1.96 ) . There was no effect on smoking cessation ( 0.78 , 0.47 to 1.28 ) . Of six possible components of secondary prevention , the baseline mean was 3.27 . The adjusted mean improvement attributable to intervention was 0.55 of a component ( 0.44 to 0.67 ) . Improvement was found regardless of practice baseline performance . Conclusions Nurse run clinics proved practical to implement in general practice and effectively increased secondary prevention in coronary heart disease . Most patients gained at least one effective component of secondary prevention and , for them , future cardiovascular events and mortality could be reduced by up to a third Although low dose aspirin reduces risk in patients with heart disease , many such patients do not receive daily prophylactic aspirin.1 We report a trial of feedback of general practitioners ' data on aspirin prescribing aim ed at increasing coded aspirin prescribing in patients with heart disease . Computerised practice s were r and omised to receive feedback on their prescribing , either of aspirin for patients with ischaemic heart disease or of hormone replacement therapy for women who had had hysterectomies . We approached 48 practice s in north London ; nine refused , and 11 were excluded . Of the 28 ( 58 % ) practice s in the study , seven were single h and ed and six had five or more partners . All participating practice s used the emis computer system except two that used Paradoc ; both systems yielded sufficiently reliable and comparable data . Eligible practice s had to have computerised information on hysterectomies and ischaemic heart disease and use their systems for repeat prescribing . Practice s were then r and omised by using sealed envelopes to Abstract Objective : To determine whether locally developed guidelines on asthma and diabetes disseminated through practice based education improve quality of care in non-training , inner city general practice s. Design : R and omised controlled trial with each practice receiving one set of guidelines but providing data on the management of both conditions . Subjects:24 inner city , non-training general practice s. Setting : East London . Main outcome measures : Recording of key variables in patient records ( asthma : peak flow rate , review of inhaler technique , review of asthma symptoms , prophylaxis , occupation , and smoking habit ; diabetes : blood glucose concentration , glycaemic control , funduscopy , feet examination , weight , and smoking habit ) ; size of practice disease registers ; prescribing in asthma ; and use of structured consultation “ prompts . ” Results : In practice s receiving diabetes guidelines , significant improvements in recording were seen for all seven diabetes variables . Both groups of practice s showed improved recording of review of inhaler technique , smoking habit , and review of asthma symptoms . In practice s receiving asthma guidelines , further improvement was seen only in recording of review of inhaler technique and quality of prescribing in asthma . Sizes of disease registers were unchanged . The use of structured prompts was associated with improved recording of four of seven variables on diabetes and all six variables on asthma . Conclusions : Local guidelines disseminated via practice based education improve the management of diabetes and possibly of asthma in inner city , non-training practice s. The use of simple prompts may enhance this improvement This study examined the blood pressure ( BP ) control and number of drugs prescribed for a sample of hypertensive patients from 18 practice s in Northeast Engl and . Out of a total of 35,379 registered patients aged 40 - 69 years , 2995 ( 8.5 % ) were on treatment for hypertension . Data was abstract ed from the practice records of a r and om sample of 691 patients . Using British Hypertension Society st and ards , BP control was optimal for systolic pressure ( less than 160 mm Hg ) in 469 ( 68 % ) , and for diastolic pressure ( less than 90 mm Hg ) in 345 ( 50 % ) , but only 269 ( 39 % ) had optimally controlled systolic and diastolic pressures . Sixty-one per cent were taking one drug and 39 % two or more ; 82 % of patients aged 40 - 49 years but only 61 % of those aged 60 - 69 years had optimally controlled systolic pressures . Forty-three per cent of the 40 to 49-year-old group and 56 % of the 60 to 69-year-old group had optimally controlled diastolic pressures . A strong inverse relationship was found between age and systolic BP control but there was no association between age and diastolic pressure or the number of drugs being prescribed . Sub-optimal BP control is a major problem and remedial strategies should stress the greater gain from treating older patients OBJECTIVES To monitor the documentation of blood pressure measurements and other cardiovascular risk factors in general practice patients with hypertension . METHOD Twenty-five case notes of patients diagnosed as hypertensive were r and omly selected from each of 58 participating general practitioners in suburban general practice in Adelaide , South Australia and were monitored by two registered nurses . MAIN OUTCOME MEASURES to assess whether blood pressure readings , weight , smoking history , alcohol intake and family history were documented , and whether electrocardiogram , plasma lipids , urinalysis and biochemical screen ( which includes blood urea nitrogen , creatinine , glucose , electrolytes and uric acid ) had been undertaken . RESULTS Data from 1446 hypertensive patients showed that for the last three blood pressure values recorded , 483 ( 33 % ) had an average level of 140/90 mm Hg or less and 1100 ( 76 % ) had an average of 160/95 mm Hg or less . The other cardiovascular risk factors selected were variably recorded , with biochemical screen being most commonly recorded [ 1198 ( 83 % ) ] and family history [ 423 ( 29 % ) ] the least . CONCLUSIONS Inadequacies in the control of hypertension and in the documentation of other cardiovascular risk factors suggest that further educational initiatives are required in this common chronic illness Initiation , distribution , concomitants and follow-up of cholesterol testing were studied in Grampian . Data were examined for 4979 patients , representing all patients in one year from those general practice s who made exclusive use of the clinical chemistry laboratory for cholesterol testing . A r and om sample of 215 patients was studied in further detail . Age and sex distribution , results of cholesterol tests and their follow-up , nature and results of associated biochemical tests , test initiation , testing rates by practice , and prescription rates of lipid lowering agents by practice were measured . Cholesterol testing was mostly in line with current knowledge of cardiovascular risk , and associated with further cardiovascular and biochemical assessment . There was a 90-fold range in practice cholesterol testing rates , and a similarly wide range in prescription rates of lipid lowering agents ; there was a significant correlation between these . Rates and results of follow-up testing suggests a “ rule of halves ” for cholesterol testing BACKGROUND The appropriateness of epilepsy as a topic for general practice audit activity has been emphasized , but few audits have been undertaken to data and those that have are small scale . Historically , management of epilepsy has been a neglected area , and services for people with epilepsy remain generally poor . AIM The study was design ed to examine the process of care for people with epilepsy through a region-wide audit of general practitioner records . METHOD General practitioners in 31 r and omly selected general practice s in one UK health region undertook a notes audit for all patients identified as having active epilepsy ( patients who had had seizures in the last 2 years , or were currently seizure-free but on antiepileptic medication ) . A st and ard pro forma was used to collect information relating to diagnosis , drug treatment , and primary and secondary care contacts . RESULTS Recording of information in the notes was generally good , but poor for some key items essential to the effective management of the condition ; results suggest that a number of recommendations about provision of care for epilepsy are not being met : in particular , EEG and CT investigations often appear poorly directed ; prescribed antiepileptic therapy is not always optimal ; significant numbers of patients are being treated in hospital by non-neurologists ; there is little evidence of any regular review being undertaken by general practitioners of their patients with epilepsy ; and counselling about the non- clinical aspects of epilepsy often appears inadequate . CONCLUSIONS Despite recommendations in a number of recent reports , gaps and inconsistencies in epilepsy care persist , both at the primary and secondary level . The means by which such shortcomings can be reduced ( e.g. by specialist epilepsy nurses working across the primary - secondary care interface ) should now be systematic ally examined . The study has highlighted a need for evidence -based guidelines which span the primary - secondary care interface and clarify the contribution of the various practitioners involved in the provision of care for people with epilepsy Abstract Objective : To determine whether peer review medical audit in a primary care setting changes clinical behaviour in relation to the management of hypertension . Design : Review of medical records in general practice s to identify hypertensive patients followed up by assessment of the pre-educational and post-educational management of interventions . Setting : Six general practice s in north west London picked at r and om within defined criteria of geography and size . Subjects : 740 hypertensive patients managed by 25 different general practitioners . Main outcome measures : Improved level of care in terms of better diagnosis by having at least three blood pressure readings before the start of drug treatment , better level of recordings of lifestyle parameters as shown by the level of recordings of body mass index and total lipid values , and better control of blood pressure and harm minimisation as shown by the level of recordings of urea and electrolyte values . Results : Improvement was noted in the level of recordings of body mass index , total lipid concentrations , and urea and electrolyte values but not in better diagnosis or blood pressure control . Conclusion : Clinical behaviour of general practitioners can be changed by peer review but more complex behavioural changes which require the cooperation of the patients and cognitive actions by the general practitioners need further investigation . Key messages Peer review can significantly change the clinical behaviour of general practitioners with respect to undertaking simple diagnostic procedures , recording lifestyle variables , and carrying out laboratory measurements Attempts to improve control of blood pressure by general practitioners is a target less easily achieved A primary care study has shown that despite an active education programme over two years the proportion of treated patients whose blood pressure was controlled to < 160/90 mm Hg remained at only one BACKGROUND In a sample of 30,195 r and omly selected hospital records , we identified 1133 patients ( 3.7 percent ) with disabling injuries caused by medical treatment . We report here an analysis of these adverse events and their relation to error , negligence , and disability . METHODS Two physician- review ers independently identified the adverse events and evaluated them with respect to negligence , errors in management , and extent of disability . One of the authors classified each event according to type of injury . We tested the significance of differences in rates of negligence and disability among categories with at least 30 adverse events . RESULTS Drug complications were the most common type of adverse event ( 19 percent ) , followed by wound infections ( 14 percent ) and technical complications ( 13 percent ) . Nearly half the adverse events ( 48 percent ) were associated with an operation . Adverse events during surgery were less likely to be caused by negligence ( 17 percent ) than nonsurgical ones ( 37 percent ) . The proportion of adverse events due to negligence was highest for diagnostic mishaps ( 75 percent ) , noninvasive therapeutic mishaps ( " errors of omission " ) ( 77 percent ) , and events occurring in the emergency room ( 70 percent ) . Errors in management were identified for 58 percent of the adverse events , among which nearly half were attributed to negligence . CONCLUSIONS Although the prevention of many adverse events must await improvements in medical knowledge , the high proportion that are due to management errors suggests that many others are potentially preventable now . Reducing the incidence of these events will require identifying their causes and developing methods to prevent error or reduce its effects Several r and omised controlled trials have shown that warfarin treatment for patients with atrial fibrillation substantially reduces their risk of stroke.1 Studies have found low treatment rates among patients with atrial fibrillation in hospital2 and in primary care,3 but these have been limited by their reliance on identifying patients with atrial fibrillation from coding of records and prescription of antiarrhythmic drugs . We report the use of warfarin among patients with atrial fibrillation in a community survey . Concern has been expressed about the high rates of exclusion of subjects from r and omised trials of warfarin treatment . It has been suggested that the use of similar exclusions in clinical practice would greatly reduce the number of patients eligible for treatment,4 which might explain the low treatment rates . We therefore applied exclusion criteria similar to one of these trials BACKGROUND The aim of this study was to apply recommendations from r and omized controlled trials and guidelines on the detection and control of hypertension in the elderly to a district health authority population . METHODS A cross-sectional audit of Northamptonshire general practitioners ' ( GPs ' ) records from February to June 1993 was carried out . RESULTS A total of 2428 notes of men and women aged 65 or over registered with their GP was audited . A large proportion of patients , 86 per cent ( 95 per cent CI 84.6 - 87.4 per cent ) , had a blood pressure record taken in the last 10 years . Of those with raised blood pressure ( BP > or = 160/90 mmHg ) 49 per cent ( 95 per cent CI 46.2 - 51.8 per cent ) were untreated , and 58 per cent ( 95 per cent CI 54 - 61.9 per cent ) of those labelled as hypertensive were not adequately controlled . The prevalence of labelled hypertension was 25 per cent ( 95 per cent CI 23.3 - 26.7 per cent ) . CONCLUSIONS From these results it is estimated that between 11 and 29 fatal and non-fatal strokes could be prevented in the 65 - 74-year-old age population of Northamptonshire each year if current guidelines were followed . Improved detection and management of elderly hypertensive patients in primary care could contribute significantly towards the target for stroke reduction set in the Health of the nation strategy BACKGROUND Regular aspirin is beneficial after myocardial infa rct ion ( MI ) . Community-based surveys appear to show unsatisfactory uptake of aspirin after MI . This could be due to over-the-counter ( OTC ) use not being recorded . In a pilot study in one practice , 39 % of patients on aspirin after MI used OTC preparations . In addition , women and older patients were less likely to use aspirin . OBJECTIVES We aim ed to describe aspirin use following MI in general practice s in West London , including regimens and OTC use , and to demonstrate any association between aspirin use and gender , age or social class . METHODS We used a postal question naire survey . The setting was a r and om sample of six general practice s in Ealing , Hammersmith and Hounslow Health Authority who use Egton Medical Information Systems ( EMIS ) to store morbidity data . The subjects were registered patients with a history of MI . The main outcome measures were question naire data on aspirin use , regimen , OTC use , prescription charge exemption , age , gender , ethnic group and social class . RESULTS The prevalence of previously recorded MI in all age groups was 0.64 % . The response rate was 89 % . Regular aspirin was used by 80 % . Of these , 22 % use OTC aspirin . OTC use was significantly more common in those paying prescription charges . Aspirin use was not associated with gender , age or social class . CONCLUSION This study demonstrated a high uptake of aspirin among patients with previous MI as recorded by computer . OTC aspirin use was significant , and should be inquired about and recorded |
12,282 | 19,828,674 | The risk of developing late complications after chlamydia lower genital tract infection appears low .
In screening programmes , chlamydia antibody testing , as an intermediate marker for potential adverse sequelae , might enable more precise estimates | BACKGROUND The majority of Chlamydia trachomatis infections in women are asymptomatic , but may give rise to pelvic inflammatory disease ( PID ) and tubal infertility .
Screening programmes aim at reducing morbidity in individuals by early detection and treatment , and at decreasing the overall prevalence of infection in the population .
A number of modelling studies have tried to calculate the threshold prevalence of chlamydia lower genital tract infection above which screening becomes cost-effective .
There is considerable debate over the exact complication rates after chlamydia infections , and more precise estimates of PID and tubal infertility are needed , for instance to be inserted in economic models . | OBJECTIVES To determine lower genital tract carriage rates of C. trachomatis , N. gonorrhoeae and bacterial vaginosis among women seeking termination of pregnancy . To compare two clinical management strategies for minimising the risks of infective morbidity after induced abortion . DESIGN Prevalence of infections was assessed by screening women undergoing abortion . Clinical management strategies were compared by a r and omised trial . SETTING The gynaecology departments of four hospitals in Scotl and . PARTICIPANTS 1672 women undergoing induced abortion . INTERVENTIONS Women r and omised to prophylaxis received metronidazole 1 g rectally before abortion plus doxycycline 100 mg twice daily for seven days . Women r and omised to screen- and -treat received appropriate antibiotics only if screening proved positive for one or more infection . MAIN OUTCOME MEASURES Prevalences of infections ; morbidity in the eight weeks following abortion as assessed by reported symptoms , general practitioner consultation and prescription rates and hospital re-attendances ; costs to the NHS of alternative managements . RESULTS Prevalence rates : C. trachomatis 5.6 % ; N gonorrhoeae 0.19 % ; bacterial vaginosis 17.5 % . Overall , women allocated to receive prophylaxis had lower rates of measures of short term infective morbidity than those allocated to screen- and -treat . These differences only reached statistical significance for women who were reported negative on screening . The direct costs to the NHS of prophylaxis and screen- and -treat were calculated to be 8.17 and 18.34 per woman , respectively . CONCLUSIONS Prevalences of lower genital tract infections which have been implicated in increased rates of infective morbidity after abortion are similar to those reported elsewhere . Universal antibiotic prophylaxis is at least as effective as a policy of screen- and -treat in minimising the risk of short term infective morbidity and is far more cost efficient We compared the Gen-Probe transcription-mediated amplification assay ( AMP CT ) , the Abbott LCx assay , and the Roche COBAS AMPLICOR assay for the detection of Chlamydia trachomatis in a mixed population in urine sample s. First-void urine , urethral specimens , and cervical specimens in females were obtained from 1,000 patients ( 544 males and 456 females ) visiting the outpatient sexually transmitted disease clinic of our hospital . The prevalence of C. trachomatis infection was 7.7 % as determined by tissue culture of urethral and cervical specimens . The sensitivities of LCx , COBAS AMPLICOR , and AMP CT compared to cell culture were 79 , 86 , and 78 % , respectively . Sensitivity and specificity were recalculated by using a new " gold st and ard " , i.e. , a sample was considered to be true positive if two or more techniques yielded positive results . Specimens positive only by cell culture or positive in only one commercial amplification technique were retested by a previously described in-house PCR . After discordance analysis the sensitivities of LCx , COBAS AMPLICOR , and AMP CT were 84 , 93 , and 85 % , respectively . Specificity exceeded 99 % for all three assays . With each method the sensitivity was lower for urine sample s from females compared to urine sample s from males . By application of this new gold st and ard , existing differences between methods are highlighted ; future evaluations of new techniques should be vali date d against two or more amplification assays AIM : To test a new assay for the detection of human papillomavirus ( HPV ) DNA , hybrid capture II ( HC II ) , compared with the previous commercialized hybrid capture I ( HC I ) and polymerase chain reaction ( PCR ) results on cervical scrapes from fresh cone excision biopsy sample s. METHODS : The three methods were used on cervical scrapes from 42 fresh cone excision biopsy sample s. There were nine metaplastic and inflammatory lesions , five low grade lesions , and 28 high grade lesions . PCR was performed using the general primers GP5+/GP6 + . The viral load of high risk HPV DNA was estimated by the ratio of relative light units to positive control values in the sample s. RESULTS : The sensitivity of HC I for the detection of high grade lesions was 71.4 % , while it was 92.8 % for HC II and 96.4 % for the PCR . Considering only the absence of detectable cervical in situ neoplasia , the specificity was 88.9 % for HC I , 66.7 % for HC II , and 66.7 % for PCR . With HC II , for a ratio of cervical sample to normal control of > 200 , the sensitivity for the detection of high grade lesion was only 34.6 % with a specificity of 66.7 % . CONCLUSIONS : HPV detection with the HC II assay is more sensitive than the previous HC I and represents a more convenient and easier test than PCR for routine use . Nevertheless the viral load estimated with this test can not be a reliable predictive indicator of high grade lesions CONTEXT Treatment recommendations assume that repeated mass antibiotic distributions can control , but not eradicate or even locally eliminate , the ocular strains of chlamydia that cause trachoma . Elimination may be an important end point because of concern that infection will return to communities that have lost immunity to chlamydia after antibiotics are discontinued . OBJECTIVE To determine whether biannual treatment can eliminate ocular chlamydial infection from preschool children and to compare results with the World Health Organization-recommended annual treatment . DESIGN , SETTING , AND PARTICIPANTS A cluster-r and omized clinical trial of biannual vs annual mass azithromycin administrations to all residents of 16 rural villages in the Gurage Zone , Ethiopia , from March 2003 to April 2005 . INTERVENTIONS At scheduled treatments , all individuals aged 1 year or older were offered a single dose of oral azithromycin either annually or biannually . MAIN OUTCOME MEASURE Village prevalence of ocular chlamydial infection and presence of elimination at 24 months in preschool children determined by polymerase chain reaction , correcting for baseline prevalence . Antibiotic treatments were performed after sample collection s. RESULTS Overall , 14,897 of 16,403 eligible individuals ( 90.8 % ) received their scheduled treatment . In the villages in which residents were treated annually , the prevalence of infection in preschool children was reduced from a mean of 42.6 % ( range , 14.7%-56.4 % ) to 6.8 % ( range , 0.0%-22.0 % ) at 24 months . In the villages in which residents were treated biannually , infection was reduced from 31.6 % pretreatment ( range , 6.1%-48.6 % ) to 0.9 % ( range , 0.0%-4.8 % ) at 24 months . Biannual treatment was associated with a lower prevalence at 24 months ( P = .03 , adjusting for baseline prevalence ) . At 24 months , no infection could be identified in 6 of 8 of those treated biannually and in 1 of 8 of those treated annually ( P = .049 , adjusting for baseline prevalence ) . CONCLUSION Local elimination of ocular chlamydial infection appears feasible even in the most severely affected areas , although it may require biannual mass antibiotic distributions at a high coverage level . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00221364 Background Screening and active case finding for Chlamydia trachomatis ( CT ) is recommended to prevent reproductive morbidity . However insight in community prevalence of gonococcal infections and co-infections with Neisseria gonorrhoea ( NG ) is lacking . Methods Nested study within a large population -based Chlamydia Screening Pilot among 21.000 persons 15–29 year . All CT-positive ( 166 ) and a r and om sample of 605 CT-negative specimens were as well tested for gonococcal infection . Results Overall Chlamydia prevalence in the Pilot was 2.0 % ( 95 % CI : 1.7–2.3 ) , highest in very urban setting s ( 3.2 % ; 95 % CI : 2.4–4.0 ) and dependent of several risk factors . Four gonococcal infections were found among 166 participants with CT infection ( 4/166 = 2.4 % ; 95 % CI : 0.1%–4.7 % ) . All four had several risk factors and reported symptoms . Among 605 CT-negative persons , no infection with NG could be confirmed . Conclusion A low rate of co-infections and a very low community prevalence of gonococcal infections were found in this population based screening programme among young adults in the Netherl and s. Population screening for asymptomatic gonococcal infections is not indicated in the Netherl and s. Although co-infection with gonorrhoea among CT-positives is dependent on symptoms and well-known algorithms for elevated risks , we advise to test all CT-positives also for NG , whether symptomatic or asymptomatic In a prospect i ve study , the Gen-Probe PACE 2 ( GP ) assay was compared with Abbott Laboratories ' ligase chain reaction ( LCR ) assay for the detection of Chlamydia trachomatis . A total of 493 female patients consented to collection of two cervical sample s ; a first-void urine ( FVU ) sample was collected also from 446 of the participants . Cervical sample s were tested by both GP and LCR ; 16 sample s ( 3.1 % ) tested positive by both methods and no discrepant results were observed . All but one of the FVU sample s collected from patients with a positive cervical sample was positive for C. trachomatis by LCR . The stability of FVU sample s over time in the LCR test was also evaluated and proved to be significantly longer than the 4 days stated by the manufacturer . While LCR proved to be highly sensitive in detecting chlamydial infection in FVU sample s , no difference was noted between LCR and GP in the detection of cervical C. trachomatis infection in this study population Two antigen detection systems ( MicroTrak [ MT ] , Syva Co. , Palo Alto , Calif. ; and Chlamydiazyme [ CZ ] , Abbott Laboratories , North Chicago , Ill. ) were compared with semiquantitative culture for diagnosis of chlamydial infection in 1,059 patients . Cultures were done on microtiter plates and blind passaged once . Culture-negative but CZ- or MT-positive specimens were recultured . True positives were positive by either initial or repeat cultures . Of 827 nonpregnant and 231 pregnant patients , 9.1 and 12.1 % , respectively , had positive cultures . Overall sensitivity of the initial culture was 48.5 % without passage and 86.4 % with passage . The sensitivity of CZ was 67 % . The sensitivity of MT in our laboratory was 50 % ; however , further review of these specimens by Syva employees gave a combined sensitivity of 71.6 % . MT and CZ were more sensitive for pregnant patients ( MT , 84.6 % ; CZ , 85.7 % ) than for nonpregnant patients ( MT , 65.5 % ; CZ , 60.0 % ) . All the tests had specificities above 95 % . Of the specimens that were positive after initial culture without subculture , MT-negative specimens had a mean of 3.7 inclusion s in culture , and MT-positive specimens had a mean of 24.8 ( P = 0.002 ) ; CZ-negative specimens had a mean of 4.3 inclusion s , and CZ-positive specimens had a mean of 20.0 ( P = 0.026 ) . In addition , cultures of specimens from pregnant patients had more inclusion s than did those from gynecology patients , but this was not statistically significant ( P = 0.096 ) . No method is ideal ; however , MT and CZ were less sensitive than was this culture system for detecting chlamydial infection in patients in gynecology clinics and were of comparable sensitivity for pregnant patients Objectives : Chlamydia trachomatis ( Chlamydia ) is the most prevalent sexually transmitted bacterial infection and can cause considerable reproductive morbidity in women . Chlamydia screening programmes have been considered but policy recommendations are hampered by the lack of population based data . This paper describes the prevalence of Chlamydia in 15–29 year old women and men in rural and urban areas , as determined through systematic population based screening organised by the Municipal Public Health Services ( MHS ) , and discusses the implication s of this screening strategy for routine implementation . Methods : Stratified national probability survey according to “ area address density ” ( AAD ) . 21 000 r and omly selected women and men in four regions , aged 15–29 years received a home sampling kit . Urine sample s were returned by mail and tested by polymerase chain reaction ( PCR ) . Treatment was via the general practitioner , STI clinic , or MHS clinic . Results : 41 % ( 8383 ) responded by sending in urine and question naire . 11 % ( 2227 ) returned a refusal card . Non-responders included both higher and lower risk categories . Chlamydia prevalence was significantly lower in rural areas ( 0.6 % , 95 % CI 0.1 to 1.1 ) compared with very highly urbanised areas ( 3.2 % , 95 % CI 2.4 to 4.0 ) . Overall prevalence was 2.0 % ( 95 % CI 1.7 to 2.3 ) : 2.5 % ( 95 % CI 2.0 to 3.0 % ) in women and 1.5 % ( 95 % CI 1.1 to 1.8 ) in men . Of all cases 91 % were treated . Infection was associated with degree of urbanisation , ethnicity , number of sex partners , and symptoms . Conclusion : This large , population based study found very low prevalence in rural population s , suggesting that nationwide systematic screening is not indicated in the Netherl and s and that targeted approaches are a better option . Further analysis of risk profiles will contribute to determine how selective screening can be done The effect of 2 population -based outreach screening strategies that used in-home sampling was compared with usual care practice s for Chlamydia trachomatis infection . All 30,439 persons 21 - 23 years old in Aarhus County , Denmark , were divided r and omly into 3 groups : group 1 ( n=4500 ) had a home sampling kit mailed directly to their central ly registered home address ; group 2 ( n=4500 ) had a reply card mailed to their home address with which a home sampling kit could be ordered ; and group 3 ( n=21,439 ) had access to usual care . For women in groups 1 and 2 , the relative risks of being tested were 4.1 ( 95 % confidence interval [ CI ] , 3.8 - 4.4 ) and 3.5 ( 95 % CI , 3.2 - 3.9 ) , respectively , compared with usual care . The corresponding figures for men were 19.1 ( 95 % CI , 16.0 - 22.8 ) and 11.8 ( 95 % CI , 9.8 - 14.2 ) , respectively . Both screening strategies were highly effective , but men benefited the most from having the home sampling kit provided directly Background : Studies of the natural history of genital chlamydial infections in humans are sparse and have had study design limitations . An improved underst and ing of chlamydial natural history may influence recommendations for elements of control efforts such as chlamydia screening frequency or time parameters for partner notification . Methods : Addressing limitations of prior studies in part , we are prospect ively study ing chlamydial natural history in sexually transmitted diseases clinic patients in the interval between screening and returning for treatment of positive chlamydial tests . Results of repeat chlamydial testing and clinical outcomes and their associated predictors are being evaluated . Results : In the initial 129 subjects , 89 % were female , 88 % were black , median age was 21 years , and the median interval between screening and treatment was 13 days . Based on nucleic acid amplification testing at treatment , spontaneous resolution of chlamydia occurred in 18 % . Resolution was somewhat more common in subjects with longer intervals between screening and treatment . Persisting infections more often progressed to develop clinical signs at the time of treatment ( e.g. , urethritis or cervicitis ) . Two women and one man developed chlamydial complications between screening and treatment . Conclusions : Our findings demonstrate that although spontaneous resolution of chlamydia is common , many persons with persisting chlamydia progress to develop signs of infection and some develop complications Background : In Engl and , screening for genital chlamydial infection has begun ; however , screening frequency for women is not yet determined . Aim : To measure chlamydia incidence and reinfection rates among young women to suggest screening intervals . Methods : An 18-month prospect i ve cohort study of women aged 16–24 years recruited from general practice s , family planning clinics and genitourinary medicine ( GUM ) clinics : baseline-negative women followed for incidence and baseline-positive women for reinfection ; urine tested every 6 months via nucleic acid amplification ; and behavioural data collected . Extra test and question naire completed 3 months after initial positive test . Factors associated with infection and reinfection investigated using Cox regression stratified by healthcare setting of recruitment . Results : Chlamydia incidence was mean ( 95 % CI ) 4.9 ( 2.7 to 8.8 ) per 100 person-years ( py ) among women recruited from general practice s , 6.4 ( 4.2 to 9.8 ) from family planning clinics and 10.6 ( 7.4 to 15.2 ) from GUM clinics . Incidence was associated with young age , history of chlamydial infection and acquisition of new sexual partners . If recently acquiring new partners , condom use at last sexual intercourse was independently associated with lower incidence . Chlamydia reinfection was mean ( 95 % CI ) 29.9 ( 19.7 to 45.4 ) per 100/person-year from general practice s , 22.3 ( 15.6 to 31.8 ) from family planning clinics and 21.1 ( 14.3 to 30.9 ) from GUM clinics . Factors independently associated with higher reinfection rates were acquisition of new partners and failure to treat all partners . Conclusions : Sexual behaviours determined incidence and reinfection , regardless of healthcare setting . Our results suggest annual screening of women aged 16–24 years who are chlamydia negative , or sooner if partner change occurs . Rescreening chlamydia-positive women within 6 months of baseline infection may be sensible , especially if partner change occurs or all partners are not treated OBJECTIVE To use st and ard molecular methods to define the prevalence and metabolic characteristics of Chlamydia trachomatis during infection of fallopian tubes in women with ectopic pregnancies . DESIGN Polymerase chain reaction (PCR)- and reverse transcription-PCR (RT-PCR)-based assessment of presence of chlamydial DNA and various RNA species in fallopian tube biopsy sample s. SETTING Hospital and molecular genetics laboratory . PATIENTS Ten women of varying ages , each presenting with ectopic pregnancy . MAIN OUTCOME MEASURE(S ) Positive signal in specific chlamydia-directed PCR and RT-PCR assays . RESULT ( S ) Nucleic acid preparations from 7 of the 10 fallopian tube patient sample s were PCR-positive for C. trachomatis DNA . Each of the 7 PCR-positive sample s also showed the presence of several transcripts from the bacterium , including primary transcripts from the ribosomal RNA operons . CONCLUSION ( S ) A higher proportion of ectopic pregnancies than was believed previously may be attributable to infection of the fallopian tubes by C. trachomatis . The presence of various chlamydial RNA molecules suggests that viable , metabolically active bacteria were present in fallopian tubes of the patients studied We compared the efficacy of a screening program for urogenital Chlamydia trachomatis infections based on home sampling with that of a screening program based on conventional swab sampling performed at a physician 's office . Female subjects , comprising students at 17 high schools in the county of Aarhus , Denmark , were divided into a study group ( tested by home sampling ) and a control group ( tested in a physician 's office ) . We assessed the number of new infections and the number of subjects who reported being treated for pelvic inflammatory disease ( PID ) at 1 year of follow-up ; 443 ( 51.1 % ) of 867 women in the intervention group and 487 ( 58.5 % ) of 833 women in the control group were available for follow-up . Thirteen ( 2.9 % ) and 32 ( 6.6 % ) new infections were identified in the intervention group and the control group , respectively ( Wilcoxon exact value , P=.026 ) . Nine ( 2.1 % ) women in the intervention group and 20 ( 4.2 % ) in the control group reported being treated for PID ( P=.045 ) , indicating that a screening strategy involving home sampling is associated with a lower prevalence of C. trachomatis and a lower proportion of reported cases of PID BACKGROUND The objective of the present study was to compare the likelihood of abnormal Chlamydia trachomatis antibody test results with that of abnormal hysterosalpingography ( HSG ) test results in patients with tubal factor infertility . METHODS Anti-C. trachomatis immunoglobulin G antibodies were determined prospect ively in 295 infertility patients by means of an indirect fluorescent antibody technique . In 48 of the 295 patients both HSG and laparoscopy with chromotubation were performed . The results of C. trachomatis antibody testing were compared with the results of HSG with respect to their predictive value of tubal factor infertility . Likelihood ratios for abnormal C. trachomatis antibody and HSG test results were determined in infertility patients , as assessed by laparoscopy . RESULTS The positive likelihood ratio for C. trachomatis antibody testing was 1.8 . This was comparable with the HSG , which had a positive likelihood ratio of 1.7 . CONCLUSIONS The predictive value of C. trachomatis antibody testing was equal to that of HSG , but ratios of 1.7 and 1.8 indicate a poor test , so both C. trachomatis antibody testing and HSG have a poor predictive value . C. trachomatis antibody testing causes minimal inconvenience to the patient , in contrast to HSG , and therefore should be maintained in infertility examinations Background Pelvic inflammatory disease ( PID ) is common and can lead to tubal factor infertility , ectopic pregnancy or chronic pelvic pain . Despite major UK government investment in the National Chlamydia Screening Programme , evidence of benefit remains controversial . The main aim of this trial was to investigate whether screening and treatment of chlamydial infection reduced the incidence of PID over 12 months . Secondary aims were to conduct exploratory studies of the role of bacterial vaginosis ( BV ) in the development of PID and of the natural history of chlamydial infection . Design R and omised controlled trial with follow up after 12 months . Setting non-healthcareCommon rooms and lecture theatres at 20 universities and further education colleges in Greater London . Participants 2500 sexually active female students were asked to complete a question naire on sexual health and provide self-administered vaginal swabs and smears . InterventionVaginal swabs from intervention women were tested for chlamydia by polymerase chain reaction ( PCR ) and those infected referred for treatment . Vaginal swabs from control women were stored and analysed after a year . Vaginal smears were Gram stained and analysed for BV.Main outcome measureIncidence of clinical PID over 12 months in intervention and control groups . Possible cases of PID will be identified from question naires and record search es . Confirmation of the diagnosis will be done by detailed review of medical records by three independent research ers blind to whether the woman is in intervention or control group . Trial registration Clinical Trials NCT Context Annual screening for Chlamydia trachomatis in sexually active women younger than 25 years of age is cost-effective , but the economic implication s of more recent recommendations to exp and screening to older women and to test more frequently in women with previous infection are unknown . Contribution The cost-effectiveness of annual screening in women 15 to 29 years of age followed by semiannual screening in those with previous infection is well within the range of other accepted health care interventions . In some scenarios , such as high-prevalence population s , screening was cost-saving . Implication s Recently proposed screening recommendations for Chlamydia trachomatis are cost-effective . The Editors Genital infection with Chlamydia trachomatis is the most widespread bacterial sexually transmitted disease in the United States and is associated with annual costs that exceed $ 2 billion ( 1 - 3 ) . Women sustain the most severe consequences of untreated infection , including pelvic inflammatory disease , chronic pelvic pain , ectopic pregnancy , and tubal infertility ( 1 , 4 ) . Since most chlamydial infections are asymptomatic , screening and early treatment are the most promising public health interventions to prevent serious sequelae ( 5 - 7 ) . The availability of nucleic acid amplification technology to detect C. trachomatis that can be used on urine , as well as cervical and vaginal specimens ( 8 - 10 ) , has enhanced the enthusiasm for screening by making it more feasible in non clinical setting s ( 11 - 13 ) . Although early guidelines advised annual C. trachomatis screening for all sexually active women younger than 25 years of age ( 14 - 16 ) , reports of high recurrence rates have led to suggestions for more frequent testing in previously infected women ( 17 - 21 ) . In fact , the Centers for Disease Control and Prevention ( CDC ) now advocates a follow-up test in women who have tested positive for C. trachomatis ( 16 ) . While annual C. trachomatis screening for sexually active adolescent and young adult women is cost-effective ( 22 - 24 ) , the costs and clinical benefits of selectively targeting women with a history of chlamydial infection for more intensive screening have not been evaluated . Furthermore , most guidelines specifically target women between 15 and 25 years of age ; however , recent reports of substantial risk in older women have prompted questions about the potential value of extending the upper age limit to 30 years ( 24 - 26 ) . We sought to use the best available data in a decision analytic model to assess the cost-effectiveness of new C. trachomatis screening policies . Methods Analytic Overview We developed a computer-based mathematical model ( by using DATA 4.0 , TreeAge Software , Inc. , Williamstown , Massachusetts ) to simulate screening , diagnosis , and treatment of chlamydial infection in a representative cohort of sexually active U.S. women , incorporating infection severity , treatment setting , and risk for long-term complications . Strategies were 1 ) no screening ; 2 ) annual screening for all women ; 3 ) annual screening for all women followed by 1 repeated test within 3 to 6 months after a positive test result ; and 4 ) annual screening for all women except those with a history of at least 1 infection , who are rescreened every 6 months . We evaluated the implication s of targeting these strategies to 3 specific age groups ( 15 to 19 years , 15 to 24 years , and 15 to 29 years ) in the base case and the possibility of extending the upper age limit of screening to 39 years in the sensitivity analysis . Model outcomes include intermediate events ( for example , pelvic inflammatory disease , chronic pelvic pain , ectopic pregnancy , and infertility ) and long-term outcomes ( for example , average per-person lifetime costs , life expectancy , and quality -adjusted life expectancy ) . Following the reference case recommendations of the Panel of Cost-Effectiveness in Health and Medicine ( 27 ) , we measured the comparative performance of alternate strategies by using the incremental cost-effectiveness ratio ( defined as the additional cost of a specific screening strategy divided by its additional clinical benefit compared with the next least expensive strategy ) . In addition to deterministic 1-way and 2-way sensitivity analyses , we conducted probabilistic sensitivity analyses by using a second-order Monte Carlo simulation . Finally , we analyzed the indirect effects of an effective screening program on the reduced force of infection ( that is , the per-susceptible rate of infection ) . We reassessed the cost-effectiveness of alternative screening strategies by using a dynamic framework that permits the probability of infection in uninfected women to be a function of the number of infectious individuals in the population at that time . Model Health states in the model are defined to reflect important characteristics that affect prognosis , quality of life , and re source use . The time horizon incorporates a woman 's entire lifetime and is divided into equal 6-month increments ( that is , cycles ) during which women transition from one health state to another . A cohort of 100000 sexually active nonpregnant women enters the model at 15 years of age . In each cycle , uninfected women have an age-specific probability of developing an acute C. trachomatis infection that may be symptomatic or asymptomatic . We assume that women with symptomatic infections seek care and are treated according to the most recent CDC guidelines ( 16 ) . Women with asymptomatic infection ( or treatment failure ) may be spontaneously cured , remain persistently infected ( defined as a detectable infection for more than 6 months after the initial acute infection ) , or develop pelvic inflammatory disease . In our model , spontaneous cure refers to lower genital tract infection that , despite treatment failure or the absence of treatment , resolves spontaneously ( does not progress to pelvic inflammatory disease or persist in the lower genital tract as sub clinical infection ) because of a successful immune response against the organism . A proportion of patients with pelvic inflammatory disease may develop long-term complications ( such as infertility , ectopic pregnancy , and chronic pelvic pain ) , may remain chronically but asymptomatically ( sub clinical ly ) infected , or may be cured by effective treatment . Once cured of infection , a woman may subsequently become reinfected . To estimate the effect of screening , the model distinguishes between detected and undetected acute infection . We assume that all eligible women are offered and adhere to screening in the base-case analysis , but we examine alternative assumptions in the sensitivity analysis . In a design ated screening cycle , a woman with a positive test result moves temporarily to a detected state and is offered treatment ( 16 ) . If a woman with a true-positive result returns for and adheres to treatment , she may be cured , although she will retain her history of infection . Women treated for acute infection are subject to the risk and costs of medication side effects . Women who develop long-term sequelae ( such as chronic pelvic pain ) are no longer considered part of the general screening cohort . Data Table 1 presents selected model variables and their plausible ranges ( 1 , 4 , 6 , 8 , 9 , 22 , 28 - 63 ) . When several estimates were available , we considered the strength of the study design , sample size , presence of control group , similarity of patient population s , and comparability of outcomes measurements . A wide plausible range was established for each variable by using the highest and lowest values reported in the literature . Table 1 . Model Variables : Baseline Values and Ranges Used in Sensitivity Analyses The annual incidence of acute chlamydial infection varies widely depending on the age group , population , and clinical setting ( 1 , 28 - 30 ) . We assumed an annual incidence of 6 % in women 15 to 19 years of age ( 28 , 29 ) , which was reduced by 13 % per year beginning at age 20 years to reflect the age-related decrease in infection risk ( 31 - 33 ) . We assumed that 80 % of women who were notified of a positive test result ( determined by using nucleic acid amplification technology on a urine sample ) would return for treatment ( 34 , 35 ) and 96 % of women treated with azithromycin would be cured , in accordance with a 1996 r and omized , controlled trial comparing cure rates for C. trachomatis infection in persons treated with azithromycin versus doxycycline ( 36 ) . We estimated that 30 % of women with untreated or uncured acute chlamydial infection would remain persistently infected ( 37 - 39 ) , 40 % would be spontaneously cured of infection ( 38 , 39 ) , and 30 % would develop acute pelvic inflammatory disease within 6 months of an initial infection ( 1 , 4 , 6 ) . These estimates translate to an average duration of infection of 0.93 year , which closely approximates the estimate of 0.96 year cited by Groseclose and colleagues ( 2 ) and Buhaug and colleagues ( 32 ) . Women with a history of C. trachomatis infection have a relative risk for reinfection approximately twice that of women with first-time acute infection . In women 15 to 19 years of age , this translates to a reinfection risk of 12 % , which is in agreement with values ( 9 % to 13 % ) reported in published studies ( 18 , 64 ) . On the basis of studies of women with untreated C. trachomatis infection , 28 % to 50 % of women have positive results on follow-up tests ( range , 45 days to 16 months ) ( 38 , 39 ) . Because of the potential for misclassification bias , the degree to which repeated test positivity represents persistent infection versus reinfection in these studies is uncertain , and we examined the effect of this uncertainty in a 2-way sensitivity analysis . Because chlamydia prevalence has substantially decreased in regions with large-scale screening programs ( 65 , 66 ) , we analyzed the indirect effects of an effective 10-year screening program on the reduced force of infection . For this analysis , the probability of infection in uninfected women ( that is , per-susceptible rate of infection ) The effect of sulphadiazine and trimethoprim ( T-S ) was compared with that of a placebo in the treatment of 75 men with nongonococcal urethritis ( NGU ) and their female sexual partners . Forty ( 53 % ) men and 30 ( 40 % ) women had positive culture results for Chlamydia trachomatis before treatment was started . Thirty-four patients of each sex received active treatment . Of these , 19 men and 15 women had positive culture results for C trachomatis before treatment with T-S and one of each sex had a positive culture result after treatment . C trachomatis had been isolated in 21 men and 15 women before treatment with placebo . At follow up four weeks after treatment had been started , 16 men and 15 women still harboured C trachomatis . Five of the chlamydia-positive patients treated with placebo developed complications ( epididymitis , arthritis , or salpingitis ) so the trial was discontinued The natural course of asymptomatic Chlamydia trachomatis infections in women was studied during one year in a cohort based nested case-control study . Healthy women ( n = 744 , from four company health services in Amsterdam ) with a medical check-up prior to job engagement were included . C. trachomatis-positive women ( n = 30 , cases ) and a r and omly selected control group of C. trachomatis-negative women ( n = 186 , controls ) were followed for one year . Urine specimens ( at one , six and 12 months ) were analysed for the presence of C. trachomatis-DNA and the C. trachomatis-serovars , and question naires were filled in . The C trachomatis prevalence and natural course in relation to demographic and sexual characteristics after one , six and 12 months were studied . The main outcome measures were 1 ) the prevalence of C. trachomatis using urine specimens ; 2 ) self-reported complaints ; 3 ) clinical symptoms reported to the coordinating physicians . The prevalence of asymptomatic C. trachomatis infections was 4 % and there was no correlation with demographic and sexual characteristics . The person/year clearance rate was 44.7 % per year . None of the C. trachomatis-positive women developed clinical symptoms or used C. trachomatis specific antibiotic treatment . Women with or without an asymptomatic infection had the same number of self-reported urogenital complaints during follow-up . In persisting infections twice as many C. trachomatis-serovar E infections were detected as compared to clearing infections . Our findings showed that almost half of the asymptomatic C. trachomatis infections in women cleared during one year of follow-up and none developed clinical pelvic inflammatory disease ( PID ) , which is a much lower figure than previously suggested . Therefore these data are important for cost effectiveness calculations in screening programmes for asymptomatic C. trachomatis infections OBJECTIVE To investigate the association between lower genital tract infections and sub clinical PID . Fallopian tube damage is a common complication of acute symptomatic pelvic inflammatory disease ( PID ) , yet most women with tubal factor infertility do not have a history of acute PID . Sub clinical PID is believed to be an important cause of tubal factor infertility . METHODS We conducted a cross‐sectional study among women attending a sexually transmitted diseases or ambulatory gynecology clinic . A convenience sample of 556 women with bacterial vaginosis , gonorrhea , or chlamydia , or women at risk for gonorrhea or chlamydia were enrolled . Women diagnosed with acute PID were not eligible to participate . The main outcome was sub clinical PID , as defined by the presence of histologic endometritis . RESULTS Sub clinical PID was more common in women with lower genital tract infection than in uninfected women . Sub clinical PID was present in 27 % of women with Chlamydia trachomatis ( odds ratio 3.4 ; 95 % confidence interval [ CI ] 1.8 , 6.3 ) and in 26 % of women infected with Neisseria gonorrhoeae ( odds ratio 2.4 ; 95 % CI 1.1 , 5.1 ) . Among women with bacterial vaginosis , 15 % had endometritis ( odds ratio 2.7 ; 95 % CI 1.02 , 7.2 ) . CONCLUSION Sub clinical PID is common among women with lower genital tract infections . Additional prospect i ve studies are necessary to determine the reproductive impact of these asymptomatic upper genital tract infections BACKGROUND Chlamydia trachomatis is a frequent cause of pelvic inflammatory disease . However , there is little information from clinical studies about whether screening women for cervical chlamydial infection can reduce the incidence of this serious illness . METHODS We conducted a r and omized , controlled trial to determine whether selective testing for cervical chlamydial infection prevented pelvic inflammatory disease . Women who were at high risk for disease were identified by means of a question naire mailed to all women enrollees in a health maintenance organization who were 18 to 34 years of age . Eligible respondents were r and omly assigned to undergo testing for C. trachomatis or to receive usual care ; both groups were followed for one year . Possible cases of pelvic inflammatory disease were identified through a variety of data bases and were confirmed by review of the women 's medical records . We used an intention-to-screen analysis to compare the incidence of pelvic inflammatory disease in the two groups of women . RESULTS Of the 2607 eligible women , 1009 were r and omly assigned to screening and 1598 to usual care . A total of 645 women in the screening group ( 64 percent ) for chlamydia ; 7 percent tested positive and were treated . At the end of the follow-up period , there had been 9 verified cases of pelvic inflammatory disease among the women in the screening group and 33 cases among the women receiving usual care ( relative risk , 0.44 ; 95 percent confidence interval , 0.20 to 0.90 ) . We found similar results when we used logistic-regression analysis to control for potentially confounding variables . CONCLUSIONS A strategy of identifying , testing , and treating women at increased risk for cervical chlamydial infection was associated with a reduced incidence of pelvic inflammatory disease OBJECTIVE To determine the presence of the major outer-membrane protein of Chlamydia trachomatis in fallopian tube tissue specimens of infertile women with chronic salpingitis and /or salpingitis isthmica nodosa with tubal occlusion . DESIGN Prospect i ve controlled study . SETTING Department of Obstetrics and Gynecology , University of Bochum , Herne , Germany . PATIENT(S ) Fifty-six consecutive infertile women with histologically documented chronic salpingitis and /or salpingitis isthmica nodosa and bilateral tubal occlusions were evaluated . They were compared with 28 fertile women . INTERVENTION(S ) Fallopian tube tissue specimens were taken during reconstructive infertility surgery , including cesarean section and tubal ligation . MAIN OUTCOME MEASURE(S ) Detection of the major outer-membrane protein of C. trachomatis in fallopian tube tissue specimens by a direct fluorescent antibody test . RESULT ( S ) The major outer-membrane protein of C. trachomatis was found in fallopian tube tissue specimens in 11 of 56 infertile patients ( 20 % ) with chronic salpingitis and /or salpingitis isthmica nodosa . The median titer of IgG serum antibodies to Chlamydia was significantly higher in women with the major outer-membrane protein of C. trachomatis than in patients without this antigen . In comparison , the major outer-membrane protein of C. trachomatis was not found in any of the fallopian tube tissue specimens of the control group . CONCLUSION ( S ) The presence of the major outer-membrane protein of C. trachomatis is associated with chronic salpingitis and /or salpingitis isthmica nodosa with tubal occlusion Abstract Objective To measure the coverage and uptake of systematic postal screening for genital Chlamydia trachomatis and the prevalence of infection in the general population in the United Kingdom . To investigate factors associated with these measures . Design Cross sectional survey of people r and omly selected from general practice registers . Invitation to provide a specimen collected at home . Setting Engl and . Participants 19 773 men and women aged 16 - 39 years invited to participate in screening . Main outcome measures Coverage and uptake of screening ; prevalence of chlamydia . Results Coverage of chlamydia screening was 73 % and was lower in areas with a higher proportion of non-white residents . Uptake in 16 - 24 year olds was 31.5 % and was lower in men , younger adults , and practice s in disadvantaged areas . Overall prevalence of chlamydia was 2.8 % ( 95%confidence interval 2.2 % to 3.4 % ) in men and 3.6 % ( 3.1 % to 4.9 % ) in women , but it was higher in people younger than 25 years ( men 5.1 % ; 4.0 % to 6.3 % ; women 6.2 % ; 5.2 % to 7.8 % ) . Prevalence was higher in the subgroup of younger women who were harder to engage in screening . The strongest determinant of chlamydial infection was having one or more new sexual partners in the past year . Conclusions Postal chlamydia screening was feasible , but coverage was incomplete and uptake was modest . Lower coverage of postal screening in areas with more non-white residents along with poorer uptake in more deprived areas and among women at higher risk of infection could mean that screening leads to wider inequalities in sexual health |
12,283 | 24,163,112 | The trials showed or reported no significant difference between study groups for pregnancy or HIV , but favorable effects were evident for some STI .
We found few studies and little clinical evidence of effectiveness for interventions promoting condom use for dual protection .
We did not find favorable results for pregnancy or HIV , and only found some for other STI .
Effective interventions for improving condom use are needed to prevent pregnancy and HIV/STI transmission . | BACKGROUND Unprotected sex is a major risk factor for disease , disability , and mortality in many areas of the world due to the prevalence and incidence of sexually transmitted infections ( STI ) including HIV .
The male condom is one of the oldest contraceptive methods and the earliest method for preventing the spread of HIV .
When used correctly and consistently , condoms can provide dual protection , i.e. , against both pregnancy and HIV/STI .
OBJECTIVES We examined comparative studies of behavioral interventions for improving condom use .
We were interested in identifying interventions associated with effective condom use as measured with biological assessment s , which can provide objective evidence of protection . | BACKGROUND Seeking screening and treatment for chlamydia ( CT ) and gonorrhea ( GC ) by young women is critical to reduction of asymptomatic cervicitis and its complications . OBJECTIVES To evaluate the efficacy of a client-centered motivational behavioral intervention ( MBI ) , to promote seeking of sexually tranmitted infection ( STI ) checkups by young women . METHODS Three hundred seventy-six of 770 eligible sexually active , nonpregnant , English-speaking women ( mean age 18.5 years ) were recruited from an urban reproductive health clinic and r and omized to two groups : intervention plus st and ard care ( MBI ) or st and ard care alone ( SC ) . MBI ( two sessions plus booster ) was based on the Transtheoretical Model of Change and employed motivational interviewing . Outcome measures monitored for 12 months included : client-initiated clinic visits for STI checkups in response to seven high-risk sexual behaviors by self-report ( primary ) , consistent condom use , number of CT and GC episodes , and movement along the stages of change obtained at baseline and 6- and 12-month follow-up assessment s ( secondary ) . Analyses included chi-square , logistic regression , and generalized estimating equations . RESULTS At baseline , more than 70 % endorsed the action stage of change for seeking STI checkups for three of seven high-risk sexual behaviors . No significant differences were noted between the two groups for the primary or secondary outcomes . Across groups , having multiple partners and being pregnant or thinking one might be pregnant were associated with STI checkups . CONCLUSIONS This is the first known client-centered clinical trial to promote STI screening . Risk-taking and health-seeking behaviors are complex and interrelated with STI and pregnancy concerns . The intervention may have an effect if it is targeted to women in a less medically connected community-based sample 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 CONTEXT Adolescent females often have questions or concerns about their contraceptive methods , and they may discontinue use if these questions are not answered . Little evidence exists on whether follow-up phone calls to address young women 's concerns can help sustain contraceptive use . METHODS Between 2005 and 2007 , a total of 805 females aged 14 - 18 attending a reproductive health clinic in San Francisco were r and omly assigned to receive either regular clinic services or regular clinic services plus nine follow-up phone calls over 12 months . The young women were surveyed at baseline and roughly six , 12 and 18 months later to measure condom and contraceptive use , rates of pregnancy and STDs , and other outcomes and mediators . Multiple linear and logistic regression repeated measures analyses were used to assess the program 's effects . RESULTS Clinic counselors completed only 2.7 calls per patient , and made 7.8 attempts for every completed call . Although contraceptive use increased from baseline to follow-up at six months in both groups , levels of condom and contraceptive use , and rates of pregnancy and STDs , did not differ between the intervention and control groups at any of the follow-up assessment s. Moreover , the intervention did not improve clinic utilization or satisfaction or have consistent positive effects on participants ' attitudes . CONCLUSIONS Reaching young women by phone after a clinic visit for contraception is challenging and does not appear to provide significant benefits beyond those provided by basic clinic services . More intensive interventions may be needed to markedly change adolescent sexual and contraceptive behavior OBJECTIVE To determine whether condom use among high-risk female adolescents could be increased by a behavioral intervention , with the use of infection with Chlamydia trachomatis as a biomarker of condom practice s. DESIGN Prospect i ve , r and omized , controlled intervention . SETTING Urban family planning and sexually transmitted disease clinics . PARTICIPANTS Two hundred nine female adolescents , aged 15 through 19 years , who were treated for C. trachomatis genitourinary infection , were r and omly assigned to st and ard ( control ) or experimental ( behavioral intervention ) groups . One hundred twelve subjects returned for follow-up 5 to 7 months after enrollment and comprise the study subjects . MEASUREMENTS Subjects completed a multiinstrument question naire measuring sexual behavior , condom practice s , attitudes and beliefs , cognitive complexity , sociodemographics , and motivation at enrollment and follow-up . Endourethral and endocervical sites were sample d for C. trachomatis . RESULTS Among the 112 subjects who returned for repeated examination , those who had received the experimental intervention reported increased use of condoms by their sexual partners for protection against sexually transmitted diseases ( odds ratio = 2.4 ; p = 0.02 ) and for vaginal intercourse ( odds ratio = 3.1 ; p = 0.005 ) at the 6-month follow-up . Multivariable logistic regression analysis controlling for condom use at enrollment demonstrated that the experimental intervention ( odds ratio = 2.8 ; p = 0.03 ) and the higher cognitive complexity ( odds ratio = 4.6 ; p = 0.02 ) independently contributed to greater condom use at follow-up . Despite greater use of condoms among the group who had received the intervention , use remained inconsistent and rates of reinfection with C. trachomatis were not significantly different ( 26 % vs 17 % ; p = 0.3 ) . CONCLUSION Although a brief behavioral intervention among high-risk female adolescents can increase condom use by their sexual partners , incident infection does not appear to be reduced , because condom use remained inconsistent PURPOSE To evaluate an intervention ( based on one which had previously been successful in reducing adolescent human immunodeficiency virus ( HIV ) risk behaviors in the United States ) among adolescents residing in Namibia , a country located in sub-Saharan Africa . METHODS A r and omized trial of a 14-session face-to-face intervention emphasizing abstinence and safer sex was conducted among 515 youth ( median age 17 years ; median grade 11 ) attending 10 secondary schools located in two districts in Namibia . Knowledge , attitudes , intentions , and HIV risk behaviors were assessed at baseline and in the immediate postintervention period . RESULTS Knowledge increased significantly among intervention compared to control youth ( 88 % vs. 82 % ; correct responses , p < .0001 ) . At postintervention follow-up , more intervention than control youth believed that they could be intimate without having sex , could have a girlfriend or boyfriend for a long time without having sex , could explain the process of impregnation , knew how to use a condom , and could ask for condoms in a clinic . Fewer intervention than control youth believed that if a girl refused to have sex with her boyfriend it was permissible for him to strike her , and that condoms took away a boy 's pleasure . More intervention than control youth anticipated using a condom when they did have sex , and fewer expected to drink alcohol . Finally , after intervention , there was a trend for increased condom use . There were significant gender-related differences at baseline , although intervention impact was generally equivalent . CONCLUSIONS These findings provide support for the judicious adaptation of successful Western HIV prevention programs in other cultural setting s. A single intervention approach appears to be effective in short-term follow-up with both genders BACKGROUND The American Academy of Pediatrics , the Special Supplemental Nutrition Program for Women , Infants , and Children ( WIC ) , and the World Health Organization recommend that infants receive only breast milk or formula for the first 4 to 6 months of life , followed by the introduction of complementary foods . Despite these recommendations , many infants , particularly those with adolescent mothers , receive solid foods ( often cereal mixed with formula in a bottle ) and liquids other than formula or breast milk in the first few weeks of life . Decisions on early feeding are often guided by gr and mothers and influenced by beliefs that infants need complementary food to counteract signals of hunger , reduce crying , and sleep through the night . OBJECTIVE This investigation evaluated the efficacy of an intervention to delay the early introduction of complementary feeding among first-time , black , adolescent mothers living in multigenerational households . The intervention focused on reducing the cultural barriers to the acceptance of the recommendations of the American Academy of Pediatrics , WIC , and World Health Organization on complementary feeding by highlighting 3 topics : 1 ) recognition of infants ' cues ; 2 ) nonfood strategies for managing infant behavior ; and 3 ) mother-gr and mother negotiation strategies . The intervention was delivered through a mentorship model in which a videotape made by an advisory group of black adolescent mothers was incorporated into a home-visiting program and evaluated through a r and omized , controlled trial . METHODS One hundred eighty-one first-time , low-income , black mothers < 18 years old , living in multigenerational households were recruited from 3 urban hospitals . Infants were born at term , with birth weight appropriate for gestational age and no congenital problems . Shortly after delivery , mothers and gr and mothers completed a baseline assessment and mothers were r and omized into an intervention or control group . Intervention group mothers received home visitation every other week for 1 year . At 3 months , a subset of 121 adolescent mothers reported on their infant 's intake through a food frequency question naire . Mothers who fed their infant only breast milk , formula , or water were classified as optimal feeders . Mothers who provided complementary foods other than breast milk , formula , or water were classified as less optimal feeders . RESULTS Sixty-one percent of the infants received complementary foods before 3 months old . Multivariate hierarchical logistic regression was used to evaluate the determinants of being in the optimal versus less optimal feeders group . After controlling for infant age and family income , mothers of infants in the optimal feeders group were more likely to report accurate messages from WIC regarding the timing of complementary food and nearly 4 times more likely to be in the intervention group . The most common complementary food was cereal mixed with formula in the bottle . CONCLUSIONS The success of this relatively brief intervention demonstrates the importance of using ecological theory and ethnographic research to design interventions that enable participants to alter their behavior in the face of contradictory cultural norms . The intervention focused on interpreting infants ' cues , nonfood methods of managing infant behavior , and mother-gr and mother negotiations . It was delivered through methods that were familiar and acceptable to adolescent mothers-a mentorship model incorporating home visits and videotape . The skill-oriented aspects of the intervention delivered in a culturally sensitive context may have enabled the young mothers to follow the guidelines that they received from WIC and from their pediatricians . Strategies , such as those used in this intervention , may be effective in promoting other caregiving recommendations , thereby enabling providers to meet the increasing dem and s from parents for advice regarding children 's early growth and development Background : HIV prevention among young people in southern Africa is a public health priority . There is little rigorous evidence of the effectiveness of different intervention approaches . We describe findings of a cluster r and omized trial of a community-based , multicomponent HIV , and reproductive health intervention aim ed at changing social norms for adolescents in rural Zimbabwe . Methods : Thirty rural communities were r and omized to early or deferred implementation of the intervention in 2003 . Impact was assessed in a representative survey of 18–22-year-olds after 4 years . Participants self-completed a question naire and gave a dried blood spot sample for HIV and herpes simplex virus-2 ( HSV-2 ) antibody testing . Young women had a urinary pregnancy test . Analyses were by intention-to-treat and were adjusted for clustering . Findings : Four thous and six hundred and eighty-four , 18–22-year-olds participated in the survey ( 97.1 % of eligible c and i date s , 55.5 % women ) . Just over 40 % had been exposed to at least 10 intervention sessions . There were modest improvements in knowledge and attitudes among young men and women in intervention communities , but no impact on self-reported sexual behavior . There was no impact of the intervention on prevalence of HIV or HSV-2 or current pregnancy . Women in intervention communities were less likely to report ever having been pregnant . Interpretation : Despite an impact on knowledge , some attitudes , and reported pregnancy , there was no impact of this intervention on HIV or HSV-2 prevalence , further evidence that behavioral interventions alone are unlikely to be sufficient to reverse the HIV epidemic . The challenge remains to find effective HIV prevention approaches for young people in the face of continued and unacceptably high HIV incidence , particularly among young women OBJECTIVE To describe study design , methods and baseline findings of a behavioural intervention alone and in combination with improved management of sexually transmitted diseases ( STDs ) aim ed at reducing HIV incidence and other STDs . DESIGN A three-arm community r and omized controlled trial ( RCT ) of 18 rural communities ( approximately 96 000 adults ) in SW Ug and a. A st and ardized behavioural intervention was implemented in 12 communities ( arms A and B ) through community-based education , meetings and information leaflets . Six of these communities in addition received improved STD management through government and private health units ( arm B ) . Arm C communities received routine government health services . Impact assessment was through three question naire and serological surveys of 750 - 1000 adults in each community at 18 - 24-month intervals . The primary outcome measure was HIV incidence and secondary measures were syphilis and herpes simplex virus type 2 incidence , prevalence of Neisseria gonorrhoea and Chlamydia trachomatis and sexual behaviour changes . RESULTS Approximately 15 000 adults ( 72 % of eligible population ) were enrolled at baseline . HIV baseline prevalence rates were 9 - 10 % in all arms and demographic and behavioural characteristics and STD prevalence were also similar . In intervention communities , there were 391 995 attendance at 81 502 activities ( 6.1 per target adult ) , 164 063 leaflets distributed ( 2.6 per person ) and 1 586 270 condoms ( 16.5 condoms per adult ) . In the STD communities a total of 12 239 STD cases ( 65 % women ) were seen over a 5-year period ( 7.7 per 100 adults/year ) . CONCLUSION This is the first community RCT of its type with a behavioural component . There is fair baseline comparability between study arms and process data suggest that interventions were adequately implemented 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. Objective : To evaluate an HIV risk-reduction intervention among Namibian adolescents . Methods : A r and omized trial of a 14-session face-to-face intervention emphasizing abstinence and safer sexual practice s conducted among 515 youths ( median age 17 years and median grade 11 ) attending 10 secondary schools located in two districts in Namibia . Youths were r and omly assigned to the intervention or control condition at the level of the individual . HIV risk behaviours , intentions and perceptions were assessed at baseline , immediately post-intervention and at 6 and 12 months post-intervention . Results : Among all 515 youths who enrolled in the programme , rates of either abstinence or sex with a condom were not different between control and intervention youths at baseline or in the follow-up period . However , analyses conducted among the subset of youths who were sexually inexperienced at baseline ( n = 255 ) revealed that a higher percentage of intervention youths ( 17 % ) than control youths ( 9 % , P < 0.05 ) remained sexually inexperienced one year later . Moreover , in the immediate post-intervention period , among baseline virgins who subsequently initiated sex , intervention youths were more likely than control youths to use a condom ( 18 versus 10 % , P < 0.05 ) . Additional HIV-related risk behaviours ( failure to discuss previous HIV risk exposure with one 's sexual partner and alcohol use ) , intentions to use condoms , and perceptions of the ability to use condoms were positively affected by the intervention . Conclusions : There is evidence that the ‘ My Future is My Choice ’ ( MFMC ) intervention is reducing HIV risk behaviours among sexually inexperienced participants aged 15–18 . Related risk behaviours and perceptions are also positively impacted by the intervention Objective To assess the impact of Stepping Stones , a HIV prevention programme , on incidence of HIV and herpes simplex type 2 ( HSV-2 ) and sexual behaviour . Design Cluster r and omised controlled trial . Setting 70 villages ( clusters ) in the Eastern Cape province of South Africa . Participants 1360 men and 1416 women aged 15 - 26 years , who were mostly attending schools . Intervention Stepping Stones , a 50 hour programme , aims to improve sexual health by using participatory learning approaches to build knowledge , risk awareness , and communication skills and to stimulate critical reflection . Villages were r and omised to receive either this or a three hour intervention on HIV and safer sex . Interviewers administered question naires at baseline and 12 and 24 months and blood was tested for HIV and HSV-2 . Main outcome measures Primary outcome measure : incidence of HIV . Other outcomes : incidence of HSV-2 , unwanted pregnancy , reported sexual practice s , depression , and substance misuse . Results There was no evidence that Stepping Stones lowered the incidence of HIV ( adjusted incidence rate ratio 0.95 , 95 % confidence interval 0.67 to 1.35 ) . The programme was associated with a reduction of about 33 % in the incidence of HSV-2 ( 0.67 , 0.46 to 0.97 ; P=0.036)—that is , Stepping Stones reduced the number of new HSV-2 infections over a two year period by 34.9 ( 1.6 to 68.2 ) per 1000 people exposed . Stepping Stones significantly improved a number of reported risk behaviours in men , with a lower proportion of men reporting perpetration of intimate partner violence across two years of follow-up and less transactional sex and problem drinking at 12 months . In women desired behaviour changes were not reported and those in the Stepping Stones programme reported more transactional sex at 12 months . Conclusion Stepping Stones did not reduce incidence of HIV but had an impact on several risk factors for HIV — notably , HSV-2 and perpetration of intimate partner violence . Trial Registration Clinical Trials NCT00332878 Challenges in the accurate measurement of sexual behavior in human immunodeficiency virus ( HIV ) prevention research are well documented and have prompted discussion about whether valid assessment s are possible . Audio computer-assisted self-interviewing ( ACASI ) may increase the validity of self-reported behavioral data . In 2006 - 2007 , Zimbabwean women participated in a r and omized , cross-sectional study that compared self-reports of recent vaginal sex and condom use collected through ACASI or face-to-face interviewing ( FTFI ) with a vali date d objective biomarker of recent semen exposure ( prostate-specific antigen ( PSA ) levels ) . Of 910 study participants , 196 ( 21.5 % ) tested positive for PSA , an indication of semen exposure during the previous 2 days . Of these 196 participants , 23 ( 11.7 % ) reported no sex in the previous 2 days , with no difference in reported sexual activity between interview modes ( 12.5 % ACASI vs. 10.9 % FTFI ; Fisher 's exact test : P = 0.72 ) . In addition , 71 PSA-positive participants ( 36.2 % ) reported condom-protected vaginal sex only ; their reports also indicated no difference between interview modes ( 33.7 % ACASI vs. 39.1 % FTFI ; P = 0.26 ) . Only 52 % of PSA-positive participants reported unprotected sex during the previous 2 days . Self-report was a poor predictor of recent sexual activity and condom use in this study , regardless of interview mode , providing evidence that such data should be interpreted cautiously BACKGROUND The rate of unintended pregnancy in the United States is much higher than in other developed nations . Approximately half of unintended pregnancies are due to contraceptive failure , largely owing to inconsistent or incorrect use . METHODS We design ed a large prospect i ve cohort study to promote the use of long-acting reversible contraceptive methods as a means of reducing unintended pregnancies in our region . Participants were provided with reversible contraception of their choice at no cost . We compared the rate of failure of long-acting reversible contraception ( intrauterine devices [ IUDs ] and implants ) with other commonly prescribed contraceptive methods ( oral contraceptive pills , transdermal patch , contraceptive vaginal ring , and depot medroxyprogesterone acetate [ DMPA ] injection ) in the overall cohort and in groups stratified according to age ( less than 21 years of age vs. 21 years or older ) . RESULTS Among the 7486 participants included in this analysis , we identified 334 unintended pregnancies . The contraceptive failure rate among participants using pills , patch , or ring was 4.55 per 100 participant-years , as compared with 0.27 among participants using long-acting reversible contraception ( hazard ratio after adjustment for age , educational level , and history with respect to unintended pregnancy , 21.8 ; 95 % confidence interval , 13.7 to 34.9 ) . Among participants who used pills , patch , or ring , those who were less than 21 years of age had a risk of unintended pregnancy that was almost twice as high as the risk among older participants . Rates of unintended pregnancy were similarly low among participants using DMPA injection and those using an IUD or implant , regardless of age . CONCLUSIONS The effectiveness of long-acting reversible contraception is superior to that of contraceptive pills , patch , or ring and is not altered in adolescents and young women . ( Funded by the Susan Thompson Buffet Foundation . ) HIV care and treatment setting s provide an opportunity to reach people living with HIV/AIDS ( PLHIV ) with prevention messages and services . Population -based surveys in sub-Saharan Africa have identified HIV risk behaviors among PLHIV , yet data are limited regarding HIV risk behaviors of PLHIV in clinical care . This paper describes the baseline sociodemographic , HIV transmission risk behaviors , and clinical data of a study evaluating an HIV prevention intervention package for HIV care and treatment clinics in Africa . The study was a longitudinal group-r and omized trial in 9 intervention clinics and 9 comparison clinics in Kenya , Namibia , and Tanzania ( N = 3538 ) . Baseline participants were mostly female , married , had less than a primary education , and were relatively recently diagnosed with HIV . Fifty-two percent of participants had a partner of negative or unknown status , 24 % were not using condoms consistently , and 11 % reported STI symptoms in the last 6 months . There were differences in demographic and HIV transmission risk variables by country , indicating the need to consider local context in design ing studies and using caution when generalizing findings across African countries . Baseline data from this study indicate that participants were often engaging in HIV transmission risk behaviors , which supports the need for prevention with PLHIV ( PwP ) . Trial Registration Clinical Trials.gov OBJECTIVE --To determine whether HIV testing and counselling increased condom use and decreased heterosexual transmission of HIV in discordant couples . DESIGN -- Prospect i ve study . SETTING --Kigali , the capital of Rw and a. SUBJECTS -- Cohabiting couples with discordant HIV serology results . MAIN OUTCOME MEASURES --Condom use in the couple and HIV seroconversion in the negative partners . RESULTS --60 HIV discordant couples were identified , of whom 53 were followed for an average of 2.2 years . The proportion of discordant couples using condoms increased from 4 % to 57 % after one year of follow up . During follow up two of the 23 HIV negative men and six of the 30 HIV negative women seroconverted ( seroconversion rates of 4 and 9 per 100 person years ) . The rate among women was less than half that estimated for similar women in discordant couples whose partners had not been serotested . Condom use was less common among those who seroconverted ( 100 % v 5 % , p = 0.01 in men ; 67 % v 25 % , p = 0.14 in women ) . CONCLUSIONS --Roughly one in seven cohabiting couples in Kigali have discordant HIV serological results . Confidential HIV serotesting with counselling caused a large increase in condom use and was associated with a lower rate of new HIV infections . HIV testing is a promising intervention for preventing the spread of HIV in African cities Background Peer-led sex education is widely believed to be an effective approach to reducing unsafe sex among young people , but reliable evidence from long-term studies is lacking . To assess the effectiveness of one form of school-based peer-led sex education in reducing unintended teenage pregnancy , we did a cluster ( school ) r and omised trial with 7 y of follow-up . Methods and Findings Twenty-seven representative schools in Engl and , with over 9,000 pupils aged 13–14 y at baseline , took part in the trial . Schools were r and omised to either peer-led sex education ( intervention ) or to continue their usual teacher-led sex education ( control ) . Peer educators , aged 16–17 y , were trained to deliver three 1-h classroom sessions of sex education to 13- to 14-y-old pupils from the same schools . The sessions used participatory learning methods design ed to improve the younger pupils ' skills in sexual communication and condom use and their knowledge about pregnancy , sexually transmitted infections ( STIs ) , contraception , and local sexual health services . Main outcome measures were abortion and live births by age 20 y , determined by anonymised linkage of girls to routine ( statutory ) data . Assessment of these outcomes was blind to sex education allocation . The proportion of girls who had one or more abortions before age 20 y was the same in each arm ( intervention , 5.0 % [ 95 % confidence interval ( CI ) 4.0%–6.3 % ] ; control , 5.0 % [ 95 % CI 4.0%–6.4 % ] ) . The odds ratio ( OR ) adjusted for r and omisation strata was 1.07 ( 95 % CI 0.80–1.42 , p = 0.64 , intervention versus control ) . The proportion of girls with one or more live births by 20.5 y was 7.5 % ( 95 % CI 5.9%–9.6 % ) in the intervention arm and 10.6 % ( 95 % CI 6.8%–16.1 % ) in the control arm , adjusted OR 0.77 ( 0.51–1.15 ) . Fewer girls in the peer-led arm self-reported a pregnancy by age 18 y ( 7.2 % intervention versus 11.2 % control , adjusted OR 0.62 [ 95 % CI 0.42–0.91 ] , weighted for non-response ; response rate 61 % intervention , 45 % control ) . There were no significant differences for girls or boys in self-reported unprotected first sex , regretted or pressured sex , quality of current sexual relationship , diagnosed sexually transmitted diseases , or ability to identify local sexual health services . Conclusion Compared with conventional school sex education at age 13–14 y , this form of peer-led sex education was not associated with change in teenage abortions , but may have led to fewer teenage births and was popular with pupils . It merits consideration within broader teenage pregnancy prevention strategies . Trial registration : IS RCT N ( IS RCT N94255362 ) CONTEXT Given levels of unintended pregnancy and STDs , an effective counseling intervention is needed to improve women 's consistent use of effective prevention methods . METHODS A sample of 764 women aged 16 - 44 who were at risk of unintended pregnancy were enrolled in a r and omized controlled trial in North Carolina in 2003 - 2004 . Intervention participants received pregnancy and STD prevention counseling , adapted from motivational interviewing , both at enrollment and two months later ; controls received only a session of general health counseling . Levels of contraceptive use ( categorized as high , low or none on the basis of the effectiveness of the method and the consistency of use ) and barriers to use were measured at two , eight and 12 months ; chi-square tests were used to compare selected outcomes between the groups . Rates of unintended pregnancy and chlamydia infection were assessed over the study period . RESULTS At baseline , 59 % of all participants reported a high level of contraceptive use , 19 % a low level and 22 % nonuse . At two months , the proportions of intervention and control participants who had improved their level of use or maintained a high level ( 72 % and 66 % , respectively ) were significantly larger than the proportions who had reported a high level of use at baseline ( 59 % and 58 % , respectively ) . No significant differences were found between the groups at 12 months , or between baseline and 12 months for either group . During the study , 10 - 11 % of intervention and control participants became pregnant , 1 - 2 % received a chlamydia diagnosis and 7 - 9 % had another STD diagnosed . CONCLUSIONS Repeated counseling sessions may be needed to improve contraceptive decision-making and to reduce the risk of unintended pregnancy and STDs CONTEXT . Rates of rapid second births among low-income black adolescent mothers range from 20 % to 50 % . Most efforts to prevent rapid second births have been unsuccessful . OBJECTIVES . There were 4 objectives : ( 1 ) to examine whether a home-based mentoring intervention was effective in preventing second births within 2 years of the adolescent mother 's first delivery ; ( 2 ) to examine whether greater intervention participation increased the likelihood of preventing a second birth ; ( 3 ) to examine whether second births were better predicted from a risk practice perspective or a family formation perspective , based on information collected at delivery ; and ( 4 ) to examine how risk practice s or family formation over the first 2 years of parenthood were related to a second birth . DESIGN . We conducted a r and omized , controlled trial of a home-based intervention curriculum , based on social cognitive theory , and focused on interpersonal negotiation skills , adolescent development , and parenting . The curriculum was delivered biweekly until the infant 's first birthday by college-educated , black , single mothers who served as mentors , presenting themselves as “ big sisters . ” The control group received usual care . Follow-up evaluations were conducted in the homes 6 , 13 , and 24 months after recruitment . METHODS . Participants were recruited from urban hospitals at delivery and were 181 first time , black adolescent mothers ( < 18 years of age ) ; 82 % ( 149 of 181 ) completed the 24-month evaluation . RESULTS . Intent-to-treat analyses revealed that control mothers were more likely than intervention mothers to have a second infant . The complier average causal effect was used to account for variability in intervention participation . Having ≥2 intervention visits increased the odds of not having a second infant more than threefold . Only 1 mother who completed ≥6 visits had a second infant . At delivery of their first infant , mothers who had a second infant were slightly older ( 16.7 vs 16.2 years ) and were more likely to have been arrested ( 30 % vs 14 % ) . There were no differences in baseline contraceptive use or other measures of risk or family formation . At 24 months , mothers who had a second infant reported high self-esteem , positive life events , and romantic involvement and residence with the first infant 's father . At 24 months , there were no differences in marital rates ( 2 % ) , risk practice s , or contraceptive use between mothers who did and did not have a second infant . Mothers who did not have a second infant were marginally more likely to report no plans for contraception in their next sexual contact compared with mothers who had a second infant ( 22 % vs 8 % , respectively ) . CONCLUSIONS . A home-based intervention founded on a mentorship model and targeted toward adolescent development , including negotiation skills , was effective in preventing rapid repeat births among low-income , black adolescent mothers . The effectiveness of the intervention could be seen after only 2 visits and increased over time . There were no second births among mothers who attended ≥8 sessions . There was no evidence that risk behavior or contraceptive use was related to rapid second births . There was some evidence that rapid second births among adolescent mothers were regarded as desirable and as part of a move toward increasing autonomy and family formation , thereby undermining intervention programs that focus on risk avoidance . Findings suggest the merits of a mentoring program for low-income , black adolescent mothers , based on a relatively brief ( 6–8 sessions ) curriculum targeted toward adolescent development and interpersonal negotiation skills OBJECTIVE To describe the study design , methods and baseline findings of a behavioural intervention trial aim ed at reducing HIV incidence . METHOD A cluster r and omized-controlled trial ( RCT ) conducted in 70 villages in rural South Africa . A behavioural intervention , Stepping Stones , was implemented in 35 communities in two workshops of 20 men and 20 women in each community who met for 17 sessions ( 50 h ) over a period of 3 - 12 weeks . Individuals in the control arm communities attended a single session of about 3 h on HIV and safer sex . Impact assessment was conducted through two question naire and serological surveys at 12-month intervals . The primary outcome was HIV incidence and secondary measures included changes in knowledge , attitude and sexual behaviours . Qualitative research was also undertaken with 10 men and 10 women from two sites receiving the intervention ( one rural and one urban ) and five men and five women from one village in the control arm . They were interviewed individually three times prior to the workshops and then 9 - 12 months later . RESULTS A total of 2776 participants ( 1409 intervention and 1367 control ) were enrolled at baseline and had an interview , and HIV sero-status was established . HIV baseline prevalence rates in women were 9.8 % in the intervention arm and 12.8 % in the control arm . In men the prevalence was 1.7 % in the intervention arm and 2.1 % in the control arm . Demographic and behavioural characteristics were similar in the two arms . In the intervention groups 59.9 % of participants attended more than 75 % of the sessions . In the control group 66.3 % attended the control session . CONCLUSION This is the third RCT to be conducted in sub-Saharan Africa evaluating a behavioural intervention using HIV incidence as a primary outcome . It is of particular interest as the intervention in question is used in many developing countries . There is good baseline comparability between the study arms and the process data on the workshops suggested that the interventions were feasible and adequately implemented PURPOSE One-quarter of adolescent mothers bear another child within 2 years , compounding their risk of poorer medical , educational , economic , and parenting outcomes . Most efforts to prevent rapid subsequent birth to teenagers have been unsuccessful but have seldom addressed motivational processes . METHODS We conducted a r and omized trial to determine the effectiveness of a computer-assisted motivational intervention ( CAMI ) in preventing rapid subsequent birth to adolescent mothers . Pregnant teenagers ( N = 235 ) , aged 18 years and older who were at more than 24 weeks ’ gestation , were recruited from urban prenatal clinics serving low-income , predominantly African American communities . After completing baseline assessment s , they were r and omly assigned to 3 groups : ( 1 ) those in CAMI plus enhanced home visit ( n = 80 ) received a multi-component home-based intervention ( CAMI+ ) ; ( 2 ) those in CAMI−only ( n = 87 ) received a single component home-based intervention ; ( 3 ) and those in usual-care control ( n = 68 ) received st and ard usual care . Teens in both intervention groups received CAMI sessions at quarterly intervals until 2 years ’ postpartum . Those in the CAMI+ group also received monthly home visits with parenting education and support . CAMI algorithms , based on the transtheoretical model , assessed sexual relationships and contraception-use intentions and behaviors , and readiness to engage in pregnancy prevention . Trained interventionists used CAMI risk summaries to guide motivational interviewing . Repeat birth by 24 months ’ postpartum was measured with birth certificates . RESULTS Intent-to-treat analysis indicated that the CAMI+ group compared with the usual-care control group exhibited a trend toward lower birth rates ( 13.8 % vs 25.0 % ; P = .08 ) , whereas the CAMI-only group did not ( 17.2 % vs 25.0 % ; P = .32 ) . Controlling for baseline group differences , the hazard ratio ( HR ) for repeat birth was significantly lower for the CAMI+ group than it was with the usual-care group ( HR = 0.45 ; 95 % CI , 0.21–0.98 ) . We developed complier average causal effects models to produce unbiased estimates of intervention effects accounting for variable participation . Completing 2 or more CAMI sessions significantly reduced the risk of repeat birth in both groups : CAMI+ ( HR = 0.40 ; 95 % CI , 0.16–0.98 ) and CAMI−only ( HR = 0.19 ; 95 % CI , 0.05–0.69 ) . CONCLUSIONS Receipt of 2 or more CAMI sessions , either alone or within a multicomponent home-based intervention , reduced the risk of rapid subsequent birth to adolescent mothers Background : Dual contraception is important for averting HIV-1 transmission , unintended pregnancy , and maternal-to-child HIV-1 transmission . Few studies have explored contraceptive use in HIV-1 serodiscordant couples , a population at high risk for HIV-1 transmission . Methods : Data from a prospect i ve study of 3407 women in HIV-1 heterosexual serodiscordant partnerships were analyzed to describe use and correlates of contraception . Results : Among 2298 HIV-1 seropositive women , 23.5 % used contraception at enrollment and 30.2 % used contraception after 24 months of follow-up ; among 1109 HIV-1 seronegative women , contraceptive use decreased from 21.3 % to 14.2 % . For both HIV-1 seropositive and seronegative women , contraceptive use was less common among women from East Africa compared to women from southern Africa ( adjusted odds ratio [ AOR ] , 0.6 ; 95 % confidence interval [ CI ] , 0.5 - 0.8 and AOR , 0.6 ; 95 % CI , 0.4 - 0.8 , respectively ) and more common among women with at least one child ( AOR , 2.4 ; 95 % CI , 1.7 - 3.4 and AOR , 2.3 ; 95 % CI , 1.2 - 4.5 , respectively ) . Condom use increased significantly during follow-up from 71.2 % to 92.6 % and 73.5 % to 95.6 % among HIV-1 seropositive and HIV-1 seronegative women , respectively , at baseline and 24 months . However , contraceptive use was associated with unprotected sexual activity among both HIV-1 seropositive and seronegative women ( AOR , 1.3 ; 95 % CI , 1.1 - 1.5 and AOR , 1.4 ; 95 % CI , 1.1 - 1.8 , respectively ) , although not among women who initiated contraception during follow-up . Conclusions : Counseling and provision of dual contraception should receive high priority in programs that care for women in HIV-1 serodiscordant partnerships Objective : To compare prevention effectiveness of multisession group counseling with st and ard HIV prevention counseling for reducing risk behaviors and new sexually transmitted diseases ( STDs ) . Methods : Small groups of consenting STD clinic patients were r and omized to four 1‐hour small group counseling interventions based on the information‐motivation‐behavioral skills ( IMB ) model with a booster session at 2 months or to the st and ard two 20‐minute individual counseling sessions . Follow‐up interviews and examinations were 2 , 6 , 9 , and 12 months after enrollment . Results : From March 1992 through June 1993 , 996 ( 59 % ) of 1,681 eligible persons were enrolled ; 32 ( 3 % ) tested HIV‐positive and were excluded . Intervention attendance was 98 % for one session , and 47 % attended four or five counseling sessions . Follow‐up was similar for both groups : 72 % attended at least once ; 47 % returned at 12 months . Both groups had similar increases in condom use and decreases in number of partners , and similar number of new infections with gonorrhea ( 14 % ) , chlamydia ( 10 % ) , or syphilis ( 2 % ) . Conclusions : Two 20‐minute counseling sessions were as effective as four 1‐hour group sessions for reducing risk behavior and STD incidence in an STD clinic patient population BACKGROUND Improvement of sex education in schools is a key part of the UK government 's strategy to reduce teenage pregnancy in Engl and . We examined the effectiveness of one form of peer-led sex education in a school-based r and omised trial of over 8000 pupils . METHODS 29 schools were r and omised to either peer-led sex education ( intervention ) or to continue their usual teacher-led sex education ( control ) . In intervention schools , peer educators aged 16 - 17 years delivered three sessions of sex education to 13 - 14 year-old pupils from the same schools . Primary outcome was unprotected ( without condom ) first heterosexual intercourse by age 16 years . Analysis was by intention to treat . FINDINGS By age 16 years , significantly fewer girls reported intercourse in the peer-led arm than in the control arm , but proportions were similar for boys . The proportions of pupils reporting unprotected first sex did not differ for girls ( 8.4 % intervention vs 8.3 % control ) or for boys ( 6.2 % vs 4.7 % ) . Stratified estimates of the difference between arms were -0.4 % ( 95 % CI -3.7 % to 2.8 % , p=0.79 ) for girls and -1.4 % ( -4.4 % to 1.6 % , p=0.36 ) for boys . At follow-up ( mean age 16.0 years [ SD 0.32 ] ) , girls in the intervention arm reported fewer unintended pregnancies , although the difference was borderline ( 2.3 % vs 3.3 % , p=0.07 ) . Girls and boys were more satisfied with peer-led than teacher-led sex education , but 57 % of girls and 32 % of boys wanted sex education in single-sex groups . INTERPRETATION Peer-led sex education was effective in some ways , but broader strategies are needed to improve young people 's sexual health . The role of single-sex sessions should be investigated further BACKGROUND Treatment of sexually-transmitted infections ( STIs ) and behavioural interventions are the main methods to prevent HIV in developing countries . We aim ed to assess the effect of these interventions on incidence of HIV-1 and other sexually-transmitted infections . METHODS We r and omly allocated all adults living in 18 communities in rural Ug and a to receive behavioural interventions alone ( group A ) , behavioural and STI interventions ( group B ) , or routine government health services and community development activities ( group C ) . The primary outcome was HIV-1 incidence . Secondary outcomes were incidence of herpes simplex virus type 2 ( HSV2 ) and active syphilis and prevalence of gonorrhoea , chlamydia , reported genital ulcers , reported genital discharge , and markers of behavioural change . Analysis was per protocol . FINDINGS Compared with group C , the incidence rate ratio of HIV-1 was 0.94 ( 0.60 - 1.45 , p=0.72 ) in group A and 1.00 ( 0.63 - 1.58 , p=0.98 ) in group B , and the prevalence ratio of use of condoms with last casual partner was 1.12 ( 95 % CI 0.99 - 1.25 ) in group A and 1.27 ( 1.02 - 1.56 ) in group B. Incidence of HSV2 was lower in group A than in group C ( incidence rate ratio 0.65 , 0.53 - 0.80 ) and incidence of active syphilis for high rapid plasma reagent test titre and prevalence of gonorrhoea were both lower in group B than in group C ( active syphilis incidence rate ratio , 0.52 , 0.27 - 0.98 ; gonorrhoea prevalence ratio , 0.25 , 0.10 - 0.64 ) . INTERPRETATION The interventions we used were insufficient to reduce HIV-1 incidence in rural Ug and a , where secular changes are occurring . More effective STI and behavioural interventions need to be developed for HIV control in mature epidemics OBJECTIVES To characterize dual- method protection users and report the prevalence of dual- method use among young adult African American women residing in the Southeastern United States . DESIGN Analysis of baseline data from a r and omized controlled trial . SETTING A clinic-based sample of young women enrolled in a r and omized trial of a human immunodeficiency virus (HIV)-prevention program in Atlanta , Georgia , from June 2005 to June 2007 . PARTICIPANTS African American women aged 14 to 20 years who reported unprotected sexual activity in the past 6 months . Of the eligible adolescents , 94 % ( N = 701 ) were enrolled in the study and completed baseline assessment s. OUTCOME MEASURES Dual- method protection use as well as sociodemographic , individual-level , interpersonal-level , and community-level factors and interpersonal communication skills . Only data from the baseline assessment , before r and omization , were used for the analysis . RESULTS A total of 102 participants ( 14.6 % ) were classified as dual- method protection users . After controlling for age and clinic , significant differences between dual- method users and non-dual- method users were found for impulsivity , self-esteem , social support , relationship style , partner communication self-efficacy , and fear of condom negotiation . CONCLUSIONS Dual- method protection use is low . Identification of factors that differentiate dual- method users from non-dual- method users at the individual , interpersonal , and community levels in this young African American sample suggests that HIV , sexually transmitted disease , and unintended pregnancy risk-reduction programs should address factors at each level , not simply the individual level , and that this may involve structural and /or clinical counseling practice changes in clinics that serve young women , to optimally facilitate dual- method protection use among young African American women in the Southeastern United States PURPOSE Teenage girls in low-income urban setting s are at an elevated risk for HIV , sexually transmitted infections , and unintended pregnancies . The purpose of this study was to evaluate the efficacy of a sexual risk-reduction ( SRR ) intervention , supplemented with postintervention booster sessions , targeting low-income , urban , sexually active teenage girls . METHOD R and omized controlled trial in which sexually active urban adolescent girls ( n = 738 ) recruited in a midsize northeastern U.S. city were r and omized to a theory-based SRR intervention or to a structurally equivalent health promotion control group . Assessment s and behavioral data were collected using audio computer-assisted self-interview at baseline , then at 3 , 6 , and 12 months postintervention . Both interventions included four small-group sessions and two booster sessions . RESULTS Relative to girls in the control group , girls receiving the SRR intervention were more likely to be sexually abstinent ; if sexually active , they showed decreases in ( a ) total episodes of vaginal sex at all follow-ups , ( b ) number of unprotected vaginal sex acts at 3 and 12 months , and ( c ) total number of sex partners at 6 months . Medical record audits for girls recruited from a clinical setting ( n = 322 ) documented a 50 % reduction in positive pregnancy tests at 12 months . CONCLUSIONS Theory-based behavioral interventions tailored to adolescent girls can help to reduce sexual risk and may also reduce unintended pregnancies . Although sexually active at enrollment , many of the girls receiving the intervention were more likely to practice secondary abstinence . Continued refinement of SRR interventions for girls is needed to ensure they are feasible , appealing , and effective 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 OBJECTIVE We evaluated the impact of human immunodeficiency virus ( HIV ) testing and counseling on self-reported condom and spermicide use and on corresponding HIV seroconversion and gonorrhea rates in urban Rw and an women . DESIGN Prospect i ve cohort study with 2 years of follow-up , comparison of outcome variables before and after an intervention , and condom use measured in a control group that did not receive the intervention . SETTING Outpatient research clinic in Kigali , the capital of Rw and a. PARTICIPANTS One thous and four hundred fifty-eight childbearing women , 32 % of whom were infected with HIV , were enrolled in a prospect i ve study in 1988 , and followed at 3- to 6-month intervals for 2 years . Follow-up was available for 95 % of subjects at year 1 and 92 % at year 2 . INTERVENTIONS An acquired immunodeficiency syndrome ( AIDS ) educational videotape , HIV testing and counseling , and free condoms and spermicide were provided to all participants and interested sexual partners . MAIN OUTCOME MEASURES Self-report of compliance with condom-spermicide use and observed incidence of HIV and gonorrhea . RESULTS Only 7 % of women reported ever trying condoms before the intervention , but 22 % reported condom use with good compliance 1 year later . Women who were HIV-positive were more likely to adopt condom use than HIV-negative women ( 36 % vs 16 % ; P < .05 ) . Independent predictors of condom use , both in HIV-positive and in HIV-negative women , included HIV testing and counseling of the male partner , having a nonmonogamous relationship , and believing condoms were not dangerous . Human immunodeficiency virus seroconversion rates decreased significantly ( from 4.1 to 1.8 per 100 person-years ; P < .04 ) in women whose partners were tested and counseled . The prevalence of gonorrhea decreased substantially ( 13 % to 6 % ; P < .05 ) among HIV-positive women , with the greatest reduction among condom users ( 16 % to 4 % ; P < .05 ) . CONCLUSION A confidential HIV testing and counseling program was associated with increased use of condoms and reduced rates of gonorrhea and HIV in urban Rw and an women . The lack of risk reduction in HIV-negative women whose partner 's serostatus was unknown was of concern . Interventions that promote HIV testing and counseling for both members of a couple should be considered in other high-prevalence areas OBJECTIVES We sought to determine whether an HIV prevention program bundled with group prenatal care reduced sexually transmitted infection ( STI ) incidence , repeat pregnancy , sexual risk behavior , and psychosocial risks . METHODS We conducted a r and omized controlled trial at 2 prenatal clinics . We assigned pregnant women aged 14 to 25 years ( N = 1047 ) to individual care , attention-matched group care , and group care with an integrated HIV component . We conducted structured interviews at baseline ( second trimester ) , third trimester , and 6 and 12 months postpartum . RESULTS Mean age of participants was 20.4 years ; 80 % were African American . According to intent-to-treat analyses , women assigned to the HIV-prevention group intervention were significantly less likely to have repeat pregnancy at 6 months postpartum than individual-care and attention-matched controls ; they demonstrated increased condom use and decreased unprotected sexual intercourse compared with individual-care and attention-matched controls . Subanalyses showed that being in the HIV-prevention group reduced STI incidence among the subgroup of adolescents . CONCLUSION HIV prevention integrated with prenatal care result ed in reduced biological , behavioral , and psychosocial risks for HIV Objective : To evaluate the efficacy of a cognitive/behavioral skills-building intervention to prevent sexually transmitted diseases ( STD ) in high-risk heterosexual adults . Design : A r and omized controlled trial with assessment s at baseline , and at 3 and 5 months . Setting : San Francisco STD Clinic . Patients : A total of 399 patients were r and omly assigned to a four-session , individual , multi-component , cognitive/behavioral intervention ( n = 199 ) , or a brief st and ardized counseling session offered to all patients ( n = 200 ) . Intervention : Based on the AIDS Risk-Reduction Model , the aims of the intervention were to increase prevention knowledge , reduce high-risk psychosocial factors , and build decision-making and communication skills to modify sexual behaviors . Main outcome measures : The primary outcome of interest was STD . The secondary outcome was number of risky sexual activities . Results : There were no differences between the intervention ( 13 % ) and control ( 11 % ) groups in their acquisition of STD . Among men , condom use increased more at 3 months in the intervention group than the control group ( 56.8 versus 42.3 % ; P < 0.05 ) . In addition , the mean number of sexual partners without condom use was lower in the intervention group than in the control group at 5 months ( 0.6 versus 0.9 ; P < 0.01 ) . Conclusions : The results suggest that a cognitive/behavioral , skills-building intervention consisting of individual , multiple sessions and follow-up assessment s can be implemented and evaluated with high-risk heterosexually active adults attending public STD clinics . Our intervention did not have a significant impact on STD , although it had some impact on behavior in men , but not in women Objective To evaluate the efficacy of an intervention to reduce HIV transmission risk behaviors and sexually transmitted diseases ( STDs ) and enhance HIV-preventive psychosocial and structural factors among women living with HIV . Design A r and omized controlled trial of 366 women living with HIV in Alabama and Georgia . InterventionThe intervention emphasized gender pride , maintaining current and identifying new network members , HIV transmission knowledge , communication and condom use skills , and healthy relationships . Primary Outcome Unprotected vaginal intercourse . Other Outcomes Proportion never used condoms , incident STDs , psychosocial factors , and number of supportive network members . Results Over the 12-month follow-up , women in the WiLLOW intervention , relative to the comparison , reported fewer episodes of unprotected vaginal intercourse ( 1.8 vs. 2.5 ; P = 0.022 ) ; were less likely to report never using condoms ( odds ratio [ OR ] = 0.27 ; P = 0.008 ) ; had a lower incidence of bacterial infections ( Chlamydia and gonorrhea ) ( OR = 0.19 ; P = 0.006 ) ; reported greater HIV knowledge and condom use self-efficacy , more network members , fewer beliefs that condoms interfere with sex , and fewer partner-related barriers to condom use ; and demonstrated greater skill in using condoms . Conclusion This is the first trial to demonstrate reductions in risky sexual behavior and incident bacterial STDs and to enhance HIV-preventive psychosocial and structural factors among women living with HIV OBJECTIVE To assess the effectiveness of a community-based HIV prevention intervention for adolescents in terms of its impact on ( 1 ) HIV and Herpes simplex virus type 2 ( HSV-2 ) incidence and on rates of unintended pregnancy and ( 2 ) reported sexual behaviour , knowledge and attitudes . METHODS Cluster r and omised trial of a multi-component HIV prevention intervention for adolescents based in rural Zimbabwe . Thirty communities were selected and r and omised in 2003 to early or deferred intervention implementation . A baseline bio-behavioural survey was conducted among 6791 secondary school pupils ( 86 % of eligibles ) prior to intervention implementation . RESULTS Baseline prevalences were 0.8 % ( 95 % CI : 0.6 - 1.0 ) for HIV and 0.2 % ( 95 % CI : 0.1 - 0.3 % ) for HSV-2 . Four girls ( 0.12 % ) were pregnant . There was excellent balance between study arms . Orphans who made up 35 % of the cohort were at increased risk of HIV [ age-sex adjusted odds ratio 3.4 ( 95 % CI : 1.7 - 6.5 ) ] . 11.9 % of young men and 2.9 % of young women reported that they were sexually active ( P < 0.001 ) ; however , there were inconsistencies in the sexual behaviour data . Girls were less likely to know about reproductive health issues than boys ( P < 0.001 ) and were less likely to have used and to be able to access condoms ( P < 0.001 ) . CONCLUSION This is one of the first rigorous evaluations of a community-based HIV prevention intervention for young people in southern Africa . The low rates of HIV suggest that the intervention was started before this population became sexually active . Inconsistency and under-reporting of sexual behaviour re-emphasise the importance of using externally vali date d measures of sexual risk reduction in behavioural intervention studies BACKGROUND Dual protection is recommended for prevention of unwanted pregnancies and protection against sexually transmitted infections , including HIV . It is critical for HIV-negative women to prevent seroconversion and HIV transmission to their infants during pregnancy and breastfeeding . METHODS Women were followed up after delivery , monthly for the first 9 months and then 3-monthly to 24 months , in a cohort study investigating postnatal HIV transmission . Study nurses discussed family planning , including condom use , at each visit . Contraceptive methods used since the last visit were recorded . All women knew their HIV status , and most women breastfed for a minimum of 6 months . RESULTS Among 1,137 HIV-positive and 1 220 HIV-negative women the most common contraceptive method was the hormonal injectable ; few women used condoms alone or as dual contraception ( 0 - 3 months 6.8 % ; 7 - 12 months 16.3 % ; 19 - 24 months 14.4 % ) . Compared with uninfected women , HIV-positive women were more likely to use condoms in years 1 and 2 after delivery ( adjusted odds ratio ( AOR ) 1.72 , 95 % confidence interval ( CI ) 1.38 - 2.14 , p<0.001 ; AOR 1.61 , 95 % CI 1.15 - 2.25 , p=0.006 respectively ) . Compared with women with a flush toilet , those with a pit latrine were less likely to use condoms in years 1 and 2 ( AOR 0.22 , 95 % CI 01.7 - 0.28 , p<0.001 ; AOR 0.27 , 95 % CI 0.19 - 0.39 , p<0.001 ) . Older women were more likely to use condoms in the first postpartum year ( AOR 1.78 , 95 % CI 1.03 - 3.09 , p=0.040 ) . CONCLUSIONS More creative ways of promoting condoms and dual contraception need to be found if new HIV infections , in women and children , are to be prevented 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 Little is known about pregnancy rates among sex workers ( SWs ) or the factors that predispose SWs to this risk . We aim ed to estimate the pregnancy incidence rate among Madagascar SWs participating in an intervention trial promoting use of male and female condoms and assess the influence of various predictive factors on pregnancy risk . METHODS SWs from two study clinics in Madagascar participated in a r and omized trial to assess the effect of peer education and clinic-based counseling on use of male and female condoms and prevalence of sexually transmitted infections ( STIs ) . Women were seen every 2 months for up to 18 months ; they received structured interviews at every visit , and physical exams at baseline and every 6 months thereafter . Site staff recorded information on pregnancies during interviews ; pregnancy data were then merged with trial data for this analysis . RESULTS Of 935 SWs in the analysis population , 250 became pregnant during follow-up . The cumulative probability of pregnancy was 0.149 at 6 months and 0.227 at 12 months . Comparable proportions of nonpregnant and pregnant SWs reported using highly effective contraception at baseline ( approximately 16 % ) ; these users were younger and were more consistent condom users . Method switching and discontinuation were frequent . In multivariate analysis , nonuse of effective contraceptives and any self-reported unprotected sex were associated with higher incidence of pregnancy . Approximately 51 % of women delivered , 13 % reported a spontaneous abortion , 13 % reported an induced abortion and 23 % had missing pregnancy outcomes . CONCLUSIONS Women traditionally targeted for STI/HIV preventive interventions need more comprehensive reproductive health services . In particular , SWs could benefit from targeted family planning counseling and services BACKGROUND Few cognitive-behavioral interventions have focused on preventing sexually transmitted infections ( STIs ) and unintended pregnancies ( UPs ) in young , sexually active women in a single study . Military recruit training provides a well-defined , national , nonclinic sample in which to evaluate such an intervention . METHODS All female Marine recruits ( N=2,288 ) in training were approached . Of these , 2,157 ( 94.3 % ) voluntarily agreed and were r and omly assigned , by platoons , to participate in cognitive-behavioral interventions to prevent STIs or UPs or to prevent physical training injuries and cancer . Participants completed self-administered question naires and were screened for pregnancy , Chlamydia trachomatis , Neisseria gonorrhoeae , and Trichomonas vaginalis at baseline and , on average , 1 and 14 months postintervention . RESULTS A higher proportion of the control group had a postintervention STI or UP [ odds ratio (OR)=1.41 , 95 % confidence interval (CI)=1.01 - 1.98 ] . Among participants who had no history of STIs or pregnancy , but who engaged in risky sexual behaviors just before recruit training , the control group was more likely to acquire a postintervention STI ( OR=3.24 , CI=1.74 - 6.03 ) . Among participants who were not sexually experienced at baseline , the control group was more likely to have casual ( OR=2.05 , 95 % CI=1.04 - 4.08 ) and multiple ( OR=1.87 , 95 % CI=1.01 - 3.47 ) sexual partners postintervention . CONCLUSIONS This r and omized controlled trial indicates that cognitive-behavioral interventions are effective for reducing behavioral risk and preventing STIs and UPs in young , sexually active women who are not seeking health care This article discusses the design of an ongoing cluster-r and omized trial comparing two forms of school-based sex education in terms of educational process and sexual health outcomes . Twenty-nine schools in southern Engl and have been r and omized to either peer-led sex education or to continue with their traditional teacher-led sex education . The primary objective is to determine which form of sex education is more effective in promoting young people 's sexual health . The trial includes an unusually detailed evaluation of the process of sex education as well as the outcomes . The sex education programs were delivered in school to pupils ages 13 - 14 years who are being followed until ages 19 - 20 . Major trial outcomes are unprotected sexual intercourse and regretted intercourse by age 16 and cumulative incidence of abortion by ages 19 - 20 . We discuss the rationale behind various aspects of the design , including ethical issues and practical challenges of conducting a r and omized trial in schools , data linkage for key outcomes to reduce bias , and integrating process and outcome measures to improve the interpretation of findings |
12,284 | 21,833,968 | There is limited evidence available from RCTs to guide the choice between surgical or non-surgical repair of first- or second-degree perineal tears sustained during childbirth .
Therefore , at present there is insufficient evidence to suggest that one method is superior to the other with regard to healing and recovery in the early or late postnatal periods .
Until further evidence becomes available , clinicians ' decisions whether to suture or not can be based on their clinical judgement and the women 's preference after informing them about the lack of long-term outcomes and the possible chance of a slower wound healing process , but possible better overall feeling of well being if left un-sutured | BACKGROUND Perineal tears commonly occur during childbirth .
They are sutured most of the time .
Surgical repair can be associated with adverse outcomes , such as pain , discomfort and interference with normal activities during puerperium and possibly breastfeeding .
Surgical repair also has an impact on clinical workload and human and financial re sources .
OBJECTIVES To assess the evidence for surgical versus non-surgical management of first- and second-degree perineal tears sustained during childbirth . | Background : To compare the postpartum pelvic floor function of women with sutured second-degree perineal lacerations , unsutured second-degree perineal lacerations , and intact perineums . Methods : A prospect i ve cohort of nurse-midwifery patients consented to mapping of genital trauma at birth and an assessment of postpartum pelvic floor outcomes . Women completed vali date d question naires for perineal pain and urinary and anal incontinence at 12 weeks postpartum and underwent physical examination to assess pelvic floor strength and anatomy at 6 weeks postpartum . Results : One hundred seventy-two of 212 ( 80 % ) eligible women provided follow-up assessment data at 6 or 12 weeks postpartum . Women with an intact perineum ( n = 89 ) used fewer analgesics ( P < .002 ) and had lower pain scores at the time of hospital discharge than women with second-degree lacerations ( sutured , n = 46 ; unsutured , n = 37 ; intact , n = 89 ) ( P ≤ .02 ) . The sutured group was more likely to use analgesics ( 52 % ) than the unsutured ( 35 % ) or intact ( 23 % ) groups at time of hospital discharge ( P < .002 ) , although pain scores were not different between sutured and unsutured groups . Postpartum reports of urinary or anal incontinence , sexual inactivity , or sexual function scores did not vary between groups . Weak pelvic floor exercise strength was more common among the women with second-degree lacerations compared with women with an intact perineum ( 53 % vs. 28 % ; P = .03 ) but did not differ between sutured ( 58 % ) and unsutured ( 47 % ) groups ( P = not significant ) . Likewise , perineal body or genital hiatus measurements did not vary between groups ( P = not significant ) . Conclusions : Women with sutured lacerations report increased analgesic use at the time of hospital discharge compared with women with intact perineums or unsutured lacerations . At 12 weeks postpartum , no differences were noted between groups regarding complaints of urinary or anal incontinence , sexual inactivity , or sexual function In a prospect i ve clinical investigation of 2,144 deliveries , we eluci date the indications for episiotomy and how different methods of anesthesia affect the frequency of episiotomy and the perineal problems after episiotomy compared with those after spontaneous perineal laceration . We found a significantly higher infection rate ( p less than 0.001 ) and a longer healing period in the episiotomy group . These differences remain even if only primigravida or the indication , imminent perineal laceration , is studied . The results indicate that many women will unnecessarily suffer after an episiotomy . The patient 's subjective problems are significantly increased , both immediately and at the 3-month postoperative follow-up Objective To assess the long term implication s of four alternative approaches to postpartum perineal repair . BACKGROUND The full extent of genital tract trauma in spontaneous births is not well documented . The purpose of this study was to describe the range and extent of childbirth trauma and related postnatal pain using data from a large r and omized clinical trial of perineal management techniques ( n = 5471 ) . METHODS Descriptive analysis was conducted on trial participants who delivered spontaneously at term and were examined by their midwife after birth ( n = 5404 ) . Data are reported for sites of trauma , and the relation to episiotomy , suturing , and maternal reports of pain at 2 days , 10 days , and 3 months after birth . RESULTS Eighty-five percent of all women experienced some form of trauma , with first- or second-degree perineal lacerations occurring in two-thirds of women and outer vaginal tears occurring in one-half . Tears to the rectum and vaginal vault were more common with episiotomy . Nearly all unsutured trauma was restricted to perineal first- or second-degree , outer vaginal , and labial sites . Pain declined over time , and a gradient in pain was observed according to the site and complexity of trauma . CONCLUSIONS Genital tract trauma is extremely common with spontaneous vaginal birth . Effective measures to prevent or reduce its occurrence would benefit many new mothers Objective . Surgical repair of perineal lesions after delivery is frequently associated with pain and discomfort , interfering with the normal activities of the puerperium . The aim of this study was to compare perineal skin repair after episiotomy with adhesive glue versus a subcuticular suture , regarding the incidence of pain and wound complications . Study design . R and omized clinical trial . Setting . Tertiary care university hospital . Material and methods . One hundred women having mediolateral episiotomy at vaginal delivery were enrolled . They were r and omized to receive skin adhesive ( n = 53 ) or subcuticular suture ( n = 47 ) for closure of perineal skin . The main outcome measure was self‐evaluated pain in the 30 days following delivery . Secondary outcome measures were technical difficulties reported with the procedure , duration of surgical repair , wound complications observed at 42–68 hours post‐partum and re‐initiation of sexual activity by 30 days post‐partum . Results . No significant differences were observed between the two groups in incidence of technical difficulties and failed procedures , pain during the procedure , wound complications at hospital discharge , self‐evaluated measures of pain at 7 and 30 days or re‐initiation of sexual activity by 30 days post‐partum . The skin adhesive group had a significantly shorter mean duration of the procedure ( four minutes less ) . Conclusion . Perineal skin closure using adhesive glue is faster than subcuticular suture , and associated with a similar incidence of complications and pain in the first 30 days The association between episiotomy and severe ( third- and fourth-degree ) perineal lacerations was studied in 24,114 women . The overall rates of severe lacerations were 8.3 and 1.5 % for primiparous and multiparous women , respectively . Women who had midline episiotomies were nearly 50 times more likely and women who had mediolateral episiotomies were over eight times more likely to suffer a severe laceration than were women who did not undergo an episiotomy . Severe lacerations were also more common after use of forceps , in occiput transverse and posterior presentations , among women with smaller pelvic outlet measurements or lower prepregnant weight , and with larger fetuses . The same factors that caused a woman to have an increased risk of laceration also made performance of an episiotomy more likely . After statistical adjustment for these risk factors , mediolateral episiotomy was associated with a 2.5-fold reduction in the risk of severe lacerations among primiparous women , and a statistically nonsignificant 2.4-fold increase among multiparous women , compared with no episiotomy . Midline episiotomy was associated with statistically significant 4.2- and 12.8-fold increases in the risk of lacerations among primiparous and multiparous women , respectively . We conclude that the risks and benefits of midline episiotomy should be evaluated in a r and omized clinical trial that compares policies of “ usual ” versus conservative use of episiotomy Summary . Histoacryl‐tissue adhcsive ( B. Braun Melsungen AG W. Germany ) was used in place of skin sutures ( 2/0 chromic catgut , Ethicon Ltd , Edinburgh , Scotl and ) for episiotomy repair in a group of 20 women . This group was compared with two groups of women undergoing first and repeat episiotomy . Variables analysed included pain in the episiotomy site , pain while walking , sitting , sleeping , lying down , breast‐feeding , micturating and defaecating . The Histoacryl group was superior with regard to all the variables . This simple , new method can reduce pain and inconvenience for patients , especially following the first delivery Objective To compare the effect of two methods of perineal management used during spontaneous vaginal delivery on the prevalence of perineal pain reported at 10 days after birth OBJECTIVES The purpose of the study was to evaluate the use of enbucrilate tissue adhesive compared with subcuticular polyglycolic acid sutures in episiotomy wound closure . METHODS In a prospect i ve controlled trial , two groups were studied after undergoing an episiotomy skin wound repair using either enbucrilate tissue adhesive ( n=32 ) or a subcuticular polyglycolic acid suture ( n=30 ) . The variables measured included pain scores during selected activities in the first 5 postnatal days , the time taken to become pain free after childbirth and the time taken to resume pain free sexual intercourse . Suitable patients were invited by the midwives to participate in the trial . If they gave consent to the trial , the gynecologist was contacted . If available , he would perform a repair using enbucrilate tissue adhesive . If he was not available , one of the midwives would perform a repair using subcuticular polyglycolic acid sutures . In this group , 90 % of the women were recruited and sutured by one midwife . RESULTS Patients treated with enbucrilate were found to have significantly less postnatal pain while walking , became pain free in a shorter period ( mean=25 days vs. 18 days ; P<0.01 ) and were able to resume pain-free intercourse sooner ( mean=34 days vs. 52 days ; P<0.001 ) . CONCLUSIONS Tissue adhesives incorporate the qualities of an ideal skin-closure material . The results demonstrate their advantage over the current st and ard suture-based methods of repair in the perineum . The use of adhesives merits further evaluation Objective To examine differences in outcome between primiparous women who do and who do not have suturing to first or second degree perineal lacerations sustained during spontaneous vaginal births after 37 weeks of gestation Summary . Three methods of episiotomy repair were r and omly assigned after 900 consecutive deliveries . The three procedures were : ( 1 ) continuous No. 00‐plain catgut in the vagina ; No. 00‐plain catgut interrupted stiches in the perineal muscles and fascia , and No. 00‐nylon interrupted stiches in the skin . ( 2 ) The same technique as in ( l ) , but with No. 0‐polyglycolic acid ( Dexon ) in all layers . ( 3 ) The suture material as in ( 2 ) , but used with a subcuticular technique . The women treated with method 3 reported statistically significant less pain and disabilities in the early puerperium . Three months after delivery 262 women ( 33 % ) still had perineal complaints which could be directly related to the episiotomy in 25 % ( 8 % of total number ) . The group treated with method 3 had the best long‐term results and we conclude that the subcuticular technique using polyglycolic acid should be the method of choice BACKGROUND Midwives tend to leave minor perineal lacerations to heal spontaneously , and clinical experience and studies show that women can suffer from their stitched lacerations . The study purpose was to determine any differences in the healing process and experience of minor perineal lacerations when they were sutured or not sutured . METHODS Eighty term pregnant primiparas with minor perineal lacerations of grade s I-II were r and omized after childbirth . The experimental group was nonsutured and the control group was sutured . A follow-up examination was performed at 2 to 3 days , 8 weeks , and 6 months after the delivery . Participants were asked about the type of discomfort , and the effect of the laceration on breastfeeding and sexual intercourse . RESULTS No significant differences were found in the healing process . The type of pain differed between the groups , but the amount of discomfort was the same . The sutured group had to visit the midwife more often because of discomfort from the stitches . Sixteen percent of the women in the sutured group , but none in the nonsutured group ( p = 0.0385 ) , considered that the laceration had had a negative influence on breastfeeding . CONCLUSIONS Minor perineal lacerations can be left to heal spontaneously . The benefits for the woman include the possibility of having a choice , avoiding the discomfort of anesthesia and suturing , providing positive affects on breastfeeding One thous and women were allocated at r and om to one of two perineal management policies , both intended to minimise trauma during spontaneous vaginal delivery . In one the aim was to restrict episiotomy to fetal indications ; in the other the operation was to be used more liberally to prevent perineal tears . The result ant episiotomy rates were 10 % and 51 % respectively . An intact perineum was more common among those allocated to the restrictive policy . This group experienced more perineal and labial tears , however , and included four of the five cases of severe trauma . There were no significant differences between the two groups either in neonatal state or in maternal pain and urinary symptoms 10 days and three months post partum . Women allocated to the restrictive policy were more likely to have resumed sexual intercourse within a month after delivery . These findings provide little support either for liberal use of episiotomy or for cl aims that reduced use of the operation decreases postpartum morbidity Changes in sexual function are common in postpartum women . In this comparative , descriptive study , a prospect i ve cohort of midwifery patients consented to documentation of genital trauma at birth and assessment of sexual function at 3 months postpartum . The impact of spontaneous genital trauma on postpartum sexual function was the focus of the study . Trauma was categorized into minor trauma ( no trauma or first-degree perineal or other trauma that was not sutured ) or major trauma ( second- , third- , or fourth-degree lacerations or any trauma that required suturing ) . Women who underwent episiotomy or operative delivery were excluded . Fifty-eight percent ( 326/565 ) of enrolled women gave sexual function data ; of those , 276 ( 85 % ) reported sexual activity since delivery . Seventy percent ( 193 ) of women sustained minor trauma and 30 % ( 83 ) sustained major trauma . Sexually active women completed the Intimate Relationship Scale ( IRS ) , a 12-item question naire vali date d as a measure of postpartum sexual function . Both trauma groups were equally likely to be sexually active . Total IRS scores did not differ between trauma groups nor did complaints of dyspareunia . However , for two items , significant differences were demonstrated : women with major trauma reported less desire to be held , touched , and stroked by their partner than women with minor trauma , and women who required perineal suturing reported lower IRS scores than women who did not require suturing Commonly used suture material s and techniques for perineal repair following vaginal delivery were compared in a r and omized controlled trial involving 1574 women . Three comparisons were made using a modified factorial design . In the comparison of teflon‐coated polyglycolic acid ( Dexon plus ) with chromic catgut for repair of the vagina and deep perineal tissues there was no clear difference other than less short‐term analgesia being required in association with polyglycolic acid . Outcome was also similar after skin repair with either polyglycolic acid or chromic catgut or silk , although silk repair required more packets of material and was associated with delay in resuming sexual intercourse ; polyglycolic acid was more likely to need removal than chromic catgut but it appeared to reduce the need for resuturing . There was no clear difference between continuous subcuticular and interrupted transcutaneous sutures for repair of perineal skin |
12,285 | 23,597,814 | There were important inconsistencies among studies in the factors that were associated with screening .
Receiving recommendations from clinicians was the most consistent predictor identified across studies .
The review also revealed a consistent pattern of association with predictors related to familial aspects of CRC , such as strength of family history , and relationship to the affected relative .
Among the psychological constructs , " social influence " emerged as the most consistent predictor of screening participation .
This review provides evidence that clinicians , as well as use of family history and social networks , offer the most promising avenues to promoting and improving screening participation by individuals at increased risk of colorectal cancer | CONTEXT People with a family history of colorectal cancer ( CRC ) are at increased risk of developing the disease .
Information on the screening practice s of this segment of the population is scarce . | Colorectal carcinoma ranks as the second most common cancer and the second leading cause of cancer death in the United States . Hispanics are less likely than their non‐Hispanic white counterparts to have ever received a fecal occult blood test ( FOBT ) or sigmoidoscopy/colonoscopy . Little is known about the barriers to screening in the Hispanic population This study aim ed to identify the social , cultural and psychological characteristics influencing behaviour in a cancer mass screening campaign in a French population . The intention to take a screening test and actually doing it was studied , in particular . A self reported- question naire was mailed in December 1992 to a r and om sample of people living in Caen ( western France ) , and aged from 45 - 74 years . The sample was formed by r and om selection from electoral registers . The study was population based , in the Caen area , department of Calvados , France . The question naire comprised 26 open and close questions . Starting in February 1993 , the occult blood screening test ( haemoccult IIR ) for colorectal cancer was offered by general practitioners ( GPs ) , occupational health doctors and pharmacists in the Caen area to all those aged 45 - 74 years . From 1 February 1993 to 30 June 1994 , the data on the mass screening campaign were central ized and the study population divided into those who took the screening test and those who did not . Of the 1,129 persons contacted , 645 ( 57.1 % ) returned the question naire . After exclusions , 585 question naires were used for analysis . The results show that whether a person will actually take a screening test can not be predicted from their intention to do so . The sociodemographic and cultural characteristics influencing the intention to take the test differ from those influencing execution of the test . Among the variables tested here , the following four sociodemographic and cultural characteristics were independently predictive of actually taking the screening test for colorectal cancer : compliance with the health insurer 's advice ; low or medium sociodemographic status , living with a partner ( or widowhood ) ; and not knowing someone with cancer . The analysis of the quantitative and qualitative differences between the intention to take the test and actually doing it could eluci date the reasons underlying refusal . Poor screening compliance has multiple causes . A record of intention to take a screening test alone is not appropriate . This type of study should no longer be carried out to determine the mechanisms underlying behaviour towards secondary prevention Objective — To survey screening practice s , knowledge , and attitudes towards screening among first degree relatives of people with colon cancer . Setting — A r and om sample of people with colon cancer listed on the New South Wales ( NSW ) Cancer Registry were mailed a question naire to be passed on to an appropriate first degree relative . Methods — Two hundred and twenty five first degree relatives completed a self administered question naire . Results — Although there were high levels of awareness about colorectal cancer , and attitudes towards colorectal cancer were generally positive , screening rates were low , and only three relatives had been screened in accordance with current Australian recommendations . Factors associated with previous participation in any type of screening test ( usually once ) included receiving a medical recommendation to screen , having more than one relative with colorectal cancer , being a sibling of the relative with colon cancer , the relative with cancer being female , and perceiving screening as messy , but not painful . Conclusions — Strategies to enhance screening awareness and participation among relatives need to be considered . This study provides some insight into factors to be considered in developing awareness programmes . Further research is required to explore these factors , and to identify ways to overcome barriers BACKGROUND Breast cancer is the most prevalent malignancy among women in Israel , and routine screening is recommended for early detection . In 1997 , a health management organization primary care centre in rural Israel established a 1-year programme wherein family physicians were encouraged to remind their patients to undergo breast cancer examinations . This study evaluates the impact of the physicians ' intervention on patient compliance . METHODS Family practitioners from two practice s were requested to discuss the importance of early breast cancer detection with all eligible patients who visited the clinic for any reason and to assist them in scheduling an appointment for screening . The files of the patients who received the recommendation were stamped accordingly . On completion of the programme , the physicians ' files were audited , and the potential c and i date s for breast cancer screening were divided into two groups : those who had received the intervention ( n = 251 ) and those who had not ( n = 187 ) ; results were also compared with those of a third group of patients who had gone for an examination on their own initiative ( n = 100 ) prior to the study ( i.e. did not require intervention ) . A r and om sample of half the patients also completed an ad hoc question naire covering sociodemographic variables and the impact of the doctors ' intervention on their behaviour . RESULTS Patients in the intervention group showed a significantly greater change in behaviour regarding breast cancer screening than the controls ( 32 % versus 13 % , P = 0.001 ) . This change was manifested particularly in the group of women aged 50 - 74 years who received the recommendation for mammography to be performed ( according to the guidelines ) . CONCLUSION Although this is a study in only two practice s , the results suggest that primary care physicians can significantly alter the behaviour of their patients regarding regular breast examinations . The use of a special reminder can also help the individual doctor to ensure that each patient has been properly instructed BACKGROUND An explanatory framework referred to as the Preventive Health Model was used to identify factors associated with prospect i ve adherence to colorectal cancer screening . METHODS Data on sociodemographic , psychosocial , social influence , and program factors were collected via telephone survey for 501 older adult members of an independent practice association-type health maintenance organization . Subjects were later mailed fecal occult blood tests for completion and return . Adherence was defined as the return of the tests within 90 days . RESULTS Structural analysis shows that for men ( N = 145 ) , perceived self-efficacy ( OR = 1.4 ) , salience and coherence of testing ( OR = 2.3 for a 5-point increment on a 30-point scale ) , and exposure to health education interventions ( OR = 6.8 ) were significant independent predictors of intention to adhere and of adherence . Among women ( N = 185 ) , predictors were age ( OR = 1.8 ) and salience and coherence of testing ( OR = 1.8 for a 5-point increment on a 30-point scale ) . CONCLUSIONS These findings indicate that for both men and women , adherence is influenced strongly by the extent to which the behavior is judged to make sense in everyday life . It also appears that additional education and encouragement may persuade men and younger women to participate in screening BACKGROUND Even though colorectal cancer ( CRC ) screening tests for persons 50 years of age or over are recommended to reduce colorectal cancer mortality , screening rates remain disturbingly low . METHODS Using r and om digit dialing , 355 telephone interviews were conducted with black and white men and women , 50 - 79 years of age , who resided in Genesee County , Michigan . The Health Belief Model provided the framework to assess attitudes and practice s regarding CRC screening . RESULTS For both endoscopic procedures , significantly higher percentages of whites than blacks were aware of the screening procedure ( P < 0.05 ) . Overall , fewer than 30 % of respondents were adherent to current CRC screening guidelines . Adherence was lowest for black females : 21 % for fecal occult blood test , 20 % for flexible sigmoidoscopy , and 12 % for colonoscopy . Black males compared to black females were about 2.8 times more likely to have had either flexible sigmoidoscopy or colonoscopy ( P < 0.05 ) . Physician recommendation was a powerful motivator to screening . Two consistent barriers to screening were the belief that : ( a ) the test is not needed ; and ( b ) the test is embarrassing . CONCLUSIONS Interventions directed at physicians and patients are essential to enhance CRC screening rates . CRC survival rates may be improved by physician-guided promotion of screening that focuses on identified barriers |
12,286 | 18,283,204 | Some studies suggest that glucosamine may provide greater benefit to patients with less severe radiographic osteoarthritis than to patients with more severe disease ( 5 , 6 ) . | Context Although many patients use glucosamine to treat osteoarthritis , available studies have reported inconsistent effects of glucosamine on symptoms and joint changes .
In addition , previous studies have more often included patients with knee than with hip osteoarthritis .
The Editors The effectiveness of glucosamine sulfate for treating osteoarthritis is controversial .
In the Netherl and s and other countries , glucosamine is sold as an over-the-counter dietary supplement and is used by many patients , often on the advice of their physicians .
Although osteoarthritis of the knee is more common than hip osteoarthritis , hip osteoarthritis is common enough to warrant assessment of glucosamine for this condition .
To date , only 2 trials have published data on the effects of glucosamine sulfate on joint structure ( 10 , 11 ) .
Some expressed concern about the radiography protocol used in these trials ( 1214 ) , and further study is needed to clarify these findings . | BACKGROUND Glucosamine and chondroitin sulfate are used to treat osteoarthritis . The multicenter , double-blind , placebo- and celecoxib-controlled Glucosamine/chondroitin Arthritis Intervention Trial ( GAIT ) evaluated their efficacy and safety as a treatment for knee pain from osteoarthritis . METHODS We r and omly assigned 1583 patients with symptomatic knee osteoarthritis to receive 1500 mg of glucosamine daily , 1200 mg of chondroitin sulfate daily , both glucosamine and chondroitin sulfate , 200 mg of celecoxib daily , or placebo for 24 weeks . Up to 4000 mg of acetaminophen daily was allowed as rescue analgesia . Assignment was stratified according to the severity of knee pain ( mild [ N=1229 ] vs. moderate to severe [ N=354 ] ) . The primary outcome measure was a 20 percent decrease in knee pain from baseline to week 24 . RESULTS The mean age of the patients was 59 years , and 64 percent were women . Overall , glucosamine and chondroitin sulfate were not significantly better than placebo in reducing knee pain by 20 percent . As compared with the rate of response to placebo ( 60.1 percent ) , the rate of response to glucosamine was 3.9 percentage points higher ( P=0.30 ) , the rate of response to chondroitin sulfate was 5.3 percentage points higher ( P=0.17 ) , and the rate of response to combined treatment was 6.5 percentage points higher ( P=0.09 ) . The rate of response in the celecoxib control group was 10.0 percentage points higher than that in the placebo control group ( P=0.008 ) . For patients with moderate-to-severe pain at baseline , the rate of response was significantly higher with combined therapy than with placebo ( 79.2 percent vs. 54.3 percent , P=0.002 ) . Adverse events were mild , infrequent , and evenly distributed among the groups . CONCLUSIONS Glucosamine and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients with osteoarthritis of the knee . Exploratory analyses suggest that the combination of glucosamine and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain . ( Clinical Trials.gov number , NCT00032890 . ) Background Pharmacological treatment for osteoarthritis ( OA ) can be divided into two groups : symptom-modifying drugs and disease-modifying drugs . Symptom-modifying drugs are currently the prescription of choice for patients with OA , as disease-modifying drugs are not yet available in usual care . However , there has recently been a lot of debate about glucosamine sulphate ( GS ) , a biological agent that is thought to have both symptom-modifying and disease-modifying properties . This assumption has yet to be proved . The objective of this article is to present the design of a blind r and omised clinical trial that examines the long-term symptom-modifying and disease-modifying effectiveness of GS in patients with hip OA . This trial is ongoing and will finish in March 2006 . Methods / design Patients with hip OA meeting the ACR- criteria are r and omly allocated to either 1500 mg of oral GS or placebo for the duration of two years . The primary outcome measures , which are joint space narrowing ( JSN ) , and change in the pain and function score of the Western Ontario McMaster Universities Osteoarthritis index ( WOMAC ) , are determined at baseline and after two years of follow-up during the final assessment . Intermediate measures at three-month intervals throughout the trial are used to study secondary outcome measures . Secondary outcome measures are changes in WOMAC stiffness score , quality of life , medical consumption , side effects and differences in biomarker CTX-II Summary A new preparation of pure glucosamine sulphate , in injectable and oral form , was investigated in a controlled clinical trial in patients with osteoarthrosis . Two groups of 15 in- patients received either 400 mg glucosamine sulphate daily ( 12by the intramuscular and 3 by the intra-articular route ) for 7 days , followed by 2 weeks at 1.5 g daily of oral glucosamine sulphate in 3 divided doses , or an intramuscular injection daily of a piperazine/chlorbutanol combination for 7 days , followed by oral placebo during the following 2 weeks . Semi-quantitative scoring of pain at rest and during active and passive movements , of restricted function and , where possible , of walking time over 20 metres , were taken as therapeutic activity indices , and tested before and after 1 and 3 weeks of treatment . Patients were positively question ed daily for possible intolerance symptoms . Laboratory tests were recorded before and after treatment . With both initial parenteral treatments , each symptom significantly improved , wit BACKGROUND Treatment of osteoarthritis is usually limited to short-term symptom control . We assessed the effects of the specific drug glucosamine sulphate on the long-term progression of osteoarthritis joint structure changes and symptoms . METHODS We did a r and omised , double-blind placebo controlled trial , in which 212 patients with knee osteoarthritis were r and omly assigned 1500 mg sulphate oral glucosamine or placebo once daily for 3 years . Weightbearing , anteroposterior radiographs of each knee in full extension were taken at enrolment and after 1 and 3 years . Mean joint-space width of the medial compartment of the tibiofemoral joint was assessed by digital image analysis , whereas minimum joint-space width -- ie , at the narrowest point -- was measured by visual inspection with a magnifying lens . Symptoms were scored by the Western Ontario and McMaster Universities ( WOMAC ) osteoarthritis index . FINDINGS The 106 patients on placebo had a progressive joint-space narrowing , with a mean joint-space loss after 3 years of -0.31 mm ( 95 % CI -0.48 to -0.13 ) . There was no significant joint-space loss in the 106 patients on glucosamine sulphate : -0.06 mm ( -0.22 to 0.09 ) . Similar results were reported with minimum joint-space narrowing . As assessed by WOMAC scores , symptoms worsened slightly in patients on placebo compared with the improvement observed after treatment with glucosamine sulphate . There were no differences in safety or reasons for early withdrawal between the treatment and placebo groups . INTERPRETATION The long-term combined structure-modifying and symptom-modifying effects of gluosamine sulphate suggest that it could be a disease modifying agent in osteoarthritis BACKGROUND Conventional symptomatic treatments for osteoarthritis do not favorably affect disease progression . The aim of this r and omized , placebo-controlled trial was to determine whether long-term ( 3-year ) treatment with glucosamine sulfate can modify the progression of joint structure and symptom changes in knee osteoarthritis , as previously suggested . METHODS Two hundred two patients with knee osteoarthritis ( using American College of Rheumatology criteria ) were r and omized to receive oral glucosamine sulfate , 1500 mg once a day , or placebo . Changes in radiographic minimum joint space width were measured in the medial compartment of the tibiofemoral joint , and symptoms were assessed using the algo-functional indexes of Lequesne and WOMAC ( Western Ontario and McMaster Universities ) . RESULTS Osteoarthritis was of mild to moderate severity at enrollment , with average joint space widths of slightly less than 4 mm and a Lequesne index score of less than 9 points . Progressive joint space narrowing with placebo use was -0.19 mm ( 95 % confidence interval , -0.29 to -0.09 mm ) after 3 years . Conversely , there was no average change with glucosamine sulfate use ( 0.04 mm ; 95 % confidence interval , -0.06 to 0.14 mm ) , with a significant difference between groups ( P = .001 ) . Fewer patients treated with glucosamine sulfate experienced predefined severe narrowings ( > 0.5 mm ) : 5 % vs 14 % ( P = .05 ) . Symptoms improved modestly with placebo use but as much as 20 % to 25 % with glucosamine sulfate use , with significant final differences on the Lequesne index and the WOMAC total index and pain , function , and stiffness subscales . Safety was good and without differences between groups . CONCLUSION Long-term treatment with glucosamine sulfate retarded the progression of knee osteoarthritis , possibly determining disease modification OBJECTIVE To assess whether improvement in knee pain biased the determination of the structure-modifying effect reported for glucosamine sulfate in two recent 3-year , r and omised , placebo-controlled clinical trials , in which conventional st and ing antero-posterior full extension knee radiographs were used for the measurement of joint space narrowing , and in which pain relief might have improved knee full extension . DESIGN Patients completing the 3-year treatment course were selected based on a WOMAC pain decrease at least equal to the mean improvement in the glucosamine sulfate arms in either of the original studies , irrespective of treatment with glucosamine sulfate or placebo ( drug responders or placebo responders ) . In a second approach , 3-year completers were selected if their baseline st and ing knee pain ( item # 5 of the WOMAC pain scale ) was ' severe ' or ' extreme ' and improved by any degree at the end of the trials . In both cases , changes in minimum joint space width were compared between treatment groups . RESULTS Global knee pain was mild-to-moderate in the two study population s and in all patient subsets identified . There were obviously more pain improvers in the glucosamine sulfate subsets ( N=76 in the two studies combined ) than in the placebo subsets ( N=57 ) , but WOMAC pain scores improved to the same extent , which was as large as over 50 % relative to baseline . Nevertheless , the placebo subsets in both studies underwent an evident mean ( SD ) joint space narrowing , which in the pooled analysis of both studies was -0.22 ( 0.80 ) mm , and was not observed with glucosamine sulfate : + 0.15 ( 0.60 ) mm ( P=0.003 vs placebo ) . Similar results were found in the smaller subsets with > or = severe baseline st and ing knee pain that improved after 3 years , with a joint space narrowing nevertheless of -0.28 ( 0.76 ) mm with placebo ( N=26 ) , not observed with glucosamine sulfate : + 0.21 ( 0.68 ) mm ( N=31 ; P=0.014 vs placebo ) . CONCLUSIONS Knee pain relief did not bias the report of a structure-modifying effect of glucosamine sulfate in two recent long-term trials using conventional st and ing antero-posterior radiographs , possibly due to the mild-to-moderate patient characteristics OBJECTIVE To assess the effects of the prescription formulation of glucosamine sulfate ( 1,500 mg administered once daily ) on the symptoms of knee osteoarthritis ( OA ) during a 6-month treatment course . METHODS Three hundred eighteen patients were enrolled in this r and omized , placebo-controlled , double-blind trial in which acetaminophen , the currently preferred medication for symptomatic treatment of OA , was used as a side comparator . Patients were r and omly assigned to receive oral glucosamine sulfate 1,500 mg once daily ( n = 106 ) , acetaminophen 3 gm/day ( n = 108 ) , or placebo ( n = 104 ) . The primary efficacy outcome measure was the change in the Lequesne index after 6 months . Secondary parameters included the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) and response according to the Osteoarthritis Research Society International criteria . These outcome measures were assessed using an intent-to-treat analysis . RESULTS At baseline , the study patients had moderately severe OA symptoms ( mean Lequesne index approximately 11 points ) . Glucosamine sulfate was more effective than placebo in improving the Lequesne score , with a final decrease of 3.1 points , versus 1.9 with placebo ( difference between glucosamine sulfate and placebo -1.2 [ 95 % confidence interval -2.3 , -0.8 ] ) ( P = 0.032 ) . The 2.7-point decrease with acetaminophen was not significantly different from that with placebo ( difference -0.8 [ 95 % confidence interval -1.9 , 0.3 ] ) ( P = 0.18 ) . Similar results were observed for the WOMAC . There were more responders to glucosamine sulfate ( 39.6 % ) and acetaminophen ( 33.3 % ) than to placebo ( 21.2 % ) ( P = 0.004 and P = 0.047 , respectively , versus placebo ) . Safety was good , and was comparable among groups . CONCLUSION The findings of this study indicate that glucosamine sulfate at the oral once-daily dosage of 1,500 mg is more effective than placebo in treating knee OA symptoms . Although acetaminophen also had a higher responder rate compared with placebo , it failed to show significant effects on the algofunctional indexes OBJECTIVE To assess the effect of st and ing position on joint space width ( JSW ) measurements of the hips with and without osteoarthritis ( OA ) on pelvic radiographs . METHODS Adult patients aged 18 or more had pelvic anteroposterior conventional radiographs st and ing and supine performed by a single radiologist in the same radiology unit according to st and ardised guidelines . JSW measurements in mm were made by a single reader blind to patients ’ identity and type of view , using a 0.1 mm graduated magnifying glass directly laid over the radiograph , at the narrowest point for OA hips or at the vertical joint space for non-OA hips . Agreement of JSW between both views was assessed using the Bl and and Altman graphical analysis . RESULTS JSW was greater on st and ing than supine radiographs , for example , 7.1 % for OA hips . Mean ( SD ) differences and limits of agreement ( mm ) between both views were 0.08 ( 0.27 ) and −0.46 to 0.62 for the 70 non-OA hips , 0.02 ( 0.31 ) and −0.60 to 0.64 for the 46 OA hips . Corresponding 95 % confidence intervals of mean differences were 0.02 , −0.14 mm and −0.07 , −0.11 mm . CONCLUSIONS Measurements of JSW of the hip on pelvic st and ing and supine radiographs are concordant . Changes less than or equal to 0.64 mm between the two views are similar or inferior to radiological progression of OA Joint space width ( JSW ) and narrowing ( JSN ) measurements on radiographs are currently the best way to assess disease severity or progression in hip osteoarthritis , yet we lack data regarding the most accurate and sensitive measurement technique . This study was conducted to determine the optimal radiograph and number of readers for measuring JSW and JSN . Fifty pairs of radiographs taken three years apart were obtained from patients included in a structure modification trial in hip osteoarthritis . Three radiographs were taken with the patient st and ing : pelvis , target hip anteroposterior ( AP ) and oblique views . Two trained readers , blinded to each other 's findings , time sequence and treatment , each read the six radiographs gathered for each patient twice ( time interval ≥15 days ) , using a 0.1 mm graduated magnifying glass . Radiographs were r and omly coded for each reading . The interobserver and intraobserver cross-sectional ( M0 and M36 ) and longitudinal ( M0–M36 ) reproducibilities were assessed using the intraclass coefficient ( ICC ) and Bl and –Altman method for readers 1 and 2 and their mean . Sensitivity to change was estimated using the st and ardized response mean ( SRM = change/st and ard deviation of change ) for M0–M36 changes . For interobserver reliability on M0–M36 changes , the ICCs ( 95 % confidence interval [ CI ] ) were 0.79 ( 0.65–0.88 ) for pelvic view , 0.87 ( 0.78–0.93 ) for hip AP view and 0.86 ( 0.76–0.92 ) for oblique view . Intraobserver reliability ICCs were 0.81 ( 0.69–0.89 ) for observer 1 and 0.97 ( 0.95–0.98 ) for observer 2 for the pelvic view ; 0.87 ( 0.78–0.92 ) and 0.97 ( 0.96–0.99 ) for the hip AP view ; and 0.73 ( 0.57–0.84 ) and 0.93 ( 0.88–0.96 ) for the oblique view . SRMs were 0.61 ( observer 1 ) and 0.82 ( observer 2 ) for pelvic view ; 0.64 and 0.75 for hip AP view ; and 0.77 and 0.70 for oblique view . All three views yielded accurate JSW and JSN . According to the best reader , the pelvic view performed slightly better . Both readers exhibited high precision , with SRMs of 0.6 or greater for assessing JSN over three years . Selecting a single reader was the most accurate method , with 0.3 mm precision . Using this cutoff , 50 % of patients were classified as ' progressors ' BACKGROUND Hip and knee osteoarthritis are frequent causes of primary care consultations . They are considered slowly progressive disorders , often result ing in severe pain or disability and the need for joint replacements . There have been few longitudinal studies of progression to inform individual prognoses in primary care . AIM To describe the degree of progression and investigate predictors of change in hip or knee pain and disability . DESIGN OF STUDY Prospect i ve community-based cohort . SETTING An age-sex stratified survey of 27 000 people registered with 40 general practice s in Avon and Somerset yielded 2437 reporting hip and /or knee symptoms at baseline ( 1992 - 1994 ) . A 25 % r and om sample of 587 individuals was followed up between 1998 and 1999 . METHOD Pain or disability was measured at baseline and followup using the New Zeal and score . For the worst joint according to the New Zeal and score at baseline , hip and knee problems were analysed separately . Regression models ascertained characteristics of nonresponders and factors associated with change in scores . Seven sociodemographic , seven comorbidity , and two healthcare utilisation variables were considered . RESULTS Generally pain and disability worsened over the 7 years , but 35 % and 29 % of those initially reporting hip and knee pain respectively had improved . Reporting " other health problems " was associated with greater deterioration for both hip and knee disease , as was cardiovascular morbidity for hip disease and lower social class , being retired , hypertension , and higher body mass index for knee disease . Deteriorations in scores were strongly associated with individuals consulting their GP about joint problems . CONCLUSION Osteoarthritis does not invariably deteriorate , but when it does social as well as biological factors appear to be important . These findings may aid outcome prediction . Future research on osteoarthritis should be conducted within a biopsychosocial rather than a purely biological paradigm OBJECTIVE To determine the effectiveness of glucosamine in reducing pain from osteoarthritis of the knee . DESIGN R and omized , double-blind parallel trial of glucosamine 500 mg three times daily or a placebo for 2 months . SETTING Veterans Affairs Medical Center , Prescott , AZ . PARTICIPANTS Ninety-eight patients aged 34 to 81 being treated for osteoarthritis of the knee . MAIN OUTCOME MEASURES Pain intensity both at rest and while walking as assessed by a visual analog scale at baseline and after 30 and 60 days of treatment . RESULTS Forty-nine patients were r and omly allocated to each group . There was no statistical difference between the two groups in scores on the visual analog scale at 30 days for resting ( mean [ SD ] score placebo group 3.5 [ 2.7 ] vs 3.3 [ 2.4 ] glucosamine group , P = 0.66 ) or walking ( 5.1 [ 2.6 ] vs 5.3 [ 2.4 ] , P = 0.69 ) ; there was also no difference at 60 days for resting ( 3.4 [ 2.5 ] vs 3.2 [ 2.5 ] , P = 0.81 ) or walking ( 4.9 [ 2.2 ] vs 4.9 [ 2.8 ] , P = 0.90 ) . There was also no statistical difference between groups in the mean change from baseline in scores on the visual analog scale ( mean [ SD ] change for walking at 60 days placebo group -1.5 [ 2.5 ] vs glucosamine group -1.4 [ 3.0 ] , P = 0.77 ) . Two participants taking glucosamine and 4 taking placebo withdrew from the study due to adverse side effects ( P = 0.67 ) . CONCLUSION Glucosamine was no better than placebo in reducing pain from osteoarthritis of the knee in this group of patients Within the context of a double blind r and omized controlled parallel trial of 2 nonsteroidal antiinflammatory drugs , we vali date d WOMAC , a new multidimensional , self-administered health status instrument for patients with osteoarthritis of the hip or knee . The pain , stiffness and physical function subscales fulfil conventional criteria for face , content and construct validity , reliability , responsiveness and relative efficiency . WOMAC is a disease-specific purpose built high performance instrument for evaluative research in osteoarthritis clinical trials OBJECTIVE Previous studies of knee osteoarthritis ( OA ) have yielded variable estimates of the rate of joint space narrowing ( JSN ) in the st and ing anteroposterior ( AP ) radiograph , due largely to longitudinal changes in the alignment of the medial tibial plateau ( MTP ) and x-ray beam . To characterize this bias , we examined serial radiographs of subjects with knee OA in population -based and clinical OA cohorts from 3 locations in the United States and the United Kingdom . METHODS Radiographic features of knee OA ( e.g. , osteophytosis , JSN ) and MTP alignment in 428 OA knees were evaluated by consensus of 2 readers . Alignment was considered satisfactory if the anterior and posterior margins of the MTP were superimposed within 1 mm . Readers were blinded to subject identity , and films were read in r and om order . The minimum medial joint space width was also measured manually ( st and ard error of repeated measurements 0.20 mm ) in serial knee images . RESULTS Only 14 % of serial radiographs exhibited alignment of the MTP in both images . In OA knees with satisfactory alignment in both images , the mean rate of JSN over 2 - 3 years ( 0.26 mm/year ) was significantly larger ( P = 0.004 ) than that in OA knees with misalignment in 1 or both radiographs and was 86 % more rapid than the mean JSN in all OA knees . Moreover , the within-group st and ard deviation of JSN was significantly smaller among knees with reproduced alignment of the MTP than in knees in which misalignment occurred in 1 or both images ( P = 0.006 ) . CONCLUSION Poor st and ardization of knee positioning in serial st and ing AP radiographs in previous studies of OA progression has obscured the rate and variability of articular cartilage loss in subjects with knee OA . True JSN ( i.e. , JSN that is not attributable to longitudinal changes in the alignment of the MTP with the x-ray beam in serial radiographic examinations ) may occur more rapidly , and with less between-subject variability , than that previously thought to be characteristic of knee OA BACKGROUND The OARSI St and ing Committee for Clinical Trials Response Criteria Initiative had developed two sets of responder criteria to present the results of changes after treatment in three symptomatic domains ( pain , function , and patient 's global assessment ) as a single variable for clinical trials ( 1 ) . For each domain , a response was defined by both a relative and an absolute change , with different cut-offs with regard to the drug , the route of administration and the OA localization . OBJECTIVE To propose a simplified set of responder criteria with a similar cut-off , whatever the drug , the route or the OA localization . METHODS Data driven approach : ( 1 ) Two data bases were considered : the " elaboration " data base with which the formal OARSI sets of responder criteria were elaborated , and the " revisit " data base . ( 2 ) Six different scenarios were evaluated : The two formal OARSI sets of criteria ; Four proposed scenarios of simplified sets of criteria . Data from clinical r and omized blinded placebo controlled trials were used to evaluate the performances of the two formal scenarios with two different data bases ( " elaboration " versus " revisit " ) and those of the four proposed simplified scenarios within the " revisit " data base . The placebo effect , active effect , treatment effect , and the required sample arm size to obtain the placebo effect and the active treatment effect observed were the performances evaluated for each of the six scenarios . Experts ' opinion approach : Results were discussed among the participants of the OMERACT VI meeting , who voted to select the definite OMERACT-OARSI set of criteria ( one of the six evaluated scenarios ) . RESULTS Data driven approach : Fourteen trials totaling 1886 OA patients and fifteen studies involving 8164 OA patients were evaluated in the " elaboration " and the " revisit " data bases respectively . The variability of the performances observed in the " revisit " data base when using the different simplified scenarios was similar to that observed between the two data bases ( " elaboration " versus " revisit " ) when using the formal scenarios . The treatment effect and the required sample arm size were similar for each set of criteria . Experts ' opinion approach : According to the experts , these two previous performances were the most important of an optimal set of responder criteria . They chose the set of criteria considering both pain and function as evaluation domain and requiring an absolute change and a relative change from baseline to define a response , with similar cut-offs whatever the drug , the route of administration or the OA localization . CONCLUSION This data driven and experts ' opinion approach is the basis for proposing an optimal simplified set of responder criteria for OA clinical trials . Other studies , using other sets of OA patients , are required in order to further vali date this proposed OMERACT-OARSI set of criteria Efficacy and tolerance of a new preparation of pure glucosamine sulphate , in injectable and oral form , were investigated in 30 patients with osteoarthrosis . Two groups of in- patients with chronic degenerative articular disorders received daily for 7 days either 400 mg glucosamine sulphate or a piperazine/chlorbutanol combination by intravenous or intramuscular injection . During the 2 following weeks , the patients receiving glucosamine had oral glucosamine capsules ( 6 x 250 mg daily ) ; the other group had placebo . Efficacy was tested by semi-quantitative scoring of pain at rest and during active and passive movements , as well as limitation of articular function , before and after 7 and 21 days of treatment . Patients were positively question ed daily for possible intolerance symptoms . Haematology , circulatory data and urine analysis were tested before and after treatment . During both initial parenteral treatments , each symptom significantly improved , but to a faster and greater extent in the group treated with glucosamine . During the maintenance period , a further improvement was recorded in the patients treated with glucosamine , whereas in those on placebo the symptom scores increased almost to the pre-treatment level . This was considered the major difference between basic therapy , such as with glucosamine , as purely symptomatic treatment . Clinical and biological tolerance were excellent with both treatments , and no definitely drug-related complaints were recorded . It is suggested that parenteral and /or oral treatment with pure glucosamine sulphate should be considered as basic therapy for the management of primary or secondary degenerative osteoarthrosis disorders OBJECTIVES To compare the reliability and validity in a large open population of three frequently used radiological definitions of hip osteoarthritis ( OA ) : Kellgren and Lawrence grade , minimal joint space ( MJS ) , and Croft grade ; and to investigate whether the validity of the three definitions of hip OA is sex dependent . METHODS SUBJECTS from the Rotterdam study ( aged > or= 55 years , n = 3585 ) were evaluated . The inter-rater reliability was tested in a r and om set of 148 x rays . The validity was expressed as the ability to identify patients who show clinical symptoms of hip OA ( construct validity ) and as the ability to predict total hip replacement ( THR ) at follow up ( predictive validity ) . RESULTS Inter-rater reliability was similar for the Kellgren and Lawrence grade and MJS ( kappa statistics 0.68 and 0.62 , respectively ) but lower for Croft 's grade ( kappa statistic , 0.51 ) . The Kellgren and Lawrence grade and MJS showed the strongest associations with clinical symptoms of hip OA . Sex appeared to be an effect modifier for Kellgren and Lawrence and MJS definitions , women showing a stronger association between grading and symptoms than men . However , the sex dependency was attributed to differences in height between women and men . The Kellgren and Lawrence grade showed the highest predictive value for THR at follow up . CONCLUSIONS Based on these findings , Kellgren and Lawrence still appears to be a useful OA definition for epidemiological studies focusing on the presence of hip OA OBJECTIVES : To determine a cut off value for changes in radiological joint space width that allowed definition of radiological progression of hip osteoarthritis not related to measurement method errors and , thereafter , to determine factors predictive of radiological progression of hip osteoarthritis and to evaluate the correlations between clinical and radiological parameters . METHODS : A prospect i ve , longitudinal ( one year duration ) , multicentre study was made of patients with osteoarthritis of the hip ( American College of Rheumatology criteria ) . Data on clinical activity ( pain , functional impairment ) , demographic data ( age , gender , body mass index ) , and femoral head migration ( superolateral , superomedial , concentric ) were collected when the patient entered the study ; radiological grade ( joint space width in millimetres at the narrowest point using a 0.1 mm graduated magnifying glass , evaluated by a single observer unaware of the chronology of the films ) was recorded at the patient 's entry to the study and after one year . RESULTS : Analysis of the means of the differences between two analyses performed by a single observer of 30 pairs of radiographs ( one performed after an interval of one year ) ( 0.06 ( SD 0.23 ) ) suggested that a change of more than 0.56 mm ( 2 SD ) after a one year follow up could define progression of osteoarthritis of the hip . Of the 508 patients recruited , 461 ( 91 % ) completed the one year follow up and radiological progression was observed in 102 ( 22 % ) . The factors predictive of radiological progression that were identified in the multivariate analysis were : radiological joint space width at entry < or = 2 mm , superolateral migration of the femoral head , female gender , Lequesne 's functional index > 10 , age at entry > 65 years ( odds ratios 2.11 , 4.25 , 2.51 , 2.66 , 1.90 , respectively ) . The level of clinical parameters ( pain , functional impairment ) and the amount of symptomatic treatment required ( non-steroidal anti-inflammatory drugs and analgesic intake ) accounted for 20 % ( p < 0.0001 ) of the variability of the changes in radiological joint space width over the one year study period . CONCLUSION : These data suggest that radiological progression of hip osteoarthritis could be defined by a change in joint space width of at least 0.6 mm after a one year follow up period , is correlated with the changes in clinical status of the patients , and is related not only to demographic data ( age , gender ) , but also to some specific characteristics of osteoarthritis ( localisation , radiological severity , clinical activity ) OBJECTIVE This preliminary study sought to determine whether using 1500/1200 mg of glucosamine hydrochloride and chondroitin sulfate ( GH/CS ) is effective , both separately and combined with exercise , compared to a placebo plus exercise program in improving physical function , pain , strength , balance , and mobility in older adults with knee osteoarthritis ( OA ) . METHODS This double-blind , placebo-controlled , r and omized clinical trial lasted 12 months . Participants included 89 older adults ( age>/=50 years ) with knee OA r and omized to either GH/CS or placebo group . Phase I was a 6-month trial comparing the effects of assignment to either GH/CS or placebo . Phase II added 6 months of exercise for both groups . The primary outcome measure was Western Ontario and McMaster University Osteoarthritis Index ( WOMAC ) function , and secondary outcome measures included WOMAC pain , 6-min walk , balance , and knee strength . RESULTS Of the 89 r and omized participants , 72 ( 81 % ) completed the study . The median pill compliance was 94 % and 95 % in Phase I , and , in Phase II , 97 % and 91 % for the GH/CS and placebo groups , respectively . Median exercise compliance during Phase II was 77 % for the GH/CS group and 78 % for the placebo group . WOMAC function and pain did not differ significantly between the groups at 6- or 12-month follow-up . There were also no significant differences between the groups in 6-min walk or knee strength ; however , balance was better in the placebo group with approximately a 10 % difference compared to the GH/CS group . CONCLUSIONS The GH/CS group was not superior to the placebo group in function , pain , or mobility after both phases of the intervention ( pill only and pill plus exercise ) OBJECTIVE Pharmacokinetic data on glucosamine are scant , limiting the underst and ing of glucosamine sulfate mechanism of action in support of its treatment effects in osteoarthritis . This study investigated the oral pharmacokinetics and dose-proportionality of glucosamine after administration of the patented crystalline glucosamine sulfate in man . METHODS Twelve healthy volunteers received three consecutive once-daily oral administrations of glucosamine sulfate soluble powder at the doses of 750 , 1,500 , and 3,000 mg , in an open , r and omised , cross-over fashion . Glucosamine was determined in plasma collected up to 48 h after the last dose by a vali date d Liquid Chromatography method with Mass Spectrometry detection . Pharmacokinetic parameters were calculated at steady state . RESULTS Endogenous plasma levels of glucosamine were detected ( 10.4 - 204 ng/ml , with low intra-subject variability ) . Glucosamine was rapidly absorbed after oral administration and its pharmacokinetics were linear in the dose range 750 - 1,500 mg , but not at 3,000 mg , where the plasma concentration-time profiles were less than expected based on dose-proportionality . Plasma levels increased over 30-folds from baseline and peaked at about 10 microM with the st and ard 1,500 mg once-daily dosage . Glucosamine distributed to extravascular compartments and its plasma concentrations were still above baseline up to the last collection time . Glucosamine elimination half-life was only tentatively estimated to average 15 h. CONCLUSIONS Glucosamine is bioavailable after oral administration of crystalline glucosamine sulfate , persists in circulation , and its pharmacokinetics support once-daily dosage . Steady state peak concentrations at the therapeutic dose of 1,500 mg were in line with those found to be effective in selected in vitro mechanistic studies . This is the only glucosamine formulation for which pharmacokinetic , efficacy and safety data are now available |
12,287 | 26,724,488 | Although superiority of LAAO over NOACs was not demonstrated by RCTs in terms of stroke prevention , LAAO was found to be consistently associated with a lower rate of both thromboembolic and hemorrhagic events as compared with NOACs in observational studies | BACKGROUND A direct comparison of the efficacy and safety profiles of left atrial appendage occlusion ( LAAO ) devices and novel oral anticoagulants ( NOACs ) for stroke prevention in atrial fibrillation is warranted but currently unavailable .
OBJECTIVE The aim of this study was to compare the > 1-year efficacy and safety of LAAO devices and NOACs for stroke prevention in patients with atrial fibrillation . | BACKGROUND Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use . Dabigatran is a new oral direct thrombin inhibitor . METHODS In this noninferiority trial , we r and omly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive , in a blinded fashion , fixed doses of dabigatran--110 mg or 150 mg twice daily -- or , in an unblinded fashion , adjusted-dose warfarin . The median duration of the follow-up period was 2.0 years . The primary outcome was stroke or systemic embolism . RESULTS Rates of the primary outcome were 1.69 % per year in the warfarin group , as compared with 1.53 % per year in the group that received 110 mg of dabigatran ( relative risk with dabigatran , 0.91 ; 95 % confidence interval [ CI ] , 0.74 to 1.11 ; P<0.001 for noninferiority ) and 1.11 % per year in the group that received 150 mg of dabigatran ( relative risk , 0.66 ; 95 % CI , 0.53 to 0.82 ; P<0.001 for superiority ) . The rate of major bleeding was 3.36 % per year in the warfarin group , as compared with 2.71 % per year in the group receiving 110 mg of dabigatran ( P=0.003 ) and 3.11 % per year in the group receiving 150 mg of dabigatran ( P=0.31 ) . The rate of hemorrhagic stroke was 0.38 % per year in the warfarin group , as compared with 0.12 % per year with 110 mg of dabigatran ( P<0.001 ) and 0.10 % per year with 150 mg of dabigatran ( P<0.001 ) . The mortality rate was 4.13 % per year in the warfarin group , as compared with 3.75 % per year with 110 mg of dabigatran ( P=0.13 ) and 3.64 % per year with 150 mg of dabigatran ( P=0.051 ) . CONCLUSIONS In patients with atrial fibrillation , dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin , as well as lower rates of major hemorrhage . Dabigatran administered at a dose of 150 mg , as compared with warfarin , was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage . ( Clinical Trials.gov number , NCT00262600 . BACKGROUND Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects . The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known . METHODS We conducted a r and omized , double-blind , double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation ( median follow-up , 2.8 years ) . The primary efficacy end point was stroke or systemic embolism . Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period . The principal safety end point was major bleeding . RESULTS The annualized rate of the primary end point during treatment was 1.50 % with warfarin ( median time in the therapeutic range , 68.4 % ) , as compared with 1.18 % with high-dose edoxaban ( hazard ratio , 0.79 ; 97.5 % confidence interval [ CI ] , 0.63 to 0.99 ; P<0.001 for noninferiority ) and 1.61 % with low-dose edoxaban ( hazard ratio , 1.07 ; 97.5 % CI , 0.87 to 1.31 ; P=0.005 for noninferiority ) . In the intention-to-treat analysis , there was a trend favoring high-dose edoxaban versus warfarin ( hazard ratio , 0.87 ; 97.5 % CI , 0.73 to 1.04 ; P=0.08 ) and an unfavorable trend with low-dose edoxaban versus warfarin ( hazard ratio , 1.13 ; 97.5 % CI , 0.96 to 1.34 ; P=0.10 ) . The annualized rate of major bleeding was 3.43 % with warfarin versus 2.75 % with high-dose edoxaban ( hazard ratio , 0.80 ; 95 % CI , 0.71 to 0.91 ; P<0.001 ) and 1.61 % with low-dose edoxaban ( hazard ratio , 0.47 ; 95 % CI , 0.41 to 0.55 ; P<0.001 ) . The corresponding annualized rates of death from cardiovascular causes were 3.17 % versus 2.74 % ( hazard ratio , 0.86 ; 95 % CI , 0.77 to 0.97 ; P=0.01 ) , and 2.71 % ( hazard ratio , 0.85 ; 95 % CI , 0.76 to 0.96 ; P=0.008 ) , and the corresponding rates of the key secondary end point ( a composite of stroke , systemic embolism , or death from cardiovascular causes ) were 4.43 % versus 3.85 % ( hazard ratio , 0.87 ; 95 % CI , 0.78 to 0.96 ; P=0.005 ) , and 4.23 % ( hazard ratio , 0.95 ; 95 % CI , 0.86 to 1.05 ; P=0.32 ) . CONCLUSIONS Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes . ( Funded by Daiichi Sankyo Pharma Development ; ENGAGE AF-TIMI 48 Clinical Trials.gov number , NCT00781391 . ) OBJECTIVES This study assessed the feasibility of implanting a device in the left atrial appendage ( LAA ) in patients with atrial fibrillation ( AF ) to prevent thromboembolic stroke . BACKGROUND Meta-analyses confirmed that in cases of left atrial thrombus in nonrheumatic AF patients approximately 90 % of them are in the LAA . METHODS The WATCHMAN Left Atrial Appendage System ( Atritech Inc. , Plymouth , Minnesota ) is a nitinol device implanted percutaneously to seal the LAA . Patients were followed by clinical and transesophageal echocardiography at 45 days and 6 months with annual clinical follow-up thereafter . RESULTS Sixty-six patients underwent device implantation . Mean follow-up was 740 + /- 341 days . At 45 days , 93 % ( 54 of 58 ) devices showed successful sealing of LAA according to protocol . Two patients experienced device embolization , both successfully retrieved percutaneously . No embolizations occurred in 53 patients enrolled after modification of fixation barbs . There were 2 cardiac tamponades , 1 air embolism , and 1 delivery wire fracture ( first generation ) with surgical explantation but no long-term sequelae for the patient . Four patients developed a flat thrombus layer on the device at 6 months that resolved with additional anticoagulation . Two patients experienced transient ischemic attack , 1 without visible thrombus . There were 2 deaths , neither device related . Autopsy documented a stable , fully endothelialized device 9 months after implantation . No strokes occurred during follow-up despite > 90 % of patients with discontinuation of anticoagulation . CONCLUSIONS Preliminary data suggest LAA occlusion with the WATCHMAN System to be safe and feasible . A r and omized study is ongoing comparing oral anticoagulation with percutaneous closure BACKGROUND Currently , 2 different left atrial appendage ( LAA ) closure systems are available for stroke prevention in nonvalvular atrial fibrillation but comparative data are lacking . OBJECTIVES To prospect ively compare procedural data and patient outcome for 2 contemporary LAA closure systems and to investigate an alternative antithrombotic treatment regimen in high-risk patients . METHODS Patients with nonvalvular atrial fibrillation , with high risk for stroke , and who either had contraindication or were not willing to accept oral anticoagulation were prospect ively enrolled . Watchman ( Boston Scientific , Natick , MA ; group A ) or Amplatzer Cardiac Plug ( St Jude Medical , Minneapolis , MN ; group B ) devices were implanted . All patients received antithrombotic therapy for 6 weeks . After repeat transesophageal echocardiography , patients were switched to aspirin . RESULTS Eighty patients were enrolled . There was no statistical difference in patient characteristics in groups A and B : CHA2DS2VASC score : 4.1 ± 1.5 versus 4.5 ± 1.8 ; HASBLED score : 3.1 ± 1.1 versus 3.1 ± 1.1 , respectively . LAA closure was achieved in 78 of 80 patients ( 98 % ) ( group A : 38 of 40 [ 95 % ] vs group B : 40 of 40 [ 100 % ] ) . There was no difference in procedure time ( group A : 48 ± 16 minutes vs group B : 47 ± 15 minutes ; P = .69 ) and fluoroscopy time ( group A : 6.0 ± 4.7 minutes vs group B : 7.3 ± 4.4 minutes ; P = .25 ) . Major complications included 1 air embolism and delayed tamponade in each group . After 6 weeks , 1 device dislodgment and 4 device-related thrombi were detected . Ninety-four percent of the patients ( 73 of 77 ) were switched to aspirin after 6 weeks . During a median follow-up of 364 days ( Q1-Q3 : 283 - 539 days ) , no systemic embolism occurred , but 3 patients died ( heart failure : n = 2 ; bleeding : n = 1 ) . CONCLUSIONS Implantation of both LAA closure devices can be performed with high success rates in high-risk patients . Postprocedural 6 weeks antithrombotic therapy followed by aspirin therapy needs to be confirmed in a larger study BACKGROUND Atrial fibrillation ( AF ) is the most common sustained cardiac arrhythmia and it is associated with an increased stroke risk , due mainly to cardiac embolism from the left atrial appendage ( LAA ) . Percutaneous LAA closure is a method to reduce stroke risk in AF without using anticoagulant agents . In this study we report data from an Italian experience with the LAA occluder Amplatzer Cardiac Plug ( ACP ) device ( Aga Medical Corporation , Plymouth , MN , USA ) . METHODS The study was design ed to evaluate the safety of LAA closure using ACP and the efficacy of the procedure in preventing strokes during a 1-year follow-up . Patients with permanent or paroxysmal AF , high stroke risk , and contraindication to warfarin therapy were selected for the procedure . RESULTS The LAA closure was attempted in 37 patients and succeeded in 34 cases ( 91.9 % ) . Four patients experienced serious complications ( one cardiac tamponade requiring pericardiocentesis , two device embolizations , one low-rate response AF requiring artificial pacing ) . During a 1-year follow-up , ischemic stroke occurred in one of 34 patients , result ing in a stroke rate of 2.94 % ; thus there was a stroke rate reduction of 50.2 % and 26.5 % compared to the expected stroke rate , according to CHADS2 and CHA2 DS2 VASc score . None of the patients who received ACP experienced major bleeding during the follow-up . CONCLUSION LAA closure using ACP is a relatively feasible procedure which can be performed by highly experienced operators to reduce stroke rate in patients with AF , high stroke risk , and contraindication to oral anticoagulants OBJECTIVES The purpose of this study was to assess the safety and efficacy of left atrial appendage ( LAA ) closure in nonvalvular atrial fibrillation ( AF ) patients ineligible for warfarin therapy . BACKGROUND The PROTECT AF ( Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation ) trial demonstrated that LAA closure with the Watchman device ( Boston Scientific , Natick , Massachusetts ) was noninferior to warfarin therapy . However , the PROTECT AF trial only included patients who were c and i date s for warfarin , and even patients r and omly assigned to the LAA closure arm received concomitant warfarin for 6 weeks after Watchman implantation . METHODS A multicenter , prospect i ve , nonr and omized study was conducted of LAA closure with the Watchman device in 150 patients with nonvalvular AF and CHADS₂ ( congestive heart failure , hypertension , age ≥75 years , diabetes mellitus , and prior stroke or transient ischemic attack ) score ≥1 , who were considered ineligible for warfarin . The primary efficacy endpoint was the combined events of ischemic stroke , hemorrhagic stroke , systemic embolism , and cardiovascular/unexplained death . RESULTS The mean CHADS₂ score and CHA₂DS₂-VASc ( CHADS₂ score plus 2 points for age ≥75 years and 1 point for vascular disease , age 65 to 74 years , or female sex ) score were 2.8 ± 1.2 and 4.4 ± 1.7 , respectively . History of hemorrhagic/bleeding tendencies ( 93 % ) was the most common reason for warfarin in eligibility . Mean duration of follow-up was 14.4 ± 8.6 months . Serious procedure- or device-related safety events occurred in 8.7 % of patients ( 13 of 150 patients ) . All-cause stroke or systemic embolism occurred in 4 patients ( 2.3 % per year ) : ischemic stroke in 3 patients ( 1.7 % per year ) and hemorrhagic stroke in 1 patient ( 0.6 % per year ) . This ischemic stroke rate was less than that expected ( 7.3 % per year ) based on the CHADS₂ scores of the patient cohort . CONCLUSIONS LAA closure with the Watchman device can be safely performed without a warfarin transition , and is a reasonable alternative to consider for patients at high risk for stroke but with contraindications to systemic oral anticoagulation . ( ASA Plavix Feasibility Study With Watchman Left Atrial Appendage Closure Technology [ ASAP ] ; NCT00851578 ) The effectiveness and safety of dabigatran for stroke prevention in atrial fibrillation ( SPAF ) demonstrated in RE-LY needs to be confirmed in daily care . To evaluate treatment persistence , effectiveness and safety of dabigatran therapy in SPAF patients in daily care , we used data from an ongoing , prospect i ve , non-interventional registry of more than 2,500 patients on novel oral anticoagulants in daily care . Between October 1 , 2011 and February 28 , 2013 , a total of 341 SPAF patients receiving dabigatran were enrolled . The combined endpoint of stroke/transient ischaemic attack/systemic embolism occurred at a rate of 2.93/100 patient-years in the intention-to-treat analysis ( 95%-CI 1.6 - 4.9 ) and at 1.9/100 patient-years in the on treatment analysis ( events within three days after last intake ) . On-treatment rates were higher in patients selected for 110 mg dabigatran ( n=183 ) BID compared to the 158 patients selected for 150 mg BID ( 2.88 [ 95 % CI 1.16- 5.93 ] vs 0.86/100 patient-years [ 95 % CI 0.10 , 3.12 ] ) . On treatment , major bleeding occurred at a rate of 2.3/100 patient-years and numerically more often in patients receiving the 110 mg BID dose compared to the 150 mg BID dose ( 2.9 vs 1.7/100 patient-years ) . Dabigatran treatment discontinuation occurred in a total of 124 patients during follow-up ( 25.8 per 100 patient-years in Kaplan Meier analysis ) . Main reasons for treatment discontinuation were non-bleeding side effects . Our data contribute to the confirmation of effectiveness and relative safety of dabigatran in unselected patients in daily care . However , discontinuation rates are not lower than those reported for patients treated with vitamin K antagonists Aims The r and omized PROTECT AF trial demonstrated non-inferiority of left atrial appendage ( LAA ) closure to oral anticoagulation with warfarin . Current guidelines give a class IIb recommendation for LAA closure . We evaluated the efficacy and safety of LAA closure in a consecutive series of non-valvular atrial fibrillation patients with contraindications to long-term oral anticoagulation or at high bleeding risk . Methods and results 101 consecutive non-valvular atrial fibrillation patients ( age 74.7 ± 7.5 years ) at high risk for stroke ( CHA2DS2-VASc Score 4.4 ± 1.6 ) and high bleeding risk ( HAS-BLED Score 4.2 ± 1.3 ) received LAA closure with either the Watchman closure device ( n = 38 ) or the Amplatzer cardiac plug ( n = 63 ) . Dual antiplatelet therapy with aspirin and clopidogrel was recommended for 3–6 months after device implantation , followed by long-term antiplatelet therapy with aspirin . No anticoagulation was given after device implantation . Mean follow-up was 400 days . One patient ( 1 % ) experienced a transient ischemic attack , and two patients ( 2 % ) suffered from ischemic stroke . While on recommended antiplatelet therapy , bleeding occurred in 12/101 patients ( 12 % ) . Bleeding was significantly reduced with 3 compared with 6 months dual antiplatelet therapy ( 3.0 vs. 16.2 % , p < 0.05 ) while ischemic or thrombotic events were similar . Conclusion Left atrial appendage closure in patients with non-valvular atrial fibrillation and high risk for stroke and bleeding events effectively prevented stroke and reduced cerebral ischemic events compared to expected stroke rate according to CHA2DS2-VASc Score . Dual antiplatelet therapy for 3 months reduced the rate of bleeding events compared to 6 months therapy with no increase of thrombotic events Abstract Aims Although non-vitamin K antagonist oral anticoagulants are recommended for stroke prevention in patients with non-valvular atrial fibrillation ( NVAF ) based on clinical trial results , there is a need for safety and efficacy data from unselected patients in everyday clinical practice . XANTUS investigated the safety and efficacy of the Factor Xa inhibitor rivaroxaban in routine clinical use in the NVAF setting . Methods and results Consecutive consenting patients with NVAF newly started on rivaroxaban were eligible and were followed up at ∼3-month intervals for 1 year , or for at least 30 days after permanent discontinuation . All adverse events ( AEs ) were recorded as AEs or serious AEs ; major outcomes ( including major bleeding , symptomatic thromboembolic events [ stroke , systemic embolism , transient ischaemic attack , and myocardial infa rct ion ] , and all-cause death ) were central ly adjudicated . There were 6784 patients treated with rivaroxaban at 311 centres in Europe , Israel , and Canada . Mean patient age was 71.5 years ( range 19–99 ) , 41 % were female , and 9.4 % had documented severe or moderate renal impairment ( creatinine clearance < 50 mL/min ) . The mean CHADS2 and CHA2DS2-VASc scores were 2.0 and 3.4 , respectively ; 859 ( 12.7 % ) patients had a CHA2DS2-VASc score of 0 or 1 . The mean treatment duration was 329 days . Treatment-emergent major bleeding occurred in 128 patients ( 2.1 events per 100 patient-years ) , 118 ( 1.9 events per 100 patient-years ) died , and 43 ( 0.7 events per 100 patient-years ) suffered a stroke . Conclusion XANTUS is the first international , prospect i ve , observational study to describe the use of rivaroxaban in a broad NVAF patient population . Rates of stroke and major bleeding were low in patients receiving rivaroxaban in routine clinical practice . Trial registration number Clinical trials.gov : NCT01606995 Aims The aim of the present study was to evaluate the procedural feasibility , the safety and the 1-year outcome following left atrial appendage ( LAA ) closure using the Amplatzer cardiac plug ( ACP ) in Belgium . Methods and results Data were prospect ively collected among 90 consecutive patients , undergoing LAA closure with an ACP in 7 Belgian centres between June 2009 and September 2012 . The patients ( 56 males , 74 ± 8 years ) were at high risk for stroke ( CHA2DS2-VASc = 4.4 ± 1.8 ) and bleeding ( HAS-BLED = 3.3 ± 1.3 ) . Technical success was obtained in all but one patient and procedural success was 95 % . Procedural major adverse events ( MAE ) were 3 tamponades result ing in death in one case . Minor complications were 3 insignifi ca nt pericardial eff usions , 2 transient myocardial ischaemia due to air embolism and 1 femoral pseudoaneurysm . At 1-y follow-up , there were 4 deaths , 2 minor strokes , 1 tamponade and 1 myocardial infa rct ion . Overall survival was 94 % and freedom from MAE was 88 % . In our population , the expected annual stroke risk according to the CHA2DS2-VASc score was 5.08 % , while the observed stroke rate was 2.14%/year . Conclusions The Belgian registry shows that LAA closure using the ACP device is feasible and safe . At 1-y follow-up , the observed stroke rate was 2.14%/year , less than predicted by the CHA2DS2-VASc score . Longer follow-up is needed to evaluate the long-term safety and its effi cacy in reducing stroke BACKGROUND Watchman and Lariat left atrial appendage ( LAA ) occlusion devices are associated with LAA leaks postdeployment . OBJECTIVE The purpose of this study was to compare the incidence , characteristics , and clinical significance of these leaks . METHODS We performed a multicenter prospect i ve observational study of all patients who underwent LAA closure . Baseline , procedural , and imaging variables along with LAA occlusion rates at 30 - 90 days and 1-year postprocedure were compared . RESULTS A total of 478 patients ( 219 with the Watchman device and 259 with the Lariat device ) with successful implants were included . Patients in the Lariat group had a higher CHADS2 ( congestive heart failure , hypertension , age > 74 years , diabetes , stroke ) score and a larger left atrium and LAA . A total of 79 patients ( 17 % ) had a detectable leak at 1 year . More patients in the Watchman group had a leak compared with those in the Lariat group ( 46 [ 21 % ] vs 33 [ 14 % ] ; P = .019 ) . All the leaks were eccentric ( edge effect ) in the Watchman group and concentric ( gunny sack effect ) in the Lariat group . The size of the leak was larger in the Watchman group than in the Lariat group ( 3.10 ± 1.5 mm vs 2.15 ± 1.3 mm ; P = .001 ) . The Watchman group had 1 device embolization requiring surgery and 2 pericardial effusions requiring pericardiocentesis . In the Lariat group , 4 patients had cardiac tamponade requiring urgent surgical repair . Three patients in each group had a cerebrovascular accident and were not associated with device leaks . CONCLUSION The Lariat device is associated with a lower rate of leaks at 1 year as compared with the Watchman device , with no difference in rates of cerebrovascular accident . There was no correlation between the presence of residual leak and the occurrence of cerebrovascular accident BACKGROUND Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations . Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin . METHODS In this r and omized , double-blind trial , we compared apixaban ( at a dose of 5 mg twice daily ) with warfarin ( target international normalized ratio , 2.0 to 3.0 ) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke . The primary outcome was ischemic or hemorrhagic stroke or systemic embolism . The trial was design ed to test for noninferiority , with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause . RESULTS The median duration of follow-up was 1.8 years . The rate of the primary outcome was 1.27 % per year in the apixaban group , as compared with 1.60 % per year in the warfarin group ( hazard ratio with apixaban , 0.79 ; 95 % confidence interval [ CI ] , 0.66 to 0.95 ; P<0.001 for noninferiority ; P=0.01 for superiority ) . The rate of major bleeding was 2.13 % per year in the apixaban group , as compared with 3.09 % per year in the warfarin group ( hazard ratio , 0.69 ; 95 % CI , 0.60 to 0.80 ; P<0.001 ) , and the rates of death from any cause were 3.52 % and 3.94 % , respectively ( hazard ratio , 0.89 ; 95 % CI , 0.80 to 0.99 ; P=0.047 ) . The rate of hemorrhagic stroke was 0.24 % per year in the apixaban group , as compared with 0.47 % per year in the warfarin group ( hazard ratio , 0.51 ; 95 % CI , 0.35 to 0.75 ; P<0.001 ) , and the rate of ischemic or uncertain type of stroke was 0.97 % per year in the apixaban group and 1.05 % per year in the warfarin group ( hazard ratio , 0.92 ; 95 % CI , 0.74 to 1.13 ; P=0.42 ) . CONCLUSIONS In patients with atrial fibrillation , apixaban was superior to warfarin in preventing stroke or systemic embolism , caused less bleeding , and result ed in lower mortality . ( Funded by Bristol-Myers Squibb and Pfizer ; ARISTOTLE Clinical Trials.gov number , NCT00412984 . ) Objective : To evaluate the safety and feasibility of percutaneous left atrial appendage occlusion ( LAAO ) in patients with atrial fibrillation ( AF ) and previous intracranial hemorrhage ( ICH ) . Methods : In an explorative , prospect i ve , single-center , observational study , LAAO was performed in patients with previous ICH and AF using the Amplatzer Cardiac Plug device . Risks of ischemic strokes and hemorrhagic complications were estimated using the CHA2DS2Vasc score and the HAS-BLED score . Before and 1 , 6 , 12 , and 24 months after the procedure , clinical status and complications were recorded . Major complications were predefined as periprocedural stroke , death , pericardial effusion , and device embolism . Results : LAAO was performed in 20 patients . Based on CHA2DS2Vasc score ( mean 4.5 ± 1.4 ) and HAS-BLED score ( mean 4.7 ± 1.0 ) , annual risks of stroke and hemorrhagic complications were 4.0%–6.7 % and 8.7%–12.5 % , respectively . No patient had a procedure-related complication . Minor postprocedural complications were observed in 4/20 patients ( 2 inguinal hematoma , 1 self-limiting asystole , and 1 thrombus formation on device ) . No ischemic or hemorrhagic stroke occurred during a mean follow-up of 13.6 ± 8.2 months . Conclusions : In this first study of LAAO in patients with previous ICH , LAAO appears feasible and safe . A larger , controlled trial is needed to assess the efficacy and safety of the procedure compared to other preventive measures . Classification of evidence : This study provides Class III evidence that in patients with a history of previous ICH and AF , percutaneous LAAO is safe and feasible |
12,288 | 27,127,634 | This meta- analysis shows the addition of a P2Y12 inhibitor is superior to placebo , with a trend favouring the use of prasugrel in patients with diabetes with ACS , particularly those undergoing PCI | BACKGROUND Patients with diabetes are at increased risk of acute coronary syndromes ( ACS ) and their mortality and morbidity outcomes are significantly worse following ACS events , independent of other comorbidities .
This systematic review sought to establish the optimum management strategy with focus on P2Y12 blockade in patients with diabetes with ACS . | CONTEXT The worldwide epidemic of diabetes mellitus is increasing the burden of cardiovascular disease , the leading cause of death among persons with diabetes . The independent effect of diabetes on mortality following acute coronary syndromes ( ACS ) is uncertain . OBJECTIVE To evaluate the influence of diabetes on mortality following ACS using a large data base spanning the full spectrum of ACS . DESIGN , SETTING , AND PATIENTS A subgroup analysis of patients with diabetes enrolled in r and omized clinical trials that evaluated ACS therapies . Patients with ACS in 11 independent Thrombolysis in Myocardial Infa rct ion ( TIMI ) Study Group clinical trials from 1997 to 2006 were pooled , including 62,036 patients ( 46,577 with ST-segment elevation myocardial infa rct ion [ STEMI ] and 15,459 with unstable angina/non-STEMI [ UA/NSTEMI ] ) , of whom 10 613 ( 17.1 % ) had diabetes . A multivariable model was constructed to adjust for baseline characteristics , aspects of ACS presentation , and treatments for the ACS event . MAIN OUTCOME MEASURES Mortality at 30 days and 1 year following ACS among patients with diabetes vs patients without diabetes . RESULTS Mortality at 30 days was significantly higher among patients with diabetes than without diabetes presenting with UA/NSTEMI ( 2.1 % vs 1.1 % , P < .001 ) and STEMI ( 8.5 % vs 5.4 % , P < .001 ) . After adjusting for baseline characteristics and features and management of the ACS event , diabetes was independently associated with higher 30-day mortality after UA/NSTEMI ( odds ratio [ OR ] , 1.78 ; 95 % confidence interval [ CI ] , 1.24 - 2.56 ) or STEMI ( OR , 1.40 ; 95 % CI , 1.24 - 1.57 ) . Diabetes at presentation with ACS was associated with significantly higher mortality 1 year after UA/NSTEMI ( hazard ratio [ HR ] , 1.65 ; 95 % CI , 1.30 - 2.10 ) or STEMI ( HR , 1.22 ; 95 % CI , 1.08 - 1.38 ) . By 1 year following ACS , patients with diabetes presenting with UA/NSTEMI had a risk of death that approached patients without diabetes presenting with STEMI ( 7.2 % vs 8.1 % ) . CONCLUSION Despite modern therapies for ACS , diabetes confers a significant adverse prognosis , which highlights the importance of aggressive strategies to manage this high-risk population with unstable ischemic heart disease Background — The antiplatelet effects of the Platelet Inhibition and Patient Outcomes ( PLATO ) trial dose of ticagrelor in patients nonresponsive to clopidogrel and after they switch agents are unknown . Methods and Results — Patients with stable coronary artery disease on aspirin therapy received a 300-mg clopidogrel load ; nonresponders were identified by light transmittance aggregometry . In a 2-way crossover design , nonresponders ( n=41 ) and responders ( n=57 ) r and omly received clopidogrel ( 600 mg/75 mg once daily ) or ticagrelor ( 180 mg/90 mg twice daily ) for 14 days during period 1 . In period 2 , all nonresponders switched treatment ; half of the responders continued the same treatment , whereas the others switched treatment . Inhibition of platelet aggregation was higher in nonresponders treated with ticagrelor compared with clopidogrel ( P<0.05 ) . Treatment with ticagrelor among nonresponders result ed in a > 10 % , > 30 % , and > 50 % decrease in platelet aggregation from baseline in 100 % , 75 % , and 13 % of patients , respectively . Platelet aggregation fell from 59±9 % to 35±11 % in patients switched from clopidogrel to ticagrelor and increased from 36±14 % to 56±9 % in patients switched from ticagrelor to clopidogrel ( P<0.0001 for both ) . Platelet reactivity was below the cut points previously associated with ischemic risk measured by light transmittance aggregometry , VerifyNow P2Y12 assay , and vasodilator-stimulated phosphoprotein phosphorylation in 98 % to 100 % of patients after ticagrelor therapy versus 44 % to 76 % of patients after clopidogrel therapy . Conclusions — Ticagrelor therapy overcomes nonresponsiveness to clopidogrel , and its antiplatelet effect is the same in responders and nonresponders . Nearly all clopidogrel nonresponders and responders treated with ticagrelor will have platelet reactivity below the cut points associated with ischemic risk . Clinical Trial Registration — http://www . clinical trials.gov . Unique Identifier : NCT00642811 OBJECTIVE It has been postulated that prasugrel might be the preferred treatment option in diabetes mellitus ( DM ) patients with acute coronary syndrome ( ACS ) undergoing percutaneous coronary intervention ( PCI ) . We aim ed to compare the pharmacodynamic action of ticagrelor versus prasugrel . RESEARCH DESIGN AND METHODS In a prospect i ve , single-center , single-blind , crossover study , 30 consecutive ACS patients with DM who had been pretreated with clopidogrel were r and omized to either 90 mg ticagrelor twice daily or 10 mg prasugrel once daily with a 15-day treatment period . Platelet reactivity ( PR ) was assessed with the VerifyNow P2Y12 function assay , measured in P2Y12 reaction units ( PRU ) . RESULTS PR was significantly lower after ticagrelor ( 45.2 PRU [ 95 % CI 27.4–63.1 ] ) compared with prasugrel ( 80.8 PRU [ 63.0–98.7 ] ) , with a least squares mean difference of –35.6 PRU ( −55.2 to −15.9 , P = 0.001 ) . High PR rate was 0 % for ticagrelor and 3.3 % for prasugrel ( P = 1.0 ) . CONCLUSIONS In DM patients with ACS who had been pretreated with clopidogrel and who undergo PCI , ticagrelor achieves a significantly higher platelet inhibition than prasugrel . Both antiplatelet agents effectively treat high PR . The relevance of these findings to the clinical efficacy and safety of ticagrelor and prasugrel in DM patients needs further elucidation Aims Patients with diabetes mellitus ( DM ) have increased platelet reactivity and reduced platelet response to clopidogrel compared with patients without DM . Prasugrel , a more potent antiplatelet agent , is associated with greater reductions in ischaemic events compared with clopidogrel , particularly in patients with DM . The aim of this study was to perform serial pharmacodynamic assessment s of prasugrel with high-dose clopidogrel in patients with DM . Methods and results Optimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 was a prospect i ve , r and omized , double-blind , crossover study in patients with type 2 DM and coronary artery disease ( CAD ) . Patients ( n= 35 ) were r and omly assigned to either prasugrel 60 mg loading dose (LD)/10 mg maintenance dose ( MD ) or clopidogrel 600 mg LD/150 mg MD over two 1-week treatment periods separated by a 2-week washout period . Platelet function was assessed by VerifyNow ® P2Y12 assay , light transmission aggregometry , and vasodilator-stimulated phosphoprotein phosphorylation at 0 , 1 , 4 , and 24 h and 7 days . Greater platelet inhibition by VerifyNow ® P2Y12 was achieved by prasugrel compared with clopidogrel at 4 h post-LD ( least squares mean , 89.3 vs. 27.7 % , P < 0.0001 ; primary endpoint ) . The difference in platelet inhibition between prasugrel and clopidogrel was significant from 1 h through 7 days ( P < 0.0001 ) . Similar results were obtained using all other platelet function measures . Prasugrel result ed in fewer poor responders at all time points irrespective of definition used . Conclusion In patients with type 2 DM and CAD , st and ard-dose prasugrel is associated with greater platelet inhibition and better response profiles during both the loading and maintenance periods when compared with double-dose clopidogrel . Clinical trial identifier : www . clinical trials.gov — In acute coronary syndromes ( ACS ) , a dual antiplatelet regimen with an adenosine diphosphate ( ADP ) receptor antagonist plus aspirin has become the cornerstone of treatment . The third-generation thienopyridine prasugrel and the cyclopentyl-triazolo-pyrimidine ticagrelor provide a greater , more rapid and consistent platelet inhibition compared to their predecessor clopidogrel . Based on their advantages over clopidogrel in two l and mark studies , both drugs received a class I recommendation for their use in ACS patients with and without ST segment elevation . Due to differences in ACS population s and conditions investigated , the relative merits of ticagrelor versus prasugrel in the treatment of ACS patients with planned invasive strategy can not be reliably estimated from independent trials . To date , no direct head-to-head comparison of ticagrelor and prasugrel in terms of clinical outcome exists . The aim of this multicenter , r and omized , open-label trial is to assess whether ticagrelor is superior to prasugrel in ACS patients with planned invasive strategy Background —Ticagrelor and prasugrel provide stronger platelet inhibition compared with clopidogrel . Direct pharmacodynamic comparison between them has not yet been reported in ST-segment – elevation myocardial infa rct ion patients . Methods and Results —In a prospect i ve , single-center , single-blind study , 55 out of 117 ( 47 % ) screened consecutive ST-segment – elevation myocardial infa rct ion patients undergoing primary percutaneous coronary intervention were r and omized to either ticagrelor 180 mg loading followed by 90 mg bid , or prasugrel 60 mg loading followed by 10 mg od for 5 days . Platelet reactivity ( PR ) was assessed with the VerifyNow P2Y12 function assay and the Multiplate Analyzer at 0 , 1 , 2 , 6 , 24 hours , and 5 days postr and omization . The primary end point , PR with VerifyNow at hour 1 , did not differ significantly between patients r and omized to ticagrelor versus prasugrel ( 257.3 P2Y12 reaction unit [ PRU ] , 95 % CI 230.8–283.8 versus 231.3 PRU , 95 % CI 205.3–257.4 ; P=0.2 ) . PR did not differ at 2 , 6 , and 24 hours , although at day 5 it was lower with ticagrelor than prasugrel ( 25.6 PRU , 95 % CI 12.3–38.9 versus 50.3 PRU , 95 % CI 36.4–64.1 ; P=0.01 ) . At hour 2 , high on-treatment PR rates ( cutoff 208 PRU ) were 46.2 % and 34.6 % for ticagrelor and prasugrel , respectively , decreased significantly thereafter , whereas did not differ significantly between the 2 agents at all the time points of the study . Conclusions —In patients with ST-segment – elevation myocardial infa rct ion undergoing primary percutaneous coronary intervention , both ticagrelor and prasugrel exhibit an initial delay in the onset of their antiplatelet action . Ticagrelor did not appear superior to prasugrel in reducing PR during the first 24 hours of ST-segment – elevation myocardial infa rct ion . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT01463163 BACKGROUND Patients ' responses to oral antiplatelet therapy are subject to variation . Bedside monitoring offers the opportunity to improve outcomes after coronary stenting by individualizing therapy . METHODS We r and omly assigned 2440 patients scheduled for coronary stenting at 38 centers to a strategy of platelet-function monitoring , with drug adjustment in patients who had a poor response to antiplatelet therapy , or to a conventional strategy without monitoring and drug adjustment . The primary end point was the composite of death , myocardial infa rct ion , stent thrombosis , stroke , or urgent revascularization 1 year after stent implantation . For patients in the monitoring group , the VerifyNow P2Y12 and aspirin point-of-care assays were used in the catheterization laboratory before stent implantation and in the outpatient clinic 2 to 4 weeks later . RESULTS In the monitoring group , high platelet reactivity in patients taking clopidogrel ( 34.5 % of patients ) or aspirin ( 7.6 % ) led to the administration of an additional bolus of clopidogrel , prasugrel , or aspirin along with glycoprotein IIb/IIIa inhibitors during the procedure . The primary end point occurred in 34.6 % of the patients in the monitoring group , as compared with 31.1 % of those in the conventional-treatment group ( hazard ratio , 1.13 ; 95 % confidence interval [ CI ] , 0.98 to 1.29 ; P=0.10 ) . The main secondary end point , stent thrombosis or any urgent revascularization , occurred in 4.9 % of the patients in the monitoring group and 4.6 % of those in the conventional-treatment group ( hazard ratio , 1.06 ; 95 % CI , 0.74 to 1.52 ; P=0.77 ) . The rate of major bleeding events did not differ significantly between groups . CONCLUSIONS This study showed no significant improvements in clinical outcomes with platelet-function monitoring and treatment adjustment for coronary stenting , as compared with st and ard antiplatelet therapy without monitoring . ( Funded by Allies in Cardiovascular Trials Initiatives and Organized Networks and others ; A RCT IC Clinical Trials.gov number , NCT00827411 . ) Background — After treatment with clopidogrel , patients with type 2 diabetes mellitus ( T2DM ) have reduced platelet inhibition compared with patients who are not diabetic . Whether platelet inhibition can be enhanced by increasing clopidogrel maintenance dosage in T2DM patients is unknown . The aim of this pilot study was to assess the functional impact of a high maintenance dose in T2DM patients with suboptimal clopidogrel-induced antiplatelet effects . Methods and Results — T2DM patients on chronic dual antiplatelet therapy were screened to identify suboptimal clopidogrel responders . The latter were r and omized to 30-day treatment with a st and ard ( 75 mg ; n=20 ) or high ( 150 mg ; n=20 ) daily maintenance dose . Platelet function was assessed at 3 time points : baseline , 30 days after r and omization , and 30 days after resuming st and ard dosing . Platelet function parameters included adenosine diphosphate – induced ( 20 and 5 & mgr;mol/L ) maximal and late platelet aggregation , inhibition of platelet aggregation , platelet disaggregation , and P2Y12 reactivity index . A total of 64 T2DM patients were screened to identify 40 suboptimal responders . After r and omization , maximal adenosine diphosphate – induced ( 20 & mgr;mol/L ) platelet aggregation was significantly reduced in the 150-mg group compared with the 75-mg group ( P=0.002 ; primary end point ) . However , suboptimal clopidogrel response was still present in 60 % of patients on the 150-mg regimen . All other platelet function parameters showed enhanced clopidogrel-induced antiplatelet effects with 150 mg , which returned to baseline values after resumption of st and ard dosing . Conclusions — A 150-mg maintenance dose of clopidogrel is associated with enhanced antiplatelet effects compared with 75 mg in high-risk T2DM patients . However , enhanced ex vivo platelet reactivity continues to persist , the clinical implication s of which are unknown and need to be evaluated in large-scale clinical trials BACKGROUND Despite current treatments , patients who have acute coronary syndromes without ST-segment elevation have high rates of major vascular events . We evaluated the efficacy and safety of the antiplatelet agent clopidogrel when given with aspirin in such patients . METHODS We r and omly assigned 12,562 patients who had presented within 24 hours after the onset of symptoms to receive clopidogrel ( 300 mg immediately , followed by 75 mg once daily ) ( 6259 patients ) or placebo ( 6303 patients ) in addition to aspirin for 3 to 12 months . RESULTS The first primary outcome --a composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , or stroke -- occurred in 9.3 percent of the patients in the clopidogrel group and 11.4 percent of the patients in the placebo group ( relative risk with clopidogrel as compared with placebo , 0.80 ; 95 percent confidence interval , 0.72 to 0.90 ; P<0.001 ) . The second primary outcome --the first primary outcome or refractory ischemia -- occurred in 16.5 percent of the patients in the clopidogrel group and 18.8 percent of the patients in the placebo group ( relative risk , 0.86 ; 95 percent confidence interval , 0.79 to 0.94 ; P<0.001 ) . The percentages of patients with in-hospital refractory or severe ischemia , heart failure , and revascularization procedures were also significantly lower with clopidogrel . There were significantly more patients with major bleeding in the clopidogrel group than in the placebo group ( 3.7 percent vs. 2.7 percent ; relative risk , 1.38 ; P=0.001 ) , but there were not significantly more patients with episodes of life-threatening bleeding ( 2.2 percent [ corrected ] vs. 1.8 percent ; P=0.13 ) or hemorrhagic strokes ( 0.1 percent vs. 0.1 percent ) . CONCLUSIONS The antiplatelet agent clopidogrel has beneficial effects in patients with acute coronary syndromes without ST-segment elevation . However , the risk of major bleeding is increased among patients treated with clopidogrel BACKGROUND Dual-antiplatelet therapy with aspirin and a thienopyridine is a cornerstone of treatment to prevent thrombotic complications of acute coronary syndromes and percutaneous coronary intervention . METHODS To compare prasugrel , a new thienopyridine , with clopidogrel , we r and omly assigned 13,608 patients with moderate-to-high-risk acute coronary syndromes with scheduled percutaneous coronary intervention to receive prasugrel ( a 60-mg loading dose and a 10-mg daily maintenance dose ) or clopidogrel ( a 300-mg loading dose and a 75-mg daily maintenance dose ) , for 6 to 15 months . The primary efficacy end point was death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . The key safety end point was major bleeding . RESULTS The primary efficacy end point occurred in 12.1 % of patients receiving clopidogrel and 9.9 % of patients receiving prasugrel ( hazard ratio for prasugrel vs. clopidogrel , 0.81 ; 95 % confidence interval [ CI ] , 0.73 to 0.90 ; P<0.001 ) . We also found significant reductions in the prasugrel group in the rates of myocardial infa rct ion ( 9.7 % for clopidogrel vs. 7.4 % for prasugrel ; P<0.001 ) , urgent target-vessel revascularization ( 3.7 % vs. 2.5 % ; P<0.001 ) , and stent thrombosis ( 2.4 % vs. 1.1 % ; P<0.001 ) . Major bleeding was observed in 2.4 % of patients receiving prasugrel and in 1.8 % of patients receiving clopidogrel ( hazard ratio , 1.32 ; 95 % CI , 1.03 to 1.68 ; P=0.03 ) . Also greater in the prasugrel group was the rate of life-threatening bleeding ( 1.4 % vs. 0.9 % ; P=0.01 ) , including nonfatal bleeding ( 1.1 % vs. 0.9 % ; hazard ratio , 1.25 ; P=0.23 ) and fatal bleeding ( 0.4 % vs. 0.1 % ; P=0.002 ) . CONCLUSIONS In patients with acute coronary syndromes with scheduled percutaneous coronary intervention , prasugrel therapy was associated with significantly reduced rates of ischemic events , including stent thrombosis , but with an increased risk of major bleeding , including fatal bleeding . Overall mortality did not differ significantly between treatment groups . ( Clinical Trials.gov number , NCT00097591 [ Clinical Trials.gov ] . AIMS To describe the incidence of dyspnoea and its associations with demographic characteristics and clinical outcomes in patients with acute coronary syndromes ( ACS ) treated with ticagrelor or clopidogrel in the PLATelet inhibition and patient Outcomes ( PLATO ) study . METHODS AND RESULTS In the PLATO study , 18 624 patients were r and omized to receive either clopidogrel [ 300 - 600 mg loading dose ( LD ) , 75 mg daily ] or ticagrelor ( 180 mg LD , 90 mg b.i.d . ) . The occurrence of reported dyspnoea adverse events ( AEs ) was analysed in the 18 421 patients who received at least one dose of study medication in relation to demographic characteristics , clinical outcomes and other associations of patients with and without dyspnoea . A total of 1339 ticagrelor-treated patients ( 14.5 % ) and 798 clopidogrel-treated patients ( 8.7 % ) had a dyspnoea AE following r and omization , with respectively 39 ( 0.4 % ) and 24 ( 0.3 % ) classified as severe in intensity . Excluding dyspnoea AEs occurring after the secondary endpoint of myocardial infa rct ion ( MI ) , the yearly rates of the efficacy endpoints in dyspnoea AE patients in the ticagrelor and clopidogrel groups were : for the primary composite of CV death , MI , and stroke , 8.8 and 10.4 % ( unadjusted P = 0.25 ; adjusted P = 0.54 ) ; for CV death , 3.1 and 4.8 % ( unadjusted P = 0.024 ; adjusted P = 0.18 ) ; and for total death 3.7 and 6.2 % ( unadjusted P = 0.004 ; adjusted P = 0.06 ) , respectively . CONCLUSIONS Ticagrelor-related dyspnoea is usually mild or moderate in intensity and does not appear to be associated with differences concerning any efficacy or safety outcomes with ticagrelor compared with clopidogrel therapy in ACS patients BACKGROUND Variation in and irreversibility of platelet inhibition with clopidogrel has led to controversy about its optimum dose and timing of administration in patients with acute coronary syndromes . We compared ticagrelor , a more potent reversible P2Y12 inhibitor with clopidogrel in such patients . METHODS At r and omisation , an invasive strategy was planned for 13 408 ( 72.0 % ) of 18 624 patients hospitalised for acute coronary syndromes ( with or without ST elevation ) . In a double-blind , double-dummy study , patients were r and omly assigned in a one-to-one ratio to ticagrelor and placebo ( 180 mg loading dose followed by 90 mg twice a day ) , or to clopidogrel and placebo ( 300 - 600 mg loading dose or continuation with maintenance dose followed by 75 mg per day ) for 6 - 12 months . All patients were given aspirin . The primary composite endpoint was cardiovascular death , myocardial infa rct ion , or stroke . Analyses were by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00391872 . FINDINGS 6732 patients were assigned to ticagrelor and 6676 to clopidogrel . The primary composite endpoint occurred in fewer patients in the ticagrelor group than in the clopidogrel group ( 569 [ event rate at 360 days 9.0 % ] vs 668 [ 10.7 % ] , hazard ratio 0.84 , 95 % CI 0.75 - 0.94 ; p=0.0025 ) . There was no difference between clopidogrel and ticagrelor groups in the rates of total major bleeding ( 691 [ 11.6 % ] vs 689 [ 11.5 % ] , 0.99 [ 0.89 - 1.10 ] ; p=0.8803 ) or severe bleeding , as defined according to the Global Use of Strategies To Open occluded coronary arteries , ( 198 [ 3.2 % ] vs 185 [ 2.9 % ] , 0.91 [ 0.74 - 1.12 ] ; p=0.3785 ) . INTERPRETATION Ticagrelor seems to be a better option than clopidogrel for patients with acute coronary syndromes for whom an early invasive strategy is planned BACKGROUND Clopidogrel and aspirin are the most commonly used antiplatelet therapies for percutaneous coronary intervention ( PCI ) . We assessed the effect of various clopidogrel and aspirin regimens in prevention of major cardiovascular events and stent thrombosis in patients undergoing PCI . METHODS The CURRENT-OASIS 7 trial was undertaken in 597 centres in 39 countries . 25,086 individuals with acute coronary syndromes and intended early PCI were r and omly assigned to double-dose ( 600 mg on day 1 , 150 mg on days 2 - 7 , then 75 mg daily ) versus st and ard-dose ( 300 mg on day 1 then 75 mg daily ) clopidogrel , and high-dose ( 300 - 325 mg daily ) versus low-dose ( 75 - 100 mg daily ) aspirin . R and omisation was done with a 24 h computerised central automated voice response system . The clopidogrel dose comparison was double-blind and the aspirin dose comparison was open label with blinded assessment of outcomes . This prespecified analysis is of the 17,263 individuals who underwent PCI . The primary outcome was cardiovascular death , myocardial infa rct ion , or stroke at 30 days . Analyses were by intention to treat , adjusted for propensity to undergo PCI . This trial is registered with Clinical Trials.gov , number NCT00335452 . FINDINGS 8560 patients were assigned to double-dose and 8703 to st and ard-dose clopidogrel ( 8558 and 8702 completed 30-day follow-up , respectively ) , and 8624 to high-dose and 8639 to low-dose aspirin ( 8622 and 8638 completed 30-day follow-up , respectively ) . Compared with the st and ard dose , double-dose clopidogrel reduced the rate of the primary outcome ( 330 events [ 3·9 % ] vs 392 events [ 4·5 % ] ; adjusted hazard ratio 0·86 , 95 % CI 0·74 - 0·99 , p=0·039 ) and definite stent thrombosis ( 58 [ 0·7 % ] vs 111 [ 1·3 % ] ; 0·54 [ 0·39 - 0·74 ] , p=0·0001 ) . High-dose and low-dose aspirin did not differ for the primary outcome ( 356 [ 4·1 % ] vs 366 [ 4·2 % ] ; 0·98 , 0·84 - 1·13 , p=0·76 ) . Major bleeding was more common with double-dose than with st and ard-dose clopidogrel ( 139 [ 1·6 % ] vs 99 [ 1·1 % ] ; 1·41 , 1·09 - 1·83 , p=0·009 ) and did not differ between high-dose and low-dose aspirin ( 128 [ 1·5 % ] vs 110 [ 1·3 % ] ; 1·18 , 0·92 - 1·53 , p=0·20 ) . INTERPRETATION In patients undergoing PCI for acute coronary syndromes , a 7-day double-dose clopidogrel regimen was associated with a reduction in cardiovascular events and stent thrombosis compared with the st and ard dose . Efficacy and safety did not differ between high-dose and low-dose aspirin . A double-dose clopidogrel regimen can be considered for all patients with acute coronary syndromes treated with an early invasive strategy and intended early PCI . FUNDING Sanofi-Aventis and Bristol-Myers Squibb BACKGROUND The Global Registry of Acute Coronary Events (GRACE)-a prospect i ve , multinational study of patients hospitalized with acute coronary syndromes (ACSs)-was design ed to improve the quality of care for patients with an ACS . Exp and ed GRACE aims to test the feasibility of a simplified data collection tool and provision of quarterly feedback to index individual hospital management practice s to an international reference cohort . METHODS We describe the objectives ; study design ; study and data management ; and the characteristics , management , and hospital outcomes of patients > or = 18 years old enrolled with a presumptive diagnosis of ACS . RESULTS From 2001 to 2007 , 31,982 patients were enrolled at 184 hospitals in 25 countries ; 30 % were diagnosed with ST-segment elevation myocardial infa rct ion , 31 % with non-ST-segment myocardial infa rct ion , 26 % with unstable angina , and 12 % with another cardiac/noncardiac final diagnosis . The median age was 65 ( interquartile range 55 - 75 ) years ; 24 % were > 75 years old , and 33 % were women . In general , increases were observed over time across the spectrum of ACS ( 1 ) in the use in the first 24 hours and at discharge of aspirin , clopidogrel , beta-blockers , and angiotensin-converting enzyme inhibitors/receptor blockers ; ( 2 ) in the use at discharge of statins ; ( 3 ) in the early use of glycoprotein IIb/IIIa inhibitors and low-molecular-weight heparin ; and ( 4 ) in the use of cardiac catheterization and percutaneous coronary intervention . An increase in the use of primary percutaneous coronary intervention and a similar decrease in the use of fibrinolysis in ST-segment elevation myocardial infa rct ion were also seen . CONCLUSIONS Over the course of 7 years , general increases in the use of evidence -based therapies for ACS patients were observed in the exp and ed GRACE BACKGROUND Intracoronary stenting can improve procedural success and reduce restenosis compared with balloon angioplasty in patients with acute coronary syndromes , but can also increase the rate of thrombotic complications including stent thrombosis . The TRITON-TIMI 38 trial has shown that prasugrel-a novel , potent thienopyridine-can reduce ischaemic events compared with st and ard clopidogrel therapy . We assessed the rate , outcomes , and prevention of ischaemic events in patients treated with prasugrel or clopidogrel with stents in the TRITON-TIMI 38 study . METHODS Patients with moderate-risk to high-risk acute coronary syndromes were included in our analysis if they had received at least one coronary stent at the time of the index procedure following r and omisation in TRITON-TIMI 38 , and were further subdivided by type of stent received . Patients were r and omly assigned in a 1 to 1 fashion to receive a loading dose of study drug ( prasugrel 60 mg or clopidogrel 300 mg ) as soon as possible after r and omisation , followed by daily maintenance therapy ( prasugrel 10 mg or clopidogrel 75 mg ) . All patients were to receive aspirin therapy . Treatment was to be continued for a minimum of 6 months and a maximum of 15 months . R and omisation was not stratified by stents used or stent type . The primary endpoint was the composite of cardiovascular death , non-fatal myocardial infa rct ion , or non-fatal stroke . Stent thrombosis was assessed using Academic Research Consortium definitions , and analysis was by intention to treat . TRITON-TIMI 38 is registered with Clinical Trials.gov , number NCT00097591 . FINDINGS 12,844 patients received at least one coronary stent ; 5743 received only drug-eluting stents , and 6461 received only bare-metal stents . Prasugrel compared with clopidogrel reduced the primary endpoint ( 9.7 vs 11.9 % , HR 0.81 , p=0.0001 ) in the stented cohort , in patients with only drug-eluting stents ( 9.0 vs 11.1 % , HR 0.82 , p=0.019 ) , and in patients with only bare-metal stents ( 10.0 vs 12.2 % , HR 0.80 , p=0.003 ) . Stent thrombosis was associated with death or myocardial infa rct ion in 89 % ( 186/210 ) of patients . Stent thrombosis was reduced with prasugrel overall ( 1.13 vs 2.35 % , HR 0.48 , p<0.0001 ) , in patients with drug-eluting stents only ( 0.84 vs 2.31 % , HR 0.36 , p<0.0001 ) , and in those with bare-metal stents only ( 1.27 vs 2.41 % , HR 0.52 , p=0.0009 ) . INTERPRETATION Intensive antiplatelet therapy with prasugrel result ed in fewer ischaemic outcomes including stent thrombosis than with st and ard clopidogrel . These findings were statistically robust irrespective of stent type , and the data affirm the importance of intensive platelet inhibition in patients with intracoronary stents An increased sensitivity of platelets to aggregation from ADP and epinephrine is described in diabetics with or without vascular disease . This sensitivity correlates with elevated levels on von Willebr and factor ( vWF ) , which , in turn appears to be influenced by growth hormone . VWF activity correlates with previously described " plasma factor " activity . Platelets from diabetic subjects are more sensitive than platelets from normal subjects to arachidonic acid-induced aggregation . This sensitivity is abolished by aspirin , which is a prostagl and in synthetase ( cyclo-oxygenase ) inhibitor . Platelets from diabetc subjects synthesize increased amounts of PGE2-like material ( iPGE ) in response to ADP , epinephrine , collagen , and arachidonic acid . The latter finding suggests that a fundamental mechanism for increased platelet aggregation in diabetes is increased prostagl and in synthetase activity . Therapeutic endeavors that would lower growth hormone levels , vWF activity , and /or prostagl and in synthetase activity may be of benefit in the prophylaxis of diabetic vascular disease . Prospect i ve studies are needed to explore these hypothesis , as are more studies on the precise mechanisms and platelet aggregation in diabetes mellitus CONTEXT The benefit of clopidogrel pretreatment before percutaneous coronary intervention ( PCI ) remains debated and its use has not been universally adopted . OBJECTIVE To determine if clopidogrel pretreatment before PCI in patients with recent ST-segment elevation myocardial infa rct ion ( STEMI ) is superior to clopidogrel treatment initiated at the time of PCI in preventing major adverse cardiovascular events . DESIGN , SETTING , AND PARTICIPANTS The PCI-Clopidogrel as Adjunctive Reperfusion Therapy ( CLARITY ) study was a prospect ively planned analysis of the 1863 patients undergoing PCI after m and ated angiography in CLARITY-Thrombolysis in Myocardial Infa rct ion ( TIMI ) 28 , a r and omized , double-blind , placebo-controlled trial of clopidogrel in patients receiving fibrinolytics for STEMI . Patients were enrolled at 319 sites in 23 countries from February 2003 through October 2004 . INTERVENTIONS Patients received aspirin and were r and omized to receive either clopidogrel ( 300 mg loading dose , then 75 mg once daily ) or placebo initiated with fibrinolysis and given until coronary angiography , which was performed 2 to 8 days after initiation of the study drug . For patients undergoing coronary artery stenting , it was recommended that open-label clopidogrel ( including a loading dose ) be administered after the diagnostic angiogram . MAIN OUTCOME MEASURES The primary outcome was the incidence of the composite of cardiovascular death , recurrent MI , or stroke from PCI to 30 days after r and omization . Secondary outcomes included MI or stroke before PCI and the aforementioned composite from r and omization to 30 days . RESULTS Pretreatment with clopidogrel significantly reduced the incidence of cardiovascular death , MI , or stroke following PCI ( 34 [ 3.6 % ] vs 58 [ 6.2 % ] ; adjusted odds ratio [ OR ] , 0.54 [ 95 % CI , 0.35 - 0.85 ] ; P = .008 ) . Pretreatment with clopidogrel also reduced the incidence of MI or stroke prior to PCI ( 37 [ 4.0 % ] vs 58 [ 6.2 % ] ; OR , 0.62 [ 95 % CI , 0.40 - 0.95 ] ; P = .03 ) . Overall , pretreatment with clopidogrel result ed in a highly significant reduction in cardiovascular death , MI , or stroke from r and omization through 30 days ( 70 [ 7.5 % ] vs 112 [ 12.0 % ] ; adjusted OR , 0.59 [ 95 % CI , 0.43 - 0.81 ] ; P = .001 ; number needed to treat = 23 ) . There was no significant excess in the rates of TIMI major or minor bleeding ( 18 [ 2.0 % ] vs 17 [ 1.9 % ] ; P>.99 ) . CONCLUSIONS Clopidogrel pretreatment significantly reduces the incidence of cardiovascular death or ischemic complications both before and after PCI and without a significant increase in major or minor bleeding . These data add further support to the early use of clopidogrel in STEMI and the strategy of routine clopidogrel pretreatment in patients undergoing PCI The design and results of the CAPRIE trial have been previously reported . 3 In brief , 3 groups of patients were eligible : patients with an ischemic stroke at least 1 week but less than 6 months before r and omization , with a persistent neurologic defi cit and no evidence of cerebral hemorrhage ; patients with AMI within the prior 35 days ; and patients with documented peripheral arterial disease , defi ned as patients with intermittent claudication and an ankle/brachial systolic blood pressure index of 0.85 in either leg on 2 separate occasions , or prior leg amputation or angioplasty . Exclusion criteria included uncontrolled hypertension , severe renal or hepatic insuffi ciency , a history of a bleeding disorder , or abnormal white or red blood cell counts . Informed consent was obtained from all but 10 patients before r and omization . Patients were treated and followed for 3 years , with an average follow-up of 1.9 years . Patients were divided into 2 groups : those who did versus those who did not develop AMI during follow-up . AMI was defi ned as the presence of 2 of the following 3 criteria : ( 1 ) characteristic ischemic pain lasting 20 minutes ; ( 2 ) elevation of creatine kinase or creatine kinase-MB , lactate dehydrogenase , or aspartate aminotransferase 2 times the upper limit of normal with no other explanation ; ( 3 ) development of new Q waves of at least 0.4 mV in 2 adjacent electrocardiographic leads or a new dominant R wave in lead V 1 ( with the R wave 1 mm greater than the S wave in V 1 ) . A central validation committee that was blinded to treatment assignment adjudicated all outcomes . Baseline clinical factors were compared between patients who developed a documented AMI during the subsequent follow-up ( 1 to 3 years ) and those who did not . The factors that were found to be signifi cantly different were entered into a multivariate analysis to identify independent predictors of AMI . The odds ratio and 95 % confi dence intervals were calculated from multivariate analysis . From this list , the signi fi ca nt factors were selected as a risk score and the number of risk factors was assigned to each individual patient in the trial . Then , the rate of AMI during follow-up was assessed according to the number of risk factors . This latter analysis was then strati fi ed by study drug assignment Background — Ticagrelor is the first reversibly binding oral P2Y12 receptor antagonist . This is the first study to compare the onset and offset of platelet inhibition ( IPA ) with ticagrelor using the PLATO ( PLATelet inhibition and patient Outcomes ) trial loading dose ( 180 mg ) with a high loading dose ( 600 mg ) of clopidogrel . Methods and Results — In a multicenter , r and omized , double-blind study , 123 patients with stable coronary artery disease who were taking aspirin therapy ( 75 to 100 mg/d ) received ticagrelor ( 180-mg load , 90-mg BID maintenance dose [ n=57 ] ) , clopidogrel ( 600-mg load , 75-mg/d maintenance dose [ n=54 ] ) , or placebo ( n=12 ) for 6 weeks . Greater IPA ( 20 & mgr;mol/L ADP , final extent ) occurred with ticagrelor than with clopidogrel at 0.5 , 1 , 2 , 4 , 8 , and 24 hours after loading and at 6 weeks ( P<0.0001 for all ) ; by 2 hours after loading , a greater proportion of patients achieved > 50 % IPA ( 98 % versus 31 % , P<0.0001 ) and > 70 % IPA ( 90 % versus 16 % , P<0.0001 ) in the ticagrelor group than in the clopidogrel group , respectively . A faster offset occurred with ticagrelor than with clopidogrel ( 4-to-72–hour slope [ % IPA/h ] −1.04 versus −0.48 , P<0.0001 ) . At 24 hours after the last dose , mean IPA was 58 % for ticagrelor versus 52 % for clopidogrel ( P = NS ) . IPA for ticagrelor on day 3 after the last dose was comparable to clopidogrel at day 5 ; IPA on day 5 for ticagrelor was similar to clopidogrel on day 7 and did not differ from placebo ( P = NS ) . Conclusions — Ticagrelor achieved more rapid and greater platelet inhibition than high-loading-dose clopidogrel ; this was sustained during the maintenance phase and was faster in offset after drug discontinuation . Clinical Trial Registration Information— URL : http://www . clinical trials.gov . Unique identifier : NCT00528411 BACKGROUND Clopidogrel and aspirin are widely used for patients with acute coronary syndromes and those undergoing percutaneous coronary intervention ( PCI ) . However , evidence -based guidelines for dosing have not been established for either agent . METHODS We r and omly assigned , in a 2-by-2 factorial design , 25,086 patients with an acute coronary syndrome who were referred for an invasive strategy to either double-dose clopidogrel ( a 600-mg loading dose on day 1 , followed by 150 mg daily for 6 days and 75 mg daily thereafter ) or st and ard-dose clopidogrel ( a 300-mg loading dose and 75 mg daily thereafter ) and either higher-dose aspirin ( 300 to 325 mg daily ) or lower-dose aspirin ( 75 to 100 mg daily ) . The primary outcome was cardiovascular death , myocardial infa rct ion , or stroke at 30 days . RESULTS The primary outcome occurred in 4.2 % of patients assigned to double-dose clopidogrel as compared with 4.4 % assigned to st and ard-dose clopidogrel ( hazard ratio , 0.94 ; 95 % confidence interval [ CI ] , 0.83 to 1.06 ; P=0.30 ) . Major bleeding occurred in 2.5 % of patients in the double-dose group and in 2.0 % in the st and ard-dose group ( hazard ratio , 1.24 ; 95 % CI , 1.05 to 1.46 ; P=0.01 ) . Double-dose clopidogrel was associated with a significant reduction in the secondary outcome of stent thrombosis among the 17,263 patients who underwent PCI ( 1.6 % vs. 2.3 % ; hazard ratio , 0.68 ; 95 % CI , 0.55 to 0.85 ; P=0.001 ) . There was no significant difference between higher-dose and lower-dose aspirin with respect to the primary outcome ( 4.2 % vs. 4.4 % ; hazard ratio , 0.97 ; 95 % CI , 0.86 to 1.09 ; P=0.61 ) or major bleeding ( 2.3 % vs. 2.3 % ; hazard ratio , 0.99 ; 95 % CI , 0.84 to 1.17 ; P=0.90 ) . CONCLUSIONS In patients with an acute coronary syndrome who were referred for an invasive strategy , there was no significant difference between a 7-day , double-dose clopidogrel regimen and the st and ard-dose regimen , or between higher-dose aspirin and lower-dose aspirin , with respect to the primary outcome of cardiovascular death , myocardial infa rct ion , or stroke . ( Funded by Sanofi-Aventis and Bristol-Myers Squibb ; Clinical Trials.gov number , NCT00335452 . BACKGROUND The effect of intensified platelet inhibition for patients with unstable angina or myocardial infa rct ion without ST-segment elevation who do not undergo revascularization has not been delineated . METHODS In this double-blind , r and omized trial , in a primary analysis involving 7243 patients under the age of 75 years receiving aspirin , we evaluated up to 30 months of treatment with prasugrel ( 10 mg daily ) versus clopidogrel ( 75 mg daily ) . In a secondary analysis involving 2083 patients 75 years of age or older , we evaluated 5 mg of prasugrel versus 75 mg of clopidogrel . RESULTS At a median follow-up of 17 months , the primary end point of death from cardiovascular causes , myocardial infa rct ion , or stroke among patients under the age of 75 years occurred in 13.9 % of the prasugrel group and 16.0 % of the clopidogrel group ( hazard ratio in the prasugrel group , 0.91 ; 95 % confidence interval [ CI ] , 0.79 to 1.05 ; P=0.21 ) . Similar results were observed in the overall population . The prespecified analysis of multiple recurrent ischemic events ( all components of the primary end point ) suggested a lower risk for prasugrel among patients under the age of 75 years ( hazard ratio , 0.85 ; 95 % CI , 0.72 to 1.00 ; P=0.04 ) . Rates of severe and intracranial bleeding were similar in the two groups in all age groups . There was no significant between-group difference in the frequency of nonhemorrhagic serious adverse events , except for a higher frequency of heart failure in the clopidogrel group . CONCLUSIONS Among patients with unstable angina or myocardial infa rct ion without ST-segment elevation , prasugrel did not significantly reduce the frequency of the primary end point , as compared with clopidogrel , and similar risks of bleeding were observed . ( Funded by Eli Lilly and Daiichi Sankyo ; TRILOGY ACS Clinical Trials.gov number , NCT00699998 . ) OBJECTIVES The study aim ed to compare the antiplatelet action of ticagrelor with prasugrel in acute coronary syndrome ( ACS ) patients with high on-treatment platelet reactivity ( HTPR ) while on clopidogrel after percutaneous coronary intervention ( PCI ) . BACKGROUND Newer P2Y12 inhibitors like prasugrel and ticagrelor provide stronger platelet inhibition compared with clopidogrel . Both agents are efficacious in patients with HTPR while on clopidogrel , but direct comparison between them has not yet been reported . METHODS In a prospect i ve , single-center , single-blind study , 44 ( of 139 screened , 31.7 % ) ACS patients with HTPR while on clopidogrel 24 h post-PCI were r and omized to either ticagrelor 90 mg twice daily or prasugrel 10 mg once daily for 15 days with a crossover directly to the alternate treatment for another 15 days . HTPR was defined as platelet reactivity units ( PRU ) ≥ 235 as assessed by the VerifyNow P2Y12 function assay . RESULTS The primary endpoint of platelet reactivity at the end of the 2 treatment periods was lower for ticagrelor ( 32.9 PRU , 95 % confidence interval [ CI ] : 18.7 to 47.2 ) compared with prasugrel ( 101.3 PRU , 95 % CI : 86.8 to 115.7 ) with a least squares mean difference of -68.3 PRU ( 95 % CI : -88.6 to -48.1 ; p < 0.001 ) . The secondary endpoint of HTPR rate was 0 % for ticagrelor and 2.4 % for prasugrel ( 1 of 42 , p = 0.5 ) . No patient exhibited a major bleeding event at either treatment group . CONCLUSIONS In patients with ACS exhibiting HTPR while on clopidogrel 24 h post-PCI , ticagrelor produces a significantly higher platelet inhibition compared with prasugrel . ( Ticagrelor Versus Prasugrel in Acute Coronary Syndromes After Percutaneous Coronary Intervention ; NCT01360437 ) |
12,289 | 30,197,947 | Conclusions The prevalence of amblyopia in Iran is very different . | Purpose The aim of this study was to determine the prevalence of amblyopia in the population of Iran . | Purpose : To determine the prevalence of amblyopia and refractive errors among 7 to 12-year-old primary school children in Tehran , Iran . Methods : This population -based cross-sectional study included 2,410 r and omly selected students . Visual acuity was tested using an E-chart on Yang vision tester . Refractive errors were measured by photorefractometry and cycloautorefraction . Strabismus was checked using cover test . Direct ophthalmoscopy was used to assess the anterior segment , lens opacities , red reflex and fundus . Functional amblyopia was defined as best corrected visual acuity ≤20/40 in one or both eyes with no anatomical problems . Results : Amblyopia was present in 2.3 % ( 95 % CI : 1.8 % to 2.9 % ) of participants with no difference between the genders . Amblyopic subjects were significantly younger than non-amblyopic children ( P=0.004 ) . Overall , 15.9 % of hyperopic and 5.9 % of myopic cases had amblyopia . The prevalence of hyperopia ≥+2.00D , myopia ≤-0.50D , astigmatism ≥0.75D , and anisometropia ( ≥1.00D ) was 3.5 % , 4.9 % , 22.6 % , and 3.9 % , respectively . With increasing age , the prevalence of myopia increased ( P<0.001 ) , that of hyperopia decreased ( P=0.007 ) , but astigmatism showed no change . Strabismus was found in 2.3 % of cases . Strabismus ( OR=17.9 ) and refractive errors , especially anisometropia ( OR=12.87 ) and hyperopia ( OR=11.87 ) , were important amblyogenic risk factors . Conclusion : The high prevalence of amblyopia in our subjects in comparison to developed countries reveals the necessity of timely and sensitive screening methods . Due to the high prevalence of amblyopia among children with refractive errors , particularly high hyperopia and anisometropia , provision of glasses should be specifically attended by parents and supported by the Ministry of Health and insurance organizations Purpose : Strabismus and anisometropia are the most common causes of amblyopia . It can be easily prevented or treated if detected early . With the changing socio-cultural-economic milieu of the society , the perspectives of strabismus in society are gradually changing but still adequate knowledge , awareness , and attitude of parents toward strabismus will help in preventing amblyopia and aid in the proper psychosocial adaptation of such children . This study aim ed to assess knowledge and attitude of parents toward children suffering from strabismus . Methods : A prospect i ve study was carried out from January 1 to February 29 , 2016 , through a structured question naire to assess the level of knowledge and attitude of parents of children suffering from strabismus . Results : One hundred and twenty parents of children with strabismus were interviewed through a question naire . Education level of 78 parents was less than graduation ( 60 % ) and of 42 parents ( 40 % ) was graduation or higher . The majority of the parents , i.e. , 116 ( 96.67 % ) were bothered due to strabismus . One hundred and one ( 84.17 % ) parents felt that their child 's strabismus was noticed by others during interaction . Seventy-four ( 61.67 % ) parents felt that their children will have difficulty in making friends . Ninety ( 75 % ) parents felt uncomfortable if someone asked something about their child 's strabismus . One hundred and ten ( 91.67 % ) parents considered strabismus as cosmetic stigma . Conclusion : Some parents , especially from the lower educated segment , had poor underst and ing of strabismus , thus result ing in late presentation and ineffective counter measures . The key to prevent strabismic amblyopia and its psychosocial impacts is to provide health education regarding strabismus PURPOSE To study the prevalence and causes of bilateral and unilateral blindness in an elderly urban Danish population . METHODS Data originated from a Danish epidemiologic cross-sectional r and om sample population eye survey conducted during the years 1986 - 1988 . The population consisted of 1,000 inhabitants aged 60 to 80 years in Copenhagen . The participants underwent an extensive ophthalmologic examination . A participation rate of 96.9 % was achieved . Any blindness was defined as best-corrected visual acuity ( VA ) worse than 0.05 ( the WHO criteria ) and VA of 0.1 or worse ( the National criteria ( NC ) of blindness ) . RESULTS The prevalence rates of bilateral and unilateral blindness were , respectively , 0.53 % and 3.38 % according to WHO , but 1.06 % and 4.44 % using NC . Bilateral blindness rose significantly with age ( p=0.02 ) . According to NC , age-related macular degeneration ( AMD ) was the leading cause of bilateral blindness , accounting for 60 % of all blind persons . Glaucoma , myopic macular degeneration , cataract and retinitis pigmentosa were jointly the second most common cause , each accounting for 10 % of all bilaterally blind persons . Diabetic retinopathy was not a cause of bilateral blindness . Amblyopia was the most frequent , AMD the second most frequent , and diabetic retinopathy was among the third most common cause of unilateral blindness accounting for , respectively , 28.60 % , 16.66 % and 9.52 % of all unilateral blindness . CONCLUSIONS Blindness was associated with increasing age . A calculation indicates that among Danes aged 60 to 80 years 7,736 are bilaterally blind and 35,503 suffer from unilateral blindness . This study highlights AMD as the most important cause OBJECTIVE To determine the prevalence of and factors associated with amblyopia in a rural Chinese population . DESIGN Population -based , cross-sectional study . PARTICIPANTS Six thous and eight hundred thirty Han Chinese aged 30 years or more , recruited from Yongnian County , H and an , Hebei Province , China . METHODS Thirteen villages in the Yongnian County of H and an were selected r and omly , and residents of these selected villages 30 years of age or older were invited to participate in the H and an Eye Study . Participants underwent a comprehensive eye examination , including st and ardized visual acuity ( VA ) tests using logarithm of the minimum angle of resolution charts . Prevalence rates were age- and gender-st and ardized to the 2000 China census . MAIN OUTCOME MEASURES The proportion of rural Chinese population aged 30 years or older with amblyopia . Unilateral amblyopia was diagnosed if best-corrected VA ( BCVA ) was 20/32 or worse in the amblyopic eye and was not attributable directly to any underlying structural abnormality of the eye or visual pathway . Bilateral amblyopia was diagnosed if BCVA was 20/32 or less in both eyes and if there was a history of form deprivation during the sensitive period of visual development , such as media opacities or high , uncorrected ametropia . RESULTS Amblyopia was diagnosed in 205 participants , with an age- and gender-adjusted prevalence of 2.8 % . Of these , 1.7 % were unilateral cases and 1.1 % were bilateral cases . Underlying causes included anisometropia ( 67.3 % ) , strabismus ( 5.4 % ) , mixed strabismus and anisometropia ( 4.4 % ) , visual deprivation ( 9.8 % ) , astigmatism association ( 9.8 % ) , and other ( 3.4 % ) . Of the amblyopia cases , 47.6 % were hypermetropic . CONCLUSIONS In this rural Chinese population , 2.8 % of adults 30 to 80 years of age had amblyopia , a prevalence rate broadly consistent with that of most other studies . One third of the cases were bilateral , and anisometropia was the most common cause of this condition 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 Objective : To estimate the distribution and predictors of some common visual problems ( strabismus , amblyopia , hypermetropia ) within a population -based cohort of children at the age of 7 years . Methods : Children participating in a birth cohort study were examined by orthoptists who carried out cover/uncover , alternate cover , visual acuity and non-cycloplegic refraction tests . Prospect ively collected data on potential risk factors were available from the study . Results : Data were available for 7825 seven-year-old children . 2.3 % ( 95 % CI 2.0 % to 2.7 % ) had manifest strabismus , 3.6 % ( 95 % CI 3.3 % to 4.1 % ) had past/present amblyopia , and 4.8 % ( 95 % CI 4.4 % to 5.3 % ) were hypermetropic . Children from the lowest occupational social class background were 1.82 ( 95 % CI 1.03 % to 3.23 % ) times more likely to be hypermetropic than children from the highest social class . Amblyopia ( p = 0.089 ) and convergent strabismus ( p = 0.066 ) also tended to increase as social class decreased . Conclusions : Although strabismus has decreased in the UK , it and amblyopia remain common problems . Children from less advantaged background s were more at risk of hypermetropia and to a lesser extent of amblyopia and convergent strabismus . Children ’s eye-care services may need to take account of this socio-economic gradient in prevalence to avoid inequity in access to care Purpose : To determine the prevalence of amblyopia , anisometropia , and strabismus in schoolchildren of Shiraz , Iran . Material s and Methods : A r and om cluster sampling was used in a cross-sectional study on schoolchildren in Shiraz . Cycloplegic refraction was performed in elementary and middle school children and high school students had non-cylcoplegic refraction . Uncorrected visual acuity ( UCVA ) and best corrected visual acuity ( BCVA ) were recorded for each participant . Anisometropia was defined as spherical equivalent ( SE ) refraction difference 1.00D or more between two eyes . Amblyopia was distinguished as a reduction of BCVA to 20/30 or less in one eye or 2-line interocular optotype acuity differences in the absence of pathological causes . Cover test was performed for investigating of strabismus . Results : Mean age of 2638 schoolchildren was 12.5 years ( response rate = 86.06 % ) . Prevalence of anisometropia was 2.31 % ( 95 % confidence interval [ CI ] , 1.45 to 3.16 ) . 2.29 % of schoolchildren ( 95 % CI , 1.46 to 3.14 ) were amblyopic . The prevalence of amblyopia in boys and girls was 2.32 % and 2.26 % , respectively ( p = 0.945 ) . Anisometropic amblyopia was found in 58.1 % of the amblyopic subjects . The strabismus prevalence was 2.02 % ( 95 % CI , 1.18 to 2.85 ) . The prevalence of exotropia and esotropia was 1.30 % and 0.59 % , respectively . Conclusions : Results of this study showed that the prevalence of anisometropia , amblyopia , and strabismus are in the mid range . The etiology of amblyopia was often refractive , mostly astigmatic , and non-strabismic . Exotropia prevalence increased with age and was the most common strabismus type ABSTRACT Purpose : To determine the prevalence of strabismus and amblyopia , and the distribution of the near point of convergence ( NPC ) , in a population of children aged 4 to 6 years . Methods : In this cross-sectional study , preschoolers in Mashhad were sample d using a r and om multistage cluster sampling approach . Examinations were done after obtaining parental consent . All participants had measurements of uncorrected visual acuity , corrected visual acuity , and non-cycloplegic refraction , and they had near and far cover tests to determine tropia and phoria . Results : Of the 3765 selected children , 3701 participated in the study . The prevalence of tropia was 1.21 % ( 95 % confidence interval [ CI ] : 0.86–1.57 ) . Near and near/far tropia was observed in 0.83 % ( 95 % CI : 0.53–1.12 ) and 0.39 % ( 95 % CI : 0.18–0.59 ) , respectively . Tropia was significantly more prevalent in boys ( P=0.005 ) . The most common type of tropia was esotropia , 0.22 % ( 95 % CI : 0.07–0.37 ) . Among participants , 63.92 % ( 95 % CI : 62.36–65.48 ) had phoria ; prevalence of far , near , and near/far phoria was 0.22 % ( 95 % CI : 0.07–0.37 ) , 60.47 % ( 95 % CI : 58.88–62.07 ) , and 3.22 % ( 95 % CI : 2.65–3.8 ) , respectively . Mean NPC was 5.1 cm ( 95 % CI : 5.05–5.14 ) . NPC increased by 0.08 cm per month of age ( P=0.033 ) and was 0.10 cm higher in boys compared to girls ( P=0.027 ) . Based on NPC , 61.58 % ( 95 % CI : 59.99–63.17 ) were symptomatic . The prevalence of amblyopia was 0.41 % ( 95 % CI : 0.20–0.61 ) . The type of amblyopia was anisometropic , strabismic , and isoametropic in 75 % , 11.1 % , and 8.5 % , respectively . Conclusion : The prevalence of amblyopia in this study population was not high ; however , the prevalence of tropia was average compared to previous studies in Iran . Describing NPC in a 4- to 6-year-old Iranian population for the first time , we found that NPC increased with age in this sample Abstract Purpose : To determine the prevalence of ptosis ( congenital/acquired ) in Iranian children aged 7 years and its relationship with amblyopia and strabismus . Methods : Eight Iranian cities were selected for this cross-sectional study using multistage r and omized cluster sampling . A number of primary schools were r and omly selected in each city . All grade 1 students in each selected primary school underwent optometric examinations including the measurement of uncorrected and corrected visual acuity , cover test , and cycloplegic and non-cycloplegic refraction . Results : Of 4614 selected students , 4106 students participated in the study ( response rate = 89 % ) . The prevalence of ptosis ( congenital/acquired ) was 1.41 % ( 95 % CI 1–1.83 ) ; 0.49 % ( 95 % CI 0.26–0.72 ) and 0.93 % ( 95 % CI 0.59–1.26 ) had unilateral and bilateral ptosis , respectively . The prevalence of ptosis had no significant correlation with sex ( p = 0.810 , OR = 1.07 , 95 % CI 0.59–1.97 ) . The prevalence of amblyopia was 48.28 % and 0.89 % in students with and without ptosis , respectively . The prevalence of tropia was significantly higher in cases with bilateral ptosis ( p < 0.001 ) . The mean cylinder error was 1.63 ± 1.72 and 0.44 ± 0.60 in ptotic and non-ptotic eyes , respectively ( p < 0.001 ) . With-the-rule ( WTR ) astigmatism was significantly more prevalent in students with ptosis . Conclusion : We report the prevalence of ptosis ( congenital/acquired ) in children in Iran and the Middle East region for the first time . Amblyopia was considerably more prevalent in ptotic patients . We found a significant correlation between ptosis and tropia . Astigmatism , especially WTR stigmatism , was more prevalent in children with ptosis Purpose . To determine the prevalence of amblyopia , strabismus , and refractive errors in children entering school . Methods . In this cross-sectional population -based study , 6-year-old children enrolling in Shahrood schools were r and omly sample d. Those with organic blindness or mental retardation were excluded . Ocular alignment , visual acuity , stereopsis , cover testing , and cycloplegic refraction were recorded for all children by an optometrist . A diagnosis of amblyopia was based on a best-corrected visual acuity of 6/12 or less in one or both eyes , or a bilateral difference of at least two best-corrected visual acuity lines . Results . A total of 902 children were invited for optometry examinations , among which 827 ( 91.7 % ) responded and 815 children ( 98.5 % ) were included in the study . The prevalence of significantly reduced visual acuity ( uncorrected VA ≤6/12 in either eye ) and amblyopia was 3.6 and 1.7 % , respectively . The prevalence of hyperopia ( + 2.00 D or worse ) , myopia ( −0.50 D or worse ) , astigmatism ( 0.75 D or worse ) , and anisometropia ( 1.00 D or more ) were 20.5 , 1.7 , 19.6 , and 2.2 % , respectively . Significant refractive error , defined as hyperopia > + 3.50 D , myopia > −3.00 D , astigmatism > 1.50 D in the orthogonal meridian or > 1.00 D in the oblique meridian , or anisometropia ( hyperopic > 1.00 D , myopic > 3.00 D ) was detected in 2.1 , 0.1 , 5.0 , and 0.9 % of the sample , respectively . Strabismus was diagnosed in 1.2 % of children . Overall , 52 children ( 6.4 % ; 95 % confidence interval [ CI ] , 4.7–8.1 % ) were at risk of amblyopia ; of these , 81 % had significant refractive errors , 11 % had strabismus , and 8 % had both . Conclusion . A considerable proportion of 6-year-old children have strabismus and /or significant , potentially amblyogenic refractive errors . The relatively high rate of hyperopia and astigmatism in the studied population needs more attention . The results of the study emphasize the need for adequate diagnostic and therapeutic eye care services for preschool children |
12,290 | 30,620,051 | For mf density there is no trend , with some trials reporting a greater reduction in mf density with albendazole and others a greater reduction with the control group .
This finding is consistent in trials evaluating albendazole alone , or added to DEC or ivermectin .
The review raises questions over whether albendazole has any important contribution to the elimination of lymphatic filariasis . | Background The Global Programme to Eliminate Lymphatic Filariasis recommends mass treatment of albendazole co‐administered with the microfilaricidal ( antifilarial ) drugs diethylcarbamazine ( DEC ) or ivermectin ; and recommends albendazole alone in areas where loiasis is endemic .
Objectives To assess the effects of albendazole alone , and the effects of adding albendazole to DEC or ivermectin , in people and communities with lymphatic filariasis . | Filariasis control programmes are moving towards a strategy of repeated single-dose mass treatment of endemic population s. Using a combination , such as albendazole ( ALB ) to diethylcarbamazine ( DEC ) gives both macrofilaricidal and anti-helmintic activity . However , the safety of the combination versus DEC alone should be established in field studies in large population s prior to incorporation into national programmes . The present study compared the safety , tolerability , and efficacy of single doses of DEC 6 mg/kg + ALB placebo with DEC 6 mg/kg + ALB 400 mg in population s living in two filariasis endemic villages in the district of Wardha in western India . The study was double blind , parallel group , and r and omized . Safety and tolerability study were studied in males and females older than 5 years . Safety was assessed by monitoring if adverse events ( AEs ) over 5 days affected daily acivities . Subjects in the 2 treatment groups experienced insignificantly different effects on daily activities and the combination was shown to be safe . Efficacy was evaluated by microfilaraemia ( Mf ) , immunochromatographic test ( ICT ) and ultrasonography ( USG ) at 0 , 3 , 6 , and 12 months of follow up . The efficacy study enrolled 103 male patients ( aged 18 - 50 years ) in microfilariae positive , clinical disease and asymptomatic , amicrofilaremic groups . There was no significant difference in efficacy between groups at 12 months . Within the Mf positive group , significant differences were seen in microfilaraemia ( P < 0.001 ) with both treatments , and in USG ( P < 0.001 and P < 0.004 respectively ) , at 12 months . The present field study has shown the combination of DEC + ALB to be as safe as the single drug DEC and thus the combination can be put in use in the national filariasis control programmes . Both drugs were adequately absorbed . The study at present does not provide evidence for the greater efficacy of the combination at 12 months follow up . While the safety of the combination has been ascertained , the incorporation or otherwise of ALB into national programmes for greater efficacy must await results of studies with longer follow up 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 r and omized , placebo-controlled trial investigated the efficacy and nutritional benefit of combining chemotherapeutic treatment for intestinal helminths ( albendazole ) and lymphatic filariasis ( ivermectin ) . Children were infected with Ascaris ( 29.2 % ) , Trichuris ( 42.2 % ) , and hookworm ( 6.9 % ) , with 54.7 % of children having one or more of these parasites . Wuchereria bancrofti microfilaria were found in 13.3 % of the children . Children were r and omly assigned to treatment with placebo , albendazole , ivermectin , or combined therapy . Combination treatment reduced the prevalence of Trichuris infections significantly more than either drug alone . Combination therapy also significantly reduced the prevalence and density of W. bancrofti microfilaremia compared with placebo or ivermectin alone . Only combination therapy result ed in significantly greater gains in height ( hookworm-infected children ) or weight ( Trichuris-infected children ) compared with the placebo group . Combined albendazole and ivermectin was a more efficacious treatment for intestinal helminth and W. bancrofti infections in children and result ed in nutritional benefits not found with either drug alone Although current programmes to eliminate lymphatic filariasis have made significant progress it may be necessary to use different approaches to achieve the global goal , especially where compliance has been poor and ‘ hot spots ’ of continued infection exist . In the absence of alternative drugs , the use of higher or more frequent dosing with the existing drugs needs to be explored . We examined the effect of higher and /or more frequent dosing with albendazole with a fixed 300 mg dose of diethylcarbamazine in a Wuchereria bancrofti endemic area in Odisha , India . Following screening , 104 consenting adults were r and omly assigned to treatment with the st and ard regimen annually for 24 months ( S1 ) , or annually with increased dose ( 800 mg albendazole)(H1 ) or with increased frequency ( 6 monthly ) with either st and ard ( S2 ) or increased ( H2 ) dose . Pre-treatment microfilaria counts ( GM ) ranged from 348 to 459 mf/ml . Subjects were followed using microfilaria counts , OG4C3 antigen levels and ultrasound scanning for adult worm nests . Microfilarial counts tended to decrease more rapidly with higher or more frequent dosing at all time points . At 12 months , Mf clearance was marginally greater with the high dose regimens , while by 24 months , there was a trend to higher Mf clearance in the arm with increased frequency and 800 mg of albendazole ( 76.9 % ) compared to other arms , ( S1:64 % , S2:69.2 % & H1:73.1 % ) . Although higher and /or more frequent dosing showed a trend towards a greater decline in antigenemia and clearance of “ nests ” , all regimens demonstrated the potential macrofilaricidal effect of the combination . The higher doses of albendazole did not result in a greater number or more severe side effects . The alternative regimens could be useful in the later stages of existing elimination programmes or achieving elimination more rapidly in areas where programmes have yet to start Background Chronic parasitic infections are associated with active immunomodulation which may include by-st and er effects on unrelated antigens . It has been suggested that pre-natal exposure to parasitic infections in the mother impacts immunological development in the fetus and hence the offspring ’s response to vaccines , and that control of parasitic infection among pregnant women will therefore be beneficial . Methodology /Principal findings We used new data from the Entebbe Mother and Baby Study , a trial of anthelminthic treatment during pregnancy conducted in Ug and a , to further investigate this hypothesis . 2705 mothers were investigated for parasitic infections and then r and omised to albendazole ( 400 mg ) versus placebo and praziquantel ( 40mg/kg ) during pregnancy in a factorial design . All mothers received sulfadoxine/pyrimethamine for presumptive treatment of malaria . Offspring received Exp and ed Programme on Immunisation vaccines at birth , six , 10 and 14 weeks . New data on antibody levels to diphtheria toxin , three pertussis antigens , Haemophilus influenzae type B ( HiB ) and Hepatitis B , measured at one year ( April 2004 –May 2007 ) from 1379 infants were analysed for this report . Additional observational analyses relating maternal infections to infant vaccine responses were also conducted . Helminth infections were highly prevalent amongst mothers ( hookworm 43.1 % , Mansonella 20.9 % , Schistosoma mansoni 17.3 % , Strongyloides 11.7 % , Trichuris 8.1 % ) and 9.4 % had malaria at enrolment . In the trial analysis we found no overall effect of either anthelminthic intervention on the measured infant vaccine responses . In observational analyses , no species was associated with suppressed responses . Strongyloidiasis was associated with enhanced responses to pertussis toxin , HiB and Hep B vaccine antigens . Conclusions / Significance Our results do not support the hypothesis that routine anthelminthic treatment during pregnancy has a benefit for the infant ’s vaccine response , or that maternal helminth infection has a net suppressive effect on the offspring ’s response to vaccines . Trial Registration IS RCT N.com IS RCT The efficacy of two strategies for control of Bancroftian filariasis using selective rather than community-wide diethylcarbamazine ( DEC ) chemotherapy was evaluated and compared in two endemic communities of north-eastern Tanzania , with pretreatment microfilariae ( mf ) prevalences of 22 % and 38 % , and geometric mean intensities ( GMIs ) of 668 mf/ml and 735 mf/ml of blood . All mf-positive cases in the first community were offered treatment with 6 mg of DEC/kg of body weight a day for 12 days ( group 1 ) , and those in the second community were offered treatment with two doses of 6 mg of DEC/kg of body weight at an interval of six months ( group 2 ) . The effect of treatment was followed both among those treated and at the community level . In treated individuals , there was a rapid decrease in the mf load that was significantly greater among those receiving the 12-day st and ard dose . One year after the start of treatment , the mf clearance rates were 59 % and 39 % and the GMIs were reduced by 99 % and 97 % among treated individuals in groups 1 and 2 , respectively . However , at the community level , the mf prevalences were 16.3 % and 27.9 % ( reduced by 27 % and 26 % ) and the GMIs were 129 mf/ml and 224 mf/ml ( reduced by 81 % and 70 % ) one year after the start of treatment with the two regimens , respectively , suggesting that transmission continued at a significant level in the villages after treatment . The limitations of selective chemotherapy are discussed , and it is argued that strategies based on mass DEC chemotherapy would be more effective in reducing the microfilarial load in the community and thereby in reducing transmission Forty male Polynesian W. bancrofti carriers with mf counts greater than or equal to 20/ml were treated with a single ivermectin 50 , 100 , 150 or 200 mcg/kg dose . Following therapy , mf levels fell to less than 1 % of pretreatment levels in the carriers treated with the 3 highest doses . After one month , negativation rate was 40 % in patients treated with a 50 mcg/kg dose , significantly lower than in patients treated with higher doses . Recurrence of microfilaremia was observed by 3 months , mf recurrence percentages were significantly lower in patients treated with the 3 highest doses than in patients treated with a 50 mcg/kg dose . At 6 months , mf recurrence percentages reached 49.8 , 12.6 , 14 and 5.4 % of pretreatment levels in carriers treated with 50 , 100 , 150 and 200 mcg/kg , respectively . No significant difference was observed between mf levels by group at 6 and 12 months . With respect to efficacy , a dose greater than or equal to 100 mcg/kg appeared superior to 50 mcg/kg dose ; no significant difference between the 3 highest doses was observed . Some patients developed headache , myalgia and fever within 24 hours following therapy , none of adverse reactions were considered serious . In vector Ae . polynesiensis fed on carriers 6 months after treatment , average numbers of mf ingested and average numbers of L3 cephalic larvae were lower than those observed in mosquitoes fed on non-treated carriers with comparable mf counts . ( ABSTRACT TRUNCATED AT 250 WORDS Integrated chemotherapy of neglected tropical diseases ( NTD ) through mass drug administration given as a single dose would increase treatment coverage and cost-effectiveness . This study reports on the safety of a combination of albendazole , ivermectin and praziquantel in the treatment of lymphatic filariasis ( LF ) , schistosomiasis and soil-transmitted helminthiasis ( STH ) in infected children . In this r and omised , controlled , single-blinded clinical trial conducted in 235 primary school children aged 5 - 18 years in Yumbe District in Northern Ug and a , the triple combination therapy was compared with the current NTD programme regimen . Liver function testing was performed for all children who received combined therapy . The study included 48 children with LF alone , 60 children with schistosomiasis ( Schistosoma mansoni ) , 41 children with STH , 49 children with schistosomiasis + LF and 37 children with all three types of infection . Children were closely monitored by a paediatrician for any adverse reactions for 7 days . No serious adverse events were experienced . However , 4 of 18 children in the test group and 2 of 3 children in the control group who did not report any ill conditions before treatment developed adverse drug reactions . The combined and conventional therapies were found to be equally safe . The efficacies of both therapies were comparable and satisfactory . [ Clinical Trials.gov identifier : NCT01050517 ] Background Once interruption of transmission of lymphatic filariasis is achieved , morbidity prevention and management becomes more important . A study in Brugia malayi filariasis from India has shown sub- clinical lymphatic pathology with potential reversibility . We studied a Wuchereria bancrofti infected population , the major contributor to LF globally . Methods Children aged 5–18 years from Odisha , India were screened for W. bancrofti infection and disease . 102 infected children , 50 with filarial disease and 52 without symptoms were investigated by lymphoscintigraphy and then r and omized to receive a supervised single oral dose of DEC and albendazole which was repeated either annually or semi-annually . The lymphatic pathology was evaluated six monthly for two years . Findings Baseline lymphoscintigraphy showed abnormality in lower limb lymphatics in 80 % of symptomatic ( 40/50 ) and 63·5 % ( 33/52 ) of asymptomatic children . Progressive improvement in baseline pathology was seen in 70·8 , 87·3 , 98·6 , and 98·6 % of cases at 6 , 12 , 18 , and 24 months follow up , while in 4·2 , 22·5 , 47·9 and 64·8 % , pathology reverted to normal . This was independent of age ( p = 0·27 ) , symptomatic status ( p = 0·57 ) and semi-annual/bi-annual dosing ( p = 0·46 ) . Six of eleven cases showed clinical reduction in lymphedema of legs . Interpretation A significant proportion of a young W. bancrofti infected population exhibited lymphatic pathology which was reversible with annual dosage of DEC and albendazole . This provides evidence for morbidity prevention & treatment of early lymphedema . It can also be used as a tool to improve community compliance during mass drug administration . Trial registration Clinical Trials.gov No In a ' blinded ' trial ( in Sri Lanka , 1996 - 98 ) of 47 male asymptomatic microfilaraemic subjects with Wuchereria bancrofti infection , the safety , tolerability and filaricidal efficacy of 3 single-dose combination regimens were compared : albendazole 400 mg with ivermectin 200 micrograms/kg , albendazole 400 mg with diethylcarbamazine citrate ( DEC ) 6 mg/kg or albendazole 600 mg with ivermectin 400 micrograms/kg . Treated subjects were followed-up for 24 months . This represents the first long-term study using combinations of albendazole with DEC or ivermectin in the above doses against bancroftian filariasis . All subjects had pre-treatment microfilaria ( mf ) counts over 100/mL. All 3 treatments significantly reduced mf counts , with the albendazole-DEC-treated group showing the lowest mf levels at 18 and 24 months post-treatment . Filarial antigen tests suggested that all 3 treatments had significant activity against adult W. bancrofti ; albendazole-DEC combination had the greatest activity according to this test , with antigen levels decreasing to 30.5 % of pre-treatment antigen levels , 24 months after therapy . All 3 treatments were clinical ly safe and well tolerated . These results suggest that a single dose of albendazole 400 mg together with DEC 6 mg/kg is a safe and effective combination for suppression of microfilaraemia of bancroftian filariasis that could be considered for use in filariasis control programmes based on mass treatment of endemic population This r and omized , placebo-controlled trial investigated the tolerance , efficacy , and nutritional benefit of combining chemotherapeutic treatment of intestinal helminths and lymphatic filariasis . Children were infected with Ascaris ( 30.7 % ) , Trichuris ( 53.4 % ) , and hookworm ( 9.7 % ) with 69.9 % having more than one of these parasites . A total of 15.8 % of the children had Wuchereria bancrofti microfilariae . Children were r and omly assigned treatment with placebo , albendazole ( ALB ) , diethylcarbamazine ( DEC ) , or combined therapy . The combination of DEC/ALB reduced microfilarial density compared with placebo , ALB , or DEC ( P < or = 0.03 ) . Albendazole and DEC/ALB reduced the prevalence of Ascaris , Trichuris , and hookworm more than placebo or DEC ( P < or = 0.03 ) . Among Trichuris-infected children , those receiving ALB and DEC/ALB demonstrated greater gains in weight compared with placebo ( P < or = 0.05 ) . Albendazole and DEC/ALB were equally efficacious in treating intestinal helminths and for children with W. bancrofti microfilaremia , DEC/ALB was more effective than DEC , with no increase in severity of adverse reactions BACKGROUND Wolbachia endosymbionts of filarial nematodes are vital for larval development and adult-worm fertility and viability . This essential dependency on the bacterium for survival of the parasites has provided a new approach to treat filariasis with antibiotics . We used this strategy to investigate the effects of doxycycline treatment on the major cause of lymphatic filariasis , Wuchereria bancrofti . METHODS We undertook a double-blind , r and omised , placebo-controlled field trial of doxycycline ( 200 mg per day ) for 8 weeks in 72 individuals infected with W bancrofti from Kimang'a village , Pangani , Tanzania . Participants were r and omly assigned by block r and omisation to receive capsules of doxycycline ( n=34 ) or placebo ( n=38 ) . We assessed treatment efficacy by monitoring microfilaraemia , antigenaemia , and ultrasound detection of adult worms . Follow-up assessment s were done at 5 , 8 , 11 , and 14 months after the start of treatment . Analysis was per protocol . FINDINGS One person from the doxycycline group died from HIV infection . Five ( doxycycline ) and 11 ( placebo ) individuals were absent at the time of ultrasound analysis . Doxycycline treatment almost completely eliminated microfilaraemia at 8 - 14 months ' follow-up ( for all timepoints p<0.001 ) . Ultrasonography detected adult worms in only six ( 22 % ) of 27 individuals treated with doxycycline compared with 24 ( 88 % ) of 27 with placebo at 14 months after the start of treatment ( p<0.0001 ) . At the same timepoint , filarial antigenaemia in the doxycycline group fell to about half of that before treatment ( p=0.015 ) . Adverse events were few and mild . INTERPRETATION An 8-week course of doxycycline is a safe and well-tolerated treatment for lymphatic filariasis with significant activity against adult worms and microfilaraemia Several new chemotherapeutic tools are now available for the control of lymphatic filariasis . Combinations of single doses of antifilarial drugs are generally superior to single drugs . The efficacy and safety of albendazole in combination with diethylcarbamazine ( DEC ) or ivermectin , for the treatment of Brugia malayi infection , were investigated , for the first time , in an open , hospital-based study . Fifty-one asymptomatic microfilaraemics ( with 108 - 4034 microfilariae/ml ; median = 531 ) of both sexes and aged 14 - 70 years were r and omly allocated to receive single-dose treatments of ivermectin ( 200 micrograms/kg ) with diethylcarbamazine ( DEC ; 6 mg/kg ) , ivermectin ( 200 micrograms/kg ) with albendazole ( 400 mg ) , DEC ( 6 mg/kg ) with albendazole ( 400 mg ) , or albendazole ( 400 mg ) alone . Albendazole alone had no effect on the microfilarial levels at the 1-year follow-up but both groups given DEC had significantly lower microfilaraemias ( P < 0.015 and P < 0.02 ) than that given ivermectin with albendazole . Overall , 47%-64 % of those given DEC but only 14 % of those given ivermectin with albendazole appeared to be amicrofilaraemic 1 year post-treatment . The adverse reactions seen in the study were mild , transient and qualitatively similar to those seen earlier with ivermectin and DEC . The combination of DEC and albendazole , both well tested drugs , offers a new option for countries such as India where there is no onchocerciasis or loiasis and where ivermectin may not be immediately available . The direct and indirect effects of albendazole on intestinal helminths would be additional benefits BACKGROUND In Africa , albendazole and ivermectin are currently used in combination for annual mass drug administration ( MDA ) for lymphatic filariasis ( LF ) elimination . Rapid and sustained clearance is desirable for public health impact and elimination of LF . Increasing the dose and /or frequency of albendazole and ivermectin treatment may be more effective in clearing microfilariae than st and ard MDA . METHODS We conducted a r and omised controlled open label trial in northern Malawi comparing three modified treatment groups to st and ard dosage of ivermectin and albendazole in adults with confirmed circulating LF antigen and microfilaria . Participants were followed-up every 6 months for 2 years for repeat microfilarial counts and safety assessment s. RESULTS A total of 1851 adults were screened and 70 with microfilarial counts > 80 microfilariae/ml were r and omised . All treatment groups achieved a significant reduction of microfilariae levels by 12- and 24-months of follow-up . Doubling the st and ard dose and administering it twice yearly showed a non-significant tendency towards faster and more complete clearance . There were no serious adverse reactions . CONCLUSIONS In this small study , all regimens effectively cleared microfilaria . St and ard treatment may be adequate in setting s like Malawi but not in all endemic setting s and larger studies are required to demonstrate benefit of higher dosages . [ Clinical Trials.gov identifier : NCT01213576 ] The efficacy of re-treatment with the combination of ivermectin ( 150 - 200 micrograms/kg bodyweight ) and albendazole ( 400 mg ) on Wuchereria bancrofti microfilaraemia was assessed in 1997 - 99 in 4 groups of individuals from coastal Ghana , which 1 year previously had received a primary treatment with placebo ( n = 38 ) , albendazole ( n = 39 ) , ivermectin ( n = 34 ) or combination of albendazole and ivermectin ( n = 42 ) , respectively . One year after the re-treatment , an overall mean reduction in microfilarial intensity of 76.2 % in relation to the intensity before re-treatment was observed , with no statistical significant difference between the 4 groups . The groups given primary treatment with placebo or the drug combination showed re-treatment reductions which were lower ( 72.5 % and 69.8 % , respectively ) but not statistically significantly different from the reduction observed 1 year after the primary treatment with the combination ( 86.7 % ) . The efficacy of the combination treatment thus appeared to be largely independent of the type of primary treatment given and multiplicative when used repeatedly To assess the efficacy of diethylcarbamazine ( DEC ) in clearing Wuchereria bancrofti microfilariae ( mf ) from the circulation , we conducted a single blind hospital-based therapeutic trial of 3 DEC regimens . All patients were assessed by filtration of 1 mL of venous blood taken before and 1 , 3 , 6 and 12 months after DEC administration . The efficacy of a 12 d course of 6 mg/kg DEC once daily was identical to that of a similar course with 2 mg/kg given 3 times daily , indicating that split-dose treatment does not improve mf clearance over single daily drug administration . Microfilarial densities in patients treated only once with 6 mg/kg DEC remained significantly higher at 1 , 3 , and 6 months after treatment . However , all 3 treatment regimens proved equally effective in controlling microfilaraemia after 12 months , when 41 , 42 and 40 % of patients in the 3 treatment groups were amicrofilaraemic . These results suggest that a single DEC dose of 6 mg/kg administered annually or biannually may be a suitable regimen to control bancroftian filariasis in Recife , Brazil BACKGROUND Available treatments for lymphatic filariasis ( LF ) are limited in their longterm clearance of microfilaria from the blood . The safety and efficacy of a single-dose triple-drug therapy of the antifilarial drugs diethylcarbamazine ( DEC ) , ivermectin ( IVM ) , and albendazole ( ALB ) for LF are unknown . METHODS We performed a pilot study to test the efficacy , safety , and pharmacokinetics of single-dose DEC , IVM , and ALB in Wuchereria bancrofti-infected Papua New Guineans . Adults were r and omized into 2 treatment arms , DEC 6 mg/kg + ALB 400 mg ( N = 12 ) or DEC 6 mg/kg + ALB 400 mg + IVM 200 μg/kg ( N = 12 ) , and monitored for microfilaria , parasite antigenemia , adverse events ( AEs ) , and serum drug levels . RESULTS Triple-drug therapy induced > 2-log reductions in microfilaria levels at 36 and 168 hours after treatment compared with approximately 1-log reduction with 2 drugs . All 12 individuals who received 3 drugs were microfilaria negative 1 year after treatment , whereas 11 of 12 individuals in the 2-drug regimen were microfilaria positive . In 6 participants followed 2 years after treatment , those who received 3 drugs remained microfilaria negative . AEs , particularly fever , myalgias , pruritus , and proteinuria/hematuria , occurred in 83 % vs 50 % of those receiving triple-drug compared to 2-drug treatment respectively ( P = .021 ) ; all resolved within 7 days after treatment . No serious AEs were observed in either group . There was no significant effect of IVM on DEC or ALB drug levels . CONCLUSIONS Triple-drug therapy is safe and more effective than DEC + ALB for Bancroftian filariasis and has the potential to accelerate elimination of lymphatic filariasis . CLINICAL TRIALS REGISTRATION NCT01975441 BACKGROUND Annual mass treatment with albendazole and ivermectin is the mainstay of current strategies to interrupt transmission of Wuchereria bancrofti in Africa . More-effective microfilarial suppression could potentially reduce the time necessary to interrupt transmission , easing the economic burden of mass treatment programs in countries with limited re sources . METHODS To determine the effect of increased dose and frequency of albendazole-ivermectin treatment on microfilarial clearance , 51 W. bancrofti microfilaremic residents of an area of W. bancrofti endemicity in Mali were r and omized to receive 2 doses of annual , st and ard-dose albendazole-ivermectin therapy ( 400 mg and 150 μg/kg ; n = 26 ) or 4 doses of twice-yearly , increased-dose albendazole-ivermectin therapy ( 800 mg and 400 μg/kg ; n = 25 ) . RESULTS Although microfilarial levels decreased significantly after therapy in both groups , levels were significantly lower in the high-dose , twice-yearly group at 12 , 18 , and 24 months . Furthermore , there was complete clearance of detectable microfilariae at 12 months in the 19 patients in the twice-yearly therapy group with data available at 12 months , compared with 9 of 21 patients in the annual therapy group ( P < .001 , by Fisher 's exact test ) . This difference between the 2 groups was sustained at 18 and 24 months , with no detectable microfilariae in the patients receiving twice-yearly treatment . Worm nests detectable by ultrasonography and W. bancrofti circulating antigen levels , as measured by enzyme-linked immunosorbent assay , were decreased to the same degree in both groups at 24 months , compared with baseline . CONCLUSIONS These findings suggest that increasing the dosage and frequency of albendazole-ivermectin treatment enhances suppression of microfilariae but that this effect may not be attributable to improved adulticidal activity The effect of single-dose ivermectin ( 150 - 200 micrograms/kg ) and albendazole ( 400 mg ) treatment alone and in combination on Wuchereria bancrofti microfilaraemia , antigenaemia and clinical manifestations was compared 12 months after treatment in a double-blind placebo-controlled field trial carried out in Ghana in 1996 - 98 , to evaluate the potential of these treatments for control . Both ivermectin and combination treatments result ed in pronounced reductions in microfilaraemia among individuals who were microfilaria positive before treatment . Among individuals who were positive for circulating filarial antigen before treatment , antigen levels increased considerably over the 1-year period after treatment in the placebo group , whereas they decreased in the ivermectin and combination groups . However , the post-treatment difference reached statistical significance in neither microfilaraemia nor antigenaemia between the ivermectin and the combination groups . Albendazole treatment alone showed only a minor effect on microfilaraemia and antigenaemia . No effect of the treatments on the incidence of new cases of microfilaraemia or antigenaemia , or on clinical manifestations , was observed . Both ivermectin and combination treatment thus appeared effective for control of W. bancrofti infections , but the difference in efficacy between the 2 treatments after 12 months appeared to be minimal OBJECTIVES To evaluate the effect of multiple rounds of annual single dose of DEC ( 6 mg/kg ) or albendazole ( 400 mg ) given alone or in combination on Wuchereria bancrofti microfilaraemia , anti-filarial IgG1 and IgG4 and antigenaemia . METHODS A total of 170 participants were r and omly assigned to albendazole ( n = 62 ) , DEC ( n = 54 ) , and DEC plus albendazole ( DEC/ALB ) combination ( n = 54 ) . Blood sample s were collected at pre-treatment in 1998 , at 1 week and 6 months after the first treatment and thereafter before subsequent treatments in 1999 and 2000 . Effects of treatment on W. bancrofti infection were determined by changes in levels of microfilaraemia , antifilarial antibodies and circulating filarial antigen . RESULTS Comparison of geometric mean microfilariae intensities between DEC/ALB combination and DEC or albendazole single therapy groups after two rounds of annual treatment and 24 months follow-up showed that combination therapy result ed in a greater reduction of microfilaraemia than single therapy with either albendazole ( p < 0.001 ) or DEC alone ( p = 0.146 ) . The overall levels of anti-filarial antibodies decreased significantly ( p = 0.028 for IgG1 and p < 0.043 for IgG4 ) in all treatment groups at 24 months follow-up . Additionally , overall reduction in geometric mean circulating filarial antigen levels at 24 months was 44 % , 60 % and 85 % for albendazole , DEC and DEC/ALB groups , respectively . CONCLUSIONS These study findings suggest that albendazole improved efficacy of DEC and mass administration of a combination of the two drugs would therefore enhance the interruption of transmission of W. bancrofti in endemic areas . This information has important implication s for the ongoing Global Program for Elimination of Lymphatic Filariasis BACKGROUND Lymphatic filariasis is a major vector-borne parasitic disease . The global programme to eliminate lymphatic filariasis was launched in 1997 and currently over 570 million people are covered under it in 48 countries . Mass annual single-dose drug administration of diethylcarbamazine ( DEC ) , co-administrated with albendazole for 5 - 6 years and mass distribution of diethylcarbamazine-fortified salt are the two strategies for elimination of filariasis . METHODS Asymptomatic volunteers residing in Puducherry , India were screened for microfilaria ( mf ) by examining nocturnal thick blood smears . Those testing positive were r and omly assigned to receive a single dose of DEC ( 6 mg/kg body weight ) or albendazole 400 mg or both . Participants were hospitalized for 5 days . Membrane filtration count was used to assess microfilaraemia and ELISA ( Og4C3 ) assay to measure circulating filarial antigens ( CFA ) . Measurements were done before treatment and at 1 , 2 and 3 years post-treatment . Viability of the adult worms was assessed by looking for the filarial dance sign ( FDS ) using ultrasound examination of the scrotum in men with hydrocele . RESULTS Fifty-four microfilaraemic Individuals were studied . The mf prevalence started decreasing only by day 180 posttreatment in the DEC group but much earlier in the other two groups ( day 30 in the albendazole and day 90 in the DEC with albendazole group ) . The decrease in mfwas marginal ( 17.6 % , 26.3 % and 27.8 % , respectively ) by the end of year 1 posttreatment , but significant ( 96.7 % , 78.6 % and 93.3 % , respectively ) by the end of year 2 post-treatment ( p < 0.05 ) . By the end of year 3 , the level decreased to 80 % in the DEC , 90 % in the albendazole and to 100 % in the DEC and albendazole groups . However , the mf intensity decreased significantly ( by 39 % ; p < 0.05 ) by day 7 post-treatment in both the DEC and DEC with albendazole groups , but only by day 30 in the albendazole group . In all the drug groups , the prevalence as well as intensity of CFA returned to pretreatment levels by the end of year 3 post-treatment . CONCLUSION Annual single-dose administration of all the 3 drug regimens significantly reduced antigenaemia levels . There were no significant differences in the efficacy and overall pattern of CFA clearance between the 3 drug regimens Abstract In filariasis-endemic areas beyond sub-Saharan Africa , the World Health Organization 's recommended strategy for interrupting transmission of the causative parasites is annual , single-dose , mass treatment with a combination of diethylcarbamazine ( DEC ; given at 6 mg/kg ) and albendazole ( ALB ; given at 400 mg ) for 4–6 years ( the minimum estimated life-span of the adult parasites ) . In an open , hospital-based , r and omized and controlled trial , with a blinded evaluation of outcome , 82 children and adolescents from Recife , all with Wuchereria bancrofti microfilaraemias , were given either DEC alone ( 6 mg/kg ) or the same dose of DEC combined with ALB ( at 400 mg/patient ) . Every 90 days for 1 year after the single treatment , each patient was checked for microfilaraemia by the filtration of up to 5 ml of venous blood collected at night . One year post-treatment , 16 ( 39 % ) of the 41 patients given DEC alone and 20 ( 49 % ) of the 41 given DEC – ALB were found microfilaraemic ( relative risk=0.8 , with a 95 % confidence interval of 0.49–1.31 ) and the corresponding geometric mean levels of microfilaraemia were 2.0 % and 1.8 % of the levels recorded immediately pre-treatment , respectively ( P>0.05 ) . In terms of the prevalences and intensities of microfilaraemia , therefore , the addition of ALB to the DEC appeared to offer no significant benefit Abstract The pharmacokinetics , safety and tolerability of single , oral doses of diethylcarbamazine ( DEC ) and albendazole , given alone or in combination , were investigated in a double-blind , r and omized and placebo-controlled trial involving 42 amicrofilaraemic subjects living in an area of India where lymphatic filariasis is endemic . The subjects ( 34 males and eight females , aged 18 - 52 years and weighing 46 - 66.5 kg ) were r and omly allocated to one of the three drug groups . Fourteen were given just DEC ( 6 mg/kg ) , another 14 were given just albendazole ( 400 mg ) and the remaining 14 were given both DEC ( 6 mg/kg ) and albendazole ( 400 mg ) . Blood sample s for pharmacokinetic study were collected at specified intervals before and after drug administration . Plasma concentrations of DEC and albendazole/albendazole sulphoxide were estimated using gas chromatography and HPLC , respectively . The safety and tolerability of the treatments were evaluated through clinical and laboratory assessment s. Both the DEC and albendazole were well tolerated when given alone or in combination , no adverse events being observed . In all three treatment groups , the drugs were rapidly absorbed from the gastro-intestinal tract although there was marked inter-individual variation . The pharmacokinetics of DEC , albendazole and albendazole sulphoxide were similar , whether each drug was given alone or in combination . These results indicate that there is no adverse pharmacokinetic or pharmacodynamic reason why DEC and albendazole should not be co-administered to control lymphatic filariasis Till today , there is no effective treatment protocol for the complete clearance of Wuchereria bancrofti ( W.b ) infection that causes secondary lymphoedema . In a double blind r and omized control trial ( RCT ) , 146 asymptomatic W. b infected individuals were r and omly assigned to one of the four regimens for 12 days , DEC 300 mg + Doxycycline 100 mg coadministration or DEC 300 mg + Albendazole 400 mg co-administration or DEC 300 mg + Albendazole 400 mg sequential administration or control regimen DEC 300 mg and were followed up at 13 , 26 and 52 weeks post-treatment for the clearance of infection . At intake , there was no significant variation in mf counts ( F(3,137)=0.044 ; P=0.988 ) and antigen levels ( F(3,137)=1.433 ; P=0.236 ) between the regimens . Primary outcome analysis showed that DEC + Albendazole sequential administration has an enhanced efficacy over DEC + Albendazole co-administration ( 80.6 Vs 64.7 % ) , and this regimen is significantly different when compared to DEC + doxycycline co-administration and control ( P<0.05 ) , in clearing microfilaria in 13 weeks . Secondary outcome analysis showed that , all the trial regimens were comparable to control regimen in clearing antigen ( F(3 , 109)=0.405 ; P=0.750 ) . Therefore , DEC + Albendazole sequential administration appears to be a better option for rapid clearance of W. b microfilariae in 13 weeks time . ( Clinical trials.gov identifier - NCT02005653 ) To compare the efficacy and tolerability of various combinations of low- and high-dose ivermectin and diethylcarbamazine ( DEC ) , 59 persons with Wuchereria bancrofti microfilaremia were enrolled in a double-blinded six-arm clinical trial in Leogane , Haiti . On day 1 , study participants were treated with low clearing doses of ivermectin , DEC , or placebo ; on day 5 they received 200 - 400 micrograms/kg of ivermectin or 6 mg/kg of DEC . Adverse reactions , which were generally mild , occurred more frequently with ivermectin than with DEC . One year after treatment , the geometric mean microfilarial density returned to 0.9 % of pretreatment levels for persons who received a total of 420 micrograms/kg of ivermectin . This rate was significantly lower than 5.6 % for persons who were treated with 220 micrograms/kg of ivermectin ( P = 0.02 ) and 9.3 % for those receiving 6 or 7 mg/kg of DEC ( P = 0.006 ) . Persons treated with a clearing dose of ivermectin followed by 6 mg/kg of DEC also had low microfilarial densities ( 1.7 % of pretreatment levels ) , suggesting an additive or synergistic effect of the two drugs . The addition of a clearing dose neither reduced the severity of adverse reactions nor improved the efficacy of high-dose ivermectin . Community-based intervention trials are now warranted to determine the feasibility and effectiveness of mass chemotherapy with single high-dose ivermectin for the prevention and control of lymphatic filariasis To assess directly the effect of various doses of diethylcarbamazine ( DEC ) on adult Wuchereria bancrofti , 31 infected men were r and omly assigned to receive an initial single DEC dose of 1 mg/kg ( n = 7 ) , 6 mg/kg ( n = 10 ) , or 12 mg/kg ( n = 14 ) . Beginning 7 d later , the dosage of DEC and duration of treatment were progressively increased for 7 - 10 weeks . Physical examinations were performed to detect scrotal nodules and the scrotal area was examined by ultrasound ( 7.5 MHz transducer ) to monitor the ' filaria dance sign ' ( FDS ) , the characteristic pattern of adult worm movement . Of 53 adult worm ' nests ' that were detected by ultrasound , 22 ( 41.5 % ) were DEC-sensitive ( FDS became non-detectable and a nodule became palpable at the site ) ; 20 ( 37.7 % ) were not sensitive ( FDS remained unchanged and detectable and no nodule developed ) , and 11 ( 20.8 % ) showed mixed responses ( FDS remained detectable but a palpable nodule developed ) . All but one sensitive or mixed response occurred within 1 week after the initial single dose . Of 39 ' nests ' in men who initially received a single 6 or 12 mg/kg dose of DEC , 20 ( 51.3 % ) had sensitive responses compared to 2 ( 14.3 % ) of 14 ' nests ' in men who received a single 1 mg/kg dose ( P = 0.04 ) . Above 6 mg/kg , the macrofilaricidal effect of DEC did not increase with dose ; a significant proportion of adult W. bancrofti were not susceptible to DEC during the study period BACKGROUND Lymphatic filariasis and intestinal helminth infections are important disorders in tropical areas . Periodic treatment with albendazole is now used in many school-based intestinal helminth-control programmes . However , few such programmes exist for lymphatic filariasis , despite evidence that single-dose treatment with ivermectin can greatly reduce the concentration of Wuchereria bancrofti microfilariae in the blood for months to years . We aim ed to assess the potential for school-based control of lymphatic filariasis by investigating the efficacy and tolerability or combined ivermectin and albendazole in Haitian schoolchildren . METHODS In January , 1996 , we collected 832 20 microL capillary blood sample s for inclusion in a r and omised controlled study from children aged 5 - 11 years , and examined them by microscopy for W bancrofti microfilariae . Infected children were r and omly assigned treatment with placebo ( n = 29 ) , a single 200 - 400 micrograms/kg dose of ivermectin ( mean , 273 micrograms/kg , n = 28 ) , 400 mg albendazole ( n = 29 ) , or a combination of 200 - 400 micrograms/kg ivermectin and 400 mg albendazole ( n = 24 ) . Children with high concentrations of microfilariae in the blood were admitted to hospital and adverse reactions were monitored for 3 - 5 days , otherwise children were examined at school or during a visit to their home . 4 months after treatment , we examined blood sample s again for microfilariae . FINDINGS 113 microfilaraemic children were enrolled ( mean age 7.8 years ) . 4 months after treatment , the proportion of children who remained positive for microfilariae was significantly lower in the ivermectin plus albendazole group ( four [ 17 % ] ) , but there were no significant changes in the other three groups ( 20 [ 69 % ] placebo , 22 [ 76 % ] albendazole alone , 17 [ 61 % ] ivermectin alone remained positive ; p = 0.004 ) . Geometric mean microfilarial concentration decreased from 9.3 to 5.3 per 20 microL blood among children who received placebo ; from 15.5 to 1.5 per 20 microL blood among those who received ivermectin only ( p = 0.032 ) ; from 14.1 to 5.1 per 20 microL blood among those who received albendazole alone ; and from 13.7 to 0.3 per 20 microL blood among those who received both ivermectin and albendazole ( p = 0.0001 ) . Systemic adverse reactions did not differ significantly between children who received ivermectin alone and those who were treated with ivermectin and albendazole [ corrected ] . INTERPRETATION For children with W bancrofti microfilaraemia , combined treatment with ivermectin and albendazole was more effective than treatment with ivermectin only , with no measurable increase in severity of adverse reactions The natural history of lymphatic disease in human filariasis remains unclear , but recurrent episodes of acute lymphangitis are believed to constitute a major risk factor for the development of chronic lymphoedema and elephantiasis . Prospect i ve analysis of 600 patients referred to the filariasis clinic of the Centro de Pesquisas Aggeu Magalhães/FIOCRUZ in Recife , Brazil , indicated that 2 distinct acute syndromes accompanied by lymphangitis occur in residents of this filariasis-endemic area . One syndrome , which we call acute filarial lymphangitis ( AFL ) , is caused by the death of adult worms . It is relatively uncommon in untreated persons , usually is asymptomatic or has a mild clinical course , and rarely causes residual lymphoedema . The second syndrome , of acute dermatolymphangioadenitis ( ADLA ) , is not caused by filarial worms per se , but probably results from secondary bacterial infections . ADLA is a common cause of chronic lymphoedema and elephantiasis in Recife as well as in other areas of Brazil where lymphatic filariasis is not present . The syndromes of AFL and ADLA can be readily distinguished from each other by simple clinical criteria Repeated , single , oral doses of combinations of ivermectin , diethylcarbamazine ( DEC ) or albendazole are recognized as important tools for parasite control in lymphatic filariasis . In order to assess the effects of re-treatment using these combinations in Brugia malayi infections , 40 asymptomatic microfilaraemics were re-treated at the end of the first year , with an additional , single , dose of the combination they had previously received . They were then followed-up for another year . The subjects , of both sexes and aged 14–70 years , each received a two-drug combination : ivermectin ( 200 µg/kg ) with DEC ( 6 mg/kg ) ; ivermectin ( 200 µg/kg ) with albendazole ( 400 mg ) ; or DEC ( 6 mg/kg ) with albendazole ( 400 mg ) . The kinetics of microfilarial clearance were similar to that seen during the first treatment , the members of the two groups given DEC having less intense microfilaraemias , 1 year after the re-treatment , than those given ivermectin with albendazole ( P<0.001 for each comparison ) . At this time , the two DEC groups also had a higher proportion of amicrofilaraemic individuals ( 22 of 26 ) than the ivermectin + albendazole group ( three of nine ) . There were fewer adverse reactions in all the groups after re-treatment than seen after the first treatment . In countries such as India , where there is no co-endemicity of onchocerciasis or loiasis , the options for control programmes in areas where brugian filariasis is endemic are DEC alone or DEC in combination with ivermectin or albendazole . Where there is no access to ivermectin , transmission control must be based on DEC alone or in combination with albendazole To determine the effectiveness of single oral dosages of ivermectin ranging between 20 and 200 micrograms/kg and to make detailed observations of both the kinetics of parasite killing and the adverse reactions induced by treatment , the present double-blind study on ivermectin treatment of lymphatic filariasis caused by Wuchereria bancrofti was undertaken with 43 microfilaremic patients in Recife , Brazil . Follow-up at one year indicated equivalent efficacy for the 20- , 100- , and 200-micrograms/kg drug dosages in reducing microfilaremia to geometric means of 13 - 25 % of pretreatment levels . Adverse clinical reactions ( predominantly fever , headache , weakness , and myalgia ) occurred to some degree in almost all patients but generally lasted only 24 - 48 hr and were easily managed symptomatically . Adverse reactions were significantly milder in those receiving the lowest ( 20 micrograms/kg ) ivermectin dose , and they were significantly correlated with individuals ' pretreatment microfilaremia levels in all groups . Posttreatment eosinophilia was a regular feature of the response to treatment , with the magnitude and kinetics also proportional to pretreatment microfilarial levels . Transient pulmonary function abnormalities ( 16 of 42 , 38 % ) , liver enzyme elevations ( 10 of 43 , 23 % ) , and hematuria ( 9 of 42 , 22 % ) developed posttreatment , but all cleared without significant complications . The results indicate that W. bancrofti from Brazil is similar to strains of the parasites studied elsewhere in susceptibility to ivermectin , that the drug 's systemic adverse reactions are essentially those result ing from parasite clearance , and that the intensity of these reactions can be significantly reduced by using the low ( 20 micrograms/kg ) dose of ivermectin . This detailed dose-finding study provides information necessary for developing optimal regimens to treat bancroftian filariasis with ivermectin either alone or in combination with other medications Examination of 1829 children from 6 primary schools in coastal Tanzania revealed overall Wuchereria bancrofti microfilaria ( mf ) and circulating filarial antigen ( CFA ) prevalences of 17.3 % and 43.7 % , respectively . A r and omized double-blind field trial with a single dose of ivermectin ( 150 - 200 microg/kg body weight ) alone or in combination with albendazole ( 400 mg ) was subsequently carried out among these children . Both treatment regimens result ed in a considerable decrease in mean mf intensities , with overall reductions being slightly but statistically significantly higher for the combination than for ivermectin alone . The difference in effect between the two treatment regimens was most pronounced at 6 months , whereas it was minor at 12 months after treatment . The relative effect of treatment on mean CFA units was less pronounced than on mf . For both treatment regimens , reductions in CFA intensity appeared to be higher in children who were both CFA and mf positive before treatment , which may suggest that treatment mainly affected the survival and /or production of mf , rather than the survival of adult worms . New cases of infection appeared after treatment with both regimens among the pre-treatment mf and CFA negative children . Adverse reactions were few and mild in both groups , and mainly reported from pre-treatment mf and CFA positive children . The alarmingly high prevalence of W. bancrofti infection in primary school children highlights the importance of also determining the reversibility of already acquired early lesions , and the development of new measures and strategies to specifically protect children from later developing clinical disease Although diethylcarbamazine ( DEC ) and albendazole are recommended to interrupt transmission of Wuchereria bancrofti , little is known about the macrofilaricidal effect of this drug combination . Forty-seven men with W. bancrofti infection were r and omly assigned to receive a single dose of either DEC alone ( 6 mg/kg ) ( n=25 ) or a combination of DEC ( 6 mg/kg ) and albendazole ( 400 mg ) ( n=22 ) . Physical examinations for scrotal nodules ( result ing from worm death ) and ultrasound examinations ( to detect living adult worms ) were performed before treatment and 7 , 14 , 30 , 45 , 60 , 90 , 180 , 270 and 360 days after treatment . Blood was examined for microfilariae before and 30 days and 360 days after treatment . Seven days post treatment , intrascrotal nodules were detected at the site of 21 ( 46.7 % ) adult worm nests in men who received DEC alone compared with 2 ( 6.1 % ) sites in men who received DEC and albendazole ( P=0.002 ) . One year after treatment , 10 ( 22.2 % ) original adult worm nests remained detectable by ultrasound among men who received DEC alone compared with 18/32 ( 56.3 % ) nests among men who received both drugs ( P=0.016 ) . Microfilaraemia prevalence and density decreased to a similar extent in both groups . Addition of albendazole appeared to decrease the macrofilaricidal effect of DEC against W. bancrofti , with no detectable enhancement in microfilarial suppression The efficacy and safety of single-dose ivermectin ( 150 - 200 micrograms/kg ) and albendazole ( 400 mg ) treatment administered separately or in combination for Wuchereria bancrofti infections were assessed in 1996 - 98 in a r and omized double-blind placebo-controlled field trial in Ghana : 1425 individuals from 4 lymphatic filariasis-endemic villages , 340 of whom were microfilaria (mf)-positive before treatment , were r and omized into 4 groups to receive albendazole alone , ivermectin alone , combination of albendazole and ivermectin , or placebo , respectively . Individuals were followed for 5 days after treatment to record any adverse reactions , and the effect of treatment on microfilaraemia was monitored in night-blood sample s after 3 , 6 and 12 months . Treatment efficacy was analysed for 236 mf-positive individuals who had > or = 100 mf/mL of blood and who were also present for examination at 12 months after treatment . Compared to the placebo group , the ivermectin and combination groups both showed statistically significant reductions in geometric mean mf intensities at the follow-up examinations ( to 6.7 % and 0.9 % , 9.9 % and 6.9 % , and 21.7 % and 11.4 % of pre-treatment levels , respectively , at 3 , 6 and 12 months after treatment ) . Compared to the ivermectin group , however , the reduction in the combination group was significantly greater only at 3 months after treatment , but not after 6 or 12 months . The albendazole group showed a slow but non-significant reduction over the same period . Adverse reactions were few and mostly mild ( no severe reactions were recorded ) , and no significant differences were observed between the treatment groups . Both ivermectin and combination treatment thus appeared effective and safe for treatment of lymphatic filariasis , but the difference in efficacy was minor and the study did not provide clear evidence for the combination drug therapy , as compared to ivermectin therapy alone , to be superior for control of lymphatic filariasis OBJECTIVE To evaluate the efficacy of doxycycline as a macrofilaricidal agent against Wuchereria bancrofti . METHOD In the Western Region of Ghana , 18 patients infected with W. bancrofti were recruited and treated with 200 mg doxycycline per day for 4 weeks . Seven untreated patients served as controls . Four months after doxycycline treatment , all patients received 150 mug/kg ivermectin . Patients were monitored for Wolbachia and microfilaria loads , antigenaemia and filarial dance sign ( FDS ) . RESULTS Four months after doxycycline treatment , cases had a significantly lower Wolbachia load than controls ; and 24 months after treatment , microfilaraemia , antigenaemia and frequency of FDS were significantly lower in cases than controls . Most importantly , 4 weeks of doxycycline killed 80 % of macrofilariae , which is comparable with the results of a 6-week regimen . Circulating filarial antigenaemia and FDS were strongly correlated . CONCLUSION A 4-week regimen of doxycycline seems sufficient to kill adult W. bancrofti and could be advantageous for the treatment of individual patients , e.g. in outpatient clinics BACKGROUND The World Health Organization has targeted lymphatic filariasis for global elimination by 2020 with a strategy of mass drug administration . This trial tested whether a single dose of a three‐drug regimen of ivermectin plus diethylcarbamazine plus albendazole results in a greater sustained clearance of microfilariae than a single dose of a two‐drug regimen of diethylcarbamazine plus albendazole and is noninferior to the two‐drug regimen administered once a year for 3 years . METHODS In a r and omized , controlled trial involving adults from Papua New Guinea with Wuchereria bancrofti microfilaremia , we assigned 182 participants to receive a single dose of the three‐drug regimen ( 60 participants ) , a single dose of the two‐drug regimen ( 61 participants ) , or the two‐drug regimen once a year for 3 years ( 61 participants ) . Clearance of microfilariae from the blood was measured at 12 , 24 , and 36 months after trial initiation . RESULTS The three‐drug regimen cleared microfilaremia in 55 of 57 participants ( 96 % ) at 12 months , in 52 of 54 participants ( 96 % ) at 24 months , and in 55 of 57 participants ( 96 % ) at 36 months . A single dose of the two‐drug regimen cleared microfilaremia in 18 of 56 participants ( 32 % ) at 12 months , in 31 of 55 participants ( 56 % ) at 24 months , and in 43 of 52 participants ( 83 % ) at 36 months ( P=0.02 for the three‐drug regimen vs. a single dose of the two‐drug regimen at 36 months ) . The two‐drug regimen administered once a year for 3 years cleared microfilaremia in 20 of 59 participants ( 34 % ) at 12 months , in 42 of 56 participants ( 75 % ) at 24 months , and in 51 of 52 participants ( 98 % ) at 36 months ( P=0.004 for noninferiority of the three‐drug regimen vs. the two‐drug regimen administered once a year for 3 years at 36 months ) . Moderate adverse events were more common in the group that received the three‐drug regimen than in the combined two‐drug – regimen groups ( 27 % vs. 5 % , P<0.001 ) . There were no serious adverse events . CONCLUSIONS The three‐drug regimen induced clearance of microfilariae from the blood for 3 years in almost all participants who received the treatment and was superior to the two‐drug regimen administered once and noninferior to the two‐drug regimen administered once a year for 3 years . ( Funded by the Bill and Melinda Gates Foundation ; Clinical Trials.gov number , NCT01975441 . |
12,291 | 28,440,858 | We found no differences between the included drugs with respect to the hazard of conversion to CDMS .
Very low- quality evidence suggests a small and uncertain benefit with early treatment compared with placebo in reducing disability-worsening and relapses .
The advantage of early treatment compared with delayed on disability-worsening was heterogeneous depending on the actual drug used and based on very low- quality evidence .
Low- quality evidence suggests that the chances of relapse are less with early treatment compared with delayed .
Early treatment reduced the hazard of conversion to CDMS compared either with placebo , no treatment or delayed treatment , both in short- and long-term follow-up .
Low- quality evidence suggests that early treatment is associated with fewer participants with at least one serious AE compared with placebo .
Very low- quality evidence suggests that , compared with placebo , early treatment leads to more withdrawals or treatment discontinuation due to AEs . | BACKGROUND The treatment of multiple sclerosis has changed over the last 20 years .
The advent of disease-modifying drugs in the mid-1990s heralded a period of rapid progress in the underst and ing and management of multiple sclerosis .
With the support of magnetic resonance imaging early diagnosis is possible , enabling treatment initiation at the time of the first clinical attack .
As most of the disease-modifying drugs are associated with adverse events , patients and clinicians need to weigh the benefit and safety of the various early treatment options before taking informed decisions .
OBJECTIVES 1 .
to estimate the benefit and safety of disease-modifying drugs that have been evaluated in all studies ( r and omised or non-r and omised ) for the treatment of a first clinical attack suggestive of MS compared either with placebo or no treatment;2 .
to assess the relative efficacy and safety of disease-modifying drugs according to their benefit and safety;3 .
to estimate the benefit and safety of disease-modifying drugs that have been evaluated in all studies ( r and omised or non-r and omised ) for treatment started after a first attack ( ' early treatment ' ) compared with treatment started after a second attack or at another later time point ( ' delayed treatment ' ) . | BACKGROUND Several controlled studies provide evidence that treatment with interferon beta in patients with a first event suggestive of multiple sclerosis ( MS ) delays conversion to clinical ly definite MS ( CDMS ) . Our aim was to determine whether early initiation of treatment with interferon beta prevents development of confirmed disability in MS . METHODS In the initial placebo-controlled phase of the double-blinded BENEFIT study , patients with a first event suggestive of MS and a minimum of two clinical ly silent lesions in MRI were r and omised to receive either interferon beta-1b 250 microg ( n=292 ) or placebo ( n=176 ) subcutaneously every other day for 2 years , or until diagnosis of CDMS . Patients were then eligible to enter the follow-up phase with open-label interferon beta-1b . In the current prospect ively planned analysis 3 years after r and omisation , the effects of early interferon beta-1b treatment were compared with those of delayed treatment initiated after diagnosis of CDMS or after 2 years on the study . The primary outcomes of this ITT analysis were time to diagnosis of CDMS , time to confirmed exp and ed disability status scale ( EDSS ) progression , and score on a patient-reported functional assessment scale ( FAMS-TOI ) . This trial is registered with Clinical Trials.gov , number NCT00185211 . FINDINGS Of the 468 patients originally r and omised , 418 ( 89 % ) entered the follow-up phase ; 392 ( 84 % ) completed 3 years ' post-r and omisation follow-up . After 3 years , 99 ( 37 % ) patients in the early group developed CDMS compared with 85 ( 51 % ) patients in the delayed treatment group . Early treatment reduced the risk of CDMS by 41 % ( hazard ratio 0.59 , 95 % CI 0.44 - 0.80 ; p=0.0011 ; absolute risk reduction 14 % ) compared with delayed treatment . Over 3 years , 42 ( 16 % ) patients in the early group and 40 ( 24 % ) in the delayed group had confirmed EDSS progression ; early treatment reduced the risk for progression of disability by 40 % compared with delayed treatment ( 0.60 , 0.39 - 0.92 ; p=0.022 ; absolute risk reduction 8 % ) . The FAMS-TOI score was high and stable in both groups over the 3-year period ( p=0.31 ) . INTERPRETATION Our data suggest that early initiation of treatment with interferon beta-1b prevents the development of confirmed disability , supporting its use after the first manifestation of relapsing-remitting MS Objective Early treatment following a first clinical demyelinating event ( FCDE ) delays further disease activity in patients with multiple sclerosis ( MS ) . This study determined the effects of early versus delayed treatment ( DT ) with subcutaneous interferon ( sc IFN ) β-1a 44 μg in patients with an FCDE up to 60 months postr and omisation . Methods Patients who completed the 24-month double-blind REFLEX ( REbif FLEXible dosing in early MS ) study entered an extension ( REFLEXION , REbif FLEXible dosing in early MS extensION ) : patients initially r and omised to sc IFN β-1a and not reaching clinical ly definite MS ( clinical ly definite MS , CDMS ( second attack or sustained Exp and ed Disability Status Scale ( EDSS ) score increase ) ) continued original treatment ( three times weekly ( tiw ) or once weekly ( qw ) ) ; placebo patients switched to tiw ( DT ) ; patients with CDMS switched to tiw . Clinical , MRI and adverse event data up to month 60 are reported . Results 402/517 ( 77.8 % ) REFLEX patients entered REFLEXION ( DT , n=133 ; tiw , n=127 ; qw , n=142 ) . At month 60 , cumulative probability of CDMS was : DT 44.6 % ; qw 40.7 % ( nominal p=0.084 vs DT ) ; tiw 39.2 % ( nominal p=0.032 vs DT ) . Cumulative probability of McDonald MS conversion ( CDMS or new MRI activity ) at month 60 was also reduced for tiw versus DT ( nominal p<0.001 ) . At month 60 , mean cumulative numbers of new T2 , gadolinium-enhancing and T1 hypointense lesions were lower with sc IFN β-1a qw ( nominal p<0.05 ) and tiw versus DT ( nominal p<0.001 ) ; T2 and T1 hypointense lesion volume change was lower for sc IFN β-1a tiw versus DT ( nominal p<0.01 ) . Treatment was well tolerated ; fewer patients receiving tiw versus qw were positive for neutralising or binding antibodies . Conclusions Over 5 years in patients presenting with an FCDE , early sc IFN β-1a tiw administration versus DT prolonged time to CDMS and McDonald MS , and reduced overall MRI activity . Trial registration number NCT00813709 ; Results BACKGROUND Several studies have confirmed the predictive value of baseline and follow-up magnetic resonance ( MR ) imaging variables for conversion to clinical ly definite multiple sclerosis ( CDMS ) , depending on the population , follow-up duration , and treatment intervention . However , the timing of follow-up imaging and the effect of treatment intervention on the predictive value of baseline MR imaging variables require further elucidation . OBJECTIVES To assess the prognostic value of baseline MR imaging variables for conversion to CDMS over 3 years and whether this was affected by treatment intervention and ( 2 ) to assess the increased risk for conversion posed by dissemination in time on follow-up MR imaging . DESIGN Cohort study . SETTING Multicenter r and omized clinical trial . PATIENTS Four hundred sixty-eight patients with a clinical ly isolated syndrome who had an initial clinical demyelinating event within the past 60 days who received early treatment ( 3 years of interferon beta-1b ) or delayed treatment ( placebo first , followed by > or = 1 year of interferon beta-1b ) . Intervention Magnetic resonance imaging . Main Outcome Measure Time to CDMS . RESULTS The overall conversion rate to CDMS was 42 % . Barkhof criteria with the strongest prognostic value were the presence at baseline of at least 9 T2-weighted lesions ( hazard ratio [ HR ] , 1.64 ; 95 % confidence interval [ CI ] , 1.15 - 2.33 ; P = .006 ) and at least 3 periventricular lesions ( 1.66 ; 1.14 - 2.41 ; P = .009 ) . No specific advantage was noted in using a fixed cutoff of at least 3 Barkhof criteria ( HR , 1.31 ; 95 % CI , 0.95 - 1.79 ; P = .10 ) . The prognostic value of all MR imaging criteria was unaffected by treatment intervention ( P > or = .20 for all ) . Dissemination in time result ed in increased risk for CDMS only in patients without dissemination in space at baseline and was most informative at the 9-month MR imaging ( HR , 2.72 ; 95 % CI , 1.26 - 5.87 ; P = .01 ) . CONCLUSIONS The modified Barkhof criteria showed moderate predictive value for conversion to CDMS , although all patients had received interferon beta-1b therapy for at least 1 year . The predictive value was unaffected by treatment intervention . Follow-up MR imaging was most informative after 9 months in patients without dissemination in space at baseline Objective To examine the long-term impact of early treatment initiation of interferon beta-1b ( IFNB1b , Betaferon/Betaseron ) in patients with a first event suggestive of multiple sclerosis ( MS ) . Methods In the original placebo-controlled phase of BENEFIT , patients were r and omised to IFNB1b 250 μg or placebo subcutaneously every other day . After 2 years or diagnosis of clinical ly definite MS ( CDMS ) , all patients were offered open-label IFNB1b treatment for a maximum duration of 5 years . Thereafter , patients were enrolled in an observational extension study for up to 8.7 years . Results Of the initial 468 patients , 284 ( 60.7 % ; IFNB1b : 178 ( 61.0 % of the original arm ) , placebo : 106 ( 60.2 % of original arm ) ) were enrolled in the extension study . 94.2 % of patients were receiving IFNB1b . Patients originally r and omised to IFNB1b had a reduced risk of developing CDMS by 32.2 % over the 8-year observation period ( HR 0.678 ; 95 % CI 0.525 to 0.875 ; p=0.0030 ) , a longer median time to CDMS by 1345 days ( 95 % CI 389 to 2301 ) , and a lower annualised relapse rate ( 0.196 ( 95 % CI 0.176 to 0.218 ) versus 0.255 ( 95 % CI 0.226 to 0.287 ) , p=0.0012 ) , with differences mainly emerging in the first year of the study . Cognitive outcomes remained higher in the early treated patients . EDSS remained low over time with a median of 1.5 in both arms . Conclusions These 8-year results provide further evidence supporting early initiation of treatment with IFNB1b in patients with a first event suggestive of MS BACKGROUND Cladribine provides immunomodulation through selective targeting of lymphocyte subtypes . We report the results of a 96-week phase 3 trial of a short-course oral tablet therapy in patients with relapsing-remitting multiple sclerosis . METHODS We r and omly assigned 1326 patients in an approximate 1:1:1 ratio to receive one of two cumulative doses of cladribine tablets ( either 3.5 mg or 5.25 mg per kilogram of body weight ) or matching placebo , given in two or four short courses for the first 48 weeks , then in two short courses starting at week 48 and week 52 ( for a total of 8 to 20 days per year ) . The primary end point was the rate of relapse at 96 weeks . RESULTS Among patients who received cladribine tablets ( either 3.5 mg or 5.25 mg per kilogram ) , there was a significantly lower annualized rate of relapse than in the placebo group ( 0.14 and 0.15 , respectively , vs. 0.33 ; P<0.001 for both comparisons ) , a higher relapse-free rate ( 79.7 % and 78.9 % , respectively , vs. 60.9 % ; P<0.001 for both comparisons ) , a lower risk of 3-month sustained progression of disability ( hazard ratio for the 3.5-mg group , 0.67 ; 95 % confidence interval [ CI ] , 0.48 to 0.93 ; P=0.02 ; and hazard ratio for the 5.25-mg group , 0.69 ; 95 % CI , 0.49 to 0.96 ; P=0.03 ) , and significant reductions in the brain lesion count on magnetic resonance imaging ( MRI ) ( P<0.001 for all comparisons ) . Adverse events that were more frequent in the cladribine groups included lymphocytopenia ( 21.6 % in the 3.5-mg group and 31.5 % in the 5.25-mg group , vs. 1.8 % ) and herpes zoster ( 8 patients and 12 patients , respectively , vs. no patients ) . CONCLUSIONS Treatment with cladribine tablets significantly reduced relapse rates , the risk of disability progression , and MRI measures of disease activity at 96 weeks . The benefits need to be weighed against the risks . ( Clinical Trials.gov number , NCT00213135 . Natural history studies have identified factors that predict evolution to multiple sclerosis or risk of disability accumulation over time . Although these studies are based on large multicentre cohorts with long follow-ups , they have limitations such as lack of st and ardized protocol s , a retrospective data collection or lack of a systematic magnetic resonance imaging acquisition and analysis protocol , often result ing in failure to take magnetic resonance and oligoclonal b and s into account as joint covariates in the prediction models . To overcome some of these limitations , the aim of our study was to identify and stratify baseline demographic , clinical , radiological and biological characteristics that might predict multiple sclerosis development and disability accumulation using a multivariate approach based on a large prospect i ve cohort of patients with clinical ly isolated syndromes . From 1995 to 2013 , 1058 patients with clinical ly isolated syndromes were included . We evaluated the influence of baseline prognostic factors on the risk for developing clinical ly definite multiple sclerosis , McDonald multiple sclerosis , and disability accumulation ( Exp and ed Disability Status Scale score of 3.0 ) based on univariate ( hazard ratio with 95 % confidence intervals ) and multivariate ( adjusted hazard ratio with 95 % confidence intervals ) Cox regression models . We ultimately included 1015 patients followed for a mean of 81 ( st and ard deviation = 57 ) months . Female/male ratio was 2.1 . Females exhibited a similar risk of conversion to multiple sclerosis and of disability accumulation compared to males . Each younger decade at onset was associated with a greater risk of conversion to multiple sclerosis and with a protective effect on disability . Patients with optic neuritis had a lower risk of clinical ly definite multiple sclerosis [ hazard ratio 0.6 ( 0.5 - 0.8 ) ] and disability progression [ hazard ratio 0.5 ( 0.3 - 0.8 ) ] ; however , this protective effect remained marginal only for disability [ adjusted hazard ratio 0.6 ( 0.4 - 1.0 ) ] in adjusted models . The presence of oligoclonal b and s increased the risk of clinical ly definite multiple sclerosis [ adjusted hazard ratio 1.3 ( 1.0 - 1.8 ) ] and of disability [ adjusted hazard ratio 2.0 ( 1.2 - 3.6 ) ] independently of other factors . The presence of 10 or more brain lesions on magnetic resonance increased the risk of clinical ly definite multiple sclerosis [ adjusted hazard ratio 11.3 ( 6.7 - 19.3 ) ] and disability [ adjusted hazard ratio 2.9 ( 1.4 - 6.0 ) ] . Disease-modifying treatment before the second attack reduced the risk of McDonald multiple sclerosis [ adjusted hazard ratio 0.6 ( 0.4 - 0.9 ) ] and disability accumulation [ adjusted hazard ratio 0.5 ( 0.3 - 0.9 ) ] . We conclude that the demographic and topographic characteristics are low-impact prognostic factors , the presence of oligoclonal b and s is a medium-impact prognostic factor , and the number of lesions on brain magnetic resonance is a high-impact prognostic factor Aim The REbif FLEXible dosing in early MS ( REFLEX ) study compared several brain MRI outcomes in patients presenting with clinical ly isolated syndromes suggestive of multiple sclerosis and treated with two dose-frequencies of subcutaneous interferon ( IFN ) β-1a or placebo . Methods Patients were r and omised ( 1:1:1 ) to IFN β-1a , 44 µg subcutaneously three times a week or once a week , or placebo three times a week for up to 24 months . MRI scans were performed every 3 months , or every 6 months if the patient developed clinical ly definite multiple sclerosis . End points analysed included : number of combined unique active lesions per patient per scan ; numbers and volumes of new T2 , T1 hypointense and gadolinium-enhancing ( Gd+ ) lesions per patient per scan ; and brain volume . Results 517 patients were r and omised ( intent-to-treat population : subcutaneous IFN β-1a three times a week , n=171 ; subcutaneous IFN β-1a once a week , n=175 ; placebo , n=171 ) . Combined unique active lesions were lower in patients treated with subcutaneous IFN β-1a versus placebo ( mean ( SD ) lesions per patient per scan : three times a week 0.6 ( 1.15 ) ; once a week 1.23 ( 4.26 ) ; placebo 2.70 ( 5.23 ) ; reduction versus placebo : three times a week 81 % ; once a week 63 % ; p<0.001 ) and with three times a week versus once a week ( 48 % reduction ; p=0.002 ) . The mean numbers of new T2 , T1 hypointense and Gd+ lesions were all significantly lower in the two active treatment arms compared with placebo ( p≤0.004 for three times a week or once a week ) and in the three times a week group compared with once a week ( p≤0.012 ) . Conclusions Both subcutaneous IFN β-1a 44 µg regimens improved MRI outcomes versus placebo , with the three times a week regimen having a more pronounced effect than once a week dosing . Trial registration clinical trial.gov identifier , NCT00404352 Background : Characteristics at clinical ly isolated syndrome ( CIS ) examination assist in identification of patient at highest risk of early second attack and could benefit the most from early disease-modifying drugs ( DMDs ) . Objective : To examine determinants of second attack and vali date a prognostic nomogram for individualised risk assessment of clinical conversion . Methods : Patients with CIS were prospect ively followed up in the MSBase Incident Study . Predictors of clinical conversion were analysed using Cox proportional hazards regression . Prognostic nomograms were derived to calculate conversion probability and vali date d using concordance indices . Results : A total of 3296 patients from 50 clinics in 22 countries were followed up for a median ( inter-quartile range ( IQR ) ) of 1.92 years ( 0.90 , 3.71 ) . In all , 1953 ( 59.3 % ) patients recorded a second attack . Higher Exp and ed Disability Status Scale ( EDSS ) at baseline , first symptom location , oligoclonal b and s and various brain and spinal magnetic resonance imaging ( MRI ) metrics were all predictors of conversion . Conversely , older age and DMD exposure post-CIS were associated with reduced rates . Prognostic nomograms demonstrated high concordance between estimated and observed conversion probabilities . Conclusion : This multinational study shows that age at CIS onset , DMD exposure , EDSS , multiple brain and spinal MRI criteria and oligoclonal b and s are associated with shorter time to relapse . Nomogram assessment may be useful in clinical practice for estimating future clinical conversion Objectives We conducted a prospect i ve study , MSBASIS , to assess factors leading to first treatment discontinuation in patients with a clinical ly isolated syndrome ( CIS ) and early relapsing-remitting multiple sclerosis ( RRMS ) . Methods The MSBASIS Study , conducted by MSBase Study Group members , enrols patients seen from CIS onset , reporting baseline demographics , cerebral magnetic resonance imaging ( MRI ) features and Exp and ed Disability Status Scale ( EDSS ) scores . Follow-up visits report relapses , EDSS scores , and the start and end date s of MS-specific therapies . We performed a multivariable survival analysis to determine factors within this data set that predict first treatment discontinuation . Results A total of 2314 CIS patients from 44 centres were followed for a median of 2.7 years , during which time 1247 commenced immunomodulatory drug ( IMD ) treatment . Ninety percent initiated IMD after a diagnosis of MS was confirmed , and 10 % while still in CIS status . Over 40 % of these patients stopped their first IMD during the observation period . Females were more likely to cease medication than males ( HR 1.36 , p = 0.003 ) . Patients treated in Australia were twice as likely to cease their first IMD than patients treated in Spain ( HR 1.98 , p = 0.001 ) . Increasing EDSS was associated with higher rate of IMD cessation ( HR 1.21 per EDSS unit , p<0.001 ) , and intramuscular interferon-β-1a ( HR 1.38 , p = 0.028 ) and subcutaneous interferon-β-1a ( HR 1.45 , p = 0.012 ) had higher rates of discontinuation than glatiramer acetate , although this varied widely in different countries . Onset cerebral MRI features , age , time to treatment initiation or relapse on treatment were not associated with IMD cessation . Conclusion In this multivariable survival analysis , female sex , country of residence , EDSS change and IMD choice independently predicted time to first IMD cessation IMPORTANCE It remains unclear whether vitamin D insufficiency , which is common in individuals with multiple sclerosis ( MS ) , has an adverse effect on MS outcomes . OBJECTIVES To determine whether serum concentrations of 25-hydroxyvitamin D ( 25[OH]D ) , a marker of vitamin D status , predict disease activity and prognosis in patients with a first event suggestive of MS ( clinical ly isolated syndrome ) . DESIGN , SETTING , AND PARTICIPANTS The Betaferon/Betaseron in Newly Emerging multiple sclerosis For Initial Treatment study was a r and omized trial originally design ed to evaluate the impact of early vs delayed interferon beta-1b treatment in patients with clinical ly isolated syndrome . Serum 25(OH)D concentrations were measured at baseline and 6 , 12 , and 24 months . A total of 465 of the 468 patients r and omized had at least 1 25(OH)D measurement , and 334 patients had them at both the 6- and 12-month ( seasonally asynchronous ) measurements . Patients were followed up for 5 years clinical ly and by magnetic resonance imaging . MAIN OUTCOMES AND MEASURES New active lesions , increased T2 lesion volume , and brain volume on magnetic resonance imaging , as well as MS relapses and disability ( Exp and ed Disability Status Scale score ) . RESULTS Higher 25(OH)D levels predicted reduced MS activity and a slower rate of progression . A 50-nmol/L ( 20-ng/mL ) increment in average serum 25(OH)D levels within the first 12 months predicted a 57 % lower rate of new active lesions ( P < .001 ) , 57 % lower relapse rate ( P = .03 ) , 25 % lower yearly increase in T2 lesion volume ( P < .001 ) , and 0.41 % lower yearly loss in brain volume ( P = .07 ) from months 12 to 60 . Similar associations were found between 25(OH)D measured up to 12 months and MS activity or progression from months 24 to 60 . In analyses using dichotomous 25(OH)D levels , values greater than or equal to 50 nmol/L ( 20 ng/mL ) at up to 12 months predicted lower disability ( Exp and ed Disability Status Scale score , -0.17 ; P = .004 ) during the subsequent 4 years . CONCLUSIONS AND RELEVANCE Among patients with MS mainly treated with interferon beta-1b , low 25(OH)D levels early in the disease course are a strong risk factor for long-term MS activity and progression Background The BENEFIT study examined interferon beta (IFNB)-1b treatment in patients with clinical ly isolated syndrome ( CIS ) and ≥ 2 clinical ly silent brain MRI lesions . Methods Subgroups of 468 patients ( IFNB-1b : n = 292 ; placebo : n = 176 ) were created for demographics , clinical , laboratory , and MRI findings at onset . The ' natural ' risk of clinical ly definite MS ( CDMS ) over 2 years was estimated by Kaplan Meier statistics in placebo-treated patients ; the IFNB-1b treatment effect was analysed by Cox proportional hazards regression . Results The risk of CDMS was increased in placebotreated patients ( overall 45 % ) if they were younger ( < 30 years : 60 % ) , were cerebrospinal fluid (CSF)-positive ( 49 % ) , or had received steroid treatment ( 48 % ) . MRI parameters implied a higher risk in placebo-treated patients with ≥ 9 T2-lesions ( 48 % ) or ≥ 1 gadolinium (Gd)-enhancing lesions ( 52 % ) . The CDMS risk was highest ( 75 % ) in placebo-treated patients with monofocal disease onset displaying MRI disease activity ( ≥ 1 Gd-lesion ) and dissemination ( ≥ 9 T2-lesions ) . Treatment effects were significant across almost all subgroups including patients with less disease dissemination/activity at onset ( monofocal : 55 % ; < 9 T2-lesions : 60 % ; no Gd-lesions : 57 % ) and patients without steroid treatment for the CIS ( 62 % ) . Monofocal patients had greater treatment effects if they had ≥ 9 T2-lesions ( 61 % ) , Gd-lesions ( 58 % ) , or both ( 65 % ) . Conclusions This study confirms the impact of age of onset , CSF and MRI findings on risk of conversion from CIS to CDMS . IFNB-1b treatment effect was robust across the study population including patients without MRI disease activity and less clinical or MRI disease dissemination at onset and patients not receiving steroids for the CIS The phase III placebo-controlled BRAVO study assessed laquinimod effects in patients with relapsing-remitting MS ( RRMS ) , and descriptively compared laquinimod with interferon beta (IFNβ)-1a ( Avonex ® reference arm ) . RRMS patients age 18–55 years with Exp and ed Disability Status Scale ( EDSS ) scores of 0–5.5 and documented pre- study relapse ( ≥ 1 in previous year , 2 in previous 2 years , or 1 in previous 1–2 years and ≥ 1 GdE lesion in the previous year ) were r and omized ( 1:1:1 ) to laquinimod 0.6 mg once-daily , matching oral placebo , or IFNβ-1a IM 30 μg once-weekly ( rater-blinded design ) , for 24 months . The primary endpoint was annualized relapse rate ( ARR ) ; secondary endpoints included percent brain volume change ( PBVC ) and 3-month confirmed disability worsening . In all , 1,331 patients were r and omized : laquinimod ( n = 434 ) , placebo ( n = 450 ) , and IFNβ-1a ( n = 447 ) . ARR was not significantly reduced with laquinimod [ −18 % , risk ratio ( RR ) = 0.82 , 95 % CI 0.66–1.02 ; p = 0.075 ] vs. placebo . Laquinimod significantly reduced PBVC ( 28 % , p < 0.001 ) . Confirmed disability worsening was infrequent ( 10 % laquinimod , 13 % placebo ) . The change in confirmed disability worsening with laquinimod measured using EDSS was −31 % [ hazard ratio ( HR ) 0.69 , p = 0.063 ] , and using Multiple Sclerosis Functional Composite ( MSFC ) z-score was −77 % ( p = 0.150 ) , vs. placebo . IFNβ-1a reduced ARR 26 % ( RR = 0.74 , 95 % CI 0.60–0.92 , p = 0.007 ) , showed no effect on PBVC loss ( + 11 % , p = 0.14 ) , and changes in disability worsening were −26 and −66 % as measured using the EDSS ( HR 0.742 , p = 0.13 ) and MSFC ( p = 0.208 ) , respectively . Adverse events occurred in 75 , 82 , and 70 % of laquinimod , IFNβ-1a , and placebo patients , respectively . Once-daily oral laquinimod 0.6 mg result ed in statistically nonsignificant reductions in ARR and disability progression , but significant reductions in brain atrophy vs. placebo . Laquinimod was well-tolerated Objective : To assess outcomes for patients treated with interferon beta-1b immediately after clinical ly isolated syndrome ( CIS ) or after a short delay . Methods : Participants in BENEFIT ( Betaferon/Betaseron in Newly Emerging MS for Initial Treatment ) were r and omly assigned to receive interferon beta-1b ( early treatment ) or placebo ( delayed treatment ) . After conversion to clinical ly definite multiple sclerosis ( CDMS ) or 2 years , patients on placebo could switch to interferon beta-1b or another treatment . Eleven years after r and omization , patients were reassessed . Results : Two hundred seventy-eight ( 59.4 % ) of the original 468 patients ( 71.3 % of those eligible at participating sites ) were enrolled ( early : 167 [ 57.2 % ] ; delayed : 111 [ 63.1 % ] ) . After 11 years , risk of CDMS remained lower in the early-treatment arm compared with the delayed-treatment arm ( p = 0.0012 ) , with longer time to first relapse ( median [ Q1 , Q3 ] days : 1,888 [ 540 , not reached ] vs 931 [ 253 , 3,296 ] ; p = 0.0005 ) and lower overall annualized relapse rate ( 0.21 vs 0.26 ; p = 0.0018 ) . Only 25 patients ( 5.9 % , overall ; early , 4.5 % ; delayed , 8.3 % ) converted to secondary progressive multiple sclerosis . Exp and ed Disability Status Scale scores remained low and stable , with no difference between treatment arms ( median [ Q1 , Q3 ] : 2.0 [ 1.0 , 3.0 ] ) . The early-treatment group had better Paced Auditory Serial Addition Task–3 total scores ( p = 0.0070 ) . Employment rates remained high , and health re source utilization tended to be low in both groups . MRI metrics did not differ between groups . Conclusions : Although the delay in treatment was relatively short , several clinical outcomes favored earlier treatment . Along with low rates of disability and disease progression in both groups , this supports the value of treatment at CIS . Clinical Trials.gov identifier : NCT01795872 . Classification of evidence : This study provides Class IV evidence that early compared to delayed treatment prolongs time to CDMS in CIS after 11 years Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies Abstract The REFLEX study ( NCT00404352 ) established that subcutaneous ( sc ) interferon ( IFN ) β-1a reduced the risks of McDonald MS ( 2005 criteria ) and clinical ly definite multiple sclerosis ( CDMS ) in patients with a first clinical demyelinating event suggestive of MS . The aim of this subgroup analysis was to assess the treatment effect of sc IFN β-1a in patient subgroups defined by baseline disease and demographic characteristics ( age , sex , use of steroids at the first event , classification of first event as mono- or multifocal , presence/absence of gadolinium-enhancing lesions , count of < 9 or ≥9 T2 lesions ) , and by diagnosis of MS using the revised McDonald 2010 MS criteria . Patients were r and omized to the serum-free formulation of IFN β-1a , 44 μg sc three times weekly or once weekly , or placebo , for 24 months or until diagnosis of CDMS . Treatment effects of sc IFN β-1a on McDonald 2005 MS and CDMS in the predefined subgroups were similar to effects found in the intent-to-treat population . McDonald 2010 MS was retrospectively diagnosed in 37.7 % of patients at baseline . Both regimens of sc IFN β-1a significantly reduced the risk versus placebo of McDonald 2005 MS and CDMS , irrespective of McDonald 2010 status at baseline ( risk reductions between 29 and 51 % ) . The effect of sc IFN β-1a was not substantially influenced by baseline patient demographic and disease characteristics , or baseline presence/absence of McDonald 2010 MS The baseline MRI studies from the Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention Study ( CHAMPS ) trial , a r and omized , longitudinal , double-blind trial of 383 patients with a first acute clinical demyelinating event and evidence of prior sub clinical demyelination on magnetic resonance imaging ( MRI ) of the brain , provides a large MRI data base for patients likely in the earliest stages of multiple sclerosis ( MS ) . High-resolution baseline MRIs revealed a median of 13 T2 lesions ( maximum=103 lesions ) and 2.05 cm3 of T2 lesion volume ( maximum 35.04 cm3 ) , with 30 % of patients having one or more enhancing lesions despite receiving a st and ardized high-dose course of intravenous corticosteroids . Periventricular , discrete , and juxtacortical T2 lesions were present in 99 % , 92 % and 67 % of the patients , respectively . Large ( > 6 mm ) , T1-hypointense , infratentorial , and corpus callosum lesions were present in 69 % , 50 % , 55 % , and 58 % , respectively . Clinical presentation groups showed differences in T2 lesion volume , and enhancing lesion number and volume . At baseline , 97 % , 81 % and 72 % of the patients met ‘ Paty ’ , ‘ Fazekas ’ , and ‘ Barkhof ’ research criteria for MS , respectively , with the percentages similar according to clinical presentation group . These results support and extend those of smaller and /or retrospective series , which have shown substantial sub clinical injury , based on brain MRI , at the earliest identifiable stages of disease Objective : B cells and the humoral immune system have been implicated in the pathogenesis of multiple sclerosis ( MS ) . This study sought to evaluate the efficacy , safety , and tolerability of add-on therapy with rituximab , a monoclonal antibody that depletes circulating B cells , in subjects with relapsing MS with breakthrough disease defined by clinical and MRI activity ( Class III evidence ) . Methods : Thirty subjects with a relapse within the past 18 months despite use of an injectable disease-modifying agent , and with at least 1 gadolinium-enhancing ( GdE ) lesion on any of 3 pretreatment MRIs , received rituximab administered at 375 mg/m2 weekly × 4 doses . Three monthly posttreatment brain MRI scans were obtained beginning 12 weeks after the first infusion . Multiple Sclerosis Functional Composite ( MSFC ) and Exp and ed Disability Status Scale ( EDSS ) were obtained at baseline and throughout the posttreatment follow-up . Results : GdE lesions were reduced after treatment with rituximab , with 74 % of posttreatment MRI scans being free of GdE activity compared with 26 % free of GdE activity at baseline ( p < 0.0001 ) . Median GdE lesions were reduced from 1.0 to 0 , and mean number was reduced from 2.81 per month to 0.33 after treatment ( 88 % reduction ) . MSFC improved as well ( p = 0.02 ) . EDSS remained stable . Conclusion : Rituximab add-on therapy was effective based upon blinded radiologic endpoints in this phase II study . In combination with st and ard injectable therapies , rituximab was well-tolerated with no serious adverse events . B-cell – modulating therapy remains a potential option for treatment of patients with relapsing MS with an inadequate response to st and ard injectable therapies . Classification of evidence : This study provides Class III evidence that add-on rituximab reduces gadolinium-enhancing brain lesions in multiple sclerosis Background : Multiple sclerosis ( MS ) is characterised by inflammatory lesions of the central nervous system . Interferon beta-1b ( IFNB-1b ) has been shown to improve clinical and magnetic resonance imaging ( MRI ) measures for patients with MS . Objective : To evaluate whether IFNB-1b in patients presenting with clinical ly isolated syndromes ( CIS ) prevented persisting T1 hypointensities on MRI ( persistent black holes ( PBHs ) ) . Methods : In the placebo-controlled phase , patients ( n = 468 ) were initially r and omised to IFNB-1b ( n = 292 ) or placebo ( n = 176 ) for two years or clinical ly definite MS ( CDMS ) . In the open-label phase ( n = 418 ) , both groups were offered IFNB-1b for up to five years . Lesions were classified as PBHs if T1 hypointensity persisted throughout the last available scan ( minimum time one year ) . Results : A total of 435 patients were evaluable for analysis . The number of PBHs/patient was lower in the early rather than the delayed treatment arm during both phases ( .42 vs .71 , p = .0102 and .70 vs 1.17 , p = .0121 ) . Exploratory analyses identified baseline characteristics that affected rate of conversion . Conclusions : Although the rate of lesions that converted to PBH showed no significant differences between groups , the numbers of PBHs per patient out of new lesions was significantly lower in IFNB-1b patients compared to patients on placebo . Trial registration number : NCT00544037 BACKGROUND B lymphocytes are implicated in the pathogenesis of multiple sclerosis . We aim ed to assess efficacy and safety of two dose regimens of the humanised anti-CD20 monoclonal antibody ocrelizumab in patients with relapsing-remitting multiple sclerosis . METHODS We did a multicentre , r and omised , parallel , double-blind , placebo-controlled study involving 79 centres in 20 countries . Patients aged 18 - 55 years with relapsing-remitting multiple sclerosis were r and omly assigned ( 1:1:1:1 ) via an interactive voice response system to receive either placebo , low-dose ( 600 mg ) or high-dose ( 2000 mg ) ocrelizumab in two doses on days 1 and 15 , or intramuscular interferon beta-1a ( 30 μg ) once a week . The r and omisation list was not disclosed to the study centres , monitors , project statisticians or to the project team at Roche . All groups were double blinded to group assignment , except the interferon beta-1a group who were rater masked . At week 24 , patients in the initial placebo , 600 mg ocrelizumab , and interferon beta-1a groups received ocrelizumab 600 mg ; the 2000 mg group received 1000 mg . Our primary endpoint was the total number of gadolinium-enhancing lesions ( GEL ) and T1-weighted MRI at weeks 12 , 16 , 20 , and 24 . Analyses were done on an intention-to-treat basis . This trial is registered with Clinical Trials.gov , number NCT00676715 . FINDINGS 218 ( 99 % ) of the 220 r and omised patients received at least one dose of ocrelizumab , 204 ( 93 % ) completed 24 weeks of the study and 196 ( 89 % ) completed 48 weeks . In the intention-to-treat population of 218 patients , at week 24 , the number of gadolinium-enhancing lesions was 89 % ( 95 % CI 68 - 97 ; p<0·0001 ) lower in the 600 mg ocrelizumab group than in the placebo group , and 96 % ( 89 - 99 ; p<0·0001 ) lower in the 2000 mg group . In exploratory analyses , both 600 mg and 2000 mg ocrelizumab groups were better than interferon beta-1a for GEL reduction . We noted serious adverse events in two of 54 ( 4 % ; 95 % CI 3·0 - 4·4 ) patients in the placebo group , one of 55 ( 2 % ; 1·3 - 2·3 ) in the 600 mg ocrelizumab group , three of 55 ( 5 % ; 4·6 - 6·3 ) in the 2000 mg group , and two of 54 ( 4 % ; 3·0 - 4·4 ) in the interferon beta-1a group . INTERPRETATION The similarly pronounced effects of B-cell depletion with both ocrelizumab doses on MRI and relapse-related outcomes support a role for B-cells in disease pathogenesis and warrant further assessment in large , long-term trials . FUNDING F Hoffmann-La Roche Ltd , Biogen Idec BACKGROUND Interferon beta reduces activity in multiple sclerosis as measured clinical ly and by magnetic resonance imaging ( MRI ) . We assessed the effect of interferon beta-1a on the occurrence of relapses in patients after first presentation with neurological events , who are at high risk of conversion to clinical ly definite multiple sclerosis . METHODS Eligible patients had had a first episode of neurological dysfunction suggesting multiple sclerosis within the previous 3 months and had strongly suggestive brain MRI findings . Patients were r and omly assigned interferon beta-1a 22 microg or placebo subcutaneously once weekly for 2 years . Neurological and clinical assessment s were done every 6 months and brain MRI every 12 months . Analyses excluded one patient assigned placebo who received no study injections . FINDINGS 241 ( 78 % ) of 308 r and omised patients received study treatment for 2 years ; 278 ( 90 % ) remained in the study until termination . 57 ( 85 % ) of 67 who stopped therapy did so after conversion to clinical ly definite multiple sclerosis . Fewer patients developed clinical ly definite multiple sclerosis in the interferon group than in the placebo group ( 52/154 [ 34 % ] vs 69/154 [ 45 % ] ; p=0.047 ) . The time at which 30 % of patients had converted to clinical ly definite multiple sclerosis was 569 days in the interferon group and 252 in the placebo group ( p=0.034 ) . The annual relapse rates were 0.33 and 0.43 ( p=0.045 ) . The number of new T2-weighted MRI lesions and the increase in lesion burden were significantly lower with active treatment . INTERPRETATION Interferon beta-1a treatment at an early stage of multiple sclerosis had significant positive effects on clinical and MRI outcomes OBJECTIVES In 85 % of young adults with multiple sclerosis ( MS ) , onset is a subacute clinical ly isolated syndrome ( CIS ) of the optic nerves , brain stem or spinal cord . The advent of disease-modifying treatments for MS has increased attention on early stages of the disease . Therefore , the aim of this study was to evaluate the effect of interferon on relapses and progression of disability in patients with a CIS . PATIENTS AND METHODS This r and omized , clinical trial was conducted in 25 patients who presented with a CIS indicative of MS . They were evaluated in two groups : 11 patients who were receiving interferon-beta(1a ) ( Rebif , Serono ) subcutaneous injections three times a week ( group A ) , and 14 patients who were not receiving disease-modifying treatment ( group B ) . The progression of disability was determined using the Kurtzke Exp and ed Disability Status Scale ( EDSS ) and the numbers of new relapses were recorded during 21 months of follow-up . RESULTS The mean numbers of new relapses and changes in EDSS at the end of study period were 0.68 ( st and ard deviation [S.D.]=0.80 ) and -1.09 ( S.D.=0.49 ) , and 1.79 ( S.D.=1.05 ) and -0.64 ( S.D.=0.49 ) in groups A and B , respectively . Statistical analysis showed that disease-modifying treatment with interferon-beta(1a ) may reduce relapses ( P=0.007 ) and prevent progressive disability ( P=0.034 ) . CONCLUSION Interferon-beta(1a ) significantly delayed progression to disability and incidence of new relapses The aim of the study was to estimate the rate of conversion from clinical ly isolated syndrome ( CIS ) to multiple sclerosis ( MS ) and to investigate variables predicting conversion in a cohort of patients presenting with symptoms suggestive of MS . Patients with a first symptom suggestive of MS in the preceding 6 months and exclusion of other diseases were enrolled in an observational prospect i ve study from December 2004 through June 2007 . Conversion from CIS to MS according to both McDonald and Clinical ly Defined Multiple Sclerosis ( CDMS ) criteria was prospect ively recorded until March 2010 . The multivariate Cox proportional hazard model was used to assess the best predictive factors of conversion from CIS to MS . Among 168 patients included in the analysis , 122 converted to MS according to McDonald criteria whereas 81 converted to MS according to CDMS criteria . The 2-year probability of conversion was 57 % for McDonald Criteria and 36 % for CDMS criteria . Variables at enrolment significantly associated with conversion according to McDonald criteria were age and positivity for Barkhof criteria , and according to Poser ’s CDMS criteria , age , positivity for Barkhof criteria and no disease modifying therapy . In this large prospect i ve cohort study the conversion rate from CIS to MS in patients presenting with recent symptoms suggestive of MS was within the range of previous observational studies and lower than that reported in the placebo arm of r and omized trials . We confirm the prognostic value of MRI in addition to the previous experimental data on the protective role of disease-modifying therapies BACKGROUND In patients presenting with a first clinical demyelinating event that is suggestive of multiple sclerosis ( MS ) , treatment with interferon beta can delay the occurrence of further attacks and the onset of MS . We investigated the effects of two dosing frequencies of subcutaneous interferon beta-1a in patients with a first clinical demyelinating event . METHODS We undertook a multicentre phase 3 study ( REbif FLEXible dosing in early MS [ REFLEX ] ) that included patients ( aged 18 - 50 years ) with a single clinical event suggestive of MS , and at least two clinical ly silent T2 lesions on brain MRI . Participants were r and omly assigned in a 1:1:1 ratio by use of a central ised interactive voice response system to receive the serum-free formulation of subcutaneous interferon beta-1a 44 μg three times a week or once a week ( plus placebo twice a week for masking ) , or placebo three times a week for up to 24 months . Patients and physicians were masked to group allocation . The primary endpoint was time to a diagnosis of MS as defined by the 2005 McDonald criteria and the main secondary endpoint was time to clinical ly definite MS ( CDMS ) as defined by the Poser criteria . Analysis was by intention to treat . The study is registered with Clinical Trials.gov , number NCT00404352 . FINDINGS 517 patients were r and omly assigned ( 171 to subcutaneous interferon beta-1a three times a week , 175 to subcutaneous interferon beta-1a once a week , and 171 to placebo ) and 515 were treated . The 2-year cumulative probability of McDonald MS was significantly lower in patients treated with subcutaneous interferon beta-1a ( three times a week 62·5 % , p<0·0001 , hazard ratio [ HR ] 0·49 [ 95 % CI 0·38 - 0·64 ] ; once a week 75·5 % , p=0·008 , HR 0·69 [ 0·54 - 0·87 ] ) versus placebo ( 85·8 % ) . 2-year rates of conversion to CDMS were lower for both interferon beta-1a dosing regimens ( three times a week 20·6 % , p=0·0004 , HR 0·48 [ 0·31 - 0·73 ] ; once a week 21·6 % , p=0·0023 , HR 0·53 [ 0·35 - 0·79 ] ) than for placebo ( 37·5 % ) . Adverse events were within the established profile for subcutaneous interferon beta-1a . INTERPRETATION Both regimens of subcutaneous interferon beta-1a delayed clinical relapses and sub clinical disease activity . The potential differences between the regimens warrant longer-term study . FUNDING Merck Serono SA , Geneva , Switzerl and Background : Patients with clinical ly isolated syndrome ( CIS ) and characteristic magnetic resonance imaging ( MRI ) lesions are at high risk for multiple sclerosis ( MS ) . However , patients with a minimal MRI lesion burden ( a low T2-hyperintense [ low T2 ] lesion count ) may have borderline formal diagnostic criteria , presenting a clinical management challenge . Objective : Compare the 10-year disease progression of patients with low and higher T2 lesion counts treated over most intervals . Methods : CIS patients from the original CHAMPS MS trial were retrospectively assigned to low-T2 ( first quartile ; 2–8 lesions ) or higher-T2 ( second through fourth quartiles ; ≥ 9 lesions ) groups using baseline T2 lesion counts . The 5- and 10-year open-label extension of CHAMPS ( CHAMPIONS ) evaluated conversion to clinical ly definite MS ( CDMS ) , MRI activity , relapses , and disability . Results : The vast majority of patients showed new disease activity by MRI and /or clinical criteria at 10 years ( low-T2 86 % ; higher-T2 98 % ) . Fewer low-T2 than higher-T2 patients developed CDMS ( 40 % vs. 63 % ; p = 0.013 ) ; low-T2 patients also had fewer new brain lesions , less brain volume loss , and less disability progression . Conclusion : CIS patients with low T2 lesion counts show continued disease activity . However , all assessment s of disease progression over 10 years indicated a significantly less severe disease course for low-T2 patients The mechanisms leading to disability and the long-term efficacy and safety of disease modifying drugs ( DMDs ) in multiple sclerosis ( MS ) are unclear . We aim ed at building a prospect i ve cohort of MS patients with st and ardized collection of demographic , clinical , MRI data and body fluids that can be used to develop prognostic indicators and biomarkers of disease evolution and therapeutic response . The Swiss MS Cohort ( SMSC ) is a prospect i ve observational study performed across seven Swiss MS centers including patients with MS , clinical ly isolated syndrome ( CIS ) , radiologically isolated syndrome or neuromyelitis optica . Neurological and radiological assessment s and biological sample s are collected every 6–12 months . We recruited 872 patients ( clinical ly isolated syndrome [ CIS ] 5.5 % , relapsing-remitting MS [ RRMS ] 85.8 % , primary progressive MS [ PPMS ] 3.5 % , secondary progressive MS [ SPMS ] 5.2 % ) between June 2012 and July 2015 . We performed 2,286 visits ( median follow-up 398 days ) and collected 2,274 serum , plasma and blood sample s , 152 cerebrospinal fluid sample s and 1,276 brain MRI scans . 158 relapses occurred and exp and ed disability status scale ( EDSS ) scores increased in PPMS , SPMS and RRMS patients experiencing relapses . Most RRMS patients were treated with fingolimod ( 33.4 % ) , natalizumab ( 24.5 % ) or injectable DMDs ( 13.6 % ) . The SMSC will provide relevant information regarding DMDs efficacy and safety and will serve as a comprehensive infrastructure available for nested research projects BACKGROUND In the Betaseron/Betaferon in Newly Emerging Multiple Sclerosis for Initial Treatment ( BENEFIT ) study , interferon beta-1b delayed conversion to multiple sclerosis in patients with a first clinical event and at least 2 clinical ly silent brain magnetic resonance imaging ( MRI ) lesions . OBJECTIVE To examine detailed MRI findings from the first 2 years of this trial . DESIGN Double-blind , placebo-controlled , r and omized , parallel-group , multicenter , phase 3 study . SETTING Ninety-eight centers worldwide . PATIENTS A total of 404 individuals with a first demyelinating event suggestive of multiple sclerosis . INTERVENTIONS Patients were r and omized to receive interferon beta-1b , 250 microg subcutaneously every other day , or placebo . After 24 months of treatment or on conversion to clinical ly definite multiple sclerosis , open-label interferon beta-1b treatment was offered . MAIN OUTCOME MEASURES Reported MRI data from patients completing 2 years of follow-up . RESULTS Data were analyzed from 248 patients taking interferon beta-1b and 156 taking placebo . Across 2 years the cumulative number of newly active lesions was lower in patients receiving interferon beta-1b vs placebo ( median , 2.0 vs 5.0 [ reduction of 60 % ] ; P < .001 ) . This corresponded to lower cumulative numbers of new T2 lesions ( median , 1.0 vs 3.0 [ reduction of 66 % ] ; P < .001 ) and new gadolinium-enhancing lesions ( median , 0.0 vs 1.0 ; P < .001 ) in patients receiving interferon beta-1b vs placebo . From screening to month 24 , T2 lesion volume decreased and was more pronounced in patients receiving interferon beta-1b ( P = .02 ) . CONCLUSIONS Interferon beta-1b treatment had a robust effect on MRI measures , supporting its value as an early intervention in this patient group . This effect was maintained despite including patients who switched from placebo to interferon beta-1b in the active treatment group . Trial Registration clinical trials.gov Identifier : NCT00185211 Objective : To determine the frequency and consequences of neutralizing antibodies ( NAbs ) in patients with a first event suggestive of multiple sclerosis ( MS ) treated with interferon β-1b ( IFNβ-1b ) . Methods : In the Betaseron/Betaferon in Newly Emerging MS For Initial Treatment ( BENEFIT ) study , patients were r and omly assigned to 250 μg IFNβ-1b ( Betaferon ) or placebo subcutaneously every other day for 2 years or until diagnosis of clinical ly definite MS ( CDMS ) . Patients were then offered open-label IFNβ-1b for up to 5 years . NAb status was assessed every 6 months by the myxovirus protein A induction assay . A titer > 20 NU/mL was considered NAb-positive , with low ( ≥20–100 NU/mL ) , medium ( ≥100–400 NU/mL ) , and high ( ≥400 NU/mL ) titer categories . Here we examine early-treated patients , who received IFNβ-1b for up to 5 years . Results : NAbs were measured in 277 of 292 early-treated patients and detected at least once in 88 ( 31.8 % ) patients , with 53 ( 60.2 % ) reverting to NAb negativity by year 5 . Time to CDMS , time to confirmed disability progression , and annualized relapse rate did not differ between NAb-positive and NAb-negative patients or between periods of NAb positivity vs NAb negativity within patients . Increases in newly active lesion number and T2 lesion volume and conversion to McDonald MS were associated with NAb positivity and were more pronounced with higher titers . Conclusions : Although NAb positivity was associated with increased brain MRI activity , no discernible effects on clinical outcomes were found . This finding may reflect the greater power of MRI compared with clinical outcomes to detect the treatment effects of IFNβ-1b and may also result from temporal changes in NAb titers and biology We evaluated 190 patients in the placebo group of the CHAMPS trial in order to assess factors associated with short-term clinical and brain magnetic resonance imaging ( MRI ) outcomes in patients with a first clinical demyelinating event involving the optic nerve , spinal cord , or brainstem/cerebellum , and sub clinical demyelination on brain MRI . The two study outcomes were 1 ) development of clinical ly definite multiple sclerosis ( CDMS ) and 2 ) development of CDMS or two or more new or enlarging brain MRI T2 lesions . The presence of gadolinium (Gd)- enhancing lesions on the baseline scan was the only MRI characteristic associated with a higher risk of both the clinical and combined outcomes ( p=0.003 and < 0.001 , respectively ) . The only demographic or clinical characteristic associated with an increased risk of these outcomes was younger age ( p<0.001 for both outcomes ) . The lowest risk subgroups we could define had a 30 % risk of CDMS and a 65 % risk of the combined clinical /MRI outcome . Our results indicate that all patients presenting with a first demyelinating event who also have brain MRI evidence of sub clinical demyelination have at least a moderate risk of short-term disease activity . This finding provides support for initiating disease-modifying therapy at the time of the first demyelinating event in patients meeting the CHAMPS enrollment criteria Glatiramer acetate ( GA ; Copaxone ) is a r and om sequence polypeptide used in the treatment of relapsing remitting multiple sclerosis ( RR MS ) . We have recently demonstrated that prior to treatment , GA induces proliferation of resting T cells and is not cross-reactive with myelin antigens . Daily GA injections induce a significant loss of this GA responsiveness , which is associated with the induction of highly cross-reactive Th2-type T cells potentially capable of suppressing inflammatory responses . The mechanism of action by which GA induces T cell nonresponsiveness leading to T cell receptor degeneracy in patients with RR MS is unknown . Here , we examined the effects of daily GA administration on the induction of T cell hyporesponsiveness . The frequency of GA-reactive T cells in peripheral blood of seven patients with RR MS was measured by limiting dilution analysis prior to and during 6 months of treatment . In addition , a model in which GA-reactive T cells were stimulated in vitro was developed to better characterize the selection of T cell population s over time . In vivo treatment with GA induced a decrease in GA-reactive T cell frequencies and hyporesponsiveness of CD4(+ ) T cell reactivity to GA in vitro that was only partially reversed by the addition of IL-2 . These data suggest that T cell peripheral tolerance to GA was achieved in vivo during treatment . Thus , our in vitro data suggest that the underlying changes in GA-reactive CD4(+ ) T cell reactivity could be explained by the induction of T cell anergy and clonal elimination OBJECTIVE To determine whether immediate initiation of treatment at the time of a clinical ly isolated syndrome in patients at high risk for clinical ly definite multiple sclerosis alters disease course over 10 years . DESIGN Prospect i ve follow-up study . SETTING Twenty-four Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention Study ( CHAMPS ) sites in the United States and Canada . PARTICIPANTS A total of 81 patients originally r and omly assigned to receive intramuscular interferon beta-1a ( the immediate-treatment group ) and 74 patients originally r and omly assigned to receive placebo ( the delayed-treatment group ) . All patients were from CHAMPS . INTERVENTION For the immediate-treatment group , treatment was initiated within a month after the onset of a clinical ly isolated syndrome , and for the delayed-treatment group , treatment was initiated a median of 30 months ( interquartile range , 24 - 35 months ) after CHAMPS r and omization . MAIN OUTCOME MEASURES Rate of developing clinical ly definite multiple sclerosis , annualized relapse rate , disease course classification , disability measures , and magnetic resonance imaging measures . RESULTS The immediate-treatment group showed a lower 10-year rate of clinical ly definite multiple sclerosis ( unadjusted hazard ratio , 0.64 [ 95 % CI , 0.48 - 0.87 ] ; P = .004 ) and a lower annualized relapse rate between years 5 and 10 ( P = .03 ) . There was no differential effect on disability , magnetic resonance imaging T2-weighted lesions , or the proportion of patients developing progressive disease at 10 years . Few patients reached the Exp and ed Disability Status Scale milestone scores of 4.0 or greater ( 9 % of patients ) or 6.0 or greater ( 6 % of patients ) . CONCLUSIONS Immediate initiation of intramuscular interferon beta-1a at the time of a clinical ly isolated syndrome in high-risk patients reduces relapse rates over 10 years but does not improve disability outcomes compared with a control group that also initiated therapy relatively early in the disease course . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00179478 This study clinical ly evaluated a novel PEGylated form of interferon beta-1a ( PEG-IFN beta-1a ) , a potential first-line treatment for relapsing multiple sclerosis , in healthy volunteers . Two r and omized , blinded phase I studies were conducted : a single-dose study ( n = 60 ) comparing subcutaneous or intramuscular PEG-IFN beta-1a ( 63 , 125 , or 188 µg ) with intramuscular unmodified IFN beta-1a 30 µg and a multiple-dose study ( n = 69 ) comparing subcutaneous PEG-IFN beta-1a dosed once every 2 or 4 weeks with placebo . Assessment s included pharmacokinetic and pharmacodynamic ( serum neopterin and 2',5'-OAS ) measures , exploratory immune assessment s , safety , and tolerability . A dose-proportional increase in PEG-IFN beta-1a exposure was observed , with a 4-fold greater exposure at 63 µg ( 6 million international units [ MIU ] ) of PEG-IFN beta-1a than with 30 µg ( 6 MIU ) intramuscular unmodified IFN beta-1a . Increases in neopterin and 2',5'-OAS levels and changes in T helper cell pathway gene expression and lymphocyte subsets were greater and more sustained with PEG-IFN beta-1a than with unmodified IFN beta-1a . PEG-IFN beta-1a was well tolerated , with only transient reductions in absolute neutrophils and some lymphocytes . Flu-like symptoms were a commonly reported adverse event . These data support the continued clinical development of PEG-IFN beta-1a as a potentially effective treatment for patients with relapsing multiple sclerosis Background : The placebo-controlled phase of the PreCISe study showed that glatiramer acetate delayed onset of clinical ly definite multiple sclerosis ( CDMS ) in patients with clinical ly isolated syndrome and brain lesions on MRI . Objective : To compare the effects of early versus delayed glatiramer acetate treatment in the open-label phase of PreCISe . Methods : Patients with a clinical ly isolated syndrome suggestive of MS with unifocal manifestation and ≥2 T2-weighted brain lesions were r and omized to receive glatiramer acetate 20 mg/d ( early-treatment , n=198 ) or placebo ( delayed-treatment , n=211 ) for 36 months or until conversion to CDMS , followed by open-label glatiramer acetate treatment for two years . Results : Early glatiramer acetate treatment reduced CDMS conversion risk by 41 % ( hazard ratio 0.59 , 95 % confidence interval 0.44–0.80 ; p=0.0005 ) versus delayed-treatment , and was associated with a 972-day delay ( 185 % ) in conversion to CDMS , less brain atrophy ( −28 % , p=0.0209 ) , fewer new T2 lesions/year ( −42 % , < 0.0001 ) and lower T2 lesion volume ( −22 % , p=0.0005 ) versus delayed treatment . Adverse events were consistent with the established safety profile of glatiramer acetate . Conclusions : Effects of early glatiramer acetate treatment on the rate of conversion to CDMS and on MRI measures of disease activity and lesion burden support initiating glatiramer acetate treatment soon after the first clinical symptoms suggestive of MS and continuing treatment to sustain benefits BACKGROUND The Betaferon/Betaseron in newly emerging multiple sclerosis for initial treatment ( BENEFIT ) trial investigated the effect of treatment with interferon beta-1b after a clinical ly isolated syndrome . The 5-year active treatment extension compares the effects of early and delayed treatment with interferon beta-1b on time to clinical ly definite multiple sclerosis ( CDMS ) and other disease outcomes , including disability progression . METHODS Patients with a first event suggestive of multiple sclerosis and a minimum of two clinical ly silent lesions in MRI were r and omly assigned to receive interferon beta-1b 250 microg ( n=292 ; early treatment ) or placebo ( n=176 ; delayed treatment ) subcutaneously every other day for 2 years , or until diagnosis of CDMS . All patients were then eligible to enter a prospect ively planned follow-up phase with open-label interferon beta-1b up to a maximum of 5 years after r and omisation . Patients and study personnel remained unaware of initial treatment allocation throughout the study . Primary endpoints were time to CDMS , time to confirmed disability progression measured with the exp and ed disability status scale , and the functional assessment of multiple sclerosis trial outcomes index ( FAMS-TOI ) at 5 years . Analysis of the primary endpoints was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00185211 . FINDINGS 235 ( 80 % ) patients from the early treatment and 123 ( 70 % ) from the delayed treatment group completed the 5-year study . Early treatment reduced the risk of CDMS by 37 % ( hazard ratio [ HR ] 0.63 , 95 % CI 0.48 - 0.83 ; p=0.003 ) compared with delayed treatment . The risk for confirmed disability progression was not significantly lower in the early treatment group ( 0.76 , 0.52 - 1.11 ; p=0.177 ) . At 5 years , median FAMS-TOI scores were 125 in both groups . No significant differences in other disability related outcomes were recorded . Frequency and severity of adverse events remained within the established safety and tolerability profile of interferon beta-1b . INTERPRETATION Effects on the rate of conversion to CDMS and the favourable long-term safety and tolerability profile support early initiation of treatment with interferon beta-1b , although a delay in treatment by up to 2 years did not affect long-term disability outcomes . FUNDING Bayer Schering Pharma BACKGROUND Glatiramer acetate , approved for the treatment of relapsing-remitting multiple sclerosis , reduces relapses and disease activity and burden monitored by MRI . We assessed the efficacy of early treatment with glatiramer acetate in delaying onset of clinical ly definite multiple sclerosis . METHODS In this r and omised , double-blind trial , undertaken in 80 sites in 16 countries , 481 patients presenting with a clinical ly isolated syndrome with unifocal manifestation , and two or more T2-weighted brain lesions measuring 6 mm or more , were r and omly assigned to receive either subcutaneous glatiramer acetate 20 mg per day ( n=243 ) or placebo ( n=238 ) for up to 36 months , unless they converted to clinical ly definite multiple sclerosis . The r and omisation scheme used SAS-based blocks stratified by centre , and patients and all personnel were masked to treatment assignment . The primary endpoint was time to clinical ly definite multiple sclerosis , based on a second clinical attack . Analysis was by intention to treat . A preplanned interim analysis was done for data accumulated from 81 % of the 3-year study exposure . This study was registered with Clinical Trials.gov , number NCT00666224 . FINDINGS All r and omly assigned participants were analysed for the primary outcome . Glatiramer acetate reduced the risk of developing clinical ly definite multiple sclerosis by 45 % compared with placebo ( hazard ratio 0.55 , 95 % CI 0.40 - 0.77 ; p=0.0005 ) . The time for 25 % of patients to convert to clinical ly definite disease was prolonged by 115 % , from 336 days for placebo to 722 days for glatiramer acetate . The most common adverse events in the glatiramer acetate group were injection-site reactions ( 135 [ 56 % ] glatiramer acetate vs 56 [ 24 % ] placebo ) and immediate post-injection reactions ( 47 [ 19 % ] vs 12 [ 5 % ] ) . INTERPRETATION Early treatment with glatiramer acetate is efficacious in delaying conversion to clinical ly definite multiple sclerosis in patients presenting with clinical ly isolated syndrome and brain lesions detected by MRI . FUNDING Teva Pharmaceutical Industries , Israel BACKGROUND Teriflunomide is a once-daily oral immunomodulator approved for the treatment of relapsing-remitting multiple sclerosis . We aim ed to assess the efficacy and safety of teriflunomide in patients with a first clinical episode suggestive of multiple sclerosis . METHODS In this r and omised , double-blind , placebo-controlled , parallel-group study , we enrolled patients aged 18 - 55 years with clinical ly isolated syndrome ( defined as a neurological event consistent with demyelination , starting within 90 days of r and omisation , and two or more T2-weighted MRI lesions ≥3 mm in diameter ) from 112 centres ( mostly hospitals ) in 20 countries . Participants were r and omly assigned ( 1:1:1 ) in a double-blind manner ( by an interactive voice response system ) to once-daily oral teriflunomide 14 mg , teriflunomide 7 mg , or placebo , for up to 108 weeks . Patients , staff administering the interventions , and outcome assessors were masked to treatment assignment . The primary endpoint was time to relapse ( a new neurological abnormality separated by ≥30 days from a preceding clinical event , present for ≥24 h in the absence of fever or known infection ) , which defined conversion to clinical ly definite multiple sclerosis . The key secondary endpoint was time to relapse or new gadolinium-enhancing or T2 lesions on MRI , whichever occurred first . The primary outcome was analysed for the modified intention-to-treat population ; safety analyses included all r and omised patients who were exposed to the study drug , as treated . This trial is registered with Clinical Trials.gov , number NCT00622700 . FINDINGS Between Feb 13 , 2008 , and Aug 22 , 2012 , 618 patients were enrolled and r and omly assigned to teriflunomide 14 mg ( n=216 ) , teriflunomide 7 mg ( n=205 ) , or placebo ( n=197 ) . Two patients in each of the teriflunomide groups did not receive the study drug , so the modified intention-to-treat population comprised 214 patients in the teriflunomide 14 mg group , 203 in the teriflunomide 7 mg group , and 197 in the placebo group . Compared with placebo , teriflunomide significantly reduced the risk of relapse defining clinical ly definite multiple sclerosis at the 14 mg dose ( hazard ratio [ HR ] 0·574 [ 95 % CI 0·379 - 0·869 ] ; p=0·0087 ) and at the 7 mg dose ( 0·628 [ 0·416 - 0·949 ] ; p=0·0271 ) . Teriflunomide reduced the risk of relapse or a new MRI lesion compared with placebo at the 14 mg dose ( HR 0·651 [ 95 % CI 0·515 - 0·822 ] ; p=0·0003 ) and at the 7 mg dose ( 0·686 [ 0·540 - 0·871 ] ; p=0·0020 ) . During the study , six patients who were r and omly assigned to placebo accidently also received teriflunomide at some point : four received 7 mg and two received 14 mg . Therefore , the safety population comprised 216 patients on teriflunomide 14 mg , 207 on teriflunomide 7 mg , and 191 on placebo . Adverse events that occurred in at least 10 % of patients in either teriflunomide group and with an incidence that was at least 2 % higher than that with placebo were increased alanine aminotransferase ( 40 [ 19 % ] of 216 patients in the 14 mg group , 36 [ 17 % ] of 207 in the 7 mg group vs 27 [ 14 % ] of 191 in the placebo group ) , hair thinning ( 25 [ 12 % ] and 12 [ 6 % ] vs 15 [ 8 % ] ) , diarrhoea ( 23 [ 11 % ] and 28 [ 14 % ] vs 12 [ 6 % ] ) , paraesthesia ( 22 [ 10 % ] and 11 [ 5 % ] vs 10 [ 5 % ] ) , and upper respiratory tract infection ( 20 [ 9 % ] and 23 [ 11 % ] vs 14 [ 7 % ] ) . The most common serious adverse event was an increase in alanine aminotransferase ( four [ 2 % ] and five [ 2 % ] vs three [ 2 % ] ) . INTERPRETATION TOPIC is to our knowledge the first study to report benefits of an available oral disease-modifying therapy in patients with early multiple sclerosis . These results extend the stages of multiple sclerosis in which teriflunomide shows a beneficial effect . FUNDING Genzyme , a Sanofi company BACKGROUND Treatment with interferon beta has been shown to help patients with established multiple sclerosis , but it is not known whether initiating treatment at the time of a first clinical demyelinating event is of value . METHODS We conducted a r and omized , double-blind trial of 383 patients who had a first acute clinical demyelinating event ( optic neuritis , incomplete transverse myelitis , or brain-stem or cerebellar syndrome ) and evidence of prior sub clinical demyelination on magnetic resonance imaging ( MRI ) of the brain . After initial treatment with corticosteroids , 193 patients were r and omly assigned to receive weekly intramuscular injections of 30 microg of interferon beta-1a and 190 were assigned to receive weekly injections of placebo . The study end points were the development of clinical ly definite multiple sclerosis and changes in findings on MRI of the brain . The trial was stopped after a preplanned interim efficacy analysis . RESULTS During three years of follow-up , the cumulative probability of the development of clinical ly definite multiple sclerosis was significantly lower in the interferon beta-1a group than in the placebo group ( rate ratio , 0.56 ; 95 percent confidence interval , 0.38 to 0.81 ; P=0.002 ) . As compared with the patients in the placebo group , patients in the interferon beta-1a group had a relative reduction in the volume of brain lesions ( P<0.001 ) , fewer new or enlarging lesions ( P<0.001 ) , and fewer gadolinium-enhancing lesions ( P<0.001 ) at 18 months . CONCLUSIONS Initiating treatment with interferon beta-1a at the time of a first demyelinating event is beneficial for patients with brain lesions on MRI that indicate a high risk of clinical ly definite multiple sclerosis BACKGROUND Patients who develop relapsing-remitting multiple sclerosis ( MS ) present with a first clinical demyelinating event . In this double-blind , multicentre , r and omised , phase 3 study we investigated the effect of oral cladribine on conversion to clinical ly definite MS in patients with a first clinical demyelinating event , when given at the same doses shown to be effective in relapsing-remitting MS . METHODS Between Oct 21 , 2008 , and Oct 11 , 2010 , we recruited patients aged 18 - 55 years , inclusive , from 160 hospitals , private clinics , or treatment centres in 34 countries . Eligible patients had a first clinical demyelinating event within 75 days before screening , at least two clinical ly silent lesions of at least 3 mm on a T2-weighted brain MRI scan , and an Exp and ed Disability Status Scale score of 5.0 or lower . Patients with a first clinical demyelinating event ≤75 days before screening were r and omly assigned ( 1:1:1 ) to receive cladribine tablets at cumulative doses of 5.25 mg/kg or 3.5 mg/kg or placebo . R and omisation was done with a central web-based r and omisation system and was stratified by geographic region . Masking was maintained using a two-physician model . The primary endpoint of this 96-week study was time to conversion to clinical ly definite MS according to the Poser criteria . This study is registered with Clinical Trials.gov , number NCT00725985 . FINDINGS Of 903 participants assessed for eligibility , 616 patients received cladribine 5.25 mg/kg ( n=204 ) , cladribine 3.5 mg/kg ( n=206 ) , or placebo ( n=206 ) . At trial termination on Oct 25 , 2011 , cladribine was associated with a risk reduction versus placebo for time to conversion to clinical ly definite MS ( hazard ratio [ HR ] for 5.25 mg/kg=0.38 , 95 % CI 0.25 - 0.58 , p<0.0001 ; HR for 3.5 mg/kg=0.33 , 0.21 - 0.51 , p<0.0001 ) . Adverse events were reported in 165 ( 81 % ) patients in the cladribine 5.25 mg/kg group , 168 ( 82 % ) patients in the cladribine 3.5 mg/kg group , and 162 ( 79 % ) patients in the placebo group . We noted no increase in risk of adverse events with active treatment versus placebo apart from lymphopenia , which was a severe event in 10 ( 5 % ) patients in the 5.25 mg/kg group and four ( 2 % ) patients in the 3.5 mg/kg group . INTERPRETATION Both doses of cladribine significantly delayed MS diagnosis compared with placebo . The safety profile of cladribine was similar to that noted in a trial in patients with relapsing-remitting MS . Further research could clarify the potential effects of oral cladribine treatment in the early stages of MS . FUNDING Merck Serono SA Geneva , a subsidiary of Merck KGaA , Darmstadt , Germany BACKGROUND There is increasing evidence that B lymphocytes are involved in the pathogenesis of multiple sclerosis , and they may be a therapeutic target . Rituximab , a monoclonal antibody , selectively targets and depletes CD20 + B lymphocytes . METHODS In a phase 2 , double-blind , 48-week trial involving 104 patients with relapsing-remitting multiple sclerosis , we assigned 69 patients to receive 1000 mg of intravenous rituximab and 35 patients to receive placebo on days 1 and 15 . The primary end point was the total count of gadolinium-enhancing lesions detected on magnetic resonance imaging scans of the brain at weeks 12 , 16 , 20 , and 24 . Clinical outcomes included safety , the proportion of patients who had relapses , and the annualized rate of relapse . RESULTS As compared with patients who received placebo , patients who received rituximab had reduced counts of total gadolinium-enhancing lesions at weeks 12 , 16 , 20 , and 24 ( P<0.001 ) and of total new gadolinium-enhancing lesions over the same period ( P<0.001 ) ; these results were sustained for 48 weeks ( P<0.001 ) . As compared with patients in the placebo group , the proportion of patients in the rituximab group with relapses was significantly reduced at week 24 ( 14.5 % vs. 34.3 % , P=0.02 ) and week 48 ( 20.3 % vs. 40.0 % , P=0.04 ) . More patients in the rituximab group than in the placebo group had adverse events within 24 hours after the first infusion , most of which were mild-to-moderate events ; after the second infusion , the numbers of events were similar in the two groups . CONCLUSIONS A single course of rituximab reduced inflammatory brain lesions and clinical relapses for 48 weeks . This trial was not design ed to assess long-term safety or to detect uncommon adverse events . The data provide evidence of B-cell involvement in the pathophysiology of relapsing-remitting multiple sclerosis . ( Clinical Trials.gov number , NCT00097188 [ Clinical Trials.gov ] . ) BACKGROUND In patients who present with clinical ly isolated syndromes suggestive of multiple sclerosis , interferon beta-1a is effective in delaying evolution to clinical ly definite disease and in reducing MRI-measured disease activity . We aim ed to assess whether this drug can also reduce the rate of brain volume decrease in such patients enrolled in the ETOMS ( early treatment of multiple sclerosis ) trial . METHODS MRI data for brain volume measurements at baseline , month 12 , and month 24 were available from 131 , 111 , and 112 patients assigned treatment ( 22 microg interferon beta-1a ) , and 132 , 98 , and 99 patients assigned placebo respectively . Normalised brain parenchymal volume ( NBV ) at baseline and percentage brain volume changes ( PBVC ) were measured with a fully-automated segmentation technique . The primary endpoint was conversion to clinical ly definite multiple sclerosis due to clinical relapse . Analysis was by intention to treat . FINDINGS 41 ( 31 % ) of 131 patients on interferon beta-1a and 62 ( 47 % ) of 132 on placebo converted to clinical ly definite multiple sclerosis ( odds ratio 0.52 [ 95 % CI 0.31 - 0.86 ] , p=0.0115 ) . Mean PBVC for patients on placebo was -0.83 % during the first year , -0.67 % during the second year , and -1.68 % during the entire study period . Respective values for treated patients were -0.62 % , -0.61 % , and -1.18 % . The changes in brain volume were significant in both groups at all timepoints . A significant treatment effect was detected for month 24 versus baseline values ( p=0.0031 ) . The number of new T2 lesions formed during the first year correlated weakly with PBVC during the second year . INTERPRETATION Early treatment with interferon beta-1a is effective in reducing conversion to clinical ly definite multiple sclerosis and in slowing progressive loss of brain tissue in patients with clinical ly isolated syndromes . The modest correlation between new lesion formation and brain volume decrease suggests that inflammatory and neurodegenerative processes are , at least partly , dissociated from the earliest clinical stage of multiple sclerosis onwards Estimates of relative efficacy between alternative treatments are crucial for decision making in health care . Bayesian mixed treatment comparison models provide a powerful methodology to obtain such estimates when head-to-head evidence is not available or insufficient . In recent years , this methodology has become widely accepted and applied in economic modelling of healthcare interventions . Most evaluations only consider evidence from r and omized controlled trials , while information from other trial design s is ignored . In this paper , we propose three alternative methods of combining data from different trial design s in a mixed treatment comparison model . Naive pooling is the simplest approach and does not differentiate between-trial design s. Utilizing observational data as prior information allows adjusting for bias due to trial design . The most flexible technique is a three-level hierarchical model . Such a model allows for bias adjustment while also accounting for heterogeneity between-trial design s. These techniques are illustrated using an application in rheumatoid arthritis In the recently proposed diagnostic criteria for multiple sclerosis ( MS ) by McDonald , the modified magnetic resonance imaging ( MRI ) Barkhof criteria have been incorporated . We examined the validity of this implementation in the Early Treatment of MS study , a r and omized , double‐blind , placebo‐controlled study of 22μg interferon β1a given subcutaneously once weekly in 309 patients with a first episode consistent with demyelinating disease ( and abnormal MRI ) . Conversion to clinical ly definite MS ( CDMS ) within 2 years of follow‐up , as evidence d by a new clinical episode , occurred in 41 % of patients ( independent of treatment ) with gadolinium enhancement or nine or more T2 lesions versus 11 % of those without either finding ( p = 0.017 ) ; similarly , proportions converting were 44 % versus 31 % for infratentorial lesions ( p = 0.026 ) , 40 % versus 35 % for juxtacortical lesions ( p = 0.413 ) , and 41 % versus 17 % for three or more periventricular lesions ( p = 0.034 ) . The rate of conversion to CDMS based on the number of modified Barkhof criteria was 22 % for two or fewer positive criteria , increasing to 47 % with four positive criteria . For a cutoff of three positive criteria , the hazard ratio for time to CDMS was 2.3 ( 95 % confidence interval , 1.17–4.55 ; p = 0.016 ) . Treatment effect seemed more evident as the number of positive criteria increased , and the number of patients needed to avoid one patient converting to CDMS decreased from 50 in patients with one or two positive criteria to 5.6 in patients with four positive criteria . However , the study was not powered to detect statistically significant treatment by variable interaction , and this remains an important issue for further study .Ann Neurol BACKGROUND Two proof-of-concept clinical trials have provided evidence that laquinimod reduces disease activity in patients with relapsing-remitting multiple sclerosis . METHODS We conducted a r and omized , double-blind , phase 3 study at 139 sites in 24 countries . A total of 1106 patients with relapsing-remitting multiple sclerosis were r and omly assigned in a 1:1 ratio to receive oral laquinimod at a dose of 0.6 mg once daily or placebo for 24 months . The primary end point was the annualized relapse rate during the 24-month period . Secondary end points included confirmed disability progression ( defined as an increase in the score on the Exp and ed Disability Status Scale that was sustained for at least 3 months ) and the cumulative number of gadolinium-enhancing lesions and new or enlarging lesions on T(2)-weighted magnetic resonance imaging . RESULTS Treatment with laquinimod as compared with placebo was associated with a modest reduction in the mean ( ±SE ) annualized relapse rate ( 0.30±0.02 vs. 0.39±0.03 , P=0.002 ) and with a reduction in the risk of confirmed disability progression ( 11.1 % vs. 15.7 % ; hazard ratio , 0.64 ; 95 % confidence interval , 0.45 to 0.91 ; P=0.01 ) . The mean cumulative numbers of gadolinium-enhancing lesions and new or enlarging lesions on T(2)-weighted images were lower for patients receiving laquinimod than for those receiving placebo ( 1.33±0.14 vs. 2.12±0.22 and 5.03±0.08 vs. 7.14±0.07 , respectively ; P<0.001 for both comparisons ) . Transient elevations in alanine aminotransferase levels to greater than three times the upper limit of the normal range were observed in 24 patients receiving laquinimod ( 5 % ) and 8 receiving placebo ( 2 % ) . CONCLUSIONS In this phase 3 study , oral laquinimod administered once daily slowed the progression of disability and reduced the rate of relapse in patients with relapsing-remitting multiple sclerosis . ( Funded by Teva Pharmaceutical Industries ; Clinical Trials.gov number , NCT00509145 . ) |
12,292 | 31,747,720 | There is high- quality evidence that NSAIDs reduce pain up to 24 hours postoperatively .
There is low- quality evidence that scalp blocks and dexmedetomidine may reduce additional analgesics requirements . | BACKGROUND Pain following brain surgery can compromise recovery .
Several pharmacological interventions have been used to prevent pain after craniotomy ; however , there is currently a lack of evidence regarding which interventions are most effective .
OBJECTIVES The objectives are to assess the effectiveness of pharmacological interventions for prevention of acute postoperative pain in adults undergoing brain surgery ; compare them in terms of additional analgesic requirements , incidence of chronic headache , sedative effects , length of hospital stay and adverse events ; and determine whether these characteristics are different for certain subgroups . | Background This r and omized controlled study evaluated the efficacy of intravenous patient-controlled analgesia ( IV-PCA ) with fentanyl and ketorolac for neurosurgical patients , and compared the effectiveness of IV-PCA with intermittent analgesics injection . Methods The patients undergoing craniotomy were r and omly assigned to two groups . Patients of group P ( n = 53 ) received fentanyl ( 0.2 µg/kg/hr ) and ketorolac ( 0.3 mg/kg/hr ) via IV-PCA , and those of group N ( n = 53 ) received intermittent fentanyl or ketorolac injection as needed . Pain was evaluated using a 0 - 10 visual analogue scale ( VAS ) at postoperative 1 , 4 , and 24 hr . The amount of infused analgesic drugs , Glasgow Coma Scale ( GCS ) score , systolic arterial pressure , heart rate , respiratory rate , and the incidence of nausea and miosis were measured at the same time points . Results Although VAS of pain ( VASp ) was comparable at postoperative 1 hr ( P = 0.168 ) between the two groups , the group P had significantly lower VASp at postoperative 4 hr ( P = 0.007 ) and 24 hr ( P = 0.017 ) . In group P , less analgesic drugs were administered at postoperative 1 hr , and more analgesic drugs were administered at postoperative 24 hr . There were no differences between two groups with respect to nausea , GCS , systolic arterial pressure , and heart rate . IV-PCA did not further incur respiratory depression or miosis . Conclusions IV-PCA with fentanyl and ketorolac after craniotomy is more effective analgesic technique , without adverse events , than the intermittent administration of analgesics OBJECTIVE Postcraniotomy headache causes considerable pain and can be difficult to treat . We therefore tested the hypothesis that a single 100-mg preoperative dose of diclofenac reduces the intensity of postcraniotomy headache , and reduces analgesic requirements . METHODS 200 patients having elective craniotomies were r and omly assigned to diclofenac ( n = 100 ) or control ( n = 100 ) . Pain severity was assessed by an independent observer using a 10-cm-long visual analog scale the evening of surgery , and on the 1st and 5th postoperative days . Analgesics given during the first five postoperative days were converted to intramuscular morphine equivalents . Results were compared using Mann-Whitney-tests ; P < 0.05 was considered statistically significant . RESULTS Baseline and surgical characteristics were comparable in the diclofenac and control groups . Visual analog pain scores were slightly , but significantly lower with diclofenac at all times ( means and 95 % confidence intervals ) : the evening of surgery , 2.47 ( 1.8 - 3.1 ) vs. 4 . 37 ( 5.0 - 3.7 ) , ( P < 0.001 ) ; first postoperative day , 3.98 ( 3.4 - 4.6 ) vs. 5.6 ( 4.9 - 6.2 ) cm ( P < 0.001 ) and 5th postoperative day : 2.8 ( 2.2 - 3.4 ) vs. 4.0 ± ( 3.3 - 4.7 ) cm ( P = 0.013 ) . Diclofenac reduced systemic analgesic requirements over the initial five postoperative days ( mean and 95 % CI ) : 3.3 ( 2.6 - 3.9 ) vs. 4.3 ( 3.5 - 5.1 ) mg morphine equivalents ( P < 0.05 ) . CONCLUSIONS Preoperative diclofenac administration reduces postcraniotomy headache and postoperative analgesic requirements - a benefit that persisted throughout five postoperative days Introduction Acute pain is common during the endotracheal extubation period , and is related to complications and adverse outcomes . Patients with delayed extubation after craniotomy are vulnerable to pain and complications of extubation . However , pain control during extubation is still inadequate . Remifentanil , a new opioid with rapid onset and short duration of action , provides adequate analgesia during procedures with minimal effect of respiratory depression . Methods and analysis The study is a prospect i ve , r and omised , double-blinded , controlled parallel-group design . Patients with delayed extubation after intracranial surgery are screened daily . Adult patients ready for extubation are enrolled and assigned r and omly to one of the two treatment study groups , labelled as the ‘ Remi group ’ or ‘ Saline group ’ . Patients in the Remi group receive an intravenous bolus dose of remifentanil 0.5 μg/kg over 60 s followed by a continuous infusion 0.05 μg/kg/min for 20 min . Patients in the Saline group receive an intravenous infusion of 0.9 % sodium chloride at a volume and rate equal to that of remifentanil . Pain intensity is measured by the visual analogue scale ( VAS ) pain score . Adverse events during drug infusion are documented and reported . Patients will be followed up until hospital discharge , death or 60 days after the trial intervention on a first come , first served basis . Details of the incidence of reintubation and reoperation within 72 h after extubation , length of stay in the intensive care unit and hospital and mortality are collected . The primary end point is the incidence of severe pain ( defined as a VAS pain score more than 5 cm ) during the periextubation period ( defined as the period of time from immediately before extubation to 20 min after extubation ) . Ethics and dissemination The study was approved by the Institutional Review Board ( IRB ) of the Beijing Tiantan Hospital , Capital Medical University . The study findings will be disseminated through peer- review ed publications and conference presentations . Trial registration number Clinical Trials ( NCT ) : ChiCTR-PRC-13003879 Background : Gender differences in access to high quality care for chronic illnesses have been suggested yet little work in this potentially vital area of health care ine quality has been undertaken in Africa . We explored the influence of patient gender on the care of people with diabetes within a multi- method , national study of diabetes management in primary care in Tunisia . Methods : Method ologies used were quantitative ( nationwide r and omized study of 2160 medical records ) and qualitative ( participant observation , focus groups and interviews of patients and health care professionals ) . Results : Differences in patient characteristics , treatments prescribed , process and outcome data and access to care variables were demonstrated . The most striking disparity found was the high female to male ratio of patients attending for diabetes care ( 61.1 % ) . A number of possible explanations for this emerged : Men were thought to under-attend for practical , financial and behavioural reasons whereas women were thought to have increased morbidity and potentially over-attend for social and psychological reasons . Conclusion : We have demonstrated a number of disparities in the care of men and women with diabetes in Tunisian primary care . In particular , a dual but related problem emerges from the data : more women than men attend for diabetes care and yet women do not get the same level of risk factor control as men . A number of local explanations for these disparities have emerged , which inform our analysis of the impact of gendered beliefs on diabetes care . Strategies to address these disparities will require a careful consideration of local beliefs and practice Context : Scalp infiltration and scalp block are being used to manage postcraniotomy pain . Dexmedetomidine has been successfully used as an adjuvant in regional anesthesia . The study was intended to compare whether addition of dexmedetomidine prolonged the duration of analgesia as well as to compare the two techniques . Aims : The primary objective was to assess whether addition of dexmedetomidine to bupivacaine prolonged the duration of analgesia . The secondary objective was to compare between scalp nerve block and scalp infiltration as techniques for pain relief . Setting s and Design : The r and omized control study was conducted in a tertiary care center from November 2013 to October 2014 . Material s and Methods : A total of 150 American Society of Anesthesiologists Physical Status I – II patients , aged 18–70 years undergoing elective craniotomy were included . Patients were r and omized into three groups of 50 patients , i.e. , Group BI ( bupivacaine infiltration ) , Group BDI ( bupivacaine and dexmedetomidine infiltration ) , and Group BDNB ( bupivacaine and dexmedetomidine scalp nerve block ) . Patient 's pain score , pain-free interval , rescue analgesic requirement , and hemodynamic and respiratory parameters were noted for 48 h. Patients were followed up at 1 and 3 months to assess postcraniotomy pain . Results : Pain-free period was significantly longer in Group BDNB than Groups BDI and BI ( P < 0.0001 ) and pain control was better in dexmedetomidine containing groups than in bupivacaine group ( BI ) ( P < 0.0001 ) . The rescue analgesic requirement was significantly lower in Group BDNB and Group BDI compared to Group BI . Conclusion : The addition of dexmedetomidine ( 1 μg/kg ) to bupivacaine prolonged the pain-free period . Scalp nerve block is a superior technique than scalp infiltration Context A clear preference for intravenous or inhalational anaesthesia has not been established for craniotomy in patients without signs of cerebral hypertension . Objectives The NeuroMorfeo trial was design ed to test equivalence of inhalational and intravenous anaesthesia maintenance techniques in the postoperative recovery of patients undergoing elective supratentorial surgery . Design This trial is a multicentre , r and omised , open-label , equivalence design . A balanced stratified r and omisation scheme was maintained using a central ised r and omisation service . Equivalence was tested using the two one-sided tests procedure . Setting Fourteen Italian neuroanaesthesia centres participated in the study from December 2007 to March 2009 . Patients Adults , 18 to 75 years old , scheduled for elective supratentorial intracranial surgery under general anaesthesia were eligible for enrolment if they had a normal preoperative level of consciousness and no clinical signs of intracranial hypertension . Interventions Patients were r and omised to one of three anaesthesia maintenance protocol s to determine if sevoflurane – remifentanil or sevoflurane – fentanyl were equivalent to propofol – remifentanil . Main outcome measures The primary outcome was the time to achieve an Aldrete postanaesthesia score of at least 9 after tracheal extubation . Secondary endpoints included haemodynamic parameters , quality of the surgical field , perioperative neuroendocrine stress responses and routine postoperative assessment s. Results Four hundred and eleven patients [ 51 % men , mean age 54.8 ( SD 13.3 ) years ] were enrolled . Primary outcome data were available for 380 . Median ( interquartiles ) times to reach an Aldrete score of at least 9 were 3.48 ( 2.02 to 7.56 ) , 3.25 ( 1.21 to 6.45 ) and 3.32 min ( 1.40 to 8.33 ) for sevoflurane – fentanyl , sevoflurane – remifentanil and propofol – remifentanil anaesthesia respectively , which confirmed equivalence using the two one-sided tests approach . Between-treatment differences in haemodynamic variables were small and not clinical ly relevant . Urinary catecholamine and cortisol responses had significantly lower activation with propofol – remifentanil . Postoperative pain and analgesic requirements were significantly higher in the remifentanil groups . Conclusion Equivalence was shown for inhalational and intravenous maintenance anaesthesia in times to reach an Aldrete score of at least 9 after tracheal extubation . Haemodynamic variables , the quality of surgical field and postoperative assessment s were also similar . Perioperative endocrine stress responses were significantly blunted with propofol – remifentanil and higher analgesic requirements were recorded in the remifentanil groups . Trial registration : Eudract 2007–005279 - 32 BACKGROUND Pain after craniotomy is often under-treated . Opiates carry distinct disadvantages . Non-steroidal anti-inflammatory drugs have an anti-platelet action and carry a bleeding risk . Cyclo-oxygenase 2 inhibitors such as parecoxib are not associated with a bleeding risk and would be welcome analgesics if shown to be effective . METHODS In a prospect i ve double-blind , r and omized , placebo-controlled study , we investigated the analgesic effect of a single dose of parecoxib 40 mg given at dural closure in 82 patients undergoing elective craniotomies . Remifentanil was used intraoperatively , and i.v . morphine was titrated to the requirement in the post-anaesthetic unit . On the ward , i.m . morphine 5 mg as required and regular acetaminophen was prescribed . Morphine use and visual analogue pain scores were recorded at 1 , 6 , 12 , and 24 h after surgery . RESULTS Parecoxib reduced pain scores at 6 h and morphine use at 6 and 12 h after operation . However , overall , it had only minimal impact on postoperative analgesia . We found a wide variability in analgesic requirements where 11 % of patients required no opioids and 16 % required more than 15 mg i.v . morphine 1 h after the surgery . CONCLUSIONS We found only limited evidence to support parecoxib as an analgesic after craniotomy Background : Control of emergence hypertension and pain is important after craniotomy for monitoring the neurological status . This prospect i ve double-blinded study investigated the hemodynamics after a single bolus of dexmedetomidine ( DEX ) infusion administered to the patient undergoing craniotomy under general anesthesia , and its effect on emergence hypertension and postsurgical pain . Methods : Adult patients scheduled for elective surgery for supratentorial tumors were r and omized to receive a 10-minute intraoperative DEX infusion of 0.4 & mgr;g/kg ( small dose , n=43 ) or 0.8 & mgr;g/kg ( medium dose , n=46 ) , or normal saline ( vehicle control , n=45 ) , ∼60 minutes before the end of anesthesia . Results : A transient increase in the blood pressure associated with DEX was observed ; 53.5 % and 91.3 % of the patients in the small-dose and the medium-dose groups , respectively , required treatment . Emergence mean arterial pressure and heart rates were significantly lower in the DEX groups compared with the control group . Incidence rates of postoperative hypertension in the small-dose ( 16.3 % ) and the medium-dose groups ( 15.2 % ) were significantly lower relative to that of the control group ( 35.6 % ) . Patients who received DEX had a lower Verbal Numerical Rating Scale ( VNRS ) score in the neurosurgical ICU than the control group , and postsurgical pain ( VNRS≥4 ) was lower in the medium-dose group ( 41.3 % ) than in the control group ( 71.1 % ) . No shivering was observed in the medium-dose group , which was significantly less than that of the other 2 groups . Conclusions : An intraoperative bolus of DEX risks a transient increase in mean arterial pressure , but controls emergence hypertension effectively . Dose-related reductions in postsurgical pain and shivering were observed In BriefThe authors design ed a r and omized , double-blinded , placebo-controlled trial to evaluate intravenous acetaminophen as a scheduled adjunct with our st and ardized craniotomy pain control regimen . No statistically significant effect was found in narcotic consumption at 24 or 48 hours after surgery . At 24 but not 48 hours , patients treated with intravenous acetaminophen did report significantly lower pain scores than patients given the placebo . These data provide only modest support for using intravenous acetaminophen to improve postoperative craniotomy pain BACKGROUND : The issue of postoperative pain after neurosurgery is controversial . It has been reported as mild to moderate and its treatment may be inadequate . Infiltration of the surgical site with local anesthetics has provided transient benefit after craniotomy , but its effect on chronic pain has not been evaluated . Accordingly , we design ed the present study to test the hypothesis that ropivacaine infiltration of the scalp reduces acute and persistent postoperative pain after intracranial tumor resection . METHODS : This was a prospect i ve , single-blinded study . Inclusion criteria were intracranial tumor resection , age ≥18 or ≤80 yr , and ability to underst and and use a visual analog scale ( VAS ) . Exclusion criteria were history of craniotomy , chronic drug abuse , and neurologic disorders . All eligible patients were r and omly included in Group I ( infiltration ) or C ( control ) . Postoperative analgesia was IV acetaminophen combined with nalbuphine . At the end of the surgery , Group I received an infiltration of the surgical site with 20 mL of ropivacaine 0.75 % . Acute pain was evaluated hourly by VAS during the first 24 h. The analgesic effect of ropivacaine was evaluated based on total consumption of nalbuphine and VAS scores . The incidence of persistent pain and neuropathic pain was assessed at the 2-mo postoperative evaluation . We used the Student ’s t-test to compare total nalbuphine consumption , repeated measures analysis of variance with post hoc Bonferroni t-test for VAS score and the Fisher ’s exact test for chronic and neuropathic pain . RESULTS : Fifty-two patients were enrolled , 25 in Group I and 27 in Group C. Demographic and intraoperative data were similar between groups . Group I showed a nonsignificant trend toward reduced nalbuphine consumption during the first postoperative day , 11.2 ± 9.2 mg vs 16.6 ± 11.0 mg for Group C ( mean ± sd , P = 0.054 ) . VAS scores were significantly higher in Group C. Two months after surgery , persistent pain was significantly lower in Group I , 2/24 ( 8 % ) vs 14/25 ( 56 % ) , P = 0.0003 . One patient ( 4.1 % ) in Group I versus six ( 25 % ) patients in Group C ( P = 0.04 ) experienced neuropathic pain . CONCLUSIONS : Because pain is moderate after intracranial tumor resection , there is limited interest in scalp infiltrations with ropivacaine in the acute postoperative period . Nevertheless , these infiltrations may be relevant for the rehabilitation of neurosurgical patients and their quality of life by limiting the development of persistent pain and particularly neuropathic pain After craniotomy , hypertension may contribute to intracerebral hemorrhage . We studied whether scalp infiltration with bupivacaine during craniotomy reduces postoperative pain and hypertension . In a double-blind fashion , 36 adult patients ( ASA physical status II or III ) undergoing elective craniotomy were r and omly assigned to receive scalp infiltration with either bupivacaine ( 0.25 % ) and epinephrine ( 1:200,000 ) or saline/epinephrine ( 1:200,000 ) for skeletal fixation , skin incision , and wound closure . Heart rate ( HR ) and mean arterial pressure ( MAP ) were measured after anesthesia induction , after skull-pin insertion , after scalp infiltration , during dural closure , during skin closure , on admission to postanesthesia care unit ( PACU ) , and 1 h after admission . Visual analog pain scores were recorded in the PACU . MAP was significantly greater in the saline group at scalp infiltration . HR was significantly faster in the saline group at dural and skin closure . The bupivacaine group reported significantly less pain than the saline group at PACU admission and 1 h after admission . Pain scores did not correlate with hemodynamic measurements . We conclude that scalp infiltration with 0.25 % bupivacaine with 1:200,000 epinephrine blunts certain intraoperative hemodynamic responses and reduces postoperative pain but has no effect on postoperative hemodynamics . Implication s : We sought to evaluate whether scalp infiltration with bupivacaine and epinephrine at the beginning and end of craniotomy would afford more intra- and postoperative hemodynamic stability and influence immediate postoperative pain . We found that intraoperative hemodynamics were not influenced greatly ; however , craniotomy patients do have significant postoperative pain , which does not seem to have an influence on hemodynamics in the postanesthesia care unit . ( Anesth Analg 1998;87:579 - 82 OBJECT Skull blockade for craniotomy may result in the reduction of sympathetic stimulation associated with the application of head pins ( " pinning " ) , improvement in intraoperative hemodynamic stability , and a decrease in intraoperative anesthetic requirements . Postoperative benefits may include a decrease in pain , in analgesic requirements , and in the incidence of nausea and vomiting . The authors examined the potential benefits of a skull block in patients in whom a maintenance anesthetic consisting of sevoflurane and a titratable remifentanil infusion was used . In other studies examining the ability of a skull block to improve perioperative outcomes , investigators have not used remifentanil . METHODS Thirty patients presenting for resection of a supratentorial tumor were prospect ively enrolled . Patients were r and omized into 2 groups as follows : 14 patients ( skull block group ) received a skull block with 0.5 % ropivacaine at least 15 minutes prior to pinning , whereas the remaining 16 patients ( control group ) did not . RESULTS Patients in the skull block group did not have a significant increase in blood pressure or heart rate with placement of head pins , whereas patients in the control group did . Nevertheless , there was no difference in blood pressure variability between the groups . The mean intraoperative concentration of sevoflurane ( 1.0 % in both groups , p = 0.703 ) and remifentanil ( 0.163 microg/kg/min compared with 0.205 microg/kg/min , p = 0.186 ) used was similar in both groups . During the postoperative period , there was no difference in the 1- , 2- , or 4-hour visual analog scale scores ; in the need for postoperative narcotic analgesia ( 0.274 morphine equivalent mg/kg compared with 0.517 morphine equivalent mg/kg , p = 0.162 ) ; or in the incidence of nausea or vomiting . CONCLUSIONS Prospect i ve analysis of perioperative skull blockade failed to demonstrate significant benefit in patients treated with a remifentanil infusion BACKGROUND Pain management in craniotomy patients is challenging , with mild-to-moderate pain intensity , moderate-to-high risk of postoperative nausea and vomiting ( PONV ) , and potentially catastrophic consequences of analgesic-related side-effects . The aim of this study was to determine whether i.v . parecoxib administered at dural closure during craniotomy decreased total morphine consumption and morphine-related side-effects compared with placebo . METHODS One hundred adult patients presenting for supratentorial craniotomy under propofol/remifentanil anaesthesia were r and omized to receive parecoxib , 40 mg i.v . , or placebo in a double-blind manner . All patients received local anaesthetic scalp infiltration , regular i.v . paracetamol , nurse-administered morphine in the post-anaesthesia care unit ( PACU ) until verbal analogue pain scores were ≤4/10 and patient-controlled morphine thereafter . Morphine consumption , pain intensity , and analgesia-related side-effects were recorded during the first 24 h after operation . RESULTS Ninety-six patients ( 49 control and 47 parecoxib ) were included in the analyses . Fifty-nine ( 61 % ) patients received morphine in the PACU and only one patient ( control ) did not receive any morphine in the postoperative period . There were no significant differences between the two groups in morphine consumption [ 20 ( range : 0 - 102 ) vs 16 ( range : 1 - 92 ) mg ; P=0.38 ] , pain intensity [ excellent/very good pain relief in 78 % of parecoxib patients ; 74 % of control patients ( P=0.72 ) ] or analgesia-related side-effects ( PONV in 51 % of parecoxib patients ; 56 % of control patients ; P=0.55 ) in the first 24 h after operation . No major morbidity was recorded . CONCLUSIONS Our study demonstrated no clinical benefit to adding i.v . parecoxib to local anaesthetic scalp infiltration , i.v . paracetamol , and patient-controlled i.v . morphine after supratentorial craniotomy STUDY OBJECTIVE To determine whether intravenous injection of lornoxicam 30 minutes before skin incision provides better pain relief after varicocelectomy than postoperative administration of lornoxicam . DESIGN Prospect i ve , double-blind , r and omized clinical investigation . SETTING Operating room and postoperative recovery area . PATIENTS 44 ASA physical status I and II adult male patients undergoing varicocelectomy . INTERVENTIONS Patients were r and omized either to receive 8 mg lornoxicam infusion 30 minutes before skin incision , followed by saline infusion immediately after skin closure ( group 1 ) , or to receive the identical injections but in reverse order ( group 2 ) . All patients received local anesthesia with bupivacaine . MEASUREMENTS Postoperative pain scores were evaluated hourly for the first 8 hours after surgery , then at 12 , 16 , 20 , and 24 hours after surgery , using a 10-cm visual analog scale . Time to first analgesic request and patients ' global assessment s also were recorded . MAIN RESULTS Patients in group 1 reported significantly lower pain scores ( P < 0.05 ) at all time intervals except at 24 hours and better global assessment ( P = 0.001 ) than did group 2 . There were significantly fewer patients in the preemptive group than group 2 who required rescue analgesic within the first 24 hours ( 0 % vs 22.7 % ; P = 0.024 ) . Mean time to first analgesic request was also significantly longer in the preemptive group ( P = 0.001 ) . CONCLUSION Intravenous lornoxicam administered before surgery has a better analgesic effect for varicocelectomy than when administered postoperatively Background Pain and agitation are common in patients after craniotomy . They can result in tachycardia , hypertension , immunosuppression , increased catecholamine production and increased oxygen consumption . Dexmedetomidine , an alpha-2 agonist , provides adequate sedation without respiratory depression , while facilitating frequent neurological evaluation . Methods / design The study is a prospect i ve , r and omized , double-blind , controlled , parallel-group design . Consecutive patients are r and omly assigned to one of the two treatment study groups , labeled ‘ Dex group ’ or ‘ Saline group . ’ Dexmedetomidine group patients receive a continuous infusion of 0.6 μg/kg/h ( 10 ug/ml ) . Placebo group patients receive a maintenance infusion of 0.9 % sodium chloride for injection at a volume and rate equal to that of dexmedetomidine . The mean percentages of time in optimal sedation , vital signs , various and adverse events , the percentage of patients requiring propofol for rescue to achieve/maintain targeted sedation ( Sedation-Agitation Scale , SAS 3 to 4 ) and total dose of propofol required throughout the study drug infusion are collected . The percentage of patients requiring fentanyl for additional rescue to analgesia and total dose of fentanyl required are recorded . The effects of dexmedetomidine on hemodynamic and recovery responses during extubation are measured . Intensive care unit and hospital length of stay also are collected . Plasma levels of epinephrine , norepinephrine , dopamine , cortisol , neuron-specific enolase and S100-B are measured before infusion ( T1 ) , at two hours ( T2 ) , four hours ( T3 ) and eight hours ( T4 ) after infusion and at the end of infusion ( T5 ) in 20 patients in each group . Discussion The study has been initiated as planned in July 2012 . One interim analysis advised continuation of the trial . The study will be completed in July 2013.Trial registration Clinical Trials ( NCT ) : ChiCTR-PRC-12002903 Abstract Background Local anesthetic infiltration has been used to manage postoperative pain in various surgeries . The present study was aim ed to investigate the effect of skin infiltration with 0.5 % ropivacaine on postoperative pain in patients undergoing craniotomy . Methods One hundred and six patients with ASA I/II scheduled to undergo elective craniotomy were enrolled during March to November in 2015 in this prospect i ve , r and omized , placebo-controlled , double-blind study . After the anesthesia induction , skin along the incision was infiltrated with 0.5 % ropicavaine ( group R , n = 53 ) or 0.9 % normal saline ( group C , n = 53 ) , respectively . Morphine was used as rescue analgesic postoperatively . Morphine consumption during the first 24 postoperative hours was recorded as the primary outcome , and the time to first rescue requirement was also recorded . Pain was assessed at 2 , 4 , 8 , 24 h , 7 days , 3 months after surgery by visual analog scale ( VAS ) . Heart rate and mean arterial pressure were recorded before anesthesia induction ( T1 ) , after anesthesia induction ( T2 ) , after scalp infiltration ( T3 ) , during skull drilling ( T4 ) , mater cutting ( T5 ) and skin closure ( T6 ) . Results Morphine consumption during the first 24 postoperative hours was significantly higher in group C than in group R ( 13.36 [ 6.5 , 20 ] vs. 6.3 [ 0 , 10 ] mg , P < 0.05 ) . The first time of patients needed rescue analgesic was prolonged in group R as compared with group C ( 6.16 [ 3.4 , 8.0 ] vs. 3.87 [ 2.3 , 4 ] h , P < 0.05 ) . Postoperative VAS and hemodynamic signs during the first 24 h showed no significant difference in two groups . The incidence of persistent pain on 7 days and 3 months postoperatively had no significant differences between two groups . Besides one patient ( 2 % ) enduring moderate pain ( VAS 4–7 ) in group C , the number of patients suffering from mild pain ( VAS 1–3 ) was 17 ( 33.3 % ) in group R and 17 ( 34 % ) in group C 3 months after surgery . Conclusion The results suggest 0.5 % ropivacaine scalp infiltration before skin incision has favorable analgesic effect in reducing morphine consumption and prolong the time of first rescue analgesic requirement after surgery . Trial registration Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ) registration number : OBJECTIVES The prevalence of moderate to severe pain is high in patients following craniotomy . Although optimal analgesic therapy is m and atory , there is no consensus regarding analgesic regimen for post-craniotomy pain exists . This study aim ed to investigate the effects of morphine and non-opioid analgesics on postcraniotomy pain . PATIENTS AND METHODS This prospect i ve , r and omized , double blind , placebo controlled study included eighty three patients ( ASA 1 , II , and III ) scheduled for elective supratentorial craniotomy . Intravenous dexketoprofen , paracetamol and metamizol were investigated for their effects on pain intensity , morphine consumption and morphine related side effects during the first 24h following supratentorial craniotomy . Patients were treated with morphine based patient controlled analgesia ( PCA ) for 24h following surgery and r and omized to receive supplemental IV dexketoprofen 50 mg , paracetamol 1 g , metamizol 1 g or placebo . The primary endpoint was pain intensity , secondary endpoint was the effects on morphine consumption and related side effects . RESULTS When the whole study period was analyzed with repeated measures of ANOVA , the pain intensity , cumulative morphine consumption and related side effects were not different among the groups ( p>0.05 ) . CONCLUSION This study showed that the use of morphine based PCA prevented moderate to severe postoperative pain without causing any life threatening side effects in patients undergoing supratentorial craniotomy with a vigilant follow up during postoperative 24h . Although we could not demonstrate statistically significant effect of supplemental analgesics on morphine consumption , it was lower in dexketoprofen and metamizol groups than control group Background : Postcraniotomy pain can be difficult to manage with opioids due to opioid-related side effects , including drowsiness , nausea/vomiting , confusion , and pupillary changes , potentially masking the signs of postoperative neurological deterioration . Intravenous ( IV ) acetaminophen , a nonopioid analgesic , has been reported to have opioid-sparing effects after abdominal and orthopedic surgeries . This study investigates whether IV acetaminophen has similar effects after craniotomy . Material s and Methods : In this prospect i ve , r and omized , placebo-controlled , double-blind clinical trial , 100 adult patients scheduled to undergo supratentorial craniotomy for excision of a brain mass were r and omized to receive either IV acetaminophen or placebo preincision and then every 6 hours for a total of 24 hours after surgery . Total 24-hour opioid consumption , pain scores , satisfaction with overall pain management , time to meet postanesthesia care unit discharge criteria , and incidence of opioid-related side effects were compared . Results : There was no difference in the 24-hour postoperative opioid consumption in morphine equivalents between the IV acetaminophen group ( median , 11 mg ; n=45 ) and the placebo group ( median , 10.1 mg ; n=41 ) . No statistically significant difference of visual analog scale pain score was observed between 2 treatment groups . Patient satisfaction with overall postoperative pain management was significantly higher in the IV acetaminophen group than the placebo group on a 1 to 10 scale ( 8.1±0.4 vs. 6.9±0.4 ; P=0.03 ) . There was no significant difference in secondary outcomes , including the incidence of opioid-related side effects . Conclusions : IV acetaminophen , as adjunctive therapy for craniotomy procedures , did not show an opioid-sparing effect in patients for the 24 hours after craniotomy ; however , it was associated with improved patient satisfaction regarding overall pain control Background : Anesthesia for craniotomies should blunt responses to noxious stimuli , whereas subsequently leaving patients sufficiently alert for early neurological evaluation . The aim was to compare postoperative blood pressure control , pain , and opioid requirement after anesthesia with dexmedetomidine versus remifentanil . We therefore tested 2 primary hypotheses : ( 1 ) intraoperative administration of dexmedetomidine provides better control of postoperative blood pressure than remifentanil ; and ( 2 ) patients given dexmedetomidine have less postoperative pain and use less opioid . Material s and Methods : Adults having elective brain tumor excisions under balanced general anesthesia with endotracheal intubation were r and omized to an infusion of remifentanil ( 0.08 to 0.15 & mgr;g/kg/min , n=71 ) or dexmedetomidine ( 0.2 to 0.7 & mgr;g/kg/h , n=68 ) . Patients also received propofol , rocuronium , fentanyl , and sevoflurane . The mean arterial pressure ( MAP ) and pain were recorded at 15 , 30 , 45 , 60 , and 90 postoperative minutes . Outcomes were assessed with joint hypothesis testing , evaluating noninferiority and superiority . Results : Compared with remifentanil , the use of dexmedetomidine was associated with reduced postoperative MAP ( 88±12 vs. 98±11 mm Hg ) , with estimated mean difference ( 97.5 % confidence interval ) of −10 ( −13 , −4 ) mm Hg , P<0.001 , and mean visual analog pain score ( 2.9±2.6 vs. 5.1±2.4 points ) , with estimated mean difference of −5 ( −10 , −3 ) points , P<0.001 , and required less median opioid consumption ( 5 [ 0 , 10 ] vs. 10 [ 7 , 15 ] mg morphine equivalents ) , with estimated median difference of −5 ( −10 , −3 ) mg , P<0.001 . Dexmedetomidine was both noninferior and superior to remifentanil in maintaining postoperative hemodynamics and providing improved pain control . Conclusions : Intraoperative dexmedetomidine better controlled postoperative MAP and provided superior analgesia in patients undergoing craniotomy Pain after craniotomy remains a significant problem . The effect of morphine and tramadol patient‐controlled analgesia ( PCA ) on arterial carbon dioxide tension is unknown in patients having such surgery . Sixty craniotomy patients were r and omly allocated to receive morphine PCA , tramadol PCA or codeine phosphate 60 mg intramuscularly . Baseline values of pain score ( 0–10 ) , sedation and arterial carbon dioxide tension were recorded at the time of first analgesic administration and at 30 min , 1 , 4 , 8 , 12 , 18 and 24 h. Patient satisfaction was assessed at 24 h. There were no differences in arterial carbon dioxide tension or sedation between groups at any time , but in all three groups some patients had rises greater than 1 kPa . Morphine produced significantly better analgesia than tramadol at all time points ( p < 0.005 ) and better analgesia than codeine at 4 , 12 and 18 h. Patients were more satisfied with morphine than with codeine or tramadol ( p < 0.001 ) . Vomiting and retching occurred in 50 % of patients with tramadol , compared with 20 % with morphine and 29 % with codeine Local anesthetic infiltration has been proposed to decrease postoperative pain . The aim of this study was to determine whether scalp infiltration with bupivacaine or ropivacaine would improve analgesia after supratentorial craniotomy for tumor resection . Eighty patients were recruited into a r and omized double-blind study . Infiltration was performed after skin closure with 20 mL of saline 0.9 % ( placebo group , n = 40 ) , of 0.375 % bupivacaine with epinephrine 1:200,000 ( bupivacaine group , n = 20 ) , or of 0.75 % ropivacaine ( ropivacaine group , n = 20 ) . Postoperative analgesia was provided with patient-controlled morphine IV analgesia ( PCA ) . The study was continued until PACU discharge , which occurred early in the morning following surgery . Results are reported on 37 patients in the placebo group , 20 in the bupivacaine group , and 19 in the ropivacaine group because 4 patients experienced postoperative complications and were excluded from the study . Morphine titration at arrival in the postanesthesia care unit was necessary more often in the placebo group ( 62 % of the patients ) than in the 2 treated groups ( 19 % in each , P = 0.02 ) . The median quantity of morphine administered during the first 2 postoperative hours , including initial titration administered by a nurse and PCA-administered morphine , was lower in each treated group than in the placebo group ( P < 0.01 ) . The median morphine consumption up to the 16th postoperative hour was not significantly different among the 3 groups . There was no difference in the visual analogue scale scores among the 3 groups at any time . Scalp infiltration with either bupivacaine or ropivacaine had a statistically significant effect on morphine consumption during the first 2 postoperative hours Background : Intraoperative movements are marker of inadequate level of sedation and are undesirable during burr-hole surgery under monitored anesthesia care ( MAC ) . It distracts surgeon , hinders surgical procedure , and may lead to iatrogenic complication . Dexmedetomidine has shown to provide excellent analgesia , cooperative sedation with fewer fluctuations in sedation level during MAC . We compared the effect of dexmedetomidine on intraoperative patient movement , postoperative recovery time , and the surgeon and patient satisfaction scores with commonly used midazolam-fentanyl combination . Methods : Fifty-two patients undergoing burr-hole surgery for chronic subdural hematoma under MAC were r and omly assigned to receive either IV dexmedetomidine 1 & mgr;g/kg over 10 minutes followed by continuous infusion 0.03 to 0.07 & mgr;g/kg/h ( group D ) or IV fentanyl 0.5 & mgr;g/kg and midazolam 0.03 mg/kg over 10 minutes followed by continuous infusion of 0.5 to 1.16 & mgr;g/kg/h fentanyl and 0.03 to 0.07 mg/kg/h midazolam ( group M/F ) titrated to maintain Ramsay sedation scale 3 . Total number of intraoperative patient movements , postoperative recovery time , and patient and surgeon satisfaction scores were recorded . Results : Demographic and baseline characteristics were comparable between the 2 groups . Intraoperative patient movements were significantly less in group D than group M/F ( median interquartile range , 1.00 [ 0.00 to 2.00 ] vs. 3.00 [ 1.00 to 3.25 ] , P=0.007 ) . Group D patients showed faster postoperative recovery ( mean±SD , 7.00±6.96 vs. 13.69±6.18 min , P=0.000 ) . Surgeon satisfaction scores were better in group D compared with group M/F ( median interquartile range , 1.00 [ 1.00 to 1.25 ] vs. 2.00 [ 1.00 to 2.00 ] , P=0.014 ) . However , patient satisfaction score and hemodynamic parameters were comparable ( P>0.05 ) between both the groups . Conclusions : Use of dexmedetomidine for MAC is associated with lesser number of intraoperative patient movements , faster postoperative recovery , better surgeon satisfaction score , and comparable patient ’s satisfaction compared with midazolam-fentanyl combination The aim of this study was to compare the analgesic efficacy of three different postoperative treatments after supratentorial craniotomy . Sixty-four patients were allocated prospect ively and r and omly into three groups : paracetamol ( the P group , n = 8) , paracetamol and tramadol ( the PT group , n = 29 ) , and paracetamol and nalbuphine ( the PN group , n = 27 ) . General anesthesia was st and ardized with propofol and remifentanil using atracurium as the muscle relaxant . One hour before the end of surgery , all patients received 30 mg/kg propacetamol intravenously then 30 mg/kg every 6 hours . Patients in the PT group received 1.5 mg/kg tramadol 1 hour before the end of surgery . For patients in the PN group , 0.15 mg/kg nalbuphine was injected after discontinuation of remifentanil , because of its & mgr;-antagonist effect . Postoperative pain was assessed in the fully awake patient after extubation ( hour 0 ) and at 1 , 2 , 4 , 8 , and 24 hours using a visual analog scale ( VAS ) . Additional tramadol ( 1.5 mg/kg ) or 0.15 mg/kg nalbuphine was administered when the VAS score was ≥ 30 mm . Analgesia was compared using the Mantha and Kaplan – Meier methods . Adverse effects of the drugs were also measured . The three groups were similar with respect to the total dose of remifentanil received ( 0.27 ± 0.1 & mgr;g/kg/min ) . In all patients , extubation was obtained within 6 ± 3 minutes after remifentanil administration . Postoperative analgesia was ineffective in the P group ; therefore , inclusion s in this group were stopped after the eighth patient . Postoperative analgesia was effective in the two remaining groups because VAS scores were similar , except at hour 1 , when nalbuphine was more effective ( P = .001 ) . Nevertheless , acquiring such a result dem and ed significantly more tramadol than nalbuphine ( P < .05 ) . More cases of nausea and vomiting were observed in the PT group but the difference was not significant ( P < .06 ) . In conclusion , pain after supratentorial neurosurgery must be taken into account , and paracetamol alone is insufficient in bringing relief to the patient . Addition of either tramadol or nalbuphine to paracetamol seems necessary to achieve adequate analgesia , with , nevertheless , a larger dose of tramadol to fulfill this objective Up to 80 % of patients report moderate to severe pain after craniotomy . In this study , we assessed the efficacy of scalp block for decreasing postoperative pain in brain surgery . Thirty patients scheduled for supratentorial craniotomy were enrolled . They were r and omly divided into two groups : Ropivacaine ( scalp block with 20 mL of ropivacaine 0.75 % ) and Saline ( scalp block with 20 mL of saline 0.9 % ) . Anesthesia was st and ardized . The scalp block was performed after skin closure and before awakening . Postoperative pain was assessed at 4 , 8 , 12 , 16 , 20 , 24 , and 48 h by using a 10-cm visual analog scale . Analgesia was provided with sub- cutaneous codeine as requested by the patient . Average visual analog scale scores were higher in the Saline group as compared with Ropivacaine ( 3.7 ± 2.4 vs 2.0 ± 1.6;P = 0.036 ) . The total dose of codeine did not differ , nor did the duration of time before the first dose of codeine was required in the Ropivacaine ( 571 ± 765 min ) versus Saline ( 319 ± 409 min;P = 0.17 ) group . In conclusion , we found that postoperative scalp block decreases the severity of pain after craniotomy and that this effect is long lasting , possibly through a preemptive mechanism Background and objectives The aim of this study was to compare the efficacy of ‘ scheduled ’ analgesia with analgesia ‘ on request ’ in patients after craniotomy . Patients and methods We performed a prospect i ve r and omized study comparing ‘ scheduled ’ analgesia with analgesia ‘ on request ’ on 126 patients aged 16–70 years undergoing craniotomy for a variety of reasons . Patients were r and omized to one of two groups ; group 1 ( 68 patients ) received lornoxicam ‘ on request ’ , and group 2 ( 58 patients ) received 8 mg of lornoxicam preoperatively , immediately after intubation , then 8 mg again 6–8 h after the first injection and 8 mg repeated every 8 h for 48 h postoperatively . Subgroup analysis was performed for patients with supratentorial and infratentorial craniotomy . We measured pain scores ( visual analogue scale ) , mean blood pressure and heart rate at 6 , 18 , 30 , 42 and 54 h after surgery and compared differences in these parameters between groups and amongst subgroups . Results and discussion Group 1 visual analogue pain scale scores were significantly higher than those in group 2 ( P < 0.05 ) . Group 1 patients with infratentorial craniotomy showed higher pain scores than supratentorial craniotomy patients ( P < 0.05 ) . No significant differences were observed in mean blood pressure between groups and subgroups ( P > 0.05 ) . We found no correlation between visual analogue scale scores , mean blood pressure and heart rate ( P > 0.05 ) . Conclusion ‘ Scheduled ’ analgesia with lornoxicam was more effective for treating postcraniotomy pain than ‘ on request ’ analgesia with lornoxicam Patients undergoing craniotomy may experience moderate to severe pain postoperatively . An audit of analgesia of post-craniotomy patients at King 's College Hospital demonstrated variable analgesic prescribing practice s and suboptimal analgesia in some patients . Prior to introducing a formal post-operative analgesic regime , a survey of the adult neurosurgical units within the United Kingdom was undertaken to ascertain whether there was a general consensus regarding post-craniotomy pain management . Questions were asked as to whether there was a st and ardized analgesic regime/ protocol ; which first , second , third , and fourth-line analgesics were used ; whether non-steroidal anti-inflammatory drugs were used ; what the preferred anti-emetic was ; and whether pain was routinely assessed . We also undertook a survey of neurosurgeons , neuroanaesthetists , intensivists , and neurosurgery high dependency nurses within our institution to ascertain what their perceptions were of post-craniotomy pain . All 31 adult neurosurgical units were surveyed . Twenty three percent ( 7 units ) had a st and ardized analgesic regime/ protocol and 65 % routinely assessed pain post-operatively ( 20 units ) . Seventy percent of units used codeine phosphate or dihydrocodeine ( 22 units ) as the first line opioid the other 30 % using morphine ( 9 units ) . Forty two percent ( 13 units ) used tramadol ; patient controlled analgesia was used in 3 units . Regular paracetamol was prescribed in all but five ( 16 % ) units . Fifty two percent of units ( 16 ) used NSAIDs ; of those that used NSAIDs 19 % ( 3/16 ) prescribed them regularly . One unit used clonidine infusions . Anti-emetics were prescribed as required in all but two units . Cyclizine was the first-line anti-emetic in 45 % of the units , ondansetron in 29 % and metoclopramide in 16 % . There is currently no consensus on pain management after craniotomy in neurosurgical centres in the UK . Until there are sufficiently powered r and omized controlled studies to address the main safety and efficacy issues progress in this area will remain slow Objective Patients who underwent skull base procedures have been noted to experience appreciable pain . This study examines pain after surgery and the effectiveness of patient controlled analgesia ( PCA ) with combination morphine ondansetron for analgesia and control of emesis . Study Design and Setting A total of 120 skull base surgery patients were r and omized to receive placebo , morphine , or morphine ondansetron . Demographic and intraoperative variables were recorded along with pain , nausea , vomiting , and rescue analgesics . Total PCA use , hospital stay , satisfaction , and cost were also compared . Results Demographically the groups were similar . Pain was elevated with placebo PCA , and this group averaged twice as many analgesic rescues . Total usage time was lower with placebo PCA . Morphine ondansetron PCA had the lowest pain score with highest satisfaction . Nausea and vomiting was similar but female patients had more vomiting regardless of PCA group . Conclusions and Significance The use of morphine PCA reduced pain and did not appreciably increase nausea or vomiting . The addition of ondansetron produced no real benefit and its PCA use can not be justified . EBM rating : A-1b © 2006 American Academy of Otolaryngology-Head and Neck Surgery Foundation . All rights reserved OBJECT The authors performed a study to evaluate the efficacy of a regimen of scheduled minor analgesic medications in managing postoperative pain in children undergoing intracranial procedures . METHODS Postoperative pain scores were analyzed in two groups of children who underwent decompressive surgery for Chiari malformation : Group A underwent a scheduled regimen of minor oral analgesic medications ( st and ing doses of acetaminophen [ 10 mg/kg ] and ibuprofen [ 10 mg/kg ] alternating every 2 hours ) and Group B received analgesic medication when requested . Fifty children underwent a st and ard occipital craniectomy ( 25 in each group ) . The pain scores were significantly lower in Group A during most of the postoperative period . Length of stay ( LOS ) was shorter ( 2.2 compared with 2.8 days ) , and narcotic and antiemetic requirements were also lower in Group A patients than in Group B patients . Patients with spinal cord syringes exhibited a similar postoperative status to those without , and similar improvements in pain scores with scheduled minor analgesic medications were also evident . CONCLUSIONS A regimen of minor analgesic therapy , given in alternating doses every 2 hours immediately after craniotomy and throughout hospitalization , significantly reduced postoperative pain scores and LOS in children in whom suboccipital craniotomy was performed . Narcotic and antiemetic requirements were also decreased in association with this regimen . Application of this postoperative analgesia protocol may benefit children and adults in whom various similar neurosurgical procedures are required OBJECTIVE : Patients undergoing craniotomies have traditionally received opiates for the management of their postoperative pain . The use of narcotic pain medications can be costly , can decrease early walking , can lengthen hospital stay , and can alter a patient 's neurological examination results . The use of alternative pain medications such as cyclooxygenase-2 ( COX-2 ) inhibitors may benefit patients by resolving many of these issues . Compared with traditional nonsteroidal anti-inflammatory drugs , these anti-inflammatory medications may be used safely in neurosurgical patients because of their selective inhibition of the COX-2 enzyme , which avoids the platelet dysfunction caused by other nonsteroidal anti-inflammatory drugs . METHODS : A r and omized , single-blinded prospect i ve study was used to evaluate the efficacy of alternative pain management strategies for patients who have undergone craniotomy . Twenty-seven patients were r and omly assigned to a control group ( n = 13 ) receiving narcotics alone or an experimental group ( n = 14 ) receiving a COX-2 inhibitor in addition to narcotic pain medications . RESULTS : The narcotics group was noted to have statistically significantly higher visual analog scale scores , increased length of stay , and increased narcotic use compared with the COX-2 group . The narcotics group also had increased hospitalization costs when compared with the COX-2 group . CONCLUSION : The use of scheduled atypical analgesics , such as COX-2 inhibitors , in addition to narcotics for the management of postoperative pain after craniotomy may provide better pain control , may decrease side effects associated with narcotic pain medications , may encourage earlier walking , and may reduce total hospitalization costs OBJECTIVES The most painful stages of craniotomy are the placement of the pin head holder and the skin incision . The primary aim of the present study is to compare the effects of the scalp block and the local anesthetic infiltration with bupivacaine 0.5 % on the hemodynamic response during the pin head holder application and the skin incision in infratentorial craniotomies . The secondary aims are the effects on pain scores and morphine consumption during the postoperative 24h . METHODS This prospect i ve , r and omized and placebo controlled study included forty seven patients ( ASA I , II and III ) . The scalp block was performed in the Group S , the local anesthetic infiltration was performed in the Group I and the control group ( Group C ) only received remifentanil as an analgesic during the intraoperative period . The hemodynamic response to the pin head holder application and the skin incision , as well as postoperative pain intensity , cumulative morphine consumption and opioid related side effects were compared . RESULTS The scalp block reduced the hemodynamic response to the pin head holder application and the skin incision in infratentorial craniotomies . The local anesthetic infiltration reduced the hemodynamic response to the skin incision . As well as both scalp block and local anesthetic infiltration reduced the cumulative morphine consumption in postoperative 24h . Moreover , the pain intensity was lower after scalp block in the early postoperative period . CONCLUSION The scalp block may provide better analgesia in infratentorial craniotomies than local anesthetic infiltration Pain after craniotomy may be underdiagnosed , despite the fact that it can increase postoperative complications for example arterial hypertension and postoperative hemorrhage . This study investigates the incidence and intensity of pain after craniotomy and characterizes the influencing parameters . During a 1-year period 256 patients undergoing elective craniotomy were prospect ively included in the study . Intensity of pain was evaluated 1 , 4 , and 24 hours after extubation using a verbal numerical rating scale ( NRS ) ranging from 0 ( no pain ) to 10 ( maximal pain ) . Routine perioperative pain management was not influenced by the investigators . Parameters including patient-related factors , drug administration , and surgical factors were correlated with incidence and intensity of postcraniotomy pain . Statistical analysis : logistic regression and χ2 using SPSS program ( Windows , version 12.0 ) . During the first 24 hours 87 % of the patients experienced pain ( NRS 1 to 3 : 32 % , NRS 4 to 7 : 44 % , NRS 8 to 10 : 11 % ) . For postoperative analgesia , the opioid piritramide ( a μ-receptor agonist ) was administered to 70 % and nonopiod analgesics to 73 % of the patients . The probability of experiencing postcraniotomy pain was reduced by 3 % for each year of life . Maintenance of anesthesia with sevoflurane increased the probability of suffering from postcraniotomy pain by 147 % and the absence of corticosteroids by 119 % . Other investigated parameters did not influence pain after craniotomy . This study shows that pain is experienced by the majority of patients after craniotomy , despite conventional pain management , emphasizing the necessity for improved and individualized pain management in this special group of patients Abstract Background : Pituitary masses are common lesions accounting for about 15–20 % of all brain tumours . Oozing blood is an annoyance in microscopic sublabial trans-sphenoidal approach for these masses . There have been many ways of reducing the ooze , having their own pros and cons . Objective : To find out the efficacy and safety of clonidine in reducing blood loss in pituitary adenoma surgery through a r and omized masked trial . Methods : It was a prospect i ve r and omized controlled trial done . Total 50 patients of pituitary adenomas were r and omized into two groups . Group A ( 25 patients ) was given 200 μg clonidine orally , while Group B ( 25 patients ) was given placebo . Surgeon , anaesthesiologist and patient were blinded for the trial . Sublabial trans-septal trans-sphenoidal approach to sella and excision of mass was performed in each patient . Patients were studied for pre- , intra- and post-operative blood pressure and heart rate , pre- and post-operative imaging findings , intra-operative blood loss , bleeding grading by surgeon , surgeon ’s satisfaction about condition of specific part and quality of surgical field , operative time and extent of resection . Results : Blood loss during the surgery , operative time and bleeding grading by the surgeon were found significantly less in the clonidine group , while quality of surgical field , condition of the specific part and extent of resection were found significantly better in the clonidine group ( p value < .05 ) . There was no untoward adverse effect of the drug in the test group . Conclusion : Clonidine is a safe and effective drug to reduce bleeding in trans-sphenoidal microscopic pituitary adenoma surgeries Background : We conducted a r and omized trial to evaluate the opioid-sparing effect of an intraoperative infusion of dexmedetomidine ( DEX ) after craniotomy . Methods : Sixty adult patients scheduled for craniotomy were divided r and omly into group A ( DEX infusion at 0.5 & mgr;g/kg/h for 10 min and then adjusted to 0.2 to 0.5 & mgr;g/kg/h from tracheal intubation to incision suturing ) and group B ( 0.9 % saline infusion ) . Additional intravenous injections and patient-controlled analgesia with morphine were used to control postoperative pain for verbal Numerical Rating Scale scores > 4 . Cumulative morphine consumption , Numerical Rating Scale pain score , and the Ramsay Sedation Scale score were evaluated at 1 , 2 , 4 , 6 , 8 , 12 , and 24 hours ; the incidence of postoperative nausea and vomiting , agitation , and respiratory depression were recorded at 24 hours after surgery . Results : Postoperative pain scores within 12 hours and Ramsay Sedation Scale scores within 6 hours of surgery were both significantly lower in group A than in group B ( P<0.001 ) . Patients in group A required 54.4 % , 43.3 % , and 31.4 % less cumulative morphine consumption during the first 4 , 12 , and 24 hours , respectively . No patient in group A and 5 patients in group B presented agitation within 1 hour after surgery . Three patients in group A and 9 patients in group B showed pruritus ( P<0.001 ) . Conclusions : An intraoperative infusion of DEX reduced cumulative morphine consumption and adverse effects after craniotomy BACKGROUND Microvascular decompression ( MVD ) is a surgical treatment for cranial nerve disorders via a small craniotomy . The postoperative pain of this procedure can be classified as surgical site somatic pain and postcraniotomy headache similar in nature to a migraine , including its association with photophobia , nausea , and vomiting . This headache can be difficult to treat and can impact on postoperative recovery . Sumatriptan is used to treat migraine-like headaches in various setting s. This single-centre r and omized controlled trial investigated whether postoperative administration of sumatriptan after MVD surgery impacts the quality of postoperative recovery . METHODS Fifty patients who complained of postoperative headache after MVD were r and omized to receive an s.c . injection of sumatriptan ( 6 mg ) or saline . The primary outcome was quality of recovery as measured by the Quality of Recovery-40 ( QoR-40 ) score at 24 h. RESULTS The QoR-40 scores were significantly higher in the sumatriptan group ( median 184 ; interquartile range 169 - 196 ) than in the placebo group ( 133 ; 119 - 155 ; P<0.01 ) , suggesting higher quality of recovery . The sumatriptan group also had significantly lower headache scores at 4 , 12 , and 24 h. There were no significant differences in other secondary outcomes . CONCLUSIONS Use of sumatriptan improved the quality of recovery as measured by the QoR-40 and reduction of headache at 24 h after surgery . Sumatriptan is a useful alternative treatment for postcraniotomy headache . The mechanism remains unknown but could be related to reduction in headache , mood modulation , or both , mediated by a serotonin effect . CLINICAL TRIAL REGISTRATION NCT01632657 Objective This study was performed to determine the effects of scalp blocks with bupivacaine versus levobupivacaine on the haemodynamic response during craniotomy and the efficacies and analgesic requirements of these drugs postoperatively . Methods This r and omized , prospect i ve , placebo-controlled , double-blind study included 90 patients ( age , 18–85 years ; American Society of Anesthesiologists physical status , I or II ) . The patients were r and omly divided into three groups : those who received 20 mL of 0.5 % bupivacaine ( Group B , n = 30 ) , 20 mL of 0.5 % levobupivacaine ( Group L , n = 30 ) , or saline as a placebo ( Group C , n = 30 ) . Scalp blocks were performed 5 min before head pinning . The primary outcome was the mean arterial pressure ( MAP ) , and the secondary outcomes were the heart rate ( HR ) , visual analogue scale ( VAS ) scores , and additional intraoperative and postoperative drug use . Postoperative pain was evaluated using a 10-cm VAS . Results During head pinning and incision , the MAP and HR were significantly higher in Group C. The additional drug requirement for intraoperative hypertension and tachycardia was significantly higher in Group C. There were no significant differences in MAP , HR , or VAS scores between Groups B and L. Conclusion Both bupivacaine and levobupivacaine can be effectively and safely used for scalp blocks to control haemodynamic responses and postoperative pain OBJECTIVE The aim of this study was to assess in-hospital ( immediate ) postoperative pain scores and analgesic consumption ( primary goals ) and preoperative anxiety and sleep quality ( secondary goals ) in patients who underwent craniotomy and were treated with pregabalin ( PGL ) . Whenever possible , out-of-hospital pain scores and analgesics usage data were obtained as well . METHODS This prospect i ve , r and omized , double-blind and controlled study was conducted in consenting patients who underwent elective craniotomy for brain tumor resection at Tel Aviv Medical Center between 2012 and 2014 . Patients received either 150 mg PGL ( n = 50 ) or 500 mg starch ( placebo ; n = 50 ) on the evening before surgery , 1.5 hours before surgery , and twice daily for 72 hours following surgery . All patients spent the night before surgery in the hospital , and no other premedication was administered . Opioids and nonsteroidal antiinflammatory drugs were used for pain , which was self-rated by means of a numerical rating scale ( score range 0 - 10 ) . RESULTS Eighty-eight patients completed the study . Data on the American Society of Anesthesiologists class , age , body weight , duration of surgery , and intraoperative drugs were similar for both groups . The pain scores during postoperative Days 0 to 2 were significantly lower in the PGL group than in the placebo group ( p < 0.01 ) . Analgesic consumption was also lower in the PGL group , both immediately and 1 month after surgery . There were fewer requests for antiemetics in the PGL group , and the rate of postoperative nausea and vomiting was lower . The preoperative anxiety level and the quality of sleep were significantly better in the PGL group ( p < 0.01 ) . There were no PGL-associated major adverse events . CONCLUSIONS Perioperative use of twice-daily 150 mg pregabalin attenuates preoperative anxiety , improves sleep quality , and reduces postoperative pain scores and analgesic usage without increasing the rate of adverse effects . Clinical trial registration no. : NCT01612832 ( clinical trials.gov ) The efficacy of scalp nerve block using 0.5 % bupivacaine with adrenaline for postoperative pain relief in craniotomy patients was evaluated in 40 ASA I or II adult patients undergoing supratentorial craniotomy . A st and ard general anaesthesia technique was followed . Patients were r and omly divided into two groups . Group B received 0.5 % bupivacaine with 1:400,000 adrenaline and group S received normal saline with 1:400,000 adrenaline , both after skin closure . Postoperative pain was assessed at 30 seconds and 1 , 2 , 4 , 6 , 8 and 12 hours using a numerical rating scale . Diclofenac IM was administered as rescue analgesia if patients reported a numerical rating scale of 40 or more . Tramadol TV was administered as second rescue analgesia . Sixty per cent of patients in group S experienced moderate to severe pain ( numerical rating scale of 40 or more ) at some time during the first 12 postoperative hours in comparison to 25 % patients in group B. Median pain scores were significantly lower in group B for up to 6 hours . Significantly more patients were pain free up to four hours in group B. Median duration for the requirement of first dose of diclofenac was longer in group B compared to group S ( 360 min vs 30 min , P<0.01 ) . The number of doses of diclofenac ( 5 vs 19 ) was significantly lower in group B compared to group S ( P<0.01 ) . Tramadol was required by six patients in group S only . Scalp nerve block using 0.5 % bupivacaine with 1:400,000 adrenaline decreases the incidence and severity of postoperative pain in patients undergoing supratentorial craniotomy An ideal analgesic for patients after craniotomy should neither cause respiratory depression , nor affect intracranial pressure ( ICP ) and cerebral perfusion pressure ( CPP ) . The aim of the study was to evaluate the effect of Tramadol ( T ) on ICP and CPP , as well as to determine its analgetic efficacy in patients ( pts ) after craniotomy . Thirty five pts aged 16 divided by 78 years ( mean 46 ) entered the study . Twelve had GCS ( Glasgow Coma Scale ) scores < or = 8 and 23 pts had scores > or = 12 . Fourteen pts were mechanically ventilated and 21 pts were breathing spontaneously ( BS ) . Tramadol was injected i.v . at a dose of 0.75 mg/kg over 3 minutes in 11 pts ( Group 1 ) , 1.0 mg/kg over 5 minutes in 13 pts ( Group 2 ) and 1.0 mg/kg over 10 minutes in 11 pts ( Group 3 ) PaCO2 was measured before T in all pts and at 8 minute after injection in 21 BS pts . Heart rate ( HR ) , mean arterial blood pressure ( MBP ) , ICP , CPP and respiratory frequency ( f ) were registered before and in the 1st , 3rd , 8th , and 15th minute after T. Analgetic effect was evaluated in 22 conscious pts by comparing the pain intensity before and 30 minutes after T using a five-point verbal response scale . Mean control ICP was 17 mmHg . ICP over 15 mmHg was diagnosed in 15 pts ( mean ICP equal 26 mmHg ) . Mean CPP for all 35 pts was 85 mmHg . There were no statistically significant changes in HR , MBP , ICP , and CPP after T in any particular group , nor were there changes in ICP in subgroups with normal and elevated ICP . No significant changes in PaCO2 and f were found in BS pts . Satisfactory analgesia was obtained in 50 % of pts of Group 1 , and in 88 % of pts of Groups 2 and 3 . We conclude that tramadol in doses of 0.75 mg/kg and 1.0 mg/kg i.v . does not affect ICP and CPP in adult postcraniotomy patients and seems to be a safe and effective analgesic at a dose of 1.0 mg/kg for postcraniotomy pain control We have compared codeine and tramadol in a prospect i ve , double-blind study of postoperative analgesia in 75 patients after elective intracranial surgery . Twenty-five patients received codeine 60 mg , tramadol 50 mg or tramadol 75 mg i.m . Patients receiving codeine had significantly lower pain scores over the first 48 h after operation ( P < 0.0001 ) . Although there was no difference in visual analogue scale ( VAS ) scores between the three groups at 24 h , the codeine group had significantly lower scores at 48 h ( P < 0.0001 ) . The tramadol 75 mg group had significantly higher scores for both sedation and nausea and vomiting ( P < 0.0001 for both scores ) . We conclude that codeine 60 mg i.m . provided better postoperative analgesia than tramadol after craniotomy and that tramadol 75 mg should be avoided because of its side effects of increased sedation and nausea and vomiting BACKGROUND : Gabapentin is an anticonvulsant drug that has analgesic properties for acute postoperative pain . However , the analgesic effect of gabapentin as an antiepileptic prophylactic drug on patients undergoing craniotomy is unclear . In this study , we evaluated the postoperative effectiveness of gabapentin on acute postoperative pain when it is used for antiepileptic prophylaxis in patients undergoing craniotomy for supratentorial tumor resection . METHODS : Eighty patients undergoing craniotomy for supratentorial tumor resection were r and omly assigned into two groups . Patients in Group G ( n = 40 ) received oral gabapentin ( 3 × 400 mg ) , and patients in Group P ( n = 40 ) received oral phenytoin ( 3 × 100 mg ) for 7 days before the operation and postoperatively . An identical anesthesia protocol was performed for both the groups . Anesthesia was maintained with propofol and remifentanil infusion . Patient-controlled analgesia with morphine was used , and pain levels were measured . The antiepileptic-related side effects , anesthetic consumption , duration of anesthesia and surgery , tracheal extubation time , postoperative pain scores , morphine consumption , and sedation scores were recorded . RESULTS : Thirty-seven patients in Group G and 38 patients in Group P completed the study . During the preoperative period in Group G , one patient had severe fatigue , one had severe dizziness , and one patient ’s surgical procedure was changed . The median plasma levels of gabapentin were 34 & mgr;mol/mL ( range , 23 - 51 & mgr;mol/mL ) in 34 patients . In Group P , one patient withdrew from the study preoperatively and one developed transient neurological symptoms postoperatively . The demographic data and mean duration of anesthesia and surgery were similar in both the groups . The total propofol and remifentanil consumption in Group G ( 1847 ± 548 mg/3034 ± 1334 & mgr;g ) was significantly less than that of Group P ( 2293 ± 580 mg/4287 ± 1282 & mgr;g ) ( P = 0.01 ) . However , tracheal extubation could be done earlier in Group P ( 4.5 ± 2 min ) than in Group G ( 16.6 ± 22 min ) ( P < 0.001 ) . Pain scores were significantly higher in Group P at 15 min , 30 min , and 1 h ( P < 0.001 ) . The total morphine consumption was also significantly higher in Group P ( 33 ± 17 mg vs 24 ± 19 mg ) ( P = 0.01 ) . The postoperative sedation scores were significantly higher in Group G at 15 min , 30 min , 1 h , and 2 h ( P < 0.001 ) . CONCLUSIONS : The administration of gabapentin to patients undergoing craniotomy for supratentorial tumor resection was effective for acute postoperative pain . It also decreased analgesic consumption after surgery . However , it may lead to side effects such as delayed tracheal extubation and increased sedation postoperatively & NA ; This prospect i ve , double‐blind , r and omized , and placebo‐controlled trial was performed to evaluate the effect of preincisional scalp infiltration with 0.25 % bupivacaine on the postoperative pain perception and analgesic requirement of patients undergoing elective supratentorial craniotomy . Twenty patients ( bupivacaine group ) received scalp infiltration with 25 mL of 0.25 % bupivacaine followed by intravenous 5 mL of saline as placebo 5 minutes before incision , and another 21 patients ( fentanyl group ) received scalp infiltration with a similar volume of 0.9 % saline solution followed by 2 & mgr;g/kg of intravenous fentanyl 5 minutes before incision . Following st and ard anesthesia technique , basal , preincisional , and postincisional hemodynamic data were recorded . Postoperative pain was assessed at 1 , 6 , 12 , 24 , and 48 hours by using a 10‐cm visual analog scale . Diclofenac sodium was used as rescue analgesic in the postoperative period . Results showed rescue analgesic was required only during the first 12 hours . In each group the same number of patients needed rescue analgesia , but bupivacaine delayed this requirement 105 ( 30–720 ; median [ range ] ) minutes compared with 60 ( 15–720 ; median [ range ] ) minutes for the fentanyl group ( P = 0.13 ) . But there was no difference in the amount of analgesic consumed at different time intervals . Six of 20 patients in the bupivacaine group required rescue analgesic at the end of 1 hour compared with 9 of 21 fentanyl patients ( P = 0.61 ) . At 6 hours , the fraction of patients who required rescue analgesia were 7 of 20 and 11 of 21 , respectively ( P = 0.44 ) . In conclusion , bupivacaine preincision scalp infiltration did not have any significant effect on postcraniotomy pain and analgesic requirement . However , bupivacaine may delay the requirement of the first analgesic dose Background : Patients undergoing craniotomy , experience moderate to severe pain in postoperative period . Flupirtine does not have side effects like sedation and increase postoperative bleeding , so it may be a useful analgesic in neurosurgical patients . We design ed this prospect i ve , r and omized , double blind , placebo-controlled study to evaluate the role of flupirtine for postcraniotomy pain and compare it with diclofenac sodium . Material s And Methods : A total of 390 adults ( 18 to 70 y ) , American Society of Anaesthesiologists I and II , of either sex , undergoing elective craniotomy , were r and omly divided into 3 equal groups of 130 each . Group 1 ( control ) received placebo , group 2 ( diclofenac ) received tablet diclofenac 50 mg , and group 3 ( flupirtine ) received capsule flupirtine 100 mg . All medications were given 8 hourly on second postoperative day for 48 hours . Visual Analogue Scale score , level of sedation and incidence of side effects were observed . Results : Nineteen patients were dropped from the study and therefore subsequent analysis was carried out for 371 patients only . There was significant reduction of Visual Analogue Scale score in flupirtine and diclofenac group when compared to control ( P<0.0001 ) . Pain relief observed in control , flupirtine , and diclofenac group was 69.8 % , 90.2 % , and 90.5 % , respectively . Need of rescue analgesia was significantly less in flupirtine and diclofenac group as compared to control ( P<0.0001 ) . No significant difference was observed among the groups in regards to adverse effects . Conclusion : We conclude that oral flupirtine 100 mg is safe and as effective as oral diclofenac sodium 50 mg in reducing postcraniotomy pain We compared transitional analgesia provided by scalp nerve block ( SNB ) or morphine after remifentanil-based anesthesia in neurosurgery . Fifty craniotomy patients were r and omly divided into two groups : morphine ( morphine 0.1 mg · kg−1 IV after dural closure and an SNB performed with 20 mL of 0.9 % saline at the end of surgery ) and block ( 10 mL of 0.9 % saline instead of morphine after dural closure and an SNB performed with a 1:1 mixture of bupivacaine 0.5 % and lidocaine 2 % at the end of surgery ) . Postoperative pain was assessed at 1 , 2 , 4 , 8 , 12 , 16 , and 24 h using a 10-point numerical rating scale . Analgesia consisted of subcutaneous codeine . Average numerical rating scale scores were similar between the two groups at each time interval . Total codeine dosage was also similar , except at 4 h postoperatively when it was higher in the block group . The delay before administration of the first dose of codeine was not statistically different between groups : 45 min ( 20–2880 ) vs 30 min ( 10–2880 ) , median and range for the block and morphine group , respectively . Postoperative hemodynamics were similar for both groups . The incidence of nausea and vomiting was slightly more frequent in the morphine group , but the occurrence of confusion did not differ between groups . In conclusion , SNB provides a quality of transitional analgesia that is similar to that of morphine with the same postoperative hemodynamic profile Background : Moderate to severe pain occurs after craniotomy in 60 % of patients . We evaluated the feasibility and safety of patient‐controlled analgesia ( PCA ) with oxycodone in neurosurgical patients , and compared the efficacy of paracetamol with ketoprofen PURPOSE Pain management for patients who have undergone a craniotomy remains challenging . This study aim ed to determine whether intraoperative dexmedetomidine could reduce postoperative pain , analgesic consumption , and possible adverse events in patients after craniotomy . METHODS Eighty patients scheduled for elective supratentorial craniotomy under sevoflurane-fentanyl anesthesia were r and omly allocated into two equal groups , to receive a continuous dexmedetomidine infusion of 0.5 µg/kg/h or placebo , beginning after induction and continuing until the start of skin closure . Intravenous tramadol ( 0.5 mg/kg ) was administered to achieve an 11-point verbal rating scale ( a discrete 0 - 10 scale ) score of 4 or less in the postanesthesia care unit and , thereafter , on the ward . Pain scores , tramadol consumption , sedation scores , postoperative nausea and vomiting ( PONV ) scores , and other adverse events were recorded in the first 24 hours postoperatively . FINDINGS Seventy-six patients were included in the analyses . Demographic data , surgical characteristics , and sedation levels were similar between the groups . Dexmedetomidine reduced pain scores ( 30 minutes , P = 0.041 ; 2 hours , P = 0.021 ) and tramadol consumption ( 0 - 2 hours , P = 0.043 ; 0 - 6 hours , P = 0.006 ; 0 - 12 hours , P = 0.023 ; 0 - 24 hours , P = 0.040 ) postoperatively . Dexmedetomidine also reduced PONV scores at 20 , 60 , 90 , 120 , and 240 minutes ( P = 0.038 , 0.022 , 0.018 , 0.037 , 0.016 , respectively ) . The dexmedetomidine group exhibited fewer PONV events that required treatment ( P = 0.005 ) . IMPLICATION S Intraoperative dexmedetomidine infusion was effective for reducing pain and analgesic consumption after craniotomy . In addition , dexmedetomidine may help to reduce PONV in patients after craniotomy treated with tramadol postoperatively . Chinese Clinical Trial Register identifier : ChiCTR-TRC-13003598 Codeine and morphine were compared in a double‐blind study of postoperative analgesia in 40 patients after intracranial neurosurgery . Eighteen patients received codeine phosphate 60 mg and 18 morphine sulphate 10 mg , both by intramuscular injection ; 4 patients ( 10 % ) required no analgesia . Both drugs provided analgesia within 20 min of injection but morphine was more effective than codeine beyond 60 min ( p = 0.01 ) . Fewer doses of morphine than codeine were required ( p = 0.003 ) . Nine patients requested one dose of morphine and 9 two doses . Seven patients required three doses of codeine and 1 patient required four doses . Neither drug caused respiratory depression , sedation , pupillary constriction or unwanted cardiovascular effects . We conclude that , in the doses used , morphine is a safe alternative to codeine for analgesia after neurosurgery and has a more persistent action PURPOSE Postcraniotomy headache ( PCH ) is a frequent perioperative complication in neuroanesthesia . The aim of the present work was to assess the incidence of PCH and to test the efficacy and safety of preoperatively administered diclofenac . METHODS Patients undergoing craniotomies for intracranial tumor resections were enrolled . In the case group 100 mg diclofenac p.o . one hour prior to surgery was used as a preemptive analgesic along with infiltration of the surgical site with a combination of lidocaine and epinephrine . In controls only surgical site infiltration was used . VAS scores were assessed preoperatively , on the day of surgery ( DoS ) , on the 1st and 5th postoperative days . RESULTS We have found that PCH of any severity is between 50 - 90 % during the first five days after surgery . The number of cases characterized as " no pain " significantly decreased in the early postoperative period , but remained in both groups still higher on the 5th postoperative day than observed preoperatively . In both groups , the number of headaches characterized as mild pain remained relatively stable and substantial increases in case numbers were observed in moderate and severe headaches , showing a declining tendency over time in the postoperative period . A significant effect of diclofenac pretreatment was observed compared to controls on DoS ( chi2 : 10.429 , p<0.015 ) , on the 1st ( chi2 : 8.75 , p<0.032 ) and 5th postoperative days ( chi2 : 14.3 , p<0.002 ) . CONCLUSIONS The relatively low incidence of severe PCH on day five in the diclofenac group may indicate that preoperatively administered diclofenac effectively reduces postcraniotomy headache . A r and omized study is encouraged to test this hypothesis BACKGROUND : The perioperative course of patients undergoing intracranial surgery is frequently complicated by hypertensive episodes . Dexmedetomidine ( DEX ) , an & agr;-2 adrenoreceptor agonist , is gaining popularity in neuroanesthesia , because its sympatholytic and antinociceptive properties may improve hemodynamic stability at critical moments of surgery . We design ed this study to assess the efficacy of DEX in controlling hypertensive responses in patients undergoing intracranial surgery . METHODS : Patients scheduled for elective craniotomy were r and omly assigned to receive either sevoflurane – opioid or sevoflurane – opioid – DEX anesthesia . Bispectral index was used to maintain a similar level of hypnosis in both groups ( 40–50 ) . Opioids , sevoflurane , and vasoactive medications were titrated in a routine manner , at the discretion of the blinded anesthesiologist managing the case , to maintain systolic blood pressure ( SBP ) targeted within 90–130 mm Hg and heart rate ( HR ) between 50 and 90 bpm . Hemodynamic variables were continuously recorded and stored on a computer for analysis . Efficacy of the anesthetic technique in controlling SBP or HR is inversely proportional to the area under the curve ( AUC ) outside the targeted range . Areas under the curves above and below targeted ranges for SBP-time ( AUCsbp mm Hg * min/h ) and HR-time ( bpm * min/h ) were compared . Coefficient of variation was used to assess hemodynamic stability . RESULTS : Seventy-two patients were recruited for the study . Computerized records of 56 patients only were analyzed because of technical problems with data collection in 14 cases . AUCsbp for above the targeted range was significantly lower for patients in the DEX group ( P = 0.044 ) . The coefficient of variation for SBP or HR did not differ between groups . A significantly smaller proportion of patients in the DEX group required treatment with antihypertensive medications ( 12 of 28 , 42 % vs 24 of 28 , 86 % , P = 0.0008 ) . The DEX group required fewer opioids in the intraoperative period , but there were no differences in the use of sevoflurane . In the postanesthesia care unit , patients in the DEX group had fewer hypertensive episodes ( 1.25 ± 1.55 vs 2.50 ± 2.00 , P = 0.0114 ) and were discharged earlier ( 91 ± 17 vs 130 ± 27 min , P < 0.0001 ) . There were no differences in the requirement for postoperative opioids or antiemetics . CONCLUSIONS : By using indices , which assess a global hemodynamic stability of the anesthetic , we determined that intraoperative DEX infusion was effective for blunting the increases in SBP perioperatively . The use of DEX did not increase the incidence of hypotension or bradycardia , common side effects of the drug Background : The aim of this double-blinded r and omized control study was to examine the role of the steroid dexamethasone as an adjuvant to lignocaine and ropivacaine in scalp nerve blocks in adults undergoing supratentorial craniotomy under general anesthesia . We compared the intraoperative anesthetic and postoperative analgesic requirement with and without the addition of dexamethasone to the local anesthetics . Methods : The consented 90 patients were r and omized into 2 groups : one group received 8 mg ( 2 mL ) of dexamethasone , whereas the other received 2 mL of normal saline along with the local anesthetics in the scalp nerve block administered soon after induction of general anesthesia . All patients received oral/intravenous dexamethasone perioperatively to decrease cerebral edema . The general anesthetic technique for induction , maintenance , and recovery was st and ardized in the 2 groups . The primary outcome assessed was the time to administration of the first dose of analgesic postoperatively . The secondary outcomes included intraoperative opioid requirement , time to emergence , and incidence of postoperative nausea and vomiting . Results : There was no significant difference between the dexamethasone and saline groups with respect to time to first analgesic requirement , intraoperative fentanyl requirements , time to emergence from general anesthesia , and incidence of postoperative nausea and vomiting . Conclusions : Addition of dexamethasone as an adjuvant to local anesthetics in scalp nerve blocks in the setting of perioperative steroid therapy does not appear to provide any additional benefit with respect to prolongation of the duration of the block OBJECTIVE Pain control is an important clinical consideration and quality -of-care metric . No studies have examined postoperative pain control following transsphenoidal surgery for pituitary lesions . The study goals were to 1 ) report postoperative pain scores following transsphenoidal surgery , 2 ) determine if multimodal opioid-minimizing pain regimens yielded satisfactory postoperative pain control , and 3 ) determine if intravenous ( IV ) ibuprofen improved postoperative pain scores and reduced opioid use compared with placebo . METHODS This study was a single-center , r and omized , double-blinded , placebo-controlled intervention trial involving adult patients with planned transsphenoidal surgery for pituitary tumors r and omized into 2 groups . Group 1 patients were treated with scheduled IV ibuprofen , scheduled oral acetaminophen , and rescue opioids . Group 2 patients were treated with IV placebo , scheduled oral acetaminophen , and rescue opioids . The primary end point was patient pain scores ( visual analog scale [ VAS ] , rated 0 - 10 ) for 48 hours after surgery . The secondary end point was opioid use as estimated by oral morphine equivalents ( OMEs ) . RESULTS Of 136 patients screened , 62 were enrolled ( 28 in Group 1 , 34 in Group 2 ) . The study was terminated early because the primary and secondary end points were reached . Baseline characteristics between groups were well matched except for age ( Group 1 , 59.3 ± 14.4 years ; Group 2 , 49.8 ± 16.2 years ; p = 0.02 ) . Mean VAS pain scores were significantly different , with a 43 % reduction in Group 1 ( 1.7 ± 2.2 ) compared with Group 2 ( 3.0 ± 2.8 ; p < 0.0001 ) . Opioid use was significantly different , with a 58 % reduction in Group 1 ( 26.3 ± 28.7 mg OME ) compared with Group 2 ( 62.5 ± 63.8 mg OME ; p < 0.0001 ) . CONCLUSIONS Multimodal opioid-minimizing pain-management protocol s result ed in acceptable pain control following transsphenoidal surgery . IV ibuprofen result ed in significantly improved pain scores and significantly decreased opioid use compared with placebo . Postoperative multimodal pain management , including a nonsteroidal antiinflammatory medication , should be considered after surgery to improve patient comfort and to limit opioid use . Clinical trial registration no. : NCT02351700 ( clinical trials.gov ) ■ CLASSIFICATION OF EVIDENCE Type of question : therapeutic ; study design : r and omized , controlled trial ; evidence : Class III BACKGROUND Scalp block or local anesthetic infiltration for craniotomy blunts hemodynamic response to noxious stimuli , reduces opioid requirement and decreases postoperative pain . Analgesia Nociception Index ( ANI ) provides objective information about the magnitude of pain ( rated from 0 to 100 with 0 indicating extreme nociception and 100 indicating absence of nociception ) and adequacy of intra-operative analgesia . This study compared intra-operative fentanyl consumption guided by ANI and postoperative pain in patients who receive scalp block with those who receive incision-site local anesthetic infiltration for craniotomy . METHODS Sixty adult patients undergoing elective supra-tentorial tumor surgery were r and omly allocated to receive scalp block or incision-site infiltration after induction of anesthesia . Throughout the intra-operative period , patients received fentanyl 0.5 µg/kg/h and ANI was continuously monitored . Fentanyl 1 µg/kg bolus was administered when ANI decreased to < 50 . Intraoperative fentanyl consumption was compared using unpaired t-test . Correlation between ANI and postoperative numerical rating scale ( NRS ) pain score was done using Spearman 's rho . RESULTS The fentanyl consumption ( µg/kg/h ) was less with scalp block when compared to incision-site infiltration ( median [ interquartile range ] ; 1.04 [ 0.92 - 1.34 ] vs. 1.34 [ 1.18 - 1.59 ] , P=0.001 ) . Postoperative pain scores were similar [ median ( interquartile range ) ; 1.5 ( 0 - 4 ) vs. 3 ( 0 - 4 ) , P=0.840 ] . No correlation was observed between postoperative NRS Score and ANI ( correlation coefficient = 0.072 ; P=0.617 ) . CONCLUSIONS ANI-guided analgesic administration during craniotomy demonstrated lower intra-operative fentanyl consumption in patients receiving scalp block as compared to incision-site local anesthetic infiltration . No correlation was seen between postoperative NRS and ANI Abstract Objective : Morphine is commonly used in post-operative analgesia , but opioid-related respiratory depression causes a general reluctance for its use . The “ Integrated Pulmonary Index ” is a tool calculated from non-invasively obtained respiratory and hemodynamic parameters . The aim of this prospect i ve , r and omized , double blind , and placebo-controlled study is to determine a more safe and effective dose for morphine in patient-controlled analgesia following supratentorial craniotomy using the “ Integrated Pulmonary Index ” . Methods : This study included 60 patients ( ASA I , II , and III ) . All patients used iv PCA for 24 h following supratentorial craniotomy . The PCA was set to administer a bolus dose of 1 mg morphine in Group 1 and 0.5 mg morphine in Group 2 . The PCA contained placebo in Group 3 and patients received dexketoprofen 50 mg iv after awakening , repeated every 8 h. The IPI and NRS scores , total morphine consumption , and morphine related side-effects were recorded at 10 min , 1 , 2 , 6 , 12 , and 24 h post-operatively . The lowest IPI score , count of apnea , and desaturation events were recorded during the study period . Results : The IPI scores were similar among the groups . Although a statistically significant difference was not observed among the groups the lowest IPI scores were observed in Group 1 ; apnea and desaturation counts were also higher in Group 1 . Statistically significant differences were not observed among the groups in terms of pain scores , but were lower in Groups 1 and 2 compared to Group 3 . Conclusion : Patient controlled analgesia with 0.5 mg morphine may be safe and effective for pain management following supratentorial craniotomies . Integrated pulmonary index can be used for detecting opioid-induced respiratory depression . Clinical Trials registration number : NCT02929147 Background : Gabapentin is an adjuvant antiepileptic agent and helps to reduce acute postoperative pain in several surgery setting s. However , the effect of gabapentin on postoperative pain from suboccipital or subtemporal craniotomy is not clear . Methods : The study was a single-center , r and omized , placebo-controlled , and double-blinded trial . A total of 122 patients undergoing elective craniotomy by a suboccipital or subtemporal approach were r and omly allocated to a placebo group and gabapentin group . The patients received gabapentin ( 600 mg , orally ) the night before surgery and 2 hours before anesthesia induction in the gabapentin group , and patients received vitamin B in the placebo group . The primary outcome was the postoperative pain score on movement at 24 hours . The secondary outcomes included the pain score at other time points , incidence of nausea and vomiting , sedation , and analgesic consumption . Results : Gabapentin significantly decreased the postoperative acute pain scores at rest ( P=0.001 ) and on movement ( P=0.000 ) within 24 hours ; however , it did not have an effect at 48 hours . Gabapentin decreased postoperative vomiting ( P=0.047 ) and rescue antiemetic use ( P=0.033 ) , whereas it increased the postoperative sedation score at 2 hours ( P<0.05 ) . Moreover , gabapentin decreased the mean consumption of intraoperative propofol ( 0.7 mg/kg/h ; P=0.021 ) and remifentanil ( 1.3 µg/kg/h ; P=0.025 ) ; however , it did not influence postoperative opioid consumption . Conclusions : Preoperative gabapentin significantly alleviated acute postoperative pain and decreased the incidence of vomiting in patients undergoing suboccipital or subtemporal craniotomy . However , more attention should be paid to early postoperative sedation when multimodal analgesia with gabapentin is administered Background Patients undergoing craniotomy operations are prone to various noxious stimuli , many strategies are commenced to provide state of analgesia , for better control of the stress response and to overcome its undesired effects on the haemodynamics and post-operative pain . Scalp nerves block are considered one of these strategies . This study was conceived to evaluate the effect of addition of hyaluronidase to the local anaesthetic mixture used in the scalp nerves block in patients undergoing elective craniotomy operations . Methods 64 patients undergoing elective craniotomy operations were enrolled in this prospect i ve r and omized , double-blind comparative study . Patients were r and omly assigned to two groups . Group LA , patients subjected to scalp nerves block with 15 ml bupivacaine 0.5 % , 15 ml lidocaine 2 % , in 1:400000 epinephrine . Group H as Group LA with15 IU /ml Hyaluronidase . Results Patients in the H group showed lower VAS values for 8 h postoperative , compared to the LA group . The haemodynamic response showed lower values in the H group , compared to the LA group . Those effects were shown in the intraoperative period and for 6 h post-operative . No difference was detected regarding the incidence of complications nor the safety profile . Conclusion Our data supports the idea that addition of hyaluronidase to the local anesthetic mixture improves the success rates of the scalp nerves block and its efficacy especially during stressful intraoperative periods and in the early postoperative period . No evident undesirable effects in relation to the addition of hyaluronidase . Trial registration Clinical Trial registry on Clinical Trials.gov , NCT 03411330 , 25 - 1 - 2018 Background In this study , we compared the quality of transitional analgesia provided by bilateral superficial cervical plexus block ( SCPB ) or morphine following a remifentanil-based anesthesia for infratentorial or occipital craniotomy . Methods In this r and omized controlled and double-blind study , 30 patients scheduled for infratentorial or occipital craniotomy were divided r and omly into two groups : group morphine ( morphine 0.1 mg·kg−1iv after dural closure and a SCPB performed with 20 mL of 0.9 % saline at the end of the surgery ) or group block ( 10 mL of 0.9 % saline iv instead of morphine after dural closure and a SCPB performed with 20 mL of a 1:1 mixture of 0.5 % bupivacaine and 2 % lidocaine at the end of the surgery ) . Postoperative pain was assessed at one , two , four , eight , 12 , 16 , and 24 hr using an 11-point ( 0 - 10 ) numerical rating scale ( NRS ) . Analgesia was provided with subcutaneous codeine . Results Average NRS scores were similar between the two groups at each time interval over the study period . The average scores ( with 95 % confidence interval ) were 3.9 ( 3.4 - 4.4 ) and 4.3 ( 3.8 - 4.9 ) for the block and morphine groups , respectively ( P = 0.25 ) . The delay before administration of the first dose of codeine was not statistically different between the two groups : 25 min ( 5 - 2,880 ) vs 21.5 min ( 5 - 90 ) , median and range for the block and morphine groups , respectively . The incidence of nausea and vomiting was similar between the two groups . Conclusion Bilateral superficial cervical plexus block provides transitional analgesia that is clinical ly equivalent to morphine following remifentanil-based anesthesia in patients undergoing occipital or infratentorial craniotomies . Résumé Context eDans le cadre de cette étude , nous avons comparé la qualité de l’analgésie transitionnelle produite par un bloc bilatéral du plexus cervical superficiel ( SCPB ) ou par la morphine à la suite d’une anesthésie au rémifentanil lors d’une craniotomie sous-tentorielle ou occipitale . MéthodeDans cette étude r and omisée et contrôlée en double aveugle , 30 patients ayant subi une craniotomie sous-tentorielle ou occipitale ont été divisés aléatoirement en deux groupes : le groupe morphine ( morphine 0,1 mg·kg−1intraveineuse après la fermeture de la dure-mère et un SCPB effectué avec 20 mL de solution salée à 0,9 % à la fin de la chirurgie ) ou le groupe bloc ( 10 mL de solution salée à 0,9 % intraveineuse au lieu de la morphine après la fermeture de la dure-mère , et un SCPB effectué avec 20 mL d’un mélange 1:1 de bupivacaïne à 0,5 % et de lidocaïne à 2 % à la fin de la chirurgie ) . La douleur postopératoire a été mesurée à une , deux , quatre , huit , 12 , 16 et 24 h à l’aide d’une échelle d’évaluation numérique de 11 points ( 0 à 10 ) . L’analgésie a été effectuée par injection sous-cutanée de codéine . RésultatsLes scores moyens sur l’échelle d’évaluation numérique étaient semblables pour les deux groupes à chaque intervalle de temps pendant toute la durée de l’étude . Le score moyen ( avec intervalle de confiance de 95 % ) était de 3,9 ( 3,4 à 4,4 ) pour le groupe bloc et de 4,3 ( 3,8 à 4,9 ) pour le groupe morphine ( P = 0,25 ) . Le délai précédant l’administration de la première dose de codéine ne représentait pas un écart important sur le plan : médiane et extrêmes de 25 min . ( 5 - 2880 ) contre 21,5 min . ( 5 - 90 ) pour les groupes bloc et morphine , respectivement . L’incidence de nausées et de vomissements était semblable pour les deux groupes . ConclusionS ur le plan clinique , le bloc bilatéral du plexus cervical superficiel produit une analgésie transitionnelle équivalente à la morphine à la suite d’une anesthésie au rémifentanil chez les patients subissant une craniotomie sous-tentorielle ou occipitale OBJECT Opioid administration following major intracranial surgery is often limited by a presumed lack of need and a concern that opioids will adversely affect postoperative outcome and interfere with the neurological examination . Nevertheless , evidence is accumulating that these patients suffer moderate to severe postoperative pain and that this pain is often undertreated . The authors hypothesized that intravenous patient-controlled analgesia ( PCA ) would safely and more effectively treat postoperative supratentorial craniotomy pain than conventional as needed ( PRN ) therapy . METHODS Following a st and ardized course of general anesthesia , adult patients who underwent elective supratentorial intracranial surgery were r and omized in the neurosciences intensive care unit to receive either PRN intravenous fentanyl 25 - 50 microg every 30 minutes or PCA intravenous fentanyl 0.5 microg/kg every 15 minutes ( maximum 4 doses/hour ) . The authors measured pain ( self-reported scale score [ 0 - 10 ] ) , sedation ( Ramsay Sedation Scale score ) , Glasgow Coma Scale score , fentanyl use , and major adverse events ( excessive sedation , respiratory depression , pruritus , nausea , or vomiting ) hourly . RESULTS Sixty-four patients with a mean age of 48 years ( range 22 - 77 years ) were r and omized to intravenous PCA ( 29 patients ) or PRN fentanyl ( 35 patients ) groups . There were no statistically significant demographic differences between the 2 groups . Patients receiving intravenous PCA had significantly lower pain scores than those receiving intravenous PRN fentanyl ( 2.53 + /- 1.96 vs 3.62 + /- 2.11 [ p = 0.039 ] ) and received significantly more fentanyl than the PRN group ( 44.1 + /- 34.5 vs 23.6 + /- 23.7 microg/hour [ p = 0.007 ] ) . There were no differences between the 2 groups regarding the number of patients with adverse events . CONCLUSIONS Intravenous PCA more effectively treats the pain of supratentorial intracranial surgery than PRN fentanyl , and patients in the former group did not experience any untoward events related to the self-administration of opioids OBJECT Patients undergoing craniotomies have traditionally received opiates with acetaminophen for the management of their postoperative pain . The use of narcotic pain medications can be costly , decrease rates of early postoperative ambulation , lengthen hospital stays , and alter a patient 's neurological examination . The use of alternative pain medications such as tramadol may benefit patients by resolving many of these issues . METHODS The authors conducted a r and omized , blinded prospect i ve study to evaluate the efficacy of alternative pain management strategies for patients following craniotomies . Fifty patients were r and omly assigned either to a control group who received narcotics and acetaminophen alone or an experimental group who received tramadol in addition to narcotic pain medications ( 25 patients assigned to each group ) . RESULTS The control group was noted to have statistically significant higher visual analog scale pain scores , an increased length of hospital stay , and increased narcotic use compared with the tramadol group . The narcotics and acetaminophen group also had increased hospitalization costs when compared with the tramadol group . CONCLUSIONS The use of scheduled atypical analgesics such as tramadol in addition to narcotics with acetaminophen for the management of postoperative pain after craniotomy may provide better pain control , decrease the side effects associated with narcotic pain medications , encourage earlier postoperative ambulation , and reduce total hospitalization costs |
12,293 | 32,297,244 | Overall , the majority of studies reported improved outcomes post-intervention .
There was evidence of impact on patient and healthcare outcomes as well as learners ’ behaviour and knowledge .
The current evidence base supports the use of education as an effective non-pharmacological approach to prevent and treat delirium .
Healthcare professional education has benefits for inpatient delirium care , as shown by the high number of good- quality studies and the majority demonstrating improved outcomes post-intervention . | Underst and ing the quality of evidence of delirium education studies will assist in design ing future education interventions that seek to improve the well-known deficits in delirium prevention , detection and care . | Purpose Systematic monitoring of sedation , pain and delirium in the ICU is of paramount importance in delivering adequate patient care . While the use of systematic monitoring instruments is widely agreed upon , these tools are infrequently implemented into daily ICU care . The aim of this study is to compare the effectiveness of two different training strategies ( training according to the local st and ard vs. modified extended method ) on the implementation rate of scoring instruments on the ICU . Methods In this experimental cohort study we analyzed the frequency of scoring on three surgical ICUs before and after training , and in a 1 year follow-up . A modified extended training included establishing a local support team helping to resolve immediate problems . In addition we evaluated the impact on patients ’ outcome . Results ICUs trained by the modified extended method showed increased documentation rates of all scores per patient and day . In a 1 year follow-up , increased scoring rates for all scores were maintained . Scoring rates with training according to the local st and ard training protocol did not increase significantly . Implementation of delirium and pain monitoring were associated with a decrease in mortality [ odds ratio ( OR ) 0.451 ; 95 % confidence interval ( CI ) : 0.22–0.924 , and , respectively , OR 0.348 ; 95 % CI : 0.140–0.863 ] . Monitoring had no significant influence on ventilation time or ICU length of stay . Conclusions A modified extended training strategy for ICU monitoring tools ( sedation , pain , delirium ) leads to higher intermediate and long-term implementation rates and is associated with improved patient outcome . However , these findings may have been biased by unmeasured confounders Recent studies suggest that delirium is associated with risk of dementia and also acceleration of decline in existing dementia . However , previous studies may have been confounded by incomplete ascertainment of cognitive status at baseline . Herein , we used a true population sample to determine if delirium is a risk factor for incident dementia and cognitive decline . We also examined the effect of delirium at the pathological level by determining associations between dementia and neuropathological markers of dementia in patients with and without a history of delirium . The Vantaa 85 + study examined 553 individuals ( 92 % of those eligible ) aged ≥85 years at baseline , 3 , 5 , 8 and 10 years . Brain autopsy was performed in 52 % . Fixed and r and om-effects regression models were used to assess associations between ( i ) delirium and incident dementia and ( ii ) decline in Mini-Mental State Examination scores in the whole group . The relationship between dementia and common neuropathological markers ( Alzheimer-type , infa rcts and Lewy-body ) was modelled , stratified by history of delirium . Delirium increased the risk of incident dementia ( odds ratio 8.7 , 95 % confidence interval 2.1–35 ) . Delirium was also associated with worsening dementia severity ( odds ratio 3.1 , 95 % confidence interval 1.5–6.3 ) as well as deterioration in global function score ( odds ratio 2.8 , 95 % confidence interval 1.4–5.5 ) . In the whole study population , delirium was associated with loss of 1.0 more Mini-Mental State Examination points per year ( 95 % confidence interval 0.11–1.89 ) than those with no history of delirium . In individuals with dementia and no history of delirium ( n = 232 ) , all pathologies were significantly associated with dementia . However , in individuals with delirium and dementia ( n = 58 ) , no relationship between dementia and these markers was found . For example , higher Braak stage was associated with dementia when no history of delirium ( odds ratio 2.0 , 95 % confidence interval 1.1–3.5 , P = 0.02 ) , but in those with a history of delirium , there was no significant relationship ( odds ratio 1.2 , 95 % confidence interval 0.2–6.7 , P = 0.85 ) . This trend for odds ratios to be closer to unity in the delirium and dementia group was observed for neuritic amyloid , apolipoprotein ε status , presence of infa rcts , α-synucleinopathy and neuronal loss in substantia nigra . These findings are the first to demonstrate in a true population study that delirium is a strong risk factor for incident dementia and cognitive decline in the oldest-old . However , in this study , the relationship did not appear to be mediated by classical neuropathologies associated with dementia Objective : To study the outcome of delirium in elderly hip surgery patients . Design : Prospect i ve matched controlled cohort study . Hip surgery patients ( n = 112 ) aged 70 years and older , who participated in a controlled clinical trial of haloperidol prophylaxis for delirium , were followed for an average of 30 months after discharge . Patients with a diagnosis of dementia or mild cognitive impairment ( MCI ) were identified using psychiatric interviews . Proportions of patients with dementia/MCI were compared across patients who had postoperative delirium and selected control patients matched for preoperatively assessed risk factors who had not developed delirium during index hospitalization . Other outcomes were mortality rate and rate of institutionalization . Results : During the follow-up period , 54.9 % of delirium patients had died compared to 34.1 % of the controls ( relative risk = 1.6 , 95 % CI = 1.0–2.6 ) . Dementia or MCI was diagnosed in 77.8 % of the surviving patients with postoperative delirium and in 40.9 % of control patients ( relative risk = 1.9 , 95 % CI = 1.1–3.3 ) . Half of the patients with delirium were institutionalized at follow-up compared to 28.6 % of the controls ( relative risk = 1.8 , 95 % CI = 0.9–3.4 ) . Conclusion : The risk of dementia or MCI at follow-up is almost doubled in elderly hip surgery patients with postoperative delirium compared with at-risk patients without delirium . Delirium may indicate underlying dementia BACKGROUND International guidelines recommend systematic assessment of pain , agitation/sedation and delirium with vali date d scales for all ICU patients . However , these evaluations are often not done . We have created an e-learning training platform for the continuous medical education , and assessed its efficacy in increasing the use of vali date d tools by all medical and nursing staff of the participating ICUs during their daily practice . METHODS Multicenter , r and omized , before and after study . The eight participating centers were r and omized in two groups , and received training at different times . The use of vali date d tools ( Verbal Numeric Rating or Behavioral Pain Scale for pain ; Richmond Agitation-Sedation Scale for agitation ; Confusion Assessment Method for the ICU for delirium ) was evaluated from clinical data recorded in medical charts during a week , with follow-up up to six months after the training . All the operators were invited to complete a question naire , at baseline and after the training . RESULTS Among the 374 nurses and physicians involved , 140 ( 37.4 % ) completed at least one of the three courses . The assessment of pain ( 38.1 vs. 92.9 % , P<0.01 ) and delirium ( 0 vs. 78.6 % , P<0.01 ) using vali date d tools significantly increased after training . Observation in the follow-up showed further improvement in delirium monitoring , with no signs of extinction for pain and sedation/agitation measurements . CONCLUSIONS This e-learning program shows encouraging effectiveness , and the increase in the use of vali date d tools for neurological monitoring in critically ill patients lasts over time Background Delirium , a common problem among hospitalized elderly patients , is not usually diagnosed by doctors for various reasons . The primary aim of this study was to evaluate the effect of a short training course on the identification of delirium and the diagnostic rate of delirium among hospitalized patients aged ≥65 years . The secondary aim was to identify the risk factors for delirium . Methods A prospect i ve study was conducted in an acute-care hospital in Moscow , Russia . Six doctors underwent a short training course on delirium . Data collected included assessment by the confusion assessment method for the intensive care units , sociodemographic data , functional state before hospitalization , comorbidity , and hospitalization indices ( indication for hospitalization , stay in intensive care unit , results of laboratory tests , length of hospitalization , and in-hospital mortality ) . Results Delirium was diagnosed in 13 of 181 patients ( 7.2 % ) who underwent assessment . Cognitive impairment was diagnosed more among patients with delirium ( 30.0 % vs 6.1 % , P=0.029 ) ; Charlson comorbidity index was higher ( 3.6±2.4 vs 2.3±1.8 , P=0.013 ) ; and Barthel index was lower ( 43.5±34.5 vs 94.1±17.0 , P=0.000 ) . The length of hospitalization was longer for patients with delirium at 13.9±7.3 vs 8.8±4.6 days ( P=0.0001 ) , and two of the 13 patients with delirium died during hospitalization compared with none of the 168 patients without delirium ( P=0.0001 ) . Conclusion Although the rate of delirium was relatively low compared with studies from the West , this study proves that an educational intervention among doctors can bring about a significant change in the diagnosis of the condition This study investigates the relationships between delirium , cognitive impairment and acute illness severity with adverse clinical outcomes ; in-hospital mortality , hospital length of stay , or new entry to a care home . It is a prospect i ve observational study of medical in patients 70 years or older , with repeated measurements of cognition , delirium status , delirium severity , and severity of physical illness every 3 days until the 18th day and then the 28th day of hospitalization . Of 94 participants , 33 had delirium and 14 recovered during their hospitalization . Predictor variables for recovery were initial Mini Mental State Examination ( MMSE ) ( p=0.003 ) and severity of delirium at second assessment ( p=0.02 ) , for mortality initial MMSE ( p=0.002 ) and for discharge to care home were initial delirium status ( p=0.008 ) and age ( p=0.004 ) . Delirious people newly discharged to care homes stayed longer in hospital than those discharged to their previous address ( p=0.016 ) . We conclude that delirium is not a transient disorder . The presence of delirium was not related to measures of the severity of physical illness or disability . High mortality was associated with delirium but was specifically associated with cognitive impairment . Prolonged length of stay of delirious people may depend on discharge destination Background and aims : Delirium is a common postoperative complication in elderly patients which has a serious impact on outcome in terms of morbidity and costs . We examined whether a postoperative multi-factorial intervention program can reduce delirium and improve outcome in patients with femoral neck fractures . Methods : One hundred and ninety-nine patients , aged 70 years and over ( mean age±SD , 82±6 , 74 % women ) , were r and omly assigned to postoperative care in a specialized geriatric ward or a conventional orthopedic ward . The intervention consisted of staff education focusing on the assessment , prevention and treatment of delirium and associated complications . The staff worked as a team , applying comprehensive geriatric assessment , management and rehabilitation . Patients were assessed using the Mini Mental State Examination and the Organic Brain Syndrome Scale , and delirium was diagnosed according to DSM-IV criteria . Results : The number of days of postoperative delirium among intervention patients was fewer ( 5.0±7.1 days vs 10.2±13.3 days , p=0.009 ) compared with controls . A lower proportion of intervention patients were delirious postoperatively than controls ( 56/102 , 54.9 % vs 73/97 , 75.3 % , p=0.003 ) . Eighteen percent in the intervention ward and 52 % of controls were delirious after the seventh postoperative day ( p<0.001 ) . Intervention patients suffered from fewer complications , such as decubitus ulcers , urinary tract infections , nutritional complications , sleeping problems and falls , than controls . Total postoperative hospitalization was shorter in the intervention ward ( 28.0±17.9 days vs 38.0±40.6 days , p=0.028 ) . Conclusions : Patients with postoperative delirium can be successfully treated , result ing in fewer days of delirium , fewer other complications , and shorter length of hospitalization Delirium is a significant problem for older hospitalized people and is associated with poor outcomes . It is poorly recognized and evidence suggests that a major reason is lack of education . Nurses , who are educated about delirium , can play a significant role in improving delirium recognition . This study evaluated the impact of a delirium specific educational website . A cluster r and omized controlled trial , with a pretest/post-test time series design , was conducted to measure delirium knowledge ( DK ) and delirium recognition ( DR ) over three time-points . Statistically significant differences were found between the intervention and non-intervention group . The intervention groups ' DK scores were higher and the change over time results were statistically significant [ T3 and T1 ( t=3.78 p=<0.001 ) and T2 and T1 baseline ( t=5.83 p=<0.001 ) ] . Statistically significant improvements were also seen for DR when comparing T2 and T1 results ( t=2.56 p=0.011 ) between both groups but not for changes in DR scores between T3 and T1 ( t=1.80 p=0.074 ) . Participants rated the website highly on the visual , functional and content elements . This study supports the concept that web-based delirium learning is an effective and satisfying method of information delivery for registered nurses . Future research is required to investigate clinical outcomes as a result of this web-based education BACKGROUND Clinical practice guidelines have been developed to improve screening , prevention and management of delirium . AIMS To implement delirium guidelines in general medical patients to reduce incidence and duration of delirium and improve outcomes in delirious patients . METHODS Implementation was led by a multidisciplinary team of clinicians and project staff on one medical ward . Evaluation was undertaken as a controlled trial in patients aged 65 years or older with/at risk of delirium , compared with a control medical ward . Interventions included risk screening , delirium detection , multidisciplinary education , ward modifications including a four-bed delirium bay , behaviour and medication protocol s , and use of nursing assistant and volunteers . Primary outcome measures were incidence and duration of delirium ; secondary outcomes were length of stay , mortality , falls and discharge destination in delirious subgroup . Process measures included ward moves , use of neuroleptics , allied health review and delirium bay use . RESULTS Of 206 consenting older medical patients , 22 % were delirious at admission and 44 % were at risk . No incident cases of delirium were identified . In the delirious subgroup , significantly fewer intervention participants were discharged with persistent delirium ( 32 % vs 71 % , P = 0.016 ) , with trends to reduced inpatient mortality ( 0 % vs 18.5 % , P = 0.07 ) and falls ( 11 % vs 22 % , P = 0.16 ) , at the expense of a longer medical ward stay ( 16 days vs 8 days , P = 0.01 ) . CONCLUSIONS Low incidence of new delirium may reflect the established interdisciplinary care environment . Improved outcomes in the delirious group are encouraging although implementation was costly , including increased length of acute ward stay This retrospective study examined delirium and related confusional diagnoses recorded in patients older than age 60 discharged from Veterans Affairs ( VA ) acute inpatient units nationally in 1996 ( n = 267,947 ) . Only 4 % of patients had delirium or related confusional diagnoses recorded . Patients with recorded delirium had significantly higher mortality than did those without recorded delirium or those with other confusional diagnoses ( “ organic psychoses ” ) ; the most common delirium types were dementia with delirium and alcohol intoxication/withdrawal delirium . Organic psychoses patients had the longest lengths of stay and significantly more admissions to nonmedical/surgical units and discharges to nursing homes ; almost 20 % were African American . The recorded rate of delirium in the VA health system likely underestimates true prevalence and possibly reflects nonrecognition of delirium in many older veterans . Certain motoric and etiologic types of delirium may be more commonly diagnosed and recorded . Future research should prospect ively examine recognition of motoric and etiologic delirium subtypes and racial differences in delirium diagnoses . ( J Geriatr Psychiatry Neurol 2003 ; 16:32 - 38 Objective : Although medical intensive care unit nurses at our institution routinely use the Intensive Care Delirium Screening Checklist ( ICDSC ) to identify delirium , physicians rely on traditional diagnostic methods . We sought to measure the effect of physicians ’ use of the ICDSC on their ability to detect delirium . Design : Before – after study . Setting : Medical intensive care unit of an academic medical center Patients and Participants : A total of 25 physicians with > = 1 month of clinical experience in the medical intensive care unit conducted 300 delirium assessment s in 100 medical intensive care unit patients . Measurements and Main Results : Physicians sequentially evaluated two patients for delirium using whatever diagnostic method preferred . Following st and ardized education regarding ICDSC use , each physician evaluated two different patients for delirium using the ICDSC . Each physician assessment was preceded by consecutive , but independent , evaluations for delirium by the patient 's nurse and then a vali date d judge using the ICDSC . Before ( PRE ) physician ICDSC use , the vali date d judge identified delirium in five patients ; the physicians and nurses identified delirium in zero and four of these patients , respectively . The physicians incorrectly identified delirium in four additional patients . After ( POST ) physician ICDSC use , the vali date d judge identified delirium in 11 patients ; the physicians and nurses identified delirium in eight and ten of these patients , respectively . The physicians incorrectly identified delirium in one patient . After physician ICDSC use , agreement improved between both the physicians and vali date d judge ( PRE [ kappa ] = ‐0.14 [ 95 % confidence interval { CI } = ‐0.27 to ‐0.02 ] to POST [ kappa ] = 0.67 [ 95 % CI = 0.38 to 0.96 ] ) and physicians and nurses ( PRE [ kappa ] = ‐0.15 [ 95 % CI = ‐0.29 to ‐0.02 ] to POST [ kappa ] = 0.58 [ 95 % CI = 0.25 to 0.91 ] ) . Nurses vs. vali date d judge agreement was strong in both periods ( PRE [ kappa ] = 0.65 [ 95 % CI = 0.29 to 1.00 ] and POST [ kappa ] = 0.92 [ 95 % CI = 0.76 to 1.00 ] ) . Conclusions : Use of the ICDSC , along with education supporting its use , improves the ability of physicians to detect delirium in the medical intensive care unit BACKGROUND Comprehensive care for frail older in patients may improve selected outcomes and reduce harm . OBJECTIVE To evaluate a Hospitalist-run Acute Care for the Elderly ( Hospitalist-ACE ) service . DESIGN Quasi-r and omized , controlled trial . SETTING Urban academic medical center . PATIENTS Medical in patients age ≥70 years . INTERVENTION Hospitalist-ACE service components : 1 ) selected hospitalist attendings ; 2 ) daily interdisciplinary rounds ; 3 ) st and ardized geriatric assessment ; 4 ) clinical focus on mitigating harm and discharge planning ; 5 ) novel inpatient geriatrics curriculum . MEASURES The primary outcome was recognition of abnormal functional status by the primary medical team . Secondary outcomes included : recognition of abnormal cognitive status and delirium by the primary medical team ; use of physical restraints and sleep aids ; documentation of code status ; hospital charges , length of stay , readmission rates , discharge location , and falls . RESULTS One hundred twenty-two Hospitalist-ACE patients were compared to 95 usual care patients . Hospitalist-ACE patients had significantly greater recognition of abnormal functional status ( 65 % vs 32 % , P < 0.0001 ) , and abnormal cognitive status ( 57 % vs 36 % , P = 0.02 ) , and greater use of " Do Not Attempt Resuscitation " orders ( 39 % vs 26 % , P = 0.04 ) . There were no differences in use of physical restraints , or sleep aids , falls , or discharge location . Hospitalist-ACE patients and usual care patients had similar mean lengths of stay in days ( 3.4 ± 2.7 vs 3.1 ± 2.7 , P = 0.52 ) , mean charges ( $ 24,617 ± $ 15,828 vs $ 21,488 ± $ 13,407 , P = 0.12 ) , and 30-day readmission rates ( 12 % vs 10 % , P = 0.50 ) . CONCLUSIONS A Hospitalist-ACE service may improve care processes without significantly increasing re source consumption . No impact on key clinical outcomes was observed OBJECTIVE To evaluate the impact of the GENE course on emergency nurses ' geriatric best practice s in the emergency department ( ED ) . SAMPLE A convenience sample of 102 emergency nurses who attended the GENE course at the San Diego convention center on October 3 , 2004 . METHOD A prospect i ve method of data collection , with data collection before , immediately after , and three months after attending the course , was used to evaluate the short-term impact of the GENE course on emergency nurses ' geriatric knowledge and geriatric care best practice s. RESULTS After attending the GENE course , emergency nurses showed increased a ) knowledge of geriatric concepts ( p < .000 , alpha = .01 ) and b ) self-rated ability to provide care in areas such as functional assessment , assessment of depression , delirium , dementia , polypharmacy , and appropriate referrals to services . ED nurses reported significantly greater utilization of particular geriatric assessment tools and greater incorporation of knowledge and skills related to the assessment of pain , polypharmacy , elder abuse and neglect , and atypical presentation of illness as part of their practice . Finally , a significant increase in the number of emergency departments that incorporated geriatric protocol s of care was reported ( p = .003 , alpha = .05 ) OBJECTIVES To analyze the effectiveness of a multicomponent intervention integrated into daily practice for the prevention of in-hospital delirium in elderly patients . DESIGN Controlled study comparing an intervention in a geriatric unit ( GI ) with usual care in two internal medicine services ( UC ) . SETTING University hospital in Madrid , Spain . PARTICIPANTS Five hundred forty-two consecutive patients ( 170 GI , 372 UC ) , aged 70 and older , with any of the risk criteria for delirium ( cognitive impairment , visual impairment , acute disease severity , dehydration ) . INTERVENTION Educational measures and specific actions in seven risk areas ( orientation , sensory impairment , sleep , mobilization , hydration , nutrition , drug use ) . Daily monitoring of adherence . MEASUREMENTS Baseline characteristics , risk factors for delirium , and quality care indicators were analyzed . The primary endpoint was incidence of delirium assessed daily . The secondary endpoint was functional decline , defined as loss of independence in any of the activities of daily living . The intervention effect was evaluated using logistic regression analysis . RESULTS Delirium affected 11.7 % of the GI group and 18.5 % of the UC group ( P=.04 ) . After adjustment for confounders , the intervention was associated with lower incidence of delirium ( odds ratio=0.4 , 95 % confidence interval=0.24 - 0.77 ; P=.005 ) . In the patients who experienced delirium , severity , length , and recurrence of episodes were similar in both groups . Adherence to the intervention protocol s was 75.7 % . The intervention reduced the rate of functional decline ( 45.5 % in GI vs 56.3 % in UC , P=.03 ) and improved other quality indicators ( e.g. , mobilization and physical restraints reduction ) . CONCLUSION A multicomponent , nonpharmacological intervention integrated into routine practice reduces delirium during hospitalization in older patients , improves quality of care , and can be implemented without additional re sources in a public healthcare system Objective : The awakening and breathing coordination , delirium monitoring/management , and early exercise/mobility bundle is an evidence -based interprofessional multicomponent strategy for minimizing sedative exposure , reducing duration of mechanical ventilation , and managing ICU-acquired delirium and weakness . The purpose of this study was to identify facilitators and barriers to awakening and breathing coordination , delirium monitoring/management , and early exercise/mobility bundle adoption and to evaluate the extent to which bundle implementation was effective , sustainable , and conducive to dissemination . Design : Prospect i ve , before-after , mixed- methods study . Setting : Five adult ICUs , one step-down unit , and a special care unit located in a 624-bed academic medical center Subjects : Interprofessional ICU team members at participating institution . Interventions and Measurements : In collaboration with the participating institution , we developed , implemented , and refined an awakening and breathing coordination , delirium monitoring/management , and early exercise/mobility bundle policy . Over the course of an 18-month period , all ICU team members were offered the opportunity to participate in numerous multimodal educational efforts . Three focus group sessions , three online surveys , and one educational evaluation were administered in an attempt to identify facilitators and barriers to bundle adoption . Main Results : Factors believed to facilitate bundle implementation included : 1 ) the performance of daily , interdisciplinary , rounds ; 2 ) engagement of key implementation leaders ; 3 ) sustained and diverse educational efforts ; and 4 ) the bundle ’s quality and strength . Barriers identified included : 1 ) intervention-related issues ( e.g. , timing of trials , fear of adverse events ) , 2 ) communication and care coordination challenges , 3 ) knowledge deficits , 4 ) workload concerns , and 5 ) documentation burden . Despite these challenges , participants believed implementation ultimately benefited patients , improved interdisciplinary communication , and empowered nurses and other ICU team members . Conclusions : In this study of the implementation of the awakening and breathing coordination , delirium monitoring/management , and early exercise/mobility bundle in a tertiary care setting , clear factors were identified that both advanced and impeded adoption of this complex intervention that requires interprofessional education , coordination , and cooperation . Focusing on these factors preemptively should enable a more effective and lasting implementation of the bundle and better care for critically ill patients . Lessons learned from this study will also help healthcare providers optimize implementation of the recent ICU pain , agitation , and delirium guidelines , which has many similarities but also some important differences as compared with the awakening and breathing coordination , delirium monitoring/management , and early exercise/mobility bundle As regular as the tide it would appear that the world of medical education research finds itself in an endless oscillation between the flood of promoting the empiricallygrounded approach that has evolved over the past many decades and the ebb of criticising the strength of the findings that have accumulated . The most recent challenge I have seen put forward to the community occurred in the past 4 months at two international conferences in which the keynote speakers , both fantastic scholars whose opinions I respect a great deal , coaxed the field towards raising its st and ards after pointing out that both the rigour and relevance of research in our field is lacking . Both used Todres , et al. ’s 2007 paper to point out that a full two thirds of medical education research studies were observational in nature while less than three per cent utilised r and omised controlled trial ( RCT ) design s. In a letter published in this issue Jones , et al. clarify that they did not intend to advocate for RCTs ( or quantitative methods more generally ) in that 2007 article , but rather , that their message was that whatever research design is used it should be used to the highest st and ards of practice for that design . This is an important clarification . One could easily be forgiven for inferring that cl aims of stagnation within medical education research accompanied by the observation that the majority of studies in the field are observational implies that observational studies ( and the qualitative research encompassed in that broad label ) are less desirable than other methods , as indicated by Dornan , et al. , in their reply |
12,294 | 32,185,630 | We found limited scientific evidence to support exercise-based strategies to prevent muscle injury in elite footballers . | Exercise-based strategies are used to prevent muscle injuries in football and studies on different competitive-level population s may provide different results .
To evaluate the effectiveness of exercise-based muscle injury prevention strategies in adult elite football . | Background This study was conducted to investigate whether the most common injuries in soccer could be prevented , and to determine if a simple question naire could identify players at increased risk . Hypothesis Introduction of targeted exercise programs to male soccer players with a history of previous injury or reduced function in the ankle , knee , hamstring , or groin will prevent injuries . Study Design R and omized controlled trial ; Level of evidence , 2 . Methods A total of 508 players representing 31 teams were included in the study . A question naire indicating previous injury and /or reduced function as inclusion criteria was used to divide the players into high-risk ( HR ) ( 76 % ) and low-risk ( LR ) groups . The HR players were r and omized individually into an HR intervention group or HR control group . Results A total of 505 injuries were reported , sustained by 56 % of the players . The total injury incidence was a mean of 3.2 ( 95 % confidence interval [ CI ] , 2.5–3.9 ) in the LR control group , 5.3 ( 95 % Cl , 4.6–6.0 ) in the HR control group ( P = .0001 vs the LR control group ) , and 4.9 ( 95 % Cl , 4.3–5.6 ) in the HR intervention group ( P = .50 vs the HR control group ) . For the main outcome measure , the sum of injuries to the ankle , knee , hamstring , and groin , there was also a significantly lower injury risk in the LR control group compared with the 2 other groups , but no difference between the HR intervention group and the HR control group . Compliance with the training programs in the HR intervention group was poor , with only 27.5 % in the ankle group , 29.2 % in the knee group , 21.1 % in the hamstring group , and 19.4 % in the groin defined as having carried out the minimum recommended training volume . Conclusion The players with a significantly increased risk of injury were able to be identified through the use of a question naire , but player compliance with the training programs prescribed was low and any effect of the intervention on injury risk could not be detected 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 A soccer-specific balance training has been shown to decrease injury incidence of the anterior cruciate ligament and ankle sprains in r and omized controlled trials . However , hamstring injuries and tendinopathy remain significant issues in soccer . Hypothesis Proprioceptive training can reduce the incidence of hamstring muscle injuries and tendinopathy in elite soccer . There is a dose-effect relationship between balance training duration and injury incidence . Study Design Cohort study ; Level of evidence , 3 . Methods Twenty-four elite female soccer players ( body mass index , 21.7 ± 1.2 ; age , 21 ± 4 years ) of a German premier league soccer team were prospect ively included . Starting in January 2004 , an additional soccer-specific proprioceptive multistation training was initiated over 3 years . Injury data /1000 hours of exposure with documentation of all occurred injuries , detailed training , and match exposure data as well as time loss data were 100 % complete . Results At the end of the 3-year proprioceptive balance training intervention , noncontact hamstring injury rates were reduced from 22.4 to 8.2/1000 hours ( P = .021 ) , patellar tendinopathy from 3.0 to 1.0/1000 hours ( P = .022 ) , and Achilles tendinopathy from 1.5 to 0.0/1000 hours ( P = .035 ) . There was no effect of balance training on contact injuries . Mean time loss of all assessed injuries significantly decreased from 14.4 days during the control period to 1.5 days during intervention periods ( P = .003 ) . The more minutes of balance training performed , the lower the rate of overall injuries ( r = −0.185 , P = .001 ) , hamstring injuries ( r = −0.267 , P = .003 ) , patellar tendinopathy ( r = −0.398 , P = .02 ) , and gastrocnemius strains ( r = −0.342 , P = .002 ) . Conclusion Soccer-specific balance training ( protective balancing ) can reduce noncontact hamstring injuries and patellar and Achilles tendinopathy . A dose-effect relationship between duration of balance training and injury incidence is evident . A proprioceptive training program reduced the rehabilitation time in noncontact injuries , which warrants further investigation Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies Background : Muscle injuries constitute a large percentage of all injuries in football . Purpose : To investigate the incidence and nature of muscle injuries in male professional footballers . Study Design : Cohort study ; Level of evidence , 2 . Methods : Fifty-one football teams , comprising 2299 players , were followed prospect ively during the years 2001 to 2009 . Team medical staff recorded individual player exposure and time-loss injuries . The first-team squads of 24 clubs selected by the Union of European Football Associations as belonging to the best European teams , 15 teams of the Swedish First League , and another 15 European teams playing their home matches on artificial turf pitches were included . A muscle injury was defined as “ a traumatic distraction or overuse injury to the muscle leading to a player being unable to fully participate in training or match play . ” Results : In total , 2908 muscle injuries were registered . On average , a player sustained 0.6 muscle injuries per season . A squad of 25 players can thus expect about 15 muscle injuries per season . Muscle injuries constituted 31 % of all injuries and caused 27 % of the total injury absence . Ninety-two percent of all muscle injuries affected the 4 major muscle groups of the lower limbs : hamstrings ( 37 % ) , adductors ( 23 % ) , quadriceps ( 19 % ) , and calf muscles ( 13 % ) . Sixteen percent of the muscle injuries were reinjuries . These reinjuries caused significantly longer absences than did index injuries . The incidence of muscle injury increased with age . When separated into different muscle groups , however , an increased incidence with age was found only for calf muscle injuries and not for hamstring , quadriceps , or hip/groin strains . Conclusion : Muscle injuries are a substantial problem for players and their clubs . They constitute almost one third of all time-loss injuries in men ’s professional football , and 92 % of all injuries affect the 4 big muscle groups in the lower limbs ‘ More research is needed ’ is a most unhelpful conclusion for the clinician reader of a systematic review . Clinicians look to research ers for the ‘ research evidence ’ part of Professor Sackett ’s ‘ three circles ’ of evidence -based practice .1 The clinician can not ignore the patient in front of him or her just because there is no evidence from systematic review s or r and omised controlled trials ( RCTs ): ‘ Kindly forget about your shoulder problem , until we have better research to tell me what to do ’ ? This will not do ! In this editorial , we share three practical tips for authors synthesis ing lower level evidence in systematic review s , when high- quality RCTs are absent . Our goal is to help authors help clinicians help patients . Consider the patient who plays tennis and presents with shoulder pain . Right now , the clinician who is seeking RCT evidence on how to progress from impairment-focused tasks in neutral shoulder positions to high-level , sport-specific tasks will be disappointed . Being able to function in shoulder elevation positions above The purpose was to test the effect of eccentric strength training and flexibility training on the incidence of hamstring strains in soccer . Hamstring strains and player exposure were registered prospect ively during four consecutive soccer seasons ( 1999 - 2002 ) for 17 - 30 elite soccer teams from Icel and and Norway . The first two seasons were used as baseline , while intervention programs consisting of warm-up stretching , flexibility and /or eccentric strength training were introduced during the 2001 and 2002 seasons . During the intervention seasons , 48 % of the teams selected to use the intervention programs . There was no difference in the incidence of hamstring strains between teams that used the flexibility training program and those who did not [ relative risk (RR)=1.53 , P=0.22 ] , nor was there a difference compared with the baseline data ( RR=0.89 , P=0.75 ) . The incidence of hamstring strains was lower in teams who used the eccentric training program compared with teams that did not use the program ( RR=0.43 , P=0.01 ) , as well as compared with baseline data for the same intervention teams ( RR=0.42 , P=0.009 ) . Eccentric strength training with Nordic hamstring lowers combined with warm-up stretching appears to reduce the risk of hamstring strains , while no effect was detected from flexibility training alone . These results should be verified in r and omized clinical trials PURPOSE To analyze the effect of an eccentric-overload training program ( ie , half-squat and leg-curl exercises using flywheel ergometers ) with individualized load on muscle-injury incidence and severity and performance in junior elite soccer players . METHODS Thirty-six young players ( U-17 to U-19 ) were recruited and assigned to an experimental ( EXP ) or control group ( CON ) . The training program consisted of 1 or 2 sessions/wk ( 3 - 6 sets with 6 repetitions ) during 10 wk . The outcome measured included muscle injury ( incidence per 1000 h of exposure and injury severity ) and performance tests ( countermovement jump [ CMJ ] , 10-m and 20-m sprint test ) . RESULTS Between-groups results showed a likely ( ES : 0.94 ) lower number of days of absence per injury and a possible decrement of incidence per 1000 h of match play in EXP than in CON . Regarding muscle performance , a substantial better improvement ( likely to very likely ) was found in 20-m sprint time ( ES : 0.37 ) , 10-m flying-sprint time ( ES : 0.77 ) , and CMJ ( ES : 0.79 ) for EXP than for CON . Within-group analysis showed an unclear effect in each variable in CON . Conversely , substantial improvements were obtained in CMJ ( ES : 0.58 ) , 20-m sprint time ( ES : 0.32 ) , 10-m flying-sprint time ( ES : 0.95 ) , and injury severity ( ES : 0.59 ) in EXP . Furthermore , a possible decrement in total injury incidence was also reported in EXP . CONCLUSIONS The eccentric-based program led to a reduction in muscle-injury incidence and severity and showed improvements in common soccer tasks such as jumping ability and linear-sprinting speed R and omised controlled trials are the best way to compare the effectiveness of different interventions . Only r and omised trials allow valid inferences of cause and effect . Only r and omised trials have the potential directly to affect patient care — occasionally as single trials but more often as the body of evidence from several trials , whether or not combined formally by meta- analysis . It is thus entirely reasonable to require higher st and ards for papers reporting r and omised trials than those describing other types of study . Like all studies , r and omised trials are open to bias if done badly.1 It is thus essential that r and omised trials are done well and reported adequately . Readers should not have to infer what was probably done , they should be told explicitly . Proper methodology should be used and be seen to have been used . Yet review s of published trials have consistently found major deficiencies in reporting,2 3 4 making the task Research and discussion s about injury rates and their prevention in elite football is one of the hottest topics in the medical and sport science literature . Over the past years , there has been an explosion of the number of publications , including surveys,1 observational , retrospective or prospect ive2 studies , training interventions and various types of expert opinions and commentaries.3 This array of information are likely useful to improve our underst and ing of what the best practice s may be and , in turn , increase our ability to better prepare , manage and treat players . However , a recent survey has shown that 83 % of UEFA clubs do not follow evidence d-based prevention programmes.1 It was also shown that hamstring injuries kept increasing over the last 13 years.2 Taken together , those two papers may suggest that the majority of elite club practitioners likely disregard research findings 1 and may therefore be the one to be blamed for those increased injury rates.2 Making supporting staff and coaches responsible for those injuries is easy , especially when considering their perceived typical personality traits ( ie , so-called type 2,4 high egos and little open-mindedness and willingness to learn—‘why could they be bothered applying the new study findings ? ’ ) . While this may be true sometimes , the reality is that The primary purpose of this study was to evaluate whether a preseason strength training programme for the hamstring muscle group - emphasising eccentric overloading - could affect the occurrence and severity of hamstring injuries during the subsequent competition season in elite male soccer players . Thirty players from two of the best premier-league division teams in Sweden were divided into two groups ; one group received additional specific hamstring training , whereas the other did not . The extra training was performed 1 - 2 times a week for 10 weeks by using a special device aim ing at specific eccentric overloading of the hamstrings . Isokinetic hamstring strength and maximal running speed were measured in both groups before and after the training period and all hamstring injuries were registered during the total observational period of 10 months . The results showed that the occurrence of hamstring strain injuries was clearly lower in the training group ( 3/15 ) than in the control group ( 10/15 ) . In addition , there were significant increases in strength and speed in the training group . However , there were no obvious coupling between performance parameters and injury occurrence . These results indicate that addition of specific preseason strength training for the hamstrings - including eccentric overloading - would be beneficial for elite soccer players , both from an injury prevention and from performance enhancement point of view Background Groin injuries represent a considerable problem in male football . Previous groin-specific prevention programmes have not shown a significant reduction in groin injury rates . An exercise programme using the Copenhagen Adduction exercise increases hip adduction strength , a key risk factor for groin injuries . However , its preventive effect is yet to be tested . Aim To evaluate the effect of a single-exercise approach , based on the Copenhagen Adduction exercise , on the prevalence of groin problems in male football players . Methods 35 semiprofessional Norwegian football teams were cluster-r and omised into an intervention group ( 18 teams , 339 players ) and a control group ( 17 teams , 313 players ) . The intervention group performed an Adductor Strengthening Programme using one exercise , with three progression levels , three times per week during the preseason ( 6–8 weeks ) , and once per week during the competitive season ( 28 weeks ) . The control group were instructed to train as normal . The prevalence of groin problems was measured weekly in both groups during the competitive season using the Oslo Sports Trauma Research Center Overuse Injury Question naire . Results The average prevalence of groin problems during the season was 13.5 % ( 95 % CI 12.3 % to 14.7 % ) in the intervention group and 21.3 % ( 95 % CI 20.0 % to 22.6 % ) in the control group . The risk of reporting groin problems was 41 % lower in the intervention group ( OR 0.59 , 95 % CI 0.40 to 0.86 , p=0.008 ) . Conclusion The simple Adductor Strengthening Programme substantially reduced the self-reported prevalence and risk of groin problems in male football players . Trial registration number IS RCT N98514933 Objective To investigate the effect of adding Nordic exercise as post-training in decreasing hamstring initial , recurrent injuries rates , and their severity . Methods In this r and omly controlled trial study , 34 professional football players aged 21 to 35 years were r and omly assigned into two groups ( 17 players each ) from Sporting clubs at Alex and ria , Egypt . For group one , Nordic hamstring exercise ( NHE ) was performed pre-training and post-training . For group two , NHE was only performed pre-training . The control group was the same team during the previous season . Length of the trial was 12 weeks . The Australian football association injury form was used to collect incidence of injuries for each subject in both groups . Results Pooled results based on total injuries showed that group one had significantly less hamstring initial injuries ( 92 % less ) than the previous season , while group two had 80 % less initial injuries and 85 % less recurrent injuries than previous season . Regarding the severity of injuries in term of mean number of absent days , it was 1 day for group one and 2.7 days for group two while it was 7.95 days for the previous season during total risk time of 116.3±13.2 and 117.6±5.7 exposure hours for group one and group two , respectively . Conclusion The use of NHE as a prevention protocol was effective in reducing all hamstring injuries with the use of NHE during pre-training and post-training having the greatest effect |
12,295 | 15,266,494 | REVIEW ERS ' CONCLUSIONS This review does not support the routine use of intramuscular penicillin to prevent EOGBSD in newborn infants . | BACKGROUND Early-onset group B streptococcal disease ( EOGBSD ) is the most frequent cause of serious infection in the newborn period .
Current strategies used to prevent EOGBSD are focused upon maternal antibiotic prophylaxis to reduce transmission of GBS to the infant .
Observational studies have suggested that the administration of intramuscular penicillin to the newborn immediately following delivery may be an effective strategy to reduce the incidence of EOGBSD .
OBJECTIVES To determine if the administration of intramuscular penicillin to newborns at birth is a safe and effective method to prevent morbidity and mortality from EOGBSD . | Neonatal Group B streptococcal infections may not respond to antimicrobial therapy and have been associated with case fatality rates of 50 per cent or greater . We evaluated the effect on colonization and disease rates of a single intramuscular dose of aqueous penicillin G given at birth in a prospect ively controlled study of 18,738 neonates during a 25-month period . The colonization rate in the mothers was 26.6 per cent , with 50 per cent concordance in the untreated infants and 12.2 per cent in the penicillin-treated infants ( P < 0.001 ) . There was a significant decrease in the incidence of disease caused by all penicillin-susceptible organisms in the penicillin group ( 0.64 vs. 2.26 cases per thous and live births , P = 0.005 ) . Disease caused by penicillin-resistant pathogens was increased in the penicillin-treated group during the first year of the study but was unaffected during the second year . Routine administration of parenteral penicillin at birth can not be recommended until the effect on the incidence of disease caused by penicillin-resistant pathogens is fully defined This prospect i ve study was design ed to identify the role of postnatal penicillin prophylaxis in the prevention of neonatal group B streptococcus ( GBS ) infection . We studied 10 998 infants . Of these , 5389 were in the penicillin prophylaxis group ( PP ) and 5609 infants did not receive penicillin prophylaxis ( NPP ) . Infants were allocated to treatment by month of birth , alternating 3‐mo blocks or 2‐mo blocks to the two groups after the first block was r and omly assigned . The use of PP reduced the incidence of clinical sepsis ( 1.7 % PP versus 2.5 % NPP , p<0.01 ) , GBS infection ( 0.4 % PP versus 0.9 % NPP , p < 0.001 ) and deaths from sepsis ( 0.1 % PP versus 0.3 % NPP , p < 0.05 ) . We conclude that the routine use of postnatal penicillin prophylaxis appears to be effective in reducing the incidence of clinical sepsis and death from sepsis in neonates . □ Antimicrobial prophylaxis , group B streptococcus , neonatal The efficacy of a single dose of aqueous penicillin G in preventing neonatal group-B streptococcal infections was demonstrated in a r and omised study conducted over 41 months . 16 082 infant received a single dose of penicillin within one hour of delivery , and 15 976 infants who received tetracycline ophthalmic ointment served as the control group . Group-B streptococcal systemic infections were significantly less common in the penicillin-treated infants ( 0.6 vs 1.7 cases per 100 live birth , p = 0.004 ) . The incidence of infection caused by penicillin-resistant pathogen was insignificantly increased in the penicillin group ( 2.2 vs 1.6 cases per thous and live birth , p = 0.32 ) . this difference was accounted for almost completely by the events of the first 12 months of the study period when , for unexplained reasons , there was a considerable increase in the number of penicillin-resistant infections in the penicillin group ( 3.6 vs 1.4 cases per 1000 live births , p = 0.09 ) . The mortality associated with penicillin-susceptible pathogens was higher in the control group ( 0.1 vs 0.4 per 1000 live births , p = 0.18 ) . However , the mortality associated with penicillin-resistant pathogens was increased in the penicillin ( 0.4 vs 1.0 per 1000 live births , p = 0.06 ) . The combined mortality rates for all pathogens were not significantly different ( 1.1 vs 0.7 per 1000 liver births , p = 0.27 , for the penicillin and control groups , respectively ) and were nearly equivalent when the excess number of deaths associated with penicillin-resistant infections in the penicillin group during the first study year was excluded from analysis . The incidence of gonococcal ophthalmia and conjunctivitis was unaffected by the use of intramuscular penicillin at birth OBJECTIVE Recommendations for the use of antenatal antibiotics in obstetrics have increased in the past few years , especially for prophylaxis against group B streptococci , for prolongation of the latency time in patients with preterm premature rupture of the membranes , and as an adjuvant treatment in preterm labor . Our objective was to determine whether the use of antenatal ampicillin affects the incidence of and resistance of early-onset neonatal sepsis with organisms other than group B streptococci . STUDY DESIGN A prospect i ve cohort study was performed between January 1 , 1991 , and December 31 , 1996 . Every case of blood culture-proven neonatal sepsis was prospect ively surveyed . The type of bacteria isolated , drug resistance , antenatal antibiotic use and treatment indication , gestational age at delivery , and other antenatal and outcome variables were gathered . Early-onset neonatal sepsis was defined as disease onset within 7 days after birth . RESULTS A total of 42 cases of early-onset neonatal sepsis among 29,897 neonates delivered were found during the 6-year period . Of these , 15 cases were due to group B streptococci and 27 were the result of non-group B streptococcal organisms ( 21 gram-negative rods and 6 gram-positive cocci ) . Among the 27 non-group B streptococcal cases , 15 mothers had received antenatal ampicillin and 13 of the 15 bacterial isolates from these neonates ( 87 % ) were resistant to ampicillin , versus only 2 ampicillin-resistant isolates ( 17 % ) among the 12 cases in which no antenatal antibiotics were administered ( P = .0004 ) . Of the 15 mothers who were treated with ampicillin , 13 received more than 1 dose . In evaluating each year of the study , the overall administration of antibiotics to pregnant women in the antenatal period increased from < 10 % in 1991 to 16.9 % in 1996 . The incidence of early-onset neonatal sepsis with group B streptococci decreased during this time , whereas the incidence of early-onset sepsis with non-group B streptococcal organisms , especially Escherichia coli , increased . CONCLUSIONS The increased administration of antenatal ampicillin to pregnant women may be responsible for the increased incidence of early-onset neonatal sepsis with non-group B streptococcal organisms that are resistant to ampicillin . At this time penicillin G , rather than ampicillin , is therefore recommended for prophylaxis against group B streptococci . In addition , future studies are needed to determine whether alternate approaches , such as immunotherapy or vaginal washing , could be of benefit Abstract . Colonization with group B streptococci of the genital tract was studied in 1115 women during the last trimester of pregnancy . 76 or 6.82 % were found to harbour this bacterium . The incidence of contamination was significantly higher among Belgian women than among parturients of Mediterranean origin ( p < 0.001 ) . It was also more frequent in primigravidae ( p<0.05 ) and in the poorer ( 0.10 < p > 0.05 ) . At the time of admission in the delivery room , it was noticed that rupture of the amniotic membranes for more than 24 hours was more often associated with group B streptococcal carriage by the mother ( p<0.001 ) . 29 out of 68 ( 42.6 % ) infants born to group B streptococci positive mothers were colonized at birth . 67 of them were su bmi tted to a controlled trial of immediate versus delayed penicillin therapy . 44.8 % and 42.1 % of the neonates were contaminated at birth in each group of treatment respectively . No instance of group B streptococcal infection developed in either group . This suggests that immediate therapy with penicillin of infants of group B streptococci positive mothers has no definite advantage upon delayed treatment This document reflects emerging clinical and scientific advances on the date issued and is subject to change . The information should not be construed as dictating an exclusive course of treatment or procedure to be followed . Local institutions can dictate amendments to these opinions . They should be well documented if modified at the local level . None of these contents may be reproduced in any form without prior written permission of the SOGC . This Clinical Practice Guideline has been prepared by the Infectious Disease Committee , review ed by the Infectious Diseases and Immunization and the Fetus and Newborn Committees of the Canadian Paediatric Society , and the SOGC Family Practice Advisory Committee , and approved by the Executive and Council of the Society of Obstetricians and Gynaecologists of Canada . We studied the effect of penicillin on early-onset Group B streptococcal disease over a 52-month period in neonates who were at high risk of infection . Shortly after birth , 1187 neonates weighing 2000 g or less had blood sample s taken for cultures and were r and omized into an early-treatment group ( given intramuscular penicillin G within 60 minutes of birth ) or a control group . The incidence of early-onset disease was 20 per 1000 live births ( 24 of 1187 ) ; the number of infants in the early-treatment group who had disease ( 10 of 589 ) was similar to that in the control group ( 14 of 598 ) . The fatality rates were similar in both groups ( 6 of 10 vs. 8 of 14 ) . Cultures from blood obtained with one hour of birth were positive in 21 of the 24 infants with disease ; 22 of the 24 were symptomatic within four hours of birth . Thus , infection was well established before the first hour of postnatal life . At autopsy , gram-positive cocci were seen in lung sections of four infants in whom cultures of blood obtained after treatment had been sterile ; this indicates that giving routine antibiotic therapy before culture sample s are obtained can obscure bacteriologic diagnosis . We conclude that penicillin given at birth to neonates weighing 2000 g or less does not prevent early-onset streptococcal disease or reduce excess mortality associated with disease Objective To determine the effect of single-dose penicillin given at birth on the rate of early-onset group B streptococcal ( GBS ) invasive disease in an inner-city population . Methods Laboratory-based surveillance of GBS disease from 1972–1994 at Parkl and Memorial Hospital and Children 's Medical Center in Dallas , Texas , was review ed retrospectively . All infants born at Parkl and Memorial Hospital from January 1 , 1972 to December 31 , 1994 , or a total of 259,049 live births , were included . Early-onset ( within 3 days ) GBS disease rates were compared for each of five observation groups to determine the efficacy of a single dose of aqueous penicillin G ( 50,000 U for infants weighing 2000 g or more and 25,000 U for those weighing less than 2000 g ) administered intramuscularly within 1 hour of delivery for prevention of GBS disease . Results The rates of early-onset GBS disease were compared in five observation groups : A ) pre- study , January 1 , 1972 to December 3 , 1977—no GBS prophylaxis ; B ) prospect i ve , controlled intervention study , December 4 , 1977 to May 31 , 1981 , including infants who received a single dose of penicillin at birth ( group B1 ) and those who did not ( group B2 ) ; C ) universal penicillin prophylaxis , June 1 , 1981 to October 31 , 1986 ; and D ) no routine penicillin prophylaxis , November 1 , 1986 to December 31 , 1994 . The incidence of early-onset GBS disease in the penicillin groups ( B1 , C ) was significantly lower than that in the untreated groups ( A , B2 , D ) : 0.25 and 0.63 per 1000 versus 1.59 , 1.19 , and 1.95 per 1000 , respectively ( P ≤ .03 ) . The incidence of late-onset GBS disease was unaffected by penicillin prophylaxis , and there was no increase in the incidence of disease caused by penicillin-resistant pathogens or associated mortality in penicillin-treated infants : 2.2 and 2.1 per 1000 versus 1.6 and 3.3 per 1000 for disease ; 1.0 and 0.5 per 1000 versus 0.4 and 0.3 per 1000 for deaths . Conclusion Universal administration of single-dose pencillin at birth is a safe and effective intervention for the prevention of early-onset GBS disease In 1992 , the Committee on Infectious Diseases and Committee on Fetus and Newborn of the American Academy of Pediatrics provided guidelines for prevention of early-onset group B streptococcal ( GBS ) disease through intrapartum chemoprophylaxis of selected maternal GBS carriers . The guidelines were based on demonstrated efficacy in r and omized , controlled clinical trials and selected only women with GBS colonization who had an obstetric risk factor . The guidelines were controversial and their implementation incomplete . Since 1992 , additional data have become available , and experience with the guidelines has been gained in numerous medical centers . Recently , consensus guidelines were developed by obstetricians , pediatricians , family practitioners , and public health authorities and published by the Centers for Disease Control and Prevention . These recommendations are supported by the American College of Obstetricians and Gynecologists and the American Academy of Pediatrics . This statement review s the selection of pregnant women for chemoprophylaxis and provides an algorithm for management of their newborns |
12,296 | 27,502,153 | Many of the desirable outcomes of exercise for people with SMI , such as mood improvement , stress reduction and increased energy , are inversely related to the barriers of depression , stress and fatigue which frequently restrict their participation in exercise .
Providing patients with professional support to identify and achieve their exercise goals may enable them to overcome psychological barriers , and maintain motivation towards regular physical activity | Exercise can improve clinical outcomes in people with severe mental illness ( SMI ) .
However , this population typically engages in low levels of physical activity with poor adherence to exercise interventions .
Underst and ing the motivating factors and barriers towards exercise for people with SMI would help to maximize exercise participation . | Background Previous qualitative studies have found that exercise may facilitate symptomatic and functional recovery in people with long-term schizophrenia . This study examined the perceived effects of exercise as experienced by people in the early stages of psychosis , and explored which aspects of an exercise intervention facilitated or hindered their engagement . Methods Nineteen semi-structured interviews were conducted with early intervention service users who had participated in a 10-week exercise intervention . Interviews discussed people ’s incentives and barriers to exercise , short- and long-term effects , and opinions on optimal interventions . A thematic analysis was applied to determine the prevailing themes . Results The intervention was perceived as beneficial and engaging for participants . The main themes were ( a ) exercise alleviating psychiatric symptoms , ( b ) improved self-perceptions following exercise , and ( c ) factors determining exercise participation , with three respective sub-themes for each . Conclusions Participants explained how exercise had improved their mental health , improved their confidence and given them a sense of achievement . Autonomy and social support were identified as critical factors for effectively engaging people with first-episode psychosis in moderate-to-vigorous exercise . Implementing such programs in early intervention services may lead to better physical health , symptom management and social functioning among service users . Trial registration Current Controlled Trials IS RCT N09150095 . Registered 10 December 2013 Objective : To examine a 1-year follow-up of a 4-month , controlled clinical trial of exercise and antidepressant medication in patients with major depressive disorder ( MDD ) . Methods : In the original study , 202 sedentary adults with MDD were r and omized to : a ) supervised exercise ; b ) home-based exercise ; c ) sertraline ; or d ) placebo pill . We examined two outcomes measured at 1-year follow-up ( i.e. , 16 months post r and omization ) : 1 ) continuous Hamilton Depression Rating Scale score ; and 2 ) MDD status ( depressed ; partial remission ; full remission ) in 172 available participants ( 85 % of the original cohort ) . Regression analyses were performed to examine the effects of treatment group assignment , as well as follow-up antidepressant medication use and self-reported exercise ( Godin Leisure-Time Exercise Question naire ) , on the two outcomes . Results : In the original study , patients receiving exercise achieved similar benefits compared with those receiving sertraline . At the time of the 1-year follow-up , rates of MDD remission increased from 46 % at post treatment to 66 % for participants available for follow-up . Neither initial treatment group assignment nor antidepressant medication use during the follow-up period were significant predictors of MDD remission at 1 year . However , regular exercise during the follow-up period predicted both Hamilton Depression Rating Scale scores and MDD diagnosis at 1 year . This relationship was curvilinear , with the association concentrated between 0 minute and 180 minutes of weekly exercise . Conclusion : The effects of aerobic exercise on MDD remission seem to be similar to sertraline after 4 months of treatment ; exercise during the follow-up period seems to extend the short-term benefits of exercise and may augment the benefits of antidepressant use . Trial Registration : clinical trials.gov Identifier : NCT00331305 . MDD = major depressive disorder ; HAM-D = Hamilton Depression Rating Scale ; SCID = Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition Axis I Disorders ; PSSS = Perceived Social Support Scale OBJECTIVE The aim of this study was to examine both single and joint associations of physical activity and conventional cardiovascular risk factors with total and cardiovascular mortality among patients with diabetes . RESEARCH DESIGN AND METHODS We prospect ively followed 3,708 Finnish patients with type 2 diabetes aged 25 - 74 years . Physical activity , smoking status , blood pressure , height , weight , and serum cholesterol level were determined at baseline . Cox proportional hazard models were used to estimate single and joint effects of physical activity and other cardiovascular risk factors on the risk of mortality . RESULTS During a mean follow-up of 18.7 years , 1,423 deaths were recorded , 906 of which were due to cardiovascular disease . Moderate or high levels of physical activity were associated with decreased total and cardiovascular mortality , whereas higher levels of BMI and blood pressure and current smoking were associated with increased total and cardiovascular mortality . High serum cholesterol levels also increased cardiovascular mortality . The protective effect of physical activity was consistent in diabetic patients with any levels of BMI , blood pressure , total cholesterol , and smoking . CONCLUSIONS A moderate or high level of physical activity was associated with a reduced risk of total and cardiovascular mortality among patients with type 2 diabetes . The favorable association of physical activity with longevity was observed regardless of the levels of BMI , blood pressure , total cholesterol , and smoking The objective of this multicenter r and omised clinical trial was to examine the effect of exercise versus occupational therapy on mental and physical health in schizophrenia patients Background : Increasingly alarmed by the health risks ( that is , weight gain , elevated lipids , and poor glucose tolerance ) posed by novel antipsychotic medications , clinicians who treat schizophrenia are attempting to help patients improve lifestyle factors . Unfortunately , schizophrenia research has neglected exercise as a legitimate adjunctive treatment for schizophrenia . Objective : To assess the extent to which stable patients with schizophrenia would adhere to an exercise program if offered access to a fitness facility . Methods : Ten of 20 stable patients with schizophrenia or schizoaffective disorder who were treated with olanzapine for at least 4 weeks had the opportunity to receive access to a Young Men 's Christian Association ( YMCA ) fitness facility , based on r and om allocation . The intervention included a free membership to the YMCA for 6 months , with access to all the fitness amenities and equipment . The mean dosage of olanzapine was 11.5 mg daily for the YMCA group . Results : Of the 10 subjects , 2 did not attend at all . One subject met criteria for full attendance for each of the 6 months and lost 15 kg . Dropout rates were as follows : 90 % at 6 months , 70 % at 5 months , and 40 % at 4 months . The main reason they gave for poor attendance was lack of motivation . The mean weight gain was 2 kg in the YMCA group . Conclusion : Most subjects did not regularly exercise or attend . They cited poor motivation as the main reason . The subject who exercised regularly lost a significant amount of weight AIM Initiating antipsychotic medication frequently induces rapid , clinical ly significant weight gain . We aim ed to evaluate the effectiveness of a lifestyle and life skills intervention , delivered within 4 weeks of antipsychotic medication initiation , in attenuating weight gain in youth aged 14 - 25 years with first-episode psychosis ( FEP ) . METHODS We undertook a prospect i ve , controlled study in two early psychosis community services . Intervention participants ( n = 16 ) received a 12-week individualized intervention delivered by specialist clinical staff ( nurse , dietician and exercise physiologist ) and youth peer wellness coaches , in addition to st and ard care . A comparison group was recruited from a similar service and received st and ard care ( n = 12 ) . RESULTS The intervention group experienced significantly less weight gain at 12 weeks compared to st and ard care ( 1.8 kg , 95 % CI -0.4 to 2.8 vs. 7.8 kg , 4.8 - 10.7 , P < 0.001 ) . Thirteen per cent ( 2/16 ) of the intervention group experienced clinical ly significant weight gain ( greater than 7 % of baseline weight ) , while 75 % ( 9/12 ) of the st and ard care group experienced this level of weight gain . Similar positive effects of the intervention were observed for waist circumference . CONCLUSIONS A lifestyle and life skills intervention delivered as part of st and ard care attenuated antipsychotic-induced weight gain in young people with FEP . The intervention was acceptable to the young people referred to the service . Such interventions may prevent the seeding of future disease risk and in the long-term help reduce the life expectancy gap for people living with serious mental illness The purpose of this prospect i ve and observational design study was to assess the feasibility of using a pedometer and step log to explore level of physical activity ( PA ) and to assess motivation to be physically active in adults with schizophrenia . Descriptive statistics were used to analyse data of 7 male and 5 female subjects . Pedometer data indicated that subjects walked an average of 4731.03 ( ±3318.19 ) steps and 5002.58 ( ±3041.03 ) during the first week and second week of the study , respectively . A minimum 30-min walk was recorded on an average of 3.67 ( ±1.82 ) days ( week one ) and 4.5 ( ±1.88 ) days ( week two ) . Step logs , inconsistently maintained by subjects , were not able to be analysed . Examination of the Motives for Physical Activity Measure-Revised ( MPAM-R ) at baseline indicates that exercise fitness and body appearance were subjects ' primary motives for PA participation . Study findings indicate that it is feasible to use a pedometer to monitor the level of PA . However , maintenance of a concurrent step log requires further consideration to determine realistic outcomes . Extrinsically focused motivations for PA in this study sample may predict low PA adherence Individuals with schizophrenia display substantial neurocognitive deficits for which available treatments offer only limited benefits . Yet , findings from studies of animals , clinical and non clinical population s have linked neurocognitive improvements to increases in aerobic fitness ( AF ) via aerobic exercise training ( AE ) . Such improvements have been attributed to up-regulation of brain-derived neurotrophic factor ( BDNF ) . However , the impact of AE on neurocognition , and the putative role of BDNF , have not been investigated in schizophrenia . Employing a proof-of-concept , single-blind , r and omized clinical trial design , 33 individuals with schizophrenia were r and omized to receive st and ard psychiatric treatment ( n = 17 ; " treatment as usual " ; TAU ) or attend a 12-week AE program ( n = 16 ) utilizing active-play video games ( Xbox 360 Kinect ) and traditional AE equipment . Participants completed assessment s of AF ( indexed by VO2 peak ml/kg/min ) , neurocognition ( MATRICS Consensus Cognitive Battery ) , and serum-BDNF before and after and 12-week period . Twenty-six participants ( 79 % ) completed the study . At follow-up , the AE participants improved their AF by 18.0 % vs a -0.5 % decline in the TAU group ( P = .002 ) and improved their neurocognition by 15.1 % vs -2.0 % decline in the TAU group ( P = .031 ) . Hierarchical multiple regression analyses indicated that enhancement in AF and increases in BDNF predicted 25.4 % and 14.6 % of the neurocognitive improvement variance , respectively . The results indicate AE is effective in enhancing neurocognitive functioning in people with schizophrenia and provide preliminary support for the impact of AE-related BDNF up-regulation on neurocognition in this population . Poor AF represents a modifiable risk factor for neurocognitive dysfunction in schizophrenia for which AE training offer a safe , nonstigmatizing , and side-effect-free intervention OBJECTIVE The objective of this study was to evaluate the effectiveness of a fitness health mentor program ( In SHAPE ) in improving physical fitness and weight loss among overweight and obese adults with serious mental illness . METHODS A r and omized controlled trial was conducted with 133 persons with serious mental illness and a body mass index ( BMI ) > 25 who were assigned either to the In SHAPE program ( one year of weekly sessions with a fitness trainer plus a fitness club membership ) or to one year of fitness club membership and education . Assessment s were conducted at baseline and three , six , nine , and 12 months later . RESULTS Participants had a mean baseline weight of 231.8±54.8 pounds and a mean BMI of 37.6±8.2 . At 12-month follow-up , In SHAPE ( N=67 ) compared with fitness club membership and education ( N=66 ) was associated with three times greater fitness club attendance , twice as much participation in physical exercise , greater engagement in vigorous physical activity , and improvement in diet . Twice the proportion of participants ( 40 % versus 20 % ) achieved clinical ly significant improvement in cardiorespiratory fitness ( > 50 m on the six-minute walk test ) . Weight loss and BMI did not differ between groups . Among In SHAPE participants , 49 % achieved either clinical ly significant increased fitness or weight loss ( 5 % or greater ) , and 24 % achieved both clinical ly significant improved fitness and weight loss . CONCLUSIONS The In SHAPE program achieved clinical ly significant reduction in cardiovascular risk for almost one-half of participants at 12 months . Although the intervention showed promise in improving fitness , optimizing weight loss may require additional intensive , multicomponent dietary interventions |
12,297 | 26,383,245 | The reduced odds of fatal bleeding with NOACs was not demonstrated after controlling for bleeding location .
AUTHOR ’S CONCLUSIONS : The odds ratio calculated in this meta- analysis showed a reduced odds of death in major bleeding associated with NOAC use .
This risk reduction was due to a disproportionate amount of intracranial bleeding in the VKA arms .
For any given bleeding site , there was no evidence of a significant difference in fatal outcomes from bleeds associated with NOAC versus VKA use . | BACKGROUND The reversibility of new/novel oral anticoagulants ( NOAC ) is not well understood , whereas the reversal strategies for bleeding associated with vitamin k antagonists ( VKA ) , such as warfarin , is well established .
It is unknown whether outcomes are different between bleeds occurring with NOAC compared to VKA use .
OBJECTIVES This systematic review and meta- analysis of r and omized controlled trials determines the relative odds of fatal bleeding given that a patient suffered a major bleed while on NOAC versus VKA therapy . | Background — Dabigatran and warfarin have been compared for the treatment of acute venous thromboembolism ( VTE ) in a previous trial . We undertook this study to extend those findings . Methods and Results — In a r and omized , double-blind , double-dummy trial of 2589 patients with acute VTE treated with low-molecular-weight or unfractionated heparin for 5 to 11 days , we compared dabigatran 150 mg twice daily with warfarin . The primary outcome , recurrent symptomatic , objective ly confirmed VTE and related deaths during 6 months of treatment occurred in 30 of the 1279 dabigatran patients ( 2.3 % ) compared with 28 of the 1289 warfarin patients ( 2.2 % ; hazard ratio , 1.08 ; 95 % confidence interval [ CI ] , 0.64–1.80 ; absolute risk difference , 0.2 % ; 95 % CI , −1.0 to 1.3 ; P<0.001 for the prespecified noninferiority margin for both criteria ) . The safety end point , major bleeding , occurred in 15 patients receiving dabigatran ( 1.2 % ) and in 22 receiving warfarin ( 1.7 % ; hazard ratio , 0.69 ; 95 % CI , 0.36–1.32 ) . Any bleeding occurred in 200 dabigatran ( 15.6 % ) and 285 warfarin ( 22.1 % ; hazard ratio , 0.67 ; 95 % CI , 0.56–0.81 ) patients . Deaths , adverse events , and acute coronary syndromes were similar in both groups . Pooled analysis of this study RE-COVER II and the RE-COVER trial gave hazard ratios for recurrent VTE of 1.09 ( 95 % CI , 0.76–1.57 ) , for major bleeding of 0.73 ( 95 % CI , 0.48–1.11 ) , and for any bleeding of 0.70 ( 95 % CI , 0.61–0.79 ) . Conclusion — Dabigatran has similar effects on VTE recurrence and a lower risk of bleeding compared with warfarin for the treatment of acute VTE . Clinical Trial Registration — URL : www . clinical trials.gov . Unique identifiers : NCT00680186 and NCT00291330 Background — Rivaroxaban and dabigatran are new oral anticoagulants that specifically inhibit factor Xa and thrombin , respectively . Clinical studies on the prevention and treatment of venous and arterial thromboembolism show promising results . A major disadvantage of these anticoagulants is the absence of an antidote in case of serious bleeding or when an emergency intervention needs immediate correction of coagulation . This study evaluated the potential of prothrombin complex concentrate ( PCC ) to reverse the anticoagulant effect of these drugs . Methods and Results — In a r and omized , double-blind , placebo-controlled study , 12 healthy male volunteers received rivaroxaban 20 mg twice daily ( n=6 ) or dabigatran 150 mg twice daily ( n=6 ) for 2½ days , followed by either a single bolus of 50 IU/kg PCC ( Cofact ) or a similar volume of saline . After a washout period , this procedure was repeated with the other anticoagulant treatment . Rivaroxaban induced a significant prolongation of the prothrombin time ( 15.8±1.3 versus 12.3±0.7 seconds at baseline ; P<0.001 ) that was immediately and completely reversed by PCC ( 12.8±1.0 ; P<0.001 ) . The endogenous thrombin potential was inhibited by rivaroxaban ( 51±22 % ; baseline , 92±22 % ; P=0.002 ) and normalized with PCC ( 114±26 % ; P<0.001 ) , whereas saline had no effect . Dabigatran increased the activated partial thromboplastin time , ecarin clotting time ( ECT ) , and thrombin time . Administration of PCC did not restore these coagulation tests . Conclusion — Prothrombin complex concentrate immediately and completely reverses the anticoagulant effect of rivaroxaban in healthy subjects but has no influence on the anticoagulant action of dabigatran at the PCC dose used in this study . Clinical Trial Registration — URL : http://www.trialregister.nl . Unique identifier : NTR2272 BACKGROUND Apixaban , an oral potent reversible direct inhibitor of activated factor X , has shown promise in the prevention of venous thromboembolism following major orthopedic surgery . We conducted a dose-ranging study in patients with deep vein thrombosis . METHODS Consecutive patients with symptomatic deep vein thrombosis were included and r and omized to receive 84 - 91 days of apixaban 5 mg twice-daily , 10 mg twice-daily , or 20 mg once-daily , or low molecular weight heparin ( LMWH ) followed by a vitamin K antagonist ( VKA ) . The primary efficacy outcome was the composite of symptomatic recurrent venous thromboembolism and asymptomatic deterioration of bilateral compression ultrasound or perfusion lung scan . The principal safety outcome was the composite of major and clinical ly relevant , non-major bleeding . RESULTS The mean age of the 520 included patients was 59 years , and 62 % were male . The primary outcome occurred in 17 of the 358 apixaban-treated patients [ 4.7 % , 95 % confidence interval ( CI ) 2.8 - 7.5 % ] and in five of the 118 LMWH/VKA-treated patients ( 4.2 % , 95 % CI 1.4 - 9.6 % ) who were evaluable . The incidence in all three apixaban groups was low and comparable without evidence of a dose response . The principal safety outcome occurred in 28 ( 7.3 % ) of the 385 apixaban-treated patients and in 10 ( 7.9 % ) of the 126 LMWH/VKA-treated patients . No dose response for apixaban was observed . CONCLUSION These observations warrant further evaluation of apixaban in phase III studies . The attractive fixed-dose regimen of this compound may meet the dem and to simplify anticoagulant treatment in patients with established venous thromboembolism BACKGROUND Apixaban , an oral factor Xa inhibitor administered in fixed doses , may simplify the treatment of venous thromboembolism . METHODS In this r and omized , double-blind study , we compared apixaban ( at a dose of 10 mg twice daily for 7 days , followed by 5 mg twice daily for 6 months ) with conventional therapy ( subcutaneous enoxaparin , followed by warfarin ) in 5395 patients with acute venous thromboembolism . The primary efficacy outcome was recurrent symptomatic venous thromboembolism or death related to venous thromboembolism . The principal safety outcomes were major bleeding alone and major bleeding plus clinical ly relevant nonmajor bleeding . RESULTS The primary efficacy outcome occurred in 59 of 2609 patients ( 2.3 % ) in the apixaban group , as compared with 71 of 2635 ( 2.7 % ) in the conventional-therapy group ( relative risk , 0.84 ; 95 % confidence interval [ CI ] , 0.60 to 1.18 ; difference in risk [ apixaban minus conventional therapy ] , -0.4 percentage points ; 95 % CI , -1.3 to 0.4 ) . Apixaban was noninferior to conventional therapy ( P<0.001 ) for predefined upper limits of the 95 % confidence intervals for both relative risk ( < 1.80 ) and difference in risk ( < 3.5 percentage points ) . Major bleeding occurred in 0.6 % of patients who received apixaban and in 1.8 % of those who received conventional therapy ( relative risk , 0.31 ; 95 % CI , 0.17 to 0.55 ; P<0.001 for superiority ) . The composite outcome of major bleeding and clinical ly relevant nonmajor bleeding occurred in 4.3 % of the patients in the apixaban group , as compared with 9.7 % of those in the conventional-therapy group ( relative risk , 0.44 ; 95 % CI , 0.36 to 0.55 ; P<0.001 ) . Rates of other adverse events were similar in the two groups . CONCLUSIONS A fixed-dose regimen of apixaban alone was noninferior to conventional therapy for the treatment of acute venous thromboembolism and was associated with significantly less bleeding ( Funded by Pfizer and Bristol-Myers Squibb ; Clinical Trials.gov number , NCT00643201 ) Background and Purpose — Intracranial hemorrhage is the most devastating complication of anticoagulation . Outcomes associated with different sites of intracranial bleeding occurring with warfarin versus dabigatran have not been defined . Methods — Analysis of 18 113 participants with atrial fibrillation in the R and omized Evaluation of Long-term anticoagulant therapY ( RE-LY ) trial assigned to adjusted-dose warfarin ( target international normalized ratio , 2–3 ) or dabigatran ( 150 mg or 110 mg , both twice daily ) . Results — During a mean of 2.0 years of follow-up , 154 intracranial hemorrhages occurred in 153 participants : 46 % intracerebral ( 49 % mortality ) , 45 % subdural ( 24 % mortality ) , and 8 % subarachnoid ( 31 % mortality ) . The rates of intracranial hemorrhage were 0.76 % , 0.31 % , and 0.23 % per year among those assigned to warfarin , dabigatran 150 mg , and dabigatran 110 mg , respectively ( P<0.001 for either dabigatran dose versus warfarin ) . Fewer fatal intracranial hemorrhages occurred among those assigned dabigatran 150 mg and 110 mg ( n=13 and n=11 , respectively ) versus warfarin ( n=32 ; P<0.01 for both ) . Fewer traumatic intracranial hemorrhages occurred among those assigned to dabigatran ( 11 patients with each dose ) compared with warfarin ( 24 patients ; P<0.05 for both dabigatran doses versus warfarin ) . Independent predictors of intracranial hemorrhage were assignment to warfarin ( relative risk , 2.9 ; P<0.001 ) , aspirin use ( relative risk , 1.6 ; P=0.01 ) , age ( relative risk , 1.1 per year ; P<0.001 ) , and previous stroke/transient ischemic attack ( relative risk , 1.8 ; P=0.001 ) . Conclusions — The clinical spectrum of intracranial hemorrhage was similar for patients given warfarin and dabigatran . Absolute rates at all sites and both fatal and traumatic intracranial hemorrhages were lower with dabigatran than with warfarin . Concomitant aspirin use was the most important modifiable independent risk factor for intracranial hemorrhage The primary objective of this study was to compare the safety of four fixed-dose regimens of edoxaban with warfarin in patients with non-valvular atrial fibrillation ( AF ) . In this 12-week , parallel-group , multicentre , multinational study , 1,146 patients with AF and risk of stroke were r and omised to edoxaban 30 mg qd , 30 mg bid , 60 mg qd , or 60 mg bid or warfarin dose-adjusted to a target international normalised ratio of 2.0 - 3.0 . The study was double-blind to edoxaban dose , but open-label to warfarin . Primary outcomes were occurrence of major and /or clinical ly relevant non-major bleeding and elevated hepatic enzymes and /or bilirubin . Mean age was 65 + /- 8.7 years and 64.4 % were warfarin-naïve . Whereas major plus clinical ly relevant non-major bleeding occurred in 3.2 % of patients r and omised to warfarin , the incidence of bleeding was significantly higher with the edoxaban 60 mg bid ( 10.6 % ; p=0.002 ) and 30 mg bid regimens ( 7.8 % ; p=0.029 ) , but not with the edoxaban 60 mg qd ( 3.8 % ) or 30 mg qd regimens ( 3.0 % ) . For the same total daily dose of 60 mg , both bleeding frequency and trough edoxaban concentrations were higher in the 30-mg bid group than in the 60-mg qd group . There were no significant differences in hepatic enzyme elevations or bilirubin values among the groups . The safety profiles of edoxaban 30 and 60 mg qd in patients with AF were similar to warfarin . In contrast , the edoxaban bid regimens were associated with more bleeding than warfarin . These results suggest that in this three-month study , edoxaban 30 or 60 mg qd are safe and well-tolerated Edoxaban is an oral , reversible , direct factor Xa inhibitor in phase III clinical development for the prevention of stroke in atrial fibrillation ( AF ) . A phase II study was undertaken to evaluate the safety and efficacy of edoxaban in Asian patients with non-valvular AF with CHADS2 score ≥1 . In a multicentre , active-controlled , double-blind edoxaban and open-label warfarin , parallel-group study , a total of 235 patients from four Asian countries were r and omly assigned to edoxaban 30 mg qd , 60 mg qd or warfarin dose adjusted to international normalised ratio of 2 - 3 for three months . The primary endpoint was the incidence of central ly adjudicated all bleeding events ( major , clinical ly relevant non-major and minor ) . Secondary endpoints included thromboembolic events , biomarkers of thrombus formation and all adverse events ( AEs ) . The incidence of all bleeding events ( 95 % CI ) was 20.3 % ( 12.9 , 30.4 ) for edoxaban 30 mg , 23.8 % ( 15.8 , 34.1 ) for edoxaban 60 mg , and 29.3 % ( 20.2 , 40.4 ) for warfarin . A subgroup analysis suggested low body weight ( ≤60 kg ) may affect the incidence of bleeding events with edoxaban . The incidence of study drug-related AEs was 22 % for edoxaban 30 mg , 29 % for edoxaban 60 mg and 33 % for warfarin . No thromboembolic events occurred in any treatment group . In conclusion , this phase II study found a trend for a reduction in the incidence of all bleeding events in Asian AF patients with edoxaban 30 mg and 60 mg compared with warfarin . Adverse events were similar between the edoxaban 60-mg and warfarin groups and were lower with the edoxaban 30-mg group BACKGROUND Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use . Dabigatran is a new oral direct thrombin inhibitor . METHODS In this noninferiority trial , we r and omly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive , in a blinded fashion , fixed doses of dabigatran--110 mg or 150 mg twice daily -- or , in an unblinded fashion , adjusted-dose warfarin . The median duration of the follow-up period was 2.0 years . The primary outcome was stroke or systemic embolism . RESULTS Rates of the primary outcome were 1.69 % per year in the warfarin group , as compared with 1.53 % per year in the group that received 110 mg of dabigatran ( relative risk with dabigatran , 0.91 ; 95 % confidence interval [ CI ] , 0.74 to 1.11 ; P<0.001 for noninferiority ) and 1.11 % per year in the group that received 150 mg of dabigatran ( relative risk , 0.66 ; 95 % CI , 0.53 to 0.82 ; P<0.001 for superiority ) . The rate of major bleeding was 3.36 % per year in the warfarin group , as compared with 2.71 % per year in the group receiving 110 mg of dabigatran ( P=0.003 ) and 3.11 % per year in the group receiving 150 mg of dabigatran ( P=0.31 ) . The rate of hemorrhagic stroke was 0.38 % per year in the warfarin group , as compared with 0.12 % per year with 110 mg of dabigatran ( P<0.001 ) and 0.10 % per year with 150 mg of dabigatran ( P<0.001 ) . The mortality rate was 4.13 % per year in the warfarin group , as compared with 3.75 % per year with 110 mg of dabigatran ( P=0.13 ) and 3.64 % per year with 150 mg of dabigatran ( P=0.051 ) . CONCLUSIONS In patients with atrial fibrillation , dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin , as well as lower rates of major hemorrhage . Dabigatran administered at a dose of 150 mg , as compared with warfarin , was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage . ( Clinical Trials.gov number , NCT00262600 . BACKGROUND The direct oral thrombin inhibitor dabigatran has a predictable anticoagulant effect and may be an alternative therapy to warfarin for patients who have acute venous thromboembolism . METHODS In a r and omized , double-blind , noninferiority trial involving patients with acute venous thromboembolism who were initially given parenteral anticoagulation therapy for a median of 9 days ( interquartile range , 8 to 11 ) , we compared oral dabigatran , administered at a dose of 150 mg twice daily , with warfarin that was dose-adjusted to achieve an international normalized ratio of 2.0 to 3.0 . The primary outcome was the 6-month incidence of recurrent symptomatic , objective ly confirmed venous thromboembolism and related deaths . Safety end points included bleeding events , acute coronary syndromes , other adverse events , and results of liver-function tests . RESULTS A total of 30 of the 1274 patients r and omly assigned to receive dabigatran ( 2.4 % ) , as compared with 27 of the 1265 patients r and omly assigned to warfarin ( 2.1 % ) , had recurrent venous thromboembolism ; the difference in risk was 0.4 percentage points ( 95 % confidence interval [ CI ] , -0.8 to 1.5 ; P<0.001 for the prespecified noninferiority margin ) . The hazard ratio with dabigatran was 1.10 ( 95 % CI , 0.65 to 1.84 ) . Major bleeding episodes occurred in 20 patients assigned to dabigatran ( 1.6 % ) and in 24 patients assigned to warfarin ( 1.9 % ) ( hazard ratio with dabigatran , 0.82 ; 95 % CI , 0.45 to 1.48 ) , and episodes of any bleeding were observed in 205 patients assigned to dabigatran ( 16.1 % ) and 277 patients assigned to warfarin ( 21.9 % ; hazard ratio with dabigatran , 0.71 ; 95 % CI , 0.59 to 0.85 ) . The numbers of deaths , acute coronary syndromes , and abnormal liver-function tests were similar in the two groups . Adverse events leading to discontinuation of the study drug occurred in 9.0 % of patients assigned to dabigatran and in 6.8 % of patients assigned to warfarin ( P=0.05 ) . CONCLUSIONS For the treatment of acute venous thromboembolism , a fixed dose of dabigatran is as effective as warfarin , has a safety profile that is similar to that of warfarin , and does not require laboratory monitoring . ( Clinical Trials.gov number , NCT00291330 . BACKGROUND Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects . The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known . METHODS We conducted a r and omized , double-blind , double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation ( median follow-up , 2.8 years ) . The primary efficacy end point was stroke or systemic embolism . Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period . The principal safety end point was major bleeding . RESULTS The annualized rate of the primary end point during treatment was 1.50 % with warfarin ( median time in the therapeutic range , 68.4 % ) , as compared with 1.18 % with high-dose edoxaban ( hazard ratio , 0.79 ; 97.5 % confidence interval [ CI ] , 0.63 to 0.99 ; P<0.001 for noninferiority ) and 1.61 % with low-dose edoxaban ( hazard ratio , 1.07 ; 97.5 % CI , 0.87 to 1.31 ; P=0.005 for noninferiority ) . In the intention-to-treat analysis , there was a trend favoring high-dose edoxaban versus warfarin ( hazard ratio , 0.87 ; 97.5 % CI , 0.73 to 1.04 ; P=0.08 ) and an unfavorable trend with low-dose edoxaban versus warfarin ( hazard ratio , 1.13 ; 97.5 % CI , 0.96 to 1.34 ; P=0.10 ) . The annualized rate of major bleeding was 3.43 % with warfarin versus 2.75 % with high-dose edoxaban ( hazard ratio , 0.80 ; 95 % CI , 0.71 to 0.91 ; P<0.001 ) and 1.61 % with low-dose edoxaban ( hazard ratio , 0.47 ; 95 % CI , 0.41 to 0.55 ; P<0.001 ) . The corresponding annualized rates of death from cardiovascular causes were 3.17 % versus 2.74 % ( hazard ratio , 0.86 ; 95 % CI , 0.77 to 0.97 ; P=0.01 ) , and 2.71 % ( hazard ratio , 0.85 ; 95 % CI , 0.76 to 0.96 ; P=0.008 ) , and the corresponding rates of the key secondary end point ( a composite of stroke , systemic embolism , or death from cardiovascular causes ) were 4.43 % versus 3.85 % ( hazard ratio , 0.87 ; 95 % CI , 0.78 to 0.96 ; P=0.005 ) , and 4.23 % ( hazard ratio , 0.95 ; 95 % CI , 0.86 to 1.05 ; P=0.32 ) . CONCLUSIONS Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes . ( Funded by Daiichi Sankyo Pharma Development ; ENGAGE AF-TIMI 48 Clinical Trials.gov number , NCT00781391 . ) BACKGROUND Dabigatran , which is administered in a fixed dose and does not require laboratory monitoring , may be suitable for extended treatment of venous thromboembolism . METHODS In two double-blind , r and omized trials , we compared dabigatran at a dose of 150 mg twice daily with warfarin ( active-control study ) or with placebo ( placebo-control study ) in patients with venous thromboembolism who had completed at least 3 initial months of therapy . RESULTS In the active-control study , recurrent venous thromboembolism occurred in 26 of 1430 patients in the dabigatran group ( 1.8 % ) and 18 of 1426 patients in the warfarin group ( 1.3 % ) ( hazard ratio with dabigatran , 1.44 ; 95 % confidence interval [ CI ] , 0.78 to 2.64 ; P=0.01 for noninferiority ) . Major bleeding occurred in 13 patients in the dabigatran group ( 0.9 % ) and 25 patients in the warfarin group ( 1.8 % ) ( hazard ratio , 0.52 ; 95 % CI , 0.27 to 1.02 ) . Major or clinical ly relevant bleeding was less frequent with dabigatran ( hazard ratio , 0.54 ; 95 % CI , 0.41 to 0.71 ) . Acute coronary syndromes occurred in 13 patients in the dabigatran group ( 0.9 % ) and 3 patients in the warfarin group ( 0.2 % ) ( P=0.02 ) . In the placebo-control study , recurrent venous thromboembolism occurred in 3 of 681 patients in the dabigatran group ( 0.4 % ) and 37 of 662 patients in the placebo group ( 5.6 % ) ( hazard ratio , 0.08 ; 95 % CI , 0.02 to 0.25 ; P<0.001 ) . Major bleeding occurred in 2 patients in the dabigatran group ( 0.3 % ) and 0 patients in the placebo group . Major or clinical ly relevant bleeding occurred in 36 patients in the dabigatran group ( 5.3 % ) and 12 patients in the placebo group ( 1.8 % ) ( hazard ratio , 2.92 ; 95 % CI , 1.52 to 5.60 ) . Acute coronary syndromes occurred in 1 patient each in the dabigatran and placebo groups . CONCLUSIONS Dabigatran was effective in the extended treatment of venous thromboembolism and carried a lower risk of major or clinical ly relevant bleeding than warfarin but a higher risk than placebo . ( Funded by Boehringer Ingelheim ; RE-MEDY and RE-SONATE Clinical Trials.gov numbers , NCT00329238 and NCT00558259 , respectively . ) Background — An effective and safe oral anticoagulant that needs no monitoring for dose adjustment is urgently needed for the treatment of diseases that require long-term anticoagulation . Rivaroxaban ( BAY 59 - 7939 ) is an oral direct factor Xa inhibitor currently under clinical development . Methods and Results — This r and omized , parallel-group phase II trial in patients with proximal deep-vein thrombosis explored the efficacy and safety of rivaroxaban 10 , 20 , or 30 mg BID or 40 mg once daily compared with enoxaparin 1 mg/kg BID followed by vitamin K antagonist . Each treatment was administered for 12 weeks . The primary efficacy end point was an improvement in thrombotic burden at day 21 ( assessed by quantitative compression ultrasonography ; ≥4-point improvement in thrombus score ) without recurrent symptomatic venous thromboembolism or venous thromboembolism – related death . The primary safety end point was major bleeding during 12 weeks of treatment . Outcomes were adjudicated central ly without knowledge of treatment allocation . The primary efficacy end point was achieved in 53 ( 53.0 % ) of 100 , 58 ( 59.2 % ) of 98 , 62 ( 56.9 % ) of 109 , and 49 ( 43.8 % ) of 112 patients receiving rivaroxaban 10 , 20 , or 30 mg BID or 40 mg once daily , respectively , compared with 50 ( 45.9 % ) of 109 patients treated with enoxaparin/vitamin K antagonist . There was no significant trend in the dose – response relationship between rivaroxaban BID and the primary efficacy end point ( P=0.67 ) . Major bleeding was observed in 1.7 % , 1.7 % , 3.3 % , and 1.7 % of patients receiving rivaroxaban 10 , 20 , or 30 mg BID or 40 mg once daily , respectively . There were no major bleeding events with enoxaparin/vitamin K antagonist . Conclusions — Results of this proof-of-concept and dose-finding study support phase III evaluation of the orally active direct factor Xa inhibitor rivaroxaban , because efficacy and safety were apparent in the treatment of proximal deep-vein thrombosis across a 3-fold range of fixed daily dosing Apixaban is a new oral anticoagulant with a specific inhibitory action on FXa . No information is available on the reversal of the antihemostatic action of apixaban in experimental or clinical setting s. We have evaluated the effectiveness of different factor concentrates at reversing modifications of hemostatic mechanisms induced by moderately elevated concentrations of apixaban ( 200 ng/ml ) added in vitro to blood from healthy donors ( n = 10 ) . Effects on thrombin generation ( TG ) and thromboelastometry ( TEM ) parameters were assessed . Modifications in platelet adhesive , aggregating and procoagulant activities were evaluated in studies with blood circulating through damaged vascular surfaces , at a shear rate of 600 s−1 . The potential of prothrombin complex concentrates ( PCCs ; 50 IU/kg ) , activated prothrombin complex concentrates ( aPCCs ; 75 IU/kg ) , or activated recombinant factor VII ( rFVIIa ; 270 μg/kg ) , at reversing the antihemostatic actions of apixaban , were investigated . Apixaban interfered with TG kinetics . Delayed lag phase , prolonged time to peak and reduced peak values , were improved by the different concentrates , though modifications in TG patterns were diversely affected depending on the activating reagents . Apixaban significantly prolonged clotting times ( CTs ) in TEM studies . Prolongations in CTs were corrected by the different concentrates with variable efficacies ( rFVIIa≥aPCC > PCC ) . Apixaban significantly reduced fibrin and platelet interactions with damaged vascular surfaces in perfusion studies ( p<0.05 and p<0.01 , respectively ) . Impairments in fibrin formation were normalized by the different concentrates . Only rFVIIa significantly restored levels of platelet deposition . Alterations in hemostasis induced by apixaban were variably compensated by the different factor concentrates investigated . However , effects of these concentrates were not homogeneous in all the tests , with PCCs showing more efficacy in TG , and rFVIIa being more effective on TEM and perfusion studies . Our results indicate that rFVIIa , PCCs and aPCCs have the potential to restore platelet and fibrin components of the hemostasis previously altered by apixaban BACKGROUND The global ROCKET AF study evaluated once-daily rivaroxaban vs. warfarin for stroke and systemic embolism prevention in patients with atrial fibrillation ( AF ) . A separate trial , J-ROCKET AF , compared the safety of a Japan-specific rivaroxaban dose with warfarin administered according to Japanese guidelines in Japanese patients with AF . METHODS AND RESULTS J-ROCKET AF was a prospect i ve , r and omized , double-blind , phase III trial . Patients ( n=1,280 ) with non-valvular AF at increased risk for stroke were r and omized to receive 15 mg once-daily rivaroxaban or warfarin dose-adjusted according to Japanese guidelines . The primary objective was to determine non-inferiority of rivaroxaban against warfarin for the principal safety outcome of major and non-major clinical ly relevant bleeding , in the on-treatment safety population . The primary efficacy endpoint was the composite of stroke and systemic embolism . Non-inferiority of rivaroxaban to warfarin was confirmed ; the rate of the principal safety outcome was 18.04 % per year in rivaroxaban-treated patients and 16.42 % per year in warfarin-treated patients ( hazard ratio [ HR ] 1.11 ; 95 % confidence interval 0.87 - 1.42 ; P<0.001 [ non-inferiority ] ) . Intracranial hemorrhage rates were 0.8 % with rivaroxaban and 1.6 % with warfarin . There was a strong trend for a reduction in the rate of stroke/systemic embolism with rivaroxaban vs. warfarin ( HR , 0.49 ; P=0.050 ) . CONCLUSIONS J-ROCKET AF demonstrated the safety of a Japan-specific rivaroxaban dose and supports bridging the global ROCKET AF results into Japanese clinical practice BACKGROUND Guidelines recommend warfarin as the st and ard of care for patients with atrial fibrillation ( AF ) at moderate or high risk for stroke . This phase II study assessed the effects of 2 doses of the factor Xa inhibitor apixaban vs. warfarin in Japanese patients with non-valvular AF . The composite primary endpoint was major and clinical ly relevant non-major ( CRNM ) bleeding . METHODS AND RESULTS Two hundred and twenty-two patients with AF and 1 or more additional risk factors for stroke were r and omized ( 1:1:1 ) to double-blind apixaban 2.5 or 5 mg b.i.d . or open-label warfarin ( target international normalized ratio 2.0 - 3.0 ; 2.0 - 2.6 if age ≥ 70 years ) for 12 weeks . The primary endpoint occurred in 1 patient ( 1.4 % ) in each apixaban group and 4 ( 5.3 % ) warfarin patients . There were no strokes , systemic emboli , myocardial infa rct ions , or deaths in either apixaban group . The warfarin group had 2 ischemic strokes and 1 subarachnoid hemorrhage , but there were no deaths . Major and CRNM bleeds each occurred with higher frequency in the warfarin group vs. either apixaban group . Most adverse events were mild or moderate . No patients had hepatic aminotransferase elevations greater than 3 times the upper limit of normal . CONCLUSIONS In Japanese patients with AF , apixaban 2.5 and 5 mg b.i.d . were well tolerated over 12 weeks . A global phase III trial , which includes Japanese patients , is ongoing ( Clinical Trials.gov Identifier NCT00787150 ) BACKGROUND Edoxaban is a once-daily ( QD ) oral , direct factor Xa inhibitor in clinical development for the prevention of stroke in patients with non-valvular atrial fibrillation ( NVAF ) . The aim of this study was to evaluate the safety of edoxaban in Japanese patients with NVAF . METHODS AND RESULTS A total of 536 NVAF patients ( CHADS2 ≥1 ) were r and omized to receive double-blinded edoxaban 30 , 45 , or 60 mg QD or open-label warfarin ( international normalized ratio [ INR ] 2.0 - 3.0 for age < 70 years ; 1.6 - 2.6 for age ≥70 years ) for 12 weeks . The primary endpoint was the incidence of all bleeding events ( major , clinical ly relevant non-major , and minor bleeds ) . Patients underwent CT and /or MRI to assess asymptomatic intracranial hemorrhage ( ICH ) . Secondary endpoints included thromboembolic events and pharmacodynamic indices . The mean incidence of all bleeding events for edoxaban 30 , 45 , and 60 mg , and warfarin was 18.5 % , 22.4 % , 27.7 % , and 20.0 % , respectively . There were no statistically significant differences among the edoxaban groups and no significant differences from the warfarin group . There were no asymptomatic ICH events in any group . One episode of cerebral infa rct ion was observed in the edoxaban 45-mg group . Subgroup analysis suggested low body weight ( ≤60 kg ) was associated with higher bleeding risk . CONCLUSIONS Edoxaban 30 , 45 , and 60 mg QD in patients with NVAF was associated with a numerical increase in all bleeding across the dose range , but this was not statistically significant , nor was any dose compared with warfarin The new anticoagulants dabigatran and rivaroxaban can be responsible for haemorrhagic complications . As for any anticoagulant , bleeding management is challenging . We aim ed to test the effect of all putative haemostatic agents on the anticoagulant activity of these new drugs using thrombin generation tests . In an ex vivo study , 10 healthy white male subjects were r and omised to receive rivaroxaban ( 20 mg ) or dabigatran ( 150 mg ) in one oral administration . After a two weeks washout period , they received the other anticoagulant . Venous blood sample s were collected just before drug administration ( H0 ) and 2 hours thereafter . Reversal of anticoagulation was tested in vitro using prothrombin complex concentrate ( PCC ) , rFVIIa or FEIBA ® at various concentrations . Rivaroxaban affects quantitative and kinetic parameters , including the endogenous thrombin potential ( ETP-AUC and more pronouncedly the thrombin peak ) , the lag-time and time to peak . PCC strongly corrected ETP-AUC , whereas rFVIIa only modified the kinetic parameters . FEIBA corrected all parameters . Dabigatran specially affects the kinetics of thrombin generation with prolonged lag-time and time to peak . Although PCC increased ETP-AUC , only rFVIIa and FEIBA corrected the altered lag-time . For both anticoagulants , lower doses of FEIBA , corresponding to a quarter to half the dose usually used , have potential reversal profile of interest . In conclusion , some non-specific reversal agents appear to be able to reverse the anticoagulant activity of rivaroxaban or dabigatran . However , clinical evaluation is needed regarding haemorrhagic situations , and a meticulous risk-benefit evaluation regarding their use in this context is required BACKGROUND Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations . Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin . METHODS In this r and omized , double-blind trial , we compared apixaban ( at a dose of 5 mg twice daily ) with warfarin ( target international normalized ratio , 2.0 to 3.0 ) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke . The primary outcome was ischemic or hemorrhagic stroke or systemic embolism . The trial was design ed to test for noninferiority , with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause . RESULTS The median duration of follow-up was 1.8 years . The rate of the primary outcome was 1.27 % per year in the apixaban group , as compared with 1.60 % per year in the warfarin group ( hazard ratio with apixaban , 0.79 ; 95 % confidence interval [ CI ] , 0.66 to 0.95 ; P<0.001 for noninferiority ; P=0.01 for superiority ) . The rate of major bleeding was 2.13 % per year in the apixaban group , as compared with 3.09 % per year in the warfarin group ( hazard ratio , 0.69 ; 95 % CI , 0.60 to 0.80 ; P<0.001 ) , and the rates of death from any cause were 3.52 % and 3.94 % , respectively ( hazard ratio , 0.89 ; 95 % CI , 0.80 to 0.99 ; P=0.047 ) . The rate of hemorrhagic stroke was 0.24 % per year in the apixaban group , as compared with 0.47 % per year in the warfarin group ( hazard ratio , 0.51 ; 95 % CI , 0.35 to 0.75 ; P<0.001 ) , and the rate of ischemic or uncertain type of stroke was 0.97 % per year in the apixaban group and 1.05 % per year in the warfarin group ( hazard ratio , 0.92 ; 95 % CI , 0.74 to 1.13 ; P=0.42 ) . CONCLUSIONS In patients with atrial fibrillation , apixaban was superior to warfarin in preventing stroke or systemic embolism , caused less bleeding , and result ed in lower mortality . ( Funded by Bristol-Myers Squibb and Pfizer ; ARISTOTLE Clinical Trials.gov number , NCT00412984 . ) BACKGROUND Whether the oral factor Xa inhibitor edoxaban can be an alternative to warfarin in patients with venous thromboembolism is unclear . METHODS In a r and omized , double-blind , noninferiority study , we r and omly assigned patients with acute venous thromboembolism , who had initially received heparin , to receive edoxaban at a dose of 60 mg once daily , or 30 mg once daily ( e.g. , in the case of patients with creatinine clearance of 30 to 50 ml per minute or a body weight below 60 kg ) , or to receive warfarin . Patients received the study drug for 3 to 12 months . The primary efficacy outcome was recurrent symptomatic venous thromboembolism . The principal safety outcome was major or clinical ly relevant nonmajor bleeding . RESULTS A total of 4921 patients presented with deep-vein thrombosis , and 3319 with a pulmonary embolism . Among patients receiving warfarin , the time in the therapeutic range was 63.5 % . Edoxaban was noninferior to warfarin with respect to the primary efficacy outcome , which occurred in 130 patients in the edoxaban group ( 3.2 % ) and 146 patients in the warfarin group ( 3.5 % ) ( hazard ratio , 0.89 ; 95 % confidence interval [ CI ] , 0.70 to 1.13 ; P<0.001 for noninferiority ) . The safety outcome occurred in 349 patients ( 8.5 % ) in the edoxaban group and 423 patients ( 10.3 % ) in the warfarin group ( hazard ratio , 0.81 ; 95 % CI , 0.71 to 0.94 ; P=0.004 for superiority ) . The rates of other adverse events were similar in the two groups . A total of 938 patients with pulmonary embolism had right ventricular dysfunction , as assessed by measurement of N-terminal pro-brain natriuretic peptide levels ; the rate of recurrent venous thromboembolism in this subgroup was 3.3 % in the edoxaban group and 6.2 % in the warfarin group ( hazard ratio , 0.52 ; 95 % CI , 0.28 to 0.98 ) . CONCLUSIONS Edoxaban administered once daily after initial treatment with heparin was noninferior to high- quality st and ard therapy and caused significantly less bleeding in a broad spectrum of patients with venous thromboembolism , including those with severe pulmonary embolism . ( Funded by Daiichi-Sankyo ; Hokusai-VTE Clinical Trials.gov number , NCT00986154 . ) We performed a r and omized dose-ranging study , double-blind for rivaroxaban doses and open-label for the comparator ( low-molecular-weight heparin followed by vitamin K antagonists ) to assess the optimal dose of rivaroxaban for the treatment of deep vein thrombosis . A total of 543 patients with acute deep-venous thrombosis received rivaroxaban 20 , 30 , or 40 mg once daily or comparator . Treatment lasted for 84 days . The primary efficacy outcome was the 3-month incidence of the composite of symptomatic venous thromboembolic complications and asymptomatic deterioration in thrombotic burden as assessed by comparison of ultrasound and perfusion lung scanning at day 84 with baseline . The main safety outcome was the composite of major bleeding and clinical ly relevant nonmajor bleeding . A total of 449 ( 83 % ) of the 543 patients could be included in the per- protocol population . The primary efficacy outcome occurred in 6.1 % , 5.4 % , and 6.6 % of the rivaroxaban 20- , 30- , and 40-mg treatment groups , respectively , and in 9.9 % of those receiving st and ard therapy . The main safety outcome occurred in 5.9 % , 6.0 % , and 2.2 % of the rivaroxaban 20- , 30- , and 40-mg treatment groups , respectively , and in 8.8 % of those receiving st and ard therapy . These results with simple fixed-dose oral regimens justify phase 3 evaluations ( www . Clinical Trials.gov no . NCT00395772 ) Background — Dabigatran 150 and 110 mg twice a day and warfarin are effective for stroke prevention in atrial fibrillation . The purpose of this study was to compare their risks of bleeding in the R and omized Evaluation of Long-Term Anticoagulant Therapy ( RE-LY ) trial . Methods and Results — The RE-LY trial r and omized 18 113 patients to receive dabigatran 110 or 150 mg twice a day or warfarin dose adjusted to an international normalized ratio of 2.0 to 3.0 for a median follow-up of 2.0 years . Compared with warfarin , dabigatran 110 mg twice a day was associated with a lower risk of major bleeding ( 2.87 % versus 3.57 % ; P=0.002 ) , whereas dabigatran 150 mg twice a day was associated with a similar risk of major bleeding ( 3.31 % versus 3.57 % ; P=0.32 ) . There was a significant treatment-by-age interaction , such that dabigatran 110 mg twice a day compared with warfarin was associated with a lower risk of major bleeding in patients aged < 75 years ( 1.89 % versus 3.04 % ; P<0.001 ) and a similar risk in those aged ≥75 years ( 4.43 % versus 4.37 % ; P=0.89 ; P for interaction < 0.001 ) , whereas dabigatran 150 mg twice a day compared with warfarin was associated with a lower risk of major bleeding in those aged < 75 years ( 2.12 % versus 3.04 % ; P<0.001 ) and a trend toward higher risk of major bleeding in those aged ≥75 years ( 5.10 % versus 4.37 % ; P=0.07 ; P for interaction < 0.001 ) . The interaction with age was evident for extracranial bleeding , but not for intracranial bleeding , with the risk of the latter being consistently reduced with dabigatran compared with warfarin irrespective of age . Conclusions — In patients with atrial fibrillation at risk for stroke , both doses of dabigatran compared with warfarin have lower risks of both intracranial and extracranial bleeding in patients aged < 75 years . In those aged ≥75 years , intracranial bleeding risk is lower but extracranial bleeding risk is similar or higher with both doses of dabigatran compared with warfarin . Clinical Trial Registration — http://www . clinical trials.gov . Unique identifier : NCT00262600 |
12,298 | 10,908,471 | The other studies supported the exp and ed roles of pharmacists in patient counselling and physician education . | BACKGROUND In recent years pharmacists ' roles have exp and ed from packaging and dispensing medications to working with other health care professionals and the public .
OBJECTIVES To examine the effect of exp and ing outpatient pharmacists ' roles on health services utilisation , costs , and patient outcomes .
Pharmacist services targeted at patients versus services delivered by other health professionals ; 2 .
Pharmacist services targeted at patients versus the delivery of no comparable service ; 3 .
Pharmacist services targeted at health professionals versus services delivered by other health professionals ; 4 . | OBJECTIVE : To implement and evaluate pharmaceutical care services for patients with hyperlipidemias in the community pharmacy setting , to evaluate the results of a pharmaceutical care training process for pharmacists by using an assessment quiz , and to measure patient outcomes result ing from provision of pharmaceutical care to patients with hyperlipidemia . DESIGN : A prospect i ve study was conducted over a 1 -year period . Patients served as their own controls . SETTING : Two independent community pharmacies in Richmond , Virginia . PARTICIPANTS : Twenty-five adult patients with confirmed dyslipidemias completed the study . INTERVENTIONS : Study pharmacists assessed each patient and assisted in setting therapeutic goals ; patients also completed a visit with a registered dietitian . Drug therapy recommendations were made to physicians by the pharmacist when appropriate . Follow-up was scheduled with the pharmacist to ensure positive outcomes and reduce adverse effects . MAIN OUTCOME MEASURES : Fasting lipoprotein profiles were measured initially and at 6 and 12 months . The SF-36 survey , the MacKeigan-Larson satisfaction survey , and a patient opinion survey were administered initially and at the conclusion of the study . RESULTS : Total cholesterol and low-density lipoprotein cholesterol values were significantly decreased at 12 months compared with either the baseline or 6-month values ( p < 0.02 ) . Significant improvement was found in several domains of the surveys ; quality of life , patient satisfaction with pharmacy services , and patient opinions on the role of the pharmacist improved after the intervention . CONCLUSIONS : Pharmaceutical care may positively affect lipid values , quality of life , and patient satisfaction The impacts of two models of pharmacist consultation on patient function and health-related quality of life ( HRQOL ) relative to a control model were studied . Patients in the r and om-assignment study and the areawide study of the Kaiser Permanente/USC Patient Consultation Study were surveyed three times over a two-year period . The patients were receiving pharmaceutical services under the Kaiser Permanente model of consultation ( KP model ) , a state model of consultation , or a control model and were stratified according to prescription drug use . A global visual-analogue scale and Short Form-36 were used to assess HRQOL . In the areawide study , only 2 of 42 comparisons of the effects of the KP or state model on HRQOL were significant ; both were associated with the state model and involved only small increases . In the r and om-assignment study , 3 of 21 estimated effects of the KP model on HRQOL were positive and significant ; 2 of these were significantly different between the KP model and the state model . Although the KP and state models of consultation were associated with some changes in HRQOL , the overall influence was not consistent and not clinical ly important The impacts of three alternative models of pharmacist consultation on the use and cost of health care services were studied . Two studies were conducted concurrently in an HMO over two years . In one , 6000 patients were r and omly assigned to one of three consultation models ; in the other , the three models were implemented in six geographic regions of California ( 4600 patients ) . The models were ( 1 ) consultation about new or changed prescriptions as m and ated by state law ( state model ) , ( 2 ) consultation focused on selected high-risk ambulatory care patients ( Kaiser Permanente [ KP ] model ) , and ( 3 ) a control model . The patients were surveyed three times about their health status and satisfaction , and computerized data on health care use and cost were collected . The effect of the consultation models on the use and cost of health care services was examined across five risk groups that were based on drug-use profiles . An additional 37,750 patients ( 10 % of the patients residing in the areawide study sites ) were included in a supplemental analysis of the use and cost of health care services . There was no indication in the r and om-assignment study that pharmacist consultations affected either drug costs or the cost of office visits . Similar results were found in the areawide study , with the exception that the KP model was associated with lower drug costs than the control model . In the 10 % sample , the KP model appeared to be associated with lower office visit costs but higher drug costs . Both models were associated with a lower likelihood of a hospital admission and with lower total health care costs for some high-risk patients compared with the control model . Counseling patients about their medications may be unlikely to reduce medication costs or the cost of office visits but may reduce the likelihood of hospital admissions and the overall costs of health care services ; a combination of counseling patients at high risk for drug-related problems and counseling all patients about any new or changed prescription should be considered This study evaluated pharmaceutical care as an adjunct to an existing , coordinated-care program at a Regional Diabetes Center . The progress of a control group receiving the st and ard pharmacist instruction was compared with two treatment groups receiving additional small group or individual supplementary education for a 2-month period . Outcome evaluation included assessment of individual diabetes management through blood glucose monitoring and responses on a pretest and posttest question naire . Patients in the treatment groups demonstrated significantly lower average weekly blood glucose levels and a decreased incidence of hyperglycemic episodes compared with the control group . Question naire data for both treatment groups demonstrated a significant increase in patient underst and ing of diabetes medications and medications for associated illnesses , an increase in knowledge about blood glucose monitoring , and a positive difference in perceptions/attitudes toward diabetes and communication with the pharmacist . This approach is consistent with the concept of pharmaceutical care in which the pharmacist helps patients avoid long-term complications and thus improve their quality of life The impact of clinical pharmacists ' consultations on geriatric drug prescribing was studied in a prospect i ve r and omized controlled trial of patients 65 years of age and over discharged on 3 or more medications for chronic conditions from a 450-bed community hospital . The pharmacists provided consultation to experimental patients and their physicians at hospital discharge and at periodic intervals for 3 months postdischarge . Using a st and ardized tool , a physician-pharmacist panel , blinded to study group assignment of patients , evaluated the appropriateness of prescribing for a r and om sample of 236 patients . Eighty-eight percent had at least one or more clinical ly significant drug problems , and 22 % had at least one potentially serious and life-threatening problem . Drug-therapy problems were divided into six categories : 1 ) inappropriate choice of therapy ; 2 ) dosage ; 3 ) schedule ; 4 ) drug-drug interactions ; 5 ) therapeutic duplication ; and 6 ) allergy . Experimental patients were less likely to have one or more prescribing problems in any of the categories ( P = 0.05 ) or in the appropriateness ( P = 0.02 ) or dosage ( P = 0.05 ) categories . A summary score , measuring the appropriateness of the patient 's total drug regimen , indicated that experimental patients ' regimens were more appropriate than those of controls ( P = 0.01 ) . Results of this trial reveal that clinical pharmacists can improve the appropriateness of geriatric drug prescribing in outpatient setting The effects of computerized drug profiles and clinical pharmacist consultation in the internal medicine clinics at a Veterans Administration hospital were studied . Population included patients ( n = 512 ) and physicians ( n = 35 ) of three internal medicine clinics during an eight-week period . The first four weeks were the preintervention period . The second four weeks were the intervention period in which a clinical pharmacist attended one clinic ( A ) and provided drug profiles on all patients . Two other clinics ( B and C ) served as controls . During the intervention , patients in clinic A experienced a significant reduction in prescribing problems as identified by the pharmacist : 49 percent of patients before the intervention versus 9.4 percent after the intervention ( p < 0.001 ) . Patients in clinic B had no significant change in prevalence in the number of problems identified ( 39 versus 40 percent ; NS ) , and patients in clinic C had a significant but less dramatic decrease ( 35 versus 22 percent ; p < 0.05 ) . The proportion of patients in clinic A with net decrease in the number of prescribed medications rose from 7.1 to 34.9 percent ( p < 0.001 ) , with a mean decrease of 0.3 medications per patient . No significant differences in number of prescribed medications were noted in clinics B or C. Accuracy of physician medication charting improved for patients in clinic A from 54 percent of charts with accurate drug lists before the intervention to 78.3 percent after the intervention ( p < 0.001 ) . No significant improvements were noted for clinics B and C. These results suggest that computerized drug profiles together with clinical pharmacist consultation can improve prescribing practice s in a hospital outpatient department . Extracto Los autores estudiaron el efecto de proveer perfiles de medicamentos computerizados y consulta por un farmaceútico clínico en las clínicas de medicina interna de un hospital de la Administración de Veteranos . La población incluyó 512 pacientes y 35 médicos de tres cl***inicas de medicina interna durante un período de ocho semanas . Las primeras cuatro semanas fue el período de pre-intervención . Las siguientes cuatro semanas fue el período de intervención en el cual un farmaceútico clínico asistió a una clínica ( A ) y proveyó perfiles de medicamentos para todos los pacientes , mientras otras dos clínicas ( B y C ) sirvieron de control . Durante la intervención los pacientes en la clínica A experimentaron una reducción significativa en los problemas de prescripción según identificados por el farmaceútico : 49 por ciento de los pacientes antes de la intervención versus 9.4 por ciento después de la intervención . Los pacientes en la clínica B no experimentaron un cambio significativo en la prevalencia del número de problemas identificados . Los pacientes en la clínica C tuvieron una disminución significativa , pero menos dramática . La proporción de pacientes en la clínica A con una disminución neta en el número de medicamentos prescritos aumentó de 7.1 por ciento a 34.9 por ciento con una disminución media de 0.3 medicamentos por paciente . No se observó una diferencia significativa en el número de medicamentos prescritos en las clínicas B y C. La precisión de las notas de medicamentos del médico mejoraron para los pacientes en la clínica A. No se observó una mejoría significativa en las clínicas B y C. Estos result ados sugieren que los perfiles de medicamentos computerizados en adición a consulta por un farmaceútico clínico pueden mejorar los patrones de prescripción en un departamento para pacientes ambulatorios de un hospital . Resume L'étude analyse l'impact de fournir le dossier-médicament des patients et de consulter avec un pharmacien clinique en médecine interne à l'hôpital Veterans Administration . Cinq cent douze sujets ont participé ainsi que les médecins ( n = 35 ) de trois cliniques en médecine interne pendant une période de huit semaines . Les quatre premières semaines constituaient la période pré-intervention . Pendant les dernières quatre semaines ( période d'intervention ) , le pharmacien clinique a participé aux activités d'une clinique ( A ) et a fourni les dossiers-médicaments pour tous les patients , alors que les deux autres cliniques ( B et C ) ont servi de contrôle . Lors de la période d'intervention , il y a eu une baisse significative pour ce qui est des problèmes de prescription pour les patients de la clinique A ( basé sur le critère modifié de King et Cheung ) : 49 pour cent des patients avant l'intervention versus 9.4 pour cent après ( p < 0.001 ) . Les patients de la clinique B n'ont eu aucun changement significatif dans la fréquence du nombre de problèmes identifiés ( 39 vs. 40 pour cent ; NS ) , et les patients de la clinique C ont vu une réduction significative mais moins dramatique ( 35 vs. 22 pour cent ; p < 0.05 ) . La proportion de patients de la clinique A avec une baisse dans le nombre de médicaments prescrits est passé de 7.1 à 34.9 pour cent ( p < 0.001 ) , avec une réduction moyenne de 0.3 médicaments par patient . Aucune différence n'a été notée pour le nombre de médicaments prescrits dans les cliniques B ou C. La précision avec laquelle le médecin a complété les dossiers s'est ameliorée pour les patients de la clinique A allant de 54 pour cent des dossiers ayant une liste correcte de médicaments avant l'intervention à 78.3 pour cent après l'intervention ( p < 0.001 ) . Aucune amélioration significative n'a été observée pour les cliniques B et C. Ces résultats démontrent que les dossiers-médicaments de patients ainsi que les consultations par le pharmacien clinique peuvent améliorer les habitudes de prescription d'un département de cliniques externes d'un hôpital OBJECTIVE : To assess the effectiveness of a pharmaceutical care model on the management of non-insulin-dependent diabetes mellitus ( NIDDM ) in urban African-American patients . DESIGN : Eligible patients were r and omized to either a pharmacist intervention or control group and followed over a 4-month period . Patients in the intervention group received diabetes education , medication counseling , instructions on dietary regulation , exercise , and home blood glucose monitoring , and evaluation and adjustment of their hypoglycemic regimen . Patients in the control group continued to receive st and ard medical care provided by their physicians . SETTING : A university-affiliated internal medicine outpatient clinic . PARTICIPANTS : The study population consisted of urban African-American patients with NIDDM currently attending the clinic . MAIN OUTCOME MEASURES : Primary outcome measures included fasting plasma glucose and glycated hemoglobin concentrations . Secondary outcome endpoints included blood pressure , serum creatinine , creatinine clearance , microalbumin to creatinine ratio , total cholesterol , triglycerides , high-density lipoprotein , and low-density lipoprotein concentrations . Quality -of-life assessment s were performed in both groups at baseline and at the end of the study . RESULTS : Thirty-nine patients ( 17 intervention , 22 control ) completed the study . The intervention group consisted of 12 women and 5 men with a mean ± SD age of 59 ± 12 years , total body weight ( TBW ) of 93 ± 22 kg , body mass index ( BMI ) of 34 ± 7 kg/m2 , and duration of NIDDM 6.8 ± 6.5 years . The control group consisted of 15 women and 7 men with a mean age of 65 ± 12 years , TBW of 88 ± 19 kg , BMI of 33 ± 7 kg/m2 , and a duration of NIDDM of 6.2 ± 4.8 y. Significant improvement in glycated hemoglobin ( p = 0.003 ) and fasting plasma glucose ( p = 0.015 ) was achieved in the intervention group . No change in glycemia was observed in the control subjects . Statistically significant differences in the final glycated hemoglobin ( p = 0.003 ) and fasting plasma glucose ( p = 0.022 ) concentrations were noted between groups . No significant changes in blood pressure control , lipid profile , renal function parameters , weight , or quality -of-life measures were noted within or between groups . CONCLUSIONS : Our data demonstrate the effectiveness of pharmaceutical care in the reduction of hyperglycemia associated with NIDDM in a group of urban African-American patients PURPOSE To evaluate the effect of sustained clinical pharmacist interventions involving elderly out patients with polypharmacy and their primary physicians . PATIENTS AND METHODS R and omized , controlled trial of 208 patients aged 65 years or older with polypharmacy ( > or = 5 chronic medications ) from a general medicine clinic of a Veterans Affairs Medical Center . A clinical pharmacist met with intervention group patients during all scheduled visits to evaluate their drug regimens and make recommendations to them and their physicians . Outcome measures were prescribing appropriateness , health-related quality of life , adverse drug events , medication compliance and knowledge , number of medications , patient satisfaction , and physician receptivity . RESULTS Inappropriate prescribing scores declined significantly more in the intervention group than in the control group by 3 months ( decrease 24 % versus 6 % , respectively ; P = 0.0006 ) and was sustained at 12 months ( decrease 28 % versus 5 % , respectively ; P = 0.0002 ) . There was no difference between groups at closeout in health-related quality of life ( P = 0.99 ) . Fewer intervention than control patients ( 30.2 % ) versus 40.0 % ; P = 0.19 ) experienced adverse drug events . Measures for most other outcomes remained unchanged in both groups . Physicians were receptive to the intervention and enacted changes recommended by the clinical pharmacist more frequently than they enacted changes independently for control patients ( 55.1 % versus 19.8 % ; P < 0.001 ) . CONCLUSIONS This study demonstrates that a clinical pharmacist providing pharmaceutical care for elderly primary care patients can reduce inappropriate prescribing and possibly adverse drug effects without adversely affecting health-related quality of life This prospect i ve , r and omized , controlled trial , based in a Veterans Administration Hospital general medicine clinic , compared the cost effectiveness of two behaviorally oriented interventions design ed to reduce physicians ' drug prescribing costs . Clinical pharmacists visited one group of 11 physicians during weekly clinic sessions to counterdetail the prescribing of certain targeted drugs . A second group of 10 physicians were given data each week comparing their individual prescribing costs to those of their colleagues ( peer-comparison feedback ) . A control group of 10 physicians received neither intervention . Written patient-specific suggestions for cost-effective prescribing were employed in both intervention groups . Baseline prescribing costs were monitored through the hospital 's computer during a three-month , preintervention period and a seven-month intervention period . The 2026 written suggestions made by the doctors of pharmacy result ed in 613 ( 30.3 percent ) prescribing changes , including deletion , substitution , or change in dosage of targeted drugs . There were no intergroup differences in the response to written suggestions . However , the group receiving face-to-face visits from the clinical pharmacists achieved lower average prescription costs than the control group during seven of eight months . Intergroup differences were statistically significant ( p < 0.05 ) during three of the last five months of the study . The face-to-face meeting intervention was cost-effective , saving $ 478 per physician over seven months after accounting for Pharm . D. salary costs . There was no significant decrease in the number of prescriptions written by the face-to-face group compared with the control group , suggesting that drug substitution rather than deletion was the method used by physicians to lower drug costs . No savings result ed from the use of peer-comparison feedback . We conclude that personal visits by a Pharm . D. are a cost-effective technique for reducing physicians ' prescribing costs , and are superior to peer-comparison feedback The objective was to study the effect of " academic group detailing " on the prescribing of lipid-lowering drugs in Swedish primary care . A r and omized controlled trial was conducted , r and omization being by group . Groups of doctors at 134 community health centres were r and omly allocated to an intervention and a control group . The 67 intervention health centres were offered four sessions , conducted by a pharmacist , with group information on guidelines for the management of hyperlipidaemia . The number of prescriptions of lipid-lowering drugs per month increased in the intervention health centres and the increase was statistically different from the corresponding change in the control health centres among women in the age group 30 - 65 years ( p = 0.03 ) . The prescription of first-line lipid-lowering drugs increased by 20 % in the intervention health centres ( p = 0.03 ) . " Academic group detailing " by pharmacists to primary care doctors can be an effective method for influencing prescribing practice We conducted a statewide controlled trial of three methods to improve antibiotic prescribing in office practice : a mailed brochure , a drug educator visit , and a physician visit . Educational topics were three antibiotics contraindicated for office practice and oral cephalosporins . Medicaid prescribing data were used to select donors who needed education . The effect of the methods was evaluated by comparing the change in prescribing ( the year before the intervention v the year after the intervention ) for the doctors receiving education with the prescribing of comparable doctors chosen as controls . The mailed brochure had no detectable effect , and the drug educator had only a modest effect . The physician visits produced strong attributable reductions in prescribing of both drug classes . For the contraindicated antibiotics , the reductions were 18 % in number of doctors prescribing , 44 % in number of patients per doctor receiving these drugs , and 54 % in number of prescriptions written per doctor . For the oral cephalosporins , both number of patients and number of prescriptions per doctor were reduced by 21 % . Doctors responded equally well to recommendations design ed to improve the quality of care and to reduce the cost of care This study assessed the impact of clinical pharmacists ' consultations on drug regimens , compliance , and health service use of geriatric hospitalized patients ( N = 706 ) discharged on 3 or more medications . Pharmacists consulted with experimental patients at discharge and 3 months thereafter , and with physicians as needed . Controls received usual care . At 6 - 8 weeks after enrollment , experimental patients were more knowledgeable about regimens than controls . At 12 - 14 weeks , they were on fewer medications and less complex regimens , and had better compliance scores . There was no effect on service use or charges , perhaps due to inadequate sample size and lack of targeted drug groups analysis . The authors conclude that clinical pharmacists ' consultations can improve geriatric patients ' drug regimens and compliance . Findings further suggest the need for replication among large cohorts of patients at high risk , due to the use of medications most likely to have a potential for serious outcomes and to be vulnerable to physician prescribing error The impacts of two models of pharmacist consultation on patient satisfaction with pharmaceutical services relative to a control model were studied . Patients in the r and om-assignment and areawide studies of the Kaiser Permanente/USC Patient Consultation Study were asked to rate their satisfaction with six aspects of the service they received at the pharmacy . The patients were receiving pharmaceutical services under the Kaiser Permanente ( KP ) model of consultation , a state-m and ated model , or a control model . They were assigned to risk categories according to their pattern of prescription drug use . Differences in satisfaction among the three consultation models for all patients and for each risk group and correlations between satisfaction items were determined . The KP and state models of consultation were associated with better satisfaction than the control model on five of the six satisfaction items . In the high-risk patient groups , the KP and state models were associated with higher levels of satisfaction than the control model . In the low-risk group , the state model was associated with higher levels of satisfaction than the control model ; results for low-risk patients assigned to the KP model were inconsistent between the r and om-assignment study and the areawide study . Overall satisfaction appeared to be a suboptimal measure of satisfaction with consultation . Overall satisfaction was more closely related to satisfaction with waiting time and with whether the pharmacy staff was helpful and caring than with the three items reflecting satisfaction with the content of the consultation . Patients were more satisfied under the state model of pharmacist consultation or the KP model of consultation , which result ed in more-intensive counseling for fewer patients , than under a control model |
12,299 | 22,754,924 | Circumstantial evidence indicates that mind body therapies may have a therapeutic benefit on endothelial dysfunction , however , the aggregate data from the three small r and omized trials to date do not support this hypothesis . | Mind body therapies appear to reduce morbidity and mortality in patients with cardiovascular diseases , but there is limited underst and ing of the mechanisms that mediate this effect .
Vascular endothelial dysfunction is a central feature of atherogenesis that is adversely impacted by mental stress .
We conducted a systematic review and meta- analysis of the effect of mind body therapies on peripheral endothelial function in patients with and without established cardiovascular disease . | BACKGROUND The aim of this study was to examine whether angiotensin-converting enzyme ( ACE ) inhibition improves coronary endothelial dysfunction in patients with atherosclerosis and its risk factors and whether this was related to the ACE insertion-deletion ( I/D ) polymorphism . METHODS AND RESULTS In 56 patients with atherosclerosis or its risk factors , we studied endothelium-dependent responses with acetylcholine and endothelium-independent function with sodium nitroprusside , before and after ACE inhibition with enalaprilat . Enalaprilat did not alter either resting coronary tone or vasodilation with sodium nitroprusside . However , it potentiated the coronary microvascular and epicardial responses with acetylcholine ; coronary blood flow increased from 82+/-7 to 90+/-8 mL/min ( P=0.05 ) after enalaprilat . Patients with depressed endothelial function ( P<0.001 ) and those with ACE DD or ID genotypes ( P=0.002 ) but not those homozygous for the I allele had the greatest improvement by multivariate analysis . Similarly , acetylcholine-mediated epicardial vasomotion improved in segments that initially constricted ( endothelial dysfunction ) : from -10.1+/-1 % to -1.4+/-2 % ( P<0.001 ) after enalaprilat . No augmentation was observed in segments that dilated ( normal endothelial dysfunction ) with acetylcholine . Patients with the D allele , hypercholesterolemia , and smokers ( all P<0.05 ) had greater improvement . CONCLUSIONS Acute ACE inhibition improves coronary epicardial and microvascular endothelium-dependent vasomotion in patients with atherosclerosis or its risk factors who have endothelial dysfunction and presence of the D allele CONTEXT Observational studies have shown that psychosocial factors are associated with increased risk for cardiovascular morbidity and mortality , but the effects of behavioral interventions on psychosocial and medical end points remain uncertain . OBJECTIVE To determine the effect of 2 behavioral programs , aerobic exercise training and stress management training , with routine medical care on psychosocial functioning and markers of cardiovascular risk . DESIGN , SETTING , AND PATIENTS R and omized controlled trial of 134 patients ( 92 male and 42 female ; aged 40 - 84 years ) with stable ischemic heart disease ( IHD ) and exercise-induced myocardial ischemia . Conducted from January 1999 to February 2003 . INTERVENTIONS Routine medical care ( usual care ) ; usual care plus supervised aerobic exercise training for 35 minutes 3 times per week for 16 weeks ; usual care plus weekly 1.5-hour stress management training for 16 weeks . MAIN OUTCOME MEASURES Self-reported measures of general distress ( General Health Question naire [ GHQ ] ) and depression ( Beck Depression Inventory [ BDI ] ) ; left ventricular ejection fraction ( LVEF ) and wall motion abnormalities ( WMA ) ; flow-mediated dilation ; and cardiac autonomic control ( heart rate variability during deep breathing and baroreflex sensitivity ) . RESULTS Patients in the exercise and stress management groups had lower mean ( SE ) BDI scores ( exercise : 8.2 [ 0.6 ] ; stress management : 8.2 [ 0.6 ] ) vs usual care ( 10.1 [ 0.6 ] ; P = .02 ) ; reduced distress by GHQ scores ( exercise : 56.3 [ 0.9 ] ; stress management : 56.8 [ 0.9 ] ) vs usual care ( 53.6 [ 0.9 ] ; P = .02 ) ; and smaller reductions in LVEF during mental stress testing ( exercise : -0.54 % [ 0.44 % ] ; stress management : -0.34 % [ 0.45 % ] ) vs usual care ( -1.69 % [ 0.46 % ] ; P = .03 ) . Exercise and stress management were associated with lower mean ( SE ) WMA rating scores ( exercise : 0.20 [ 0.07 ] ; stress management : 0.10 [ 0.07 ] ) in a subset of patients with significant stress-induced WMA at baseline vs usual care ( 0.36 [ 0.07 ] ; P = .02 ) . Patients in the exercise and stress management groups had greater mean ( SE ) improvements in flow-mediated dilation ( exercise : mean [ SD ] , 5.6 % [ 0.45 % ] ; stress management : 5.2 % [ 0.47 % ] ) vs usual care patients ( 4.1 % [ 0.48 % ] ; P = .03 ) . In a subgroup , those receiving stress management showed improved mean ( SE ) baroreflex sensitivity ( 8.2 [ 0.8 ] ms/mm Hg ) vs usual care ( 5.1 [ 0.9 ] ms/mm Hg ; P = .02 ) and significant increases in heart rate variability ( 193.7 [ 19.6 ] ms ) vs usual care ( 132.1 [ 21.5 ] ms ; P = .04 ) . CONCLUSION For patients with stable IHD , exercise and stress management training reduced emotional distress and improved markers of cardiovascular risk more than usual medical care alone BACKGROUND The renin-angiotensin system may contribute to atherogenesis through the promotion of endothelial dysfunction . The present study was performed to determine whether angiotensin-1 ( AT(1 ) ) receptor inhibition improves endothelial dysfunction . METHODS AND RESULTS In the femoral circulation of 19 patients with atherosclerosis and of 9 control subjects , we studied microvascular responses to reactive hyperemia , angiotensin II , acetylcholine , and sodium nitroprusside before and after the administration of intra-arterial losartan ( 10 mg ) . Femoral artery flow velocity was measured with a Doppler flow wire , and the femoral vascular resistance index ( FVRI ) was calculated as mean arterial pressure divided by flow velocity . Losartan induced a minor ( 5.9+/-2 % , P=0 . 02 ) reduction in FVRI and inhibited angiotensin II-mediated vasoconstriction in both patient groups ( P<0.01 ) . After the administration of losartan , acetylcholine-mediated vasodilation was augmented in patients ( 44+/-5 % to 58+/-4 % reduction in FVRI with infusion at a rate of 150 microgram/min , P<0.001 ) but not control subjects . Vasodilation during reactive hyperemia was also greater after AT(1 ) receptor inhibition ( P=0.03 ) in patients , but the response to sodium nitroprusside remained unchanged . In a separate group of 31 patients with atherosclerosis , we investigated the effect of 8 weeks of oral losartan therapy on brachial artery flow-mediated vasodilation with the use of high-resolution ultrasound . Oral losartan therapy improved flow-mediated brachial artery dilation ( 1.4+/-0.9 % to 3.2+/-0.8 % , P=0.03 ) but had no effect on the nitroglycerin response . Serum nitrogen oxide levels increased from 21.6+/-1.7 to 26.7+/-2.4 micromol/L ( P=0.008 ) . CONCLUSIONS The results of the present study indicate that inhibition of the AT(1 ) receptor in patients with atherosclerosis reverses endothelial dysfunction by improving NO availability and therefore may have long-term therapeutic benefits Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists Objective : To determine if depression contributes to incident heart disease after accounting for genetic , behavioral , and medical factors associated with both conditions . Methods : We used a prospect i ve twin study with a 12-year follow-up . In 1992 , lifetime diagnosis of depression was assessed in 1159 male-male twins and merged with longitudinal health data from the Vietnam Era Twin Registry Study of Aging . Incident heart disease was defined as having myocardial infa rct ion , heart surgery , or angina at 12-year follow-up when twins were 55.4 years ( st and ard deviation , 2.5 years ) of age . Risks for heart disease were computed in a logistic regression model that included comparing twins at different levels of phenotypic expression of depression and varying levels of genetic vulnerability at the same time adjusting for pertinent covariates . Results : After adjusting for sociodemographics , co-occurring psychopathology , smoking , obesity , diabetes , hypertension , and social isolation , twins at high genetic risk and exposed to depression remained at greater risk of developing ischemic heart disease ( IHD ) ( odds ratio , 2.55 ; 95 % confidence interval , 1.44 - 4.49 ) compared with those at low genetic risk and without phenotypic expression of depression . Odds ratios suggest that twins at genetic liability but without phenotypic expression were at risk of IHD , but the effect was not statistically significant . Conclusions : A history of depression is a risk factor for incident heart disease after adjusting for numerous covariates . Twins with both high genetic vulnerability and phenotypic expression of depression were at greatest risk of IHD . Trends suggest the genetic contribution to IHD that overlaps with depression may partly explain this association , but studies in larger sample s are warranted . IHD = ischemic heart disease ; VET Registry = Vietnam Era Twin Registry ; DSM-III-R = Diagnostic and Statistical Manual , Third Edition , Revised ; VETSA = Vietnam Era Twin Study of Aging ; MZ = monozygotic ; DZ = dizygotic ; MI = myocardial infa rct ion & NA ; Mental stress induces endothelial dysfunction , that is a reduction of the post‐occlusion brachial artery flow‐mediated vasodilation ( FMD ) . This does not occur in subjects highly susceptible to hypnosis ( Highs ) in either the waking or hypnotic state . The aim of the present experiment was to assess whether endothelial dysfunction is also induced by acute nociceptive stimulation and whether high hypnotisability and /or the specific instruction of analgesia prevent its occurrence in awake highly hypnotizable individuals . Thus , nine Highs and nine subjects with low susceptibility to hypnosis ( Lows ) underwent an experimental session including the administration of pressor pain and of pressor pain associated with the instruction of analgesia . Heart rate , basal artery diameters and brachial artery flow‐mediated vasodilation were measured during stimulation and rest conditions . Heart rate exhibited slight changes not modulated by hypnotisability . During painful stimulation both Highs and Lows showed a decrease of FMD , but it was significantly less pronounced in Highs . During the administration of painful stimulation together with the instruction of analgesia , only Highs reported analgesia and their FMD no longer decreased . This study provides the first evidence of pain‐related endothelial dysfunction and extends previous findings concerning a sort of natural protection of Highs against the vascular effects of mental stress to acute pain OBJECTIVES This study was design ed to investigate the role of cortisol in stress-induced endothelial dysfunction and impaired baroreflex sensitivity ( BRS ) by blocking cortisol production with metyrapone before subjecting healthy volunteers to mental stress . BACKGROUND Mental stress raises cortisol levels and is associated with increased coronary heart disease ( CHD ) morbidity and mortality , especially from sudden cardiac death . It also causes endothelial dysfunction and impaired BRS . METHODS We measured brachial artery flow-mediated dilation ( FMD ) , a measure of endothelial function , and BRS in 36 subjects without CHD risk factors who were then r and omized in a double-blind fashion to oral metyrapone 750 mg x 2 or placebo . Five hours later we subjected subjects to mental stress and then remeasured endothelial function and BRS . RESULTS Prestress cortisol levels were significantly higher in the placebo group at 270.5 ( 30.9 ) nmol/l versus 89.1 ( 11.8 ) nmol/l ( p = 0.01 ) , and the increase with stress was higher at 57.9 ( 17.9 ) nmol/l versus 11.2 ( 2.2 ) nmol/l ( p < 0.001 ) . In the placebo group , compared to baseline , FMD and BRS fell significantly from 4.5 % ( 0.7 % ) to 1.4 % ( 1.1 % ) ( p = 0.02 ) and 21.4 ( 2.3 ) ms/mmHg to 16.3 ( 1.5 ) ms/mmHg ( p = 0.04 ) , respectively . In the metyrapone group , FMD and BRS were unchanged from baseline : 4.3 % ( 0.9 % ) versus 5.1 % ( 0.8 % ) ( p = 0.48 ) and 26.4 ( 2.9 ) ms/mmHg versus 24.9 ( 2.6 ) ms/mmHg ( p = 0.62 ) , respectively . Analysis of covariation showed a significant effect of metyrapone on change in both FMD ( p = 0.009 ) and BRS ( p = 0.024 ) . CONCLUSIONS Stress-related endothelial dysfunction and BRS impairment can be prevented by blocking cortisol production with metyrapone , demonstrating a direct or facilitative role for cortisol in these phenomena and suggesting mechanisms by which stress contributes to CHD and sudden cardiac death The effect of right , left , and alternate nostril yoga breathing ( i.e. , RNYB , LNYB , and ANYB , respectively ) were compared with breath awareness ( BAW ) and normal breathing ( CTL ) . Autonomic and respiratory variables were studied in 21 male volunteers with ages between 18 and 45 years and experience in the yoga breathing practice s between 3 and 48 months . Subjects were assessed in five experimental sessions on five separate days . The sessions were in fixed possible sequences and subjects were assigned to a sequence r and omly . Each session was for 40 min ; 30 min for the breathing practice , preceded and followed by 5 min of quiet sitting . Assessment s included heart rate variability , skin conductance , finger plethysmogram amplitude , breath rate , and blood pressure . Following RNYB there was a significant increase in systolic , diastolic and mean pressure . In contrast , the systolic and diastolic pressure decreased after ANYB and the systolic and mean pressure were lower after LNYB . Hence , unilateral nostril yoga breathing practice s appear to influence the blood pressure in different ways . These effects suggest possible therapeutic applications PURPOSE To determine whether higher rates of mortality are observed in people reporting psychological distress , to establish the nature of any excess , and to examine the possible existence of a dose response relationship . METHODS We conducted a prospect i ve follow-up study of mortality over an eight-year period in the North West of Engl and . A total of 4,501 adults were recruited from two general practice s during a population -based survey conducted at the start of 1992 . At baseline psychological distress was assessed using the General Health Question naire ( 12-item version , GHQ-12 ) . The relationship between levels of distress and subsequent mortality was examined using Cox proportional hazard models . RESULTS Risk of all-cause mortality was greatest in subjects reporting the highest levels of distress ( hazard ratio ( HR ) 1.71 , 95 % CI 1.32 - 2.23 ) but was also raised in subjects reporting intermediate distress ( HR 1.38 95 % CI 1.06 - 1.79 ) when compared to those reporting no distress . Increased risk of mortality in subjects reporting distress appeared to be due largely to an excess of deaths from ischaemic heart disease ( high distress , HR 1.90 , 95 % CI 1.08 - 3.35 ; intermediate distress , HR 1.58 , 95 % CI 0.90 - 2.76 ) and respiratory diseases ( high distress , HR 5.39 , 95 % CI 2.70 - 10.78 ; intermediate distress , HR 2.33 , 95 % CI 1.12 - 4.22 ) . CONCLUSIONS The association between mortality and psychological distress observed in this study seems to arise largely because of premature deaths from ischaemic heart disease and respiratory diseases . The existence of a dose-response effect between distress and mortality provides further evidence to support the existence of a casual relationship OBJECTIVES To examine the influence of distinct clusters of psychiatric symptoms on subsequent cause-specific mortality in older persons living in the community . DESIGN A prospect i ve cohort study over 7.5 years . SETTING Otsuki-town , Kochi prefecture , Japan . PARTICIPANTS Nine hundred eighty community-dwelling persons , aged 65 to 84 in 1991 . MEASUREMENTS Psychiatric symptoms at baseline were measured using the 30-item version of the General Health Question naire ( GHQ-30 ) . A factor analysis was performed on the responses of all 980 subjects . The relationships between subscale scores on the identified factors and causes of deaths occurring over 7.5 years in 817 respondents with no physical disability at baseline were assessed using a proportional hazards model adjusted for age , gender , chronic conditions under treatment , regular physical activity , and availability of close or casual neighbors . RESULTS The factor analysis identified three clusters of psychiatric symptoms : depression , apathy/anergia , and anxiety . In the proportional hazards model , which included three GHQ subscales depicting these factors simultaneously , the depression subscale was associated with increased mortality from cerebrovascular disease ( multivariate adjusted hazard ratio per unit increase in the st and ard score on the depression subscale=2.04 , 95 % confidence interval (CI)=1.17 - 3.55 ) , and the apathy/anergia subscale was associated with increased mortality from noncancer and noncardiovascular causes ( multivariate adjusted hazard ratio per unit increase in the st and ard score on the apathy/anergia subscale=1.71 , 95 % CI=1.25 - 2.34 ) . The anxiety subscale was not associated with any cause of death . CONCLUSION Depressive symptoms and symptoms indicating apathy/anergia have differential influences on subsequent causes of death in older persons living in the community . Identification of specific psychiatric symptom clusters may contribute to the prevention of deaths from specific causes in older population This study examined the effects of exercise and stress management training on clinical outcomes and medical expenditures over a 5-year follow-up period in 94 male patients with established coronary artery disease ( CAD ) and evidence of ambulatory or mental stress-induced myocardial ischemia . Patients were r and omly assigned to 4 months of aerobic exercise 3 times per week or to a 1.5-hour weekly class on stress management ; patients who lived too far from Duke to participate in the weekly treatments formed the usual care control group . Follow-up was performed at the end of treatment and annually thereafter for 5 years . Stress management was associated with a significant reduction in clinical CAD events relative to usual care over each of the first 2 years of follow-up and after 5 years . Economic analyses revealed that stress management was associated with lower medical costs than usual care and exercise in the first 2 years , and that the cumulative cost over 5 years was also lower for stress management relative to usual care . These results suggest that there may be clinical and economic benefit to offering the type of preventive stress management and exercise interventions provided to patients with myocardial ischemia . Moreover , these findings suggest that the financial benefits that accrue from an appropriately targeted intervention may be substantial and immediate BACKGROUND Previous studies have demonstrated that myocardial ischemia can be elicited by mental stress in the laboratory and during daily life and that ischemia induced by mental stress is associated with an increased risk for future cardiac events in patients with coronary artery disease . OBJECTIVES To examine the extent to which ischemia induced by mental stress can be modified by exercise stress management , and to evaluate the impact of these interventions on clinical outcomes . METHODS One hundred seven patients with coronary artery disease and ischemia documented during mental stress testing or ambulatory electrocardiographic monitoring were r and omly assigned to a 4-month program of exercise or stress management training . Patients living at a distance from the facility formed a nonr and om , usual care comparison group . Myocardial ischemia was reassessed following treatment , and patients were contacted annually for as long as 5 years to document cardiac events , including death , nonfatal myocardial infa rct ion , and cardiac revascularization procedures . RESULTS Twenty-two patients ( 21 % ) experienced at least 1 cardiac event during a mean ( + /- SD ) follow-up period of 38 + /- 17 months . Stress management was associated with a relative risk of 0.26 compared with controls . The relative risk for the exercise group also was lower than that of controls , but the effect did not reach statistical significance . Stress management also was associated with reduced ischemia induced by mental stress and ambulatory ischemia . CONCLUSION These data suggest that behavioral interventions offer additional benefit over and above usual medical care in cardiac patients with evidence of myocardial ischemia |
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