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900 | 28,039,697 | CONCLUSION This systematic review suggests that S-1 plus sorafenib showed modest clinical efficacy and tolerable toxicity profile in patients with advanced HCC . | PURPOSE To assess the efficacy and safety of S-1 plus sorafenib for the treatment of advanced hepatocellular carcinoma ( HCC ) . | PURPOSE To evaluate safety and efficacy of combined transarterial chemoembolization ( TACE ) with doxorubicin-eluting beads ( DEB ) and sorafenib in patients with advanced hepatocellular carcinoma ( HCC ) . PATIENTS AND METHODS A prospect i ve single-center phase II study was undertaken involving patients with unresectable HCC . The protocol involved sorafenib 400 mg twice per day combined with DEB-TACE . Safety and response were assessed . Results DEB-TACE in combination with sorafenib was successfully administered in 35 patients : mean age , 63 years ; Child 's A , 89 % ; Barcelona Clinic Liver Cancer stage C , 64 % ; Eastern Cooperative Oncology Group performance status of 0 and 1 , 46 % and 54 % , respectively ; and mean index tumor size , 7.7 cm ( st and ard deviation , ± 4.2 cm ) . Patients underwent 128 cycles of therapy ( sorafenib plus DEB-TACE , 60 cycles ; sorafenib alone , 68 cycles ) . Median number of cycles per patient was two ( range , one to five cycles ) ; median number of days treated with sorafenib was 71 ( range , 4 to 620 days ) . The most common toxicities during cycle one were fatigue ( 94 % ) , anorexia ( 67 % ) , alterations in liver enzymes ( 64 % ) , and dermatologic adverse effects ( 48 % ) . Although most patients experienced at least one grade 3 to 4 toxicity , most toxicities were minor ( grade 1 to 2 , 83 % v grade 3 to 4 , 17 % ) . Toxicity during cycle two was decreased . Over the course of the study , there were 40 sorafenib dose interruptions and 25 sorafenib dose reductions . Sorafenib plus DEB-TACE was associated with a disease control rate of 95 % ( Response Evaluation Criteria in Solid Tumors Group)/100 % ( European Association for the Study of the Liver [ EASL ] ) , with an objective response of 58 % ( EASL ) . CONCLUSION The combination of sorafenib and DEB-TACE in patients with unresectable HCC is well tolerated and safe , with most toxicities related to sorafenib . Toxicity is manageable with dose adjustment of sorafenib . Preliminary efficacy data are promising Summary Background Sorafenib is the sole molecular-targeted agent showing a survival benefit in patients with advanced hepatocellular carcinoma ( HCC ) . We evaluated the tolerability and effectiveness of a combination of S-1 with sorafenib in patients with advanced HCC . Methods S-1 was administered during days 1–14 and sorafenib was administered every day . This treatment was repeated every 21 days . In phase I , we determined the maximum tolerated dose ( MTD ) and dose-limiting toxicities ( DLTs ) . The dose of each drug was planned as follows : cohort 1 : S-1 48 mg/m2/day and sorafenib 400 mg/day , cohort 2a : S-1 48 mg/m2/day and sorafenib 800 mg/day , cohort 2b : S-1 64 mg/m2/day and sorafenib 400 mg/day , cohort 3 : S-1 64 mg/m2/day and sorafenib 800 mg/day , and cohort 4 : S-1 80 mg/m2/day and sorafenib 800 mg/day . In phase II , the patients were treated at the MTD to evaluate safety and efficacy . Results Nineteen patients were enrolled in phase I. One of the six patients in cohort 1 and one of the six patients in cohort 3 experienced DLT . None of the three patients in cohort 2a experienced DLT and three of the four patients in cohort 4 experienced DLT . Therefore , cohort 3 was considered the MTD . Subsequently , 26 patients were enrolled in phase II . The most common grade 3/4 toxicities were an increase of aspartate aminotransferase ( 38.5 % ) , thrombocytopenia ( 23.1 % ) , neutropenia ( 19.2 % ) , hyperbilirubinemia ( 15.4 % ) , an increase of alanine aminotransferase ( 15.4 % ) , hyponatremia ( 11.5 % ) , rash ( 11.5 % ) , and hypophosphatemia ( 11.5 % ) . Sudden death occurred in one patient ( 3.8 % ) . A patient ( 3.8 % ) had a partial response , 15 ( 57.7 % ) had stable disease , and 10 ( 38.5 % ) had progressive disease . The median times to progression and overall survival were 2.4 and 10.5 months , respectively . Conclusion The MTD of S-1 and sorafenib in patients with advanced HCC was 64 mg/m2/day and 800 mg/day , respectively . This dose/regimen demonstrated substantial clinical activity among patients with advanced HCC Purpose Sorafenib improves overall survival and time to progression of advanced hepatocellular ( aHCC ) patients such as demonstrated in 2 phase III trials . However , aHCC patients ’ outcome is still poor despite these results . In order to improve the efficacy of systemic treatment for aHCC , we evaluated the combination of sorafenib plus 5-fluorouacil infusion in a phase II trial . Methods Patients with aHCC not eligible for loco-regional therapies , Child-Pugh A-B , ECOG-PS 0 - 1 , and without history of anti-cancer systemic treatment were enrolled . Treatment schedule was : sorafenib 400 mg/bid continuously and continuum infusion of 5-fluorouracil 200 mg/sqm/daily day 1–14 every 3 weeks . Results Thirty-nine patients were enrolled : ECOG-PS 0 - 1 : 29 - 10 , Child-Pugh A-B : 36 - 3 . Grade 3/4 ( % ) toxicities included : diarrhea 5.1/0 , mucositis 20.5/2.6 , h and foot skin reaction 20.5/0 , skin rash 10.5/0 , hypertension 10.3/0 , hyperbilirubinemia 5.1/2.6 , glutamic-oxaloacetic transaminase increase 10.3/0 , glutamic-pyruvic transaminase increase 7.7/0 , cardiac toxicity ( one heart failure , two atrial fibrillation cases ) 7.7/0 , and bleeding ( melena ) in 2.6/0 . One partial response was observed . Stable disease was obtained in 46.2 % of patients with a median duration of 16.2 months . Median time to progression was 8 months ( CI 95 % = 5.7–10.4 ) , and median overall survival was 13.7 months ( CI 95 % = 9.5–17.9 ) . Conclusions The results show an encouraging disease control rate , time to progression , and overall survival . The combination of sorafenib and 5-fluorouracil was feasible , and the side effects were manageable for patients carefully selected for liver function and performance status Background In Japan , transarterial infusion chemotherapy using cisplatin ( CDDP-TAI ) is frequently used for advanced hepatocellular carcinoma ( HCC ) . Moreover , oral chemotherapy with S-1 , an oral fluoropyrimidine derivative , has also elicited promising responses in HCC patients . We determined the recommended dosage for CDDP-TAI plus S-1 combination therapy for advanced HCC . Methods Twelve Child – Pugh class A or B patients with advanced HCC who met the eligibility criteria were enrolled in this phase I trial . Patients received CDDP-TAI ( infusion , day 1 ) plus S-1 ( oral administration , days 1–21 ) every 5 weeks until disease progression . Results Cisplatin ( 65 mg/m2 ) was administered with S-1 at 50 mg · m-2 day-1 ( level 1 , 3 patients ) , 60 mg · m-2 day-1 ( level 2 , 3 patients ) , or 80 mg · m-2 day-1 ( level 3 , 6 patients ) . The total number of treatment courses was 25 ( median , 2 courses/patient ; range , 1–6 courses ) . Dose-limiting toxicity was not observed in any patient at any level ; therefore , the recommended dosage for cisplatin and S-1 in combination was level 3 . Grade 3 adverse events were elevated alanine aminotransferase levels ( 2 patients ) , elevated aspartate aminotransferase levels ( 2 patients ) , anemia ( 1 patient ) , and decreased platelet counts ( 1 patient ) . Median progression-free survival and overall survival were 73 days and 328 days , respectively . The disease control rate was 58 % ( 7/12 ) ; 17 % ( 2/12 ) of patients achieved partial response and 42 % ( 5/12 ) achieved stable disease . CDDP-TAI plus S-1 is safe for the treatment of HCC . Conclusion The recommended dosage for further evaluation of this combination therapy in phase II studies is 65 mg/m2 CDDP and 80 mg/m2 S-1.Trial registration UMIN ; number : BACKGROUND & AIMS Sorafenib , a multi-kinase inhibitor with anti-angiogenic activity , was recently approved for the treatment of advanced hepatocellular carcinoma ( HCC ) . Metronomic chemotherapy using tegafur/uracil ( 4:1 molar ratio ) , an oral fluoropyrimidine , has been shown to enhance the anti-tumor effect of anti-angiogenic agents in pre clinical models . This phase II study evaluated the efficacy and safety of combining metronomic tegafur/uracil with sorafenib in patients with advanced HCC . METHODS Patients with histologically- or cytologically-proven HCC and Child-Pugh class A liver function were treated with sorafenib ( 400 mg twice daily ) and tegafur/uracil ( 125 mg/m(2 ) based on tegafur twice daily ) continuously as first-line therapy for metastatic or locally advanced disease that could not be treated by loco-regional therapies . The primary endpoint was progression-free survival ( PFS ) . RESULTS The study enrolled 53 patients . Thirty-eight patients ( 72 % ) were hepatitis B surface antigen-positive . The median PFS was 3.7 months ( 95 % C.I. , 1.9 - 5.5 ) and the median overall survival was 7.4 months ( 95 % C.I. , 3.4 - 11.4 ) . According to RECIST criteria , 4 patients ( 8 % ) had a partial response and 26 patients ( 49 % ) had a stable disease . Major grade 3/4 toxicities included fatigue ( 15 % ) , abnormal liver function ( 13 % ) , elevated serum lipase ( 10 % ) h and -foot skin reaction ( HFSR ) ( 9 % ) , and bleeding ( 8 % ) . HFSR was the major adverse event result ing in dose reduction ( 19 % ) or treatment delay ( 21 % ) . CONCLUSIONS Metronomic chemotherapy with tegafur/uracil can be safely combined with sorafenib and shows preliminary activity to improve the efficacy of sorafenib in advanced HCC patients S‐1 , an oral fluoropyrimidine derivative , has been shown to be clinical ly effective against various solid tumors , and pre clinical studies have demonstrated activity against hepatocellular carcinoma . We conducted a phase I/II study in patients with advanced hepatocellular carcinoma to examine the pharmacokinetics , recommended dose , safety and efficacy of S‐1 . In phase I , the administered dose of S‐1 was approximately 64 mg/m2 per day in three patients ( level 1 ) and approximately 80 mg/m2 per day in six patients ( level 2 ) . There was no dose‐limiting toxicity at level 1 , but two patients had dose‐limiting toxicity at level 2 ( grade 3 anorexia and grade 2 rash requiring eight or more consecutive days of rest ) . The recommended dose was finally estimated to be 80 mg/m2 per day . There were no significant differences in the pharmacokinetics of S‐1 between patients with Child‐Pugh A and those with B. In phase II , five of 23 patients ( 21.7 % ) had partial responses . The median progression‐free survival and overall survival were 3.7 and 16.6 months , respectively . The most common toxicities of grade 3 or 4 were elevated serum aspartate aminotransferase levels , hypochromia and thrombocytopenia . In conclusion , S‐1 showed an acceptable toxicity profile and promising antitumor activity for hepatocellular carcinoma , warranting further evaluation in r and omized clinical trials . ( Cancer Sci 2010 ; 101 : 2606–2611 Summary Purpose Sorafenib is a multi-kinase inhibitor , which was approved as first-line treatment for patients with advanced hepatocellular carcinoma ( HCC ) . We conducted a phase 1 study of sorafenib plus S-1 in patients with advanced HCC . Experimental design We design ed to escalate S-1 at 4 different dose levels with fixed dose of sorafenib . Four dose levels were as follows : level 1 , D1 - 14 S-1 50 mg/m2/day + D1 - 21 sorafenib 400 mg bid ; level 2 , D1 - 14 S-1 60 mg/m2/day + D1 - 21 sorafenib 400 mg bid ; level 3 , , D1 - 14 S-1 70 mg/m2/day + D1 - 21 sorafenib 400 mg bid ; level 4 , D1 - 14 S-1 80 mg/m2/day + D1 - 21 sorafenib 400 mg bid . The treatment was repeated every 3 weeks . Results From August 2009 to July 2010 , 20 patients with advanced HCC were enrolled . The median age was 48 years ( range , 29–74 ) . Eighteen ( 90 % ) patients had hepatitis B viral infection and 19 ( 95 % ) patients were rated as Child-Pugh class A. The dose-limiting toxicities were grade 4 infection and thrombocytopenia . After a median follow-up duration of 8.6 months ( range , 3.7–14.2 months ) , median PFS was 3.9 months ( 95 % CI , 0.8–7.0 months ) and median OS was 10.4 months ( 95 % CI , 0–22.4 months ) . In pharmacokinetic analysis , there was no statistically significant drug interaction between sorafenib and S-1 . Conclusions The combination of sorafenib and S-1 showed tolerable toxicity profile and modest clinical efficacy in patients with advanced HCC . The recommended dose of sorafenib and S-1 was 400 mg twice daily and 40 mg/m2 twice daily , respectively Sorafenib , an oral multikinase inhibitor , shows efficacy in renal cell and hepatocellular carcinoma ( HCC ) and is well tolerated when combined with doxorubicin in other solid tumours . Eighteen patients with inoperable HCC received doxorubicin 60 mg/m(2 ) IV for up to six 3-week cycles . Sorafenib 400 mg bid was administered continuously starting day 4 . Patients discontinuing doxorubicin were eligible for sorafenib monotherapy . The most frequent grade 3 - 4 drug-related adverse events were neutropaenia ( 61 % ) , leukopaenia ( 45 % ) and diarrhoea ( 17 % , grade 3 ) . Seven of eight patients who completed six cycles of doxorubicin continued treatment with sorafenib for at least 3 months . Doxorubicin moderately increased AUC ( 21 % ) and C(max ) ( 33 % ) when administered with sorafenib . The disease control rate for 16 evaluable patients was 69 % . Sorafenib plus doxorubicin appears to be well tolerated and more effective in the treatment of HCC than doxorubicin alone . Follow-up with single-agent sorafenib in these patients also appears to be well tolerated CONTEXT In a r and omized phase 3 trial , 400 mg of sorafenib twice daily prolonged overall survival of patients with advanced hepatocellular carcinoma ( HCC ) and Child-Pugh A disease . In a phase 1 study , sorafenib combined with doxorubicin , 60 mg/m(2 ) , was well tolerated by patients with refractory solid tumors . The combination of sorafenib and doxorubicin in patients with advanced HCC has not been evaluated in a phase 2 or 3 trial . OBJECTIVE To evaluate the efficacy and safety of doxorubicin plus sorafenib compared with doxorubicin alone in patients with advanced HCC and Child-Pugh A disease . DESIGN , SETTING , AND PATIENTS In a double-blind phase 2 multinational study , conducted from April 2005 to October 2006 , 96 patients ( 76 % male ; median age , 65 years [ range , 38 - 82 years ] ) with advanced HCC , Eastern Cooperative Oncology Group performance status 0 to 2 , Child-Pugh A status , and no prior systemic therapy were r and omly assigned to receive 60 mg/m(2 ) of doxorubicin intravenously every 21 days plus either 400 mg of sorafenib or placebo orally twice a day . The date of the last patient 's follow-up was April 2008 . MAIN OUTCOME MEASURE Time to progression as determined by independent review . RESULTS Following complete accrual , an unplanned early analysis for efficacy was performed by the independent data monitoring committee , so the trial was halted . The 2 patients remaining in the placebo group at that time were offered sorafenib . Based on 51 progressions , 63 deaths , and 70 events for progression-free survival , median time to progression was 6.4 months in the sorafenib-doxorubicin group ( 95 % confidence interval [ CI ] , 4.8 - 9.2 ) , and 2.8 months ( 95 % CI , 1.6 - 5 ) in the doxorubicin-placebo monotherapy group ( P = .02 ) . Median overall survival was 13.7 months ( 95 % CI , 8.9 - -not reached ) and 6.5 months ( 95 % CI , 4.5 - 9.9 ; P = .006 ) , and progression-free survival was 6.0 months ( 95 % CI , 4.6 - 8.6 ) and 2.7 months ( 95 % CI , 1.4 - 2.8 ) in these groups , respectively ( P = .006 ) . Toxicity profiles were similar to those for the single agents . CONCLUSIONS Among patients with advanced HCC , treatment with sorafenib plus doxorubicin compared with doxorubicin monotherapy result ed in greater median time to progression , overall survival , and progression-free survival . The degree to which this improvement may represent synergism between sorafenib and doxorubicin remains to be defined . The combination of sorafenib and doxorubicin is not yet indicated for routine clinical use . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00108953 BACKGROUND No effective systemic therapy exists for patients with advanced hepatocellular carcinoma . A preliminary study suggested that sorafenib , an oral multikinase inhibitor of the vascular endothelial growth factor receptor , the platelet-derived growth factor receptor , and Raf may be effective in hepatocellular carcinoma . METHODS In this multicenter , phase 3 , double-blind , placebo-controlled trial , we r and omly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib ( at a dose of 400 mg twice daily ) or placebo . Primary outcomes were overall survival and the time to symptomatic progression . Secondary outcomes included the time to radiologic progression and safety . RESULTS At the second planned interim analysis , 321 deaths had occurred , and the study was stopped . Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group ( hazard ratio in the sorafenib group , 0.69 ; 95 % confidence interval , 0.55 to 0.87 ; P<0.001 ) . There was no significant difference between the two groups in the median time to symptomatic progression ( 4.1 months vs. 4.9 months , respectively , P=0.77 ) . The median time to radiologic progression was 5.5 months in the sorafenib group and 2.8 months in the placebo group ( P<0.001 ) . Seven patients in the sorafenib group ( 2 % ) and two patients in the placebo group ( 1 % ) had a partial response ; no patients had a complete response . Diarrhea , weight loss , h and -foot skin reaction , and hypophosphatemia were more frequent in the sorafenib group . CONCLUSIONS In patients with advanced hepatocellular carcinoma , median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo . ( Clinical Trials.gov number , NCT00105443 . BACKGROUND Most cases of hepatocellular carcinoma occur in the Asia-Pacific region , where chronic hepatitis B infection is an important aetiological factor . Assessing the efficacy and safety of new therapeutic options in an Asia-Pacific population is thus important . We did a multinational phase III , r and omised , double-blind , placebo-controlled trial to assess the efficacy and safety of sorafenib in patients from the Asia-Pacific region with advanced ( unresectable or metastatic ) hepatocellular carcinoma . METHODS Between Sept 20 , 2005 , and Jan 31 , 2007 , patients with hepatocellular carcinoma who had not received previous systemic therapy and had Child-Pugh liver function class A , were r and omly assigned to receive either oral sorafenib ( 400 mg ) or placebo twice daily in 6-week cycles , with efficacy measured at the end of each 6-week period . Eligible patients were stratified by the presence or absence of macroscopic vascular invasion or extrahepatic spread ( or both ) , Eastern Cooperative Oncology Group performance status , and geographical region . R and omisation was done central ly and in a 2:1 ratio by means of an interactive voice-response system . There was no predefined primary endpoint ; overall survival , time to progression ( TTP ) , time to symptomatic progression ( TTSP ) , disease control rate ( DCR ) , and safety were assessed . Efficacy analyses were done by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00492752 . FINDINGS 271 patients from 23 centres in China , South Korea , and Taiwan were enrolled in the study . Of these , 226 patients were r and omly assigned to the experimental group ( n=150 ) or to the placebo group ( n=76 ) . Median overall survival was 6.5 months ( 95 % CI 5.56 - 7.56 ) in patients treated with sorafenib , compared with 4.2 months ( 3.75 - 5.46 ) in those who received placebo ( hazard ratio [ HR ] 0.68 [ 95 % CI 0.50 - 0.93 ] ; p=0.014 ) . Median TTP was 2.8 months ( 2.63 - 3.58 ) in the sorafenib group compared with 1.4 months ( 1.35 - 1.55 ) in the placebo group ( HR 0.57 [ 0.42 - 0.79 ] ; p=0.0005 ) . The most frequently reported grade 3/4 drug-related adverse events in the 149 assessable patients treated with sorafenib were h and -foot skin reaction ( HFSR ; 16 patients [ 10.7 % ] ) , diarrhoea ( nine patients [ 6.0 % ] ) , and fatigue ( five patients [ 3.4 % ] ) . The most common adverse events result ing in dose reductions were HFSR ( 17 patients [ 11.4 % ] ) and diarrhoea ( 11 patients [ 7.4 % ] ) ; these adverse events rarely led to discontinuation . INTERPRETATION Sorafenib is effective for the treatment of advanced hepatocellular carcinoma in patients from the Asia-Pacific region , and is well tolerated . Taken together with data from the Sorafenib Hepatocellular Carcinoma Assessment R and omised Protocol ( SHARP ) trial , sorafenib seems to be an appropriate option for the treatment of advanced hepatocellular carcinoma Although transcatheter arterial chemoembolization ( TACE ) is considered to be an effective treatment for advanced hepatocellular carcinoma ( HCC ) , it is difficult to achieve complete necrosis by TACE alone due to incomplete embolization and tumor angiogenesis . Recent studies have shown that tegafur/uracil ( UFT ) inhibits tumor angiogenesis in several cancer types . Therefore , this study was conducted to test the efficacy and toxicity of the UFT administration after TACE in advanced HCC . Thirty patients with HCC who had been treated with TACE alone more than three times and had a recurrence within 6 months were enrolled . All of the patients were treated with TACE and 28 patients were r and omly assigned to the UFT ( UFT 300 mg/day , three days after TACE , n=14 ) and control groups ( n=14 ) . The primary end point was the time to treatment failure ( TTF ) and the secondary end points were mainly the response rate and toxicity . Administration and observation were continued up to 6 months after TACE unless local recurrence was detected or serious adverse events developed . The median TTF in the control group was 87 days , whereas in the UFT group it was 127 days , thus significantly prolonged as compared to the control group ( P=0.0016 ) . Moreover , the overall response rate ( 35.7 % ) in the UFT group was significantly higher than that in the control group ( 0 % ) . As for toxicity , only 4 patients in the UFT group developed grade 1 - 2 toxicities such as ascites . Serious complications by TACE were not observed in either group . Notably , there were no increases in the serum VEGF levels in the UFT group whereas those in the control group increased significantly . In conclusion , UFT administration after TACE was an effective treatment and showed no severe adverse events . This regimen may have an adjuvant role and antiangiogenic function in advanced HCC |
901 | 22,280,914 | Imatinib in newly diagnosed older patients showed similar rate of cytogenetic and molecular responses compared to younger patients .
The aim of this review is , through the revision of published data , to highlight the fact that elderly CML patients can benefit from target therapy with limited adverse events | The impact of age as a poor prognostic factor in chronic myeloid leukemia ( CML ) has been well described .
In the interferon era , elderly patients diagnosed as having chronic phase chronic myeloid leukemia ( CP-CML ) had shorter survival compared to younger patients .
With the advent of target therapy with imatinib , several reports described improved responses in elderly late CP-CML patients treated with imatinib after IFN failure , with similar overall survival compared to younger population .
Few data are available relating elderly CML patients subset treated with second-generation TKIs after resistance/intolerance to imatinib : both nilotinib and dasatinib have demonstrated efficacy and limited toxicity profile as in younger patients . | Imatinib mesylate ( IM ) is the treatment of choice in patients with newly diagnosed chronic myeloid leukemia ( CML ) , irrespectively of their age . Nevertheless , information regarding tolerability and responses in advanced-age patients , a subgroup in which co-morbidities and other factors may influence outcome , is scarce , since they were excluded from most clinical trials . In this observational study ( ELDERGLI ) , information regarding demographics , concomitant medication , physical examination , performance status , hemogram , biochemistry , hematologic , cytogenetic and molecular responses , time to progression , adverse events ( AE ) and severe adverse events ( SAE ) were prospect ively recorded in a series of 36 elderly patients with CML , with a median age of 76.6 years . Most patients had cardiovascular co-morbidities , especially hypertension . Regarding IM toxicity , around one third of patients required treatment interruptions because of adverse events , especially hematologic toxicity ( 66 % of cases that needed dose interruptions ) . When analyzing non hematologic adverse events , the most frequent ones were superficial edemas and GI symptoms . Of note , 9 of patients experienced an infection episode during the follow-up , and 4 were diagnosed during the study period of another type of cancer . Finally , cardiovascular events were reported in 7 patients , most of them with prior cardiovascular risk factors . Regarding responses , after 12 months of imatinib therapy , the rate of complete hematologic response ( CHR ) , complete cytogenetic response ( CCyR ) and major molecular response ( MMolR ) were 89 % , 72 % and 55 % respectively . In summary , IM display , in advanced-age patients with chronic phase CML , an efficacy and safety profile comparable to younger patients Gender-related aspects in chronic myeloid leukemia ( CML ) have not been studied well . We therefore analyzed 856 patients with Ph/BCR-ABL-positive CML from the German r and omized CML- studies I ( interferon α ( IFN ) vs hydroxyurea ( HU ) vs busulfan ) and II ( IFN+HU vs HU alone ) . The median observation time was 8.6 years . A total of 503 patients ( 59 % ) were male . Female patients were older ( 51 vs 46 years ; P<0.0001 ) , presented with lower hemoglobin ( 11.7 vs 12.5 g/dl ; P<0.0001 ) , higher platelet counts ( 459 vs 355 × 109/l ; P<0.0001 ) , smaller spleen size ( 3 vs 4 cm below costal margin ; P=0.0097 ) , a lower rate of additional cytogenetic aberrations ( 9 vs 15 % ; P=0.018 ) and a less favorable risk profile ( P=0.036 ) . The transplantation rate was 14 % for female ( n=48 ) and 22 % for male patients ( n=113 ) . Median survival was longer in female patients ( 58 vs 49 months ; P=0.035 ) mainly attributable to better survival in the low- and intermediate-risk groups and , independent from risk groups , in the HU group . These results were confirmed by matched-pair analyses based on German population data ( n=496 , 59 vs 45 months ; P=0.0006 ) . This is the first analysis of gender aspects in CML using r and omized trials . It demonstrates the relevance of analyses of gender differences in CML and in malignant disease at large The median age of chronic myeloid leukemia ( CML ) patients is ~60 years , and age is still considered an important prognostic factor , included in Sokal and EURO risk scores . However , few data are available about the long-term outcome of older patients treated with imatinib ( IM ) frontline . We analyzed the relationship between age and outcome in 559 early chronic-phase CML patients enrolled in 3 prospect i ve clinical trials of Gruppo Italiano Malattie Ematologiche dell'Adulto CML Working Party , treated frontline with IM , with a median follow-up of 60 months . There were 115 older patients ( ≥ 65 years ; 21 % ) . The complete cytogenetic and major molecular response rates were similar in the 2 age groups . In older patients , event-free survival ( 55 % vs 67 % ) , failure-free survival ( 78 % vs 92 % ) , progression-free survival ( 62 % vs 78 % ) , and overall survival ( 75 % vs 89 % ) were significantly inferior ( all P < .01 ) because of a higher proportion of deaths that occurred in complete hematologic response , therefore unrelated to CML progression ( 15 % vs 3 % , P < .0001 ) . The outcome was similar once those deaths were censored . These data show that response to IM was not affected by age and that the mortality rate linked to CML is similar in both age groups . This trial was registered at www . clinical trials.gov as # NCT00514488 and # NCT00510926 PURPOSE To determine the response rate to interferon-alpha ( IFN-alpha ) in patients with chronic myelogenous leukemia ( CML ) aged 60 years and older . PATIENTS AND METHODS Patients with CML aged 60 years and older included in all protocol s with INF-alpha therapy for chronic phase CML at the M.D. And erson Cancer Center were analyzed . They were treated with human leukocyte or recombinant human IFN-alpha 5x10(6 ) U/m2 daily alone or in combination with hydroxyurea or IFN gamma . The clinical characteristics of the patients were analyzed and their hematologic and cytogenetic responses to IFN-alpha and survival from the initiation of therapy were determined . Results were compared with those of younger patients treated in the same protocol s. Treatment-related toxicity was also analyzed . RESULTS Thirty-five of 274 ( 13 % ) patients included in trials of IFN-alpha-based regimens for CML were 60 years and older . Older patients had a higher percentage of bone marrow blasts ( P = 0.04 ) and basophils ( P = 0.09 ) than younger patients . Sixty-nine percent achieved a complete hematologic remission with IFN-alpha therapy , and 51 % had a cytogenetic response , which was major in 26 % and complete ( Philadelphia chromosome-positive cells = 0 % ) in 20 % , Their median survival was 64 months , and the estimated 5-year survival rate was 62 % . These results were not different from those in younger patients . Twenty-two patients ( 63 % ) had at least grade 2 toxicity requiring dose adjustment . The most frequent side effects were neurotoxicity in 31 % and chronic fatigue in 29 % . CONCLUSIONS Patients with CML 60 years of age and older respond well to IFN-alpha therapy , but experience more toxicity . This therapy should be considered for these patients if they are otherwise in good condition , with careful attention to IFN-alpha toxicity and its management Thirty-five patients with Ph+ CML aged more than 60 years were treated with imatinib . Twenty-four patients ( group A ) were in late chronic phase ( CP ) and eleven patients ( group B ) were in accelerated/blastic phase ( AP/BP ) . In group A , complete haematological response ( CHR ) was achieved by all patients ; seventeen patients ( 70.8 % ) attained a complete cytogenetic response ( CCR ) , one ( 4.1 % ) attained a partial CR , one ( 4.1 % ) a minor CR ( Ph+ 70 % ) and five ( 21 % ) were resistant ( Ph+ 100 % ) , toxicity was mild : seven patients had a transient cytopenia , three a skin reaction , one a moderate oedema and one muscular pain . After a median follow-up of 15 months , 1 patient died in progression and 23 patients are alive ( 2 in BP and 21 in persisting response ) . In group B , one patient died after 3 months in aplastic phase from sepsis , three patients were resistant and seven patients ( 63.7 % ) achieved CHR ; of these , four obtained CCR . After a median follow-up of 17 months , 4 patients have died from progressive disease , 6 are alive ; 1 in AP and 5 in CHR ( 4 of them being in CCR ) . Present data indicate that imatinib is safe also in elderly with clinical results as good as in younger patients Chronic myeloid leukemia ( CML ) in older patients has not been studied well . To assess the long-term outcome of older patients with Philadelphia- and /or BCR-ABL-positive CML , 199 patients aged > /=60 years representing 23 % of 856 patients enrolled in the German r and omized CML- studies I ( interferon alpha ( IFN ) vs hydroxyurea ( HU ) vs busulfan ( BU ) and II ( IFN+HU vs HU alone ) were analyzed after a median observation time of 7 years . In all , 45 patients were treated with Bu , 63 with HU , and 91 with IFN . The 5-year survival was 38 % in patients > /=60 years and 47 % in patients < 60 years ( P<0.001 ) . Whereas 5-year survival in chemotherapy-treated older patients was inferior to that in younger patients ( 33 vs 46 % , P=0.006 for HU and 29 vs 38 % , P=0.042 for Bu ) , no significant survival difference could be verified in IFN-treated patients ( 46 vs 53 % , P=0.077 ) . Calculation of age-adjusted , relative survival confirmed these results . Adverse effects of IFN were similar in both age groups , but IFN dosage to achieve treatment goals was lower in older patients . We conclude that the course of CML is not different in the elderly . They require lower IFN doses , achieve the same hematologic and cytogenetic response rates and the same survival advantage at comparable toxicity To assess the effect of age on response and compliance to treatment in patients with chronic myeloid leukemia ( CML ) we performed a sub- analysis within a phase II trial of the GIMEMA CML Working Party ( CML/002/STI571 ) . Since the WHO cut-off age to define an older patient is 65 years , among the 284 patients considered , we identified 226 ( 80 % ) younger patients ( below 65 years ) and 58 ( 20 % ) older patients ( above 65 years ) before starting imatinib . Response rates ( hematologic and cytogenetic ) were lower in the older age group but the probabilities of progression-free survival and overall survival ( median observation time 3 years ) were the same . Moreover , among complete cytogenetic responders , no differences were found in the level of molecular response between the two age groups . As might be expected , older patients experienced more adverse events , both hematologic and non-hematologic : this worsened compliance did not , however , prevent a long-term outcome similar to that of younger patients |
902 | 27,490,698 | However , neutropenia was generally transient and had a benign clinical outcome , after vaccination with either multiple novel c and i date s or well-known licensed vaccines .
Additionally , the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees . | BACKGROUND In the context of early vaccine trials aim ed at evaluating the safety profile of novel vaccines , abnormal haematological values , such as neutropenia , are often reported .
It is therefore important to evaluate how these trials should be planned not to miss potentially important safety signals , but also to underst and the implication s and the clinical relevance . | Background Gene-based vaccination using prime/boost regimens protects animals and humans against malaria , inducing cell-mediated responses that in animal models target liver stage malaria parasites . We tested a DNA prime/adenovirus boost malaria vaccine in a Phase 1 clinical trial with controlled human malaria infection . Methodology /Principal Findings The vaccine regimen was three monthly doses of two DNA plasmids ( DNA ) followed four months later by a single boost with two non-replicating human serotype 5 adenovirus vectors ( Ad ) . The constructs encoded genes expressing P. falciparum circumsporozoite protein ( CSP ) and apical membrane antigen-1 ( AMA1 ) . The regimen was safe and well-tolerated , with mostly mild adverse events that occurred at the site of injection . Only one AE ( diarrhea ) , possibly related to immunization , was severe ( Grade 3 ) , preventing daily activities . Four weeks after the Ad boost , 15 study subjects were challenged with P. falciparum sporozoites by mosquito bite , and four ( 27 % ) were sterilely protected . Antibody responses by ELISA rose after Ad boost but were low ( CSP geometric mean titer 210 , range 44–817 ; AMA1 geometric mean micrograms/milliliter 11.9 , range 1.5–102 ) and were not associated with protection . Ex vivo IFN-γ ELISpot responses after Ad boost were modest ( CSP geometric mean spot forming cells/million peripheral blood mononuclear cells 86 , range 13–408 ; AMA1 348 , range 88–1270 ) and were highest in three protected subjects . ELISpot responses to AMA1 were significantly associated with protection ( p = 0.019 ) . Flow cytometry identified predominant IFN-γ mono-secreting CD8 + T cell responses in three protected subjects . No subjects with high pre-existing anti-Ad5 neutralizing antibodies were protected but the association was not statistically significant . Significance The DNA/Ad regimen provided the highest sterile immunity achieved against malaria following immunization with a gene-based subunit vaccine ( 27 % ) . Protection was associated with cell-mediated immunity to AMA1 , with CSP probably contributing . Substituting a low seroprevalence vector for Ad5 and supplementing CSP/AMA1 with additional antigens may improve protection . Trial Registration Clinical Trials.govNCT00870987 rDEN2/4Δ30(ME ) is an attenuated chimeric dengue virus in which the prM and E structural proteins of the DEN4 c and i date vaccine rDEN4∆30 have been replaced by those of the prototypic DEN2 NGC virus . rDEN2/4Δ30(ME ) was evaluated at a dose of 1,000 PFU in 20 healthy dengue-naïve adult volunteers . Eight volunteers received placebo . Volunteers were monitored closely for adverse events and serum was collected for determination of the level and duration of viremia and neutralizing antibody response . The vaccine was well tolerated by all volunteers . The most common adverse events observed were a transient asymptomatic rash and mild neutropenia . All vaccinees seroconverted to DEN2 and maintained significant antibody titers throughout the six-month trial duration . Eleven vaccinees had vaccine virus recovered from the blood during the study . RNA derived from virus isolates obtained from viremic volunteers was sequenced for confirmation of retention of the ∆30 mutation in the 3 ´ UTR . The Δ30 mutation remained unchanged in each isolate , confirming the stability of the Δ30 mutation . Further evaluation of this vaccine in a tetravalent formulation is warranted Tuberculosis ( TB ) is a global public health problem exacerbated by the HIV epidemic . Here we evaluate a c and i date TB vaccine , MVA85A , in a Phase I study in HIV-infected adults in Senegal . 24 patients were enrolled : Group 1∶12 , antiretroviral therapy ( ART ) naïve , adults , with CD4 counts > 300 and HIV RNA load < 100 000 copies/ml . Group 2∶12 adults , stable on ART , with CD4 counts > 300 , and an undetectable HIV RNA load . Safety was evaluated by occurrence of local and systemic adverse events ( AEs ) and by monitoring of CD4 count , HIV RNA load , haematology and biochemistry . Immunogenicity was evaluated by ex-vivo interferon-gamma ELISpot assay . 87.7 % of AEs were mild ; 11.6 % were moderate ; and 0.7 % were severe . 29.2 % of AEs were systemic ; 70.8 % were expected local AEs . There were no vaccine-related Serious Adverse Events ( SAEs ) or clinical ly significant effects on HIV RNA load or CD4 count . In ART naive subjects , the first MVA85A immunisation induced a significant immune response at 1 and 4 weeks post-immunisation , which contracted to baseline by 12 weeks . Durability of immunogenicity in subjects on ART persisted out to 24 weeks post-vaccination . A second dose of MVA85A at 12 months enhanced immunogenicity in ART naïve subjects . Subjects on ART had higher responses after the first vaccination compared with ART naïve subjects ; responses were comparable after 2 immunisations . In conclusion , MVA85A is well-tolerated and immunogenic in HIV-infected subjects in Senegal . A two dose regimen in ART naïve subjects is comparable in immunogenicity to a single dose in subjects on ART . Clinical trials.gov trial identifier NCT00731471 Background Inhibition of parasite growth is a major objective of blood-stage malaria vaccines . The in vitro assay of parasite growth inhibitory activity ( GIA ) is widely used as a surrogate marker for malaria vaccine efficacy in the down- selection of c and i date blood-stage vaccines . Here we report the first study to examine the relationship between in vivo Plasmodium falciparum growth rates and in vitro GIA in humans experimentally infected with blood-stage malaria . Methods In this phase I/IIa open-label clinical trial five healthy malaria-naive volunteers were immunised with AMA1/C1-Alhydrogel+CPG 7909 , and together with three unvaccinated controls were challenged by intravenous inoculation of P. falciparum infected erythrocytes . Results A significant correlation was observed between parasite multiplication rate in 48 hours ( PMR ) and both vaccine-induced growth-inhibitory activity ( Pearson r = −0.93 [ 95 % CI : −1.0 , −0.27 ] P = 0.02 ) and AMA1 antibody titres in the vaccine group ( Pearson r = −0.93 [ 95 % CI : −0.99 , −0.25 ] P = 0.02 ) . However immunisation failed to reduce overall mean PMR in the vaccine group in comparison to the controls ( vaccinee 16 fold [ 95 % CI : 12 , 22 ] , control 17 fold [ CI : 0 , 65 ] P = 0.70 ) . Therefore no impact on pre-patent period was observed ( vaccine group median 8.5 days [ range 7.5–9 ] , control group median 9 days [ range 7–9 ] ) . Conclusions Despite the first observation in human experimental malaria infection of a significant association between vaccine-induced in vitro growth inhibitory activity and in vivo parasite multiplication rate , this did not translate into any observable clinical ly relevant vaccine effect in this small group of volunteers . Trial Registration Clinical Trials.gov [ NCT00984763 Background : Quadrivalent meningococcal polysaccharide conjugate vaccine ( MCV4 ) is routinely recommended for healthy youth in the United States , but there are no data about its use in HIV-infected people . Methods : P1065 is a Phase I/II trial of MCV4 safety and immunogenicity in HIV-infected children and youth performed at 27 US sites of the IMPAACT network . All youth ( 11–24 years old ) received 1 dose of open-label MCV4 at entry . St and ardized question naires were used to evaluate safety . Baseline protective immunity was defined as rabbit serum bactericidal antibody ( rSBA ) titer ≥1:128 . Immunogenic response was defined as a ≥4-fold rise in rSBA against each meningococcal serogroup . Multivariable logistic regression analysis was used to evaluate the association of demographic and clinical characteristics on immunogenic response to serogroup C. Results : Among 319 subjects who received MCV4 , 10 ( 3.1 % ) reported immediate adverse events which were local and mild , and 7 ( 2.2 % ) experienced Grade ≥3 adverse events , unrelated to vaccine . The 305 subjects with serologic data had a median age of 17 years and were 59 % male , 50 % Black , and 38 % Latino . Subjects were stratified by entry CD4 % : 12 % , CD4 < 15 % ; 40 % , 15 % to 24 % ; and 48 % , ≥25 % . Baseline protective immunity varied by serogroup : A , 41 % ; C , 11 % ; W-135 , 15 % ; Y , 35 % The immunogenic response rates to serogroups A , C , W-135 , and Y were 68 % , 52 % , 73 % , and 63 % , respectively . In multivariable logistic regression models , lower entry CD4 % , higher entry viral load , and CDC Class B/C diagnosis were associated with significantly lower odds of response to serogroup C. Conclusion : Many HIV-infected youth naturally acquire meningococcal immunity . MCV4 is safe and immunogenic in HIV-infected youth , but response rates are lower than in healthy youth , particularly for those with more advanced HIV clinical , immunologic , and virologic status Background Ad35.CS.01 is a pre-erythrocytic malaria c and i date vaccine . It is a codon optimized nucleotide sequence representing the P. falciparum circumsporozoite ( CS ) surface antigen inserted in a replication deficient Adenovirus 35 backbone . A Phase 1a trial has been conducted in the USA in naïve adults and showed that the vaccine was safe . The aim of this study is to assess the safety and immunogenicity of ascending dosages in sub Saharan Africa . Methods A double blind , r and omized , controlled , dose escalation , phase Ib trial was conducted in a rural area of Balonghin , the Saponé health district ( Burkina Faso ) . Forty-eight healthy adults aged 18 - 45 years were r and omized into 4 cohorts of 12 to receive three vaccine doses ( day 0 , 28 and 84 ) of 109 , 1010 , 5X1010 , 1011 vp of Ad35.CS.01 or normal saline by intra muscular injection . Subjects were monitored carefully during the 14 days following each vaccination for non serious adverse events . Severe and serious adverse events were collected throughout the participant study duration ( 12 months from the first vaccination ) . Humoral and cellular immune responses were measured on study days 0 , 28 , 56 , 84 , 112 and 140 . Results Of the forty-eight subjects enrolled , forty-four ( 91.7 % ) received all three scheduled vaccine doses . Local reactions , all of mild severity , occurred in thirteen ( 27.1 % ) subjects . Severe ( grade 3 ) laboratory abnormalities occurred in five ( 10.4 % ) subjects . One serious adverse event was reported and attributed to infection judged unrelated to vaccine . The vaccine induced both antibody titers and CD8 T cells producing IFNγ and TNFα with specificity to CS while eliciting modest neutralizing antibody responses against Ad35 . Conclusion Study vaccine Ad35.CS.01 at four different dose levels was well-tolerated and modestly immunogenic in this population . These results suggest that Ad35.CS.01 should be further investigated for preliminary efficacy in human challenge models and as part of heterologous prime-boost vaccination strategies . Trial Registration Clinical Trials.gov NCT01018459 http:// clinical Highlights • MVA.HIVA vaccine was tested for the first time in HIV-1-exposed infants in Africa.• PedVacc 002 had 99 % retention of infants over 48 weeks of follow-up.• MVA.HIVA was safe , but not sufficiently immunogenic.• MVA.HVA did not interfere with routine childhood vaccines except for induction of HBV antibodies.• MVA is well suited as a vaccine vector for infants under 1 year of age Four serotypes of monovalent live attenuated dengue virus vaccine c and i date s were tested for reactogenicity and immunogenicity in 49 flavivirus non-immune adult human volunteers . The four monovalent c and i date s were then combined into a tetravalent formulation and given to another 10 volunteers . Neutralizing antibody seroconversion rates after a single-dose monovalent vaccination ranged from 53 % to 100 % . Solicited reactogenicity was scored by each volunteer . A composite index , the Reactogenicity Index , was derived by these self-reported scores . Reactogenicity differed among the four serotype c and i date s with serotype-1 associated with the most vaccine related side effects . A second dose of monovalent vaccines at either 30 days or 90 days was much less reactogenic but did not significantly increase seroconversion rates . Seroconversion rates in the 10 volunteers who received a single dose of tetravalent vaccine ranged from 30 % to 70 % among the four serotypes . Similar to the monovalent vaccines , a second dose of the tetravalent vaccine at one month was less reactogenic and did not increase seroconversion . A third dose of the tetravalent vaccine at four months result ed in three of four volunteers with trivalent or tetravalent high-titer neutralizing antibody responses Neisseria meningitidis serogroup B ( MnB ) is a significant cause of invasive meningococcal disease , but no broadly protective vaccine is yet approved . We assessed the safety and immunogenicity of a bivalent MnB vaccine composed of lipi date d subfamily A and B variants of recombinant LP2086 ( rLP2086 , also known as factor H binding protein , fHBP ) . Forty-eight adults , ages 18–40 y , were r and omized to receive 60 , 120 or 200 μg of the bivalent rLP2086 vaccine or control at 0 , 2 and 6 mo . Immunogenicity was assessed by rLP2086-specific immunoglobulin G ( IgG ) geometric mean titers for subfamily A and B proteins . Safety was determined by laboratory assessment s of blood and urine and by reporting of solicited and unsolicited adverse events ( AEs ) . The bivalent rLP2086 vaccine elicited high IgG titers following the second and third vaccination at all dose levels . In each of the four study arms , 11 of the 12 participating subjects reported ≥ 1 AE , and no serious AEs were reported . Local and systemic reactions were mainly mild to moderate . Laboratory abnormalities ( including increased sodium , decreased neutrophils , and proteinuria ) were not associated with clinical events and were not considered to be related to the study vaccine . Vaccinations were generally well-tolerated . Strong IgG antibody responses and the absence of clinical ly significant laboratory abnormalities support further development of the bivalent rLP2086 vaccine ( www . clinical trials.gov ; identifier : NCT00879814 ) WNV has become the leading vector-borne cause of meningoencephalitis in the United States . Although the majority of WNV infections result in asymptomatic illness , approximately 20 % of infections result in West Nile fever and 1 % in West Nile neuroinvasive disease ( WNND ) , which causes encephalitis , meningitis , or flaccid paralysis . The elderly are at particular risk for WNND , with more than half the cases occurring in persons older than sixty years of age . There is no licensed treatment for WNND , nor is there any licensed vaccine for humans for the prevention of WNV infection . The Laboratory of Infectious Diseases at the National Institutes of Health has developed a recombinant live attenuated WNV vaccine based on chimerization of the wild-type WNV NY99 genome with that of the live attenuated DENV-4 c and i date vaccine rDEN4Δ30 . The genes encoding the prM and envelope proteins of DENV-4 were replaced with those of WNV NY99 and the result ant virus was design ated rWN/DEN4Δ30 . The vaccine was evaluated in healthy flavivirus-naïve adult volunteers age 18 - 50 years in two separate studies , both of which are reported here . The first study evaluated 10³ or 10⁴ PFU of the vaccine given as a single dose ; the second study evaluated 10⁵ PFU of the vaccine given as two doses 6 months apart . The vaccine was well-tolerated and immunogenic at all three doses , inducing seroconversion to WNV NY99 in 74 % ( 10³ PFU ) , 75 % ( 10⁴ PFU ) , and 55 % ( 10⁵ PFU ) of subjects after a single dose . A second 10⁵ PFU dose of rWN/DEN4Δ30 given 6 months after the first dose increased the seroconversion rate 89 % . Based on the encouraging results from these studies , further evaluation of the c and i date vaccine in adults older than 50 years of age is planned The rDEN4Delta30 - 200,201 is a live attenuated DENV-4 vaccine c and i date specifically design ed to further attenuate the rDEN4Delta30 parent virus . In the present study , 28 healthy adult volunteers were r and omized to receive either 10(5 ) plaque-forming unit ( PFU ) of vaccine ( 20 ) or placebo ( 8) as a single subcutaneous injection . Volunteers were evaluated for safety every other day for 16 days . Serum neutralizing antibody titer against DEN4 was determined at study day 28 , 42 , and 180 . The vaccine infected all vaccinees and was well tolerated without inducing alanine aminotransferase ( ALT ) elevations . Although virus was not recovered from the serum of any vaccinee , moderate levels of neutralizing antibody were induced in all volunteers . Thus the restricted replication of rDEN4Delta30 - 200,201 previously documented in animal models was confirmed in humans . The rDEN4Delta30 - 200,201 is a promising c and i date and can be considered for inclusion in a tetravalent dengue virus ( DENV ) vaccine A Phase 1 study was conducted in 24 malaria naïve adults to assess the safety and immunogenicity of the recombinant protein vaccine apical membrane antigen 1-Combination 1 (AMA1-C1)/Alhydrogel with CPG 7909 in two different formulations ( phosphate buffer and saline ) , and given at two different dosing schedules , 0 and 1 month or 0 and 2 months . Both formulations were well tolerated and frequency of local reactions and solicited adverse events was similar among the groups . Peak antibody levels in the groups receiving CPG 7909 in saline were not significantly different than those receiving CPG 7909 in phosphate . Peak antibody levels in the groups vaccinated at a 0,2 month interval were 2.52-fold higher than those vaccinated at a 0,1 month interval ( p=0.037 , 95 % CI 1.03 , 4.28 ) . In vitro growth inhibition followed the antibody level : median inhibition was 51 % ( 0,1 month interval ) versus 85 % ( 0,2 month interval ) in antibody from sample s taken 2 weeks post-second vaccination ( p=0.056 ) Background Models of immunity to malaria indicate the importance of CD8 + T cell responses for targeting intrahepatic stages and antibodies for targeting sporozoite and blood stages . We design ed a multistage adenovirus 5 (Ad5)-vectored Plasmodium falciparum malaria vaccine , aim ing to induce both types of responses in humans , that was tested for safety and immunogenicity in a Phase 1 dose escalation trial in Ad5-seronegative volunteers . Methodology /Principal Findings The NMRC-M3V-Ad-PfCA vaccine combines two adenovectors encoding circumsporozoite protein ( CSP ) and apical membrane antigen-1 ( AMA1 ) . Group 1 ( n = 6 ) healthy volunteers received one intramuscular injection of 2 × 10∧10 particle units ( 1 × 10∧10 each construct ) and Group 2 ( n = 6 ) a five-fold higher dose . Transient , mild to moderate adverse events were more pronounced with the higher dose . ELISpot responses to CSP and AMA1 peaked at 1 month , were higher in the low dose ( geomean CSP = 422 , AMA1 = 862 spot forming cells/million ) than in the high dose ( CSP = 154 , p = 0.049 , AMA1 = 423 , p = 0.045 ) group and were still positive at 12 months in a number of volunteers . ELISpot depletion assays identified dependence on CD4 + or on both CD4 + and CD8 + T cells , with few responses dependent only on CD8 + T cells . Intracellular cytokine staining detected stronger CD8 + than CD4 + T cell IFN-γ responses ( CSP p = 0.0001 , AMA1 p = 0.003 ) , but similar frequencies of multifunctional CD4 + and CD8 + T cells secreting two or more of IFN-γ , TNF-α or IL-2 . Median fluorescence intensities were 7–10 fold higher in triple than single secreting cells . Antibody responses were low but trended higher in the high dose group and did not inhibit growth of cultured P. falciparum blood stage parasites . Significance As found in other trials , adenovectored vaccines appeared safe and well-tolerated at doses up to 1 × 10∧11 particle units . This is the first demonstration in humans of a malaria vaccine eliciting strong CD8 + T cell IFN-γ responses . Trial Registration Clinical Trials.gov CONTEXT Group A streptococcal infections and their sequelae represent a global health problem . Recent advances have allowed previous obstacles associated with group A streptococcal vaccine development to be overcome . OBJECTIVE To preliminarily evaluate the safety and immunogenicity of ascending doses of a recombinant fusion peptide group A streptococcal vaccine containing N-terminal M protein fragments from serotypes 1 , 3 , 5 , 6 , 19 , and 24 in healthy volunteers . DESIGN , SETTING , AND PARTICIPANTS An open-label , uncontrolled , dose-ascending phase 1 vaccine trial of 28 healthy adult volunteers aged 18 to 50 years recruited from the metropolitan area of Baltimore , Md , between October 5 , 1999 , and February 26 , 2003 , using newspaper advertisements and posted fliers , and evaluated in the outpatient facility of the Center for Vaccine Development . INTERVENTIONS Each volunteer received 3 spaced intramuscular injections of 50 microg ( n = 8) , 100 micro g ( n = 10 ) , or 200 microg ( n = 10 ) of hexavalent group A streptococcal vaccine formulated with aluminum hydroxide into the deltoid muscle of alternating arms . MAIN OUTCOME MEASURES Assessment s of clinical safety , including elicitation of antibodies that cross-react with host tissues , and immunogenicity as measured by enzyme-linked immunosorbent assay ( ELISA ) and assays of opsonophagocytic- and bactericidal-antibody responses . RESULTS One year of intensive follow-up revealed the vaccine to be well tolerated . There was no evidence of tissue cross-reactive antibodies or immunological complications . At the highest ( 200 microg ) dose , vaccination elicited significant increases in geometric mean antibody levels to all 6 component M antigens by ELISA ( all P<.01 ) and to 5 of 6 M types in the opsonophagocytosis assay ( all P<.05 ) . In addition , postvaccination increases in serum bactericidal activity of at least 30 % were observed in 31 ( 55 % ) of 56 assays . CONCLUSION These results provide the first evidence in humans that a hybrid fusion protein is a feasible strategy for evoking type-specific opsonic antibodies against multiple serotypes of group A streptococcus without eliciting antibodies that cross-react with host tissues , which represents a critical step in the development of a vaccine To determine the safety of 2 c and i date vaccines against human immunodeficiency virus type 1 ( HIV-1 ) , a r and omized , placebo-controlled , multicenter trial compared low , medium , and high doses of the vaccines or an adjuvant among infants born to HIV-infected women . No local or systemic reactions of grade 2 or greater were reported 48 h after the subjects underwent immunization . Grade 3 or 4 chemistry toxicities occurred in 5 ( 3 % ) and grade 3 or 4 hematologic toxicities in 17 ( 11 % ) of 154 vaccinated subjects ( not significantly different from 29 adjuvant recipients ) . CD4(+ ) cell percentages of < or = 20 % occurred at least once in 9 vaccinated subjects and 1 control subject . Sustained CD4(+ ) cell percentages of < or = 20 % occurred in 4 HIV-infected children . Fourteen infants ( 8 % ) were confirmed to be HIV-infected ; median CD4(+ ) cell counts among these children were 2074 , 1674 , 1584 , and 821 cells/mm(3 ) at birth and weeks 24 , 52 , and 104 , respectively . Thus , both vaccines were safe and well tolerated in neonates , and there was no evidence of accelerated immunologic decline in HIV-infected infants BACKGROUND . Sanofi Pasteur has developed a tetravalent dengue vaccine ( TDV ) against the world 's most common arbovirus infection . METHODS . We assessed the safety and immunogenicity of the TDV in healthy adults r and omized into 2 groups . Group 1 received 3 TDV injections at months 0 , 4 , and 12 - 15 ; group 2 received saline placebo at month 0 and then 2 TDV injections at months 4 and 12 - 15 . Adverse events were recorded , and biological parameters and viremia levels were measured . Neutralizing antibodies against 4 World Health Organization ( WHO ) reference strains were measured before and after vaccinations . RESULTS . A total of 33 participants were enrolled in each group . Demographic characteristics were comparable . No vaccine-related serious adverse event was reported . The most common systemic reactions were headache , malaise , and myalgia . Low viremia levels were detected , mainly of serotype 4 . Immune response increased with successive vaccine doses . All participants seroconverted against all 4 serotypes after receiving 3 doses at 0 , 4 , and 12 - 15-months , and almost all seroconverted after 2 doses given 8 - 11 months apart . CONCLUSIONS . Sanofi Pasteur 's TDV was well tolerated and induced full seroconversion against all WHO reference strain serotypes after 3 doses Background : Human immunodeficiency virus (HIV)-infected children are at increased risk of meningococcal infection and poor response to quadrivalent meningococcal conjugate vaccine ( MCV4 ) , but MCV4 has not been studied in preadolescent HIV-infected children . Methods : The P1065 trial enrolled 2- to 10-year-old HIV-infected children with CD4 ≥25 % to receive MCV4 at entry and at week 24 . Rates of response ( ≥4-fold increase in rabbit serum bactericidal antibody ) against each meningococcal serogroup ( A , C , Y , W-135 ) , geometric mean titers , and rates of seroprotection ( rabbit serum bactericidal antibody titer ≥1:128 ) were determined from sera obtained at entry and weeks 4 , 24 , 28 , and 72 . Adverse events were assessed for 6 weeks after each MCV4 dose . Results : At entry , 47 % of the 59 participants were male , 56 % black , 31 % Latino , median age was 6 years , 88 % were receiving antiretroviral therapy , and 75 % had viral load < 400 copies/mL. There were no serious adverse events within 6 weeks after MCV4 doses ; all vaccination reactions were mild . Response after a single MCV4 dose was high to serogroup A ( 92 % ) and W-135 ( 98 % ) ; responses improved after a second dose for serogroup C ( 43%–80 % ) ( P < 0.0001 ) and Y ( 76%–84 % ) ( P = 0.38 ) . By week 72 , seroprotection rates were 93 % , 91 % , 78 % , and 46 % for serogroups W-135 , Y , A , and C , respectively . Conclusions : Two doses of MCV4 were safe and immunogenic in 2- to 10-year-old HIV-infected children . The second dose increased the proportion of children who made a response to serogroup C. Seroprotection waned substantially for serogroups A and C within 1 year of last MCV4 dose Dengue is an emerging infectious disease that has become the most important arboviral infection worldwide . There are four serotypes of dengue virus , DENV-1 , DENV-2 , DENV-3 , and DENV-4 , each capable of causing the full spectrum of disease . rDEN1Δ30 is a live attenuated investigational vaccine for the prevention of DENV-1 illness and is also a component of an investigational tetravalent DENV vaccine currently in Phase I evaluation . A single subcutaneous dose of rDEN1Δ30 was previously shown to be safe and immunogenic in healthy adults . In the current r and omized placebo-controlled trial , 60 healthy flavivirus-naive adults were r and omized to receive 2 doses of rDEN1Δ30 ( N = 50 ) or placebo ( N = 10 ) , either on study days 0 and 120 ( cohort 1 ) or 0 and 180 ( cohort 2 ) . We sought to evaluate the safety and immunogenicity of this c and i date vaccine in 50 additional vaccinees and to test whether the humoral immune response could be boosted by a second dose administered 4 or 6 months after the first dose . The first dose of vaccine was well tolerated , infected 47/50 vaccinees and induced seroconversion in 46/50 vaccinees . Irrespective of dosing interval , the second dose of vaccine was also well tolerated but did not induce any detectable viremia or ≥4-fold rise in serum neutralizing antibody titer . Only five subjects had an anamnestic antibody response detectable by ELISA following a second dose of vaccine , demonstrating that the vaccine induced sterilizing humoral immunity in most vaccinees for at least six months following primary vaccination . The promising safety and immunogenicity profile of this vaccine confirms its suitability for inclusion in a tetravalent dengue vaccine Background : The live attenuated DEN1 vaccine c and i date virus rDEN1Δ30 has been evaluated in pre clinical animal models and found to be attenuated and immunogenic . These promising pre clinical studies have identified rDEN1Δ30 as a c and i date DEN1 vaccine virus for further testing in a human Phase I clinical trial . Methods : rDEN1Δ30 at a dose of 103 pfu was administered as a single inoculation to twenty healthy adult volunteers . Eight additional volunteers received placebo . Volunteers were monitored closely for adverse events and serum was collected on study days 0 , 28 , 42 , and 180 for determination of neutralizing antibody titer . Results : The vaccine was well tolerated by the vaccinees . The most common adverse events observed were a transient asymptomatic rash in 40 % of vaccinees and a mild neutropenia in 45 % of vaccinees . No vaccinee developed a dengue-like illness . The vaccine was highly infectious and immunogenic with 95 % of vaccinees developing a ? 4-fold rise in serum neutralizing antibody titer against DEN1 that persisted throughout the six month duration of the trial . Conclusions : The rDEN1Δ30 vaccine is safe and induced a potent and durable antibody response against DEN1 . It is a promising vaccine c and i date for inclusion in a tetravalent dengue vaccine formulation BACKGROUND Development of live attenuated influenza vaccines ( LAIV ) against avian viruses with p and emic potential is an important public health strategy . METHODS AND FINDINGS We performed open-label trials to evaluate the safety , infectivity , and immunogenicity of H5N1 VN 2004 AA ca and H5N1 HK 2003 AA ca . Each of these vaccines contains a modified H5 hemagglutinin and unmodified N1 neuraminidase from the respective wild-type ( wt ) parent virus and the six internal protein gene segments of the A/Ann Arbor/6/60 cold-adapted ( ca ) master donor virus . The H5N1 VN 2004 AA ca vaccine virus was evaluated at dosages of 10(6.7 ) TCID(50 ) and 10(7.5 ) TCID(50 ) , and the H5N1 HK 2003 AA ca vaccine was evaluated at a dosage of 10(7.5 ) TCID(50 ) . Two doses were administered intranasally to healthy adults in isolation at 4 - 8 week intervals . Vaccine safety was assessed through daily examinations and infectivity was assessed by viral culture and by realtime reverse transcription-polymerase chain reaction testing of nasal wash ( NW ) specimens . Immunogenicity was assessed by measuring hemagglutination-inhibition ( HI ) antibodies , neutralizing antibodies , and IgG or IgA antibodies to recombinant (r)H5 VN 2004 hemagglutinin ( HA ) in serum or NW . Fifty-nine participants were enrolled : 21 received 10(6.7 ) TCID(50 ) and 21 received 10(7.5 ) TCID(50 ) of H5N1 VN 2004 AA ca and 17 received H5N1 HK 2003 AA ca . Shedding of vaccine virus was minimal , as were HI and neutralizing antibody responses . Fifty-two percent of recipients of 10(7.5 ) TCID(50 ) of H5N1 VN 2004 AA ca developed a serum IgA response to rH5 VN 2004 HA . CONCLUSIONS The live attenuated H5N1 VN 2004 and HK 2003 AA ca vaccines bearing avian H5 HA antigens were very restricted in replication and were more attenuated than seasonal LAIV bearing human H1 , H3 or B HA antigens . The H5N1 AA ca LAIV elicited serum ELISA antibody but not HI or neutralizing antibody responses in healthy adults . ( Clinical Trials.gov Identifiers : NCT00347672 and NCT00488046 ) Sixteen dose formulations of our live-attenuated tetravalent dengue virus vaccines ( TDV ) were previously evaluated for safety and immunogenicity . Two of the sixteen c and i date TDV formulations ( Formulations 13 and 14 ) were selected for further evaluation . A new TDV formulation , Formulation 17 , using a higher primary dog kidney ( PDK ) cell passage Dengue-1 virus ( DENV-1 ) and a lower PDK cell passage DENV-4 , was developed to optimize the neutralizing antibody response . All three formulations consist of combinations of 10exp3 - 5 pfu/dose of the four dengue vaccine virus serotypes . This double-blind , r and omized trial in 71 healthy adult subjects evaluated vaccine safety , reactogenicity and immunogenicity . TDV ’s were given subcutaneously in the deltoid on Day 0 and 180 ( 6 months ) . Subjects were seen in clinic on Study Days 0 , 10 , 28 , 180 , 190 and 208 and filled out daily symptom diaries for 21 days after each vaccination . Formulation 13 was the most reactogenic , while both Formulations 14 and 17 were similar in reported reactions . Seventy-five percent , 31 % and 31 % of subjects were viremic on Day 10 after primary vaccination with Formulations 13 , 14 and 17 respectively . Viremia was not detected in any subject following the second dose of vaccine . The immunogenicity endpoint was neutralizing antibody titer one month after the second vaccination . Thirty-six percent , 40 % and 63 % of vaccinated subjects developed tetravalent neutralizing antibodies after two doses of Formulations 13 , 14 and 17 , respectively . Formulation 17 was selected for further clinical evaluation based on this study With the steady rise in tick-borne encephalitis virus ( TBEV ) infections in Europe , development of a live attenuated vaccine that will generate long-lasting immunity would be of considerable benefit . A chimeric flavivirus , design ated LGT/DEN4 , was previously constructed to have a genome containing the prM and E protein genes of Langat virus ( LGT ) , a naturally attenuated member of the TBEV complex , and the remaining genetic sequences derived from dengue 4 virus ( DEN4 ) . LGT/DEN4 was highly attenuated in rodents and non-human primates , and clinical trials in humans were initiated . Twenty-eight healthy seronegative adult volunteers were r and omly assigned in a 4:1 ratio to receive 10(3 ) plaque-forming units ( PFU ) of LGT/DEN4 or placebo . Volunteers were closely monitored for clinical responses and for blood chemistry and hematological changes , and the level of viremia and the magnitude and duration of the neutralizing antibody response were determined . The LGT/DEN4 vaccine was safe and viremia was seen in only one vaccinee . Infection induced a neutralizing antibody response to wild-type LGT in 80 % of volunteers with a geometric mean titer ( GMT ) of 1:63 present on day 42 post-immunization ; however the antibody response against TBEV was both much less frequent ( 35 % ) and lower in magnitude ( GMT=1:9 ) . To assess the response to a booster dose , 21 of the original 28 volunteers were re-r and omized to receive a second dose of either 10(3 ) PFU of vaccine or placebo given 6 - 18 months after the first dose . The immunogenicity against either LGT or TBEV was not significantly enhanced after the second dose of vaccine . Thus , chimerization of LGT with DEN4 yielded a vaccine virus that was highly attenuated yet infectious in humans . The level of replication was sufficiently restricted to induce only a weak cross-reactive antibody response to TBEV . To provide a sufficient level of immunity to widely prevalent , highly neurovirulent strains of TBEV in humans , vaccine c and i date s will likely need to be based on the TBEV structural protein genes A recombinant live attenuated tetravalent dengue vaccine ( TDV ) is safe and immunogenic in adults and children in dengue-naïve population s. Data are needed in dengue endemic population s. In a phase I , r and omized , controlled , blind-observer study in the Philippines , groups of participants aged 2 - 5 , 6 - 11 , 12 - 17 , and 18 - 45 years received either three TDV vaccinations at months 0 , 3.5 , and 12 ( TDV-TDV-TDV group ) or licensed typhoid vaccination at month 0 and TDV at months 3.5 and 12 ( TyVi-TDV-TDV group ) and were followed for safety ( including biological safety and vaccine virus viremia ) and immunogenicity . No serious adverse vaccine related events and no significant trends in biological safety parameters were reported . Injection site pain , headache , malaise , myalgia , fever , and asthenia were reported most frequently , as mild to moderate in most cases and transient . Reactogenicity did not increase with successive vaccinations and was no higher in children than in adults and adolescents . Low levels of vaccinal viremia were detected in both groups after each TDV vaccination . After three TDV vaccinations , the seropositivity rates against serotypes 1 - 4 were : 91 % , 100 % , 96 % , 100 % , respectively , in 2 - 5 year-olds ; 88 % , 96 % 96 % , 92 % in 6 - 11 year-olds ; 88 % , 83 % , 92 % , 96 % in adolescents ; and 100 % for all serotypes in adults . A similar response was observed after two doses for the TyVi-TDV-TDV group . The safety profile of TDV in a flavivirus endemic population was consistent with previous reports from flavivirus naïve population s. A vaccine regimen of either three TDV vaccinations administered over a year or two TDV vaccinations given more than 8 months apart result ed in a balanced antibody response to all four dengue serotypes in this flavivirus-exposed population , including children The recombinant vaccine , tgAAC09 , based on an adeno-associated virus serotype 2 ( AAV2 ) vector encoding HIV-1 subtype C Gag , protease , and part of reverse transcriptase , induced robust T cell and antibody responses in nonhuman primates . In a previous phase I study in 80 healthy HIV-seronegative European and Indian adults , the vaccine was generally safe , well tolerated , and modestly immunogenic when administered once at doses up to 3 x 10(11 ) DRP . This phase II double-blind , r and omized , placebo-controlled trial tested two administrations and a higher dosage of tgAAC009 . Ninety-one healthy HIV-seronegative adults from three African countries were given one of three dosage levels of tgAAC09 ( 3 x 10(10 ) , 3 x 10(11 ) , or 3 x 10(12 ) DRP ) intramuscularly , either at a 6- or 12-month interval ; follow-up was 18 months . Overall , 65 % and 57 % of vaccine recipients experienced local and systemic signs and symptoms , respectively , most being mild . Frequency and severity were not dose related and were similar to those in placebo recipients . No vaccine-related serious adverse events were reported . Overall , HIV-specific T cell responses were detected by IFN-gamma ELISPOT in 17/69 ( 25 % ) vaccine recipients with 38 % ( 10/26 ) responders in the highest dosage group . The response rate improved significantly with boosting at 6 , but not 12 months , in the 3 x 10(11 ) and 3 x 10(12 ) dosage groups only . Neutralizing antibody titers to the AAV2 did not alter the frequency of immune responses to HIV . Two doses of tgAAC09 were well tolerated at the dosage levels given . Fewer than half the recipients of the highest vaccine dosage , 3 x 10(12 ) DRP , had T cell responses to HIV A controlled , r and omized , double-blind clinical trial evaluated whether two attenuated recombinant poxviruses with identical Japanese encephalitis virus ( JEV ) gene insertions , NYVAC-JEV and ALVAC-JEV , were safe and immunogenic in volunteers . Groups of 10 volunteers distinguished by vaccinia immune status received two doses of each vaccine . The vaccines appeared to be equally safe and well tolerated in volunteers , but more reactogenic than licensed formalin-inactivated JE and placebo vaccines given as controls . NYVAC-JEV and ALVAC-JEV vaccine recipients had frequent occurrence of local warmth , erythema , tenderness , and /or arm pain after vaccination . There was no apparent effect of vaccinia immune status on frequency or magnitude of local and systemic reactions . NYVAC-JEV elicited antibody responses to JEV antigens in recipients but ALVAC-JEV vaccine poorly induced antibody responses . However , NYVAC-JEV vaccine induced neutralizing antibody responses only in vaccinia-nonimmune recipients while vaccinia-immune volunteers failed to develop protective antibodies ( 5/5 vs. 0/5 seroconversion , p<0.01 ) . These data suggest that preexisting immunity to poxvirus vector may suppress antibody responses to recombinant gene products BACKGROUND Live attenuated influenza vaccines ( LAIVs ) are being developed and tested against a variety of influenza viruses with p and emic potential . We describe the results of an open-label Phase I trial of a live attenuated H7N3 virus vaccine . METHODS AND FINDINGS The H7N3 BC 2004/AA ca virus is a live attenuated , cold-adapted , temperature-sensitive influenza virus derived by reverse genetics from the wild-type low pathogenicity avian influenza virus A/chicken/British Columbia/CN-6/2004 ( H7N3 ) and the A/AA/6/60 ca ( H2N2 ) virus that is the Master Donor Virus of the live , intranasal seasonal influenza vaccine . We evaluated the safety , infectivity , and immunogenicity of two doses of 10(7.5)TCID(50 ) of the vaccine administered by nasal spray 5 weeks apart to normal healthy seronegative adult volunteers in an inpatient isolation unit . The subjects were followed for 2 months after one dose of vaccine or for 4 weeks after the second dose . Twenty-one subjects received the first dose of the vaccine , and 17 subjects received two doses . The vaccine was generally well tolerated . No serious adverse events occurred during the trial . The vaccine was highly restricted in replication : 6 ( 29 % ) subjects had virus recoverable by culture or by real-time reverse transcription polymerase chain reaction ( rRT-PCR ) after the first dose . Replication of vaccine virus was not detected following the second dose . Despite the restricted replication of the vaccine , 90 % of the subjects developed an antibody response as measured by any assay : 62 % by hemagglutination inhibition assay , 48 % by microneutralization assay , 48 % by ELISA for H7 HA-specific serum IgG or 71 % by ELISA for H7 HA-specific serum IgA , after either one or two doses . Following the first dose , vaccine-specific IgG secreting cells as measured by ELISPOT increased from a mean of 0.1 to 41.6/10(6 ) P BMC s ; vaccine-specific IgA secreting cells increased from 2 to 16.4/10(6 ) P BMC s. The antibody secreting cell response after the second dose was less vigorous , which is consistent with the observed low replication of vaccine virus after the second dose and consequent lower antigenic stimulation . CONCLUSION The live attenuated H7N3 vaccine was generally well tolerated but was highly restricted in replication in healthy seronegative adults . Despite the restricted replication , the vaccine was immunogenic , with serum IgA being the most sensitive measure of immunogenicity . Further development of this vaccine is warranted ( Clinical Trials.gov Identifier : NCT00516035 ) Herpes zoster , may be severe and recurrent in HIV-infected children . We determined the safety and immunogenicity of live attenuated varicella-zoster virus ( VZV ) vaccine in 46 HIV-infected children who had experienced varicella . There were no serious adverse events . Two years after vaccination 82 % of subjects remained VZV-antibody positive and 60 % had VZV-specific cell-mediated immunity . No child developed herpes zoster VDV3 , a clonal derivative of the Mahidol live-attenuated dengue 3 vaccine was prepared in Vero cells . Despite satisfactory pre clinical evaluation , VDV3 was reactogenic in humans . We explored whether immunological mechanisms contributed to this outcome by monitoring innate and adaptive cellular immune responses for 28 days after vaccination . While no variations were seen in serum IL12 or TNFalpha levels , a high IFNgamma secretion was detected from Day 8 , concomitant to IFNalpha , followed by IL10 . Specific Th1 and CD8 responses were detected on Day 28 , with high IFNgamma/TNFalpha ratios . Vaccinees exhibited very homogeneous class I HLA profiles , and a new HLA B60-restricted CD8 epitope was identified in NS3 . We propose that , among other factors , adaptive immunity may have contributed to reactogenicity , even after this primary vaccination . In addition , the unexpected discordance observed between pre clinical results and clinical outcome in humans led us to reconsider some of our pre clinical acceptance criteria . Lessons learned from these results will help us to pursue the development of safe and immunogenic vaccines We conducted a Phase 1b study to evaluate the immunogenicity and safety of two live attenuated tetravalent dengue vaccines in healthy adult volunteers . After one injection , all subjects reported systemic reactions consistent with a mild dengue-like syndrome . Seven volunteers developed dengue 3 viraemia after vaccination . All subjects developed a neutralizing antibody response against serotype 3 with partial response against other serotypes . The trial was stopped early ( after 10 subjects enrolled ) due to formulation issues , which were related to the dengue 3 vaccine component . Managing viral interference and balancing attenuation to produce acceptable tetravalent immunogenicity with minimal reactogenicity may be a recurring problem for future multivalent live vaccines BACKGROUND Chikungunya virus -- a mosquito-borne alphavirus -- is endemic in Africa and south and southeast Asia and has recently emerged in the Caribbean . No drugs or vaccines are available for treatment or prevention . We aim ed to assess the safety , tolerability , and immunogenicity of a new c and i date vaccine . METHODS VRC 311 was a phase 1 , dose-escalation , open-label clinical trial of a virus-like particle ( VLP ) chikungunya virus vaccine , VRC-CHKVLP059 - 00-VP , in healthy adults aged 18 - 50 years who were enrolled at the National Institutes of Health Clinical Center ( Bethesda , MD , USA ) . Participants were assigned to sequential dose level groups to receive vaccinations at 10 μg , 20 μg , or 40 μg on weeks 0 , 4 , and 20 , with follow-up for 44 weeks after enrolment . The primary endpoints were safety and tolerability of the vaccine . Secondary endpoints were chikungunya virus-specific immune responses assessed by ELISA and neutralising antibody assays . This trial is registered with Clinical Trials.gov , NCT01489358 . FINDINGS 25 participants were enrolled from Dec 12 , 2011 , to March 22 , 2012 , into the three dosage groups : 10 μg ( n=5 ) , 20 μg ( n=10 ) , and 40 μg ( n=10 ) . The protocol was completed by all five participants at the 10 μg dose , all ten participants at the 20 μg dose , and eight of ten participants at the 40 μg dose ; non-completions were for personal circumstances unrelated to adverse events . 73 vaccinations were administered . All injections were well tolerated , with no serious adverse events reported . Neutralising antibodies were detected in all dose groups after the second vaccination ( geometric mean titres of the half maximum inhibitory concentration : 2688 in the 10 μg group , 1775 in the 20 μg group , and 7246 in the 40 μg group ) , and a significant boost occurred after the third vaccination in all dose groups ( 10 μg group p=0·0197 , 20 μg group p<0·0001 , and 40 μg group p<0·0001 ) . 4 weeks after the third vaccination , the geometric mean titres of the half maximum inhibitory concentration were 8745 for the 10 μg group , 4525 for the 20 μg group , and 5390 for the 40 μg group . INTERPRETATION The chikungunya VLP vaccine was immunogenic , safe , and well tolerated . This study represents an important step in vaccine development to combat this rapidly emerging pathogen . Further studies should be done in a larger number of participants and in more diverse population s. FUNDING Intramural Research Program of the Vaccine Research Center , National Institute of Allergy and Infectious Diseases , and National Institutes of Health The safety and immunogenicity of plasmid pTHr DNA , modified vaccinia virus Ankara ( MVA ) human immunodeficiency virus type 1 ( HIV-1 ) vaccine c and i date s were evaluated in four Phase I clinical trials in Kenya and Ug and a. Both vaccines , expressing HIV-1 subtype A gag p24/p17 and a string of CD8 T-cell epitopes ( HIVA ) , were generally safe and well-tolerated . At the dosage levels and intervals tested , the percentage of vaccine recipients with HIV-1-specific cell-mediated immune responses , assessed by a vali date d ex vivo interferon gamma ( IFN-gamma ) ELISPOT assay and Cytokine Flow Cytometry ( CFC ) , did not significantly differ from placebo recipients . These trials demonstrated the feasibility of conducting high- quality Phase 1 trials in Africa Objective : Breast milk transmission continues to account for a large proportion of cases of mother-to-child transmission of HIV-1 worldwide . An effective HIV-1 vaccine coupled with either passive immunization or short-term antiretroviral prophylaxis represents a potential strategy to prevent breast milk transmission . This study evaluated the safety and immunogenicity of ALVAC HIV-1 vaccine with and without a subunit envelope boost in infants born to HIV-1-infected women . Design : Placebo-controlled , double-blinded study . Methods : Infants born to HIV-1-infected mothers in the US were immunized with a prime-boost regimen using a canarypox virus HIV-1 vaccine ( vCP1452 ) and a recombinant glycoprotein subunit vaccine ( rgp120 ) . Infants ( n = 30 ) were r and omized to receive : vCP1452 alone , vCP1452 + rgp120 , or corresponding placebos . Results : Local reactions were mild or moderate and no significant systemic toxicities occurred . Subjects receiving both vaccines had gp120-specific binding serum antibodies that were distinguishable from maternal antibody . Repeated gp160-specific lymphoproliferative responses were observed in 75 % . Neutralizing activity to HIV-1 homologous to the vaccine strain was observed in 50 % of the vCP1452 + rgp120 subjects who had lost maternal antibody by week 24 . In some infants HIV-1-specific proliferative and antibody responses persisted until week 104 . HIV-1-specific cytotoxic T lymphocyte responses were detected in two subjects in each treatment group ; the frequency of HIV-1 specific cytotoxic T lymphocyte responses did not differ between vaccine and placebo recipients . Conclusion : The demonstration of vaccine-induced immune responses in early infancy supports further study of HIV-1 vaccination as a strategy to reduce breast milk transmission Laboratory-attenuated strains of each of the four dengue serotypes previously tested as monovalent vaccines in volunteers were combined and tested for immunogenicity , safety , and reactogenicity in 16 dosage combinations . Tetravalent vaccines made using combinations of high ( 10(5 - 6 ) plaque-forming units [PFU]/dose ) or low ( 10(3.5 - 4.5 ) PFU/dose ) dosage formulations of each of the four viruses were inoculated in 64 flavivirus non-immune adult volunteers to determine which , if any , formulation raised neutralizing antibodies in at least 75 % of volunteers to at least three of four dengue serotypes following one or two inoculations . Such formulations , if safe and sufficiently non-reactogenic , would be considered for an exp and ed Phase II trial in the future . Formulations 1 - 15 were each inoculated into three or four volunteers ( total = 54 ) on days 0 and 28 . Formulation 16 was tested in 10 volunteers , five volunteers inoculated on days 0 and 30 , one volunteer on days 0 and 120 , and four volunteers on days 0 , 30 , and 120 . Blood was drawn for serologic assays immediately before and one month after each vaccination , and for viremia assay on day 10 after each vaccination . The 16 formulations were safe , but variably reactogenic after the first vaccination , and nearly non-reactogenic after the second and third vaccinations . Reactogenicity was positively correlated with immunogenicity . Similar proportions of volunteers seroconverted to dengue-1 ( 69 % ) , dengue-2 ( 78 % ) , and dengue-3 ( 69 % ) , but significantly fewer volunteers seroconverted to dengue-4 ( 38 % ) . The geometric mean 50 % plaque reduction neutralization test titers in persons who seroconverted were significantly higher to dengue-1 ( 1:94 ) than to dengue-2 ( 1:15 ) , dengue-3 ( 1:10 ) , and dengue-4 ( 1:2 ) . Seven formulations met the serologic criteria required for an exp and ed trial , and three of these were sufficiently attenuated clinical ly to justify further testing There are currently no vaccines or therapeutics to prevent dengue disease which ranges in severity from asymptomatic infections to life-threatening illness . The National Institute of Allergy and Infectious Diseases ( NIAID ) Division of Intramural Research has developed live , attenuated vaccines to each of the four dengue serotypes ( DENV-1-DENV-4 ) . Two doses ( 10PFU and 1000PFU ) of three monovalent vaccines were tested in human clinical trials to compare safety and immunogenicity profiles . DEN4Δ30 had been tested previously at multiple doses . The three dengue vaccine c and i date s tested ( DEN1Δ30 , DEN2/4Δ30 , and DEN3Δ30/31 ) were very infectious , each with a human infectious dose 50%≤ 10PFU . Further , infectivity rates ranged from 90 to 100 % regardless of dose , excepting DEN2/4Δ30 which dropped from 100 % at the 1000PFU dose to 60 % at the 10PFU dose . Mean geometric peak antibody titers did not differ significantly between doses for DEN1Δ30 ( 92 ± 19 vs. 214 ± 97 , p=0.08 ) ; however , significant differences were observed between the 10PFU and 1000PFU doses for DEN2/4Δ30 , 19 ± 9 vs. 102 ± 25 ( p=0.001 ) , and DEN3Δ30/31 , 119 ± 135 vs. 50 ± 50 ( p=0.046 ) . No differences in the incidences of rash , neutropenia , or viremia were observed between doses for any vaccines , though the mean peak titer of viremia for DEN1Δ30 was higher at the 1000PFU dose ( 0.5 ± 0 vs. 1.1 ± 0.1 , p=0.007 ) . These data demonstrate that a target dose of 1000PFU for inclusion of each dengue serotype into a tetravalent vaccine is likely to be safe and generate a balanced immune response for all serotypes A Phase I/II observer-blind , r and omized , controlled trial evaluated the safety and immunogenicity of a dengue virus ( DENV ) vaccine c and i date in healthy Thai infants ( aged 12 - 15 months ) without measurable pre-vaccination neutralizing antibodies to DENV and Japanese encephalitis virus . Fifty-one subjects received two doses of either DENV ( N = 34 ; four received 1/10th dose ) or control vaccine ( N = 17 ; dose 1 , live varicella ; dose 2 , Haemophilus influenzae type b ) . After each vaccine dose , adverse events ( AEs ) were solicited for 21 days , and non-serious AEs were solicited for 30 days ; serious AEs ( SAEs ) were recorded throughout the study . Laboratory safety assessment s were performed at 10 and 30 days ; neutralizing antibodies were measured at 30 days . The DENV vaccine was well-tolerated without any related SAEs . After the second dose , 85.7 % of full-dose DENV vaccinees developed at least trivalent and 53.6 % developed tetravalent neutralizing antibodies ≥ 1:10 to DENV ( control group = 0 % ) . This vaccine c and i date , therefore , warrants continued development in this age group ( NCT00322049 ; clinical trials.gov ) |
903 | 30,466,739 | We found that patient-reported health information interventions and patient education interventions probably improve healthcare professionals ' adherence to recommended clinical practice ( moderate certainty evidence ) .
We also found that patient information interventions may improve healthcare professionals ' adherence to recommended clinical practice ( low certainty evidence ) .
Patient decision aids may make little or no difference to the number of healthcare professionals ' adhering to recommended clinical practice ( low-certainty evidence ) .
Our findings strengthen the belief that patient-mediated interventions have the potential to improve professional practice , especially patient-reported health information interventions and patient education interventions .
PRACTICE IMPLICATION S Our findings show that patient-reported health information interventions and patient education interventions are relevant approaches to improve professional practice .
Thus , it seems reasonable to conclude that these types of patient-mediated interventions can contribute to improving the quality of healthcare services | OBJECTIVE To assess the effectiveness of patient-mediated interventions on healthcare professionals ' performance . | Background : We conducted a prospect i ve trial r and omizing 75 physicians to either a control or intervention arm to evaluate the impact of providing patient-reported information on anxiety and other mental health symptoms and disorders to primary care physicians . Methods : Five hundred seventy-three patients of the study physicians who met entry criteria were r and omized to either usual care or usual care supplemented with feedback of patient-reported mental health information to physicians . This mental health information was derived from initial patient-reported question naires completed in waiting rooms of physicians contracted to a mixed-model health maintenance organization in Colorado . Main outcome measures included impact of intervention on rates of ( 1 ) chart notation of anxiety , depression , or other mental health diagnoses or symptoms ; ( 2 ) referral to mental health specialists ; ( 3 ) prescription of psychotropic medications ; ( 4 ) hospitalization ; and ( 5 ) office visits during a 5-month observation period . Results : Physicians receiving feedback on previously unrecognized and untreated anxiety patients were more likely to make chart notations ( adjusted odds ratio [ AOR ] = 2.51 , 95 percent confidence interval [ CI ] = 1.62 - 3.87 ) , to make referrals to mental health specialists ( AOR = 3.86 , 95 percent CI = 1.63 - 9.16 ) , and to see patients for more frequent outpatient visits ( AOR = 1.73 , 95 percent CI = 1.11 - 2.70 ) . Use of psychotropic medications and rate of hospitalizations did not differ significantly . Conclusions : Providing patient-reported mental health information to primary care physicians result ed in increased recognition and referral rates for previously unrecognized and untreated anxiety patients , plus an increase in primary care visits , without concomitant increases in the use of psychotropic medications or rate of hospitalizations Background Only approximately half of patients with hypertension have their blood pressure controlled , due in large part to the tendency of primary care providers ( PCPs ) not to intensify treatment when blood pressure values are elevated . Objective This study tested the effect of an intervention design ed to help patients ask questions at the point of care to encourage PCPs to appropriately intensify blood pressure treatment . Methods PCPs and their patients with hypertension ( N=500 ) were recruited by letter and r and omized into 2 study groups : ( 1 ) intervention condition in which patients used a fully automated website each month to receive tailored messages suggesting questions to ask their PCP to improve blood pressure control , and ( 2 ) control condition in which a similar tool suggested questions to ask about preventive services ( eg , cancer screening ) . The Web-based tool was design ed to be used during each of the 12 study months and before scheduled visits with PCPs . The primary outcome was the percentage of patients in both conditions with controlled blood pressure . Results Of 500 enrolled patients ( intervention condition : n=282 ; control condition : n=218 ) , 418 ( 83.6 % ) completed the 12-month follow-up visit . At baseline , 289 ( 61.5 % ) of participants had controlled blood pressure . Most ( 411/500 , 82.2 % ) participants used the intervention during at least 6 of 12 months and 222 ( 62.5 % ) reported asking questions directly from the Web-based tool . There were no group differences in asking about medication intensification and there were no differences in blood pressure control after 12 months between the intervention condition ( 201/282 , 71.3 % ) and control condition ( 143/218 , 65.6 % ; P=.27 ) groups . More intervention condition participants discussed having a creatinine test ( 92 , 52.6 % vs 49 , 35.5 % ; P=.02 ) and urine protein test ( 81 , 44.8 % vs 21 , 14.6 % ; P<.001 ) , but no group differences were observed in the rate of testing . The control condition participants reported more frequent discussion s about tetanus and pneumonia vaccines and reported more tetanus ( 30 , 13.8 % vs 15 , 5.3 % ; P=.02 ) and pneumonia ( 25 , 11.5 % vs 16 , 5.7 % ; P=.02 ) vaccinations after 12 months . Conclusions The use of an interactive website design ed to overcome clinical inertia for hypertension care did not lead to improvements in blood pressure control . Participant adherence to the intervention was high . The control intervention led to positive changes in the use of preventive services ( eg , tetanus immunization ) and the intervention condition led to more discussion s of hypertension-relevant tests ( eg , serum creatinine and urine protein ) . By providing patients with individually tailored questions to ask during PCP visits , this study demonstrated that participants were likely to discuss the questions with PCPs . These discussion s did not , however , lead to improvements in blood pressure control . Trial Registration Clinical Trials.gov NCT00377208 ; http:// clinical trials.gov/ct2/show/NCT00377208 ( Archived by WebCite at http://www.webcitation.org/6IqWiPLon ) The aim of the review was to assess the effect of patient education in ischaemic heart disease . Thirteen r and omised controlled trials of moderate to good quality including 68,556 patients were selected . The effect on mortality , cardiac morbidity , hospitalisation and health-related quality of life was assessed and only non-significant tendencies of effect were found . The authors of the review nevertheless conclude that the review supports current rehabilitation programmes that include patient education . Further research in patient education , especially concerning the most effective methods of education delivery , is needed BACKGROUND To compare three approaches for improving compliance with breast cancer screening in older women . METHODS R and omized controlled trial using three parallel group practice s at a public hospital . Subjects included women aged 65 years and older ( n = 803 ) who were seen by residents ( n = 66 ) attending the ambulatory clinic from October 1 , 1989 , through March 31 , 1990 . All provider groups received intensive education in breast cancer screening . The control group received no further intervention . Staff in the second group offered education to patients at their visit . In addition , flowsheets were used in the " Prevention Team " group and staff had their tasks redefined to facilitate compliance . RESULTS Medical records were review ed to determine documented offering/receipt of clinical breast examination and mammography . A subgroup of women without previous clinical breast examination ( n = 540 ) and without previous mammography ( n = 471 ) were analyzed to determine the effect of the intervention . During the intervention period , women without a previous clinical breast examination were offered an examination significantly more often in the Prevention Team group than in the control group , adjusting for age , race , and comorbidity and for physicians ' gender and training level . The patients in the Prevention Team group were offered clinical breast examination ( 31.5 % ) more frequently than those in the patient education or control groups , but this was not significant after adjusting for the above covariates . Likewise , mammography was offered more frequently to patients in the Prevention Team and in the patient education group than to patients in the control group , after adjusting for the factors above using logistic regression . CONCLUSIONS The results provide support for patient education and organizational changes that involve nonphysician personnel to enhance breast cancer screening among older women , particularly those without previous screening CONTEXT For patients with cancer-related pain and their physicians , routine oncology visits are an opportunity to adjust the analgesic regimen and secure better pain control . However , treatment intensification occurs haphazardly in practice . OBJECTIVES To estimate the effect of patient-centered tailored education and coaching ( TEC ) on the likelihood of analgesic treatment adjustment during oncology visits , and in turn , the influence of treatment adjustment on subsequent cancer pain control , we studied patients enrolled in a r and omized trial of TEC . METHODS Just before a scheduled oncology visit , 258 patients with at least moderate baseline pain received TEC or control ; just after the same visit , they reported on whether the physician recommended a new pain medicine or a change in dose of an existing medicine . Pain severity and pain-related impairment were measured two , six , and 12 weeks later . RESULTS Patients assigned to TEC were more likely than controls to report a change in the analgesic treatment regimen ( 60 % vs. 36 % , P<0.01 ) ; significant effects persisted after adjustment for baseline pain , study site , and physician ( adjusted odds ratio 2.61 , 95 % confidence interval 1.55 , 4.40 , P<0.01 ) . In a mixed-effects repeated measures regression , analgesic change ( but not TEC itself ) was associated with a sustained decrease in pain severity ( P<0.05 ) . CONCLUSION TEC increases the likelihood of self-reported , physician-directed adjustments in analgesic prescribing , and treatment intensification is associated with better cancer pain outcomes Introduction This study evaluated the impact of a waiting room-administered , low-literacy , computer multimedia diabetes education program on patient self-management and provider intensification of therapy . Methods In this r and omized , controlled trial , 129 participants either viewed a computer multimedia education program ( intervention group ) or read an educational brochure ( control group ) while in the waiting room . Participants were uninsured , primarily ethnic minority adults with type 2 diabetes receiving care from a county clinic in Chicago , Illinois . Wilcoxon test , t-test , and linear mixed model analyses evaluated changes in diabetes knowledge , self-efficacy , behaviors , medications prescribed , hemoglobin A1c ( HbA1c ) , and blood pressure levels over 3 months . Results During the study period , there was an increase in the number of oral diabetes medications prescribed over three months to multimedia users compared with those in the control group ( P=0.017 ) . HbA1c declined by 1.5 in the multimedia group versus 0.8 in the control group ( P=0.06 ) . There were no differences between groups in changes in blood pressure levels , self-efficacy , and most diabetes-related behaviors . Self-reported exercise increased in the control group compared with the multimedia group ( 0.9 days/week vs. 0.1 days/week , P=0.016 ) . Conclusion Multimedia users received a greater intensification of diabetes therapy , but demonstrated no difference in self-management in comparison with those receiving educational brochures . The availability of a computer multimedia program in the waiting room appears to be a novel and acceptable approach in providing diabetes education for underserved population BACKGROUND Hypertension is generally poorly controlled in primary care . One possible intervention for improving control is the harnessing of patient expertise through education and encouragement to challenge their care . AIM To determine whether encouraging patients to manage their hypertension in an ' expert ' manner , by providing them with information in a clear clinical guideline , coupled with an explicit exhortation to become involved in and to challenge their own care if appropriate , would improve their care . DESIGN OF STUDY Single blind r and omised controlled trial of detailed guideline versus st and ard information . SETTING Single urban general practice over 1 year . METHOD Patient-held guideline with written explicit exhortation to challenge care when appropriate . Two hundred and ninety-four of 536 eligible patients on the practice hypertension register were recruited , all of whom were r and omised into one of two groups . Two hundred and thirty-six patients completed the study . RESULTS PRIMARY OUTCOME average systolic blood pressure . SECONDARY OUTCOMES proportion of patients with blood pressure < 150 mmHg systolic and < 90 mmHg diastolic , average cholesterol , proportion of patients prescribed statins and aspirin according to guideline , hospital anxiety and depression score . No clinical ly , or statistically significant differences were found between intervention and control with respect to all parameters or in anxiety and depression levels . Statin and aspirin use improved throughout the course of the study in both groups . Statin use showed a trend ( P = 0.02 ) in favour of control . CONCLUSION In this study there was no clinical ly significant perceived benefit to patients as a result of providing them with a hypertension guideline . Patient guidelines are currently planned for many chronic illnesses . It is important to determine the utility of such interventions before scarce re sources are applied to them Background : Too few patients with nonvalvular atrial fibrillation ( NVAF ) receive appropriate antithrombotic therapy . We tested the short-term ( primary outcome ) and long-term ( secondary outcome ) effect of a patient decision aid on the appropriateness of antithrombotic therapy among patients with NVAF . Methods : We conducted a cluster r and omized trial with blinded outcome assessment involving 434 NVAF patients from 102 community-based primary care practice s. Patients in the intervention group received a self-administered booklet and audiotape decision aid tailored to their personal stroke risk profile . Patients in the control group received usual care . The primary outcome measure was change in antithrombotic therapy at 3 months . Appropriateness of therapy was defined using the American College of Chest Physicians ( ACCP ) recommendations . Results : The mean patient age was 72 years , and the median duration of NVAF was 5 years . In the control group , there was a 3 % decrease over 3 months in the number of patients receiving therapy appropriate to their risk of stroke ( 40 % [ 85/215 ] at baseline v. 37 % [ 79/215 ] at 3 months ) . In the intervention group , the number of patients receiving therapy appropriate to their stroke risk increased by 9 % ( 32 % [ 69/219 ] at baseline v. 41 % [ 89/219 ] at 3 months ) . Although the proportion of patients whose therapy met the ACCP treatment recommendations did not differ between study arms at baseline ( p = 0.11 ) or 3 months ( p = 0.44 ) , there was a 12 % absolute improvement in the number of patients receiving appropriate care in the intervention group compared with the control group at 3 months ( p = 0.03 ) . The beneficial effect of the decision aid did not persist ( p = 0.44 for differences between study arms after 12 months ) . Interpretation : There was short-term improvement in the appropriateness of antithrombotic care among patients with NVAF who were exposed to a decision aid , but the improvement did not persist CONTEXT . Barriers impede translating recommendations for asthma treatment into practice , particularly in inner cities where asthma morbidity is highest . METHODS . The purpose of this study was to test the effectiveness of timely patient feedback in the form of a letter providing recent patient-specific symptoms , medication , and health service use combined with guideline -based recommendations for changes in therapy on improving the quality of asthma care by inner-city primary care providers and on result ant asthma morbidity . This was a r and omized , controlled clinical trial in 5- to 11-year-old children ( n = 937 ) with moderate to severe asthma receiving health care in hospital- and community-based clinics and private practice s in 7 inner-city urban areas . The caretaker of each child received a bimonthly telephone call to collect clinical information about the child 's asthma . For a full year , the providers of intervention group children received bimonthly computer-generated letters based on these calls summarizing the child 's asthma symptoms , health service use , and medication use with a corresponding recommendation to step up or step down medications . We measured the number and proportion of scheduled visits result ing in stepping up of medications , asthma symptoms ( 2-week recall ) , and health care use ( 2-month recall ) . RESULTS . In this population , only a modest proportion of children whose symptoms warranted a medication increase actually had a scheduled visit to reevaluate their asthma treatment . However , in the 2-month interval after receipt of a step-up letter , 17.1 % of the letters were followed by scheduled visits in the intervention group compared with scheduled visits 12.3 % of the time by the control children with comparable clinical symptoms . Asthma medications were stepped up when indicated after 46.0 % of these visits in the intervention group compared with 35.6 % in the control group , and when asthma symptoms warranted a step up in therapy , medication changes occurred earlier among the intervention children . Among children whose medications were stepped up at any time during the 12-month study period , those in the intervention group experienced 22.1 % fewer symptom days and 37.9 % fewer school days missed . The intention-to-treat analysis showed no difference over the intervention year in the number of symptom days , yet there was a trend toward fewer days of limited activity and a significant decrease in emergency department visits by the intervention group compared with controls . This 24 % drop in emergency department visits result ed in an intervention that was cost saving in its first year . CONCLUSIONS . Patient-specific feedback to inner-city providers increased scheduled asthma visits , increased asthma visits in which medications were stepped up when clinical ly indicated , and reduced emergency department visits CONTEXT Pneumococcal immunization rates for elderly and high-risk patients are only one third to one half the target rate of 60 % established by the US Public Health Service . Limited or marginal literacy , which affects nearly 100 million Americans , especially the elderly , may contribute to these low rates of immunization . OBJECTIVE To determine whether the use of a simple , low-literacy educational tool enhances patient-physician dialogue about pneumococcal vaccination and increases rates of immunization . DESIGN A r and omized controlled trial conducted between May and June of 1998 . SETTING Ambulatory care clinic of a 900-bed public teaching hospital serving a predominantly indigent , low-literate , African American , inner-city population . PARTICIPANTS Of 433 patients who presented for routine primary care , had vaccine indications ( age > or = 65 years or chronic disease ) , and had not been previously vaccinated , 221 were r and omly assigned to the intervention group and 212 to the control group . Of the total patient population ( mean age , 63 years ) , 280 ( 64.7 % ) had less than a high school education , 401 ( 92.6 % ) were African American , and 300 ( 69.3 % ) were female . INTERVENTION One-page , low-literacy ( below fifth- grade level ) educational h and out encouraging patients to " ask your doctor about the pneumonia shot " vs a control group ( 1 -page , low-literacy educational h and out conveying information about nutrition ) . MAIN OUTCOME MEASURES Vaccination rates ( documented by chart audit ) of patients who received pneumococcal vaccination and rates of patients who self-reported having discussed vaccination with their physicians . RESULTS Patients in the intervention group were 4 times more likely to have discussed the pneumococcal vaccine with their physicians than patients in the control group ( 87/221 [ 39.4 % ] vs 21/212 [ 9.9 % ] ; relative risk [ RR ] , 3.97 [ 95 % confidence interval [ CI ] , 2.71 - 5.83 ] ) , and were more than 5 times as likely to have received the pneumococcal vaccine than the control group ( 44/221 [ 19.9 % ] vs 8/212 [ 3.8 % ] ; RR , 5.28 [ 95 % CI , 2.80 - 9.93 ] ) . In a multivariate analysis controlling for race , sex , education , insurance status , age , level of physician training , health status , and vaccine indication , only assignment to the intervention group was statistically significantly related to the probability of being immunized or discussing the issue with their physicians ( P<.001 for both trends ) . CONCLUSIONS A simple , low-literacy educational tool increased pneumococcal vaccination rates and patient-physician discussion s about the vaccine in an elderly , low-literate , indigent , minority population BACKGROUND Latino immigrants face a higher burden of colorectal cancer ( CRC ) and screening rates are low . OBJECTIVE To assess the effectiveness of a multilevel intervention in increasing the rate of CRC screening among Latino immigrants . DESIGN A r and omized controlled trial , with r and omization at the physician level . PARTICIPANTS Pairs of 65 primary care physicians and 65 Latino immigrant patients participated , 31 in the intervention and 34 in the control group . INTERVENTIONCRC educational video in Spanish on a portable personal digital video display device accompanied by a brochure with key information for the patient , and a patient-delivered paper-based reminder for their physician . MEASUREMENTS Completed CRC screening , physician recommendation for CRC screening , and patient adherence to physician recommended CRC screening . RESULTS The overall rate of completed screening for CRC was 55 % for the intervention and 18 % for the control group ( p = 0.002 ) . Physicians recommended CRC screening for 61 % of patients in the intervention group versus 41 % in the control group ( p = 0.08 ) . Of those that received a recommendation , 90 % in the intervention group adhered to it versus 26 % in the control group ( p = 0.007 ) . CONCLUSIONS The intervention was successful in increasing rates of completed CRC screening primarily through increasing adherence after screening was recommended . Additional efforts should focus on developing new strategies to increase physician recommendation for CRC screening , while employing effective patient adherence interventions Abstract BACKGROUND : In New Zeal and , more than 5 % of people aged 50 years and older have undiagnosed diabetes ; most of them attend family practitioners ( FPs ) at least once a year . OBJECTIVES : To test the effectiveness of patients or computers as reminders to screen for diabetes in patients attending FPs . DESIGN : A r and omized-controlled trial compared screening rates in 4 intervention arms : patient reminders , computer reminders , both reminders , and usual care . The trial lasted 2 months . The patient reminder was a diabetes risk self- assessment sheet filled in by patients and given to the FP during the consultation . The computer reminder was an icon that flashed only for patients considered eligible for screening . PARTICIPANTS : One hundred and seven FPs . MEASUREMENTS : The primary outcome was whether each eligible patient , who attended during the trial , was or was not tested for blood glucose . Analysis was by intention to treat and allowed for clustering by FP . RESULTS : Patient reminders ( odds ratio [ OR ] 1.72 , 95 % confidence interval [ CI ] 1.21 , 2.43 ) , computer reminders ( OR 2.55 , 1.68 , 3.88 ) , and both reminders ( OR 1.69 , 1.11 , 2.59 ) were all effective compared with usual care . Computer reminders were more effective than patient reminders ( OR 1.49 , 1.07 , 2.07 ) . Patients were more likely to be screened if they visited the FP repeatedly , if patients were non-European , if they were “ regular ” patients of the practice , and if their FP had a higher screening rate prior to the study . CONCLUSIONS : Patient and computer reminders were effective methods to increase screening for diabetes . However , the effects were not additive Background : Efforts to enhance patient-physician communication may improve management of underdiagnosed chronic conditions . Patient internet portals offer an efficient venue for coaching patients to discuss chronic conditions with their primary care physicians ( PCP ) . Objectives : We sought to test the effectiveness of an internet portal-based coaching intervention to promote patient-PCP discussion about chronic conditions . Research Design : We conducted a r and omized trial of a nurse coach intervention conducted entirely through a patient internet-portal . Subjects : Two hundred forty-one patients who were registered portal users with scheduled PCP appointments were screened through the portal for 3 target conditions , depression , chronic pain , mobility difficulty , and r and omized to intervention and control groups . Measures : One-week and 3-month patient surveys assessed visit experiences , target conditions , and quality of life ; chart abstract ions assessed diagnosis and management during PCP visit . Results : Similar high percentages of intervention ( 85 % ) and control ( 80 % ) participants reported discussing their screened condition during their PCP visit . More intervention than control patients reported their PCP gave them specific advice about their health ( 94 % vs. 84 % ; P = 0.03 ) and referred them to a specialist ( 51 % vs. 28 % ; P = 0.002 ) . Intervention participants reported somewhat higher satisfaction than controls ( P = 0.07 ) . Results showed no differences in detection or management of screened conditions , symptom ratings , and quality of life between groups . Conclusions : Internet portal-based coaching produced some possible benefits in care for chronic conditions but without significantly changing patient outcomes . Limited sample sizes may have contributed to insignificant findings . Further research should explore ways internet portals may improve patient outcomes in primary care . Clinical Trials.gov registration NCT00130416 BACKGROUND Provider and patient reminders can be effective in increasing rates of preventive screenings and vaccinations . However , the effect of patient-directed electronic reminders is understudied . OBJECTIVE To determine whether providing reminders directly to patients via an electronic Personal Health Record ( PHR ) improved adherence to care recommendations . DESIGN We conducted a cluster r and omized trial without blinding from 2005 to 2007 at 11 primary care practice s in the Partners HealthCare system . PARTICIPANTS A total of 21,533 patients with access to a PHR were invited to the study , and 3,979 ( 18.5 % ) consented to enroll . INTERVENTIONS Patients in the intervention arm received health maintenance ( HM ) reminders via a secure PHR “ eJournal , ” which allowed them to review and up date HM and family history information . Patients in the active control arm received access to an eJournal that allowed them to input and review information related to medications , allergies and diabetes management . MAIN MEASURES The primary outcome measure was adherence to guideline -based care recommendations .KEY RESULTS Intention-to-treat analysis showed that patients in the intervention arm were significantly more likely to receive mammography ( 48.6 % vs 29.5 % , p = 0.006 ) and influenza vaccinations ( 22.0 % vs 14.0 % , p = 0.018 ) . No significant improvement was observed in rates of other screenings . Although Pap smear completion rates were higher in the intervention arm ( 41.0 % vs 10.4 % , p < 0.001 ) , this finding was no longer significant after excluding women ’s health clinics . Additional on-treatment analysis showed significant increases in mammography ( p = 0.019 ) and influenza vaccination ( p = 0.015 ) for intervention arm patients who opened an eJournal compared to control arm patients , but no differences for any measure among patients who did not open an eJournal . CONCLUSIONS Providing patients with HM reminders via a PHR may be effective in improving some elements of preventive care PURPOSE This r and omized clinical trial tested the effectiveness of the PRO-SELF Pain Control Program compared with st and ard care in decreasing pain intensity scores , increasing appropriate analgesic prescriptions , and increasing analgesic intake in oncology out patients with pain from bone metastasis . PATIENTS AND METHODS Patients were r and omly assigned to the PRO-SELF intervention ( n = 93 ) or st and ard care ( n = 81 ) . Patients in the st and ard care arm were seen by a research nurse three times and were called three times by phone between the home visits . PRO-SELF group patients were seen by specially trained intervention nurses and received a psychoeducational intervention , were taught how to use a pillbox , and were given written instructions on how to communicate with their physician about unrelieved pain and the need for changes in their analgesic prescriptions . Patients were coached during two follow-up home visits and three phone calls on how to improve their cancer pain management . RESULTS Pain intensity scores decreased significantly from baseline ( all P < .0001 ) in the PRO-SELF group ( ie , least pain , 28.4 % ; average pain , 32.5 % ; and worst pain , 27.0 % ) compared with the st and ard care group ( ie , least increased by 14.6 % , average increased by 1.9 % , and worst decreased by 1.2 % ) . The percentage of patients in the PRO-SELF group with the most appropriate type of analgesic prescription increased significantly from 28.3 % to 37.0 % ( P = .008 ) compared with a change from 29.6 % to 32.5 % in the st and ard care group . CONCLUSION The use of a psychoeducational intervention that incorporates nurse coaching within the framework of self-care can improve the management of cancer pain Background : The objective of this study was to determine the impact of the Wellness Portal — a novel , web-based patient portal that focuses on wellness , prevention , and longitudinal health — on the delivery of patient-centered preventive care by examining the behavior and experiences of both patients and primary care clinicians and the degree to which recommended services were individualized and provided . Methods : We conducted a 3-year , systematic portal development and testing study , which included a 6-month feasibility and acceptability pilot in 2 primary care practice s followed by a 12-month cluster r and omized controlled trial in 8 clinician practice s ( 4 in each study group ) . Descriptive and bivariate analyses were conducted to compare service delivery between intervention and control arms . Results : Ninety percent of patients in the pilot study found the portal easy to use , 83 % found it to be a valuable re source , and 80 % said that it facilitated their participation in their own care . The cluster r and omized controlled trial included 422 adults 40 to 75 years of age and the parents of 116 children 2 to 5 years of age . Seventy three percent of patients used the portal during the study . Both patient activation ( measured via the 13-item Patient Activation Measure ) and participants ' perception of patient-centeredness of care ( measured via the Consumer Assessment of Healthcare Providers and Systems instrument ) increased significantly in the portal group compared with control ( P = .0014 and P = .037 , respectively ) . A greater proportion of portal users received all recommended preventive services ( 84.4 % intervention vs 67.6 % control ; P < .0001 ) ; took low-dose aspirin , if indicated ( 78.6 % intervention vs 52.3 % control ; P < .0001 ) ; and received Pneumovax because of chronic health conditions ( 82.5 % vs 53.9 % ; P < .0001 ) and age ( 86.3 % vs 44.6 % ; P < .0001 ) , despite having fewer visits over the study period compared with those in the control group ( average of 2.9 vs 4.3 visits ; P < .0001 ) . Children in the intervention group received 95.5 % of all recommended immunizations compared with 87.2 % in the control group ( P = .044 ) . Conclusions : A comprehensive patient portal integrated into the regular process of primary care can increase the patient-centeredness of care , improve patient activation , enhance the delivery of both age- and risk factor – appropriate preventive services , and promote the utilization of web-based personal health records This study evaluated the impact of two interventions : ( 1 ) detailed feedback about a patient 's mental health problem and desires for specific mental health interventions , and ( 2 ) a counseling protocol on medical residents ' management of patients with mental health problems . These patients were seen in either a control , feedback , or feedback/ protocol clinic . Immediately following their medical visit we found the following differences between feedback and control patients : feedback patients reported that the stress counseling they received was more valuable , and they were more satisfied with their physician ; feedback patients also perceived greater decreases in the amount of overall stress experienced , and reported greater increases in their perceived control over stress . There were no outcome differences between feedback and feedback/ protocol patients . We conclude that the feedback provided in this study can enhance physicians ' ability to counsel primary care patients with mental health problems Background : The percentage of patients receiving long‐term treatment with acid suppressive drugs , mainly proton pump inhibitors , is higher than the prevalence of diseases that are commonly accepted as the proper indication for long‐term proton pump inhibitor use BACKGROUND Less than 63 % of individuals with diabetes meet professional guidelines target of hemoglobin A1c < 7.0 % , and only 7 % meet combined glycemic , lipid , and blood pressure goals . The primary study aim was to assess the impact on A1c of a cell phone-based diabetes management software system used with web-based data analytics and therapy optimization tools . Secondary aims examined health care provider ( HCP ) adherence to prescribing guidelines and assessed HCPs ' adoption of the technology . METHODS Thirty patients with type 2 diabetes were recruited from three community physician practice s for a 3-month study and evenly r and omized . The intervention group received cell phone-based software design ed by endocrinologists and CDEs ( WellDoc Communications , Inc. , Baltimore , MD ) . The software provided real-time feedback on patients ' blood glucose levels , displayed patients ' medication regimens , incorporated hypo- and hyperglycemia treatment algorithms , and requested additional data needed to evaluate diabetes management . Patient data captured and transferred to secure servers were analyzed by proprietary statistical algorithms . The system sent computer-generated logbooks ( with suggested treatment plans ) to intervention patients ' HCPs . RESULTS The average decrease in A1c for intervention patients was 2.03 % , compared to 0.68 % ( P < 0.02 , one-tailed ) for control patients . Of the intervention patients , 84 % had medications titrated or changed by their HCP compared to controls ( 23 % , P = 0.002 ) . Intervention patients ' HCPs reported the system facilitated treatment decisions , provided organized data , and reduced logbook review time . CONCLUSIONS Adults with type 2 diabetes using WellDoc 's software achieved statistically significant improvements in A1c . HCP and patient satisfaction with the system was clinical ly and statistically significant Background The pneumococcal vaccine is widely underused . Patient education is one mechanism not widely explored for increasing vaccination rates . Objective To evaluate the effects of a culturally appropriate patient education videotape on pneumococcal vaccination rates among the clinic population of an inner-city public hospital . Methods R and omized , controlled trial comparing ( 1 ) a videotapebrochure group who both viewed the videotape and received a lowliteracy brochure , ( 2 ) a videotape only group , and ( 3 ) a control group . Results Of 2,962 charts review ed , 558 patients were r and omized . The study population was 94 % black , 73 % female , and elderly ( mean age 63.0 years ) and 64 % had less than a high school education . Patients in the videotape-brochure group were 2.5 ( 1.8 , 3.5 95 % CI ) times more likely to discuss the vaccine with their physician ( p < .001 ) and 3.5 ( 1.9 , 6.5 95 % CI ) times more likely to receive the vaccine ( p < .001 ) than the control group . The videotape-brochure group was 1.6 ( 1.2 , 2.1 95 % CI ) times more likely to discuss the vaccine ( p < .001 ) and 2.3 ( 1.4 , 3.8 95 % CI ) times more likely to receive the vaccine ( p = .002 ) than the video only group . Patients in the video only group were 1.6 ( 1.1 , 2.3 95 % CI ) times more likely to discuss the vaccine with their physician than the control group ( p = .041 ) but were not more likely to receive the vaccine . Conclusion A culturally appropriate videotape along with a lowliteracy brochure significantly increased pneumococcal vaccination rates and physician-patient discussion about the vaccine . These significant outcomes were not observed with use of videotape alone and were likely attributable to the effect of the brochure . We recommend that patient education initiatives to increase vaccination rates not focus solely on audiovisual media |
904 | 31,208,133 | Total flavonoids and specific subclasses , but not total polyphenols , have been apparently associated with a low risk of diabetes , cardiovascular events and all-cause mortality . | Growing evidence support association between polyphenol intake and reduced risk for chronic diseases , even if there is a broad debate about the effective amount of polyphenols able to exert such protective effect .
The present systematic review provides an overview of the last 10-year literature on the evaluation of polyphenol intake and its association with specific disease markers and /or endpoints . | BACKGROUND Flavonoids are bioactive compounds found in foods such as tea , chocolate , red wine , fruit , and vegetables . Higher intakes of specific flavonoids and flavonoid-rich foods have been linked to reduced mortality from specific vascular diseases and cancers . However , the importance of flavonoids in preventing all-cause mortality remains uncertain . OBJECTIVE The objective was to explore the association between flavonoid intake and risk of 5-y mortality from all causes by using 2 comprehensive food composition data bases to assess flavonoid intake . DESIGN The study population included 1063 r and omly selected women aged > 75 y. All-cause , cancer , and cardiovascular mortalities were assessed over 5 y of follow-up through the Western Australia Data Linkage System . Two estimates of flavonoid intake ( total flavonoidUSDA and total flavonoidPE ) were determined by using food composition data from the USDA and the Phenol-Explorer ( PE ) data bases , respectively . RESULTS During the 5-y follow-up period , 129 ( 12 % ) deaths were documented . Participants with high total flavonoid intake were at lower risk [ multivariate-adjusted HR ( 95 % CI ) ] of 5-y all-cause mortality than those with low total flavonoid consumption [ total flavonoidUSDA : 0.37 ( 0.22 , 0.58 ) ; total flavonoidPE : 0.36 ( 0.22 , 0.60 ) ] . Similar beneficial relations were observed for both cardiovascular disease mortality [ total flavonoidUSDA : 0.34 ( 0.17 , 0.69 ) ; flavonoidPE : 0.32 ( 0.16 , 0.61 ) ] and cancer mortality [ total flavonoidUSDA : 0.25 ( 0.10 , 0.62 ) ; flavonoidPE : 0.26 ( 0.11 , 0.62 ) ] . CONCLUSIONS Using the most comprehensive flavonoid data bases , we provide evidence that high consumption of flavonoids is associated with reduced risk of mortality in older women . The benefits of flavonoids may extend to the etiology of cancer and cardiovascular disease Flavonols , flavanones and flavones ( FLAV ) are sub-classes of flavonoids that exert cardioprotective and anti-carcinogenic properties in vitro and in vivo . We aim ed to estimate the FLAV dietary intake , their food sources and associated lifestyle factors in ten European countries participating in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) study . FLAV intake and their food sources for 36 037 subjects , aged between 35 and 74 years , in twenty-seven study centres were obtained using st and ardised 24 h dietary recall software ( EPIC-SOFT ) . An ad hoc food composition data base on FLAV was compiled using data from US Department of Agriculture and Phenol-Explorer data bases and was exp and ed using recipes , estimations and flavonoid retention factors in order to increase its correspondence with the 24 h dietary recall . Our results showed that the highest FLAV-consuming centre was the UK health-conscious group , with 130·9 and 97·0 mg/d for men and women , respectively . The lowest FLAV intakes were 36·8 mg/d in men from Umeå and 37·2 mg/d in women from Malmö ( Sweden ) . The flavanone sub-class was the main contributor to the total FLAV intake ranging from 46·6 to 52·9 % depending on the region . Flavonols ranged from 38·5 to 47·3 % and flavones from 5·8 to 8·6 % . FLAV intake was higher in women , non-smokers , increased with level of education and physical activity . The major food sources were citrus fruits and citrus-based juices ( especially for flavanones ) , tea , wine , other fruits and some vegetables . We concluded that the present study shows heterogeneity in intake of these three sub-classes of flavonoids across European regions and highlights differences by sex and other sociodemographic and lifestyle factors BACKGROUND The association of the polyphenol content of human diet with pulmonary function is not yet fully understood . This study aims at evaluating the association of polyphenol consumption with lung function in a novel holistic approach . METHODS A cross-sectional analysis of 4551 women and 5108 men ( age ≥35 years ) from the Moli-sani study was performed . Participants were r and omly recruited from the general population . The EPIC-FFQ was used for the dietary assessment . Polyphenol intakes were calculated using Eurofir-eBASIS , and a polyphenol antioxidant content ( PAC ) score was constructed to assess the total content of the diet in these nutrients . Pulmonary function maneuvers were performed , and the forced vital capacity ( FVC ) and forced expiratory volume in the first second ( FEV1 ) were measured ; FVC% predicted and FEV1 % predicted were computed using the European Community of Coal and Steel prediction equations that included height and age . RESULTS In both genders , in age , height , and energy intake adjusted models , the majority of classes of polyphenols ( mg/day ) showed a positive association with FEV1 , FVC , FEV1 % predicted , and FVC% predicted ( β-coef > 0 , P < .05 ) . Associations remained significant after adjustment for confounding factors in most cases ( β-coef > 0 , P < .05 ) . The PAC score was associated in both genders with an increase in pulmonary function parameters ( β-coef > 0 , P < .05 ) . The inclusion of white blood cell ( WBC ) counts in the multivariate model reduced the association in men but not in women . . CONCLUSIONS A higher overall polyphenol content of human diet was associated with better pulmonary function in a general population . The association might be partially mediated by WBC in men OBJECTIVES The effect of the polyphenol content of the human diet on mortality risk is not yet fully understood . The aim of this study was to evaluate the association of a polyphenol-rich diet with mortality rate and a possible mediation effect by inflammation , in what we believe to be a novel , holistic approach . METHODS We analyzed 21 302 participants ( 10 980 women and 10 322 men , aged ≥35 y ) from the Moli-sani cohort . The participants were followed up for a median of 8.3 y. The European Prospect i ve Investigation into Cancer and Nutrition food frequency question naire ( FFQ ) was used for dietary assessment . Flavonol , flavone , flavanone , flavanol , anthocyanin , isoflavone , and lignan intakes were calculated using European Food Information Re source -Bioactive Substances in Food Information Systems and the polyphenol antioxidant content (PAC)-score was constructed to assess the total content of these nutrients in the diet . RESULTS Participants included in the highest quintile of intake of various polyphenol classes and subclasses presented a significant lower all-cause mortality risk compared with those in the lowest group of consumption ( hazard ratio [ HR ] < 1 ; P < 0.05 ) . Cox regression analyses adjusted for potential confounders indicated that participants in higher quintiles of PAC-score had lower all-cause mortality risk ( HR < 1 ; P < 0.05 ) . When cause-specific mortality rates were considered , similar effects were observed for cardiocerebrovascular and cancer mortality ( HR < 1 ; P < 0.05 ) . CONCLUSIONS The polyphenol content of the diet was associated with reduced mortality risk in a Mediterranean population , possibly through an antiinflammatory mechanism BACKGROUND Flavonoids are plant-based phytochemicals with cardiovascular protective properties . Few studies have comprehensively examined flavonoid classes in relation to cardiovascular disease mortality . OBJECTIVE We examined the association between flavonoid intake and cardiovascular disease ( CVD ) mortality among participants in a large , prospect i ve US cohort . DESIGN In 1999 , a total of 38,180 men and 60,289 women in the Cancer Prevention Study II Nutrition Cohort with a mean age of 70 and 69 y , respectively , completed question naires on medical history and lifestyle behaviors , including a 152-item food-frequency question naire . Cox proportional hazards modeling was used to calculate multivariate-adjusted hazard RRs and 95 % CIs for associations between total flavonoids , 7 flavonoid classes , and CVD mortality . RESULTS During 7 y of follow-up , 1589 CVD deaths in men and 1182 CVD deaths in women occurred . Men and women with total flavonoid intakes in the top ( compared with the bottom ) quintile had a lower risk of fatal CVD ( RR : 0.82 ; 95 % CI : 0.73 , 0.92 ; P-trend = 0.01 ) . Five flavonoid classes-anthocyanidins , flavan-3-ols , flavones , flavonols , and proanthocyanidins-were individually associated with lower risk of fatal CVD ( all P-trend < 0.05 ) . In men , total flavonoid intakes were more strongly associated with stroke mortality ( RR : 0.63 ; 95 % CI : 0.44 , 0.89 ; P-trend = 0.04 ) than with ischemic heart disease ( RR : 0.90 ; 95 % CI : 0.72 , 1.13 ) . Many associations appeared to be nonlinear , with lower risk at intakes above the referent category . CONCLUSIONS Flavonoid consumption was associated with lower risk of death from CVD . Most inverse associations appeared with intermediate intakes , suggesting that even relatively small amounts of flavonoid-rich foods may be beneficial Background : Flavonoids exert anti-inflammatory properties and modulate oxidative stress in vitro , suggesting a protective effect on lung function , but epidemiological studies examining this association are scarce . Methods : A stratified r and om sample was drawn from the GA2LEN screening survey , in which 55,000 adults aged 15 to 75 answered a question naire on respiratory symptoms . Post-bronchodilator spirometry was obtained from 2850 subjects . Forced vital capacity ( FVC ) , the ratio between the forced exhaled volume in 1 second ( FEV1 ) and FVC ( FEV1/FVC ) , FVC below lower limit of normal ( FVC < LLN ) , and FEV1/FVC < LLN were calculated . Intake of the six main subclasses of flavonoids was estimated using the GA2LEN Food Frequency Question naire . Adjusted associations between outcomes and each subclass of flavonoids were examined with multivariate regressions . Simes ’ procedure was used to test for multiple comparisons . Results : A total of 2599 subjects had valid lung function and dietary data . A lower prevalence of FVC < LLN ( airway restriction ) was observed in those with higher total flavonoid ( adjusted odds ratio ( aOR ) , higher vs. lowest quintile intake 0.58 ; 95 % Confidence Interval ( CI ) 0.36 , 0.94 ) , and pro-anthocyanidin intakes ( aOR 0.47 ; 95 % CI 0.27 , 0.81 ) . A higher FEV1/FVC was associated with higher intakes of total flavonoids and pro-anthocyanidins ( adjusted correlation coefficient ( a β-coeff 0.33 ; 0.10 , 0.57 and a β-coeff 0.44 ; 95 % CI 0.19 , 0.69 , respectively ) . After Simes ’ procedure , the statistical significance of each of these associations was attenuated but remained below 0.05 , with the exception of total flavonoids and airway restriction . Conclusions : This population -based study in European adults provides cross-sectional evidence of a positive association of total flavonoid intake and pro-anthocyanidins and ventilatory function , and a negative association with spirometric restriction in European adults Background / Objectives : The objective of this study is to extract and assess data on the dietary intake of flavonoids and lignans in a healthy free-living Mediterranean population , using newly up date d harmonized European Union food composition data . This work also aim ed at analyzing in a holistic way the total content of the diet in major classes of polyphenols . Subjects/ Methods : Six thous and nine hundred and eighty-one men and 7048 women ( aged ⩾35years ) of the Moli-sani cohort , r and omly recruited from the general population , were analyzed . The European Prospect i ve Investigation into Cancer ( EPIC ) and Nutrition-Food Frequency Question naire was used for dietary assessment . The polyphenol content of each food group was evaluated using Eurofir BioActive Substances in Food Information System and the United States Department of Agriculture food composition tables ( FCTs ) , when data were missing . Flavonol , flavone , flavanone , flavanol , anthocyanin , isoflavone and lignan intakes were calculated and polyphenol antioxidant content ( PAC ) score ( −28 , 28 ) constructed , to assess the total content of the diet in these nutrients . Results : Seasonal and citrus fruits , leafy , grain , pod and root vegetables , and onions and garlic accounted for different proportions ( 11–70 % ) of the total intake of different polyphenols . Within the Moli-sani population , men or older , or no/former smokers , or physically active or obese/overweight individuals presented higher consumption of flavonoids , lignans and PAC score ( P for all < 0.01 ) . Multiple regression analysis showed that PAC score and its seven components were positively associated with Mediterranean diet ( MeD ) adherence in both genders ( β-coefficient > 0 , P<0.001 ) . In addition , 1 unit increase in PAC score was associated with 7.1–7.8 % increase in the likelihood of high MeD adherence ( P<0.001 ) . Conclusions : The intake of flavonoids and lignans in an European Union population was calculated using harmonized European Union FCT data . In addition , a holistic approach in dietary analysis of polyphenol intake was proposed Dietary Reference Intake ( DRI ) values exist for vitamins and minerals , and provide a guideline on the optimal dose range to avoid deficiency and prevent toxicity . Polyphenols are widely distributed in plant foods , and have been linked to improved human health through reduced risk of chronic diseases , especially cardiovascular . Although they do not cause classical deficiencies , recently they have been discussed as ' lifespan essentials because they are needed to achieve a full lifespan by reducing the risk of a range of chronic diseases . A recent meta analysis shows promising actions of polyphenols from cocoa , soya and tea on flow mediated dilation , blood pressure and LDL cholesterol . Many epidemiological studies support the action of polyphenols or polyphenol-rich foods on health , but there are still many gaps in our knowledge . More adequately powered , r and omised , placebo controlled human studies are needed on polyphenols . There is a large number of structurally different polyphenols which are relevant for health , and obtaining enough information to set a DRI for each of these will not be feasible in the foreseeable future . A new approach is needed , and a new way of thinking , which would apply not only to polyphenols but also to other phytochemicals . Today , a target intake value of polyphenols as ' lifespan essentials ' needs to be based on the amount of polyphenols in ' 5-a-day ' . We are heading in the right direction towards a DRI , but bioavailability and dose-effects , including toxic levels , need to be established before DRIs can be considered Thearubigins ( TR ) are polymeric flavanol-derived compounds formed during the fermentation of tea leaves . Comprising ∼70 % of total polyphenols in black tea , TR may contribute majorly to its beneficial effects on health . To date , there is no appropriate food composition data on TR , although several studies have used data from the US Department of Agriculture ( USDA ) data base to estimate TR intakes . We aim ed to estimate dietary TR in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) cohort and assess the impact of including TR or not in the calculation of the total dietary flavonoid intake . Dietary data were collected using a single st and ardized 24-h dietary recall interviewer-administered to 36 037 subjects aged 35–74 years . TR intakes were calculated using the USDA data base . TR intakes ranged from 0.9 mg/day in men from Navarra and San Sebastian in Spain to 532.5 mg/day in men from UK general population . TR contributed < 5 % to the total flavonoid intake in Greece , Spain and Italy , whereas in the UK general population , TR comprised 48 % of the total flavonoids . High heterogeneity in TR intake across the EPIC countries was observed . This study shows that total flavonoid intake may be greatly influenced by TR , particularly in high black tea-consuming countries . Further research on identification and quantification of TR is needed to get more accurate dietary TR estimations Background : Dietary flavonoids and lignans may protect against several chronic diseases , but there is little evidence on the relationship between flavonoid and lignan intake and mortality . We investigated the association between both all-cause and specific-cause mortality and intake of flavonoids and lignans in the Spanish European Prospect i ve Investigation into Cancer and Nutrition ( EPIC-Spain ) cohort . Methods : The EPIC-Spain study follows 40,622 participants ( 38 % men ) aged 29–69 years . A vali date d diet history question naire was administered at recruitment . A food composition data base was compiled based on US Department of Agriculture and Phenol-Explorer data bases . Cox proportional hazards models , adjusted for confounders , were used in the analyses . Results : During a mean follow-up of 13.6 years , 1915 deaths were reported , with 416 from cardiovascular diseases ( CVDs ) and 956 from cancer . After adjustment for several potential confounders , the hazard ratios ( HRs ) for the highest versus the lowest quintile of dietary flavanone and flavonol intakes were 0.60 ( 95 % confidence interval = 0.38–0.94 ) and 0.59 ( 0.40–0.88 ) . Total flavonoid intake was also associated with a decrease in all-cause mortality ( 0.71 [ 0.49–1.03 ] ) . Lignan intake was not associated with all-cause mortality . In cause-specific mortality analyses , using competing risk regressions , doubling total flavonoid intake was inversely related to mortality from CVD ( HR for log2 0.87 [ 0.77–0.98 ] ) , but not to mortality from either cancer ( HR for log2 0.96 [ 0.89–1.04 ] ) or other causes ( HR for log2 0.97 [ 0.87–1.09 ] ) . Conclusions : A diet high in flavonoids , particularly in flavanones and flavonols , is associated with a reduction in all-cause mortality , mainly of mortality from CVD Epidemiological studies suggest health-protective effects of flavan-3-ols and their derived compounds on chronic diseases . The present study aim ed to estimate dietary flavan-3-ol , proanthocyanidin ( PA ) and theaflavin intakes , their food sources and potential determinants in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) calibration cohort . Dietary data were collected using a st and ardised 24 h dietary recall software administered to 36 037 subjects aged 35 - 74 years . Dietary data were linked with a flavanoid food composition data base compiled from the latest US Department of Agriculture and Phenol-Explorer data bases and exp and ed to include recipes , estimations and retention factors . Total flavan-3-ol intake was the highest in UK Health-conscious men ( 453·6 mg/d ) and women of UK General population ( 377·6 mg/d ) , while the intake was the lowest in Greece ( men : 160·5 mg/d ; women : 124·8 mg/d ) . Monomer intake was the highest in UK General population ( men : 213·5 mg/d ; women : 178·6 mg/d ) and the lowest in Greece ( men : 26·6 mg/d in men ; women : 20·7 mg/d ) . Theaflavin intake was the highest in UK General population ( men : 29·3 mg/d ; women : 25·3 mg/d ) and close to zero in Greece and Spain . PA intake was the highest in Asturias ( men : 455·2 mg/d ) and San Sebastian ( women : 253 mg/d ) , while being the lowest in Greece ( men : 134·6 mg/d ; women : 101·0 mg/d ) . Except for the UK , non-citrus fruits ( apples/pears ) were the highest contributors to the total flavan-3-ol intake . Tea was the main contributor of total flavan-3-ols in the UK . Flavan-3-ol , PA and theaflavin intakes were significantly different among all assessed groups . This study showed heterogeneity in flavan-3-ol , PA and theaflavin intake throughout the EPIC countries Objective The aim of this study was to estimate the intake of known individual polyphenols and their major dietary sources in the Polish arm of the HAPIEE ( Health , Alcohol and Psychosocial factors In Eastern Europe ) study . Methods A total of 10,477 r and om sample ( 45–69 y ) of urban population of Krakow , Pol and , completed a vali date d 148-item food frequency question naire . Polyphenol intake was calculated by matching food consumption data with the recently developed Phenol-Explorer data base . Results The mean intake of polyphenols was 1756.5 ± 695.8 mg/d ( median = 1662.5 mg/d ) . The main polyphenol groups were flavonoids ( 897 mg/d ) and phenolic acids ( 800 mg/d ) . A total of 347 polyphenols from 19 polyphenol subclasses were found . The individual compounds with the highest intakes were isomers of chlorogenic acid ( i.e. , 5-caffeoylquinic acid and 4-caffeoylquinic acid ) among hydroxycinnamic acids ( average intake 150 mg/d ) , that largely originated from coffee , and compounds belonging to the catechin chemical family ( i.e. , [+]-gallocatechin , [-]-epigallocatechin 3-O-gallate , and [-]-epicatechin ) among flavanols ( average intake 50 mg/d ) , that mostly originated from tea and cocoa products . Conclusions The current study provides the most up date d data for individual polyphenols intake in the diet of a well-established nutritional cohort . These findings will be useful to assess potential beneficial role on health of specific foods with high polyphenol content and characterize the effects of individual phenolic compounds Dietary flavanols and flavonols , flavonoid subclasses , have been recently associated with a lower risk of type 2 diabetes ( T2D ) in Europe . Even within the same subclass , flavonoids may differ considerably in bioavailability and bioactivity . We aim ed to examine the association between individual flavanol and flavonol intakes and risk of developing T2D across European countries . The European Prospect i ve Investigation into Cancer and Nutrition (EPIC)–InterAct case-cohort study was conducted in 8 European countries across 26 study centers with 340,234 participants contributing 3.99 million person-years of follow-up , among whom 12,403 incident T2D cases were ascertained and a center-stratified subcohort of 16,154 individuals was defined . We estimated flavonoid intake at baseline from vali date d dietary question naires using a data base developed from Phenol-Explorer and USDA data bases . We used country-specific Prentice-weighted Cox regression models and r and om-effects meta- analysis methods to estimate HRs . Among the flavanol subclass , we observed significant inverse trends between intakes of all individual flavan-3-ol monomers and risk of T2D in multivariable models ( all P-trend < 0.05 ) . We also observed significant trends for the intakes of proanthocyanidin dimers ( HR for the highest vs. the lowest quintile : 0.81 ; 95 % CI : 0.71 , 0.92 ; P-trend = 0.003 ) and trimers ( HR : 0.91 ; 95 % CI : 0.80 , 1.04 ; P-trend = 0.07 ) but not for proanthocyanidins with a greater polymerization degree . Among the flavonol subclass , myricetin ( HR : 0.77 ; 95 % CI : 0.64 , 0.93 ; P-trend = 0.001 ) was associated with a lower incidence of T2D . This large and heterogeneous European study showed inverse associations between all individual flavan-3-ol monomers , proanthocyanidins with a low polymerization degree , and the flavonol myricetin and incident T2D . These results suggest that individual flavonoids have different roles in the etiology of T2D BACKGROUND Dietary flavonoids have beneficial effects on blood pressure in intervention setting s , but there is limited information on habitual intake and risk of hypertension in population -based studies . OBJECTIVE We examined the association between habitual flavonoid intake and incident hypertension in a prospect i ve study in men and women . DESIGN A total of 87,242 women from the Nurses ' Health Study ( NHS ) II , 46,672 women from the NHS I , and 23,043 men from the Health Professionals Follow-Up Study ( HPFS ) participated in the study . Total flavonoid and subclass intakes were calculated from semiquantitative food-frequency question naires collected every 4 y by using an up date d and extended US Department of Agriculture data base . RESULTS During 14 y of follow-up , 29,018 cases of hypertension in women and 5629 cases of hypertension in men were reported . In pooled multivariate-adjusted analyses , participants in the highest quintile of anthocyanin intake ( predominantly from blueberries and strawberries ) had an 8 % reduction in risk of hypertension [ relative risk ( RR ) : 0.92 ; 95 % CI : 0.86 , 0.98 ; P < 0.03 ] compared with that for participants in the lowest quintile of anthocyanin intake ; the risk reduction was 12 % ( RR : 0.88 ; 95 % CI : 0.84 , 0.93 ; P < 0.001 ) in participants ≤60 y of age and 0.96 ( 0.91 , 1.02 ) in participants > 60 y of age ( P for age interaction = 0.02 ) . Although intakes of other subclasses were not associated with hypertension , pooled analyses for individual compounds suggested a 5 % ( 95 % CI : 0.91 , 0.99 ; P = 0.005 ) reduction in risk for the highest compared with the lowest quintiles of intake of the flavone apigenin . In participants ≤60 y of age , a 6 % ( 95 % CI : 0.88 , 0.97 ; P = 0.002 ) reduction in risk was observed for the flavan-3-ol catechin when the highest and the lowest quintiles were compared . CONCLUSIONS Anthocyanins and some flavone and flavan-3-ol compounds may contribute to the prevention of hypertension . These vasodilatory properties may result from specific structural similarities ( including the B-ring hydroxylation and methyoxylation pattern ) This study examines the relationship between long-term intake of six flavonoid classes and incidence of CVD and CHD , using a comprehensive flavonoid data base and repeated measures of intake , while accounting for possible confounding by components of a healthy dietary pattern . Flavonoid intakes were assessed using a FFQ among the Framingham Offspring Cohort at baseline and three times during follow-up . Cox proportional hazards regression was used to characterise prospect i ve associations between the natural logarithms of flavonoid intakes and CVD incidence using a time-dependent approach , in which intake data were up date d at each examination to represent average intakes from previous examinations . Mean baseline age was 54 years , and 45 % of the population was male . Over an average 14·9 years of follow-up among 2880 participants , there were 518 CVD events and 261 CHD events . After multivariable adjustment , only flavonol intake was significantly associated with lower risk of CVD incidence ( hazard ratios ( HR ) per 2·5-fold flavonol increase=0·86 , P trend=0·05 ) . Additional adjustment for total fruit and vegetable intake and overall diet quality attenuated this observation ( HR=0·89 , P trend=0·20 and HR=0·92 , P trend=0·33 , respectively ) . There were no significant associations between flavonoids and CHD incidence after multivariable adjustment . Our findings suggest that the observed association between flavonol intake and CVD risk may be a consequence of better overall diet . However , the strength of this non-significant association was also consistent with relative risks observed in previous meta-analyses , and therefore a modest benefit of flavonol intake on CVD risk can not be ruled out Background Progression to chronic renal failure involves accelerated atherosclerosis and vascular calcification . Oxidative stress and endothelial dysfunction play a role in renal failure pathophysiology . In addition to improving vascular health and function , proanthocyanidins have been shown to exert renoprotective effects in animal models . Thus we hypothesize that proanthocyanidins may contribute to the maintenance of healthy renal function . Objective Determine the association of habitual proanthocyanidin intake with renal function and the risk of clinical renal outcomes in a population of elderly women . Design 948 women aged over 75 y , free of prevalent renal disease at baseline , were r and omly selected from ambulant Caucasian women . Proanthocyanidin consumption was determined using a vali date d food frequency question naire and the United States Department of Agriculture proanthocyanidin food content data base . Fasting serum cystatin C and creatinine were assessed at baseline . Renal failure hospitalisations and deaths were assessed over 5 years of follow-up through the Western Australia Data Linkage System . Results Compared to participants with low consumption , participants in the highest tertile of proanthocyanidin intake had a 9 % lower cystatin C concentration ( P<0.001 ) . High proanthocyanidin consumers were at 50 % lower risk of moderate chronic kidney insufficiency , and 65 % lower risk of experiencing a 5-year renal disease event ( P<0.05 ) . These relationships remained significant following adjustment for renal disease risk factors and diet-related potential confounders . Conclusion Increased consumption of proanthocyanidins was associated with better renal function and substantially reduced renal associated events , which has been supported by mechanistic and animal model data . Proanthocyanidin intake should be further examined as a dietary contributor to better renal health Anthocyanidins are bioactive flavonoids with potential health-promoting effects . These may vary among single anthocyanidins considering differences in their bioavailability and some of the mechanisms involved . The aim of the present study was to estimate the dietary intake of anthocyanidins , their food sources and the lifestyle factors ( sex , age , BMI , smoking status , educational level and physisical activity ) involved among twenty-seven centres in ten European countries participating in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) study . Anthocyanidin intake and their food sources for 36 037 subjects , aged between 35 and 74 years , in twenty-seven redefined centres were obtained using st and ardised 24 h dietary recall software ( EPIC-SOFT ) . An ad hoc food composition data base on anthocyanidins ( cyanidin , delphinidin , malvidin , pelargonidin , peonidin , petunidin ) was compiled using data from the US Department of Agriculture and Phenol-Explorer data bases and was exp and ed by adding recipes , estimated values and cooking factors . For men , the total anthocyanidin mean intake ranged from 19·83 ( se 1·53 ) mg/d ( Bilthoven , The Netherl and s ) to 64·88 ( se 1·86 ) mg/d ( Turin , Italy ) , whereas for women the range was 18·73 ( se 2·80 ) mg/d ( Granada , Spain ) to 44·08 ( se 2·45 ) mg/d ( Turin , Italy ) . A clear south to north gradient intake was observed . Cyanidins and malvidins were the main anthocynidin contributors depending on the region and sex . Anthocyanidin intake was higher in non-obese older females , non-smokers , and increased with educational level and physical activity . The major food sources were fruits , wine , non-alcoholic beverages and some vegetables . The present study shows differences in both total and individual anthocyanidin intakes and various lifestyle factors throughout Europe , with some geographical variability in their food sources PURPOSE Polyphenols play an important role in the prevention of degenerative diseases , particularly cardiovascular diseases and cancers . The purpose was to estimate dietary polyphenol intake in Polish adults , using own data base of food polyphenols , and to establish main dietary sources of polyphenols . MATERIAL AND METHODS Polish men and women ( 6661 ) aged 20 - 74 years were r and omly selected from the Polish National Multicenter Health Survey ( WOBASZ ) . Subjects ` daily food consumption was estimated by the 24-hour recall method and was continued for 3 years . It was determined on this basis , that 96 plant foods and plant food products were consumed . The own dietary data base of polyphenol contents in food was used to calculate polyphenol intakes in the subjects . The daily total polyphenol intakes were calculated for both genders in individual age categories : 20 - 40 years , 41 - 60 years and 61 - 74 years . RESULTS The average polyphenol consumption for the men was 1172 mg/day , and for the women it made 1031 mg/day . Plant food categories such as beverages , vegetables , fruits and cereals were found to be significant sources of polyphenols , of which tea , coffee , potatoes , apples and white bread were the main contributors . CONCLUSIONS The amount of polyphenol consumption in Polish adult population is similar to the polyphenol intake in other countries population s , accounting roughly for 1 g of polyphenols for both genders and different age groups . Patterns of polyphenol consumption , however , vary for genders and age groups . Polyphenols are characterized by a spectrum of antioxidant capabilities , therefore future studies should focus on dietary intakes of individual polyphenols BACKGROUND Observational studies have linked tea drinking , a major source of dietary flavonoids , with higher bone density . However , there is a paucity of prospect i ve studies examining the association of tea drinking and flavonoid intake with fracture risk . OBJECTIVE The objective of this study was to examine the associations of black tea drinking and flavonoid intake with fracture risk in a prospect i ve cohort of women aged > 75 y. DESIGN A total of 1188 women were assessed for habitual dietary intake with a food-frequency and beverage question naire . Incidence of osteoporotic fracture requiring hospitalization was determined through the Western Australian Hospital Morbidity Data system . Multivariable adjusted Cox regression was used to examine the HRs for incident fracture . RESULTS Over 10 y of follow-up , osteoporotic fractures were identified in 288 ( 24.2 % ) women ; 212 ( 17.8 % ) were identified as a major osteoporotic fracture , and of these , 129 ( 10.9 % ) were a hip fracture . In comparison with the lowest tea intake category ( ≤1 cup/wk ) , consumption of ≥3 cups/d was associated with a 30 % decrease in the risk of any osteoporotic fracture ( HR : 0.70 ; 95 % CI : 0.50 , 0.96 ) . Compared with women in the lowest tertile of total flavonoid intake ( from tea and diet ) , women in the highest tertile had a lower risk of any osteoporotic fracture ( HR : 0.65 ; 95 % CI : 0.47 , 0.88 ) , major osteoporotic fracture ( HR : 0.66 ; 95 % CI : 0.45 , 0.95 ) , and hip fracture ( HR : 0.58 ; 95 % CI : 0.36 , 0.95 ) . For specific classes of flavonoids , statistically significant reductions in fracture risk were observed for higher intake of flavonols for any osteoporotic fracture and major osteoporotic fracture , as well as flavones for hip fracture ( P < 0.05 ) . CONCLUSION Higher intake of black tea and particular classes of flavonoids were associated with lower risk of fracture-related hospitalizations in elderly women at high risk of fracture Epidemiological studies have indicated that dietary flavonoids generally , and flavonols specifically , may contribute to cardiovascular health . Tea consumption , which is often the main dietary source of flavonoids and flavonols , is associated with a reduced risk of cardiovascular outcomes . The primary objective of the present study was to explore the association of the habitual intake of flavonols from tea and non-tea sources with the risk of atherosclerotic vascular disease mortality in a population of elderly women . A total of 1063 women , aged over 75 years , were r and omly selected from ambulant Caucasian women living in Perth , Western Australia . Flavonoid consumption was assessed using the US Department of Agriculture Flavonoid , Flavone and Proanthocyanidin data bases . Atherosclerotic vascular disease mortality was assessed over 5 years of follow-up through the Western Australian Data Linkage System . During the follow-up , sixty-four women died from atherosclerotic vascular disease . Women in the highest compared with the lowest tertile of flavonol intake had a lower risk of atherosclerotic vascular disease death ( OR 0·27 , 95 % CI 0·13 , 0·59 ; P≤ 0·01 for trend in multivariate-adjusted models ) . Similar relationships were observed for flavonol intake derived from both tea ( OR 0·38 , 95 % CI 0·18 , 0·79 ; P < 0·01 ) and non-tea ( OR 0·41 , 95 % CI 0·20 , 0·85 ; P= 0·05 ) sources . Tea was the main contributor to flavonol intake ( 65 % ) , and the intakes of flavonols from tea and non-tea sources were not significantly correlated . In conclusion , increased consumption of flavonols was independently associated with a lower risk of atherosclerotic vascular disease mortality . Both tea and non-tea sources of flavonols were independently associated with this benefit BACKGROUND Flavonoids may have beneficial cerebrovascular effects , but evidence from racially and geographically representative cohorts in comprehensive flavonoid data bases is lacking . Given racial and geographic disparities in stroke incidence , representative cohort studies are needed . OBJECTIVES We evaluated the association between flavonoid intake and incident ischemic stroke in a biracial , national cohort using up date d flavonoid composition tables and assessed differences in flavonoid intake by sex , race , and region of residence . METHODS We evaluated 20,024 participants in the REGARDS ( REasons for Geographic and Racial Differences in Stroke ) study , a biracial prospect i ve study . Participants with stroke history or missing dietary data were excluded . Flavonoid intake was estimated by using a Block98 food frequency question naire and the USDA 's Provisional Flavonoid Addendum and Proanthocyanidin Data base . Associations between quintiles of flavonoid intake and incident ischemic stroke were evaluated by using Cox proportional hazards models , adjusting for confounders . RESULTS Over 6.5 y , 524 acute ischemic strokes occurred . Flavanone intake was lower in the Southeastern United States but higher in blacks than in whites . After multivariable adjustment , flavanone intake was inversely associated with incident ischemic stroke ( HR : 0.72 ; 95 % CI : 0.55 , 0.95 ; P-trend = 0.03 ) . Consumption of citrus fruits and juices was inversely associated with incident ischemic stroke ( HR : 0.69 ; 95 % CI : 0.53 , 0.91 ; P-trend = 0.02 ) . Total flavonoids and other flavonoid subclasses were not associated with incident ischemic stroke . There was no statistical interaction with sex , race , or region for any flavonoid measure . CONCLUSIONS Greater consumption of flavanones , but not total or other flavonoid subclasses , was inversely associated with incident ischemic stroke . Associations did not differ by sex , race , or region for the association ; however , regional differences in flavanone intake may contribute to regional disparities in ischemic stroke incidence . Higher flavanone intake in blacks suggests that flavanone intake is not implicated in racial disparities in ischemic stroke incidence BACKGROUND AND AIMS Epidemiologic and biological evidence supports an inverse association between polyphenol consumption and the risk of cardiovascular disease ( CVD ) . However , no previous studies have prospect ively evaluated the relationship between polyphenol intake and the incidence of CVD in such a comprehensive way . The aim was to evaluate the association between intakes of total polyphenol and polyphenol subgroups , and the risk of major cardiovascular events ( myocardial infa rct ion , stroke or death from cardiovascular causes ) in the PREDIMED study . METHODS AND RESULTS The present work is an observational study within the PREDIMED trial . Over an average of 4.3 years of follow-up , there were 273 confirmed cases of CVD among the 7172 participants ( 96.3 % ) who completed a vali date d 137-item food frequency question naire ( FFQ ) at baseline . Polyphenol consumption was calculated by matching food consumption data from the FFQ with the Phenol-Explorer data base on polyphenol content of each reported food . After multivariate adjustment , a 46 % reduction in risk of CVD risk was observed comparing Q5 vs. Q1 of total polyphenol intake ( HR = 0.54 ; 95 % confidence interval [ CI ] = 0.33 - 0.91 ; P-trend = 0.04 ) . The polyphenols with the strongest inverse associations were flavanols ( HR = 0.40 ; CI 0.23 - 0.72 ; P-trend = 0.003 ) , lignans ( HR = 0.51 ; CI 0.30 - 0.86 ; P-trend = 0.007 ) , and hydroxybenzoic acids ( HR = 0.47 ; CI 0.26 - 0.86 ; P-trend 0.02 ) . CONCLUSION Greater intake of polyphenols , especially from lignans , flavanols , and hydroxybenzoic acids , was associated with decreased CVD risk . Clinical trials are needed to confirm this effect and establish accurate dietary recommendations BACKGROUND Prospect i ve cohort studies have shown that the consumption of cocoa and tea is associated with lower risk of cardiovascular diseases ( CVDs ) , and cocoa and tea have been shown to improve CVD risk factors in r and omized controlled trials . Cocoa and tea are major dietary sources of the flavan-3-ol epicatechin . OBJECTIVE We investigated the associations of dietary epicatechin intake with 25-y CVD mortality in elderly Dutch men . DESIGN We used data from the Zutphen Elderly Study , which was a prospect i ve cohort study of 774 men aged 65 - 84 y in 1985 . Epicatechin intake was estimated 4 times in 15 y with the use of the crosscheck dietary history method . Time-dependent Cox proportional hazards models were used to investigate repeated measures of epicatechin intake in relation to 25-y CVD mortality . RESULTS Mean intake of epicatechin was 15.2 ± 7.7 mg/d , and the major dietary sources were tea ( 51 % ) , apples ( 28 % ) , and cocoa ( 7 % ) . During 25 y of follow-up , 329 men died from CVD , 148 died from coronary heart disease ( CHD ) , and 72 men died from stroke . Risk of CHD mortality was 38 % lower in men in the top tertile of epicatechin intake than in men in the bottom tertile of epicatechin intake ( HR : 0.62 ; 95 % CI : 0.39 , 0.98 ) . Epicatechin intake was also significantly associated with 46 % lower risk of CVD mortality in men with prevalent CVD ( HR : 0.54 ; 95 % CI : 0.31 , 0.96 ) but not in men who were free of CVD . CONCLUSIONS We show , for the first time to our knowledge , that epicatechin intake is inversely related to CHD mortality in elderly men and to CVD mortality in prevalent cases of CVD . More studies are needed before conclusions can be drawn Objective To investigate the optimal combination of dietary polyphenols associated with the long-term risk of dementia in a large prospect i ve French cohort of older persons , the Three-City ( 3C ) Study . Methods We included 1,329 older adults without dementia from the 3C study with assessment of intake of 26 polyphenol subclasses who were followed up for 12 years for dementia . Using partial least squares for Cox models , we identified a pattern of polyphenol intake associated with dementia risk . Results The pattern combined several flavonoids ( dihydroflavonols , anthocyanins , isoflavonoids , flavanones ) , stilbenes ( including resveratrol ) , lignans , and other subclasses ( hydroxybenzaldehydes , naphthoquinones , furanocoumarins ) . Compared with participants in the lower quintile of pattern score , those in the higher quintile had a 50 % lower risk of dementia ( 95 % confidence interval 20%–68 % , p for trend < 0.01 ) in multivariate models . Conclusions In this French cohort , a polyphenol pattern provided by a diet containing specific plant products ( nuts , citrus , berries , leafy vegetables , soy , cereals , olive oil ) accompanied by red wine and tea was associated with lower dementia risk BACKGROUND AND AIMS Epidemiological data have shown an inverse association between the consumption of polyphenol-rich foods and the risk of cardiovascular disease or overall mortality . A comprehensive estimation of individual polyphenol intake in nutritional cohorts is needed to gain a better underst and ing of this association . The aim of this study was to estimate the quantitative intake of polyphenols and the major dietary sources in the PREDIMED ( PREvención con DIeta MEDiterránea ) cohort using individual food consumption records . METHODS AND RESULTS The PREDIMED study is a large , parallel-group , multicentre , r and omised , controlled 5-year feeding trial aim ed at assessing the effects of the Mediterranean diet on the primary prevention of cardiovascular disease . A total of 7200 participants , aged 55 - 80 years , completed a vali date d 1-year food frequency question naire ( FFQ ) at baseline . Polyphenol consumption was calculated by matching food consumption data from the FFQ with the recently developed Phenol-Explorer data base on polyphenol content in foods . The mean total polyphenol intake was 820 ± 323 mg day⁻¹ ( 443 ± 218 mg day⁻¹ of flavonoids and 304 ± 156 mg day⁻¹ of phenolic acids ) . Hydroxycinnamic acids were the phenolic group with the highest consumption and 5-caffeoylquinic acid was the most abundantly ingested individual polyphenol . The consumption of olives and olive oil was a differentiating factor in the phenolic profile of this Spanish population compared with other countries . CONCLUSION In Mediterranean countries , such as Spain , the main dietary source of polyphenols is coffee and fruits , but the most important differentiating factor with respect to other countries is the consumption of polyphenols from olives and olive oil The purpose was to determine intake of phytoestrogens in a sample of older Australian women , and to investigate associated lifestyle factors . Subjects were an age-stratified sample of 511 women aged 40 - 80 y , r and omly selected from the electoral roll and participating in the Longitudinal Assessment of Ageing in Women at the Royal Brisbane and Women 's Hospital . A cross-sectional study was conducted to assess isoflavone and lignan intake over the past month from food and supplements using a 112-item phytoestrogen frequency question naire . Data were also collected on nutrient intakes , physical activity , smoking , alcohol , non-prescription supplements , hormone therapy , education and occupation . Logistic regression was used to evaluate associations between demographic and lifestyle variables and soy/linseed consumption while controlling for age . Isoflavone intakes were significantly higher in the younger compared to older age groups ( p<0.001 ) ; there were no age-related differences in lignan intake . Forty-five percent of women consumed at least one serve of a soy and /or linseed item and were defined as a soy/linseed consumer . Median ( range ) intakes by consumers for isoflavones and lignans ( 3.9 ( 0 - 172 ) mg/d and 2.4 ( 0.1 - 33 ) mg/d ) were higher than intakes by non-consumers ( 0.004 ( 0 - 2.6 ) mg/d and 1.57 ( 0.44 - 4.7 ) mg/d ) , respectively ( p<0.001 ) . Consumers had higher intakes of dietary fibre ( p=0.003 ) , energy ( p=0.04 ) and polyunsaturated fat ( p=0.004 ) , and higher levels of physical activity ( p=0.006 ) , socio-economic position ( p<0.001 ) , education ( p<0.001 ) and supplement use ( p<0.001 ) . Women who consumed soy or linseed foods differed in lifestyle and demographic characteristics suggesting these factors should be considered when investigating associations with chronic disease outcomes Abstract Background / Objectives Polyphenols are plant secondary metabolites with a large variability in their chemical structure and dietary occurrence that have been associated with some protective effects against several chronic diseases . To date , limited data exist on intake of polyphenols in population s. The current cross-sectional analysis aim ed at estimating dietary intakes of all currently known individual polyphenols and total intake per class and subclass , and to identify their main food sources in the European Prospect i ve Investigation into Cancer and Nutrition cohort . Methods Dietary data at baseline were collected using a st and ardized 24-h dietary recall software administered to 36,037 adult subjects . Dietary data were linked with Phenol-Explorer , a data base with data on 502 individual polyphenols in 452 foods and data on polyphenol losses due to cooking and food processing . Results Mean total polyphenol intake was the highest in Aarhus — Denmark ( 1786 mg/day in men and 1626 mg/day in women ) and the lowest in Greece ( 744 mg/day in men and 584 mg/day in women ) . When dividing the subjects into three regions , the highest intake of total polyphenols was observed in the UK health-conscious group , followed by non-Mediterranean ( non-MED ) and MED countries . The main polyphenol contributors were phenolic acids ( 52.5–56.9 % ) , except in men from MED countries and in the UK health-conscious group where they were flavonoids ( 49.1–61.7 % ) . Coffee , tea , and fruits were the most important food sources of total polyphenols . A total of 437 different individual polyphenols were consumed , including 94 consumed at a level > 1 mg/day . The most abundant ones were the caffeoylquinic acids and the proanthocyanidin oligomers and polymers . Conclusion This study describes the large number of dietary individual polyphenols consumed and the high variability of their intakes between European population s , particularly between MED and non-MED countries Background The majority of research performed to date has examined the effects of commonly known antioxidants such as vitamins C , E , and A and carotenoids on age-related macular degeneration ( AMD ) risk and progression . To date , there is limited research on promising phytochemicals with antioxidant and anti-inflammatory properties , including flavonoids . Objective In this exploratory study , we aim ed to assess the independent associations between dietary intake of total flavonoids and common flavonoid classes with the prevalence and 15-y incidence of AMD . Design In this population -based cohort study , 2856 adults aged ≥49 y at baseline and 2037 followed up 15 y later were included in prevalence and incidence analyses , respectively . Dietary intake was assessed by using a semiquantitative food-frequency question naire ( FFQ ) . Estimates of the flavonoid content of foods in the FFQ were assessed by using the USDA Flavonoid , Isoflavone , and Proanthocyanidin data bases . AMD was assessed from retinal photographs . Results In cross-sectional analysis , each 1-SD increase in total overall flavonoid intake was associated with a reduced likelihood of any AMD ( multivariable-adjusted OR : 0.76 ; 95 % CI : 0.58 , 0.99 ) . Each 1-SD increase in dietary intake of total flavonols and total flavanones was associated with reduced odds of the prevalence of any AMD [ multivariable-adjusted OR ( 95 % CI ) : 0.75 ( 0.58 , 0.97 ) and 0.77 ( 0.60 , 0.99 ) , respectively ] . A marginally significant trend ( P = 0.05 ) was observed between increasing the intake of total flavanone and hesperidin ( from the first to the fourth quartile ) and reduced likelihood of incident late AMD , after multivariable adjustment . Participants who reported ≥1 serving of oranges/d compared with those who never consumed oranges at baseline had a reduced risk of late AMD 15 y later ( multivariable-adjusted OR : 0.39 ; 95 % CI : 0.18 , 0.85 ) . Conclusions Our findings suggest an independent and protective association between dietary intake of flavonoids and the likelihood of having AMD . Additional prospect i ve cohort studies are needed to vali date these findings BACKGROUND AND AIMS Polyphenol-rich diets have been associated with reduced risk of cardiovascular disease ( CVD ) . However , few prospect i ve epidemiological studies have examined the relationship between classes of ingested polyphenols and risk of CVD . Our aim was to evaluate the association between polyphenol intake and risk of major cardiovascular events in a prospect i ve Spanish cohort . METHODS AND RESULTS We included 17,065 university graduates ( 60.7 % women , mean age : 37.2 years , age range : 20 - 89 ) followed-up for a mean of 10.1 years . Polyphenol intake was assessed at baseline using a vali date d semi-quantitative 136-item food frequency question naire and matching food consumption data with the Phenol-Explorer data base . Cox proportional hazards models were used to estimate the adjusted hazard ratios ( HR ) and 95 % confidence intervals ( 95 % CI ) for incident cardiovascular events ( myocardial infa rct ion , stroke or cardiovascular death ) . Cherries , chocolate , coffee , apples , and olives were the major sources of variability in polyphenol intake . Participants with higher flavonoids intake ( fifth quintile ) had a 47 % lower incidence of cardiovascular events compared to those in the lowest quintile ( HR : 0.53 , 95 % CI : 0.29 - 0.98 ; P for trend = 0.09 ) after adjusting for potential confounders . The results were non-significant for other polyphenol types . CONCLUSION The intake of flavonoids showed an inverse association with risk of cardiovascular events in a prospect i ve cohort of Spanish middle-aged adult university graduates . REGISTRATION NUMBER FOR CLINICAL TRIALS NCT02669602 in Clinical Trials BACKGROUND Frailty , an age-related state of increased vulnerability , is associated with a higher risk of multiple adverse events . Studies have suggested that the quality of dietary intake may affect the development of frailty . We hypothesized that frailty in older subjects would be associated with dietary total polyphenols ( DTP ) intake and its biomarker , urinary total polyphenols ( UTP ) . METHODS The Invecchiare in Chianti ( InCHIANTI ) Study is a prospect i ve cohort study set in the Chianti area ( Italy ) . We used data at baseline from 811 participants aged 65 years and older . UTP was determined using the Folin-Ciocalteu assay after solid-phase extraction . DTP was estimated using a vali date d Food Frequency Question naire and our own polyphenol data base . The frailty , prefrailty , and nonfrailty states were defined according to the Fried and colleagues ' criteria . Multinomial logistic regressions adjusted for potential confounders were used to assess the relationship between polyphenols and frailty . RESULTS Both DTP and UTP concentrations progressively decrease from nonfrail to frail participants . Participants in the highest UTP tertile compared to those in the lowest tertile were significantly less likely to be both frail ( odds ratio [ OR ] = 0.36 [ 0.14 - 0.88 ] , p = .025 ) and prefrail ( OR = 0.64 [ 0.42 - 0.98 ] , p = .038 ) . Exhaustion and slowness were the only individual frailty criteria significantly associated with UTP tertiles . No significant association was observed between frailty and DTP , after adjustment for covariates . CONCLUSIONS High concentrations of UTP were associated with lower prevalence of frailty and prefrailty in an older community-dwelling population . A polyphenol-rich diet may protect against frailty in older persons . Our findings should be confirmed in longitudinal studies The study aim ed to estimate dietary flavonol and flavone intakes and investigate major dietary sources by FFQ in Harbin of China . A total of 5,046 volunteers completed a semiquantitative food frequency question naire ( FFQ ) . A r and om sub sample of 167 healthy subjects completed the 7 consecutive 24-h dietary recalls and 2 FFQ for assessing the reproducibility and validity of FFQ . The correlation coefficients between 2 FFQ were 0.72 for flavonols and 0.65 for flavones ; and between FFQ 2 and the 24-h dietary recall , they were 0.62 for flavonols and 0.58 for flavones . When flavonol and flavone intakes were categorized by quartile , complete and partial agreement ranged from 76 % to 84 % . The total intake of flavonols and flavones was 19.13 mg/day , and the mean flavonol and flavone intakes were 14.30 mg/day and 4.82 mg/day , respectively . Quercetin was the major contributor ( 31 % ) to total intake of flavonols and flavones , followed by kaempferol ( 22 % ) . The main food sources of flavonols and flavones were apple ( 12 % ) , potato ( 8 % ) , celery ( 7 % ) , eggplant ( 7 % ) , and actinidia ( 5 % ) . This work could facilitate the investigation on the proposed relation between these flavonoids and the prevention of chronic diseases BACKGROUND Flavonoids are a diverse group of polyphenolic compounds found in high concentrations in many plant foods and beverages . High flavonoid intake has been associated with reduced risk of chronic disease . To date , population based studies have used the United States Department of Agriculture ( USDA ) food content data base to determine habitual flavonoid intake . More recently , a new flavonoid food content data base , Phenol-Explorer ( PE ) , has been developed . However , the level of agreement between the two data bases is yet to be explored . AIM To compare the methods used to create each data base , and to explore the level of agreement between the flavonoid intake estimates derived from USDA and PE data . DESIGN The study population included 1063 r and omly selected women aged over 75 years . Two separate intake estimates were determined using food composition data from the USDA and the PE data bases . RESULTS There were many similarities in methods used to create each data base ; however , there are several method ological differences that manifest themselves in differences in flavonoid intake estimates between the 2 data bases . Despite differences in net estimates , there was a strong level of agreement between total-flavonoid , flavanol , flavanone and anthocyanidin intake estimates derived from each data base . Intake estimates for flavanol monomers showed greater agreement than flavanol polymers . The level of agreement between the two data bases was the weakest for the flavonol and flavone intake estimates . CONCLUSION In this population , the application of USDA and PE source data yielded highly correlated intake estimates for total-flavonoids , flavanols , flavanones and anthocyanidins . For these sub-classes , the USDA and PE data bases may be used interchangeably in epidemiological investigations . There was poorer correlation between intake estimates for flavonols and flavones due to differences in USDA and PE method ologies . Individual flavonoid compound groups that comprise flavonoid sub-classes had varying levels of agreement . As such , when determining the appropriate data base to calculate flavonoid intake variables , it is important to consider method ologies underpinning data base creation and which foods are important contributors to dietary intake in the population of interest |
905 | 31,524,949 | Due to the wide CrIs and the very low-certainty evidence for all the outcomes , significant benefits or harms of antibiotics are possible . | BACKGROUND Approximately 2.5 % of all hospitalisations in people with cirrhosis are for spontaneous bacterial peritonitis ( SBP ) .
Antibiotics , in addition to supportive treatment ( fluid and electrolyte balance , treatment of shock ) , form the mainstay treatments of SBP .
Various antibiotics are available for the treatment of SBP , but there is uncertainty regarding the best antibiotic for SBP .
OBJECTIVES To compare the benefits and harms of different antibiotic treatments for spontaneous bacterial peritonitis ( SBP ) in people with decompensated liver cirrhosis . | OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials BACKGROUND / AIMS Cefotaxime or ceftriaxone were considered the first-choice antibiotic for empirical treatment in cirrhotic patients developing spontaneous bacterial peritonitis . It has been suggested that ciprofloxacin could be an alternative to cefotaxime or ceftriaxone in cirrhotic patients developing spontaneous bacterial peritonitis . The aim of the present study was to compare oral ciprofloxacin with cefotaxime and ceftriaxone in the treatment of spontaneous bacterial peritonitis in cirrhotic patients . METHODOLOGY Fifty-three hospitalized cirrhotic patients with spontaneous bacterial peritonitis were prospect ively included and r and omized into three groups : group A ( n = 16 ) ; received orally 500 mg ciprofloxacin every 12 h , group B ( n = 18 ) ; received intravenous cefotaxime 2 g every 8 h and group C ( n = 19 ) received intravenous ceftriaxone 2 g every 24 h. RESULTS 15 patients from the ciprofloxacin group , 17 from the cefotaxime group and 17 patients from the ceftriaxone group were finally analyzed . Spontaneous bacterial peritonitis resolution in three groups was found to be 80 % , 76 % , and 83 % , respectively ( p = NS ) . Incidence of complications and hospital mortality was similar in the three groups . No adverse events were observed in any of the three groups . The cost of the treatment was statistically lower in the ciprofloxacin group than in the cefotaxime group and ceftriaxone group ( p < 0.001 ) . CONCLUSIONS These results suggest that orally ciprofloxacin is as effective as cefotaxime and ceftriaxone in the empirical treatment of spontaneous bacterial peritonitis in cirrhotic patients , and is also less expensive and can be administered orally We compared the effectiveness and incidence of nephrotoxicity of ampicillin-tobramycin and cefotaxime in 73 cirrhotics who had severe bacterial infection . Most of these patients had spontaneous peritonitis and /or bacteremia . Patients were r and omly allocated into two groups . Group I included 36 patients treated with ampicillin-tobramycin and Group II comprised 37 patients treated with cefotaxime . Patients from both groups were similar with respect to clinical data , st and ard liver and renal function tests , types of infection and isolated organisms . Ninety-two per cent of bacteria isolated in Group I and 98 % of those isolated in Group II were susceptible in vitro to ampicillin-tobramycin and to cefotaxime , respectively . Ampicillin-tobramycin cured the infection in 56 % of Group I patients , and cefotaxime in 85 % of Group II patients ( p less than 0.02 ) . Five patients treated with ampicillin-tobramycin , and none treated with cefotaxime developed superinfections ( p = 0.024 ) . Nephrotoxicity ( impairment of renal function associated with an increase of urinary beta 2-microglobulin to over 2,000 micrograms per liter ) occurred in two patients in Group I and none in Group II . These results suggest that broad-spectrum cephalosporins should be considered as first choice antibiotics in cirrhotic patients with severe infections BACKGROUND AND AIM Spontaneous bacterial peritonitis and bacterascites prevalence in asymptomatic cirrhotic patients on large-volume paracentesis is unknown . The aim of this study was to investigate spontaneous bacterial peritonitis and bacterascites prevalence in a prospect i ve cohort of cirrhotic out patients following large-volume paracentesis with low risk of infection . METHODS We prospect ively studied all large-volume paracenteses performed in cirrhotic out patients for 1 year . Patients with fever , abdominal pain , peritonism or hepatic encephalopathy were excluded from the study . The ascitic fluid was analyzed by means of a reagent strip with a colorimetric scale from 0 to 4 . A strip test of 0 or 1 was considered negative . In those cases with a reagent strip > or = 2 , conventional polymorphonuclear count was performed . Ascitic fluid culture was done into blood culture bottles in all cases . RESULTS We performed 204 paracenteses in 40 patients . Nine cases were excluded . Culture-negative neutrocytic ascites was diagnosed in one case ( 0.5 % ) , while bacterascites was diagnosed in six out of 195 cases ( 3 % ) , mainly by gram-positive cocci . CONCLUSION The spontaneous bacterial peritonitis prevalence in outpatient cirrhotics with low risk of infection undergoing large-volume paracentesis is very low . Moreover , the prevalence of bacterascites is low and without clinical consequences . The routine analysis of ascitic fluid may be unnecessary in this clinical setting . Nevertheless , the use of reagent strips is a reasonable alternative due to its accessibility and low cost We compared cefonicid ( 2 g every 12 h ) and ceftriaxone ( 2 g every 24 h ) for their efficacy and safety in treating spontaneous bacterial peritonitis in cirrhotic patients in an open r and omized clinical trial ( 30 patients in each group ) . Clinical , laboratory , and bacteriologic characteristics were similar in both groups . Ceftriaxone-susceptible strains were isolated on 44 occasions ( 94 % ) , and cefonicid-susceptible strains were isolated on 43 occasions ( 91.5 % ) . The antibiotic concentration in ascitic fluid/MIC ratio for ceftriaxone was > 100 throughout the dose interval ( 24 h ) , while it was lower for cefonicid ( between 1 and 18 ) . A total of 100 % of patients treated with ceftriaxone , and 94 % of those treated with cefonicid were cured of their infections ( P was not significant ) . Hospitalization mortality was 37 % in the cefonicid group and 30 % in the ceftriaxone group ( P was not significant ) . The time that elapsed between the initiation of treatment and the patient 's death was shorter in the cefonicid group patients ( 5.3 + /- 3.90 days ) than in the ceftriaxone group patients ( 11.8 + /- 9.15 days ) ( P < 0.05 ) . None of the patients presented with superinfections , and only two patients treated with cefonicid and three patients treated with ceftriaxone developed colonizations with Enterococcus faecalis or C and ida albicans . Ceftriaxone and cefonicid are safe and useful agents for treating cirrhotic spontaneous bacterial peritonitis , although the pharmacokinetic characteristics of ceftriaxone seem to be more advantageous than those of cefonicid UNLABELLED Recent studies have shown that the diagnosis of spontaneous bacterial peritonitis ( SBP ) can be rapidly obtained using leukocyte esterase reagent strips . However , published studies were restricted to one or two centers , and the number of patients with SBP was thus limited . The aims of the current prospect i ve multicenter study were : ( 1 ) to assess the diagnostic accuracy of the Multistix 8SG urine test for the diagnosis of SBP ; and ( 2 ) to assess the prevalence of SBP . From January to May 2004 , 2 reactive strips were tested independently in in patients with cirrhosis and in out patients undergoing paracentesis . Cultures of ascitic fluid were performed at the bedside using aerobic and anaerobic blood culture bottles . Two thous and one hundred twenty-three paracenteses were performed in 1,041 patients from 70 centers . One hundred seventeen sample s , obtained from 91 patients , had ascites polymorphonuclear cell ( PMN ) counts > or=250/microl ( range , 250 - 34,000 ) , among which 56 were associated with positive ascitic fluid cultures . The prevalence of SBP was 5.5 % in the whole population , 9 % in in patients , and 1.3 % in out patients ( P<0.0001 ) . The prevalence of SBP was 0.57 % in asymptomatic out patients versus 2.4 % in symptomatic out patients ( P=0.04 ) . Using a threshold of 2 + for positivity of the reagent strip , sensitivity was 45.3 % for the diagnosis of SBP , specificity was 99.2 % , positive predictive value was 77.9 % , and negative predictive value was 96.9 % . CONCLUSION This study confirms the low prevalence of SBP in asymptomatic out patients according to a priori defined criteria , and indicates an absence of diagnostic efficacy for this specific strip test Royal Free Hospital , London , UK Introduction Background of the European Liver Transplant RegistrySince 1968 the European Liver Transplant Registry ( ELTR ) collects prospect ively the data of liver transplantation ( LT ) in 145 centersall over Europe . It represents more than 95 % of the overallEuropean data compared to the published official figures [ 1 ] . This collection ismade prospect ivelythroughast and ardized question -naire . The first part of the question naire includes items regarding date and indicationfor LT , donor and recipient data , surgical tech-niqueofLT , and theimmediatepostoperativeimmunosuppressiontherapy . The second part concerns graft and patient outcome , and immunosuppressive regimen follow-up . Participation in the ELTRis voluntary and a st and ard computerized data base is provided tocontributing centers with detailed instructions for the collection of accurate and uniform information [2].Along with reports concerning LT for specific hepatic diseases[3–12],ELTRhasallowedthedevelopmentofriskmodelsforliver-transplantation mortality according to the characteristics of thedonor and recipient , and of the transplant procedure [ 13,14 ] . Quality ofthe data isassessedroutinely . Aregularauditingpro-cessisconductedeachyeartoensurethereliabilityofthescientific analysis of the data , a control of the good adequacy between ELTR question naire and patient charts is performed by r and omly con-ductedauditvisits . Results oftheseauditvisitshaveindicatedthatELTR data were reliable and the scientific results of ELTR can beconsidered credible and representative of LT in Europe [15–18].In addition , a control quality program has been developed inter-nally . The data are subjected to checks for completeness , consis-tency , and range . Comprehensive logical intra- and inter-up date sare performed . Moreover , the ELTR has established agreementswith the European Organ Sharing Organizations ( OSO ) : UnitedKingdom Transplant Service Support Authority (UKTransplant),Spanish Organizacion Nacional de Transplantes ( ONT ) , Sc and ina-vian Sc and itransplant ( SKT ) , Dutch Transplant Foundation (NTS),Eurotransplant ( ET ) , French Agence de la Biomedecine ( ABM ) toexchange data collectedfromEuropeanCenters and tocrosscheckcommon data between OSO and ELTR . Patients and methods We have first considered all data since 1968 to show the evolu-tion of results of LT in Europe since its initial development . Therest of the analysis has been undertaken during two differentperiods : ( a ) from January 1988 to December 2009 ( 89,865 LT –80,347 patients ) , where the date from January 1988 was chosenJournal of Hepatology 2012 vol . AIM To evaluate effective alternative antibiotics in treatment of cefotaxime-resistant spontaneous bacterial peritonitis . METHODS One hundred cirrhotic patients with spontaneous bacterial peritonitis [ ascitic fluid polymorphonuclear cell count ( PMNLs ) ≥ 250 cells/mm(3 ) at admission ] were empirically treated with cefotaxime sodium 2 g/12 h and volume expansion by intravenous human albumin . All patients were subjected to history taking , complete examination , laboratory tests ( including a complete blood cell count , prothrombin time , biochemical tests of liver and kidney function , and fresh urine sediment ) , chest X-ray , a diagnostic abdominal paracentesis , and the sample subjected to total and differential cell count , chemical examination , aerobic and anaerobic cultures . Patients were divided after 2 d by a second ascitic PMNL count into group I ; patients sensitive to cefotaxime ( n = 81 ) , group II ( n = 19 ) ; cases resistant to cefotaxime ( less than 25 % decrease in ascitic PMNL count ) . Patients of group II were r and omly assigned into meropenem ( n = 11 ) or levofloxacin ( n = 8) subgroups . All patients performed an end of treatment ascitic PMNL count . Patients were considered improved when : PMNLs decreased to < 250 cells/mm(3 ) , no growth in previously positive culture cases , and improved clinical manifestations with at least 5 d of antibiotic therapy . RESULTS Age , sex , and Child classes showed no significant difference between group I and group II . Fever and abdominal pain were the most frequent manifestations and were reported in 82.7 % and 80.2 % of patients in group I and in 94.7 % and 84.2 % of patients in group II , respectively . Patients in group II had a more severe ascitic inflammatory response than group I and this was demonstrated by more ascitic lactate dehydrogenase ( LDH ) [ median : 540 IU/L ( range : 150 - 1200 IU/L ) vs median : 240 IU/L ( range : 180 - 500 IU/L ) , P = 0.000 ] and PMNL [ median : 15,000 cell/mm(3 ) ( range : 957 - 23,822 cell/mm(3 ) ) vs 3400 cell/mm(3 ) ( range : 695 - 26,400 cell/mm(3 ) ) , P = 0.000 ] counts . Ascitic fluid culture was positive in 32 % of cases . Cefotaxime failed in 19 % of patients ; of these patients , 11 ( 100 % ) responded to meropenem and 6 ( 75 % ) responded to levofloxacin . Two patients with failed levofloxacin therapy were treated according to the in vitro culture and sensitivity ( one case was treated with vancomycin and one case was treated with ampicillin/sulbactam ) . In group II the meropenem subgroup had higher LDH ( range : 108 - 860 IU/L vs 120 - 491 IU/L , P = 0.042 ) and PMNL counts ( range : 957 - 23,822 cell/mm(3)vs 957 - 15,222 cell/mm(3 ) , P = 0.000 ) at initiation of the alternative antibiotic therapy ; there was no significant difference in the studied parameters between patients responsive to meropenem and patients responsive to levofloxacin at the end of therapy ( mean ± SD : 316.01 ± 104.03 PMNLs/mm(3)vs 265.63 ± 69.61 PMNLs/mm(3 ) , P = 0.307 ) . The isolated organisms found in group II were ; enterococci , acinetobacter , exp and ed-spectrum β-lactamase producing Escherichia coli , β-lactamase producing Enterobacter and Staphylococcus aureus . CONCLUSION Empirical treatment with cefotaxime is effective in 81 % of cases ; meropenem is effective in cefotaxime-resistant cases AIM To compare the incidence of spontaneous bacterial peritonitis in cirrhotic out patients and in patients undergoing therapeutic paracentesis METHODS From January 1 to May 31 , 2004 , 1041 patients from 70 different hospitals underwent 2123 therapeutic abdominal paracentesis ( AP ) performed as a outpatient procedure in 355 and as inpatient procedure in 686 cases respectively . The following parameters were compared prospect ively between out patients and in patients : spontaneous bacterial peritonitis ( SBP ) prevalence , age , gender , cause of cirrhosis , symptoms , score and grade according to Child-Pugh classification , cirrhosis complications , antibiotics treatment , serum creatinine , platelet count and ascitic protein concentration . RESULTS SBP was observed in 91 patients . In the whole population the SBP prevalence was 8.7 % ( 95%CI : 7.2 - 10.6 ) it was 11.7 % ( 95%CI : 9.5 - 14.3 ) in in patients and 3.1 % ( 95%CI : 1.7 - 5.5 ) in out patients ( P < 0.00001 ) . SBP prevalence was 8.3 % ( 95%CI : 4.3 - 15.6 ) in symptomatic out patients vs 1.2 % ( 95%CI : 0.4 - 3.4 ) in asymptomatic out patients ( P < 0.002 ) . Patients undergoing outpatient AP were significantly different from those undergoing inpatient AP ; they were older ( 61.1 ± 11.1 years vs 59.4 ± 11.7 years ; P = 0.028 ) , cause of cirrhosis was less often alcohol ( 83 .7 vs 88.2 % ; P < 0.001 ) , Child-Pugh score was lower ( 8.9 vs 10.1 ; P < 0.001 ) and more often B than C ( 63.7 % vs 38 % ; P < 0.001 ) . In addition , in out patients the platelet count was higher ( 161 ± 93 Giga/L vs 143 ± 89 Giga/L ; P = 0.003 ) , serum total bilirubin concentration was lower ( 38.2 ± 60.7 μmol/L vs 96.3 ± 143.3 μmol/L ; P < 0.0001 ) , and ascitic protein concentration higher ( 17.9 ± 10.7 g/L vs 14.5 ± 10.9 g/L ; P < 0.001 ) than in in patients . CONCLUSION In asymptomatic cirrhotic out patients , the incidence of spontaneous bacterial peritonitis is low thus exploratory paracentesis could be avoided in these patients without significant risk BACKGROUND / AIMS Hepatic cirrhosis is a common , chronic disease . Spontaneous bacterial peritonitis ( SBP ) is a dangerous complication , which must be treated as soon as it has been diagnosed . This usually requires hospitalization of the patient and parenteral antibiotic therapy for 10 to 14 days . The present study was carried out to compare the therapeutic effects of pefloxacin with ampicillin plus gentamicin in the management of SBP . METHODOLOGY The patients were divided into two groups at r and om . Group A consisted of nine patients who received parenteral ampicillin plus gentamicin . Group B consisted of thirteen patients who received pefloxacin . RESULTS 55 % of patients in group A and 100 % of patients in group B responded to treatment . No major side effects were observed in either of the groups . CONCLUSIONS Considering the benefits of oral treatment and the low incidence of side effects of pefloxacin we conclude that this regimen should be the treatment of choice for SBP patients , especially when there is a shortage of hospital beds BACKGROUND / AIM Cefotaxime is considered the first-choice antibiotic for empirical treatment in cirrhotic patients developing bacterial infections . It has been suggested that amoxicillin-clavulanic acid could be an alternative to cefotaxime , particularly in patients developing bacterial infections while on prophylactic norfloxacin . The aim of the present study was to compare amoxicillin-clavulanic acid with cefotaxime in the treatment of bacterial infections in cirrhosis . METHODS Ninety-six hospitalized cirrhotic patients with suspicion of bacterial infection were prospect ively included and r and omized into two groups : one group ( n=48 ) received amoxicillin-clavulanic acid , first intravenously 1 g-0.2 g every 8 h , and then orally 500 mg-125 mg every 8 h , and the other group ( n=48 ) received intravenous cefotaxime 1 g every 6 h. Patients were stratified for previous prophylaxis with norfloxacin and ascitic fluid infection . RESULTS Sixteen patients were excluded from the analysis because bacterial infection was not demonstrated or because of secondary peritonitis . Therefore , 38 patients from the amoxicillin-clavulanic acid group and 42 from the cefotaxime group were finally analyzed . There were 24 ascitic fluid infections in each group . Infection resolution ( 86.8 % vs 88 % , 95 % CI : -0.15 to 0.13 , p NS ) , spontaneous bacterial peritonitis resolution ( 87.5 % vs 83.3 % , 95 % CI : -0.15 to 0.24 , p NS ) , duration of treatment , incidence of complications , time of hospitalization and hospital mortality were similar in both groups . Considering patients on prophylactic norfloxacin , infection resolution was also similar ( 100 % vs 83.3 % , 95 % CI : -0.04 to 0.37 , p NS ) . No adverse events were observed in either of the two groups . The cost of antibiotics was statistically lower in the amoxicillin-clavulanic acid group ( p<0.001 ) . CONCLUSIONS Amoxicillin-clavulanic acid is as effective as cefotaxime in the treatment of bacterial infections in cirrhotic patients , but is less expensive and can be administered orally . These results suggest that amoxicillin-clavulanic acid is an effective alternative to cefotaxime for the empirical treatment of bacterial infections in cirrhosis Aztreonam and cefotaxime were compared in 44 cirrhotic patients who had 52 episodes of gramnegative spontaneous peritonitis . Patients were r and omized into two therapeutic groups of similar characteristics . Group A ( 28 episodes ) received 0.5 gm of aztreonam every 8 hr , and group B ( 24 episodes ) received 1 gm of cefotaxime every 6 hr , for a planned 14‐day period . Peak and trough serum and ascitic fluid levels of both antibiotics were several times higher than the minimum inhibitory concentrations of causative microorganisms . Eleven patients ( 21 % ) died within the first 48 hr after beginning therapy , which included seven in the aztreonam group and four in the cefotaxime group . In the remaining patients , signs and symptoms of infection were promptly controlled , and ascitic fluid cultures became negative after 48 hr in all cases , except in one patient from the aztreonam group , who was a clinical failure . Two patients from the aztreonam group and one from the cefotaxime group relapsed after treatment . The overall mortality rate was 50 % , which was lower than classically reported : 12 patients ( 43 % ) died in the aztreonam group , and 14 ( 58 % ) died in the cefotaxime group ( p = 0.265 , NS ) . Hepatorenal syndrome and digestive tract hemorrhage were the most frequent causes of death occurring after the first 48 hr of treatment . Streptococcal superinfections developed in three patients ( 14.2 % ) in the aztreonam group . We conclude that both antibiotics at the low doses used in this study are similarly well tolerated and effective in controlling this infection . Because the use of aztreonam as the initial empirical treatment requires a concomitant antibiotic against gram‐positive infections and the possibility of streptococcal superinfections , cefotaxime seems to be a more advantageous therapeutic alternative for this patient population . ( HEPATOLOGY1991;14:91–98 . BACKGROUND & AIMS Spontaneous bacterial peritonitis ( SBP ) , in the presence of bacterial resistance or failure of third generation cephalosporins ( 3rd GC ) has poor outcome . Empirical antibiotic(s ) options are limited in these scenarios . METHODS Consecutive cirrhotics with SBP because of hospital acquired SBP ( > 48 h of admission ) , microbial resistance or non-response ( no resolution of SBP at 48 h ) were r and omized to Cefepime ( n = 88 ) or Imipenem ( n = 87 ) plus st and ard medical therapy . We assessed for ' response at 48 h ' ( reduction in ascitic fluid absolute neutrophil count ( ANC ) by > 25 % at 48 h ) , resolution of SBP ( < 250 cu/mm ANC at day 5 ) and their clinical outcome . RESULTS Of 957 paracentesis in 1200 hospitalized cirrhotics , 253 ( 26.4 % ) had SBP and 175 ( 69.6 % ) were r and omized . Baseline parameters were comparable in two groups . Response at 48 h ( 58.6 % vs. 51.7 % ; P = 0.4 ) and resolution of SBP in those with response at 48 h were comparable with no difference in mortality at week 2 , month 1 and 3 . Patients with ' No response at 48 h ' had higher mortality compared with responders ( 73.8 % vs. 25 % ; P < 0.001 ) . Resolution of SBP was associated with ' response at 48 h ' and septic shock , latter being main pre-terminal event . AKI at enrolment [ Hazard ratio ( HR ) , 2.6 ] , pneumonia [ HR , 2.9 ] , septic shock [ HR , 2.2 ] and response at 48 h [ HR , 4.6 ] predicted poor outcome . CONCLUSIONS In hospitalized cirrhotics with SBP and risk factors for treatment failure , cefepime showed comparable efficacy and survival to imipenem . Non-response to therapy at 48 h is a reliable predictor of treatment failure and mortality . Antibiotic combinations and novel options are needed for these patients UNLABELLED Spontaneous bacterial peritonitis ( SBP ) is a common , life-threatening complication of liver cirrhosis . Third-generation cephalosporins have been considered the first-line treatment of SBP . In 2014 , a panel of experts suggested a broader spectrum antibiotic regimen for nosocomial SBP , according to the high rate of bacteria resistant to third-generation cephalosporins found in these patients . However , a broader-spectrum antibiotic regimen has never been compared to third-generation cephalosporins in the treatment of nosocomial SBP . The aim of our study was to compare meropenem plus daptomycin versus ceftazidime in the treatment of nosocomial SBP . Patients with cirrhosis and nosocomial SBP were r and omized to receive meropenem ( 1 g/8 hours ) plus daptomycin ( 6 mg/kg/day ) or ceftazidime ( 2 g/8 hours ) . A paracentesis was performed after 48 hours of treatment . A reduction in ascitic fluid neutrophil count < 25 % of pretreatment value was considered a treatment failure . The primary outcome was the efficacy of treatment defined by the resolution of SBP after 7 days of treatment . Thirty-two patients were r and omized and 31 were analyzed . The combination of meropenem plus daptomycin was significantly more effective than ceftazidime in the treatment of nosocomial SBP ( 86.7 vs. 25 % ; P < 0.001 ) . Ninety-day transplant-free survival ( TFS ) was not significantly different between the two groups . In the multivariate analysis , ineffective response to first-line treatment ( hazard ratio [ HR ] : 20.6 ; P = 0.01 ) , development of acute kidney injury during hospitalization ( HR : 23.2 ; P = 0.01 ) , and baseline mean arterial pressure ( HR : 0.92 ; P = 0.01 ) were found to be independent predictors of 90-day TFS . CONCLUSION The combination of meropenem plus daptomycin is more effective than ceftazidime as empirical antibiotic treatment of nosocomial SBP . Efficacy of the empirical antibiotic treatment is a strong predictor of 90-day survival in patients with nosocomial SBP Published evidence suggests that aspects of trial design lead to biased intervention effect estimates , but findings from different studies are inconsistent . This study combined data from 7 meta-epidemiologic studies and removed overlaps to derive a final data set of 234 unique meta-analyses containing 1973 trials . Outcome measures were classified as " mortality , " " other objective , " " or subjective , " and Bayesian hierarchical models were used to estimate associations of trial characteristics with average bias and between-trial heterogeneity . Intervention effect estimates seemed to be exaggerated in trials with inadequate or unclear ( vs. adequate ) r and om-sequence generation ( ratio of odds ratios , 0.89 [ 95 % credible interval { CrI } , 0.82 to 0.96 ] ) and with inadequate or unclear ( vs. adequate ) allocation concealment ( ratio of odds ratios , 0.93 [ CrI , 0.87 to 0.99 ] ) . Lack of or unclear double-blinding ( vs. double-blinding ) was associated with an average of 13 % exaggeration of intervention effects ( ratio of odds ratios , 0.87 [ CrI , 0.79 to 0.96 ] ) , and between-trial heterogeneity was increased for such studies ( SD increase in heterogeneity , 0.14 [ CrI , 0.02 to 0.30 ] ) . For each characteristic , average bias and increases in between-trial heterogeneity were driven primarily by trials with subjective outcomes , with little evidence of bias in trials with objective and mortality outcomes . This study is limited by incomplete trial reporting , and findings may be confounded by other study design characteristics . Bias associated with study design characteristics may lead to exaggeration of intervention effect estimates and increases in between-trial heterogeneity in trials reporting subjectively assessed outcomes |
906 | 22,421,188 | Grade d activity plus Treatment Based Classification targeted to people with high movement-related fear was more effective than Treatment Based Classification at reducing movement-related fear at 4 weeks .
Active rehabilitation ( physical exercise classes with cognitive-behavioural principles ) was more effective than usual GP care at reducing activity limitation at 12 months , when targeted to people with higher movement-related pain . | BACKGROUND There is considerable interest in whether best practice management of nonspecific low back pain ( NSLBP ) should include the targeting of treatment to subgroups of people with identifiable clinical characteristics .
However , there are no published systematic review s of the efficacy of targeted psychosocial interventions .
AIM This review aim ed to determine if the efficacy of interventions for psychosocial risk factors of persistent NSLBP is improved when targeted to people with particular psychosocial characteristics . | OBJECTIVE For long-term treatment effects , patients with subacute back pain need to adhere to treatment recommendations beyond the prescribed exercise treatment . Adherence rates are as low as 30 % , so we developed a cognitive-behavioural training programme to enhance patients ' self-efficacy , maximise severity perceptions and reduce barrier perceptions . METHOD A 2 x 4 ( group x time ) repeated measurement design was applied . Forty-seven patients with non-specific , subacute back pain were r and omly assigned to a training group ( exercise treatment plus cognitive-behavioural training programme ) or a control group ( exercise treatment only ) . RESULTS Repeated measures ANOVA revealed significant main and interaction effects ; the training group reported enhanced self-efficacy and severity perceptions , reduced barrier perceptions , and self-reported that they exercised more often than the control group over time . However , no group differences regarding pain intensity emerged . CONCLUSION Our findings demonstrate that a short and inexpensive cognitive-behavioural training programme is an effective tool to enable back pain patients to follow treatment recommendations on a regular basis . PRACTICE IMPLICATION S The short and simple intervention can easily be conducted by personnel , other than psychologists , i.e. , physiotherapists This investigation was an initial attempt to explore psychological factors that might help or hinder the effect of exposure in vivo for patients with musculoskeletal pain and pain‐related fear . The study was based on data from a r and omized‐controlled trial for patients with non‐specific spinal pain ( Linton et al. , 2008 ) The objective of this study was to report on secondary analyses of a merged trial data set aim ed at exploring the potential importance of patient factors associated with clinical ly relevant improvements in non-acute , non-specific low back pain ( LBP ) . From 273 predominantly male army workers ( mean age 39 ± 10.5 years , range 20–56 years , 4 women ) with LBP who were recruited in three r and omized clinical trials , baseline individual patient factors , pain-related factors , work-related psychosocial factors , and psychological factors were evaluated as potential prognostic variables in a short-term ( post-treatment ) and a long-term logistic regression model ( 6 months after treatment ) . We found one dominant prognostic factor for improvement directly after treatment as well as 6 months later : baseline functional disability , expressed in Rol and –Morris Disability Question naire scores . Baseline fear of movement , expressed in Tampa Scale for Kinesiophobia scores , had also significant prognostic value for long-term improvement . Less strongly associated with the outcome , but also included in our final models , were supervisor social support and duration of complaints ( short-term model ) , and co-worker social support and pain radiation ( long-term model ) . Information about initial levels of functional disability and fear-avoidance behaviour can be of value in the treatment of patient population s with characteristics comparable to the current army study population ( e.g. , predominantly male , physically active , working , moderate but chronic back problems ) . Individuals at risk for poor long-term LBP recovery , i.e. , individuals with high initial level of disability and prominent fear-avoidance behaviour , can be distinguished that may need additional cognitive-behavioural treatment Study Design . A r and omized controlled design superimposed on treatment as usual was used to compare the effects of a cognitive-behavior intervention aim ed at preventing chronicity with two different forms of information . Objective . To develop a coping-oriented preventive intervention applicable in primary care , and to compare its impact with educational information . Summary of Background Data . Preventing long-term disability result ing from spinal pain has proved difficult . The information provided by health care professions and early interventions aim ed at preventing long-term disability may be important , but little scientific evidence exists concerning their use . Methods . A protocol for a six-session cognitive-behavior group intervention was developed on the basis of earlier research . The main focus was to prevent long-term disability by changing patients ’ behaviors and beliefs so they can cope better with their problems . Comparison groups received either a pamphlet shown earlier to have an effect , or a more extensive information package consisting of six installments . All the groups continued to receive treatment as usual in primary care . There were 243 patients with acute or subacute spinal pain who perceived that they were at risk for developing a chronic problem . These patients were r and omized to the cognitive-behavioral intervention or one of the two information groups . Because the aim was to prevent long-term disability , the key outcome variables at the 1-year follow-up assessment were sick absenteeism and health care use . Other variables were pain , function , fear-avoidance beliefs , and cognitions . Results . The comparison groups reported benefits . However , the risk for a long-term sick absence developing was lowered ninefold for the cognitive-behavior intervention group as compared with the risk for the information groups ( relative risk , 9.3 ) . Participants in the cognitive-behavior group also reported a significant decrease in perceived risk . In addition , the cognitive-behavior group demonstrated a significant decrease in physician and physical therapy use as compared with two groups receiving information , in which such use increased . All three groups tended to improve on the variables of pain , fear-avoidance , and cognitions . Conclusions . This study demonstrates that a cognitive-behavior group intervention can lower the risk of a long-term disability developing . These findings underscore the significance of early interventions that specifically aim to prevent chronic problems . This approach might be applied to primary care setting Introduction It was postulated that workers , at the sub-acute stage after injury , respond differently to clinical and occupational interventions offered in a workers ’ compensation environment . Individual worker risk of disability , it was further believed , would influence the effectiveness of early intervention . The objective of the current pilot study was to evaluate return to work ( RTW ) outcomes following proactive , combined clinical , occupational and case management-based interdisciplinary early intervention , provided in a workers ’ compensation environment 4–10 weeks of onset of back pain , to workers with medium and high risk for disability . Methods The project was a controlled study comparing conventional workers ’ compensation case management with integrated , interdisciplinary and multimodal early intervention ( hereinafter referred to as “ EI ” ) . At baseline , risk status was determined by a vali date d Risk for Disability Question naire by Carragee et al. ( Spine 5(1):24–35 , 2005 ) . Seventeen workers at high risk of protracted disability and 20 workers at moderate risk of disability received conventional case management , and 17 workers assessed at high risk of protracted disability and 18 workers at moderate risk of disability received the Early Intervention . Results At 3 months post back pain onset , no statistically significant differences were identified in RTW outcomes between conventional case management and the Early Intervention . However , by 6 months post back pain onset , workers at high risk of work disability who received the Early Intervention were significantly more likely to RTW than high risk workers who received conventional case management . In contrast , moderate risk workers continued to exhibit no statistically significant differences in RTW outcomes . Conclusion Multimodal Early Intervention in the workers ’ compensation case management context is likely effective for workers with sub-acute back pain who are at high risk of occupational disability . The comprehensive Early Intervention is , however , likely redundant for workers who are not at high risk for disability and should not be applied indiscriminately . Further studies are required to determine longer-term Early Intervention outcomes , and to replicate the findings using a r and omized control design . Also , with a larger sample size , it will be possible to determine predictors of occupational outcomes In a prospect i ve trial , 222 adults with low-back pain of at least 2 weeks ' duration in a Health Maintenance Organization ( HMO ) were r and omly assigned to usual care ( UC ) , a 4-hour back school psychoeducational session ( LBS ) , or the same back school plus a 1-year “ compliance package ” program design ed to encourage appropriate self-management for back pain ( CP ) . Sixty-four percent of LBS and CP subjects attended their back school sessions . Follow-up measurement of pain level ( using the Visual Analogue Scale ) , functional status ( using the Sickness Impact Profile ) , and various other indicators of health status showed no measurable effect of either treatment condition ( LBS or CP ) compared with UC at 3 , 6 , 12 , and 18 months after entry into the study . Initial disability resolved by 3 months in most patients , and a minority of subjects ( 10–15 % ) showed residual or recurrent functional Impairment 1 year after entry . Health care utilization tended to be slightly higher after intervention In the CP group . With or without follow-up encouragement , back school instructions given in a single 4-hour session had no measurable impact on the comfort or functional status of the majority of patients with new onset back pain in this HMO Abstract Psychological factors consistent with fear‐avoidance models are associated with the development of chronic low back pain ( LBP ) . As a result , grade d activity ( GA ) and grade d exposure ( GX ) have been suggested as behavioral treatment options . This clinical trial compared the effectiveness of treatment‐based classification ( TBC ) physical therapy alone to TBC augmented with GA or GX for patients with acute and sub‐acute LBP . Our primary hypothesis was that GX would be most effective for those with elevated pain‐related fear . In total , 108 patients enrolled in this clinical trial and were r and omly assigned to receive TBC , GA , or GX . Outcomes were assessed by a blinded evaluator at 4 weeks and by mail at 6 months . The primary outcomes for this trial were disability and pain intensity , and the secondary outcomes were fear‐avoidance beliefs , pain catastrophizing , and physical impairment . There were no differences in 4‐week and 6‐month outcomes for reduction of disability , pain intensity , pain catastrophizing , and physical impairment . GX and TBC were associated with larger reductions in fear‐avoidance beliefs at 6 months only . Six‐month reduction in disability was associated with reduction in pain intensity , while 6‐month reduction in pain intensity was associated with reductions in fear‐avoidance beliefs and pain catastrophizing . This trial suggests that supplementing TBC with GA or GX was not effective for improving important outcomes related to the development of chronic LBP A clinical prediction rule to identify patients most likely to respond to spinal manipulation has been published and widely cited but requires further testing for external validity . We performed a pre-planned secondary analysis of a r and omised controlled trial investigating the efficacy of spinal manipulative therapy in 239 patients presenting to general practice clinics for acute , non-specific , low back pain . Patients were r and omised to receive spinal manipulative therapy or placebo 2 to 3 times per week for up to 4 weeks . All patients received general practitioner care ( advice and paracetamol ) . Outcomes were pain and disability measured at 1 , 2 , 4 and 12 weeks . Status on the clinical prediction rule was measured at baseline . The clinical prediction rule performed no better than chance in identifying patients with acute , non-specific low back pain most likely to respond to spinal manipulative therapy ( pain P = 0.805 , disability P = 0.600 ) . At 1-week follow-up , the mean difference in effect of spinal manipulative therapy compared to placebo in patients who were rule positive rather than rule negative was 0.3 points less on a 10-point pain scale ( 95 % CI −0.8 to 1.4 ) . The clinical prediction rule proposed by Childs et al. did not generalise to patients presenting to primary care with acute low back pain who received a course of spinal manipulative therapy STUDY DESIGN A double-blind , r and omized controlled trial of a novel educational booklet compared with a traditional booklet for patients seeking treatment in primary care for acute or recurrent low back pain . OBJECTIVE To test the impact of a novel educational booklet on patients ' beliefs about back pain and functional outcome . SUMMARY OF BACKGROUND DATA The information and advice that health professionals give to patients may be important in health care intervention , but there is little scientific evidence of their effectiveness . A novel patient educational booklet , The Back Book , has been developed to provide evidence -based information and advice consistent with current clinical guidelines . METHODS One hundred sixty-two patients were given either the experimental booklet or a traditional booklet . The main outcomes studied were fear-avoidance beliefs about physical activity , beliefs about the inevitable consequences of back trouble , the Rol and Disability Question naire , and visual analogue pain scales . Postal follow-up response at 1 year after initial treatment was 78 % . RESULTS Patients receiving the experimental booklet showed a statistically significant greater early improvement in beliefs which was maintained at 1 year . A greater proportion of patients with an initially high fear-avoidance beliefs score who received the experimental booklet had clinical ly important improvement in fear-avoidance beliefs about physical activity at 2 weeks , followed by a clinical ly important improvement in the Rol and Disability Question naire score at 3 months . There was no effect on pain . CONCLUSION This trial shows that carefully selected and presented information and advice about back pain can have a positive effect on patients ' beliefs and clinical outcomes , and suggests that a study of clinical ly important effects in individual patients may provide further insights into the management of low back pain & NA ; The effects of outpatient group cognitive therapy , relaxation training , and cognitive therapy in combination with relaxation training on chronic low back pain and associated physical and psychosocial disability were evaluated and compared . One‐hundred and two mildly disabled chronic low back pain patients were assigned r and omly to a waiting‐list ( WL ) control condition and the 3 treatments . Patient self‐report and observational measures were obtained pretreatment and post‐treatment for all conditions , and at 6‐ and 12‐month follow‐ups for the treatment conditions . Pain intensity decreased significantly pre‐ to post‐treatment for patients in all 3 treatment conditions , but not the WL condition . Depressive symptoms and disability improved significantly in all conditions ( including the waiting list ) from pretreatment to post‐treatment , with no statistically significant differences among treatments . At both follow‐ups , all 3 treatment groups remained significantly improved from pretreatment , with no statistically significant differences between treatments OBJECTIVES To determine the prevalence ranges of low back pain ( LBP ) together with any related disability in Australian adults . DESIGN A population -based survey . METHODS The survey was mailed in June 2001 to a stratified r and om sample of 3000 Australian adults selected from the Electoral Roll . Demographic variables of respondents were compared with the Australian population . Selective response bias was investigated using wave analysis . A range of prevalence data was derived , as were disability scores using the Chronic Pain Grade . RESULTS There was a 69 % response rate . There was little variation between the sample and the Australian adult population . There was no significant selective response bias found . The sample point prevalence was estimated at 25.6 % ( 95 % confidence interval [ CI ] , 23.6 - 27.5 ) , 12-month prevalence was 67.6 % ( 95 % CI , 65.5 - 69.7 ) , and lifetime prevalence was 79.2 % , ( 95 % CI , 77.3 - 81.0 ) . In the previous 6-month period , 42.6 % ( 95 % CI , 40.4 - 44.8 ) of the adult population had experienced low-intensity pain and low disability from it . Another 10.9 % ( 95 % CI , 9.6 - 12.3 ) had experienced high intensity-pain but still low disability from this pain . However , 10.5 % ( 95 % CI , 9.2 - 11.9 ) had experienced high-disability LBP . CONCLUSION LBP is a common problem in the Australian adult population , yet most of this is low-intensity and low-disability pain . Nevertheless , over 10 % had been significantly disabled by LBP in the past 6 months . Data from this study will provide a better underst and ing of the magnitude of the LBP problem in Australia , the need for access to health care re sources , and also strategic research directions Clinical research of grade d exposure in vivo with behavioral experiments in patients with chronic low back pain who reported fear of movement/(re)injury shows abrupt changes in self-reported pain-related fears and cognitions . The abrupt changes are more characteristics of insight learning rather than the usual gradual progression of trial and error learning . The educational session at the start of the exposure might have contributed to this insight . The current study examines the contribution of education and grade d exposure versus grade d activity in the reduction of pain-related fear and associated disability and physical activity . Six consecutive patients with chronic low back pain who reported substantial fear of movement/(re)injury were included in the study . After a no-treatment baseline measurement period , all the patients received a single educational session , followed again by a no-treatment period . Patients were then r and omly assigned to either a grade d exposure with behavioral experiments or an operant grade d activity program . A diary was used to assess daily changes in pain intensity , pain-related fear , pain catastrophizing , and activity goal achievement . St and ardized question naires of pain-related fear , pain vigilance , pain intensity , and pain disability were administered before and after each intervention and at the 6-month follow-up . An activity monitor was carried at baseline , during the interventions , and 1 week at 6-month follow-up . R and omization tests of the daily measures showed that improvements in pain-related fear and catastrophizing occurred after the education was introduced . The results also showed a further improvement when exposure in vivo followed the no-treatment period after the education and not during the operant grade d activity program . Performance of relevant daily activities , however , were not affected by the educational session and improved significantly only in the exposure in vivo condition . All improvements remained at half-year follow-up only in patients receiving the exposure in vivo . These patients also reported a significant decrease in pain intensity at follow-up Abstract Objective To compare the effects of a minimal intervention strategy aim ed at assessment and modification of psychosocial prognostic factors and usual care for treatment of (sub)acute low back pain in general practice . Design Cluster r and omised clinical trial . Setting 60 general practitioners in 41 general practice s. Participants 314 patients with non-specific low back pain of less than 12 weeks ' duration , recruited by their general practitioner . Interventions In the minimal intervention strategy group the general practitioner explored the presence of psychosocial prognostic factors , discussed these factors , set specific goals for reactivation , and provided an educational booklet . The consultation took about 20 minutes . Usual care was not st and ardised . Main outcome measures Functional disability ( Rol and -Morris disability question naire ) , perceived recovery , and sick leave because of low back pain assessed at baseline and after 6 , 13 , 26 , and 52 weeks . Results The dropout rate was 8 % in the minimal intervention strategy group and 9 % in the usual care group . Multilevel analyses showed no significant differences between the groups on any outcome measure during 12 months of follow-up in the whole group or in relevant subgroups ( patients with high scores on psychosocial measures at baseline or a history of frequent or prolonged low back pain ) . Conclusion This study provides no evidence that ( Dutch ) general practitioners should adopt our new treatment strategy aim ed at psychosocial prognostic factors in patients with (sub)acute low back pain . Further research should examine why our new strategy was not more effective than usual care STUDY DESIGN A r and omized clinical trial . OBJECTIVES To examine the relative efficacy of three active therapies for chronic low back pain . SUMMARY OF BACKGROUND DATA There is much evidence documenting the efficacy of exercise in the conservative management of chronic low back pain , but many questions remain regarding its exact prescription and method of application . The most successful method must be identified to enable refinement of future rehabilitation programs to target the specific needs of the patient with chronic low back pain and the budget of the healthcare provider . METHODS One hundred forty-eight patients with chronic low back pain were r and omized to one of the following treatments , which they attended twice a week for 3 months : 1 ) modern active physiotherapy , 2 ) muscle reconditioning on training devices , or 3 ) low-impact aerobics . Pretherapy and posttherapy , objective measurements of lumbar mobility were performed , and question naires were administered inquiring about self-rated pain and disability , and psychosocial factors . Similar question naires were administered 6 months after therapy . The data were analyzed using the intention-to-treat principle . RESULTS Of the 148 patients , 16 ( 10.8 % ) dropped out of the therapy . One hundred thirty-seven question naires ( 93 % ) were available for analysis at all three time points . After therapy , significant reductions were observed in pain intensity , frequency , and disability ; Fear-Avoidance Beliefs about physical activity ( FABQactivity ) ; and " praying/hoping , " " catastrophizing , " and " pain behavior " coping strategies -- each with no group differences in the extent of the response . These effects were maintained over the subsequent 6 months , with the exception of disability and FABQactivity for the physiotherapy group . There were small but significant posttherapy increases in lumbar mobility , with aerobics and devices showing a greater response than physiotherapy . CONCLUSION The general lack of treatment specificity suggests that the main effects of the therapies were educed not through the reversal of physical weaknesses targeted by the corresponding exercise modality , but rather through some " central " effect , perhaps involving an adjustment of perception in relation to pain and disability . The direct costs associated with administering physiotherapy were three times as great , and devices four times as great , as those for aerobics . Administration of aerobics as an efficacious therapy for chronic low back pain has the potential to relieve some of the huge financial burden associated with the condition Background Non-specific spinal pain ( NSP ) , comprising back and /or neck pain , is one of the leading disorders in long-term sick-listing . During 2000 - 2004 , 125 Swedish primary -care patients with non-acute NSP , full-time sick-listed 6 weeks-2 years , were included in a r and omized controlled trial to compare a cognitive-behavioural programme with traditional primary care . This prospect i ve cohort study is a re- assessment of the data from the r and omized trial with the 2 treatment groups considered as a single cohort . The aim was to investigate which baseline variables predict a stable return-to-work during a 2-year period after baseline : objective variables from function tests , socioeconomic , subjective and /or treatment variables . Stable return-to-work was a return-to-work lasting for at least 1 month from the start of follow-up . Methods Stable return-to-work was the outcome variable , the above-mentioned factors were the predictive variables in multiple-logistic regression models , one per follow-up at 6 , 12 , 18 and 24 months after baseline . The factors from univariate analyzes with a p-value of at most .10 were included . The non-significant variables were excluded stepwise to yield models comprising only significant factors ( p < .05 ) . As the comparatively few cases made it risky to associate certain predictors with certain time-points , we finally considered the predictors which were represented in at least 3 follow-ups . They are presented with odds ratios ( OR ) and 95 % confidence intervals . Results Three variables qualified , all of them represented in 3 follow-ups : Low total prior sick-listing ( including all diagnoses ) was the strongest predictor in 2 follow-ups , 18 and 24 months , OR 4.8 [ 1.9 - 12.3 ] and 3.8 [ 1.6 - 8.7 ] respectively , High self prediction ( the patients ' own belief in return-to-work ) was the strongest at 12 months , OR 5.2 [ 1.5 - 17.5 ] and Young age ( max 44 years ) the second strongest at 18 months , OR 3.5 [ 1.3 - 9.1 ] . Conclusions In primary -care patients with non-acute NSP , the strong predictors of stable return-to-work were 2 socioeconomic variables , Low total prior sick-listing and Young age , and 1 subjective variable , High self-prediction . Objective variables from function tests and treatment variables were non-predictors . Except for Young age , the predictors have previously been insufficiently studied , and so our study should widen knowledge within clinical practice .Trial registration Trial registration number for the original trial NCT00488735 & NA ; Since pain‐related fear may contribute to the development and maintenance of chronic low back pain ( CLBP ) , an exposure in vivo treatment ( EXP ) was developed for CLBP patients . We examined the effectiveness as well as specific mediating mechanisms of EXP versus operant grade d activity ( GA ) directly and 6 months post‐treatment in a multi‐centre r and omized controlled trial . In total , 85 patients suffering from disabling non‐specific CLBP reporting at least moderate pain‐related fear were r and omly allocated to EXP or GA . It was demonstrated that EXP , despite excelling in diminishing pain catastrophizing and perceived harmfulness of activities , was equally effective as GA in improving functional disability and main complaints , although the group difference almost reached statistical significance favouring EXP . Both treatment conditions did not differ in pain intensity and daily activity levels either . Nor was EXP superior to GA in the subgroup of highly fearful patients . Irrespective of treatment , approximately half the patients reported clinical ly relevant improvements in main complaints and functional disability , although for the latter outcome the group difference was almost significant favouring EXP . Furthermore , the effect of EXP relative to GA on functional disability and main complaints was mediated by decreases in catastrophizing and perceived harmfulness of activities . In sum , this study demonstrates that up to 6 months after treatment EXP is an effective treatment , but not more effective than GA , in moderately to highly fearful CLBP patients , although its superiority in altering pain catastrophizing and perceived harmfulness of activities is clearly established . Possible explanations for these findings are discussed Study Design . A 5-year follow-up of a r and omized , controlled trial . Objective . To evaluate the long-term health and economic consequences of a cognitive behavioral intervention . Summary of Background Data . Linton and And ersson ( Spine 2000;25:2825–31 ) provide 1 of only a few studies on the preventive effects of a cognitive behavioral intervention . The present study is a 5-year follow-up . Methods . In the original study , 213 participants were r and omized to the cognitive-behavioral group intervention or to usual care plus information on self-care ( information comparison group ) . Of participants , 97 % completed a follow-up question naire 5 years after the intervention , and supplemental records were obtained from the National Insurance Authority . Results . The cognitive behavioral group had significantly less pain , was more active , enjoyed better quality of life , and had better general health relative to the information comparison group . There was no difference on health care use . The risk of long-term sick leave was 3 times higher in the information comparison group . The cognitive behavioral group had significantly less lost productivity costs and a lower total cost/y/person ( 16,514 Swedish kronor ) compared to the information comparison group ( 45,990 Swedish kronor ) . Conclusions . A cognitive-behavioral group intervention produces long-term health and economic benefits . Usual medical care might be improved considerably by implementing these psychologic methods Background In the industrial world , non-specific back and neck pain ( BNP ) is the largest diagnostic group underlying sick-listing . For patients with subacute and chronic (= full-time sick-listed for 43 – 84 and 85 – 730 days , respectively ) BNP , cognitive-behavioural rehabilitation was compared with primary care . The specific aim was to answer the question : within an 18-month follow-up , will the outcomes differ in respect of sick-listing and number of health-care visits ? Methods After stratification by age ( ≤ 44/≥ 45 years ) and subacute/chronic BNP , 125 Swedish primary -care patients were r and omly allocated to cognitive-behavioural rehabilitation ( rehabilitation group ) or continued primary care ( primary -care group ) . Outcome measures were Return-to-work share ( percentage ) and Return-to-work chance ( hazard ratios ) over 18 months , Net days ( crude sick-listing days × degree ) , and the number of Visits ( to physicians , physiotherapists etc . ) over 18 months and the three component six-month periods . Descriptive statistics , Cox regression and mixed-linear models were used . Results All patients : Return-to-work share and Return-to-work chance were equivalent between the groups . Net days and Visits were equivalent over 18 months but decreased significantly more rapidly for the rehabilitation group over the six-month periods ( p < .05 ) . Subacute patients : Return-to-work share was equivalent . Return-to-work chance was significantly greater for the rehabilitation group ( hazard ratio 3.5 [ 95%CI1.001 – 12.2 ] ) . Net days were equivalent over 18 months but decreased significantly more rapidly for the rehabilitation group over the six-month periods and there were 31 days fewer in the third period . Visits showed similar though non-significant differences and there were half as many in the third period . Chronic patients : Return-to-work share , Return-to-work chance and Net days were equivalent . Visits were equivalent over 18 months but tended to decrease more rapidly for the rehabilitation group and there were half as many in the third period ( non-significant ) . Conclusion The results were equivalent over 18 months . However , there were indications that cognitive-behavioural rehabilitation in the longer run might be superior to primary care . For subacute BNP , it might be superior in terms of sick-listing and health-care visits ; for chronic BNP , in terms of health-care visits only . More conclusive results concerning this possible long-term effect might require a longer follow-up . Trial registration NCT00488735 Background Clinical guidelines for the management of back pain frequently recommend ' manual therapy ' as a first line intervention , with psychosocial screening and ' active rehabilitation ' for those not improving at 6 weeks post onset . The potential for psychosocial factors to predict treatment response and therefore outcome has not been adequately explored . The purpose of this pilot study was to determine the feasibility of a study to compare manual therapy and active rehabilitation outcomes for subjects with sub-acute/chronic back pain , investigate whether any difference in outcome was related to psychosocial factors , and to inform the design of a main study . Methods A convenience sample of 39 patients with non-specific low back pain referred to the physiotherapy department of an acute NHS Trust hospital was recruited over a nine month period . Patients completed the Linton and Hallden psychological screening question naire ( LH ) and were allocated to a low LH ( 105 or below ) or high LH ( 106 or above ) scoring group . The low or high LH score was used to sequentially allocate patients to one of two treatment groups – Manual Therapy comprising physiotherapy based on manual means as chosen by the treating therapist or Active Rehabilitation comprising a progressive exercise and education programme – with the first low LH scoring patient being allocated to active rehabilitation and the next to manual therapy and so on . Treatment was administered for eight sessions over a four-week period and outcome measures were taken at baseline and at four weeks . Measures used were the Rol and Morris Question naire ( RMQ ) , two components of the Short Form McGill ( total pain rating index [ PRI ] and pain intensity via visual analogue scale [ VAS ] ) , and the LH . Results The manual therapy group demonstrated a greater treatment effect compared with active rehabilitation for RMQ ( mean difference 3.6 , 95 % CI 1.1 – 6.2 , p = 0.006 ) and PRI ( 7.1 , 95 % CI 2.0 – 12.2 , p = 0.007 ) and marginally significant results for VAS ( 15 , 95 % CI -1.1 to 31.2 , p = 0.067 ) . A linear model allowing for confounding effects and the interaction between high or low LH scores supported these results . The interaction effect was not significant for any outcome measure but this could be due to an insufficient number of subjects to detect this effect . Conclusion Comparative evaluation of manual therapy and active rehabilitation with reference to LH psychosocial scores is likely to be detectable by the methods used here . However several alterations to the study design are recommended for the main study . A pragmatic trial using a r and omisation process with stratification on the LH score and priori power analysis to determine sample size are suggested for the main study Study Design . R and omized parallel-group comparative trial with a 6-month follow-up period . Objective . To compare , in chronic low back pain patients , the effectiveness of a functional restoration program , including intensive physical training , occupational therapy , and psychological support to an active individual therapy consisting of 3 hours physical therapy per week during 5 weeks . Summary of Background Data . Controlled studies conducted in the United States showed a benefit of functional restoration in patients with low back pain , especially on return to work . R and omized Canadian and European trials had less favorable results . In France , there has been up to now no r and omized study . Controlled studies suggested a positive effect of functional restoration programs . Methods . Eighty-six patients with low back pain were r and omized to either the functional restoration ( 44 patients ) or the active individual therapy ( 42 patients ) program . One person in each group never started the program . Two patients did not complete the functional restoration program , and one was lost to follow-up at 6 months . The mean number of sick-leave days in the 2 previous years was 6 months . Results . After adjustment on the variable ≪ workplace enrolled in an ergonomic program ≫ , the mean number of sick-leave days was significantly lower in the functional restoration group . Physical criteria and treatment appreciation were also better . There was no significant difference in the intensity of pain , the quality of life and functional indexes , the psychological characteristics , the number of contacts with the medical system , and the drug intake . Conclusions . This study demonstrates the effectiveness of a functional restoration program on important outcome measures , such as sick leave , in a country that has a social system that protects people facing difficultiesat work OBJECTIVE To investigate the effectiveness of a TTM-based motivational counselling approach by trained practice nurses to promote physical activity of low back pain patients in a German primary care setting . METHODS Data were collected in a cluster-r and omized controlled trial with three study arms via question naires and patient interviews at baseline and after 6 and 12 months . We analysed total physical activity and self-efficacy by using r and om effect models to allow for clustering . RESULTS A total of 1378 low back pain patients , many with acute symptoms , were included in the study . Nearly 40 % of all patients reported sufficient physical activity at baseline . While there were significant improvements in patients ' physical activity behaviour in all study arms , there was no evidence for an intervention effect . CONCLUSION The outcome may be explained by insufficient performance of the practice nurses , implementation barriers caused by the German health care system and the heterogenous sample . PRACTICE IMPLICATION S Given the objective to incorporate practice nurses into patient education , there is a need for a better basic training of the nurses and for a change towards an organizational structure that facilitates patient-nurse communication . Counselling for low back pain patients has to consider more specificated aims for different subgroups Study Design . Cluster r and omized controlled trial with 6 and 8 quarters of follow-up . Objective . To test the effects of giving evidence -based information addressing psychosocial risk factors for pain-related disability and of screening workplaces for physical health hazards at work on reducing new episodes and duration of pain-related and general absence taking . Summary of Background Data . The “ flag strategy ” for h and ling low back pain problems is recommended in many Western countries but , so far , r and omized intervention studies addressing psychosocial risk factors for disability related to low back pain show mixed results . Methods . We followed employees from 39 different work sites in western Denmark , who had received interventions consisting of either a carefully prepared booklet providing evidence -based information on common musculoskeletal pain problems alone or in combination with systematic workplace screening for physical work hazards . Absence due to pain for at least 7 days and the cumulative numbers of absence days were the main outcome measures . General absence taking was analyzed , too . Company registration s of sickness absence in combination with self-report on the cause of a given absence spell was used to inform absence spells . Results . A total of 3808 of 4006 eligible employees provided information . Among 1063 participants in the control arm , 1458 in the information arm , and 1287 in the information and workplace screening arm , 4.6 % , 6.9 % , and 4.6 % , respectively , experienced pain-related absence , and 27.8 % , 27.2 % , and 24.0 % , respectively , experienced general absence taking during follow-up . No positive effect on the risk of the 2 measures of absence or on the cumulative duration of absence among cases was seen . Conclusion . Results did not support population -based interventions addressing psychosocial risk factors for pain-related disability alone or in combination with workplace screening as effective in reducing the risk of pain-related absence taking or the duration of absence STUDY DESIGN An investigation of the efficacy of an individually scheduled , risk factor-based cognitive behavioral therapy and a st and ardized electromyographic biofeedback intervention in the prevention of chronicity in patients with acute sciatica and psychosocial risk factors for chronicity . OBJECTIVES To investigate the possibility of enhancing pain relief and preventing chronicity in patients with acute sciatica , based on a screening for psychosocial high-risk factors of chronification . SUMMARY OF BACKGROUND DATA Psychological interventions were evaluated mainly in patients with chronic low back pain . Numerous r and omized trials have demonstrated their efficacy , whereas the amount of pain relief was found to be marginal . METHODS Subjective and behavioral outcome parameters were compared with the respective parameters in age- , gender- , and diagnosis-matched high- and low-risk patients . No additional behavioral treatment for in-patient medical therapy was offered to the patients . Outcome of these patients also was compared with that of a group of refusers of behavioral therapy . Psychological , functional , and behavioral variables were measured before and after treatment and at 3- , 6- , 12- and 18-month follow-up visits . Changes over time , group differences , and possible group x time interactions were analyzed by analysis of variance and nonparameteric comparisons . RESULTS Data analysis showed a statistically and clinical ly significant , beneficial effect of both behavioral interventions . However , risk factor-based cognitive behavioral therapy was superior to electromyographic biofeedback intervention with respect to pain relief and application for early retirement . The cognitive behavioral therapy showed a similar good outcome ( e.g. , 90 % showed a clinical significant pain reduction ) as the low-risk patients ( 83 % pain reduction ) . High risk patients and refusers of therapy showed a poor outcome in pain ( 33 % and 20 % pain reduction , respectively ) , disability , and work performance . CONCLUSIONS Individually scheduled , risk factor-based cognitive behavior therapy could be a beneficial treatment modality , which can be offered , in addition to a medical treatment , to patients with acute sciatica and psychosocial high risk factors for chronicity . It may be an effective way to prevent chronification in these patients Study Design A 1-year prospect i ve study in industry , assessing effects of an educational pamphlet on various psychosocial parameters and absenteeism result ing from low back trouble . Objectives To determine the value of distributing an educational psychosocial pamphlet to reduce absenteeism result ing from back trouble . The pamphlet was design ed to alter avoidance behaviors by encouraging a positive , active approach . Summary of Background Data Attempts to control back-pain disability have failed . Fear of pain and activity seemingly leads to avoidance behaviors that contribute to chronicity and work loss . Avoidance behaviors are mediated by attitudes and beliefs ; such attitudes and beliefs are a reasonable target for educational interventions design ed to change “ inappropriate ” behaviors ( e.g. , extended absenteeism ) . Health education pamphlets are advocated widely but tested rarely . Methods Three factories participated in the study . Psychosocial data were collected by question naires ; absence data were extracted from company records . A psychosocial pamphlet was distributed in one factory ; the control subjects received either a nonspecific pamphlet or no intervention . The pamphlet emphasized a positive approach to low back trouble ( reduction of negative beliefs and attitudes ) . Results In the company whose employees received pamphlets , a significant reduction occurred for the number of spells with extended absence and the number of days of absence ( 70 % and 60 % , respectively ) compared with extrapolated values . A concomitant positive shift in beliefs concerning the locus of pain control and the inevitable consequences of low back trouble was found . Conclusions A simple industrial intervention using a psychosocial pamphlet , which was design ed to reduce avoidance behaviors by fostering positive beliefs and attitudes , successfully reduced extended absence result ing from low back trouble This r and omized controlled clinical trial compares the effectiveness of a biopsychosocial treatment with a solely conventional biomedical therapy in patients with subacute low back pain using parameters for pain intensity , functional status , depressive dysfunction and work performance . Sixty-four patients with a first-time sick leave between 3 and 12 weeks due to low back pain were r and omly assigned to either a conventional biomedical therapy ( MT ; n=33 ) group , or a biopsychosocial therapy ( BT ; n=31 ) group including a psychotherapeutic module ; both in accordance with a st and ardized 3 weeks inpatient treatment . Pain intensity , functional back capacity , clinical parameters and depressive dysfunction revealed significant improvement in both treatment groups at end of 3 weeks therapy ( T1 ) . However , at 6 months ( T2 ) , analysis revealed significant better results for nearly all parameters in the BT group that showed further improvement from T1 to T2 , whereas the values in the MT group deteriorated from T1 back to the baseline values . During the 2-year period after therapy , 10 % in MT and 59 % in BT required no further sick leave due to low back pain . The results of the study indicate that a psychotherapeutic element in the treatment of low back pain appears to positively influence pain , functional status and work performance when conducted at an early stage of chronification and helps in the achievement of a better outcome Study Design . A critical appraisal of the literature . Objectives . To increase awareness of the importance of applicability and clinical relevance of the results of r and omized controlled trials ( RCTs ) in the field of spinal disorders by formulating a list of items for assessment of applicability and clinical relevance of results of RCTs . Summary of Background Data . In systematic review s of r and omized controlled trials ( RCTs ) , critical appraisal of method ologic quality is considered important . Less attention has been paid to the assessment of the applicability and the clinical relevance of the results . Methods . RCTs in an up date of the Cochrane review on exercise therapy for low back pain were used . Most of the trials did not score positively on the five Cochrane Back Review Group basic items describing patients : intervention and setting , outcome , effect size , and benefits related to adverse effects . Item 1 was met by 88 % of the trials , but item 2 only by 51 % , item 3 by 67 % , item 4 by 35 % , and item 5 by 0 % . Subsequently , a more comprehensive list of items for the assessment of applicability and clinical relevance of results of RCTs was developed . These criteria were pilot tested on the RCTs . After pilot testing and a subsequent consensus meeting , the list of items was drafted and circulated among the members of the Editorial Board of the Cochrane Back Review Group . Changes were made in response to comments . Results . The final list consists of 40 items . The items are ordered on two headings : Does the report enable the assessment of applicability ? Are the study results clinical ly relevant ? We present examples of informative and noninformative reporting of RCTs in order to illustrate how information on applicability and clinical relevance of results can be assessed . Conclusions . Authors of RCTs should adequately report on items that are essential to assess the applicability and clinical relevance of results . The presented list of items may help clinicians reading RCTs and authors of systematic review s to draw more balanced conclusions on applicability and clinical relevance of results OBJECTIVES To evaluate the effects of a behavioral medicine intervention , relative to an attention control , in preventing chronic pain and disability in patients with first-onset , subacute low back pain ( LBP ) with limitations in work-role function . DESIGN A 2-group , experimental design with r and omization to behavioral medicine or attention control groups . SETTING Orthopedic clinic at a Naval Medical Center . PARTICIPANTS Sixty-seven participants with first-onset LBP of 6 to 10 weeks of duration and impairment in work function , of whom 50 completed all 4 therapy sessions and follow-up 6 months after pain onset . INTERVENTION Four 1-hour individual treatment sessions of either behavioral medicine , focused on back function and pain education , self-management training , grade d activity increases , fear reduction , and pain belief change ; or attention control condition , focused on empathy , support , and reassurance . MAIN OUTCOME MEASURES The primary outcome was proportion of participants classified as recovered , according to pre-established clinical cutoffs on st and ardized measures , signifying absence of chronic pain and disability at 6 months after pain onset . Secondary analyses were conducted on pain , disability , health status , and functional work category . Intervention credibility and pain belief manipulation checks were also evaluated . RESULTS Chi square analyses comparing proportions recovered at 6 months after pain onset for behavioral medicine and attention control participants found relative rates of 52 % versus 31 % in the modified intent-to-treat sample ( P=.09 ) and 54 % versus 23 % for those completing all 4 sessions and 6-month follow-up ( P=.02 ) . At 12 months , 79 % of recovered and 68 % of chronic pain participants still met criteria for their respective groups ( P<.0001 ) . Recovered participants also had higher rates of functional work status recovery at 12 months ( recovered : 96 % full duty and 4 % light duty ; chronic pain : 61 % full duty , 18 % light duty , and 21 % medical discharge , respectively ; P=.03 ) . CONCLUSIONS Early intervention using a behavioral medicine rehabilitation approach may enhance recovery and reduce chronic pain and disability in patients with first-onset , subacute LBP . Effects are stronger for participants attending all 4 sessions and the follow-up assessment Background Clinical prediction rules ( CPRs ) for treatment selection in musculoskeletal conditions have become increasingly popular . Purpose The purpose s of this review are : ( 1 ) to critically appraise studies evaluating CPRs and ( 2 ) to consider the clinical utility and stage of development of each CPR . Data Sources Pertinent data bases were search ed up to April 2009 . Studies aim ing to develop or evaluate a CPR for treatment response in musculoskeletal conditions were included . Two independent review ers assessed eligibility and extracted method ological data , stage of development , and effect size information . Study Selection / Data Extraction and Synthesis Eighteen studies , evaluating 15 separate CPRs , were included . Fourteen CPRs were at the derivation stage , and all CPRs had been evaluated using a single-arm trial design , thus it is not possible to determine whether the CPRs identify prognosis ( regardless of treatment ) or specifically response to treatment . The CPR at the validation stage investigated spinal manipulative therapy ( SMT ) for low back pain and had been evaluated in 2 separate well-conducted r and omized controlled trials . The first trial demonstrated a clinical ly meaningful effect of the SMT CPR ; the additional effect from SMT in patients “ positive-on-the-rule ” was 15 Oswestry disability units at week 1 and 9 units at week 4 . The second trial showed that the CPR did not generalize to a different clinical setting , including a modified treatment . Limitations Due to differences in methods of reporting and journal publication restraints ( eg , word count restrictions ) , some quality assessment items may have been completed in the included studies , but not captured in this review . Conclusions There is , at present , little evidence that CPRs can be used to predict effects of treatment for musculoskeletal conditions . The principal problem is that most studies use design s that can not differentiate between predictors of response to treatment and general predictors of outcome . Only 1 CPR has been evaluated within an RCT design ed to predict response to treatment . Validation of these rules is imperative to allow clinical application BACKGROUND CONTEXT Cognitive behavioral therapy has been used successfully in acute low back pain ( LBP ) treatment , but the use of a cognitive behavioral videotape as an adjunct to treatment has not been studied . PURPOSE To determine outcomes for patients with acute LBP receiving a videotape design ed to change beliefs and behaviors compared with a st and ard instructional videotape . STUDY DESIGN / SETTING R and omized controlled trial ; multidisciplinary clinic in an academic setting . PATIENT SAMPLE Consecutive subjects with less than 3 months of LBP . Of 224 eligible subjects , 138 participated and completed the initial question naires . OUTCOME MEASURES Oswestry Disability Index , Pain and Impairment Relationship Scale , Fear-Avoidance Beliefs Question naire ; medical costs related to LBP and total medical costs incurred by participants during 1 year of follow-up . METHODS Subjects were r and omly assigned to receive a behavioral videotape or a control videotape . Other than the videotape , usual care was provided to each patient . RESULTS No significant differences in any outcome measures or medical costs between the two groups at 12 months . However , baseline Vermont Disability Prediction Question naire was significantly lower in those who completed the entire study compared with those who did not complete the study . CONCLUSIONS Compared with a st and ard instructional videotape , a behavioral videotape did not change beliefs , outcomes , or costs over 1 year . Cost-effective behavioral interventions with high patient retention rates are needed , especially for those at greatest risk of high utilization of re sources BACKGROUND Pain-related fear is related to disability in persistent pain conditions . Exposure treatment has been reported to be of great benefit in replicated single case experiments . AIM To evaluate the effects of exposure in vivo on fear and function in patients with persistent pain and work disability . METHOD We recruited 46 patients suffering from long-term back pain and reduced function , who also were deemed fearful according to st and ardized measures . Participants were r and omized into either an exposure plus usual treatment or waiting list control plus usual treatment group . After the waiting period the control group crossed over and received the exposure treatment . RESULTS Between group comparisons showed a significantly better result for the exposure group on function , but not for fear or pain and effect sizes were modest ( function=.6 ; fear=.4 ; pain=.1 ) . When the control group crossed over to treatment significant treatment effects were noted for fear and function . For all patients treated , the pre to post-treatment effect sizes were large ( function=.7 ; fear=1.1 ; pain=.9 ) . There were 12 dropouts ( 8 in exposure and 4 in the control ) during the first treatment phase and an additional 4 when the control group crossed over to exposure . CONCLUSIONS Compared to a group receiving usual treatment and waiting for exposure , the exposure in vivo group demonstrated a significantly larger improvement on function . Overall exposure had moderate effects on function , fear and pain intensity . We conclude that exposure may be important in treatment , but is not recommended as a " st and alone " adjunct to usual treatment OBJECTIVE To evaluate the short-term effect of physical exercise and a cognitive intervention in low back pain . DESIGN R and omized controlled trial . SUBJECTS Ninety-three patients sick-listed for 8 - 12 weeks for sub-acute low back pain were r and omized to an exercise regime ( n = 30 ) , a cognitive intervention ( n = 34 ) or a control group ( n = 29 ) . METHODS Primary outcome measures were pain , disability , sick-listing and satisfaction with care . Secondary outcome measures were self-efficacy for pain and for function , fear-avoidance beliefs , emotional distress , generic health status and life satisfaction . RESULTS Eighteen percent of subjects dropped out . Drop-out was most frequent in the exercise group . At 18 weeks after inclusion fear-avoidance beliefs were reduced in both intervention groups . The cognitive group demonstrated significant improvement in disability , self-efficacy for pain , emotional distress , general health and life satisfaction . Patients in the exercise group were significantly more satisfied with the treatment , and patients following the exercise protocol reduced pain significantly . No effect on sick-listing was seen . CONCLUSION Cognitive intervention improved disability and may be feasible for most patients sick-listed in the sub-acute phase . Physical exercise reduced patients ' symptoms , but requires high motivation by patients . Despite positive effects in intervention groups on variables considered as negative prognostic factors for long-term disability and sickness absence , interventions had no effect on sick-listing & NA ; Fear‐avoidance beliefs have been identified as an important psychosocial variable in patients with chronic disability doe to low back pain . The importance of fear‐avoidance beliefs for individuals with acute low back pain has not been explored . Seventy‐eight subjects with work‐related low back pain of less than 3 weeks ' duration were studied . Measurements of pain intensity , physical impairment , disability , nonorganic signs and symptoms , and depression were taken at the initial evaluation . Fear‐avoidance beliefs were measured with the work and physical activity subscales of the Fear‐avoidance Beliefs Question naire . Disability and work status were re‐assessed after 4 weeks of physical therapy . Patterns of correlation between fear‐avoidance beliefs and other concurrently‐measured variables were similar to those reported in patients with chronic low back pain . Fear‐avoidance beliefs did not explain a significant amount of the variability in initial disability levels after controlling for pain intensity and physical impairment . Fear‐avoidance beliefs about work were significant predictors of 4‐week disability and work status even after controlling for initial levels of pain intensity , physical impairment , and disability , and the type of therapy received . Fear‐avoidance beliefs are present in patients with acute low back pain , and may be an important factor in explaining the transition from acute to chronic conditions . Screening for fear‐avoidance beliefs may be useful for identifying patients at risk of prolonged disability and work absence & NA ; The current investigation studied the effectiveness of a secondary prevention program for nurses with back pain who were deemed at risk for developing a chronic problem . A 2 × 3 repeated measures design was employed with 2 groups and 3 assessment periods . The treatment group received an intervention design ed to reduce current problems , but above all to prevent reinjury and minor pains from becoming chronic medical problems , and it included a physical and behavioral therapy package . The control group was placed on a waiting‐list . Results indicated that the treatment group had significantly greater improvements than the control group for pain intensity , anxiety , sleep quality and fatigue ratings , observed pain behavior , activities , mood , and helplessness . These differences were generally maintained at the 6 month follow‐up . In addition , the treatment group broke a trend for increasing amounts of pain‐related absenteeism , while the control group did not . Taken as a whole , the results suggest that a secondary prevention program aim ed at altering life style factors may represent an effective method for dealing with musculoskeletal pain problems Study Design . A subgroup analysis of patient outcomes from a r and omized controlled trial comparing a Back to Fitness program with usual general practitioner care . Objectives . To test whether patients with high scores on measures of fear-avoidance and distress/depression benefit the most . Summary of Background Data . A fitness program , ongoing since the 1980s , was developed for use in the community and has been shown to be effective in reducing disability . Detailed analyses are needed to identify patient groups who benefit . Recent evidence points to the potentially important role of fear , distress , and depression . Method . Data from 98 patients allocated to normal general practitioner care and 89 patients allocated to a group exercise program were analyzed after categorizing baseline scores on fear-avoidance beliefs ( high/low ) and distress/depression ( at risk/normal ) . The main outcome measure was the Rol and Disability Question naire . Outcomes were compared between the intervention and control groups at 6 weeks , 6 months , and 12 months . Results . High fear-avoiders fared significantly better in the exercise program than in usual general practitioner care at 6 weeks and at 1 year . Low fear-avoiders did not . Patients who were distressed or depressed were significantly better off at 6 weeks , but the benefits were not maintained long-term . Conclusion . Patients with high levels of fear-avoidance beliefs could significantly benefit from the Back to Fitness program . The benefits of the exercise program for patients with high levels of distress/depression appear to be short-term only . Average attendance was only 4 to 5 classes , which may not be sufficient for more recalcitrant cases . Further research is indicated Objectives Given the individual and economic burden of chronic work disability in low back pain patients , there is a need for effective preventive interventions . The aim of the present study was to investigate whether problem-solving therapy had a supplemental value when added to behavioral grade d activity , regarding days of sick leave and work status . Design R and omized controlled trial . Patients and Setting Employees who were recently on sick leave as a result of nonspecific low back pain were referred to the rehabilitation center by general practitioner , occupational physician , or rehabilitation physician . Forty-five employees had been r and omly assigned to the experimental treatment condition that included behavioral grade d activity and problem-solving therapy ( GAPS ) , and 39 employees had been r and omly assigned to behavioral grade d activity and group education ( GAGE ) . Outcome Measures Days of sick leave and work status . Data were retrieved from occupational health services . Results Data analyses showed that employees in the GAPS group had significantly fewer days of sick leave in the second half-year after the intervention . Moreover , work status was more favorable for employees in this condition , in that more employees had a 100 % return-to-work and fewer patients ended up receiving disability pensions one year after the intervention . Sensitivity analyses confirmed these results . Conclusions The addition of problem-solving therapy to behavioral grade d activity had supplemental value in employees with nonspecific low back pain OBJECTIVES Interventions that take psychosocial factors into account are recommended for patients with persistent back or neck pain . We compared the effectiveness of a brief physiotherapy pain management approach using cognitive-behavioural principles ( Solution-Finding Approach-SFA ) with a commonly used method of physical therapy ( McKenzie Approach-McK ) . METHODS Eligible patients referred by GPs to physiotherapy departments with neck or back pain lasting at least 2 weeks were r and omized to McK ( n= 161 ) or to SFA ( n= 154 ) . They were further r and omized to receive an educational booklet or not . The primary outcome was the Tampa Scale of Kinesiophobia ( TSK ) ( Activity-Avoidance scale used as a proxy for coping ) at 6 weeks , and 6 and 12 months . RESULTS Of 649 patients assessed for eligibility , 315 were recruited ( 219 with back pain , 96 with neck pain ) . There were no statistically significant differences in outcomes between the groups , except that at any time point SFA patients supported by a booklet reported less reliance on health professionals ( Multidimensional Health Locus of Control Powerful Others Scale ) , while at 6 months McK patients showed slightly more improvement on activity-avoidance ( TSK ) . At 6 weeks , patient satisfaction was greater for McK ( median 90 % compared with 70 % for SFA ) . Both interventions result ed in modest but clinical ly important improvements over time on the Rol and Disability Question naire Scores and Northwick Park Neck Pain Scores . CONCLUSIONS The McK approach result ed in higher patient satisfaction overall but the SFA could be more cost-effective , as fewer ( three vs four ) sessions were needed Objective To test the predictive utility of the Örebro Musculoskeletal Pain Screening Question naire in identifying patients at risk for developing persistent back pain problems . Design Prospect i ve , where participants completed the question naire and their cases were followed for 6 months to assess outcome with regard to pain , function , and absenteeism due to sickness . Participants One hundred seven patients , recruited from seven primary care units . Results Discriminant analyses showed that the items on the question naire were significantly related to future problems . For absenteeism due to sickness , 68 % of the patients were correctly classified into one of three groups , whereas an even distribution would have produced 33 % . The analyses for function correctly classified 81 % , and for pain 71 % , into one of two groups , compared with a chance level of 50 % . A total score analysis demonstrated that a cutoff score of 90 points had a sensitivity of 89 % and a specificity of 65 % for absenteeism due to sickness , and a sensitivity of 74 % and a specificity of 79 % for functional ability . Conclusions The results underscore that psychological variables are related to outcome 6 months later , and they replicate and extend earlier findings indicating that the Örebro Screening Question naire is a clinical ly reliable and valid instrument . The total score was a relatively good predictor of future absenteeism due to sickness as well as function , but not of pain . The results suggest that the instrument could be of value in isolating patients in need of early interventions and may promote the use of appropriate interventions for patients with psychological risk factors Background : Low back pain is a common medical and social problem associated with disability and absence from work . Knowledge on effective return to work ( RTW ) interventions is scarce . Objective : To determine the effectiveness of grade d activity as part of a multistage RTW programme . Design : R and omised controlled trial . Setting : Occupational healthcare . Subjects : 112 workers absent from work for more than eight weeks due to low back pain were r and omised to either grade d activity ( n = 55 ) or usual care ( n = 57 ) . Intervention : Grade d activity , a physical exercise programme aim ed at RTW based on operant-conditioning behavioural principles . Main outcome measures : The number of days off work until first RTW for more then 28 days , total number of days on sick leave during follow up , functional status , and severity of pain . Follow up was 26 weeks . Results : Grade d activity prolonged RTW . Median time until RTW was equal to the total number of days on sick leave and was 139 ( IQR = 69 ) days in the grade d activity group and 111 ( IQR = 76 ) days in the usual care group ( hazard ratio = 0.52 , 95 % CI 0.32 to 0.86 ) . An interaction between a prior workplace intervention and grade d activity , together with a delay in the start of the grade d activity intervention , explained most of the delay in RTW ( hazard ratio = 0.86 , 95 % CI 0.40 to 1.84 without prior intervention and 0.39 , 95 % CI 0.19 to 0.81 with prior intervention ) . Grade d activity did not improve pain or functional status clinical ly significantly . Conclusions : Grade d activity was not effective for any of the outcome measures . Different interventions combined can lead to a delay in RTW . Delay in referral to grade d activity delays RTW . In implementing grade d activity special attention should be paid to the structure and process of care & NA ; The aim of the present study was to evaluate the long‐term outcome of a behavioural medicine rehabilitation programme and the outcome of its two main components , compared to a ‘ treatment‐as‐usual ’ control group . The study employed a 4 × 5 repeated‐ measures design with four groups and five assessment periods during a 3‐year follow‐up . The group studied consisted of blue‐collar and service/care workers on sick leave , identified in a nationwide health insurance scheme in Sweden . After inclusion , the subjects were r and omised to one of the four conditions : behaviour‐oriented physiotherapy ( PT ) , cognitive behavioural therapy ( CBT ) , behavioural medicine rehabilitation consisting of PT+CBT ( BM ) and a ‘ treatment‐as‐usual ’ control group ( CG ) . Outcome variables were sick leave , early retirement and health‐related quality of life . A cost‐effectiveness analysis , comparing the programmes , was made . The results showed , consistently , the full‐time behavioural medicine programme being superior to the three other conditions . The strongest effect was found on females . Regarding sick leave , the mean difference in the per‐ protocol analysis between the BM programme and the control group was 201 days , thus reducing sick leave by about two‐thirds of a working year . Rehabilitating women has a substantial impact on costs for production losses , whereas rehabilitating men seem to be effortless with no significant effect on either health or costs . In conclusion , a full‐time behavioural medicine programme is a cost‐effective method for improving health and increasing return to work in women working in blue‐collar or service/care occupations and suffering from back/neck pain Patients with nonspecific mechanical low back pain ( n = 103 ) , examined by an orthopaedic surgeon and a social worker , were r and omized to an activity group ( n = 51 ) and a control group ( n = 52 ) . Patients with defined orthopaedic , medical , or psychiatirc diagnoses were excluded before r and omization . No patients were excluded due to place of birth or difficulties in speaking or underst and ing the Swedish language . The purpose of the study was to compare mobility , strength and fitness after traditional care and after traditional care plus a grade d activity program with a behavioral therapy approach . A grade d activity program , with a behavioral therapy approach was given under the guidance of a physical therapist . The endpoint of the grade d activity program was return to work . This program significantly increased mobility , strength , and fitness more than could be explained by only a time recovery effect , especially in males . The patients in the activity group returned to work earlier than did the patients in the control group . Spinal rotation , abdominal muscle endurance time and lifting capacity were significantly correlated to rate of return to work . Traditional care plus a grade d activity program were superior to only traditional care , evaluated in terms of mobility , strength and fitness . The grade d activity program proved to be a successful method of restoring occupational function and facilitating return to work in subacute low back pain patients . The patients in the grade d activity program learned that it is safe to move , while regaining function Introduction In an earlier study , Gatchel et al. ( J Occup Rehabil 13:1–9 , 2003 ) demonstrated that participants at high risk for developing chronic low back pain disability ( CLBPD ) , who received a biopsychosocial early intervention treatment program , displayed significantly more symptom improvement , as well as cost savings , relative to participants receiving st and ard care . The purpose of the present study was to exp and on these results by examining whether the addition of a work-transition component would further strengthen the effectiveness of this early intervention treatment . Methods Using an existing algorithm , participants were identified as being high-risk ( HR ) or low-risk ( LR ) for developing CLBPD . HR participants were then r and omly assigned to one of three groups : early intervention ( EI ) ; early intervention with work transition ( EI/WT ) ; or st and ard care ( SC ) . Participants provided information regarding pain , disability , work status , and psychosocial functioning at baseline , periodically during treatment , and again 1 year following completion of treatment . Results At 1-year follow-up , no significant differences were found between the EI and EI/WT groups in terms of occupational status , self-reports of pain and disability , coping ability or psychosocial functioning . However , significant differences in all these outcomes were found comparing these groups to st and ard care . Conclusion The addition of a work transition component to an early intervention program for the treatment of ALBP did not significantly contribute to improved work outcomes . However , results further support the effectiveness of early intervention for high-risk ALBP patients There has been a recent increase in research evaluating treatment-based subgroups of non-specific low back pain . The aim of these sub-classification schemes is to identify subgroups of patients who will respond preferentially to one treatment as opposed to another . Our article provides accessible guidance on to how to interpret this research and determine its implication s for clinical practice . We propose that studies evaluating treatment-based subgroups can be interpreted in the context of a three-stage process : ( 1 ) hypothesis generation-proposal of clinical features to define subgroups ; ( 2 ) hypothesis testing-a r and omised controlled trial ( RCT ) to test that subgroup membership modifies the effect of a treatment ; and ( 3 ) replication-another RCT to confirm the results of stage 2 and ensure that findings hold beyond the specific original conditions . At this point , the bulk of research evidence in defining subgroups of patients with low back pain is in the hypothesis generation stage ; no classification system is supported by sufficient evidence to recommend implementation into clinical practice Study Design . A controlled clinical trial . Objectives . To examine the long‐term effect of an informative approach to low back pain . Summary of Background Data . In management and prevention of low back pain , back school based on an ergonomic approach have played an important role . The effect of such informative interventions is not clear . Methods . A 5‐year follow‐up study was done on patients included in a previous study . The outcome was measured by return to work or still on sick leave . The patients were allocated to an intervention group ( n = 245 ) and a control group ( n = 244 ) . Only the intervention group was called in for examination and intervention and answered a battery of tests for psychological and health factors . The intervention apart from the clinical examination consisted of education in a " mini back school . " The program was based on a new medical model for low back pain . Results . Forty‐seven ( 19 % ) of the patients in the intervention group , compared with 84 patients ( 34 % ) in the control group , were still on sick leave after 5 years ( P < 0.001 ) . There were fewer recurrences of sick leave ( P < 0.03 ) in the intervention group than in the control group . Based on Internal Health Locus of Control , number of children , and income , 75 % were correctly classified as nonreturners in the intervention group . Conclusions . This study indicates that subchronic low back pain may be managed successfully with an approach that includes clinical examination combined with information for patients about the nature of the problem , provided in a manner design ed to reduce fear and give them reason to resume light activity & NA ; Back pain is a significant health care problem that has been managed unsatisfactorily in primary care setting s. Providers typically address medical issues but do not adequately address patient concerns or functional limitations related to back pain . We evaluated a brief intervention for primary care back pain patients design ed to provide accurate information about back pain , instill attitudes favorable towards self care , reduce fears and worries , assist patients in developing personalized action plans to manage their back pain , and improve functional outcomes . Patients enrolled in a large health maintenance organization were invited to participate in an educational program to improve back pain self care skills 6–8 weeks after a primary care back pain visit . Patients ( n=226 ) were r and omly assigned to a Self Care intervention or to Usual Care , and were assessed at baseline , 3‐ , 6‐ , and 12‐months . The intervention involved a two‐session Self Care group and an individual meeting and telephone conversation with the group leader , a psychologist experienced in chronic pain management . The intervention was supplemented by educational material s ( book and videos ) supporting active management of back pain . The control group received usual care supplemented by a book on back pain care . Participants assigned to the Self Care intervention showed significantly greater reductions in back‐related worry and fear‐avoidance beliefs than the control group . Modest , but statistically significant , effects on pain ratings and interference with activities were also observed OBJECTIVES We sought to estimate the effects of recreational physical activity and back exercises on low back pain , related disability , and psychological distress among patients r and omized to chiropractic or medical care in a managed care setting . METHODS Low back pain patients ( n=681 ) were r and omized and followed for 18 months . Participation in recreational physical activities , use of back exercises , and low back pain , related disability , and psychological distress were measured at baseline , at 6 weeks , and at 6 , 12 , and 18 months . Multivariate logistic regression modeling was used to estimate adjusted associations of physical activity and back exercises with concurrent and subsequent pain , disability , and psychological distress . RESULTS Participation in recreational physical activities was inversely associated -- both cross-sectionally and longitudinally -- with low back pain , related disability , and psychological distress . By contrast , back exercise was positively associated -- both cross-sectionally and longitudinally -- with low back pain and related disability . CONCLUSIONS These results suggest that individuals with low back pain should refrain from specific back exercises and instead focus on nonspecific physical activities to reduce pain and improve psychological health Context In this r and omized , controlled trial , spinal manipulation plus exercise produced outcomes for low back pain similar to those produced by exercise alone . Yet , some patients did respond to spinal manipulation , and it would be helpful for doctors to be able to identify such patients . Contribution Patients were most likely to benefit from spinal manipulation if they met 4 of 5 of the following criteria : symptom duration less than 16 days , no symptoms distal to knee , score less than 19 on a fear-avoidance measure , at least 1 hypomobile lumbar segment , and at least 1 hip with more than 35 degrees of internal rotation . Implication s Clinicians may be able to use these criteria to identify patients with low back pain who are good c and i date s for spinal manipulation . The Editors Next to the common cold , low back pain is the most common reason that individuals visit a physician 's office ( 1 ) . Billions of dollars in medical expenditures and lost labor costs for this condition are incurred each year ( 2 , 3 ) . Attempts to identify effective interventions for individuals with low back pain have been largely unsuccessful ( 4 ) . In particular , conflicting evidence exists about the effectiveness of spinal manipulation ; some r and omized trials have shown a benefit , while other trials have not ( 5 - 7 ) . These conflicting conclusions are reflected in the various recommendations in national clinical practice guidelines , with some recommending manipulation and others not ( 8) . The variety of conclusions in trials of manipulation may be attributable to the failure of research ers to adequately consider the importance of classification . Using broad inclusion criteria results in a heterogeneous sample that may include many patients for whom no benefit is expected , thus masking the intervention 's true value ( 9 , 10 ) . Consequently , developing methods for matching patients with low back pain to treatments that are most likely to benefit them has become an important research priority ( 11 ) . Clinical prediction rules are tools design ed to assist clinicians in decision making when caring for patients ( 12 ) . Several clinical prediction rules have been developed and vali date d to improve clinical decision making for the use of imaging in patients with ankle , knee , cervical spine , or minor head injuries ( 13 - 16 ) . Few studies have attempted to develop rules that establish prognosis on the basis of outcome from a specific intervention , such as spinal manipulation . Recently , Flynn and colleagues ( 17 ) developed a clinical prediction rule for identifying patients with low back pain who are likely to benefit from manipulation . They examined a series of patients with low back pain who received a manipulation intervention . Five factors formed the most parsimonious set of predictors for identifying patients who achieved at least 50 % improvement in disability within 1 week with a maximum of 2 manipulation interventions ( Table 1 ) ( 17 ) . The positive likelihood ratio among patients who met at least 4 of 5 of the criteria was 24.4 ( 95 % CI , 4.6 to 139.4 ) . Table 1 . Five Criteria in the Spinal Manipulation Clinical Prediction Rule Clinical prediction rules must be vali date d in separate population s before being recommended for widespread implementation ( 18 ) . A clinical prediction rule for identifying which patients with low back pain are most likely to respond to manipulation could improve clinical efficiency and re source utilization . Thus , we aim ed to vali date the spinal manipulation clinical prediction rule in a multicenter trial . Methods We considered consecutive patients with a primary symptom of low back pain who were referred to physical therapy for participation . We used 14 physical therapists at 8 clinics in various U.S. regions and setting s ( 2 academic medical centers and smaller outpatient practice setting s ) . Most participating sites were health care facilities within the U.S. Air Force . Each site 's institutional review board approved the study before we began recruitment and data collection . Inclusion criteria were age 18 to 60 years ; a primary symptom of low back pain , with or without referral into the lower extremity ; and an Oswestry Disability Question naire ( ODQ ) score of at least 30 % . We excluded patients who had red flags for a serious spinal condition ( for example , tumor , compression fracture , or infection ) , those who had signs consistent with nerve root compression ( that is , positive straight-leg increase < 45 degrees or diminished reflexes , sensation , or lower-extremity strength ) , those who were pregnant , or those who had previous surgery to the lumbar spine or buttock . These criteria are consistent with those used in Flynn and colleagues ' study ( 17 ) and were design ed to include patients without a contraindication to manipulation . Once patients were admitted to the study , we used intention-to-treat principles , and no patient was removed for nonadherence . History and Physical Examination Before r and omization , patients completed several self-report measures and then received a st and ardized history and physical examination . We collected demographic information , including age and sex ; medical history ; and location and nature of symptoms . Self-report measures included a body diagram to assess the symptom distribution ( 19 ) . We used an 11-point pain-rating scale ranging from 0 ( no pain ) to 10 ( worst imaginable pain ) to assess current pain intensity and the best and worst level of pain during the last 24 hours ( 20 ) . We used the average of the 3 ratings . We used the Fear-Avoidance Beliefs Question naire ( FABQ ) to quantify the patient 's fear of pain and beliefs about avoiding activity ( 21 ) . Previous studies have found a high level of testretest reliability for both the FABQ physical activity and work subscales ( 22 ) . Fearavoidance beliefs have been associated with current and future disability and work loss in patients with acute ( 23 ) and chronic ( 24 ) low back pain . The modified ODQ is a region-specific disability scale for patients with low back pain ( 25 ) that has high levels of reliability , validity , and responsiveness ( 26 ) . Physical examination measures included lumbar active range of motion ( 27 ) and various tests purported to identify dysfunction in the lumbopelvic region ( 28 ) . Complete details of the physical examination are described elsewhere ( 26 ) . Specific components pertinent to validation of the rule were assessment s of segmental mobility and hip internal rotation range of motion , the performance of which is described in Appendix 1 and Appendix 3 video . Each physical therapist received a detailed manual that operationally defined each examination and treatment procedure and was trained in the study procedures by an investigator before data collection began . Supplement . Appendix 3 video : A Clinical Prediction Rule To Identify Patients with Low Back Pain Most Likely To Benefit from Spinal Manipulation Determining Status on the Clinical Prediction Rule A physical therapist who was blinded to the patients ' treatment group assignment assessed the 5 criteria in the rule ( Table 1 , Appendix 1 , and Appendix 3 video ) . To further minimize bias , examiners were not instructed in the rule 's criteria and were unaware of the patient 's status on the rule . After completion of the study , an examiner who was blinded to the patient 's treatment assignment determined the patient 's status on the rule by using the results of the baseline examination . As was done in the initial study ( 17 ) , we classified patients as positive if they met at least 4 of 5 criteria and were therefore likely to respond to manipulation . We classified patients with 3 or fewer criteria as negative . An examiner who was blinded to the patient 's status on the rule repeated the history and physical examination 1 and 4 weeks after r and omization . Patients also completed a 6-month follow-up postal question naire to assess disability , work status , and health care utilization . Treatment Groups We used a r and om-number generator to generate a r and omization list before the study began . We prepared individual , sequentially numbered index cards with the r and omization assignments . We folded the cards and placed them in sealed envelopes . After the baseline examination , the physical therapist who conducted the examination opened the next envelope , indicating the treatment group assignment . We r and omly assigned patients to 1 of 2 groups : 1 ) spinal manipulation plus an exercise program ( manipulation group ) or 2 ) an exervideocise program alone ( exercise group ) . Patients in both groups attended physical therapy twice during the first week and then once a week for the next 3 weeks , for a total of 5 sessions . We initiated treatment immediately after completion of the baseline examination , unless prohibited by time constraints ; in that case the first treatment session took place 24 to 48 hours after the baseline examination . All patients received an exercise instruction booklet that outlined the proper performance and frequency of each exercise and were instructed to perform their assigned exercise program once daily on the days that they did not attend therapy . On the basis of the benefits associated with remaining active ( 29 ) , patients in both groups were given advice to maintain usual activity within the limits of pain . Manipulation Group The treatment received by the manipulation group differed from that of the exercise group during the first 2 physical therapy sessions . During these 2 sessions , patients received high-velocity thrust spinal manipulation and a range-of-motion exercise only . First , the physical therapist performed the manipulation by using the same technique used by Flynn and colleagues ( 17 ) . Appendix 2 describes and Figure 1 and Appendix 3 video illustrate the procedures used to perform the manipulation technique . Figure 1 . Manipulative intervention used in developing and validating the spinal manipulation clinical prediction rule . Exercise Group We treated patients in the exercise group with a low-stress & NA ; Forty‐five low back pain patients were r and omly assigned to either a st and ard inpatient rehabilitation program or the st and ard program with additional psychological components . The st and ard program emphasized education , support , and physical reconditioning through exercise . Patients receiving the psychological program were given additional training in relaxation and other coping skills and received contingent reinforcement for exercise . Both programs included reduction of medication intake and an emphasis on family involvement after discharge . Measures of functional status were taken prior to the program , at discharge from the 3‐week inpatient program , and at a 6‐month follow‐up appointment . These data revealed that patients improved their overall functioning at discharge and maintained these gains at the follow‐up assessment . A similar pattern of findings was obtained for self‐reported pain and interference . Furthermore , 81 % of the patients had returned to work or were engaged in active job retraining by the follow‐up . Using a conservative measure of full‐time return to the same or an equivalent job , 57 % were employed by the follow‐up . Patient improvement , however , was not differentially affected by treatment group assignment , suggesting that the psychological treatment failed to add to the effectiveness obtained by the st and ard rehabilitation program . Results are discussed in the context of improving patient outcomes from rehabilitation for low back pain A preliminary investigation was undertaken on 117 acute back pain cases , to assess the utility of counseling at the acute stage upon the course of recovery over the subsequent 6 months . In addition , the extent to which psychological reactions to acute injury would allow the ' tagging ' of individuals at risk for chronic pain problems , was studied . The minimal rehabilitation counseling proved inadequate to effect the course of recovery , but remarkably accurate predictions were possible at the sub-chronic point ( 3 months ) as to who would make complete recoveries Abstract Background : Many clinicians and research ers believe that there are subgroups of people with spinal pain who respond differently to treatment and have different prognoses . There has been considerable interest in this topic recently . However , problems occur when conclusions about subgroups are made that are inappropriate given the r and omized controlled trial design used . The research design to choose , when developing a study protocol that investigates the effect of treatment subgroups , depends on the particular research question . Similarly , the inferences that can be drawn from an existing study will vary , depending on the design of the trial . Objectives : This paper discusses the r and omized controlled trial design s that are suitable to answer particular questions about treatment subgroups . It focuses on trial design s that are suitable to answer four questions : ( 1 ) ' Is the treatment effective in a pre-specified group of patients ? ' ; ( 2 ) ' Are outcomes of treatment applied using a subgrouping clinical reasoning process , better than a control treatment ? ' ; ( 3 ) ' Are the outcomes for a patient subgroup receiving a particular treatment ( compared to a control treatment ) better than for patients not in the subgroup who receive the same treatment ? ' ; and ( 4 ) ' Are outcomes for a number of treatments better if those treatments are matched to patients in specific subgroups , than if the SAME treatments are r and omly given to patients ? ' . Illustrative examples of these studies are provided . Conclusion : If the clinical usefulness of targeting treatments to subgroups of people is to be determined , an important step is a shared underst and ing of what different RCT design s can tell us about subgroups & NA ; The aim of this study was to investigate the influence of non‐pain‐related failure experiences and pain‐related fear on pain report , pain tolerance and pain avoidance in chronic low back pain ( CLBP ) patients . Moreover , the mediating and moderating role of negative affectivity ( trait‐NA ) in the relationship between failure experiences and pain was examined . Seventy‐six patients were divided into high and low pain‐related fear groups and within each group they were r and omly assigned to the failure or success feedback condition . In the first part of the study patients completed a ‘ social empathy test ’ and experimenter 1 subsequently delivered false failure or success feedback . A second experimenter , who was blind for the condition , subsequently administered two lifting tasks in order to obtain measures of pain report , tolerance and avoidance . Failure feedback did have an effect on pain avoidance but unexpectedly , and not as hypothesized , pain avoidance was reduced instead of enhanced . With regard to pain report and pain tolerance similar patterns were found , but these were not statistically significant . The effect of failure feedback on pain avoidance was moderated by trait‐NA . Only in the subgroup of patients who scored low on trait‐NA did failure feedback decrease pain avoidance . State‐NA did not mediate the effects of feedback . In line with previous findings , pain‐related fear result ed in lower pain tolerance . Moreover , this study was the first to show that pain‐related fear predicted higher pain report in CLBP patients . Pain‐related fear did not predict pain avoidance when pre‐lifting pain and gender were controlled for . Finally , pre‐lifting pain turned out to be the strongest predictor with regard to all pain measures . The role of pain‐related fear and unexpected findings with regard to feedback are discussed as well as some clinical implication STUDY DESIGN Prospect i ve series of consecutive cases . OBJECTIVES To observe if kinesiophobia was altered through an education- and quota-based exercise physical therapy program , and to observe the relationship of kinesiophobia with other measures related to chronic low back pain . BACKGROUND The role of kinesiophobia in worsening the chronic low back pain predicament has been documented in numerous studies . However , less is known of the effect of an exerciseonly-based physical therapy program 's ability to alter kinesiophobia and improve functional abilities in patients with chronic low back pain . METHODS Eighty-two patients with at least 3 months of low back pain , and a moderate level of disability ( Oswestry score greater than or equal to 20 ) were willing to participate in this study . Sixty-eight of these patients completed treatment . For 68 compliant patients , females comprised 56 % , the mean age was 43 years , the mean duration of symptoms was 28 months , and the primary anatomic diagnosis was disc degeneration ( 70 % ) . Patients underwent a course of non-pain-contingent , quota-based physical therapy to address impairments in flexibility , strength , and lifting capacity . These were quantified prior to and following treatment using vali date d methods . Before and after treatment , patients completed the Fear-Avoidance Beliefs Question naire ( FABQ ) , Tampa Scale of Kinesiophobia ( TSK ) Question naire , Oswestry Disability Index ( ODI ) Question naire , and a 0-to-10 visual analog scale for back and lower extremity pain . A 12-month follow-up was conducted using mailed question naires . RESULTS The mean number of physical therapy visits was 14 . Clinical ly and statistically significant ( P<.001 ) improvement in flexibility , strength , and lifting ability were observed . Statistically significant ( P<.001 ) improvement in back pain , disability , and measures of kinesiophobia were also noted at discharge and maintained at 12-month follow-up . At discharge , Oswestry scores correlated with TSK ( r = .59 , P<.001 ) , FABQ-Activities ( r = .55 , P<.001 ) , and FABQ-Work ( r = .50 , P<.001 ) scores . CONCLUSION In this study we observed that kinesiophobia decreased during an intensive physical therapy program in which exercises were performed in a quota-based manner . Following the successful performance of non-pain-contingent , quota-based exercise , patients ' fears of injury lessened , and this may have had a positive influence on disability BACKGROUND Recommendations for the management of low back pain in primary care emphasise the importance of recognising and addressing psychosocial factors at an early stage . We compared the effectiveness of a brief pain-management programme with physiotherapy incorporating manual therapy for the reduction of disability at 12 months in patients consulting primary care with subacute low back pain . METHODS For this pragmatic , multicentre , r and omised clinical trial , eligible participants consulted primary care with non-specific low back pain of less than 12 weeks ' duration . They were r and omly assigned either a programme of pain management ( n=201 ) or manual therapy ( n=201 ) . The primary outcome was change in the score on the Rol and and Morris disability question naire at 12 months . Analysis was by intention to treat . FINDINGS Of 544 patients assessed for eligibility , 402 were recruited ( mean age 40.6 years ) and 329 ( 82 % ) reached 12-month follow-up . Mean disability scores were 13.8 ( SD 4.8 ) for the pain-management group and 13.3 ( 4.9 ) for the manual-therapy group . The mean decreases in disability scores were 8.8 ( 6.4 ) and 8.8 ( 6.1 ) at 12 months ( difference 0 [ 95 % CI -1.3 to 1.4 ] , p=0.99 ) , and median numbers of physiotherapy visits per patient were three ( IQR one to five ) and four ( two to five ) , respectively ( p=0.001 ) . One adverse reaction ( an exacerbation of pain after the initial assessment ) was recorded . INTERPRETATION Brief pain management techniques delivered by appropriately trained clinicians offer an alternative to physiotherapy incorporating manual therapy and could provide a more efficient first-line approach for management of non-specific subacute low back pain in primary care Objective : Recent recommendations suggest that reassuring patients with an acute bout of low back pain and encouraging a return to normal activities may be helpful in preventing the development of chronic disability . There is also a question as to whether psychologic or physical therapy interventions actually add anything to such reassurance and advice in terms of preventing chronicity . This study aim ed to ascertain the preventive effects on future sick leave and health-care utilization of adding on a cognitive-behavioral group intervention or a cognitive-behavioral group intervention and preventive physical therapy ( focused on activity and exercise ) relative to a minimal treatment group ( examination , reassurance , and activity advice ) . Subjects : A total of 185 patients seeking care for nonspecific back or neck pain who were employed and at risk for developing long-term disability volunteered to participate in the study . Of these 185 , 158 ( 85 % ) completed the pre- and 1-year follow-up assessment s. Results : Significant differences were observed on the key outcome variables of future health-care utilization and work absenteeism . For health-care utilization , the cognitive-behavioral intervention group and preventive physical therapy group had significantly fewer healthcare visits than did the Minimal Treatment Group . For work absenteeism , the cognitive-behavioral intervention group and cognitive-behavioral intervention and preventive physical therapy group had fewer days during the 12-month follow-up than did the Minimal Treatment Group . The risk for developing long-term sick disability leave was more than five-fold higher in the Minimal Group as compared with the other 2 groups . However , there was no difference between the cognitive-behavioral intervention group and cognitive-behavioral intervention and preventive physical therapy group on sick leave . Conclusion : Taken as a whole , this study shows that adding cognitive-behavioral intervention and cognitive-behavioral intervention and preventive physical therapy can enhance the prevention of long-term disability . There was no substantial difference in the results between the cognitive-behavioral intervention group and cognitive-behavioral intervention and preventive physical therapy group Study design . Population -based r and omized controlled trial . Objective . To assess the effectiveness of workplace intervention and grade d activity , separately and combined , for multidisciplinary rehabilitation of low back pain ( LBP ) . Summary of Background Data . Effective components for multidisciplinary rehabilitation of LBP are not yet established . Methods . Participants sick-listed 2 to 6 weeks due to nonspecific LBP were r and omized to workplace intervention ( n = 96 ) or usual care ( n = 100 ) . Workplace intervention consisted of workplace assessment , work modifications , and case management involving all stakeholders . Participants still sick-listed at 8 weeks were r and omized for grade d activity ( n = 55 ) or usual care ( n = 57 ) . Grade d activity comprised biweekly 1-hour exercise sessions based on operant-conditioning principles . Outcomes were lasting return to work , pain intensity and functional status , assessed at baseline , and at 12 , 26 , and 52 weeks after the start of sick leave . Results . Time until return to work for workers with workplace intervention was 77 versus 104 days ( median ) for workers without this intervention ( P = 0.02 ) . Workplace intervention was effective on return to work ( hazard ratio = 1.7 ; 95 % CI , 1.2–2.3 ; P = 0.002 ) . Grade d activity had a negative effect on return to work ( hazard ratio = 0.4 ; 95 % CI , 0.3–0.6 ; P < 0.001 ) and functional status . Combined intervention had no effect . Conclusion . Workplace intervention is advised for multidisciplinary rehabilitation of subacute LBP . Grade d activity or combined intervention is not advised In this multicentre intervention study , we compared an integrated group treatment program which combines psychological and education methods into a more active training approach , with the traditional individual approach of physiotherapy and physical procedures for sub-chronic and chronic low back pain . Our 411 patients had a 4-week inpatient treatment : 243 patients in an experimental program and 168 in a traditional program . Outcomes of 283 patients were assessed 3 months and 1 year after entry . The dropout rate was 31.1 % . Both conditions demonstrated favourable initial effects on functional and psychological parameters , but the integrated approach showed better long-term results for work rehabilitation than the traditional approach . The most successful patients ( n = 58 ) were younger and had a higher educational level in comparison to the unsuccessful subgroup ( n = 71 ) . The main conclusion is that an integrated approach promoting self control and behaviour change through educational measures achieves better long-term results than the traditional individual physiotherapy approach OBJECTIVE To identify subgroups of workers absent from work due to low back pain who are more or less likely to return to work earlier as a result of a grade d activity intervention , and to investigate whether this intervention is effective in reducing pain-related fears and if so , whether these reductions in pain-related fears mediate return to work . METHODS A subgroup analysis was conducted on data from a previous r and omized controlled trial of 134 Dutch airline workers , which found that a behaviorally-oriented grade d activity intervention was more effective than usual care in stimulating return to work . The subgroup analyses added interaction terms to a Cox regression model that described the relationship between treatment allocation and return to work over 12 months of followup . Furthermore , we studied the effects of grade d activity on pain-related fears and added variables indicating a reduction in pain-related fears to the model in order to investigate their influence on return to work . RESULTS Statistically significant interactions were found for disability , fear-avoidance beliefs about physical activity , and fear-avoidance beliefs about work . No indication was found that the reduction in pain-related fears in the grade d activity group mediated more favorable return-to-work results in this group . CONCLUSION Workers who perceive their disability to be moderate and workers with moderate scores for fear-avoidance beliefs return to work more rapidly as a result of the grade d activity intervention than workers with higher scores . The return to work of workers receiving the grade d activity intervention is possibly independent from the reductions in pain-related fears caused by this intervention Study Design . A r and omized clinical trial with 4-week and 6-month follow-up periods . Objective . To compare the effect of a fear-avoidance – based physical therapy intervention with st and ard care physical therapy for patients with acute low back pain . Summary of Background Data . The disability reduction strategy of secondary prevention involves providing specific treatment for patients that are likely to have chronic disability from low back pain . Previous studies have indicated that elevated fear-avoidance beliefs are a precursor to chronic disability from low back pain . However , the effectiveness of physical therapy intervention based on a fear-avoidance model is unknown . Methods . Sixty-six consecutive patients referred to physical therapy with low back pain of less than 8 weeks ’ duration were r and omly assigned to receive fear-avoidance – based physical therapy ( n = 34 ) or st and ard care physical therapy ( n = 32 ) . The intervention period lasted 4 weeks for this study . Disability , pain intensity , and fear-avoidance beliefs measures were recorded before and after treatment . A 6-month follow-up of the same measures was obtained by mail . Results . An intention-to-treat principle ( last value forward ) was used for data analyses that tested the primary and secondary hypotheses . The prediction of disability at 4 weeks and 6 months after treatment was significantly improved by considering the interaction between the type of treatment and the initial level of fear-avoidance beliefs . Both groups had significant within group improvements for disability and pain intensity . The fear-avoidance treatment group had a significant improvement in fear-avoidance beliefs , and fear-avoidance beliefs about physical activity were significantly lower than the st and ard care group at 4 weeks and 6 months after treatment . Conclusion . Patients with elevated fear-avoidance beliefs appeared to have less disability from fear-avoidance – based physical therapy when compared to those receiving st and ard care physical therapy . Patients with lower fear-avoidance beliefs appeared to have more disability from fear-avoidance – based physical therapy , when compared to those receiving st and ard care physical therapy . In addition , physical therapy supplemented with fear-avoidance – based principles contributed to a positive shift in fear-avoidance beliefs |
907 | 32,221,188 | The quality of therapeutic alliance correlates with clinical symptoms , insight , social and family support , the therapist 's qualities , the availability of shared therapeutic decision making , and the types of hospitalization .
Although current evidence needs to be completed with further studies , it is already clear that group and family psychoeducation , cognitive remediation , community-based psychiatric services , and shared therapeutic decision making are essential approaches in the management of patients with psychosis | Abstract Therapeutic alliance determines medical treatment adherence , the success of psychotherapy , and the effectiveness of care .
This systematic review aims at better underst and ing its determinants . | This column presents preliminary findings of an intervention to support shared decision making in psychopharmacology consultation . The waiting area in an urban psychiatric medication clinic was transformed into a peer-run Decision Support Center featuring a user-friendly , Internet-based software program with which clients could create a one-page computer-generated report for use in the medication consultation . The Decision Support Center was used 662 times by 189 unique users from a young-adult and general adult case management team from October 2006 to September 2007 . All clients had severe mental disorders . Only ten clients refused to use the intervention at some point during the pilot study . Focus groups with medical staff ( N=4 ) , clients ( N=16 ) , case managers ( N=14 ) , and peer-specialist staff ( N=3 ) reported that the intervention helped to create efficiencies in the consultation and empower clients to become more involved in treatment-related decision making . A r and omized controlled trial is currently in process We investigated associations between adult attachment , symptoms and interpersonal functioning , including therapeutic relationships in 96 patients with psychosis . Using a prospect i ve design , we also assessed changes in attachment in both psychiatrically unstable and stable groups . We measured attachment using the Psychosis Attachment Measure ( PAM ) and interpersonal problems and therapeutic relationships were assessed from both psychiatric staff and patient perspectives . Avoidant attachment was associated with positive symptoms , negative symptoms and paranoia . Attachment ratings were relatively stable over time , although changes in attachment anxiety were positively correlated with changes in symptoms . Predicted associations between high levels of attachment anxiety and avoidance and interpersonal problems were supported , and attachment avoidance was associated with difficulties in therapeutic relationships . Findings suggest that adult attachment style is a meaningful individual difference variable in people with psychosis and may be an important predictor of symptoms , interpersonal problems and difficulties in therapeutic relationships over and above severity of illness BACKGROUND A better therapeutic relationship predicts better outcomes . However , there is no trial-based evidence on how to improve therapeutic relationships in psychosis . AIMS To test the effectiveness of communication training for psychiatrists on improving shared underst and ing and the therapeutic relationship ( trial registration : IS RCT N94846422 ) . METHOD In a cluster r and omised controlled trial in the UK , 21 psychiatrists were r and omised . Ninety-seven ( 51 % of those approached ) out- patients with schizophrenia/schizoaffective disorder were recruited , and 64 ( 66 % of the sample recruited at baseline ) were followed up after 5 months . The intervention group received four group and one individualised session . The primary outcome , rated blind , was psychiatrist effort in establishing shared underst and ing ( self-repair ) . Secondary outcome was the therapeutic relationship . RESULTS Psychiatrists receiving the intervention used 44 % more self-repair than the control group ( adjusted difference in means 6.4 , 95 % CI 1.46 - 11.33 , P<0.011 , a large effect ) adjusting for baseline self-repair . Psychiatrists rated the therapeutic relationship more positively ( adjusted difference in means 0.20 , 95 % CI 0.03 - 0.37 , P = 0.022 , a medium effect ) , as did patients ( adjusted difference in means 0.21 , 95 % CI 0.01 - 0.41 , P = 0.043 , a medium effect ) . CONCLUSIONS Shared underst and ing can be successfully targeted in training and improves relationships in treating psychosis Background The quality of the therapeutic alliance ( TA ) has been invoked to explain the equal effectiveness of different psychotherapies , but prior research is correlational , and does not address the possibility that individuals who form good alliances may have good outcomes without therapy . Method We evaluated the causal effect of TA using instrumental variable ( structural equation ) modelling on data from a three-arm , r and omized controlled trial of 308 people in an acute first or second episode of a non-affective psychosis . The trial compared cognitive behavioural therapy ( CBT ) over 6 weeks plus routine care ( RC ) v. supportive counselling ( SC ) plus RC v. RC alone . We examined the effect of TA , as measured by the client-rated CALPAS , on the primary trial 18-month outcome of symptom severity ( PANSS ) , which was assessed blind to treatment allocation . Results Both adjunctive CBT and SC improved 18-month outcomes , compared to RC . We showed that , for both psychological treatments , improving TA improves symptomatic outcome . With a good TA , attending more sessions causes a significantly better outcome on PANSS total score [ effect size −2.91 , 95 % confidence interval ( CI ) −0.90 to −4.91 ] . With a poor TA , attending more sessions is detrimental ( effect size + 7.74 , 95 % CI + 1.03 to + 14.45 ) . Conclusions This is the first ever demonstration that TA has a causal effect on symptomatic outcome of a psychological treatment , and that poor TA is actively detrimental . These effects may extend to other therapeutic modalities and disorders Background Long acting injections ( LAI ) have been associated with perceptions of coercion in cross sectional studies but there have been no longitudinal studies of the effects on clinical relationships with newer depot medications . Method R and omized controlled trial with ( 50 ) participants with a diagnosis of schizophrenia r and omized to risperidone LAI or oral atypical antipsychotic medication . The main outcome was the Working Alliance Inventory ( WAI ) with background variables ( symptoms , side effect , social functioning , quality of life ) measured before r and omization and at two years . Results At follow-up ( 14 risperidone LAI and 16 oral medication ) analyses including predictors of missing data and baseline score showed a trend for those on risperidone LAI to reduce WAI score and those on oral medication showing no change . Sensitivity analyses showed ( i ) a significant detrimental effect of LAI on WAI and ( ii ) the pattern of results was not affected by change in symptoms over the study . Conclusion This is the first study to show that the prescription of depot atypical depot medication is associated with detrimental effects on clinical relationships after 2 years of continual treatment BACKGROUND The CRIMSON ( CRisis plan IMpact : Subjective and Objective coercion and eNgagement ) study is an individual level , r and omised controlled trial that compared the effectiveness of Joint Crisis Plans ( JCPs ) with treatment as usual for people with severe mental illness . The JCP is a negotiated statement by a patient of treatment preferences for any future psychiatric emergency , when he or she might be unable to express clear views . We assessed whether the additional use of JCPs improved patient outcomes compared with treatment as usual . METHODS Patients were eligible if they had at least one psychiatric admission in the previous 2 years and were on the Enhanced Care Programme Approach register . The study was done with 64 generic and specialist community mental health teams in four English mental health care provider organisations ( trusts ) . Hypotheses tested were that , compared with the control group , the intervention group would experience : fewer compulsory admissions ( primary outcome ) ; fewer psychiatric admissions ; shorter psychiatric stays ; lower perceived coercion ; improved therapeutic relationships ; and improved engagement . We stratified participants by centre . The research team but not participants nor clinical staff were masked to allocation . This study is registered with Clinical Trials.gov , number IS RCT N11501328 . FINDINGS 569 participants were r and omly assigned ( 285 to the intervention group and 284 to the control group ) . No significant treatment effect was seen for the primary outcome ( 56 [ 20 % ] sectioned in the control group and 49 [ 18 % ] in the JCP group ; odds ratio 0·90 [ 95 % CI 0·58 - 1·39 , p=0·63 ] ) or any secondary outcomes , with the exception of an improved secondary outcome of therapeutic relationships ( 17·3 [ 7·6 ] vs 16·0 [ 7·1 ] ; adjusted difference -1·28 [ 95 % CI -2·56 to -0·01 , p=0·049 ] ) . Qualitative data supported this finding . INTERPRETATION Our findings are inconsistent with two earlier JCP studies , and show that the JCP is not significantly more effective than treatment as usual . There is evidence to suggest the JCPs were not fully implemented in all study sites , and were combined with routine clinical review meetings which did not actively incorporate patients ' preferences . The study therefore raises important questions about implementing new interventions in routine clinical practice . FUNDING Medical Research Council UK and the National Institute for Health Research Psychoeducation improves adherence and motivates patients to accept a maintenance therapy as recommended by the guidelines . This would mean a daily consumption of at least 300 chlorpromazine ( CPZ ) units in the long run and should lead to an increase of the antipsychotic dosage in comparison to patients with treatment as usual ( TAU ) . This raises 2 important questions : whether more side effects are provoked and do the patients have a corresponding benefit with a better outcome . A total of 41 patients with a diagnosis of schizophrenic or schizoaffective disorder were r and omized at study entry , either to bifocal psychoeducation ( 21 ) , or to st and ard treatment ( 20 ) . They were compared concerning compliance , type of medication , dosage ( CPZ equivalents ) , motor side effects and number of days in hospital . The average daily antipsychotic medication 2 and 7 years after index discharge was 365 and 354 CPZ-units respectively in the intervention group ( IG ) , but 247 and 279 , respectively in the control group ( CG ) . The extent of motor side effects was slightly smaller in the IG , but they showed a small and statistically not significant increase in the rate of tardive dyskinesia ( TD ) after 7 years . At the 7-year follow-up the patients in the IG had spent 74.7 days in hospital compared to 243.4 days for the patients in the CG ( P < .05 ) . The course of illness was significantly better in the IG without increasing motor side-effects . Therefore , psychoeducation should be integrated more systematic ally into the routine treatment . These data are part of a previous study , published 2007 , with a sample size of 48 patients . Seven patients -3 of the IG and 4 of the CG-could not be included , because they were not able to complete the very complex " Computer-based kinematic analysis of motor performance . " In this article all conclusions are referred to the new sample size , therefore some results are slightly different in comparison to the previous data The importance of therapeutic alliance in predicting treatment outcomes is well established , but less is known about client characteristics that predict alliance . Clients with co-occurring psychosis and substance misuse ( n = 116 ) who received integrated motivational interviewing and cognitive behavior therapy in the context of a large r and omized controlled trial completed the Working Alliance Inventory . Their trial therapists also completed Working Alliance Inventories . Rating perspectives were compared , and in a cross-sectional study , client predictors of therapeutic alliance were examined . As hypothesized , clients ' negative attitudes to treatment , including lack of insight , were predictive of poorer alliance . Therapist-rated alliance was also predicted by the client 's attitude to medication , self-reported depression , and living situation . Symptom severity and substance use measures were unrelated to alliance . Consistent with previous studies , rating perspectives differed , with clients rating alliance more positive than therapists This study examined the relationship of the therapeutic alliance to the treatment course and outcome of 143 patients with nonchronic schizophrenia . Results showed that patients who formed good alliances with their therapists within the first 6 months of treatment were significantly more likely to remain in psychotherapy , comply with their prescribed medication regimens , and achieve better outcomes after 2 years , with less medication , than patients who did not . These results underscored the prognostic value of assessing the alliance and the need to identify factors that contribute to its development and maintenance with schizophrenic patients OBJECTIVES Outpatient and inpatient mental health service outcomes for out patients with schizophrenia or schizoaffective disorder who received psychoeducational multiple-family group treatment were compared with outcomes for similar patients who received st and ard care . METHODS A total of 106 out patients with schizophrenia or schizoaffective disorder who were receiving services from a large community mental health center were r and omly assigned to receive st and ard care or st and ard care plus multiple-family group treatment . The two-year multiple-family intervention consisted of weekly group sessions design ed to educate patients and their family members about the biological basis of mental illness and treatment , to improve illness management and coping skills , and to provide social support . The group sessions were conducted by two clinicians using a st and ardized protocol . Each multiple-family group included five to eight families and consumers . Service records for the year before and after r and om assignment to the study groups were examined in an intent-to-treat analysis . RESULTS During the year after r and om assignment to study groups , multiple-family group treatment was associated with a lower rate of psychiatric hospitalization than st and ard care . It was only marginally associated with lower use of crisis services , and it was not associated with the amount of outpatient service time . CONCLUSIONS The findings suggest that implementation of multiple-family group treatment in a capitated community mental health setting improves hospitalization outcomes without increasing the overall volume of outpatient mental health services |
908 | 15,495,083 | REVIEW ERS ' CONCLUSIONS Telephone consultation appears to reduce the number of surgery contacts and out-of-hours visits by general practitioners . | BACKGROUND Telephone consultation is the process where calls are received , assessed and managed by giving advice or by referral to a more appropriate service .
In recent years there has been a growth in telephone consultation developed , in part , as a response to increased dem and for General Practitioner ( GP ) and Accident and Emergency ( A&E ) department care .
OBJECTIVES To assess the effects of telephone consultation on safety , service usage and patient satisfaction and to compare telephone consultation by different health care professionals . | We recently published the results of a r and omised controlled trial of a nurse telephone consultation service in primary care out of hours.1 The new service , operating at evenings and weekends , significantly reduced general practitioners ’ workload and was at least as safe as the existing out of hours service . Contacts diminish sharply after about 10 pm,2 and , anecdotally , a higher proportion of night calls necessitate consultation with a general practitioner . We report here a parallel trial aim ed at establishing whether nurse telephone consultation was equally effective in managing workload at night Objective : To investigate the potential impact for ambulance services of telephone assessment and triage for callers who present with non-serious problems ( Category C calls ) as classified by ambulance service call takers . Design : Pragmatic controlled trial . Calls identified using priority dispatch protocol s as non-serious were allocated to intervention and control groups according to time of call . Ambulance dispatch occurred according to existing procedures . During intervention sessions , nurses or paramedics within the control room used a computerised decision support system to provide telephone assessment , triage and , if appropriate , offer advice to permit estimation of the potential impact on ambulance dispatch . Setting : Ambulance services in London and the West Midl and s. Subjects : Patients for whom emergency calls were made to the ambulance services between April 1998 and May 1999 during four hour sessions sample d across all days of the week between 0700 and 2300 . Main outcome measures : Triage decision , ambulance cancellation , attendance at an emergency department . Results : In total , there were 635 intervention calls and 611 controls . Of those in the intervention group , 330 ( 52.0 % ) were triaged as not requiring an emergency ambulance , and 119 ( 36.6 % ) of these did not attend an emergency department . This compares with 55 ( 18.1 % ) of those triaged by a nurse or paramedic as requiring an ambulance ( odds ratio 2.62 ; 95 % CI 1.78 to 3.85 ) . Patients triaged as not requiring an emergency ambulance were less likely to be admitted to an inpatient bed ( odds ratio 0.55 ; 95 % CI 0.33 to 0.93 ) , but even so 30 ( 9.2 % ) were admitted . Nurses were more likely than paramedics to triage calls into the groups classified as not requiring an ambulance . After controlling for age , case mix , time of day , day of week , season , and ambulance service , the results of a logistic regression analysis revealed that this difference was significant with an odds ratio for nurses : paramedics of 1.28 ( 95 % CI 1.12 to 1.47 ) . Conclusions : The findings indicate that telephone assessment of Category C calls identifies patients who are less likely to require emergency department care and that this could have a significant impact on emergency ambulance dispatch rates . Nurses were more likely than paramedics to assess calls as requiring an alternative response to emergency ambulance despatch , but the extent to which this relates to aspects of training and professional perspective is unclear . However , consideration should be given to the acceptability , reliability , and cost consequences of this intervention before it can be recommended for full evaluation BACKGROUND Telephone working is an increasingly important way of managing general practice workload , particularly out of hours . The role of telephone triage , however , in managing acute consultations during the day has not been adequately research ed . AIM To determine the impact of telephone triage , conducted by a practice nurse , on the management of same day consultations in a general practice . METHOD A general practice of 11,300 patients in South Tyneside collected prospect i ve telephone and surgery consultation data over three months . Patient satisfaction , for those who had received only telephone advice , was measured using a postal question naire . Four outcomes were measured : changes in doctor and nurse workload ; repeat consultations with the same problem ; prescriptions issued ; and patient satisfaction with the service . RESULTS In three months , 1263 consultations were recorded . Doctor workload fell by 54 % , from 1522 to 664 consultations , compared with the previous three months . A total of 325 ( 26 % ) telephone requests to see the doctor were managed by the nurse on the telephone without them visiting the surgery . Also , 273 ( 21 % ) patients saw the nurse in the surgery , 565 ( 45 % ) saw the doctor in the surgery , and 99 ( 8 % ) saw the doctor and the nurse in the surgery . The response rate to the postal question naire was 192/271 ( 71 % ) ; 154 ( 88 % ) were satisfied with nurse telephone advice . CONCLUSIONS Telephone triage , by a practice nurse , of patients who wish to see the doctor on the same day , reduced doctor workload . This was a service that patients liked Abstract Objective : To undertake an economic evaluation of nurse telephone consultation using decision support software in comparison with usual general practice care provided by a general practice cooperative . Design : Cost analysis from an NHS perspective using stochastic data from a r and omised controlled trial . Setting : General practice cooperative with 55 general practitioners serving 97 000 registered patients in Wiltshire , Engl and . Subjects : All patients contacting the service , or about whom the service was contacted during the trial year ( January 1997 to January 1998 ) . Main outcome measures : Costs and savings to the NHS during the trial year . Results : The cost of providing nurse telephone consultation was £ 81 237 per annum . This , however , determined a £ 94 422 reduction of other costs for the NHS arising from reduced emergency admissions to hospital . Using point estimates for savings , the cost analysis , combined with the analysis of outcomes , showed a dominance situation for the intervention over general practice cooperative care alone . If a larger improvement in outcomes is assumed ( upper 95 % confidence limit ) NHS savings increase to £ 123 824 per annum . Savings of only £ 3728 would , however , arise in a scenario where lower 95 % confidence limits for outcome differences were observed . To break even , the intervention would have needed to save 138 emergency hospital admissions per year , around 90 % of the effect achieved in the trial . Additional savings of £ 16 928 for general practice arose from reduced travel to visit patients at home and fewer surgery appointments within three days of a call . Conclusions : Nurse telephone consultation in out of hours primary care may reduce NHS costs in the long term by reducing dem and for emergency admission to hospital . General practitioners currently bear most of the cost of nurse telephone consultation and benefit least from the savings associated with it . This indicates that the service produces benefits in terms of service quality , which are beyond the reach of this cost analysis BACKGROUND General practitioners ( GPs ) in the United Kingdom have recently begun to adopt the use of telephone consultation during daytime surgery as a means of managing dem and , particularly requests for same-day appointments . However , it is not known whether the strategy actually reduces GP workload . AIM To investigate how the use of telephone consultations impacts on the management of requests for same-day appointments , on re source use , indicators of clinical care , and patient perceptions of consultations . DESIGN OF STUDY R and omised controlled trial . SETTING All patients ( n = 388 ) seeking same-day appointments in each surgery in two urban practice s ( total population = 10,420 ) over a four-week period . METHOD The primary outcome measure was use of doctor time for the index telephone or face-to-face consultation . Secondary outcomes were subsequent use of investigations and of services in the two-week period following consultation , frequency of blood pressure measurement and antibiotic prescriptions , and number of problems considered at consultation . Patient perceptions were measured by the Patient Enablement Instrument ( PEI ) and reported willingness to use telephone consultations in the future . RESULTS Telephone consultations took less time ( 8.2 minutes versus 6.7 minutes ; diff = 1.5 , 95 % confidence interval [ CI ] = 0.6 to 2.4 , P = 0.002 ) . Patients consulting by telephone reconsulted the GP more frequently in the two weeks that followed ( 0.6 consultations versus 0.4 consultations ; diff = 0.2 , 95 % CI = 0.0 to 0.3 , P = 0.01 ) . Blood pressure was measured more often in the group of patients managed face-to-face ( 25/188 [ 13.3 % ] versus 12/181 [ 6.6 % ] ; diff = 6.7 % , 95 % CI = 0.6 % to 12.7 % ) . There was no significant difference in patient perceptions or other secondary outcomes . CONCLUSION Use of telephone consultations for same-day appointments was associated with time saving , and did not result in lower PEI scores . Possibly , however , this short-term saving was offset by higher re-consultation and less use of opportunistic health promotion BACKGROUND Advice nurse call centers are used to ensure access to medical advice , thereby potentially reducing the costs of health services . OBJECTIVE To determine if medical advice from advice nurses and on-call physicians delays significant medical treatment in a general pediatrics population . DESIGN R and omized controlled trial . SETTING A university general pediatrics faculty practice . PARTICIPANTS Parents or guardians calling for after-hours advice regarding their children . Intervention After-hours medical advice calls were r and omized at the time of the call to an advice nurse or an on-call pediatrician . MAIN OUTCOME MEASURES The proportion of callers who sought medical care not advised by the advice nurse or on-call pediatrician and the proportion who received unadvised significant care . RESULTS There were 1182 advice calls : 566 in the pediatrician group and 616 in the advice nurse group . There were no significant differences in the types of telephone triage advice in the physician and advice nurse groups . There was no significant difference in the proportion of callers who sought unadvised care ( 108 [ 19.9 % ] in the physician group vs 110 [ 19.0 % ] in the advice nurse group ) or in the proportion of callers who received unadvised significant care ( 23 [ 4.2 % ] in the physician group vs 25 [ 4.3 % ] in the advice nurse group ) . CONCLUSIONS The proportions of callers who sought unadvised medical care and who received unadvised significant care were not significantly different in the advice nurse and pediatrician groups . This suggests that advice nurses do not delay significant medical treatment when compared with pediatricians Objective . Telephone triage programs are becoming very common at children 's hospitals across the nation . One of the proposed benefits of these programs is the more efficient use of health care re sources by triaging patients to the appropriate level of health care . The purpose of this study is to examine the appropriateness of referrals to a pediatric emergency department ( ED ) by the Pediatric Health Information Line ( PHIL ) , a hospital-based telephone triage program , versus all other sources of referrals . Methods . A blinded Delphi rating system was used to review the physician 's sheets of 133 consecutive ED referrals by PHIL for medical appropriateness . A total of 260 r and omly selected control patients seen in the ED during the same period were similarly review ed . If 2 of 3 pediatric emergency medicine physicians agreed that an ED visit was appropriate , then it was considered appropriate . A comparison of the 2 groups ' ED appropriateness was made using a contingency table χ2 test . An odds ratio with confidence limits was also calculated . Demographic data were collected for both groups including age , race , gender , and insurance status . Results . The PHIL group had an appropriateness rate of 80.2 % , compared with 60.5 % for the control group ( χ2 = 14.6369 ; odds ratio = 2.65 ; 95 % confidence interval [ 1.5759,4.5008 ] ) . Conclusions . This demonstrated that for the period studied , PHIL referrals to the ED had a 33 % higher rate of appropriateness than controls . This evidence supports telephone triage as an efficient gatekeeper for health care re sources Abstract Objective : To compare the outcome of out of hours care given by general practitioners from patients ' own practice s and by commercial deputising services . Design : R and omised controlled trial . Setting : Four urban areas in Manchester , Salford , Stockport , and Leicester . Subjects : 2152 patients who requested out of hours care , and 49 practice doctors and 183 deputising doctors ( 61 % local principals in general practice ) who responded to the requests . Main outcome measures : Health status outcome , patient satisfaction , and subsequent health service use . Results : Patients seen by deputising doctors were less satisfied with the care they received . The mean overall satisfaction score for practice doctors was 70.7 ( 95 % confidence interval 68.1 to 73.2 ) and for deputising doctors 61.8 ( 59.9 to 63.7 ) . The greatest difference in satisfaction was with the delay in visiting . There were no differences in the change in health or overall health status measured 24 to 120 hours after the out of hours call or subsequent use of the health service in the two groups . Conclusions : Patients are more satisfied with the out of hours care provided by practice doctors than that provided by deputising doctors . Organisation of doctors into large groups may produce lower levels of patient satisfaction , especially when associated with increased delays in the time taken to visit . There seem to be no appreciable differences in health outcome between the two types of service . Key messages Between 24 and 120 hours after a request for out of hours care patients cared for by deputising services and practice doctors show no difference in health status There is no difference in health service use between the two groups in the two weeks after a request for out of hours care Patients are more satisfied with out of hours care provided by their own practice doctors Though patients are more satisfied with out of hours care provided by practice doctors , their health outcomes are no better than when care is provided by a deputising The authors examined the effect of after-hours telephone access to physicians and physician access to computerized medical records on hospitalizations and emergency room ( ER ) visits in an inner-city , adult , general medicine clinic . Patients were r and omly assigned to a control ( C ) and two study groups ( S1 and S2 ) . Patients in study groups S1 and S2 had after-hours telephone access to physicians . Computerized medical records were accessible to physicians only for callers in study group S2 . During the initial 18 months of study , only 7.6 % of eligible patients called the after-hours service , a rate of 6 calls/1,000 patients / month ( 200 calls/1,849 patients /18 months ) . Repeated promotion of the service was subsequently undertaken , and 19.4 % of the patients used the service during the final 12 months of study , a rate of 24.1 calls/1,000 patients /month ( 467 calls/1,616 patients /12 months ) . There were no significant differences in hospitalizations or ER visits among the control and two study groups OBJECTIVE To compare caller satisfaction with after-hours medical advice provided by a for-profit nurse advice service with advice provided by on-call pediatricians . METHODS The study setting was the general pediatrics faculty practice of an urban university medical center . Participants were parents or guardians of a population of approximately 6000 children calling for after-hours medical advice over a 10-month period from January 18 to November 20 , 2000 . After-hours medical advice calls were r and omized to either a nurse advice service or the on-call pediatrician . Caller satisfaction and subsequent health care utilization were measured by a telephone survey of callers and review of all health care visits within 3 days of the initial telephone advice call . RESULTS Five hundred sixty-six ( 48 % ) callers were enrolled in the on-call pediatrician group , and 616 ( 52 % ) were enrolled in the advice nurse group . Caller satisfaction was rated as very good or excellent significantly more often for the on-call pediatrician than for the nurse advice service as follows : telephone call overall ( 68.5 % vs 55.0 % ; 95 % confidence interval [ CI ] of difference : 8.0%-19.0 % ) , thoroughness and competence of the person they spoke with ( 74.0 % vs 59.1 % ; 95 % CI of difference : 9.6%-20.2 % ) , courtesy and friendliness of the person they spoke with ( 77.4 % vs 73.9 % ; 95 % CI of difference : -1.4%-8.4 % ) , length of time spent waiting ( 70.8 % vs 60.1 % ; 95 % CI of difference : 5.4%-16.2 % ) , time spent talking with the on-call pediatrician or advice nurse ( 68.2 % vs 52.4 % ; 95 % CI of difference : 10.2%-21.3 % ) , and the medical advice given ( 68.6 % vs 53.9 % ; 95 % CI of difference : 9.2%-20.1 % ) . Compliance with the advice given was significantly higher for office care in the on-call pediatrician group ( 51.5 % vs 29.6 % ; 95 % CI of difference : 8.9%-34.2 % ) . Repeat calls for advice were significantly more frequent for the nurse advice service , both within 4 hours ( 13.0 % vs 4.8 % ; 95 % CI of difference : 5.0%-11.4 % ) , and within 72 hours ( 23.4 % vs 13.3 % ; 95 % CI of difference : 5.8%-14.5 % ) . CONCLUSION Callers were less satisfied with medical advice provided by a nurse advice service compared with the traditional on-call pediatrician . The lower satisfaction was associated with somewhat poorer compliance with recommended triage dispositions and more frequent repeat calls for medical advice Abstract Objective To assess the relative effects on consultation workload and costs of off-site triage by NHS Direct for patients requesting same day appointments compared with usual on-site nurse telephone triage in general practice . Design Cluster r and omised controlled trial . Setting Three primary care sites in York , Engl and . Participants 4703 patients : 2452 with practice based triage , 2251 with NHS Direct triage . All consecutive patients making requests for same day appointments during study weeks were eligible for the trial . Main outcome measures Type of consultation after request for same day appointment ( telephone , appointment , or visit ) ; time taken for consultation ; service use during the month after same day contact ; costs of same day , follow up , and emergency care . Results Patients in the NHS Direct group were less likely to have their call resolved by a nurse and were more likely to have an appointment with a general practitioner . Mean total time per patient in the NHS Direct group was 7.62 minutes longer than in the practice based group . Costs were greater in the NHS Direct group—£2.88 ( £ 0.88 to £ 4.87 ) per patient triaged — as a result of the difference between the groups in proportions of patients at each final point contact after triage . Conclusions External management of requests for same day appointments by nurse telephone triage through NHS Direct is possible but comes at a higher cost than practice nurse delivered triage in primary care . If NHS Direct could achieve the same proportions of consultation types as practice based triage , costs would be comparable A r and omized clinical trial of pediatric protocol s administered by health assistants demonstrated an alternate method of h and ling telephone complaints in a large emergency room . The new system advised a higher medical examination rate than the current system in the emergency room probably bacause the current system has deficits with respect to collecting necessary information and making explicit decisions . This higher rate of recommended visits demonstrated in the emergency room was not confirmed in the two pediatric primary -care setting s in which the protocol system was also tested . In addition to this use , the telephone protocol s may also be useful in training medical and nursing students , in h and ling telephone complaints similar to a poison control center , in triaging problems in a rural or emergency medical service , and in providing a record of the telephone call BACKGROUND After-hours telephone calls are a stressful and frustrating aspect of pediatric practice . At the request of private practice pediatricians in Denver , a metropolitan area-wide system was created to manage after-hours pediatric telephone calls and after-hours patient care . This system , the After-Hours Program ( AHP ) , uses specially trained pediatric nurses with st and ardized protocol s to provide after-hours telephone triage and advice for the patients of 92 Denver pediatricians , representing 56 practice s. OBJECTIVES This report describes the AHP , presents data from 4 years ' experience with the program , and describes results of our evaluation of the following aspects of the program : subscribing physician satisfaction , parent satisfaction , the accuracy and appropriateness of telephone triage , and program costs . METHODS After-Hours Program records ( including quality assurance data ) for all 4 years of operation were retrospectively review ed , tabulated , and analyzed . The results of two subscribing physician surveys and one parent caller satisfaction survey are presented . A retrospective review of after-hours patient care encounter forms assessed the necessity for after-hours visits triaged by the AHP . An analysis of the total cost of this program to 10 r and omly selected subscribing physicians was conducted using current AHP data and a survey of the 10 physicians . RESULTS In 4 years , 107,938 calls have been successfully managed without an adverse clinical outcome . Minor errors in using protocol s occurred in one call out of 1450 after-hours calls . After-hours phoen calls necessitated an after-hours patient visit 20 % of the time and generated one after-hours hospital admission out of every 88 calls . Just over half of the patients were managed with home care advice only , and 28 % were given home care advice after-hours and seen the next day in the primary physician 's office . Of all patients directed by the telephone triage nurses to be seen after hours , 78 % were determined to have a condition necessitating after-hours care . Data are presented regarding call volumes by time of day , day of week , patient age , and patient 's initial complaint . The 6 most common complaints accounted for more than one half of the calls , and 38 complaints accounted for more than 95 % of all after-hours calls . Utilization by subscribing physicians is described . Satisfaction among subscribing pediatricians was 100 % , and among parents was 96 % to 99 % on a variety of issues . The total cost to participating Denver pediatricians ( which includes revenues " given up " as a result of not seeing patients after hours ) ranged from 1 % to 12 % of their annual net income , depending on a variety of factors . CONCLUSIONS Large-scale after-hours telephone coverage systems can be effective and well-received by patients , parents , and primary physicians . Data presented in this report can assist in planning the training of personnel who provide after-hours telephone advice and triage . Controversies associated with this type of program are discussed . Suggestions are made regarding the direction of future programs and research Use of the Emergency Department ( ED ) for nonurgent conditions results in increased cost and discontinuous health care . This prospect i ve study evaluated a program ( KenPAC ) that required 24-hour access to a primary care physician ( PCP ) with ED gatekeeping responsibility . Following established criteria , medical records were review ed for appropriateness of ED use by an urban indigent pediatric population . Emergency Department visits declined ( 10 % to 7.6 % ( P=0.00005 ) and inappropriate visits dropped ( 41 % to 8 % ) ( P<0.00001 ) before KenPAC and after KenPAC , respectively . Parental experience , as judged by age and number of children , played a significant role in ED use . The institution of gatekeeping activity contributed to the reduced overall and inappropriate use of the ED The purpose of this research was to determine whether a specialized telephone service could cut down on unscheduled visits to ambulatory care and improve satisfaction with care . Patients who were to receive care ( N=561 ) were assigned r and omly to a specialized telephone service or a control group . They were measured with regard to satisfaction with care before being assigned and 6 months later . The number of scheduled and unscheduled visits also were monitored for a 1-year follow-up period . The telephone service , which provided a triage system for referrals as well as a source of central contact for scheduling or for complaints , helped to improve satisfaction and reduce the number of unscheduled visits within 6 months . Such a service also may have application in other problem areas in the delivery of quality ambulatory care STUDY OBJECTIVES We sought to compare triage design ations derived from in-person and telephone interviews and systematic ally examine the effect of visual cues , vital signs , and complaint-based protocol s on the triage process . METHODS We conducted a 2-phase , prospect i ve , observational study employing a r and omized , crossover design in a university teaching hospital emergency department . In both phases , every eligible patient underwent sequential in-person and telephone triage interviews conducted by certified ED triage nurses . After taking a history , each nurse chose 1 of 5 hypothetical triage design ations and , after being told the patient 's vital signs , again selected a design ation . Phase 1 design ations were based solely on nurses ' clinical expertise . In phase 2 , both nurses used complaint-based protocol s. RESULTS Agreement between telephone and in-person design ations was poor ( percent agreement , 43.1 % to 48.8 % ; kappa,.19 to.26 ; taub,.34 to.45 for the 4 primary comparisons ) . Knowledge of vital signs and use of protocol s did not improve agreement or increase identification of patients requiring admission to hospital . CONCLUSION These data establish that telephone and in-person triage are not equivalent and suggest that visual cues may play an important role in the triage process . It is unclear whether telephone triage is an adequate method of assigning patients to an appropriate level of care |
909 | 17,443,541 | Extended intervention when compared with brief intervention was associated with a non-significantly greater reduction in alcohol consumption ( mean difference = -28 , 95%CI : -62 to 6 grams/week , I2 = 0 % ) AUTHORS ' CONCLUSIONS Brief interventions consistently produced reductions in alcohol consumption .
When data were available by gender , the effect was clear in men at one year of follow up , but unproven in women .
Longer duration of counselling probably has little additional effect . | BACKGROUND Many trials reported that brief interventions are effective in reducing excessive drinking .
However , some trials have been criticised for being clinical ly unrepresentative and unable to inform clinical practice . | BACKGROUND Brief interventions for problem drinking in medical setting s are effective but rarely conducted , mainly due to insufficient time . A stepped care approach ( starting with a very brief intervention and intensifying efforts in case of no success ) could save re sources and enlarge effectiveness ; however , research is lacking . The present study compares a full care brief intervention for patients with at-risk drinking , alcohol abuse or dependence with a stepped care approach in a r and omized controlled trial . METHODS Participants were proactively recruited from general practice s in two northern German cities . In total , 10,803 screenings were conducted ( refusal rate : 5 % ) . Alcohol use disorders according to DSM-IV were assessed with the Munich-Composite International Diagnostic Interview ( M-CIDI ) . Eligible participants were r and omly assigned to one of three conditions : ( 1 ) stepped care ( SC ) : a computerized intervention plus up to three 40-min telephone-based interventions depending on the success of the previous intervention ; ( 2 ) full-care ( FC ) : a computerized intervention plus a fixed number of four 30-min telephone-based interventions that equals the maximum of the stepped care intervention ; ( 3 ) an untreated control group ( CG ) . Counseling effort in the intervention conditions and quantity/frequency of drinking were assessed at 12-month follow-up . RESULTS SC participants received roughly half of the amount of intervention in minutes compared to FC participants . Both groups did not differ in drinking outcomes . Compared to CG , intervention showed small to medium effect size for at-risk drinkers . CONCLUSIONS Study results reveal that a stepped care approach can be expected to increase cost-effectiveness of brief interventions for individuals with at-risk drinking STUDY OBJECTIVE This study compares the effect of a brief motivational intervention for alcohol plus a booster given to emergency department ( ED ) patients with subcritical injuries from a motor vehicle crash with the effect of brief motivational intervention for alcohol plus a booster in patients treated for non-motor vehicle crash-related injuries . METHODS A r and omized controlled trial ( n=539 ) was conducted at an urban Level I trauma center of brief intervention ( 1 ED session of brief intervention ) , brief motivational intervention for alcohol plus a booster ( 1 ED session plus booster session ) , or st and ard care for injured ED patients with an alcohol use problem who were being discharged home . At 12 months , alcohol-related negative consequences and injuries were measured . We performed a secondary analysis comparing motor vehicle crash-injured patients and non-motor vehicle crash-injured patients in the study sample . RESULTS Subcritically injured ED patients with harmful or hazardous alcohol use who received brief motivational intervention for alcohol plus a booster had fewer alcohol-related negative consequences and alcohol-related injuries than those receiving brief intervention or st and ard care at 12-month follow-up ( previously reported ) . A secondary analysis of this result showed that motor vehicle crash patients ( n=133 ) given brief motivational intervention for alcohol plus a booster ( n=34 ) had fewer alcohol-related injuries than those receiving st and ard care ( n=46 ; P = .001 ) . Moreover , there were no significant differences in alcohol-related injuries among the non-motor vehicle crash-injured patients who received brief intervention or st and ard care . CONCLUSION Brief motivational intervention for alcohol plus a booster is a useful intervention for subcritically injured ED patients with harmful or hazardous alcohol use . Its effects may be moderated by the cause of injury OBJECTIVE Alcohol screening and brief intervention ( SBI ) has gained widespread acceptance as an effective method for reducing problem drinking in at-risk population s. This study examines the cost and cost-effectiveness of an SBI pilot program delivered in an inner-city hospital emergency department ( ED ) to a traditionally underserved population . METHOD A total of 1,036 subjects were screened for problem drinking during their visit to an ED . Eligible participants ( N = 294 ) were r and omly assigned to either a brief intervention group or a control group . As the result of attrition , a final sample of 194 ( 90 brief intervention ; 104 control ) participants remained at follow-up . The intervention consisted of a brief counseling session and a health information packet . The control group received only the packet . Intervention cost data were collected and analyzed using the Drug Abuse Treatment Cost Analysis Program . Selected outcomes at the 3-month follow-up included the raw Alcohol Use Disorders Identification Test score , average weekly number of drinks and engaging in heavy drinking in the past month ( > 6 drinks on one occasion for men , > 4 for women ) . Outcome differences between the intervention and control groups were estimated with both bivariate and multivariate techniques . RESULTS The average economic cost of the brief intervention was dollars 632 per subject , of which screening ( dollars 497 ) was the largest component . In all cases , intervention subjects had better 3-month outcomes than control subjects , but the differences were not always statistically significant . Cost-effectiveness ratios were relatively small for all three outcomes , suggesting this type of intervention has the potential to be cost-effective under full implementation . CONCLUSIONS The preliminary results demonstrate the potential advantage of further research in this area with larger sample s and a longer follow-up period AIM To establish the efficacy of a brief motivational intervention compared to feedback only when delivered in an emergency department for reducing alcohol use and problems among young adults . DESIGN Two-group r and omized controlled trial with follow-up assessment s at 6 and 12 months . SETTING Level I Trauma Center . PARTICIPANTS A total of 198 18 - 24-year-old patients who were either alcohol positive upon hospital admission or met screening criteria for alcohol problems . INTERVENTION Participants were assigned r and omly to receive a one-session motivational intervention ( MI ) that included personalized feedback , or the personalized feedback report only ( FO ) . All participants received additional telephone contact 1 month and 3 months after baseline . MEASUREMENTS Demographic information , alcohol use , alcohol problems and treatment seeking . FINDINGS Six months after the intervention MI participants drank on fewer days , had fewer heavy drinking days and drank fewer drinks per week in the past month than did FO patients . These effects were maintained at 12 months . Clinical significance evaluation indicated that twice as many MI participants as FO participants reliably reduced their volume of alcohol consumption from baseline to 12 months . Reductions in alcohol-related injuries and moving violations , and increases in alcohol treatment-seeking were observed across both conditions at both follow-ups with no differences between conditions . CONCLUSIONS This study provides new data supporting the potential of the motivational intervention tested to reduce alcohol consumption among high-risk youth AIMS This study aim ed at testing the effectiveness of a brief motivational intervention ( BI ) compared with a minimal intervention ( MI ) for reducing alcohol consumption in adult , alcohol-positive traffic casualties . METHODS Patients were recruited at the emergency room of a trauma hospital and screened for alcohol by a qualitative saliva test ( positive from a blood alcohol concentration of 0.02 g/l ) . Positive patients ( 13.3 % ) who accepted entering the study were r and omly allocated into BI and MI . Baseline assessment was the same for all patients . Blind telephone follow-ups were performed at months 3 , 6 , and 12 , and results were analysed by protocol and by intention-to-treat analysis . RESULTS After 1 year of follow-up , 67 % of the patients had reduced their consumption , the percentage of heavy drinkers had dropped by 47 % , and 62 % of baseline AUDIT-C positive patients ( hazardous drinkers ) had become negative . Binge drinking dropped significantly ( P < 0.05 ) . Results at month 12 were in line with the previous ones . CONCLUSIONS The effectiveness of BI compared with MI has not been verified , but a significant reduction in consumption has been observed in the whole sample , without significant differences by type of intervention . The persistence and dimension of changes suggest a real effect of both interventions , although the lack of a pure control group does not allow definitive conclusions . Traffic casualties are in a teachable moments to benefit from easy and cheap interventions Objectives : Brief intervention for excessive alcohol consumption is effective yet not implemented widely . Alcohol misuse is implicated in unsafe sex and sexually transmitted infections and is common in clients of sexual health services . Our aims were to assess feasibility , acceptability and effectiveness of screening and brief intervention for risky alcohol consumption by a nurse in a sexual health clinic . Methods : Patients completed the AUDIT question naire on h and held computers . Those scoring ⩾8 on AUDIT were asked to participate in the study and the 3 months ’ follow-up and were r and omised to intervention or control groups . The Drink-less package ( based on WHO vali date d methods ) was used to implement the brief intervention by a trained registered nurse . Results : Of 519 ( 87 % ) who completed screening , 204 ( 39 % ) scored ⩾8 on AUDIT ( eligible ) , 184 agreed to follow-up and 133 completed it . At follow-up , both groups showed significant reductions in AUDIT scores . Mean scores decreased from 13.7 to 11.5 ( control group ) and 14.0 to 10.7 ( intervention group ) ; most ( 94 % ) recalled the intervention and 62 % reported reducing drinking compared with 47 % of controls ( p<0.001 ) . The nurse screening and intervention process was reported acceptable by 74 % of patients at follow-up and a majority ( 71 % ) of staff . Conclusions : Screening and brief intervention in a sexual health clinic for risky alcohol consumption is feasible , acceptable and effective in producing significant reductions in drinking as measured by AUDIT . Both intervention and control groups decreased consumption , suggesting that screening alone is sufficient to influence behaviour . Further study of brief intervention in this setting is appropriate OBJECTIVE To identify predictors of smoking cessation success or failure with and without transdermal nicotine patch treatment . DESIGN Two independent r and omized , double-blind , placebo-controlled studies using the nicotine patch assessing outcome at the end of treatment and at 6-month follow-up ; each study used a different mode of adjuvant counseling . PATIENTS Subjects were daily smokers ( > or = 15 cigarettes per day ) , aged 21 to 65 years with expired air carbon monoxide levels of at least 10 ppm , and motivated to quit . Eighty-eight subjects participated in study 1 , and 112 subjects participated in study 2 . INTERVENTION Study 1 consisted of 8 weeks of 22-mg nicotine patch therapy with intensive group counseling . Study 2 consisted of 4 weeks of 22-mg nicotine patch therapy and 2 weeks of 11-mg nicotine patch therapy with brief individual counseling . MAIN OUTCOME MEASURES The prediction of smoking cessation ( at end of treatment and after 6 months ) based on pretreatment and intratreatment measures in smokers using active or placebo nicotine patches . RESULTS Pretreatment markers , such as the Fagerstrom Tolerance Question naire score , number of cigarettes smoked per day , years smoked , expired air carbon monoxide level , or baseline blood nicotine and cotinine levels , showed no consistent relationship with successful smoking cessation across both studies . Of the intratreatment markers examined , withdrawal severity and nicotine replacement levels also were not consistently predictive of cessation success . However , any smoking during the second week of treatment was a consistent and powerful predictor of failure at the end of treatment and after 6 months . Among active nicotine patch patients who smoked at all during week 2 after quitting , 83 % and 97 % ( studies 1 and 2 , respectively ) were smoking at 6-month follow-up . Conversely , abstinence during the second week of treatment predicted successful smoking cessation . Among active nicotine patch patients who were totally abstinent during week 2 after quitting , 46 % and 41 % ( studies 1 and 2 , respectively ) were abstinent at 6-month follow-up . Of all nicotine patch patients in both studies who were smoking at 6-month follow-up , 74 % began smoking during week 1 or 2 . Among all placebo patch patients who were smoking at 6-month follow-up , 86 % began smoking during week 1 or 2 . CONCLUSIONS Smoking status ( abstinent or smoking ) during the first 2 weeks of nicotine patch therapy , particularly week 2 , was highly correlated with clinical outcome and can serve as a powerful predictor of smoking cessation . Early smoking behavior also predicted outcome among placebo patch users . Traditional measures of dependence are not consistently predictive of cessation success . Clinicians are advised to emphasize the importance of total abstinence after a quit attempt and to follow-up with patients within the first 2 weeks of quitting ; smoking during this critical time should be assessed and treatment may be altered as appropriate Risk factors associated with the progression from impaired glucose tolerance ( IGT ) to NIDDM were examined in data from six prospect i ve studies . IGT and NIDDM were defined in all studies by World Health Organization ( WHO ) criteria , and baseline risk factors were measured at the time of first recognition of IGT . The studies varied in size from 177 to 693 participants with IGT , and included men and women followed from 2 to 27 years after the recognition of IGT . Across the six studies , the incidence rate of NIDDM was 57.2/1,000 person-years and ranged from 35.8/1,000 to 87.3/1,000 person-years . Although baseline measures of fasting and 2-h postchallenge glucose levels were both positively associated with NIDDM incidence , incidence rates were sharply higher for those in the top quartile of fasting plasma glucose levels , but increased linearly with increasing 2-h postchallenge glucose quartiles . Incidence rates were higher among the Hispanic , Mexican-American , Pima , and Nauruan population s than among Caucasians . The effect of baseline age on NIDDM incidence rates differed among the studies ; the rates did not increase or rose only slightly with increasing baseline age in three of the studies and formed an inverted U in three studies . In all studies , estimates of obesity ( including BMI , waist-to-hip ratio , and waist circumference ) were positively associated with NIDDM incidence . BMI was associated with NIDDM incidence independently of fasting and 2-h post challenge glucose levels in the combined analysis of all six studies and in three cohorts separately , but not in the three studies with the highest NIDDM incidence rates . Sex and family history of diabetes were generally not related to NIDDM progression . This analysis indicates that persons with IGT are at high risk and that further refinement of risk can be made by other simple measurements . The ability to identify persons at high risk of NIDDM should facilitate clinical trials in diabetes prevention Seventy two women drinking 21 units ( 210 g ) or more of alcohol per week were recruited from an opportunistic screening programme in eight English general practice s. The women were r and omized into control and treatment groups . Women in the treatment group received ten minutes advice from their general practitioner to reduce alcohol consumption . At one year follow-up , when analyzed by intention to treat , women in the treatment group had reduced their alcohol consumption from an average of 35 - 24 units per week . Similar reductions were found in the control group ( from 37 - 27 units per week ) . The lack of evidence for a treatment effect may be explained by contamination of the control group by informal interventions Abstract Rationale . The subjective , psychomotor , and physiological effects of prescription compounds containing the opioid hydrocodone have not been studied in a population of non-drug-abusing people who might be prescribed these compounds for cough or pain relief . Objectives . To characterize the effects of a hydrocodone combination product , Hycodan , which contains hydrocodone and a peripherally-acting anticholinergic , homatropine , in non-drug-abusing volunteers . Methods . Eighteen volunteers participated in a crossover , double-blind study in which they received placebo ; 5 mg hydrocodone/1.5 mg homatropine , 10 mg hydrocodone/3 mg homatropine , 20 mg hydrocodone/6 mg homatropine ( all PO ) ; 40 mg morphine ( PO ) ; and 2 mg lorazepam ( PO ) . Measures were assessed before and for 300 min after drug administration . End-of-session and 24-h measures were taken to assess residual drug effects and overall subjects ' assessment of the drug effects . Results . Subjective effects of the hydrocodone/homatropine combination were dose-related , although the majority of statistically significant effects were limited to the highest dose combination tested . A combination of 20 mg hydrocodone/6 mg homatropine and morphine had a similar profile of subjective effects , which included both pleasant and unpleasant effects . Peak liking ratings were increased by 20 mg hydrocodone/6 mg homatropine and morphine , and trough ratings of liking ( dislike ) were lower in the 20 mg hydrocodone/6 mg homatropine condition , relative to the placebo condition . Post-session ratings of overall liking were not significant , either at the end of the session or 24 h later . Cognitive and psychomotor impairment were more marked with lorazepam than with hydrocodone/homatropine and morphine . Miosis and exophoria were increased in a dose-related manner by hydrocodone/homatropine . Conclusions . Hycodan at the highest dose tested had effects similar to that of a prototypic mu agonist , morphine . Both drugs produced pleasant ( including drug liking ) as well as unpleasant subjective effects . Post-session ratings of overall liking and " want to take drug again " were not significant BACKGROUND Only a few intervention studies aim ing to change high-risk drinking behavior have involved university students with heredity for alcohol problems . This study evaluated the effects after 2 years on drinking patterns and coping behavior of intervention programs for students with parents with alcohol problems . METHOD In total , 82 university students ( 57 women and 25 men , average age 25 years ) with at least 1 parent with alcohol problems were included in the study . The students were r and omly assigned to 1 of the 3 programs : ( i ) alcohol intervention program , ( ii ) coping intervention program , or ( iii ) combination program . All the 3 intervention programs were manual based and individually implemented during 2 2-hour sessions , 4 weeks apart . Before the participants were r and omly assigned , all were subjected to an individual baseline assessment . This assessment contained both a face-to-face interview and 6 self-completion question naires : the Alcohol Use Disorders Identification Test , estimated Blood Alcohol Concentration , Short Index of Problems , the Symptom Checklist-90 , Coping with Parents ' Abuse Question naire , and The Interview Schedule for Social Interaction ( ISSI ) . Follow-up interviews were conducted after 1 and 2 years , respectively . The results after 1 year have previously been reported . RESULTS All participants finished the baseline assessment , accepted and completed the intervention . Ninety-five percent of the students completed the 24-month follow-up assessment . Only the group receiving the combination program continued to improve their drinking pattern significantly ( p < 0.05 ) from the 12-month follow-up to the 24-month follow-up . The improvements in this group were significantly better than in the other 2 groups . The group receiving only alcohol intervention remained at the level of improvement achieved at the 12-month follow-up . The improvements in coping behavior achieved at the 12-month follow-up remained at the 24-month follow-up for all the 3 groups , i.e. , regardless of intervention program . CONCLUSION Positive effects of alcohol intervention between 1 and 2 years were found only in the combined intervention group , contrary to the 1-year results with effects of alcohol intervention with or without a combination with coping intervention In a controlled evaluation of general practitioner (GP)-based brief intervention , 378 excessive drinkers identified opportunistically by screening in 40 group practice s in metropolitan Sydney were assigned to groups receiving : ( i ) a five-session intervention by the GP ( the Alcoholscreen Program ) ; ( ii ) a single session of 5 minutes ' advice by the GP plus a self-help manual ( minimal intervention ) ; ( iii ) an alcohol-related assessment but no intervention ; ( iv ) neither intervention nor assessment . Among all patients allocated to receive it , the Alcoholscreen Program did not result in a significantly greater reduction in consumption at follow-up than control conditions but patients offered Alcoholscreen reported a significantly greater reduction in alcohol-related problems in the period to 6 months follow-up . A greater proportion of patients who returned for the second Alcoholscreen visit were drinking below recommended levels at follow-up than in the remainder of the sample . There was no evidence that minimal intervention or alcohol-related assessment were effective in reducing alcohol consumption or problems . Implication s for further research into GP-based brief interventions are discussed Rationale Acute cravings , often provoked by exposure to smoking cues , appear to be important triggers for smoking relapse . Relief of acute craving may therefore be an important step in preventing relapse . Objectives This study was undertaken to assess the effectiveness of nicotine gum in relieving acute craving . Methods A multi-center , r and omized , placebo-controlled study was conducted with smokers ( n=296 ) who quit by using either active or inactive gum for 3 days . On their third day of abstinence , smokers participated in a laboratory session in which they were exposed to a provocative smoking cue , chewed active or inactive gum , and then rated their craving at 5-min intervals for 35 min . Results Craving initially decreased in both groups . After 15 min , however , the smokers using active nicotine gum experienced significantly greater craving reductions . Conclusions These results suggest that nicotine gum can effectively reduce acute craving following exposure to smoking cues Objective : We sought to estimate the effect of screening and brief intervention ( SBI ) for risky alcohol use on the health care utilization of risky drinkers in 4 managed care organizations . Research Design : A quasi-experimental group design was implemented in which 12 participating primary care clinics r and omly were assigned to 1 of 3 study conditions . In one condition , physicians , physician assistants , and nurse practitioners delivered the brief intervention . In another condition , midlevel professionals ( usually nurses ) performed the brief intervention . In the third condition , SBI was not performed . Using administrative cl aims data , we estimated the effect of SBI on individual-level annual days of total and inpatient health care utilization ; annual outpatient visits ; annual emergency room visits ; and annual visits related to alcohol , drug , or mental health conditions . Negative binomial regression models were used to control for other factors that may affect health care utilization . Results : Across all categories of care , the pre- to postintervention change in average health care utilization among risky drinkers in the intervention clinics was not significantly different from that of risky drinkers in the comparison clinics . Conclusions : Our findings suggest that there is no effect of SBI on the health care utilization of risky drinkers in the year following the intervention . Although SBI does not appear to reduce health care utilization , previous studies find that it significantly reduces the alcohol consumption of risky drinkers . Because these reductions presumably improve patients ’ overall health and well-being , managed care organizations may still find it beneficial to implement SBI on a broad scale OBJECTIVE To compare the effects of three brief methods of reducing alcohol consumption among family practice patients . DESIGN Patients r and omly assigned to one of three interventions were assessed initially and at 3- , 6- , and 12-month follow-up appointments . SETTING Family practice clinic composed of 12 primary care physicians seeing approximately 6000 adults monthly in a small urban community , population 40,000 . PARTICIPANTS Through a screening question naire , 134 men and 131 women were identified as hazardous drinkers ( five or more drinks at least once monthly ) during an 11-month screening of 1420 patients . Of 265 patients approached , 180 agreed to participate and 159 ( 83 men and 76 women ) actually participated in the study . INTERVENTIONS Three interventions were studied : brief physician advice ( 5 minutes ) , two 30-minute sessions with a physician using cognitive behavioural strategies or two 30-minute sessions with a nurse practitioner using identical strategies . MAIN OUTCOME MEASURES Quantity and frequency ( QF ) of drinking were used to assess reduction in hazardous drinking and problems related to drinking over 12 months of follow up . RESULTS No statistical difference between groups was found . The QF of monthly drinking was reduced overall by 66 % ( among men ) and 74 % ( among women ) for those reporting at least one hazardous drinking day weekly at assessment ( N = 96 ) . Men reported drinking significantly more than women . CONCLUSIONS These results indicated that offering brief , specific advice can motivate patients to reduce their alcohol intake . There was no difference in effect between brief advice from their own physician or brief intervention by a physician or a nurse Sixteen general practitioners participated in a controlled trial of the Scottish Health Education Group 's DRAMS ( drinking reasonably and moderately with self-control ) scheme . The scheme was evaluated by r and omly assigning 104 heavy or problem drinkers to three groups - a group participating in the DRAMS scheme ( n = 34 ) , a group given simple advice only ( n = 32 ) and a non-intervention control group ( n = 38 ) . Six month follow-up information was obtained for 91 subjects ( 87.5 % of initial sample ) . There were no significant differences between the groups in reduction in alcohol consumption , but patients in the DRAMS group showed a significantly greater reduction in a logarithmic measure of serum gamma-glutamyl-transpeptidase than patients in the group receiving advice only . Only 14 patients in the DRAMS group completed the full DRAMS procedure . For the sample as a whole , there was a significant reduction in alcohol consumption , a significant improvement on a measure of physical health and well-being , and significant reductions in the logarithmic measure of serum gamma-glutamyl transpeptidase and in mean corpuscular volume . The implication s of these findings for future research into controlled drinking minimal interventions in general practice are discussed The objective of the study was to estimate the effect of a brief alcohol-reduction intervention on health care use . Male veterans aged 55 years and older drinking more than guideline limits participated in an effective primary care-based r and omized clinical trial to reduce drinking . Repeated measures ANCOVA assessed short-term and long-term changes in both inpatient and outpatient utilization . Stage of change ( SOC ) was assessed in a sub sample to test for interaction between SOC and the intervention . Veterans exposed to the intervention used more outpatient medical services in the short term . Long-term effects on inpatient/outpatient use were not observed . SOC did not moderate the effect of the intervention but was associated with differential use of health care services . A cost-effective brief intervention to reduce drinking may spur increased efforts to seek health care . Early detection and management of alcohol-related or other illnesses might be expected to accrue savings in later years Abstract Objective : To determine the effectiveness of health checks , performed by nurses in primary care , in reducing risk factors for cardiovascular disease and cancer . Design : R and omised controlled trial . Setting : Five urban general practice s in Bedfordshire . Subjects : 2205 men and women who were r and omly allocated a first health check in 1989 - 90 and a re-examination in 1992 - 3 ( the intervention group ) ; 1916 men and women who were r and omly allocated an initial health check in 1992 - 3 ( the control group ) . All subjects were aged 35 - 64 at recruitment in 1989 . Main outcome measures : Serum total cholesterol concentration , blood pressure , body mass index , and smoking prevalence ( with biochemical validation of cessation ) ; self reported dietary , exercise , and alcohol habits . Results : Mean serum total cholesterol was 3.1 % lower in the intervention group than controls ( difference 0.19 mmol/l ( 95 % confidence interval 0.12 to 0.26 ) ; in women it was 4.5 % lower ( P<0.0001 ) and in men 1.6 % ( P<0.05 ) , a significant difference between the sexes ( P<0.01 ) . Self reported saturated fat intake was also significantly lower in the intervention group . Systolic and diastolic blood pressures and body mass index were respectively 1.9 % , 1.9 % , and 1.4 % lower in the intervention group ( P<0.005 in all cases ) . There was a 3.9 % ( 2.4 to 5.3 ) difference in the percentage of subjects with a cholesterol concentration > /=8 mmol/l , but no significant differences in the number with diastolic blood pressure > /=100 mm Hg or body mass index > /=30 kg/m2 . There was no significant difference between the two groups in prevalence of smoking or excessive alcohol use . Annual rechecks were no more effective than a single recheck at three years , but health checks led to a significant increase in visits to the nurse according to patients ' degree of cardiovascular risk . Conclusions : The benefits of health checks were sustained over three years . The main effects were to promote dietary change and reduce cholesterol concentrations ; small differences in blood pressure may have been attributable to accommodation to measurement . The benefits of systematic health promotion in primary care are real , but must be weighed against the costs in relation to other priorities . Key messages Key messages There is little effect on smoking or alcohol use , and more targeted approaches to modifying these behaviours may be appropriate Systematic implementation of health checks might lead to a reduction in risk of myocardial infa rct ion among those who attend of about 5 - 15 % ; men , who are at higher risk , show less change than women Health checks consume substantial re sources , and their effect is attenuated by non-attendance The benefits of health promotion through primary care must be weighed against their costs and in relation to other OBJECTIVE : To determine effectiveness of advice from general practitioners to heavy drinkers to reduce their excessive alcohol consumption ( 35 U or more a week for men , 21 U or more for women ) . DESIGN : R and omised , controlled double blind trial over 12 months with interim assessment at six months . SETTING : Group practice s ( n = 47 ; list size averaging 10,000 ) recruited from Medical Research Council 's general practice research framework , mostly in rural or small urban setting s. PATIENTS : Patients recruited after question naire survey . Of total of 2571 ( 61.2 % ) of 4203 patients invited for interview who attended , 909 ( 35.4 % ) stated that in past seven days they had drunk above the limits set for study and had not received advice ; they were r and omised to control and treatment groups . INTERVENTIONS : Patients in treatment group were interviewed by general practitioner ( who had had a training session ) and received advice and information about how to reduce consumption and also given a drinking diary . END POINT : Study aim ed at detecting a reduction in proportion of men with excessive alcohol consumption of 30 % in treatment group and 20 % in control group ( for women 40 % and 20 % , respectively ) with a power of 90 % at 5 % level of significance . In addition , corroborative measures such as estimation of gamma-glutamyltransferase activity were included . MEASUREMENTS AND MAIN RESULTS : At one year a mean reduction in consumption of alcohol of 18.2 ( SE 1.5 ) U/week had occurred in treated men compared with a reduction of 8.1 ( 1.6 ) U/week in controls ( p less than 0.001 ) . The proportion of men with excessive consumption at interview had dropped by 43.7 % in the treatment group compared with 25.5 % in controls ( p less than 0.001 ) . A mean reduction in weekly consumption of 11.5 ( 1.6 ) U occurred in treated women compared with 6.3 ( 2.0 ) U in controls ( p less than 0.05 ) , with proportionate reductions of excessive drinkers in treatment and control groups of 47.7 % and 29.2 % respectively . Reduction in consumption increased significantly with number of general practitioner interventions . At one year the mean value for gamma-glutamyltransferase activity had dropped significantly more in treated men ( -2.4 (0.9)IU/l ) than in controls ( + 1.1(1.0)IU/l ; t = 2.7 , p less than 0.01 ) . Reduction in gamma-glutamyltransferase activity tended to increase with number of intervention sessions in men . Changes in gamma-glutamyltransferase activity in women and changes in other indicators in both sexes did not differ significantly between treatment and control groups . CONCLUSIONS : If the results of this study were applied to the United Kingdom intervention by general practitioners could each year reduce to moderate levels the alcohol consumption of some 250000 men and 67500 women who currently drink to excess . General practitioners and other members of the primary health care team should therefore be encouraged to include counselling about alcohol consumption in their preventive activities AIM To analyse gender differences in the efficacy of stepped care brief interventions for general practice patients with alcohol problems . METHODS Data are part of " Stepped Interventions for Problem Drinkers , " in which 10,803 patients from 85 general practitioners were screened using alcohol related question naires ; 408 patients were r and omized ( 32 % were female ) to a control ( booklet only ) or two different intervention groups : stepped care ( feedback , manual , and up to three counselling sessions depending on the success of the previous intervention ) and fixed care ( four sessions ) . Response rate for the 12 months follow-up was 91.7 % . RESULTS Regression analysis revealed a significant effect size only in women ( P = 0.039 ) . After excluding alcohol dependents and binge drinkers , an effect size ( R(2 ) ) of 0.031 ( P = 0.050 ) in women and an effect size ( R(2 ) ) of 0.069 ( P = 0.057 ) in men was obtained . Among the patients in stepped care who , by the first assessment point , had reduced drinking to within safe-drinking limits , there was a tendency for females to have achieved this more often than males ( 40 % vs. 24 % ; P = 0.089 ) . CONCLUSIONS In a heterogeneous sample , the intervention was only effective for women . Women tended to profit more from the first , less intensive intervention than men . When analysis was limited to those reporting " at risk " average daily consumption and " alcohol abuse , " the gender differences in efficacy appeared to be less , but the study was not sufficiently powered to affirm that OBJECTIVE To determine whether office-based interventions change adolescents ' alcohol beliefs and alcohol use . DESIGN R and omized , controlled trial . SETTING Five managed care group practice s in Washington , DC . PARTICIPANTS Consecutive 12- to 17-year-olds ( N = 409 ) seeing primary care providers ( N = 26 ) for general check-ups . Most of the adolescents ( 79 % ) were African American , 44 % were male , and 16 % currently drank . INTERVENTIONS Usual care ( Group I ) , adolescent priming with alcohol self- assessment just prior to check-up ( Group II ) , adolescent priming and provider prompting with adolescent self- assessment and brochure ( Group III ) . MAIN OUTCOME MEASURES Adolescent alcohol beliefs at exit interview and self-reported behaviors at 6- and 12-month follow-up . RESULTS At exit interview , Groups II and III reported that less alcohol was needed for impaired thinking and a greater intent to drink alcohol in the next 3 months than Group I. At 6 months , Group III reported more resistance to peer pressure to drink , and Groups II and III reported more bingeing than Group I. At 1-year follow-up , controlling for baseline levels , Groups II ( odds ratio [ OR ] , 3.44 ; 95 % confidence interval [ CI ] , 1.44 - 6.24 ) and III ( OR , 2.86 ; CI , 1.13 - 7.26 ) reported more bingeing in the last 3 months than Group I. Group II reported more drinking in the last 30 days ( OR , 2.31 ; CI , 1.31 - 4.07 ) and in the last 3 months ( OR , 1.76 ; CI , 1.12 - 2.77 ) than Group I. CONCLUSION Brief office-based interventions were ineffective in reducing adolescent alcohol use but may increase adolescent reporting of alcohol use Abstract Objective : To explore the suitability of a screening based intervention for excessive alcohol use by describing the experiences of general practitioners who tried such an intervention in their everyday practice . Design : Qualitative interviews with general practitioners who had participated in a pragmatic study of a combined programme of screening and a brief intervention for excessive alcohol use . Doctors were interviewed either individually or in focus groups . A computer based , descriptive , phenomenological method was used to directly analyse the digitally recorded interviews . Setting and participants : 24 of 39 general practitioners in four Danish counties who volunteered to take part in the pragmatic study were interviewed . Results : The doctors were surprised at how difficult it was to establish rapport with the patients who had a positive result on the screening and to ensure compliance with the intervention . Although the doctors considered the doctor-patient relationship robust enough to sustain targeting of alcohol use , they often failed to follow up on initial interventions , and some expressed a lack of confidence in their ability to counsel patients effectively on lifestyle issues . The doctors question ed the rationale of screening in young drinkers who may grow out of excessive drinking behaviour . The programme needed considerable re sources , and it interrupted the natural course of consultations and was inflexible . The doctors could not recommend the screening and brief intervention programme , although they thought it important to counsel their patients on drinking . Conclusions : Screening for excessive alcohol use created more problems than it solved for the participating doctors . The results underline the value of carrying out pragmatic studies on the suitability of seemingly efficacious healthcare programmes OBJECTIVE To evaluate the feasibility and efficacy of routine opportunistic screening and brief intervention ( BI ) by ED staff to reduce high-risk alcohol consumption . METHODS This was an open , r and omized controlled trial with allocation blinding performed over 12 months . Using the Paddington Alcohol Test , adult patients were screened for high-risk alcohol use . Consenting patients who were screened positive were eligible for r and omization to no counselling ( st and ard care , SC ) , same-day BI by an emergency nurse or doctor or motivational intervention ( MI ) within 1 week by off-site drug and alcohol counsellors . Telephone follow up was performed at 1 and 3 months . The primary outcome was maximum self-reported daily st and ard drinks consumed . Analysis was by intention to treat . RESULTS Of 32,965 eligible patients , 10,274 were screened , 1043 were positive , 468 consented to the study , and 161 , 159 and 148 were allocated to SC , BI and MI , respectively . In the MI group , 133 declined intervention or failed to attend . At 3 months , 96 , 81 and 74 participants in the SC , BI and MI groups , respectively , were contactable and consented to telephone interview . Overall , maximum daily alcohol consumption decreased from a median of 13.5 st and ard drinks at enrolment to 9.25 drinks at 3 months . At 3 months , SC participants reported fewer drinks than those r and omized to MI . CONCLUSION In the present study , neither BI nor MI was better than SC in reducing high-risk alcohol consumption . Uptake of opportunistic screening by ED staff was poor , as was patient compliance with off-site counselling BACKGROUND Alcohol use in older adults is common . It is associated with depression , hypertension , diabetes , drug interactions , accidents , and increased rates of emergency department visits and hospitalizations . METHODS A controlled clinical trial ( Project GOAL --Guiding Older Adult Lifestyles ) tested the efficacy of brief physician advice in reducing the alcohol use and use of health care services of older adult problem drinkers . Twenty-four community-based primary care practice s in Wisconsin ( 43 family physicians and internists ) participated in the trial . Of the 6073 patients screened , 105 men and 53 women met inclusion criteria and were r and omized into a control group ( n = 71 ) or an intervention group ( n = 87 ) . Intervention group patients received two 10- to 15-minute physician-delivered counseling sessions that included advice , education , and contracting using a scripted workbook . A total of 146 patients ( 92.4 % ) participated in the 12-month follow-up procedure . RESULTS No significant differences were found between the control and intervention groups at baseline in alcohol use , age , socioeconomic status , depression , onset of alcohol use , smoking status , activity level , or use of mood-altering drugs . The older adults who received the physician intervention demonstrated a significant reduction in 7-day alcohol use , episodes of binge drinking , and frequency of excessive drinking ( P < .005 ) compared with the control group at 3 , 6 , and 12 months after the intervention . There was a 34 % reduction in 7-day alcohol use , 74 % reduction in mean number of binge-drinking episodes , and 62 % reduction in the percentage of older adults drinking more than 21 drinks per week in the intervention group compared with the control group . There were no significant changes in health status . Patterns of health care utilization were not extensively analyzed because of the small number of events . CONCLUSIONS This study provides the first direct evidence that brief physician advice can decrease alcohol use by older adults in community-based primary care practice STUDY OBJECTIVE To determine the efficacy of emergency practitioner-performed brief intervention for hazardous/harmful drinkers in reducing alcohol consumption and negative consequences in an emergency department ( ED ) setting . METHODS A r and omized clinical trial ( Project ED Health ) was conducted in an urban ED from May 2002 to November 2003 for hazardous/harmful drinkers . Patients 18 years or older who screened above National Institute for Alcohol Abuse and Alcoholism guidelines for " low-risk " drinking or presented with an injury in the setting of alcohol ingestion were eligible . The mean number of drinks per week and binge-drinking episodes during the past 30 days were collected at 6 and 12 months ; negative consequences and use of treatment services , at 12 months . A Brief Negotiation Interview performed by emergency practitioners was compared to scripted Discharge Instructions . RESULTS A total of 494 hazardous/harmful drinkers were studied . The 2 groups were similar with respect to baseline characteristics . In the Brief Negotiation Interview group , the mean number of drinks per week at 12 months was 3.8 less than the 13.6 reported at baseline . The Discharge Instructions group decreased 2.6 from 12.4 at baseline . Likewise , binge-drinking episodes per month decreased by 2.0 from a baseline of 6.0 in the Brief Negotiation Interview group and 1.5 from 5.4 in the Discharge Instructions group . For each outcome , the time effect was significant and the treatment effect was not . CONCLUSION Among ED patients with hazardous/harmful drinking , we did not detect a difference in efficacy between emergency practitioner-performed Brief Negotiation Interview and Discharge Instructions . Further studies to test the efficacy of brief intervention in the ED are needed The relation between alcohol consumption and blood pressure is well recognized , and advice to reduce alcohol plays an important part in the management of hypertensive patients . We have evaluated the effectiveness of this advice in a r and omized , controlled , single-blind clinical study . After a 2-week run-in period , hypertensive men regularly consuming more than 20 units/wk ( 1 unit = 10 g ) of alcohol were r and omly assigned either to the " advice " or control group and were seen at 2-week intervals over an 8-week study period . The outcome measures were : reported alcohol consumption ( 1-week retrospective diary ) , markers of alcohol consumption ( serum gamma-glutamyl transpeptidase , aspartate aminotransferase , uric acid , mean corpuscular volume ) , and blood pressure ( sitting and st and ing ) . Over 18 months , 67 men who drank more than 20 units/wk of alcohol were seen . Twenty-six either were excluded , refused to participate , or dropped out due to nonattendance . Forty-one patients completed the study . After intervention , reported alcohol consumption fell from 60 units/wk to around 30 units/wk in the advice group , whereas it remained between 50 and 60 units/wk in the control group ( analysis of variance [ ANOVA ] F = 7.1 , p less than 0.05 ) . This was accompanied by falls in gamma-glutamyl transpeptidase ( 20.9 % ) and aspartate aminotransferase ( 18.1 % ) , but no significant changes were seen in the control group . St and ing diastolic blood pressure fell significantly in the advice group ( from 101.5 mm Hg to 96.3 mm Hg ) compared with the control group ( ANOVA F = 4.8 , p less than 0.05 ) . The results suggest that advice to reduce alcohol consumption is a useful form of treatment for hypertensive patients who drink excessively The aim of this research was to evaluate the effectiveness of long-term brief intervention in routine general practice . In five primary care out-patient clinics in a Finnish town , 296 male early-phase heavy drinkers consulting a general practitioner ( GP ) for various reasons were identified . Control group C ( n = 88 ) was informed of the risks of drinking after the screening and were advised at the subsequent feedback about 2 weeks later to reduce their drinking . Groups A ( n = 109 ) and B ( n = 99 ) were offered in addition seven and three brief intervention sessions , respectively . All GPs took part , whether or not they indicated a special interest . The main outcome measures were differences between beginning and end-point at 3 years in self-reported alcohol consumption , mean corpuscular volume ( MCV ) , and serum carbohydrate-deficient transferrin , aspartate aminotransferase , alanine aminotransferase and gamma-glutamyltransferase . There were no statistically significant differences between study groups A , B and C in mean changes in outcome measures . Within all the groups , MCV decreased . Depending on the outcome measure used and the study group analysed , clinical ly significant reduction of drinking was found in 25 - 53 % of the subjects . In routine general practice , giving additional sessions of brief intervention may not be as effective as in special research conditions . Factors reducing the effectiveness of brief intervention programmes should be investigated , so that primary health care staff can be better supported in their efforts AIMS Evaluate effectiveness and costs of brief interventions for patients screening positive for at-risk drinking in managed health care organizations ( MCOs ) . METHODS A pre-post , quasi-experimental , multi-site evaluation conducted at 15 clinic sites within five MCO setting s. At-risk drinkers ( N = 1329 ) received either : ( i ) brief intervention delivered by licensed practitioners ; or ( ii ) brief intervention delivered by mid-level professional specialists ( nurses ) ; or ( iii ) usual care ( comparison condition ) . Clinics were r and omly assigned to three study conditions . Data were collected on the cost of screening and brief intervention . Follow-up interviews were conducted at 3 and 12 months . RESULTS Participants in all three study conditions were drinking significantly less at 3-month follow-up , but the decline was significantly greater in the two intervention groups than in the control group . There were no significant differences between the two intervention conditions . Of the patients in the intervention conditions 60 % reduced their alcohol consumption by > or = 1 drink per week , compared with 53 % of those in the control condition . No differences were found on a measure of the quality of life . Differential reductions in weekly alcohol consumption between intervention and control groups were significant at 12-month follow-up . Average incremental costs of the interventions were 4.16 US dollar per patient using licensed practitioners and 2.82 US dollar using mid-level specialists . CONCLUSION Alcohol screening and brief intervention when implemented in managed care organizations produces modest , statistically significant reductions in at-risk drinking . Interventions delivered to a common protocol by mid-level specialists are as effective as those delivered by licensed practitioners at about two-thirds the cost Cue exposure paradigms have been used to examine reactivity to smoking cues . However , it is not known whether cue-provoked craving is associated with smoking cessation outcomes or whether cue reactivity can be attenuated by nicotine replacement therapy ( NRT ) in clinical sample s. Cue-provoked craving ratings and reaction time responses were measured on the 1st day of abstinence among 158 smokers who had been r and omized to high-dose nicotine ( 35 mg ) or placebo patch . The nicotine patch reduced overall levels of craving but did not attenuate cue-provoked craving increases or reaction time responses . Cue-provoked craving predicted relapse among participants on the nicotine patch but not among those on placebo . In summary , NRT users could benefit from treatment that attenuates cue-provoked craving AIMS To evaluate the effectiveness of brief alcohol intervention ( BAI ) in reducing alcohol use among hazardous drinkers treated in the emergency department ( ED ) after an injury ; in addition it tests whether assessment of alcohol use without BAI is sufficient to reduce hazardous drinking . DESIGN R and omized controlled clinical trial with 12-month follow-up conducted between January 2003 and June 2005 . SETTING Urban academic emergency department ( ED ) of the Lausanne University Hospital , Lausanne , Switzerl and . PARTICIPANTS A total of 5136 consecutive patients attending ED after an injury completed a seven-item general and a three-item alcohol screen and 1472 ( 28.7 % ) were positive for hazardous drinking according to the National Institute on Alcohol Abuse and Addiction definition ; of these 987 ( 67.1 % ) were r and omized into a BAI group ( n = 310 ) or a control group with screening and assessment ( n = 342 ) or a control group with screening only ( n = 335 ) and then a total of 770 patients ( 78.0 % ) completed the 12-month follow-up procedures . INTERVENTION A single 10 - 15-minute session of st and ardized BAI conducted by a trained research assistant . MEASUREMENTS Percentage of participants who have changed to low-risk drinking at follow-up . FINDINGS Data obtained at 12 months indicated that similar proportions were low-risk drinkers in BAI versus control groups with and without assessment ( 35.6 % , 34.0 % , 37.0 % , respectively , P = 0.71 ) . Data also indicated similar reductions in drinking frequency , quantity , binge drinking frequency and Alcohol Use Disorders Identification Test ( AUDIT ) scores across groups . All groups reported similar numbers of days hospitalized and numbers of medical consults in the last 12 months . A model including age groups , gender , AUDIT and injury severity scores indicated that BAI had no influence on the main alcohol use outcome . CONCLUSIONS This study provides the evidence that a 10 - 15-minute BAI does not decrease alcohol use and health re source utilization in hazardous drinkers treated in the ED , and demonstrates that commonly found decreases in hazardous alcohol use in control groups can not be attributed to the baseline alcohol assessment The Trial for Early Alcohol Treatment , Project TrEAT , was a r and omized controlled trial of screening and brief intervention in primary care clinics . One of the few such trials to be analyzed in terms of cost-effectiveness , Project TrEAT was examined from two perspectives . The analysis from the perspective of medical care providers focused on clinic and hospital costs , contrasting the benefits that directly reduced medical expenditures with the costs to providers . The analysis from the societal perspective took all of the intervention ’s costs and benefits into account . Both components of this study revealed that Project TrEAT led to a reduction in alcohol consumption by high-risk drinkers and a corresponding reduction in medical and societal costs . Overall , this study supported the cost-effectiveness of Project TrEAT , concluding that its costs were outweighed by its benefits BACKGROUND Studies suggest that 14 % of women age 18 to 40 drink alcohol above recommended limits . Of special concern is the increasing use of alcohol by women during pregnancy . This article reports 48 month follow-up data from a sub analysis of a trial for early alcohol treatment ( Project TrEAT ) focused on women of childbearing age . METHODS Project TrEAT was conducted in the offices of 64 primary care , community-based physicians from 10 Wisconsin counties . Of 5979 female patients ages 18 to 40 who were screened for problem drinking , 205 were r and omized into an experimental group ( n = 103 ) or control group ( n = 102 ) . The intervention consisted of two 15 min , physician-delivered counseling visits that included advice , education , and contracting by using a scripted workbook . A total of 174 subjects ( 85 % ) completed the 48 month follow-up procedures . RESULTS No significant differences were found between the experimental and control groups at baseline for alcohol use , age , socioeconomic status , smoking , depression or anxiety , conduct disorder , lifetime drug use , or health care utilization . The trial found a significant treatment effect in reducing both 7 day alcohol use ( p = 0.0039 ) and binge drinking episodes ( p = 0.0021 ) over the 48 month follow-up period . Women in the experimental group who became pregnant during the follow-up period had the most dramatic decreases in alcohol use . A logistic regression model based on a 20 % or greater reduction in drinking found an odds ratio of 1.93 ( confidence interval 1.07 - 3.46 ) in the sample exposed to physician intervention . Age , smoking , depression , conduct disorder , antisocial personality disorder , and illicit drug use did not reduce drinking significantly . No significant differences were found in health care utilization and health status between groups . CONCLUSIONS This trial provides the first direct evidence that brief intervention is associated with sustained reductions in alcohol consumption by women of childbearing age . The results have enormous implication s for the U.S. health care system AIMS To examine the prevalence of different substances used by adolescents admitted to hospital emergency departments ( ED ) ; to evaluate the impact of an ED based brief intervention ( BI ) on hospital events ; to compare outcomes for those using " alcohol alone " , " alcohol plus illicit+/-licit drugs " ( " alcohol plus " ) , or " other drugs " excluding alcohol , and investigate the relationship between hazardous alcohol consumption patterns and hospital events . DESIGN We used hospital record linkage to follow-up a r and omised control trial cohort . PARTICIPANTS Adolescents ( 12 - 19 years ) recruited in ED with presentations involving alcohol or other drugs ( AOD ) : 67 received usual care and 60 a BI that facilitated attendance at community drug agencies . MEASUREMENTS Drug-use categories were assigned from the substances used at the baseline presentation . Outcomes were assessed as hospital admissions plus ED presentations in the 12-month post-intervention . " Hazardous " alcohol use was categorised via the AUDIT-3 . RESULTS The drug-use categories were " alcohol alone " ( n=67 , 53 % ) , " alcohol plus " ( n=31 , 24 % ) and " other drugs " ( n=28 , 22 % ) . In the 12-month post-intervention , the r and omisation groups had similar numbers of AOD hospital events . A Cox regression showed that in the usual care but not the BI group , for " other drugs " there was a 8-fold increased hazard ( " risk " ) of an AOD hospital event compared with " alcohol alone " and a 10-fold increase compared to ' alcohol plus ' . Each pre-recruitment AOD event doubled the hazard of an AOD event . For the BI group , these were not significant predictors . The " other drugs " group had more AOD events than either of the other groups . " Hazardous " ( 77 % ) alcohol use was common but was not a predictor of AOD hospital events . CONCLUSIONS BI can be delivered in ED and reduce hospital AOD morbidity associated with the use of drugs other than alcohol . Interventions should focus on those with prior AOD events and " other drugs " presentations BACKGROUND Because 40 % of motor vehicle fatalities in the United States are alcohol-related , interventions delivered by trauma clinicians targeted to reduce drinking are of particular importance to public health . The objective of this study was to test the effectiveness of hospital-based brief intervention strategies to reduce alcohol consumption and other health-related outcomes in the year after an alcohol-related vehicular injury . Brief interventions are clinical ly based strategies including assessment and direct feedback about drinking alcohol , goal setting , behavioral modification techniques , and the use of a self-help manual . METHODS The study was a r and omized controlled trial of two types of brief intervention with a 12-month follow-up . Participants with alcohol-related vehicular injury who were admitted to Level I trauma centers were eligible for enrollment . Enrolled participants were r and omized to a control , simple advice , or brief counseling condition . Primary outcome variables were alcohol consumption ( st and ard drinks/month , binges/month ) , adverse driving events ( driving citations , traffic crashes ) , and changes in health status ( hospital and emergency department admissions ) . RESULTS The study enrolled 187 participants at baseline and retained 100 across 12 months . Participants had a significant decrease in alcohol consumption and traffic citations at 12 months as compared with baseline . Mean st and ard drinks/month declined from 56.80 ( SD 63.89 ) at baseline to 32.10 ( SD 53.20 ) at 12 months . Mean binges/month declined from 5.79 ( SD 6.98 ) at baseline to 3.21 ( SD 6.17 ) at 12 months . There were no differences in alcohol consumption , adverse driving events , or health status by condition . CONCLUSIONS Whether the reductions in alcohol consumption and traffic citations were a result of the crash , hospitalization for injury , screening for alcohol use , or combination of these factors is difficult to determine . Further work is needed to underst and the mechanisms involved in reductions of health-related outcomes and the role of brief intervention in this population BACKGROUND Type 2 diabetes mellitus is increasingly common , primarily because of increases in the prevalence of a sedentary lifestyle and obesity . Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known . METHODS We r and omly assigned 522 middle-aged , overweight subjects ( 172 men and 350 women ; mean age , 55 years ; mean body-mass index [ weight in kilograms divided by the square of the height in meters ] , 31 ) with impaired glucose tolerance to either the intervention group or the control group . Each subject in the intervention group received individualized counseling aim ed at reducing weight , total intake of fat , and intake of saturated fat and increasing intake of fiber and physical activity . An oral glucose-tolerance test was performed annually ; the diagnosis of diabetes was confirmed by a second test . The mean duration of follow-up was 3.2 years . RESULTS The mean ( + /-SD ) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group ; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group ( P<0.001 for both comparisons between the groups ) . The cumulative incidence of diabetes after four years was 11 percent ( 95 percent confidence interval , 6 to 15 percent ) in the intervention group and 23 percent ( 95 percent confidence interval , 17 to 29 percent ) in the control group . During the trial , the risk of diabetes was reduced by 58 percent ( P<0.001 ) in the intervention group . The reduction in the incidence of diabetes was directly associated with changes in lifestyle . CONCLUSIONS Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects Integrating health promotion into daily clinical practice is a challenging undertaking . This project was a prospect i ve trial of a brief physician intervention program , performed as part of routine patient care , that addressed six areas of patients ' lifestyle risks ( nutrition , exercise , alcohol use , smoking , stress , and seat belt use ) . The components of the program were lifestyle assessment , physician prescription of lifestyle change , and educational material s. Patients visiting a family practice residency model office for any reason were selected to receive all program components , parts of the program , or no program components . Lifestyle behavior changes over the ensuing four-week period were measured for all groups by a structured phone interview . Patients who received one or more components of the program reported significantly more change at follow-up than those who received no program components ( P = .001 ) ; the greatest change was seen in the group that received all of the program components . Demographic variables that were significantly related to a higher degree of change were female sex , previous contact with the physician , and being married . In this sample age , income , and education were not related to behavior change . Motivation to change -- an expressed desire to work on a given lifestyle area -- was a stronger predictor of change than any demographic variable We evaluated the 12-month outcomes of a brief intervention , enhanced by a consistent support person , which aim ed to facilitate referral attendance for substance use treatment following a hospital alcohol or other drug ( AOD ) presentation . Outcomes were assessed as : attendance for substance use treatment ; the number of hospital AOD ED presentations ; change in AOD consumption and psychological wellbeing ( GHQ-12 ) . We recruited 127 adolescents , with 60 r and omised to the intervention and 67 receiving usual care . At 12 months , 87 ( 69 % ) were re-interviewed . Significantly more of the intervention than the usual care group ( 12 versus 4 ) had attended a treatment agency . Excluding the index presentations , there were 66 AOD hospital presentations post intervention , with the proportion of AOD events falling for the intervention group , whilst no change occurred for the usual care group . Irrespective of r and omisation , those who attended for substance use treatment had a greater decline in total self-reported drug use than the remainder . Both intervention and usual care groups had improved GHQ-12 scores by 12 months , with reduction in GHQ scores correlated with reduced drug use . In conclusion , while brief intervention in ED only has limited success in facilitating adolescents to attend for subsequent AOD treatment , it can significantly reduce the number of AOD related ED presentations 1 . We assessed whether a lifestyle modification programme implemented by nurse counsellors in a general practice setting would improve blood pressure ( BP ) control in treated hypertensive patients CONTEXT There is little information on the extent of persistent pain across cultures . Even though pain is a common reason for seeking health care , information on the frequency and impacts of persistent pain among primary care patients is inadequate . OBJECTIVE To assess the prevalence and impact of persistent pain among primary care patients . DESIGN AND SETTING Survey data were collected from representative sample s of primary care patients as part of the World Health Organization Collaborative Study of Psychological Problems in General Health Care , conducted in 15 centers in Asia , Africa , Europe , and the Americas . PARTICIPANTS Consecutive primary care attendees between the age of majority ( typically 18 years ) and 65 years were screened ( n = 25 916 ) and stratified r and om sample s interviewed ( n = 5438 ) . MAIN OUTCOME MEASURES Persistent pain , defined as pain present most of the time for a period of 6 months or more during the prior year , and psychological illness were assessed by the Composite International Diagnostic Interview . Disability was assessed by the Groningen Social Disability Schedule and by activity-limitation days in the prior month . RESULTS Across all 15 centers , 22 % of primary care patients reported persistent pain , but there was wide variation in prevalence rates across centers ( range , 5.5%-33.0 % ) . Relative to patients without persistent pain , pain sufferers were more likely to have an anxiety or depressive disorder ( adjusted odds ratio [ OR ] , 4.14 ; 95 % confidence interval [ CI ] , 3.52 - 4.86 ) , to experience significant activity limitations ( adjusted OR , 1.63 ; 95 % CI , 1.41 -1.89 ) , and to have unfavorable health perceptions ( adjusted OR , 1.26 ; 95 % CI , 1.07 - 1.49 ) . The relationship between psychological disorder and persistent pain was observed in every center , while the relationship between disability and persistent pain was inconsistent across centers . CONCLUSIONS Persistent pain was a commonly reported health problem among primary care patients and was consistently associated with psychological illness across centers . Large variation in frequency and the inconsistent relationship between persistent pain and disability across centers suggests caution in drawing conclusions about the role of culture in shaping responses to persistent pain when comparisons are based on patient sample s drawn from a limited number of health care setting s in each culture AIMS To examine the long-term impact of brief and early interventions for hazardous and harmful alcohol consumption . DESIGN A 9-month and 10-year follow-up of subjects recruited into a r and omized controlled trial of a range of alcohol-related brief interventions . SETTING General practice s , the outpatient or acute care services of a major city hospital , and a privately run health screening programmeme . PARTICIPANTS The cohort of 554 ( non-dependent ) hazardous and harmful drinkers recruited into the Australian arm of the Phase II World Health Organization collaborative project on identification and treatment of persons with harmful alcohol consumption . INTERVENTION The effectiveness of three forms of intervention , ranging from 5 to 60 minutes in duration , were compared with a no-treatment control condition . MEASUREMENTS Included drinking behaviour and biological markers of alcohol use . In addition , at 10 years subjects were asked about symptoms of diagnosable alcohol use disorders and their experience of alcohol-related psychological , social and physical harm . Mortality was also assessed . FINDINGS Results provide further evidence for the short-term effectiveness of alcohol-related brief interventions . In comparison to controls , subjects offered intervention : ( 1 ) report significantly lower consumption ; and ( 2 ) less unsafe drinking at 9-month follow-up . The intensity of intervention was not related to the amount of change in drinking behaviour . Analysis at 10 years failed to find any differences in outcomes between intervention and control groups in median consumption , mean reduction in consumption from baseline to follow-up , mortality and ICD-10 diagnoses of alcohol dependence or harmful alcohol use . CONCLUSIONS This study failed to find evidence that brief advice and counselling without regular follow-up and reinforcement can sustain significant long-term reductions in drinking behaviour at 10-year follow-up The pooled results of 99 subjects from our Veterans Affairs population show that naltrexone-treated subjects had a greater reduction in alcohol craving , number of drinking days , and alcoholic relapse rates when compared with placebo-treated subjects . Based on our findings and results from other double-blind trials of naltrexone , we conclude that naltrexone is a safe and useful adjunct in the rehabilitation of alcohol-dependent patients . Increased baseline levels of psychological distress and craving as well as higher levels of somatic distress , anxiety , phobic anxiety , and obsessive-compulsive symptoms predicted an increased number of drinking days during the study . Significant interactions between naltrexone treatment , initial craving , and somatic distress suggest that naltrexone may be useful for subjects who present with high levels of craving and somatic symptoms BACKGROUND : The objective of this study was to determine the effects of a brief primary care provider-delivered counseling intervention on the reduction of alcohol consumption by high-risk drinkers . The intervention was implemented as part of routine primary care medical practice . METHODS : We performed a controlled clinical trial with 6- and 12-month follow-up . Three primary care practice s affiliated with an academic medical center were r and omly assigned to special intervention ( SI ) or usual care ( UC ) . A total of 9,772 primary care patients were screened for high-risk drinking . A fourth site was added later . From the group that was screened , 530 high-risk drinkers entered into the study , with 447 providing follow-up at 12 months . The intervention consisted of brief ( 5–10 minute ) patient-centered counseling plus an office system that cued providers to intervene and provided patient educational material s. RESULTS : At 12-month follow-up , after controlling for baseline differences in alcohol consumption , SI participants had significantly larger changes ( P=.03 ) in weekly alcohol intake compared to UC ( SI=−5.7 drinks per week ; UC=−3.1 drinks per week ) , and of those who changed to safe drinking at 6 months more SI participants maintained that change at 12 months than UC . CONCLUSIONS : Project Health provides evidence that screening and very brief ( 5–10 minute ) advice and counseling delivered by a patient ’s personal physician or nurse practitioner as a routine part of a primary care visit can reduce alcohol consumption by high-risk drinkers Symptoms of depression have been associated with increased smoking prevalence and failure to quit smoking in several cross-sectional and population -based studies . Few studies , however , have prospect ively examined the ability of current symptoms of depression to predict failure to quit smoking in treatment-motivated smokers . Pretreatment depressed mood was assessed by 3 different methods in 3 separate sample s , 2 of which comprised smokers receiving combined pharmacological and behavioral treatments and a 3rd in which smokers received self-help material s only . In all studies , time in days from quit day until the 1st cigarette was ascertained to document survival . Survival analyses showed that in all 3 studies survival time was significantly and negatively related to measures of even very low levels of pretreatment depressed mood . Results were replicated across 3 independent sample s and were robust and uniformly clear , indicating that low levels of depressive symptoms assessed at baseline predict time to 1st cigarette smoked after attempted quitting In a continuing screening and intervention programme in Malmó , elevated serum-gamma-glutamyltransferase ( GGT ) values were used for selection of heavy drinkers . The study population consisted of 585 individuals born 1926 - 1933 with two consecutive GGT values in the upper decile of the GGT distribution , r and omly allocated either to an intervention group of to a control group . The subjects in the intervention group were further investigated and 75 % of them were judged to have elevated GGT values caused by alcohol consumption . These individuals were repeatedly encouraged to lower their overall alcohol consumption and GGT measurements were used as biofeedback method in the treatment program . The controls were informed by letter to be restrictive with their alcohol consumption and that they should receive new invitations for measurements of their liver enzymes after 2 , 4 , and 6 years . The intervention and control groups were well matched and followed over a 2 - 6-year period . Two and 4 years after the screening investigation , the GGT values in both groups were significantly decreased . There were differences , however , between the two groups with regard to sick absenteeism , hospitalization , and mortality . A significant reduction was found in sick absence during 4 years by 80 % , in hospital days during 5 years by 60 % , and in mortality during 6 years by 50 % in the intervention group compared with the control group . Thus , the intervention program was effective in preventing medico-social consequences of heavy drinking OBJECTIVE To evaluate the effectiveness of medical counselling in reducing alcohol consumption in male heavy drinkers . DESIGN A controlled , r and omised , simple-blind intervention study . SETTING Four Primary Care teams in Area 10 , Madrid . PATIENTS 152 men who attended for on-dem and treatment from the four teams and whose alcohol consumption was over 21 International Units ( IU ) a week . INTERVENTION Brief medical counselling backed up by didactic material . Two question naires on alcohol consumption in IU , consumption habits and problems related to alcohol were administered , separated by an interval of between 6 and 18 months . Non-parametric tests for paired sample s ( McNemar ) were applied . RESULTS 60 % answered the second question naire . Neither sociodemographic nor health habit differences were found between those who responded and those who did not , except for social class . There were no appreciable differences between the intervention and control groups . The percentage of drinkers above 35 IU decreased significantly in the intervention group . CONCLUSIONS The intervention was clearly effective in reducing the percentage of drinkers whose weekly consumption was over 35 IU The impact of a transdermal nicotine patch on smokers ' craving for cigarettes and reactivity to smoking cues was investigated . Sixty-one smokers were assessed during 2 sessions separated by 6 hr . Cue reactivity to imaginal and in vivo smoking and nonsmoking stimuli was evaluated during both sessions . During the interval between sessions , participants were abstinent from cigarettes and wore either a nicotine transdermal ( 21 mg ) or placebo patch . In both sessions , exposure to in vivo and imaginal smoking stimuli elicited cue-specific increases in craving , negative affect , vividness , heart rate , and skin conductance . The nicotine patch attenuated craving and other effects induced by abstinence from cigarettes but had no selective impact on craving or any other reaction elicited by smoking cues . These results are discussed in terms of models of craving and clinical implication s of transdermal nicotine for craving reduction BACKGROUND In a health survey of more than 21,000 men and women ages 12 - 62 years , measurement of gamma-glutamyltransferase ( GGT ) and answers on five questions on alcohol consumption were used as a basis for selecting an intervention population of early-stage risk drinkers . Altogether 290 men and 48 women met the criteria for inclusion . METHODS The 338 subjects were r and omized to a control group and two intervention groups . The minor intervention consisted of a single consultation during which possible reasons for the elevated GGT were discussed and a pamphlet with advice on changes in drinking habits was h and ed out . In the major intervention group the intervention was directed more specifically toward alcohol , with an extensive interview on drinking habits . In addition , the subjects in this group were offered follow-up consultations for new measurements of GGT . RESULTS All three groups were examined after 1 year with GGT determination and an interview on change in drinking habits during the past year . At follow-up , significant decreases in mean GGT ( 26.5 U/liter ) and self-reported alcohol intake ( 24.7 g/day ) were observed in the intervention groups compared with the control group . No significant differences were , however , observed between the intervention groups . CONCLUSION The study indicates that modest and simple interventions may yield important changes in drinking habits in early-stage risk drinkers BACKGROUND High-risk alcohol use in persons 18 to 30 years of age is a critical public health problem . It is the number 1 cause of death in this population . This article reports the results of a sub analysis of young adults ( aged 18 to 30 years ) who participated in Project TrEAT ( Trial of Early Alcohol Treatment ) conducted in the offices of 64 primary care physicians located in 10 counties in southern Wisconsin . METHODS Project TrEAT was a r and omized clinical trial design ed to test the efficacy of a brief intervention protocol to reduce alcohol use , improve health status , and decrease health care utilization . A total of 226 young adults were r and omly assigned to either a usual care or brief intervention group . RESULTS There were no significant differences between the 2 groups at baseline on a number of potential confounders . During the 4-year follow-up period , there were significant reductions in number of persons drinking more than 3 drinks per day , average 7-day alcohol use , number of persons drinking 6 or more drinks per occasion , and number of binge drinking episodes in the previous 30 days ( P < .01 to P < .001 ) . There were also significant differences ( P < .05 ) in emergency department visits ( 103 vs 177 ) , motor vehicle crashes ( 9 vs 20 ) , total motor vehicle events ( 114 vs 149 ) , and arrests for controlled substance or liquor violation ( 0 vs 8) . CONCLUSION In this 4-year sub analysis of young adults who participated in Project TrEAT , we found long-term reductions in high-risk drinking behaviors and consequences . The findings of this study support more widespread implementation of brief interventions in primary care setting OBJECTIVE Alcoholism is the leading risk factor for injury . The authors hypothesized that providing brief alcohol interventions as a routine component of trauma care would significantly reduce alcohol consumption and would decrease the rate of trauma recidivism . METHODS This study was a r and omized , prospect i ve controlled trial in a level 1 trauma center . Patients were screened using a blood alcohol concentration , gamma glutamyl transpeptidase level , and short Michigan Alcoholism Screening Test ( SMAST ) . Those with positive results were r and omized to a brief intervention or control group . Reinjury was detected by a computerized search of emergency department and statewide hospital discharge records , and 6- and 12-month interviews were conducted to assess alcohol use . RESULTS A total of 2524 patients were screened ; 1153 screened positive ( 46 % ) . Three hundred sixty-six were r and omized to the intervention group , and 396 to controls . At 12 months , the intervention group decreased alcohol consumption by 21.8+/-3.7 drinks per week ; in the control group , the decrease was 6.7+/-5.8 ( p = 0.03 ) . The reduction was most apparent in patients with mild to moderate alcohol problems ( SMAST score 3 to 8) ; they had 21.6+/-4.2 fewer drinks per week , compared to an increase of 2.3+/-8.3 drinks per week in controls ( p < 0.01 ) . There was a 47 % reduction in injuries requiring either emergency department or trauma center admission ( hazard ratio 0.53 , 95 % confidence interval 0.26 to 1.07 , p = 0.07 ) and a 48 % reduction in injuries requiring hospital admission ( 3 years follow-up ) . CONCLUSION Alcohol interventions are associated with a reduction in alcohol intake and a reduced risk of trauma recidivism . Given the prevalence of alcohol problems in trauma centers , screening , intervention , and counseling for alcohol problems should be routine Separate and combined effects of nicotine and the nicotinic antagonist mecamylamine were studied in 32 healthy volunteer smokers after overnight abstinence from smoking . Subjects participated in three sessions ( 3 h each ) , during which they wore skin patches delivering either 0 mg/24 h , 21 mg/24 h or 42 mg/24 h nicotine . Thirty-two subjects were r and omly assigned to two groups receiving oral mecamylamine hydrochloride ( 10 mg ) vs. placebo capsules . Two and one-half hours after drug administration , subjects were allowed to smoke ad lib , rating the cigarettes for rewarding and aversive effects . Transdermal nicotine produced a dose-related reduction in the subjective rewarding qualities of smoking . Nicotine also reduced craving for cigarettes and this effect was attenuated , but not eliminated , by mecamylamine . Mecamylamine blocked the discriminability of high vs. low nicotine puffs of smoke , and increased nicotine intake substantially during the ad lib smoking period . Some of the psychophysiological effects of each drug ( elevation in blood pressure from nicotine , sedation and decreased blood pressure from mecamylamine ) were offset by the other drug . The results supported the hypothesis that nicotine replacement can alleviate tobacco withdrawal symptoms even in the presence of an antagonist such as mecamylamine . Mecamylamine did not precipitate withdrawal beyond the level associated with overnight cigarette deprivation , suggesting its effects were primarily due to off setting the action of concurrently administered nicotine as opposed to blocking endogenous cholinergic transmission BACKGROUND Providing doctors with new research findings or clinical guidelines is rarely sufficient to promote changes in clinical practice . An implementation strategy is required to provide clinicians with the skills and encouragement needed to alter established routines . AIM To evaluate the effectiveness and cost-effectiveness of different training and support strategies in promoting implementation of screening and brief alcohol intervention ( SBI ) by general practitioners ( GPs ) . METHOD Subjects were 128 GPs , one per practice , from the former Northern and Yorkshire Regional Health Authority , who agreed to use the ' Drink-Less ' SBI programme in an earlier dissemination trial . GPs were stratified by previous marketing conditions and r and omly allocated to three intensities of training and support : controls ( n = 43 ) received the programme with written guidelines only , trained GPs ( n = 43 ) received the programme plus practice -based training in programme usage , trained and supported GPs ( n = 42 ) received the programme plus practice -based training and a support telephone call every two weeks . GPs were requested to use the programme for three months . Outcome measures included proportions of GPs implementing the programme and numbers of patients screened and intervened with . RESULTS Seventy-three ( 57 % ) GPs implemented the programme and screened 11,007 patients for risk drinking . Trained and supported GPs were significantly more likely to implement the programme ( 71 % ) than controls ( 44 % ) or trained GPs ( 56 % ) ; they also screened , and intervened with , significantly more patients . Costs per patient screened were : trained and supported GPs , 1.05 Pounds ; trained GPs , 1.08 Pounds ; and controls , 1.47 Pounds . Costs per patient intervened with were : trained and supported GPs , 5.43 Pounds ; trained GPs , 6.02 Pounds ; and controls , 8.19 Pounds . CONCLUSION Practice -based training plus support telephone calls was the most effective and cost-effective strategy to encourage implementation of SBI by GPs The subjects were recruited from participants in a health examination of r and om sample s of the adult population in Stockholm county . Those aged 18 - 64 years who admitted a high alcohol consumption ( greater than 40 g 100 % ethanol/day ) among men and greater than 30 g among women ) or had an elevated value of serum-gammaglutamyltransferase ( GGT ) ( cut-off point 1.0 microkatal/l for men and 0.6 microkatal/l for women ) or had certain other indications of a high alcohol consumption were included . More severe cases , and those with an elevated GGT due to reasons other than alcohol , were excluded . The remaining subjects , 70 men and 13 women , were allocated at r and om to either an intervention or a comparison group . An elevated GGT was the main inclusion criteria . The subjects in the comparison group were advised by the general practitioner to cut their alcohol consumption , while those in the intervention group made further visits to their general practitioner , who gave general support and used an elevated GGT as an indication of the recent level of alcohol consumption at consecutive visits . There were three visits on average , so we are comparing a group receiving advice with a group receiving further minimal intervention . At the one-year follow-up there were greater , however not significant , reduction in GGT-level , in self-reported alcohol consumption and in a ' problem index ' in the minimal intervention group than in the comparison group BACKGROUND Few studies have estimated the economic costs and benefits of brief physician advice in managed care setting s. OBJECTIVE To conduct a benefit-cost analysis of brief physician advice regarding problem drinking . DESIGN Patient and health care costs associated with brief advice were compared with economic benefits associated with changes in health care utilization , legal events , and motor vehicle accidents using 6- and 12-month follow-up data from Project TrEAT ( Trial for Early Alcohol Treatment ) , a r and omized controlled clinical trial . SUBJECTS 482 men and 292 women who reported drinking above a threshold limit were r and omized into control ( n = 382 ) or intervention ( n = 392 ) groups . MEASURES Outcomes included alcohol use , emergency department visits , hospital days , legal events , and motor vehicle accidents . RESULTS No significant differences between control and intervention subjects were present for baseline alcohol use , age , socioeconomic status , smoking , depression or anxiety , conduct disorders , drug use , crimes , motor vehicle accidents , or health care utilization . The total economic benefit of the brief intervention was $ 423,519 ( 95 % CI : $ 35,947 , $ 884,848 ) , composed of $ 195,448 ( 95 % CI : $ 36,734 , $ 389,160 ) in savings in emergency department and hospital use and $ 228,071 ( 95 % CI : -$191,419 , $ 757,303 ) in avoided costs of crime and motor vehicle accidents . The average ( per subject ) benefit was $ 1,151 ( 95 % CI : $ 92 , $ 2,257 ) . The estimated total economic cost of the intervention was $ 80,210 , or $ 205 per subject . The benefit-cost ratio was 5.6:1 ( 95 % CI : 0.4 , 11.0 ) , or $ 56,263 in total benefit for every $ 10,000 invested . CONCLUSIONS These results offer the first quantitative evidence that implementation of a brief intervention for problem drinkers can generate positive net benefit for patients , the health care system , and society OBJECTIVE Individuals with impaired glucose tolerance ( IGT ) have a high risk of developing NIDDM . The purpose of this study was to determine whether diet and exercise interventions in those with IGT may delay the development of NIDDM , i.e. , reduce the incidence of NIDDM , and thereby reduce the overall incidence of diabetic complications , such as cardiovascular , renal , and retinal disease , and the excess mortality attributable to these complications . RESEARCH DESIGN AND METHODS In 1986 , 110,660 men and women from 33 health care clinics in the city of Da Qing , China , were screened for IGT and NIDDM . Of these individuals , 577 were classified ( using World Health Organization criteria ) as having IGT . Subjects were r and omized by clinic into a clinical trial , either to a control group or to one of three active treatment groups : diet only , exercise only , or diet plus exercise . Follow-up evaluation examinations were conducted at 2-year intervals over a 6-year period to identify subjects who developed NIDDM . Cox 's proportional hazard analysis was used to determine if the incidence of NIDDM varied by treatment assignment . RESULTS The cumulative incidence of diabetes at 6 years was 67.7 % ( 95 % CI , 59.8–75.2 ) in the control group compared with 43.8 % ( 95 % CI , 35.5–52.3 ) in the diet group , 41.1 % ( 95 % CI , 33.4–49.4 ) in the exercise group , and 46.0 % ( 95 % CI , 37.3–54.7 ) in the diet-plus-exercise group ( P < 0.05 ) . When analyzed by clinic , each of the active intervention groups differed significantly from the control clinics ( P < 0.05 ) . The relative decrease in rate of development of diabetes in the active treatment groups was similar when subjects were stratified as lean or overweight ( BMI < or ≥ 25 kg/m2 ) . In a proportional hazards analysis adjusted for differences in baseline BMI and fasting glucose , the diet , exercise , and diet-plus-exercise interventions were associated with 31 % ( P < 0.03 ) , 46 % ( P < 0.0005 ) , and 42 % ( P < 0.005 ) reductions in risk of developing diabetes , respectively . CONCLUSIONS Diet and /or exercise interventions led to a significant decrease in the incidence of diabetes over a 6-year period among those with IGT OBJECTIVE The study aim was to test whether a brief motivational intervention , with or without a booster session , would improve drinking-related outcomes more than st and ard Emergency Department ( ED ) treatment . METHOD The study population consisted of 539 ( 78 % male ) injured patients treated in the ED and discharged to the community following their treatment . Injured patients met inclusion criteria if they were assessed as hazardous or harmful drinkers by scoring eight or more on the AUDIT and /or having alcohol in their system at the time of their injury or ED visit . Patients were r and omly assigned to either st and ard care ( SC ) , brief intervention ( BI ) or brief intervention plus a booster session ( BIB ) . At 1-year follow-up , 447 patients ( 83 % of the sample ) were re-interviewed to measure alcohol-related negative consequences , injuries and drinking . RESULTS Patients receiving BIB , but not B1 patients , reduced alcohol-related negative consequences and alcohol-related injuries more than did those in the SC group . All three groups reduced their days of heavy drinking . Patients with histories of hazardous drinking responded to BIB , whether or not they had consumed alcohol prior to their injury . CONCLUSIONS Together , these results indicate that the effects of a booster session that is added to a brief intervention in the ED can be helpful to injured patients with a history of hazardous or harmful drinking , irrespective of whether they have consumed alcohol prior to their injury INTRODUCTION The study was design ed to test a brief intervention for reducing alcohol consumption among moderate to heavy ( hazardous ) drinkers in a busy HMO primary care setting . METHODS In a r and omized controlled trial , hazardous drinkers ( n = 516 ) were identified by the AUDIT screening question naire . Intervention included brief clinician advice ( 30 seconds ) , a 15-minute motivational session by counselors , and printed material s. RESULTS At six-month follow-up , intervention subjects reported fewer total st and ard drinks in the past three months ( 176 versus 216 , P = .04 , one-tailed ) and fewer drinking days per week ( 2.8 versus 3.3 , P = .02 ) than controls , but similar drinks per drinking day ( 3.3 versus 3.5 ; P = .13 ) . At 12 months , intervention subjects again reported fewer drinking days per week ( 2.7 versus 3.1 ; P = .04 ) than controls , but similar numbers of st and ard drinks ( 157 versus 179 ; P = .13 ) and drinks per drinking day ( 3.6 versus 3.3 ; P = .20 ) . Intervention subjects were somewhat more likely than controls to report drinking within daily recommended limits ( < or = 3 for men , < or = 2 for women ) at both six months ( 79 % versus 71 % ; P = .06 ) and 12 months ( 80 % versus 73 % ; P = .07 ) , but did not differ significantly from controls on other drinking outcomes ( percent abstinent , frequency of drinking > or = 6 drinks per drinking occasion , estimated peak blood alcohol concentration ) , or use of medical care in the year following intervention . CONCLUSIONS A one-time , brief motivational intervention using minimal clinician time supplemented by trained counselors result ed in a modest reduction in frequency of alcohol consumption in a busy primary care population . Future research should focus on strengthening and maintaining intervention effects Purpose sTo test the effectiveness of motivational interviewing in a population of hazardous drinkers utilizing community health care centers in rural southeastern Idaho . Data sources This study targeted rural people at risk for alcohol dependence utilizing low-income community health care centers in rural southeastern Idaho . The Alcohol Use Disorders Identification Test ( AUDIT ) was used to screen interested clients ' alcohol use . Clients achieving an AUDIT score indicating hazardous alcohol use were recruited into the study and r and omized into a control or treatment group . Twenty-six hazardous drinkers attending five low-income community health centers participated in the study . The experimental group participated in one motivational interviewing session with the investigator , a family nurse practitioner ( NP ) . The comparison group received no treatment . Alcohol use was tracked for 6 weeks after successful recruitment into the program . Conclusions Participants in the study significantly decreased their average number of drinks per day . At time 1 ( pretreatment ) , the control group drank 4.37 drinks per day and the treatment group drank 4.65 drinks per day . At time 2 ( posttest ) , the control group drank 3.77 drinks per day and the treatment group drank 1.95 drinks per day . The effects of the motivational interviewing treatment on hazardous drinking also were measured by serum gamma-glutamyltransferase ( GGT ) , a liver function test . There was also a significant decrease in the GGT from pretest to posttest in the treatment group . Implication s for practice The results of this investigation found that motivational interviewing shows promise as an effective intervention for hazardous drinkers attending low-income community clinics . Although other possible explanations could be postulated for the positive changes in sample participants , the data indicate that the motivational interviewing approach was responsible for a significant portion of the positive changes within the current sample . The information collected from the study adds to the literature on hazardous drinking , research , and treatment of this significant problem . Negotiating change in behavior is part of the practice of NPs . People struggling with alcohol use are more likely to encounter NPs , family doctors , or social workers than counselors specializing in alcohol treatment . Motivational interviewing is specifically design ed for preparing people for change . Because most people resist being told what to do , that is , “ you have to stop drinking , ” use of motivational interviewing principles can decrease resistance and optimize change . Additionally , identifying and intervening with hazardous drinking in a primary care setting can reduce healthcare costs and reduce the stigma of specialist care . Adding this valuable communication skill to the competencies of NPs is important to both clients and NPs OBJECTIVE Alcohol biomarkers are being developed to improve a physician 's ability to identify and intervene with patients with chronic medical problems adversely affected by heavy alcohol use . This article reports the findings of a brief intervention trial which included feedback to patients of their carbohydrate-deficient transferrin ( CDT ) test results . METHOD A pilot study was conducted to test the efficacy of brief clinician advice to reduce alcohol use and improve health status in a sample of 151 patients being treated for Type 2 diabetes and hypertension . The intervention included informing patients of their CDT levels . The patients were r and omized to a usual care or brief intervention group . RESULTS There were no significant differences at baseline between the two groups in alcohol use , CDT levels , addiction rates , age , gender , socioeconomic status or health status measures . Following brief intervention , significant differences were observed in the intervention group in alcohol use and CDT : The proportion of heavy drinkers at the 12-month follow-up compared with baseline decreased from 35.8 % to 24.7 % in the intervention group , with no change in the control group ( p < .044 ) . CDT levels decreased as well from 2.79 % to 2.41 % ( 16 % change ) in the control group and 3.05 % to 2.35 % ( 28 % change ) in the intervention group , with significantly more intervention-group patients reducing their CDT level by at least 25 % ( p < .006 ) . CONCLUSIONS The study provides new information suggesting brief intervention , combined with feedback on CDT levels , can reduce alcohol use and % CDT in a sample of primary care patients being treated for Type 2 diabetes and hypertension AIMS To assess the impact of a brief intervention on antepartum alcohol consumption . DESIGN A r and omized clinical trial . SETTING The obstetrics practice s of the Brigham and Women 's Hospital in Boston , MA , USA . PARTICIPANTS Two hundred and fifty eligible women initiating prenatal care . INTERVENTION A comprehensive assessment of alcohol use ( assessment only , AO ) or the same comprehensive assessment with a brief intervention ( BI ) . MEASUREMENT Demographic background and obstetric history of subjects , current and lifetime use of alcohol and substances , composite Addiction Severity Index scores , and antepartum alcohol use . FINDINGS Of the 250 , 247 ( 99 % ) subjects provided information on their antepartum drinking . Both the AO and BI groups had reductions in antepartum alcohol consumption , but differences in reductions by group were not statistically significant ( p > 0.05 ) . Risk of antepartum drinking after either the AO or BI was increased nearly threefold if the subject had any prenatal alcohol consumption before assessment ( p = 0.0001 ) . For the 143 subjects who were abstinent pre- assessment , however , those who received the BI maintained higher rates of abstinence ( 86 % versus 72 % , p = 0.04 ) . CONCLUSIONS After a comprehensive assessment of alcohol use , subjects in both the AO and BI groups reduced their antepartum alcohol consumption . The importance of screening for prenatal alcohol use is underscored by the findings that any prenatal alcohol consumption increases the risk of continued antepartum drinking Problem drinking is common among patients in primary medical care , but often unrecognized . Brief physician interventions can be helpful , but several barriers hinder their adoption in practice , notably a lack of time . We conducted a r and omized pilot study of written behavioral contracts that patients wrote with help from a computer program . In eight family medicine practice s , 2684 patients were approached and 2399 screened with the Alcohol Use Disorders Identification Test ( AUDIT ) . Of those , 186 screened positive , 154 were eligible , and 80 enrolled . Follow‐up interviews were completed with 69 ( 86 % ) . At 12 months , the AUDIT and Addiction Severity Index alcohol scores decreased nonsignificantly more in the intervention group than in the controls . The study demonstrated that computer‐based interventions are acceptable to patients and physicians , feasible in busy primary care practice s , and have effect sizes comparable to those of physician‐based interventions . Computer‐based interventions may be an effective and efficient tool to enhance identification of and intervention with problem drinkers in primary care Present methods to screen for alcohol abuse are generally obtrusive and result in referral to services that deal mainly with alcoholics . These factors deter physicians from identifying alcohol abuse patients at an early stage . In the present study , 81 % of all primary care physicians of a single city evaluated ( i ) the efficiency and the acceptability of a nonobtrusive screening method for the identification of problem drinkers and ( ii ) the effectiveness of brief cognitive behavioral counseling given by a nurse in a lifestyle context . Patients ( n = 15,686 ) attending the private practice s of 42 primary -care physicians were asked four alcohol-neutral trauma questions in the reception area . Physicians asked about alcohol use and alcohol-related problems only to patients with previous trauma . Problem drinkers by defined criteria were offered an appointment with a nurse who , by r and om assignment , gave either 3-hr of cognitive behavioral counseling over 1 year or simply advised patients to reduce their alcohol intake . The screening method identified 62 - 85 % of expected number of problem drinkers in this population . Following the application of exclusion criteria , 105 problem drinkers were entered in the intervention part of the study . After 1 year , patients who received counseling showed significant reductions in reported alcohol consumption ( -70 % ; p < 0.001 ) , psychosocial problems ( -85 % ; p < 0.001 ) and serum gamma glutamyl transferase ( -32 % to -58 % ; p < 0.02 ) . Physician visits were reduced ( -34 % ; p < 0.02 ) following counseling . Patients receiving only advice showed neither reductions in psychosocial problems nor in serum gamma glutamyl transferase or physician visits , but reported a 46 % reduction ( p < 0.01 ) in alcohol consumption . Data indicate that asking patients about recent trauma is efficient and is well accepted as the first screening instrument in the identification of the problem drinker . Cost of screening per patient is under one dollar . Counseling of 3 hr given by a nurse is markedly superior ( p < 0.05 ) to simple advice in reducing alcohol consumption , objective indicators of alcohol-related morbidity , and the frequency of physician visits Transdermal nicotine in doses up to 21 mg/24 hr is used to facilitate smoking cessation . However , this dose does not achieve the nicotine plasma levels seen among heavy smokers , and underdosing may be one of the reasons for the limited efficacy of transdermal nicotine . There are some concerns about the adverse cardiovascular effects of nicotine , especially with concomitant smoking . Treatment with higher doses of transdermal nicotine has been proposed for highly dependent smokers , but the effects of such treatment on the cardiovascular system have not been determined . The objective of this study was to determine the cardiovascular effects of high‐dose transdermal nicotine with concomitant smoking OBJECTIVE Project TrEAT ( Trial for Early Alcohol Treatment ) was design ed to test the efficacy of brief physician advice in reducing alcohol use and health care utilization in problem drinkers . DESIGN R and omized controlled clinical trial with 12-month follow-up . SETTING A total of 17 community-based primary care practice s ( 64 physicians ) located in 10 Wisconsin counties . PARTICIPANTS Of the 17695 patients screened for problem drinking , 482 men and 292 women met inclusion criteria and were r and omized into a control ( n=382 ) or an experimental ( n=392 ) group . A total of 723 subjects ( 93 % ) participated in the 12-month follow-up procedures . INTERVENTION The intervention consisted of two 10- to 15-minute counseling visits delivered by physicians using a scripted workbook that included advice , education , and contracting information . MAIN OUTCOME MEASURES Alcohol use measures , emergency department visits , and hospital days . RESULTS There were no significant differences between groups at baseline on alcohol use , age , socioeconomic status , smoking status , rates of depression or anxiety , frequency of conduct disorders , lifetime drug use , or health care utilization . At the time of the 12-month follow-up , there were significant reductions in 7-day alcohol use ( mean number of drinks in previous 7 days decreased from 19.1 at baseline to 11.5 at 12 months for the experimental group vs 18.9 at baseline to 15.5 at 12 months for controls ; t=4.33 ; P<.001 ) , episodes of binge drinking ( mean number of binge drinking episodes during previous 30 days decreased from 5.7 at baseline to 3.1 at 12 months for the experimental group vs 5.3 at baseline to 4.2 at 12 months for controls ; t=2.81 ; P<.001 ) , and frequency of excessive drinking ( percentage drinking excessively in previous 7 days decreased from 47.5 % at baseline to 17.8 % at 12 months for the experimental group vs 48.1 % at baseline to 32.5 % at 12 months for controls ; t=4.53 ; P<.001 ) . The chi2 test of independence revealed a significant relationship between group status and length of hospitalization over the study period for men ( P<.01 ) . CONCLUSIONS This study provides the first direct evidence that physician intervention with problem drinkers decreases alcohol use and health re source utilization in the US health care system We tested whether a brief motivational interview ( MI ) would reduce alcohol-related consequences and use among adolescents treated in an emergency department ( ED ) after an alcohol-related event . Patients aged 13 to 17 years ( N = 152 ) with a positive blood alcohol concentration ( BAC ) by lab test or self-report were recruited in the ED and r and omly assigned to receive either MI or st and ard care ( SC ) . Both conditions result ed in reduced quantity of drinking during the 12-month follow-up , whereas alcohol-related negative consequences were relatively low and stayed low at follow-up . Adolescents who screened positive for problematic alcohol use at baseline reported significantly more improvement on 2 of 3 alcohol use outcomes ( average number of drinking days per month and frequency of high-volume drinking ) if they received MI compared with SC . We conclude that brief interventions are recommended for adolescents who present to an ED with an alcohol-related event and report preexisting problematic alcohol use BACKGROUND The aim of this study was to analyse and to verify the efficacy of systematic advice for alcoholism prevention , assessing the reduction of the number in risk drinkers . PATIENTS AND METHODS A multicenter r and omized controlled clinical trial was design ed , to perform in general practitioner setting , on a sample of risk drinkers ( alcohol intake > 280 g weekly , without dependence ) sent by r and om in intervention group ( systematic brief advice with support material and a five visit program during a year ) and control group ( once brief advice and a control in 1 year ) . The procedure to incorporate in both groups included physical exam , a blood test and the MALT question naire . A descriptive and analytic study on included variables was realised , assessing the percentage of drinkers who reduced alcohol intake below risk limit at the end of a year follow up , as well as the reduction intake in each group . RESULTS Of the 139 included males , 75 were in the intervention group and 64 in the control group . The percentage of patients not excluded by MALT > 10 , and /or liver disease , that finished the 1 year follow up , was 46 % , being the sample average age of 43 + /- 11.8 . Patients included in both groups were initially comparable . At the end of a year follow up there were statistically significant differences in : percentage of risk drinkers who decreased alcohol intake below 280 g weekly ( 82 % intervention group ; 47 % control group ) ; percentage of reduction in GPT , GGT , triglycerides , systolic blood pressure and the MALT question naire . CONCLUSIONS The efficacy of isolated advice of general practitioner was proved to achieve the alcohol intake reduction below the risk limit accepted in male risk drinkers without alcohol dependence . The systematic follow up during a year significantly improves the results achieved with the isolated advice AIMS Recommendations for routine alcohol screening and brief counselling intervention in primary health care rest on results from intervention efficacy studies . By conducting a pragmatic controlled trial ( PCT ) , we aim ed at evaluating the effectiveness of the WHO recommendations for screening and brief intervention ( SBI ) in general practice . METHODS A r and omized PCT ( brief counselling intervention vs no intervention ) involving 39 Danish general practitioners ( GPs ) . Systematic screening of 6897 adults led to inclusion of 906 risky drinkers , and research follow-up on 537 of these after 12 - 14 months . Outcome measures focused on patients ' acceptance of screening and intervention and their self-reported alcohol consumption . RESULTS Patient acceptance of screening and intervention -10.3 % ( N = 794 ) of the target population ( N = 7 , 691 ) explicitly refused screening . All intervention group subjects ( N = 442 ) were exposed to an instant brief counselling session while only 17.9 % of them ( 79/442 ) attended a follow-up consultation that was offered by their GP . Consumption Changes At one-year follow-up , average weekly consumption had increased by 0.7 drinks in both comparison groups . As secondary findings , we observed an indiscriminate absolute risk reduction ( ARR = 0.08 ( 95 % CI : -0.02 ; 0.18 ) ) in male binge drinking , but adverse intervention effects for women on the secondary outcomes ( binge drinking ARR = -0.30 ( 95 % CI : -0.47 ; -0.09 ) ) . CONCLUSIONS The results of brief interventions in everyday general practice performed on the basis of systematic question naire screening may fall short of theoretical expectations . When applied to non-selected groups in everyday general practice SBI may have little effect and engender diverse outcome . Women may be more susceptible to defensive reactions than men BACKGROUND This report describes the 48-month efficacy and benefit-cost analysis of Project TrEAT ( Trial for Early Alcohol Treatment ) , a r and omized controlled trial of brief physician advice for the treatment of problem drinking . METHODS Four hundred eighty-two men and 292 women , ages 18 - 65 , were r and omly assigned to a control ( n = 382 ) or intervention ( n = 392 ) group . The intervention consisted of two physician visits and two nurse follow-up phone calls . Intervention components included a review of normative drinking , patient-specific alcohol effects , a worksheet on drinking cues , drinking diary cards , and a drinking agreement in the form of a prescription . RESULTS Subjects in the treatment group exhibited significant reductions ( p < 0.01 ) in 7-day alcohol use , number of binge drinking episodes , and frequency of excessive drinking as compared with the control group . The effect occurred within 6 months of the intervention and was maintained over the 48-month follow-up period . The treatment sample also experienced fewer days of hospitalization ( p = 0.05 ) and fewer emergency department visits ( p = 0.08 ) . Seven deaths occurred in the control group and three in the treatment group . The benefit-cost analysis suggests a 43,000 dollars reduction in future health care costs for every 10,000 dollars invested in early intervention . The benefit-cost ratio increases when including the societal benefits of fewer motor vehicle events and crimes . CONCLUSIONS The long-term follow-up of Project TrEAT provides the first direct evidence that brief physician advice is associated with sustained reductions in alcohol use , health care utilization , motor vehicle events , and associated costs . The report suggests that a patient 's personal physician can successfully treat alcohol problems and endorses the implementation of alcohol screening and brief intervention in the US health care system This national pilot project commenced in 2004 . It was promoted by the Istituto Superiore di Sanità and financed by the Italian Ministry of Health . The Italian Society of General Practitioners supported implementation of the study in general medical practitioner setting s and coordination was undertaken by the Alcohol Centre of the University Hospital of Florence . The objectives of the study are to create a brief intervention package , suitable for use within the Italian primary health care system for screening and treating “ hazardous drinkers ” ; to survey alcohol consumption in a sample of the population aged 18 or over , who the general practitioners assessed as suitable for brief intervention using the project 's instruments ; to conduct an experimental trial of brief intervention procedures , with “ hazardous drinkers ” r and omly allocated to intervention or control conditions ; to assess the effectiveness of brief intervention as a primary preventive measure . The early stage of this study concentrated on creating a strong research partnership to foster the involvement of general medical practitioners on a national scale . Subsequently , re sources were devoted to the creation of the brief intervention package , including support material and the training of the general medical practitioners in its implementation The study examined the effectiveness of routine intervention in alcohol abuse by a general practitioner , with help of a laboratory test . Patients diagnosed as abusers because of high erythrocyte mean cell volume value ( MCV ) and having no other cause for it were r and omly allocated to two groups : 1 ) an intervention group , comprising 92 patients ( 69 men and 23 women ) , who were invited for follow-up at three-monthly intervals for a year ; 2 ) a control ( mini-intervention ) group , 86 patients ( 71 men and 15 women ) , who were followed-up only after 12 months . Follow-up attendance was poor , particularly in the intervention group . In general , MCV-values were unchanged in the groups at the end of the study , though there was a clear trend for the female controls to have lower values ( 101.9 fl at the start , 98.5 fl at the end , p = 0.06 ) . Altogether 11 % ( 4/38 ) of the women and 7 % ( 10/140 ) of the men had clearly reduced their alcohol consumption after one year , and this was also seen in their MCV-values . Mini-intervention , especially in women with an abnormal laboratory value , seems to be , with the help of MCV , at least as effective a way of counselling nonalcoholic abusers as a more systematic intervention BACKGROUND Alcohol as a cause of death in middle-aged patients is well-known from clinical studies . A similarly important correlation in the general population of urban middle-aged men is highly underestimated . Health screening investigations have shown that mortality related to alcohol is five times more common in non participants than in participants . From the mid-70s , the Malmoe Screening and Intervention Study ( MSIS ) commenced screening investigations including a large number of residents of Malmoe . One goal was to find intervention programs for individuals in an early development of problem drinking , thereby preventing development of serious complications of endstage alcoholism . Herein , we report on the mortality of heavy drinkers ( drinking more than 40 g alcohol/day ) who were r and omized to an intervention or control procedure and whose median survival was 13 years postentry into the MSIS . METHODS Health-screened men , aged 45 - 49 years at the initial screening examination and displaying serum gamma-glutamyltransferase ( GT ) in the top decentile of the GT distribution , were included . A total of 978 out of 11,257 participants met this criteria . A r and omized intervention and control study was performed for four years and consisted of men ( n = 667 ) who were born between 1927 - 1937 and who had two consecutive high GT values within 3 weeks along with heavy alcohol consumption . Half the individuals were informed of the test results and invited for further assessment by a senior physician ( n = 365 ) . The principles for brief intervention ( DiClemente et al.,1991 ; Miller and Sanchez , 1993 ; National Institute of Alcohol Abuse and Alcoholism , 1999 ) were applied . The other half of the men ( n = 302 ) were left with the information that they had a high GT value and were followed up with laboratory checkups every 2nd year . Mortality was followed up until 1991 and information on deaths was obtained from hospital and police records , necropsy reports , and death certificates . RESULTS Long-term follow-up of mortality for 10 - 16 years ( median , 13 years ) showed that 124 of the 978 men had died ( 12.7 % ) . Autopsy was performed in 96.5 % of the cases . In 59 men ( 48 % ) , death was alcohol-related . In the intervention group ( n = 365 ) , 38 ( 10.4 % ) men were dead and in the control group ( n = 302 ) , 42 ( 13.9 % ) men had died . There was a statistically significant difference ( p = 0.026 ) , with advantage for treatment . Less alcohol-related deaths and deaths occurring later during follow-up were found in the intervention group compared with the control group . The difference between the groups in total mortality , coronary heart disease , and cancer death was not statistically significant . CONCLUSIONS These findings support previous results from the MSIS study indicating that long-term intervention in urban males with alcohol-induced GT increases may be beneficial in terms of survival OBJECTIVES The relative effects of simple advice and brief counseling were evaluated with heavy drinkers identified in primary care and other health setting s in eight countries . METHODS Subjects ( 1260 men , 299 women ) with no prior history of alcohol dependence were selected if they consumed alcohol with sufficient frequency or intensity to be considered at risk of alcohol-related problems . Subjects were r and omly assigned to a control group , a simple advice group , or a group receiving brief counseling . Seventy-five percent of subjects were evaluated 9 months later . RESULTS Male patients exposed to the interventions reported approximately 17 % lower average daily alcohol consumption than those in the control group . Reductions in the intensity of drinking were approximately 10 % . For women , significant reductions were observed in both the control and the intervention groups . Five minutes of simple advice were as effective as 20 minutes of brief counseling . CONCLUSIONS Brief interventions are consistently robust across health care setting s and sociocultural groups and can make a significant contribution to the secondary prevention of alcohol-related problems if they are widely used in primary care BACKGROUND The workplace provides a useful setting for early identification and intervention with individuals who have unhealthy lifestyles . The objective was to evaluate the effects of a workplace-based lifestyle intervention ( Workscreen ) to reduce excessive drinking . METHOD There were eight Australia Post networks r and omly allocated to experimental and control conditions , comprising 67 worksites and 1206 employees . The experimental condition involved a broad spectrum lifestyle campaign , incorporating support from management , employee awareness of health , and brief interventions for high-risk behaviors , including excessive alcohol use . Focus groups identified relevant cultural factors . Changes in workplace culture and employee behavior were assessed 10 months after baseline . Males and females were analyzed separately . RESULTS Over half of APOST employees participated at each screening point . In the experimental condition 61 % of employees overall and 58 % of those identified as excessive drinkers in Phase 1 responded to the lifestyle campaign by attending health assessment s. Analyses focusing on the organization as a whole did not reveal significant reductions in excessive alcohol consumption among men or women . However , a significant reduction in number of drinks was observed in the experimental condition among women for whom completion of baseline and follow-up could be confirmed ( P < 0.001 ) . CONCLUSIONS The present study indicates that a workplace-based lifestyle campaign can assist self-selected employees in reducing their alcohol consumption . There was a moderately high level of participation among those identified as drinking excessively , which supports our approach of embedding a low-intensity alcohol program within the context of a broader health promotion campaign AIMS To evaluate the effectiveness of a brief intervention enhanced by a consistent support person in facilitating attendance for substance use treatment following a hospital alcohol or other drug ( AOD ) presentation . PARTICIPANTS We recruited 127 adolescents ( aged 12 - 19 years ) from hospital emergency departments , 57 were female . Sixty were r and omly assigned to receive the intervention and 67 to receive st and ard hospital care . For the purpose of comparison , normative data were also collected ( at baseline ) from 122 non-AOD presenting adolescents . INTERVENTION The brief intervention involved identifying impediments to treatment service attendance and facilitating attendance via a consistent support person . RESULTS At 4 months , a significantly greater proportion of the intervention group , both daily and " occasional " drug users , had attended treatment than the usual care group . Regardless of attendance at the treatment service the intervention group showed a greater improvement in GHQ-12 scores than the usual care group . Across groups , a greater proportion of those who attended treatment moved to " safer " drug use behaviour ( non-hazardous alcohol consumption and /or non-injecting drug use ( IDU ) ) , and showed a greater decline on a composite total drug use score . CONCLUSIONS Adolescent attendance for treatment can be improved by brief intervention with harmful substance use behaviours reduced for both " occasional " and daily users . Improvements in psychosocial well-being is observed regardless of attendance at a treatment service OBJECTIVE To evaluate the effect of a nurse-conducted intervention on excessive drinkers . DESIGN R and omized , controlled trial . SETTING Vårby Health Centre , Stockholm . INTERVENTION The intervention group visited a nurse three times during a 12-month period . The controls met once with a general practitioner ( GP ) . PATIENTS Patients were recruited at a health screening on the basis of a raised gamma-glutamyl transferase ( GGT ) . Of 2338 subjects , aged 25 - 54 years , 222 had a screening GGT of > or = 0.9 mukat/l . 100 were r and omized to the treatment and 122 to the control group . MAIN OUTCOME MEASURES GGT , self-reported alcohol consumption ( g/week ) , sickness allowance and use of health care . RESULTS After 2 years a reduction of GGT from 1.52 to 1.21 mukat/l ( p = 0.02 ) had occurred in the treatment group . The controls increased their mean level of GGT from 1.75 to 2.16 mukat/l . Mean weekly alcohol consumption in the intervention group was reduced from 337 to 228 g/week ( p = 0.02 ) . The controls did not quantify their alcohol consumption initially , but reported a reduced weekly consumption at follow-up . CONCLUSION The intervention had an impact on GGT and self-reported consumption . The controls also reported decreased consumption possibly because their appointment with the GP functioned as a very brief intervention The Diabetes Prevention Program ( DPP ) is a multicenter r and omized controlled trial design ed to test whether diet and exercise or medication can prevent or delay the onset of type 2 diabetes in persons with impaired glucose tolerance , who are at increased risk of the disease . This paper describes DPP recruitment methods , strategies , performance , and costs . The DPP developed an organizational structure for comprehensive management and continuous monitoring of recruitment efforts . The DPP utilized a variety of recruitment strategies , alone or in combination , and a stepped informed consent procedure leading to r and omization . Study wide and clinic-specific recruitment data were monitored , analyzed , and used to modify recruitment approaches . DPP recruitment was completed slightly ahead of schedule , meeting goals for the proportion of women enrolled and nearly meeting goals for the proportion of racial/ethnic minorities . Clinics varied widely in the recruitment strategies they used , and these strategies also varied by participant age , gender , and race/ethnicity . Staff time devoted to recruitment averaged 86.8 hours per week per clinic , with the majority of effort by staff specifically assigned to recruitment . The number of staff hours required to recruit a participant varied by recruitment strategy . Recruitment cost ( excluding staff cost ) was about 1075 US dollars per r and omized participant . The DPP experience offers lessons for those planning similar efforts : ( 1 ) a method for ongoing assessment and revision of recruitment strategies is valuable ; ( 2 ) a range of recruitment strategies may be useful ; ( 3 ) the most effective methods for recruiting potential subjects may vary according to the gender , age , and race/ethnicity of those individuals ; ( 4 ) recruitment strategies vary in the amount of staff time required to r and omize a participant ; and ( 5 ) a stepped screening may make it easier to identify and recruit volunteers who underst and the requirements of the study OBJECTIVE Brief interventions for hazardous and low-dependent drinkers in the primary care setting have considerable empirical support . The purpose of this study was to ( 1 ) evaluate the effects of brief advice ( BA ) and motivational enhancement ( ME ) interventions on alcohol consumption . In addition , a hindsight matching design was used to ( 2 ) study the moderator effects of patient readiness to change ( alcohol use ) on alcohol consumption . METHOD The subjects ( N = 301 , 70 % men ) were patients 21 years of age or older who presented for treatment at one of 12 primary care clinics . After screening for eligibility and providing consent to participate in the study , the patients completed a baseline assessment and were r and omly assigned to the BA , ME or st and ard care ( SC ) interventions condition . Follow-up assessment s were completed at 1- , 3- , 6- , 9- and 12-months postbaseline assessment . RESULTS Evaluation of the first hypothesis ( n = 232 for these analyses ) showed that all participants tended to reduce their alcohol use considerably between the baseline and 12-month assessment s. In addition , evaluation of the second hypothesis showed a moderator effect of readiness to change in predicting the number of drinks at 12 months , such that the BA intervention seemed more effective for patients relatively low in readiness to change compared to those higher in readiness . Readiness to change did not seem to be related to changes in drinking of participants in the SC or ME conditions . CONCLUSIONS The results confirm that , among primary care patients , substantial changes in alcohol consumption are possible . They further suggest that matching studies of patient readiness to change their alcohol use , as well as other variables , are warranted Smokers who recently quit ( N = 214 ) monitored smoking urges for up to 26 days after quitting . Computers administered 4 - 5 assessment s daily at r and om times ; participants rated urges on waking and when they experienced temptation episodes . Urge intensity after cessation did not generally exceed urges reported during baseline ad lib smoking . Urge intensity and temptation frequency consistently declined over the quit period . Controlling for urge intensity at baseline , all daily urge intensity measures predicted lapse the following day in proportional hazards survival analyses . Average duration of temptation episodes also predicted lapses ; frequency of temptation did not . To isolate the effect of day-to-day variations in urges , participants ' nicotine dependence and urge intensity on quit day were controlled for . Only urge intensity at waking still predicted lapse risk ; this was not because of this measured being closer in time to the day 's lapses . Among lapsers , urge intensity at waking and in temptations rose preceding a lapse The objective of the study was to determine the effectiveness of advice from general practitioners to heavy drinking men ( consuming 350 - 1050 grams of alcohol per week ) to reduce their alcohol consumption . One hundred and fifty-four men recruited from eight general practice s were allocated r and omly to treatment and control groups . Men in the treatment group received advice from their own general practitioner . At one year follow-up , when analyzed according to intention to treat , the treatment group had reduced their consumption by an excess of 65 grams of alcohol per week when compared with the control group ( p less than 0.05 ) . General practitioners should be recommended to screen for alcohol consumption amongst their patients and to give advice to those found to be at risk because of their drinking This prospect i ve study evaluated changes in patients ' health-risk behavior one year after preventive intervention by primary care physicians . The trial used a quasiexperimental design with 2,218 adults ( 1,409 study subjects and 809 controls ) at five multispecialty , group practice sites in three regions of the United States . Pre- and postintervention surveys showed that the treated study patients with behavioral risks were more likely to report positive changes than were controls in regard to beginning regular exercise ( P = .02 ) , using auto seat belts , ( P less than .001 ) , losing weight ( P = .05 ) , decreasing alcohol intake ( P = .01 ) , and to performance of monthly breast self-examination by women ( P less than .001 ) . The smoking cessation rate was greater among the treated study group compared with the controls , although the change was not significantly different . Greater behavioral risk changes also occurred among the total study group ( treated and untreated ) in comparison with the control group . An additive index of these behavioral risks showed greater reduction among the treated and the total group of study patients compared with controls . These initial results suggest that clinical preventive services , which include risk factor education and counseling by primary care physicians , can improve short-term health-related behavior of patients Two brief ( 3-session ) interventions were evaluated in a community sample of 98 non-dependent heavy drinking adults . Three weeks of intensive daily monitoring of drinking using a h and -held computer were completed before and after a 3-week intervention phase in which participants were r and omly assigned to a brief coping skills , brief motivational enhancement , or waiting list condition . Waiting list participants drank more before , during , and after the brief intervention than brief intervention subjects , but all participants demonstrated reductions in drinking amount and frequency . No differences in drinking were found between the two brief interventions . The potential value of intensive daily monitoring as a tool for non-alcohol dependent individuals interested in reducing their drinking was considered We followed 235 adults for one year after a self-initiated attempt to stop smoking cigarettes . Relapse rates were much larger than expected in the early days and weeks after the quit attempt . Approximately 62 % had relapsed by 2 weeks after their quit date s. Those who smoked any cigarettes at all in the post-cessation period ( i.e. , lapsed ) had a 95 % probability of resuming their regular pattern of smoking subsequently . Shorter periods of abstinence on prior quit attempts , greater pre-cessation consumption of alcoholic beverages , and lower pre-cessation levels of confidence in quitting were related to relapse . In addition , abstainers who reported decreased confidence after cessation concerning their ability to maintain abstinence were more likely to relapse thereafter . The presence of a greater proportion of smokers in the subjects ' environment also increased the likelihood of relapse . Demographic variables such as age , gender , and education level did not predict relapse . Likewise , neither baseline psychosocial stress levels , nor post-cessation increases in stress were related prospect ively to relapse . Clinical implication s of finding are discussed The efficacy of specialist versus general practitioner ( GP ) treatment of problem drinkers was assessed in a r and omised controlled trial . 40 problem drinkers referred consecutively to a specialist alcohol clinic by their GP were , after assessment , r and omly allocated to either GP or specialist clinic treatment groups . All subjects received initial advice and counselling in the clinic about their drinking . The specialist clinic group received continued care from the clinic including , if necessary , admission to hospital . Patients in the GP group were returned to the care of the GP who was contacted and supported by the specialist . After 6 months of follow-up , there were significant reductions in alcohol consumption and alcohol-related problems in both groups . No significant difference was found between the two groups with respect to the main outcome measures . No differential treatment effect was found with the more severely dependent drinkers . The findings show that after an initial detailed assessment and advice session , the treatment provided by GPs is at least as effective as that from a specialist clinic with respect to improvements in drinking behaviour and alcohol-related problems . After initial assessment and advice , specialist clinics should encourage GPs to become more involved in the subsequent care of problem drinkers . Such a practice should be based on the individual patient 's needs and the adequacy of support offered to GPs This study evaluated the use of a brief motivational interview ( MI ) to reduce alcohol-related consequences and use among adolescents treated in an emergency room ( ER ) following an alcohol-related event . Patients aged 18 to 19 years ( N = 94 ) were r and omly assigned to receive either MI or st and ard care ( SC ) . Assessment and intervention were conducted in the ER during or after the patient 's treatment . Follow-up assessment s showed that patients who received the MI had a significantly lower incidence of drinking and driving , traffic violations , alcohol-related injuries , and alcohol-related problems than patients who received SC . Both conditions showed reduced alcohol consumption . The harm-reduction focus of the MI was evident in that MI reduced negative outcomes related to drinking , beyond what was produced by the precipitating event plus SC alone This study examined whether a brief intervention to reduce hazardous alcohol consumption among primary care patients reduced use of medical care . In a parent , r and omized controlled trial , at-risk drinkers identified in HMO outpatient waiting rooms were r and omly assigned to receive usual care or brief clinician advice plus a 15-minute motivational counseling session . The current study ( n=514 ) examined the groups ' use of outpatient and inpatient medical services during two years after intervention . Although the intervention reduced alcohol consumption at six-month follow-up , intervention and control groups made similar numbers of outpatient visits ( M=17.7 vs. 18.3 , respectively;p=.47 ) , were equally likely to be hospitalized ( 21.2 % vs. 22.0%;p=.81 ) , and , among those hospitalized , had similar lengths of stay ( 4.7 vs. 6.6 days;p=.37 ) . Although brief interventions to reduce hazardous drinking may potentially reduce medical care utilization , more evidence is needed to substantiate their practicality and cost-effectiveness BACKGROUND The aim of this study was to identify therapist behaviors during a brief motivational intervention ( BMI ) given to injured emergency department patients that predicted participant return for a second BMI session and 12-month alcohol-related outcomes . METHOD This was a secondary data analysis of a r and omized controlled trial ( n = 539 ) previously demonstrating that r and om assignment to a BMI and booster session result ed in a significant reduction of 12-month post-intervention alcohol-related injuries and negative consequences relative to st and ard care . RESULTS Participants who actually received 2 BMI sessions had significantly less alcohol-related negative consequences than those who received only 1 BMI session . Therapists who reported a higher focus on emotional support and low focus on participant drinking behaviors during the initial BMI session were more likely to have assigned participants return for the second BMI session . CONCLUSION The results of these secondary analyses show that compliance with a 2-session therapeutic intervention ( BIB ) predicted fewer negative alcohol-related consequences , and that therapists ' supportive emotional emphasis during the first BMI session was important in predicting participants returning for the second MI session Context Brief interventions can reduce problem drinking , but physicians infrequently use them . Contribution This r and omized trial , from an academic primary care setting , tested whether prompting physicians with positive alcohol screening results that are linked to specific management recommendations works . Prompted faculty , but not residents , tended to discuss alcohol problems and counsel patients more often than did their counterparts who were not prompted . At 6 months , however , only patients of prompted residents had reduced their drinking . Implication s Prompting physicians with positive alcohol screening results and recommendations for action may or may not be effective , depending on patient , physician , and setting characteristics . The Editors Alcohol use disorders are a leading cause of disability and are as common and costly as coronary artery disease and depression ( 1 - 6 ) . Primary care setting s are ideal for alcohol screening and intervention ( 7 ) . Valid , brief , practical screening tools exist , and brief interventions can reduce drinking and improve health when delivered to primary care patients with alcohol problems ( 8 - 11 ) . However , alcohol problems are often unrecognized and untreated in primary care setting s ( 12 - 16 ) . Barriers to screening and intervention include issues related specifically to addictions ( such as patient readiness and physician discomfort , frustration , lack of confidence or skills , or pessimism about efficacy of intervention ) and issues related to the delivery of preventive services in general ( such as cost , acceptability , priorities , and time ) ( 17 , 18 ) . Physician prompting can improve the likelihood of cancer screening , administration of immunizations , and smoking cessation interventions ( 19 - 21 ) . Screening and intervention for alcohol problems , however , involve more complex assessment and intervention . The effectiveness of providing physicians with screening results and a prompt without training is unknown . Such a systems intervention would be easier and less costly to implement than training all physicians about addressing alcohol problems . We tested the hypotheses that providing physicians with patients ' alcohol screening results and simple individualized recommendations would increase physician alcohol counseling and decrease patient drinking . Methods Study Description The study was a cluster r and omized trial at the physician level because r and omization at the patient level would have risked contamination . The institutional review board of the Boston University Medical Center in Boston , Massachusetts , approved the study . Patients gave informed consent and were told that the physician may be given the results of alcohol screening questions . We obtained a Certificate of Confidentiality from the federal government . Participants Physicians were recruited , enrolled , and r and omly assigned before patients were enrolled . All faculty and resident primary care physicians in an urban academic practice ( excluding the authors ) were eligible . Physicians who had seen fewer than 80 patients in the previous 3 years or who anticipated leaving the practice within 6 months were excluded . We informed physicians that we would conduct a health screening study . We used a self-administered question naire to screen and enroll patients who spoke English or Spanish ( staff were available to assist ) ( 22 ) . This was done before a visit with one of the enrolled physicians . Eligible patients were current hazardous drinkers [ 23 ] , which was defined as having consumed alcohol in the past month and either 1 ) answered yes to one or more of the CAGE ( 24 - 26 ) alcohol screening questions ( modified to refer to the past year rather than lifetime ) [ 27 ] or 2 ) drank hazardous amounts in the past month ( 28 , 29 ) . Hazardous amounts for men and women , respectively , were defined as more than 4 st and ard drinks per occasion or 14 drinks per week and as more than 3 st and ard drinks per occasion or 7 drinks per week in the past 30 days ( 26 , 30 ) . Assessment s Before patients were enrolled , physicians completed a confidential written survey ( July 1997 ) . They were asked about their attitudes toward patients with addictions ; their professional satisfaction when caring for patients with alcohol problems ; whether they or someone they knew had an alcohol or drug problem ; and other issues related to alcohol and physicians , including the physician 's usual practice s ( 18 ) . A trained staff research er interviewed enrolled patients before and after their visits with a physician ( between February 1998 and August 1999 ) . All questions not available in Spanish ( 31 ) were translated , back-translated , and checked for accuracy . The assessment visit that occurred before the physician visit addressed demographic characteristics , previous counseling for alcohol problems , and readiness to change ( 32 , 33 ) . Patients were also asked about medication use , medical comorbidity ( 34 , 35 ) , psychiatric comorbidity ( 36 , 37 ) , and tobacco and other drug use . Immediately after the physician visit , patients were interviewed to determine whether counseling had occurred , drinking amounts ( 38 , 39 ) , the quality of communication with the physician ( 40 ) , alcohol dependence symptoms ( 41 ) , and alcohol problems ( Short Inventory of Problems [ SIP-2R ] ) ( 42 ) . Six months later , patients were interviewed by telephone to determine alcohol consumption in the past 30 days ; the vali date d Timeline Followback method was used ( 43 ) . Patients and staff research ers were not blinded to group assignment ( in addition , patients were not necessarily given this information ) ; at follow-up , interviews were done without knowledge of group assignment . R and omization and Intervention Physicians were stratified by level of training ( resident or faculty ) and were r and omly assigned to the intervention or control group at the start of the study . The computer-generated r and omization was done by off-site data management personnel who had no patient or physician contact . The staff research er attached the intervention , a sheet of paper , to the encounter record the physician routinely received immediately before each patient visit . One side of the paper provided the patient 's alcohol screening results , a preliminary assessment , and specific recommendations . The screening results included answers to each of the CAGE questions , reports of usual weekly and per occasion maximum drinking amounts , and the patient 's report of readiness to change on a 10-point scale ( 44 ) ( see Appendix Figure ) . For patients reporting hazardous drinking amounts but no affirmative CAGE question naire responses , the assessment was drinking hazardous amounts and the recommendation was consider advising safe drinking limits and consider providing patients with a pamphlet provided by the study titled How to Cut Down on Your Drinking ( 27 ) . For patients reporting any affirmative CAGE responses but no hazardous drinking amounts , the assessment was possible alcohol problems and recommendations were consider advising abstinence , provide the pamphlet , and referral to addiction treatment . For patients reporting affirmative CAGE question naire responses and hazardous drinking amounts , the assessment was both possible alcohol problems and drinking hazardous amounts and recommendations were consider advising abstinence and referral to addiction treatment . The other side of the paper provided the predictive value of CAGE based on the prevalence of alcohol abuse or dependence in the practice ( 26 , 31 ) , definitions of hazardous drinking , an approach for patients who are not ready to change , a list of abuse or dependence symptoms , and referral information . To increase counseling rates ( not for data collection ) , we attached a Post-it note to the encounter form asking physicians to indicate whether alcohol was discussed and , if not , why ( 45 ) . Physicians in the control group did not receive any information from the study . Statistical Analysis All analyses were performed by using SAS software , version 8.1 [ SAS Institute , Inc. , Cary , North Carolina ] . The primary prespecified outcomes of the study were the occurrence of physician discussion s regarding alcohol problems during the physicianpatient encounter and a decrease in patient drinking . Patients were asked whether they had 1 ) received alcohol counseling , defined as advice on safe drinking limits , advice to cut down or abstain , or referral to an alcohol specialist or treatment program ; 2 ) received any advice [ including counseling ] ; or 3 ) participated in any discussion about alcohol ( including advice ) . An example question was : Did the doctor give you any advice about your drinking habits ? Drinks per drinking day was the primary drinking outcome . We examined additional measures in secondary analyses : days drinking ( any day on which a drink was taken ) , days binge drinking ( any day on which per occasion amounts noted previously were exceeded ) , proportion drinking hazardous amounts , proportion binge drinking , and proportion abstinent . We compared sociodemographic characteristics , level of training , and mean number of patients enrolled for physicians in the intervention and control groups by using the two independent sample s t-test and the Fisher exact test , as applicable . We then compared patients who were seen by physicians in the intervention and control groups with respect to measured characteristics . We compared patients who were available and unavailable at the 6-month follow-up by r and omized group , physician level of training , and sociodemographic characteristics . Outcomes were compared between physicians in the intervention and control groups by using an intention-to-treat analysis ( physicians were analyzed in the groups to which they were r and omly assigned ) . Generalized estimating equations ( GEE ) were used to adjust for clustering of patients by physician ( PROC GENMOD , SAS software , version 8.1 ) ( 46 ) . For continuous outcomes , we specified the identity link function ; for dichotomous outcomes , we specified the logit link The aim of this study was to compare two short-term treatments for alcohol-related problems . The study was performed at an outpatient clinic for substance misuse , and subjects ( 65 men and 28 women ) were recruited through advertisements in the local newspaper . The subjects were r and omized to either a four-session guided self-change group or a one-session advice group . Alcohol consumption , degree of alcohol dependence , negative consequences of drinking , and health-related quality of life were measured or assessed , respectively , by using the timeline follow-back technique , the Short Alcohol Dependence Data ( SADD ) question naire , The Drinker Inventory of Consequences question naire , and the Nottingham Health Profile question naire . Biological markers for high alcohol consumption [ carbohydrate-deficient transferrin ( CDT ) and gamma-glutamyl transferase ( gamma-GT ) levels ] were analyzed . All assessment s were made at baseline and at 9- and 23-month follow-up periods after treatment . Self-reported alcohol consumption was significantly reduced ( P < .0001 ) in both treatment groups at the 23-month follow-up period , as were measures of alcohol dependence , negative consequences of drinking , and health-related quality of life , whereas no corresponding reduction was found in CDT or gamma-GT values . No statistically significant differences in self-reported alcohol consumption were found between the two groups . Patient satisfaction was significantly higher with the four-session guided self-change treatment than with the one session of advice . This finding seems to indicate that individuals , although suffering from alcohol-related problems of relatively low severity , appreciate more time with a therapist AIM To evaluate the effectiveness of a brief motivational intervention on alcohol consumption and misuse in young males with alcohol-related face injury . DESIGN R and omized controlled trial . SETTING Oral and maxillofacial surgery out-patient clinic in an urban teaching hospital . PARTICIPANTS One hundred and fifty-one participants were r and omized to motivational intervention and control conditions . INTERVENTIONS Control was treatment as usual . The intervention was treatment as usual plus a one-session brief motivational intervention administered by a nurse . MEASUREMENTS Three sets of measurements were taken at baseline , 3-month and 1-year follow-up . Collateral measurements were also taken at 1-year follow-up . Primary outcome measures were total alcohol consumption , typical weeks consumption and days abstinent in preceding 3 months . Other outcome measures included the Alcohol Use Disorders Identification Test , a short form of the Alcohol Problems Question naire , and a measure of satisfaction with social relationships . RESULTS There was a significant decrease in 84-day total alcohol consumption across the year ( P < 0.006 ) and further , a significant effect for the motivational intervention was demonstrated ( P < 0.029 ) . This pattern was repeated for days abstinent and alcohol consumption in a typical week as well as alcohol-related problems . There was a significantly greater reduction in the percentage of hazardous drinkers in the motivational intervention group ( from 60 % to 27 % , P < 0.009 ) compared to the control group ( from 54 % to 51 % , NS ) . CONCLUSION A proportion of young men change their alcohol consumption following alcohol-related injury . A nurse-led psychological intervention adds significantly to the proportion and magnitude of response AIMS This study examined the effects of two primary care interventions ( a physician intervention and a clinic-based psychoeducational group ) on drinking patterns , psychosocial problems and blood test results ( MCV , GGT , SGOT and SGPT ) . DESIGN Subjects were r and omized into one of four treatment groups : physician intervention , psychoeducation , both interventions , or no intervention . Follow-up data were collected at 12 and 18 months . SETTING Subjects were recruited from a family practice outpatient clinic managed by a public hospital . PARTICIPANTS Included 175 Mexican-American female and male primary care patients who screened positive for alcohol abuse or dependence . These patients were not seeking help for alcohol problems . INTERVENTIONS Included a brief physician intervention and a 6-week patient psychoeducational group . MEASUREMENTS The Diagnostic Interview Schedule assessed subjects for alcohol abuse ; the Addiction Severity Index measured alcohol-related problems , including psychosocial issues . FINDINGS All four treatment groups demonstrated significant improvement over time , with few differences between intervention and control groups . CONCLUSIONS Assessment can be confounded with brief interventions ; future investigators should use non-assessed control groups AIM This paper reports an evaluation of the effectiveness and cost-effectiveness of nurse-led screening and brief intervention in reducing excessive alcohol consumption among patients in primary health care . BACKGROUND Excessive alcohol consumption is a major source of social , economic and health problems . However , such consumption is responsive to brief alcohol intervention . To date , brief intervention research in primary health care has focused on general practitioner-led interventions , and there is only circumstantial evidence of effectiveness in nurse-led interventions . However , nurses are increasingly taking a lead in health promotion work in primary care . METHODS A pragmatic cluster-r and omized controlled trial was carried out between August 2000 and June 2003 to evaluate the effects of a brief intervention compared with st and ard advice ( control condition ) . A total of 40 general practice clusters ( intervention = 21 and control = 19 ) recruited 127 patients ( intervention = 67 and control = 60 ) to the trial . Excessive consumption was identified opportunistically via the Alcohol Use Disorders Identification Test . After baseline assessment , patients received either a 5 - 10 minutes brief intervention using the ' Drink-Less ' protocol or st and ard advice ( control condition ) . Follow-up occurred at 6 and 12 months postintervention . RESULTS Analysis of variance weighted for cluster size revealed no statistically significant differences between intervention and control patients at follow up . A majority of patients in both conditions reduced their alcohol consumption between assessment and subsequent measurement . Economic analysis suggested that the brief intervention led to no statistically significant changes in subsequent health service re source use relative to st and ard treatment . CONCLUSION The brief intervention evaluated in this trial had no effect over st and ard advice delivered by nurses in primary health care . However , there was a reduction in excessive drinking across both arms of the trial over time . Due to nurse drop-out , this trial was significantly underpowered . Future research should explore barriers to nurses ' involvement in research trials , particularly with an alcohol focus . A larger trial is required to evaluate the effectiveness of nurse-led screening and brief alcohol intervention in primary care BACKGROUND Today , heavy drinking is a common health hazard among women . The evidence in favor of providing some kind of brief intervention to reduce drinking is quite convincing . However , we do not know if intervention works in a natural environment of routine health care . The purpose of this study was to evaluate the effectiveness of long-lasting , brief alcohol intervention counseling for women in a routine general practice setting . METHODS In five primary care outpatient clinics in a Finnish town , 118 female early-phase heavy drinkers who consulted their general practitioners for various reasons were given brief alcohol intervention counseling . Intervention groups A ( n = 40 ) and B ( n = 38 ) were offered seven and three brief intervention sessions , respectively , over a 3-yr period . The control group C ( n = 40 ) was advised to reduce drinking at baseline . Main outcome measures were self-reported weekly alcohol consumption , carbohydrate-deficient transferrin , mean corpuscular volume ( MCV ) , aspartate aminotransferase , alanine aminotransferase , and gamma-glutamyltransferase . RESULTS Depending on the outcome measure and the study group , clinical ly meaningful reduction of drinking was found in 27 % to 75 % of the heavy drinkers . Within all the groups , MCV significantly decreased . However , there were no statistically significant differences between study groups A , B , and C in the mean changes between the beginning and endpoint in the main outcome measures . CONCLUSIONS The present study indicated that minimal advice , as offered to group C , was associated with reduced drinking as much as the brief intervention , as offered to groups A and B , given over a 3-yr period . Furthermore , in the routine setting of the general practice office , the effectiveness of the brief intervention may not be as good as in special research conditions . The factors possibly reducing the effectiveness in a routine setting are unknown . Thus , different methods of implementing brief intervention need to be evaluated to find better ways to support general practice personnel in their efforts to help heavy-drinking female patients to reduce their drinking A total of 424 smokers were r and omized in a 2 x 2 factorial experiment . A pharmacologic factor contained 2 levels : transdermal nicotine path ( TNP ; 21 mg ) and placebo . A self-help behavioral treatment factor contained 2 levels : video-enhanced self-help treatment manual and self-help treatment manual only . At 2 months , TNP produced a higher level of abstinence ( 36 % ) than placebo ( 20 % ) , p < .001 . No other comparison was significant . In secondary analyses , ( at 2 months ) and compliance with patch treatment regimen ( at 2 , 6 , and 12 months ) were associated with less relapse . Although nicotine replacement therapy has improved our ability to produce smoking cessation , the production of sustained , longer term abstinence remains an elusive goal The current study examined the impact of a brief motivational interviewing ( MI ) intervention ( Project CHAT ) on alcohol consumption and drug use for high-risk teens in a primary care clinic that provides health care for underserved population s. Youth ( N=42 , 48 % male ) were screened , and those eligible completed a baseline survey . Baseline survey completers were r and omly assigned to usual care or to an MI intervention and completed a 3-month follow-up survey . The sample ( age 12 to 18 years ) was 85.7 % Hispanic or Latino , 9.5 % African American , and 4.8 % White . At the 3-month follow-up , Project CHAT teens reported less marijuana use , lower perceived prevalence of marijuana use , fewer friends who used marijuana , and lower intentions to use marijuana in the next 6 months , as compared to teens assigned to usual care . Providing this type of brief intervention is a viable approach to working with high-risk teens to decrease substance use OBJECTIVE The project was design ed to compare the effectiveness of brief intervention ( BI ) versus simple advice ( SA ) in the secondary prevention of hazardous alcohol consumption . METHODS A r and omized controlled trial with a 12-month follow-up was conducted . A total of 74 community-based primary care practice s ( 328 physicians ) located in 13 Spanish autonomous regions were recruited initially . Out of 546 men screened , only 229 were r and omized into BI ( n = 104 ) and SA ( n = 125 ) ; 44.6 % of practice s finalized the study . The interventions on the BI group consisted of a 15-minute counselling visit carried out by physicians which included : ( i ) alcohol quantification , ( ii ) information on safe limits , ( iii ) advice , ( iv ) drinking limits agreement , ( v ) self-informative booklet with drinking diary record and ( vi ) unscheduled reinforcement visits . The SA group spent 5 minutes which included ( i ) , ( ii ) and ( iii ) . RESULTS There were no significant differences between both groups at baseline on alcohol use , age , socioeconomic status and CAGE score . After the 12-month follow-up there was a significant decrease in frequency of excessive drinkers ( 67 % of BI group reached targeted consumption , versus 44 % of SA ; P < 0.001 ) as well as weekly alcohol intake reduction ( BI reached 52 versus 32 % in SA ; P < 0.001 ) . A trend to improve outcome with the number of reinforcement visits was found with BI . The only predictor of success was the initial alcohol consumption level . CONCLUSIONS Brief intervention is more effective than simple advice to reduce alcohol intake on adult men who attend primary care services in Spain We present the cost and cost-effectiveness of referral to an alcohol health worker ( AHW ) and information only control in alcohol misusing patients . The study was a pragmatic r and omised controlled trial conducted from April 2001 to March 2003 in an accident and emergency department ( AED ) in a general hospital in London , Engl and . A total of 599 adults identified as drinking hazardously according to the Paddington Alcohol Test were r and omised to referral to an alcohol health worker who delivered a brief intervention ( n = 287 ) or to an information only control ( n = 312 ) . Total societal costs , including health and social services costs , criminal justice costs and productivity losses , and clinical measures of alcohol consumption were measured . Levels of drinking were observably lower in those referred to an AHW at 12 months follow-up and statistically significantly lower at 6 months follow-up . Total costs were not significantly different at either follow-up . Referral to AHWs in an AED produces favourable clinical outcomes and does not generate a significant increase in cost . A decision-making approach revealed that there is at least a 65 % probability that referral to an AHW is more cost-effective than the information only control in reducing alcohol consumption among AED attendees with a hazardous level of drinking We sought to determine if Brief Interventions [ BIs , Motivational Enhancement ( ME ) , and Brief Advice ( BA ) ] reduced alcohol consumption among hazardous alcohol drinking elderly ( 65 years or older ) and whether the elderly responded similarly to younger population s. In 12 primary care offices from 10 1995 to 12 1997 , we screened 13,438 patients of whom 2702 were elderly ( 180 were hazardous drinkers ) . Forty-five elderly enrollees were r and omized to receive ME ( n = 18 ) , BA ( n = 12 ) , and St and ard Care ( SC , n = 12 ) . At baseline , the elderly drank more alcohol and abstained fewer days than the younger cohort ( p<0.05 ) . During the year , the elderly in ME , BA , and SC intervention arms increased the number of days abstained , decreased the number of drinks per day , and reduced the number of total days per month drinking . There were trends toward decreases in the alcohol consumption measures in the ME and BA treatment arms compared to SC . The elderly 's response to all interventions was similar to that of the younger cohort . This study suggests that hazardous alcohol consumption in the elderly is common and that BIs reduce alcohol consumption in the elderly similar to younger population From a population of 2,114 patients attending somatic outpatient clinics , 78 patients were selected who had either an excessive consumption of alcohol according to question naires or a raised gamma glutamyltransferase ( GGT ) value ( above 0.6 mu kat/l ) due to alcohol . They had not undergone treatment for problem drinking previously , and had no serious alcohol dependence . They were thereby classified as excessive consumers of alcohol , and r and omly allocated to an intervention ( n = 36 ) or to a control group ( n = 42 ) . Those in the intervention group were followed up by a nurse once a month and by a doctor every third month for a total of 12 months . Laboratory tests were taken monthly . Consumption of alcohol , GGT and triglyceride levels , and sickness allowance days were decreased in the intervention group compared to the time before intervention . In contrast , the number of sickness allowance days in the control group increased . There was also a tendency towards a positive effect of intervention on the number of consultations made with a statistically not significant decrease of consultations after intervention . The study thus indicates that an early and relatively simple intervention programme for problem drinkers may be effective and can be carried out at a low cost and with a positive response from the patients BACKGROUND Alcohol misuse is highly prevalent among people attending emergency departments , but the effect of intervention by staff working in these departments is unclear . We investigated the effect of screening and referral of patients found to be misusing alcohol while attending an emergency department . METHODS We undertook a single-blind pragmatic r and omised controlled trial . Patients received either an information leaflet or an information leaflet plus an appointment with an alcohol health worker . Outcome data were collected by patient interview and examination of hospital records at 6 and 12 months . FINDINGS 599 patients were r and omised over a 12-month period . At 6 months , those referred to an alcohol health worker were consuming a mean of 59.7 units of alcohol per week compared with 83.1 units in the control group ( t -2.4 , p=0.02 ) . At 12 months those referred were drinking 57.2 units per week compared with 70.8 in controls ( t -1.7 , p=0.09 ) . Those referred to the alcohol health worker had a mean of 0.5 fewer visits to the emergency department over the following 12 months ( 1.2 compared with 1.7 , t -2.0 , p=0.046 ) . Differences in quality of life were not found . INTERPRETATION Opportunistic identification and referral for alcohol misuse in an emergency department is feasible , associated with lower levels of alcohol consumption over the following 6 months , and reduces reattendance at the department . Short-term reductions in alcohol consumption associated with referral for brief intervention for alcohol misuse benefit patients and reduce dem and for accident and emergency department services OBJECTIVE This study used a r and omized controlled trial design to compare the effectiveness of four interventions at reducing alcohol consumption , consequences , and heavy episodic drinking among injured , at-risk drinkers in the emergency department ( ED ) . METHOD Injured patients ( n=4,476 ) completed a computerized survey ; 575 at- risk drinkers were r and omly assigned to one of four intervention conditions : tailored message booklet with brief advice , tailored message booklet only , generic message booklet with brief advice , and generic message booklet only . Regression models using the generalized estimating equation approach were constructed comparing the intervention conditions at baseline , 3-month follow-up , and 12-month follow-up . Gender and age were entered in models along with their interaction . RESULTS Each of the intervention groups significantly decreased their alcohol consumption from baseline to 12-month follow-up ; subjects in the tailored message booklet with brief advice group significantly decreased their average weekly alcohol consumption by 48.5 % ( p<.0001 ) . Those in the brief advice conditions ( tailored or generic ) significantly decreased their average consumption during the 12 months of the study compared with the no brief advice conditions . Younger adult women ( ages 19 - 22 ) who received some brief advice were the most likely to decrease their heavy episodic drinking . CONCLUSIONS This was the first large-scale , brief intervention trial that included development and testing of computerized , highly tailored interventions with injured drinkers in the ED . ED-based interventions for alcohol problems would benefit from computerized screening , brief advice , and booklets to positively impact risky drinking practice OBJECTIVE Prior research supports the effectiveness of brief interventions for reducing alcohol misuse among patients in the emergency department ( ED ) . However , limited information is available regarding the mechanisms of change , which could assist clinicians in streamlining or amplifying these interventions . This article examines moderators of outcomes among ED patients , ages 19 and older , who participated in a r and omized controlled trial of a brief intervention for alcohol misuse . METHOD Injured patients ( N= 4,476 ) completed a computerized survey ; 575 at-risk drinkers were r and omly assigned to one of four brief intervention conditions , and 85 % were interviewed again at 3-month and 12-month follow-ups . RESULTS Regression models using the generalized estimating equations approach examined interaction effects between intervention condition ( advice/no advice ) and hypothesized moderator variables ( stage of change , self-efficacy , acute alcohol use , attribution of injury to alcohol ) on alcohol outcomes over time . Overall , participants who reported higher levels of self-efficacy had lower weekly consumption and consequences , whereas those with higher readiness to change had greater weekly consumption and consequences . Furthermore , individuals who attributed their injury to alcohol and received advice had significantly lower levels of average weekly alcohol consumption and less frequent heavy drinking from baseline to 12-month follow-up compared with those who attributed their injury to alcohol but did not receive advice . CONCLUSIONS This study provides novel data regarding attribution for alcohol-related injury as an important moderator of change and suggests that highlighting the alcohol/injury connection in brief , ED-based alcohol interventions can augment their effectiveness BACKGROUND There is a need for primary care providers to have brief effective methods to intervene with high-risk drinkers during a regular outpatient visit . OBJECTIVE To determine whether brief physician- and nurse practitioner-delivered counseling intervention is efficacious as part of routine primary care in reducing alcohol consumption by high-risk drinkers . METHODS Academic medical center-affiliated primary care practice sites were r and omized to special intervention or to usual care . From a screened population of 9772 patients seeking routine medical care with their primary care providers , 530 high-risk drinkers were entered into the study . Special intervention included training providers in a brief ( 5- to 10-minute ) patient-centered counseling intervention , and an office support system that screened patients , cued providers to intervene , and made patient education material s available . The primary outcome measures were change in alcohol use from baseline to 6 months as measured by weekly alcohol consumption and frequency of binge drinking episodes . RESULTS Participants in the special intervention and usual care groups were similar on important background variables and potential confounders except that special intervention participants had significantly higher baseline levels of alcohol usage ( P = .01 ) . At 6-month follow-up , in the 91 % of the cohort who provided follow-up information , alcohol consumption was significantly reduced when adjusted for age , sex , and baseline alcohol usage ( special intervention , -5.8 drinks per week ; usual care , -3.4 drinks per week ; P = .001 ) . CONCLUSIONS This study provides evidence that screening and very brief ( 5- to 10-minute ) advice and counseling delivered by a physician or nurse practitioner as part of routine primary care significantly reduces alcohol consumption by high-risk drinkers BACKGROUND Numerous reports document that preinjury alcohol use is associated with all modes of injury requiring treatment in a trauma center , with 25 % to 50 % or more of patients testing positive for alcohol at the time of admission . There is evidence that in trauma patients unaddressed alcohol use problems result in recurrent injury requiring readmission to a trauma center and /or death . METHODS A r and omized clinical trial was conducted to assess the effectiveness of two types of brief interventions to reduce drinking and the consequences of drinking . Trauma patients defined as at-risk alcohol users ( n=497 ) were r and omized into two treatment options : a brief personalized motivational intervention ( PMI ) , or brief information and advice ( BIA ) . After a brief assessment , PMI subjects received a motivational session , feedback letter , and two postdischarge telephone contacts , whereas the BIA group received a brochure and one postdischarge telephone contact . Both groups were reassessed at 6 and 12 months postinjury . RESULTS Both the PMI and BIA groups had statistically significant reductions in drinking , binge episodes , and consequences related to drinking that persisted from the 6- to the 12-month follow-up . However , although not statistically significant , for those classified as lower-level drinkers ( < or=1 drink per day ) , there was a consistent pattern of maintaining reductions for the PMI group at 12 months compared with the BIA group . CONCLUSION Our results suggest that brief interventions ( PMI and BIA ) that link alcohol consumption with trauma injury and consequences of drinking can be effective in reducing drinking and consequences related to drinking in a significant portion of at-risk nondependent drinkers OBJECTIVES To investigate the effectiveness of brief interventions to reduce alcohol intake in traffic casualties with a positive blood alcohol concentration . METHODS Nine hundred forty-eight eligible casualties ( 97.6 % of eligible casualties within a universe of 1106 ) were screened for alcohol and 126 ( 13.3 % ) were identified as positive . Interventions were performed in 85 , r and omly allocated to a minimal intervention ( simple advice ) or a brief intervention ( motivational intervention ) . Telephone follow-up was scheduled for months 3 , 6 and 12 . The present study reports the results of follow-up at month 3 . RESULTS Fifty-seven patients ( 67 % ) were followed up at month 3 . A total of 73.7 % had reduced their alcohol intake and this percentage was greater in the group who underwent the brief intervention ( p = 0.06 ; effect size 0.5 ) and among heavy drinkers ( p < 0.05 ) . CONCLUSIONS The data indicate the effectiveness of the brief intervention , although the sample size does not allow definitive conclusions to be drawn This r and omized trial evaluated an intervention for reducing at-risk drinking practice s in a sample of 307 patients . Eligible drinking patterns included chronic drinking ( > or = 2 drinks per day in the past month ) , binge drinking ( > or = 5 drinks per occasion at least twice in the past month ) , and drinking and driving ( driving after > 2 drinks in the past month ) . Members of the intervention group received a message from their physician during their regularly scheduled visit , a self-help manual , written personalized feedback , and up to 3 telephone counseling calls . Dropout was significantly higher in the intervention than control group BACKGROUND Transdermal nicotine therapy is widely used to aid smoking cessation , but there is uncertainty about its safety in patients with cardiac disease . METHODS In a r and omized , double-blind , placebo-controlled trial at 10 Veterans Affairs medical centers , we r and omly assigned 584 out patients ( of whom 576 were men ) with at least one diagnosis of cardiovascular disease to a 10-week course of transdermal nicotine or placebo as an aid to smoking cessation . The subjects were monitored for a total of 14 weeks for the primary end points of the study ( death , myocardial infa rct ion , cardiac arrest , and admission to the hospital due to increased severity of angina , arrhythmia , or congestive heart failure ) ; the secondary end points ( admission to the hospital for other reasons and outpatient visits necessitated by increased severity of heart disease ) ; any side effects of therapy ; and abstinence from smoking . RESULTS There were 48 primary and 78 secondary end points noted in a total of 95 subjects . At least one of the primary end points was reached by 5.4 percent of the subjects in the nicotine group and 7.9 percent of the subjects in the placebo group ( difference , 2.5 percent ; 95 percent confidence interval , -1.6 to 6.5 percent ; P=0.23 ) . In the nicotine group , 11.9 percent of the subjects had at least one of the secondary end points , as compared with 9.7 percent in the placebo group ( difference , 2.2 percent ; 95 percent confidence interval , -2.2 to 7.4 percent ; P= 0.37 ) . After 14 weeks the rate of abstinence from smoking was 21 percent in the nicotine group , as compared with 9 percent in the placebo group ( P=0.001 ) , but after 24 weeks the abstinence rates were not significantly different ( 14 percent vs. 11 percent , P= 0.67 ) . CONCLUSIONS Transdermal nicotine does not cause a significant increase in cardiovascular events in high-risk out patients with cardiac disease . However , the efficacy of transdermal nicotine as an aid to smoking cessation in such patients is limited and may not be sustained over time STUDY OBJECTIVE Brief interventions for high-risk alcohol use for injured emergency department ( ED ) patients have demonstrated effectiveness and may have a more pronounced effect with motor vehicle crash patients . We report on 3-month outcome data of a r and omized controlled trial of injured patients , using a novel model of telephone-delivered brief interventions after ED discharge . METHODS ED research assistants recruited adult injured patients who screened positive for high-risk alcohol use and were to be discharged home . After discharge , participants received by telephone an assessment of alcohol use and impaired driving and then were r and omized to treatment ( n=140 ) or st and ard care ( n=145 ) . Treatment consisted of 2 sessions of brief interventions done by telephone , focusing on risky alcohol use . At 3 months , both groups had an assessment of alcohol use and impaired driving . RESULTS Two hundred eighty-five patients were r and omized and had a baseline mean Alcohol Use Disorders Inventory Test ( AUDIT ) score of 11.0 ( SD=7.4 ) . Three-month follow-up assessment s were completed on 273 ( 95 % ) . Mean AUDIT score decreased in both the treatment ( mean change=-3.4 ; 95 % confidence interval [ CI ] -4.5 to -2.3 ) and st and ard care group ( mean change=-3.2 ; 95 % CI -4.2 to -2.2 ) . Measures of impaired driving decreased for the treatment group ( mean change=-1.4 95 % ; CI -3.0 to 0.2 ) compared with st and ard care group ( mean change=1.0 ; 95 % CI -0.9 to 2.9 ; P=.04 ; d=0.31 ) . Participants were stratified post hoc into 3 groups by baseline alcohol problem , with the treatment effect only being in the highest-scoring group ( d=.30 ) . CONCLUSION Telephone brief interventions decreased impaired driving in our treatment group . Telephone brief intervention appears to offer an alternative mechanism to deliver brief intervention for alcohol in this at-risk ED population Rationale The subjective , psychomotor , and physiological effects of a widely prescribed and abused prescription opioid , oxycodone , have not been studied in a population of non-drug-abusing people . Objectives To characterize the effects of oxycodone in non-drug-abusing volunteers . Methods Eighteen volunteers participated in a crossover , r and omized , double-blind study in which they received , all p.o . , placebo , 10 mg oxycodone , 20 mg oxycodone , 30 mg oxycodone , 40 mg morphine , and 2 mg lorazepam . Measures were assessed before and for 300 min after drug administration . End-of-session and 24-h post-session measures were taken to assess residual drug effects and overall subjects ' assessment s of the drug effects . Results Subjective effects of oxycodone were dose related , with the majority of statistically significant effects limited to the two higher doses tested . Oxycodone produced a profile of subjective effects that included both pleasant and unpleasant effects . Morphine in general produced effects similar in magnitude to those of 10 mg and 20 mg oxycodone . Peak liking and drug-wanting ratings were increased by all doses of oxycodone and by morphine , and trough ratings of liking ( dislike ) were lower in the 20-mg and 30-mg oxycodone conditions , relative to the placebo condition . Post-session ratings of overall liking and drug wanting were not statistically significant , either at the end of the session or 24 h later . Cognitive and psychomotor impairment were obtained with the higher doses of oxycodone , but to a much lesser degree than that of lorazepam . Miosis and exophoria were increased in a dose-related manner by oxycodone . Conclusions Oxycodone produced effects similar to those of other mu opioid agonists . Although oxycodone produced abuse liability-related subjective effects , it also produced unpleasant effects , a phenomenon we have observed in other opioid studies in non-drug-abusing volunteers BACKGROUND Brief interventions ( BIs ) are effective methods to reduce problematic drinking . It is not known , if the effectiveness of BI differs between patients with or without comorbid depression or anxiety disorders . METHODS In a r and omized controlled BI study with two intervention groups and one control condition , data were collected from 408 general practice ( GP ) patients with alcohol use disorders , at-risk drinking or binge drinking . 88 participants were diagnosed with comorbid anxiety and /or depressive disorders . The effectiveness of BI was assessed at a 12-month follow-up in relation to the presence and absence of comorbidity . Reduction of drinking in six ordered categories ( g/alcohol ) between baseline and follow-up served as the outcome variable . RESULTS BI were significantly related to reduction of drinking in the non-comorbid ( -2.64 g/alcohol vs. -8.61 g/alcohol ; p=.03 ) but not in the comorbid sub sample ( -22.06 g/alcohol vs. -22.09 g/alcohol ; p=.76 ) . Compared to non-comorbid participants , a significantly higher reduction of drinking was found for comorbid individuals ( -6.55 g/alcohol vs. -22.08 g/alcohol ; p=.01 ) . An ordinal regression analysis revealed comorbidity to be a positive predictor for reduction of drinking ( estimator=.594 ; CI=.175 - 1.013 ; p<.01 ) . When entering the variables amount of drinking at baseline , intervention and classification of problematic drinking , these became significant predictors , whereas comorbidity showed only a tendency . CONCLUSION BI did not significantly effect a reduction of drinking in comorbid patients . As BI are known to be less effective for dependent drinkers , a larger proportion of dependents among the comorbid might have limited the effectiveness of BI . Future studies with larger sample sizes of comorbid problem drinkers are necessary to confirm the results |
910 | 28,454,113 | Additionally , the efficacy of triplet regimens was superior to that of single or doublet regimens .
The same trend was observed in a subgroup analysis of daratumumab and elotuzumab .
Elotuzumab and daratumumab improved the ORR , at least VGPR , and PFS compared to non-mAb-based regimens .
In a pooled analysis , both mAbs had promising efficacy and safety profiles , particularly in triplet regimens .
The same trend was observed in daratumumab- and elotuzumab-based regimens .
Daratumumab triplet therapy ( daratumumab , lenalidomide , and dexamethasone ) was superior to other triplet regimens for the treatment of RRMM , and daratumumab monotherapy was more effective than either single agent in heavily pretreated MM patients , suggesting CD38 is an effective target for treatment of RRMM . | Although two newly launched monoclonal antibodies ( mAbs ) , elotuzumab and daratumumab , performed well in patients with relapsed or relapsed/refractory multiple myeloma ( RRMM ) , their efficacy and safety remain uncertain .
We therefore performed a systematic review and meta- analysis of the most recent clinical trials that evaluated elotuzumab and /or daratumumab for the treatment of patients with RRMM . | In this proof-of-concept , open-label , phase 2 study , patients with relapsed/refractory multiple myeloma ( RRMM ) received elotuzumab with bortezomib and dexamethasone ( EBd ) or bortezomib and dexamethasone ( Bd ) until disease progression/unacceptable toxicity . Primary endpoint was progression-free survival ( PFS ) ; secondary /exploratory endpoints included overall response rate ( ORR ) and overall survival ( OS ) . Two-sided 0.30 significance level was specified ( 80 % power , 103 events ) to detect hazard ratio ( HR ) of 0.69 . Efficacy and safety analyses were performed on all r and omized patients and all treated patients , respectively . Of 152 r and omized patients ( 77 EBd , 75 Bd ) , 150 were treated ( 75 EBd , 75 Bd ) . PFS was greater with EBd vs Bd ( HR , 0.72 ; 70 % confidence interval [ CI ] , 0.59 - 0.88 ; stratified log-rank P = .09 ) ; median PFS was longer with EBd ( 9.7 months ) vs Bd ( 6.9 months ) . In an up date d analysis , EBd-treated patients homozygous for the high-affinity FcγRIIIa allele had median PFS of 22.3 months vs 9.8 months in EBd-treated patients homozygous for the low-affinity allele . ORR was 66 % ( EBd ) vs 63 % ( Bd ) . Very good partial response or better occurred in 36 % of patients ( EBd ) vs 27 % ( Bd ) . Early OS results , based on 40 deaths , revealed an HR of 0.61 ( 70 % CI , 0.43 - 0.85 ) . To date , 60 deaths have occurred ( 28 EBd , 32 Bd ) . No additional clinical ly significant adverse events occurred with EBd vs Bd . Grade 1/2 infusion reaction rate was low ( 5 % EBd ) and mitigated with premedication . In patients with RRMM , elotuzumab , an immunostimulatory antibody , appears to provide clinical benefit without added clinical ly significant toxicity when combined with Bd vs Bd alone . Registered to Clinical Trials.gov as NCT01478048 PURPOSE This phase I study evaluated elotuzumab , lenalidomide , and dexamethasone in patients with relapsed or refractory multiple myeloma ( MM ) . PATIENTS AND METHODS Three cohorts were enrolled and treated with elotuzumab ( 5.0 , 10 , or 20 mg/kg intravenously ) on days 1 , 8 , 15 , and 22 of a 28-day cycle in the first two cycles , and days 1 and 15 of each subsequent cycle ; lenalidomide 25 mg orally [ PO ] on days 1 to 21 ; and dexamethasone 40 mg PO weekly . Dose-limiting toxicities ( DLTs ) were assessed during cycle 1 of each cohort , and clinical responses were evaluated during each cycle . The first five patients received up to six cycles of therapy ; subsequent patients were treated until disease progression . RESULTS Twenty-nine patients with advanced MM and a median of three prior MM therapies were enrolled ; 28 patients were treated , three each in the 5.0-mg/kg and 10-mg/kg cohorts and 22 in the 20-mg/kg cohort . No DLTs were observed up to the maximum proposed dose of 20 mg/kg . The most frequent grade 3 to 4 toxicities were neutropenia ( 36 % ) and thrombocytopenia ( 21 % ) . Two patients experienced a serious infusion reaction ( one grade 4 anaphylactic reaction and one grade 3 stridor ) during the first treatment cycle . Objective responses were obtained in 82 % ( 23 of 28 ) of treated patients . After a median of 16.4 months follow-up , the median time to progression was not reached for patients in the 20-mg/kg cohort who were treated until disease progression . CONCLUSION The combination of elotuzumab , lenalidomide , and low-dose dexamethasone was generally well tolerated and showed encouraging response rates in patients with relapsed or refractory MM Daratumumab , a human CD38 immunoglobulin G1 kappa ( IgG1κ ) monoclonal antibody , has activity as monotherapy in multiple myeloma ( MM ) . This phase 1/2 study investigated daratumumab plus lenalidomide/dexamethasone in refractory and relapsed/refractory MM . Part 1 ( dose escalation ) evaluated 4 daratumumab doses plus lenalidomide ( 25 mg/day orally on days 1 - 21 of each cycle ) and dexamethasone ( 40 mg/week ) . Part 2 ( dose expansion ) evaluated daratumumab at the recommended phase 2 dose ( RP2D ) plus lenalidomide/dexamethasone . Safety , efficacy , pharmacokinetics , immunogenicity , and accelerated daratumumab infusions were studied . In part 1 ( 13 patients ) , no dose-limiting toxicities were observed , and 16 mg/kg was selected as the R2PD . In part 2 ( 32 patients ) , median time since diagnosis was 3.2 years , with a median of 2 prior therapies ( range , 1 - 3 prior therapies ) , including proteasome inhibitors ( 91 % ) , alkylating agents ( 91 % ) , autologous stem cell transplantation ( 78 % ) , thalidomide ( 44 % ) , and lenalidomide ( 34 % ) ; 22 % of patients were refractory to the last line of therapy . Grade 3 to 4 adverse events ( ≥5 % ) included neutropenia , thrombocytopenia , and anemia . In part 2 , infusion-related reactions ( IRRs ) occurred in 18 patients ( 56 % ) ; most were grade ≤2 ( grade 3 , 6.3 % ) . IRRs predominantly occurred during first infusions and were more common during accelerated infusions . In part 2 ( median follow-up of 15.6 months ) , overall response rate was 81 % , with 8 stringent complete responses ( 25 % ) , 3 complete responses ( 9 % ) , and 9 very good partial responses ( 28 % ) . Eighteen-month progression-free and overall survival rates were 72 % ( 95 % confidence interval , 51.7 - 85.0 ) and 90 % ( 95 % confidence interval , 73.1 - 96.8 ) , respectively . Daratumumab plus lenalidomide/dexamethasone result ed in rapid , deep , durable responses . The combination was well tolerated and consistent with the safety profiles observed with lenalidomide/dexamethasone or daratumumab monotherapy . This trial was registered at www . clinical trials.gov as # NCT01615029 BACKGROUND Few effective treatments exist for patients with refractory or relapsed and refractory multiple myeloma not responding to treatment with bortezomib and lenalidomide . Pomalidomide alone has shown limited efficacy in patients with relapsed multiple myeloma , but synergistic effects have been noted when combined with dexamethasone . We compared the efficacy and safety of pomalidomide plus low-dose dexamethasone with high-dose dexamethasone alone in these patients . METHODS This multicentre , open-label , r and omised phase 3 trial was undertaken in Australia , Canada , Europe , Russia , and the USA . Patients were eligible if they had been diagnosed with refractory or relapsed and refractory multiple myeloma , and had failed at least two previous treatments of bortezomib and lenalidomide . They were assigned in a 2:1 ratio with a vali date d interactive voice and internet response system to either 28 day cycles of pomalidomide ( 4 mg/day on days 1 - 21 , orally ) plus low-dose dexamethasone ( 40 mg/day on days 1 , 8 , 15 , and 22 , orally ) or high-dose dexamethasone ( 40 mg/day on days 1 - 4 , 9 - 12 , and 17 - 20 , orally ) until disease progression or unacceptable toxicity . Stratification factors were age ( ≤75 years vs > 75 years ) , disease population ( refractory vs relapsed and refractory vs bortezomib intolerant ) , and number of previous treatments ( two vs more than two ) . The primary endpoint was progression-free survival ( PFS ) . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT01311687 , and with EudraCT , number 2010 - 019820 - 30 . FINDINGS The accrual for the study has been completed and the analyses are presented . 302 patients were r and omly assigned to receive pomalidomide plus low-dose dexamethasone and 153 high-dose dexamethasone . After a median follow-up of 10·0 months ( IQR 7·2 - 13·2 ) , median PFS with pomalidomide plus low-dose dexamethasone was 4·0 months ( 95 % CI 3·6 - 4·7 ) versus 1·9 months ( 1·9 - 2·2 ) with high-dose dexamethasone ( hazard ratio 0·48 [ 95 % CI 0·39 - 0·60 ] ; p<0·0001 ) . The most common grade 3 - 4 haematological adverse events in the pomalidomide plus low-dose dexamethasone and high-dose dexamethasone groups were neutropenia ( 143 [ 48 % ] of 300 vs 24 [ 16 % ] of 150 , respectively ) , anaemia ( 99 [ 33 % ] vs 55 [ 37 % ] , respectively ) , and thrombocytopenia ( 67 [ 22 % ] vs 39 [ 26 % ] , respectively ) . Grade 3 - 4 non-haematological adverse events in the pomalidomide plus low-dose dexamethasone and high-dose dexamethasone groups included pneumonia ( 38 [ 13 % ] vs 12 [ 8 % ] , respectively ) , bone pain ( 21 [ 7 % ] vs seven [ 5 % ] , respectively ) , and fatigue ( 16 [ 5 % ] vs nine [ 6 % ] , respectively ) . There were 11 ( 4 % ) treatment-related adverse events leading to death in the pomalidomide plus low-dose dexamethasone group and seven ( 5 % ) in the high-dose dexamethasone group . INTERPRETATION Pomalidomide plus low-dose dexamethasone , an oral regimen , could be considered a new treatment option in patients with refractory or relapsed and refractory multiple myeloma . FUNDING Celgene Corporation BACKGROUND Daratumumab showed promising efficacy alone and with lenalidomide and dexamethasone in a phase 1 - 2 study involving patients with relapsed or refractory multiple myeloma . METHODS In this phase 3 trial , we r and omly assigned 569 patients with multiple myeloma who had received one or more previous lines of therapy to receive lenalidomide and dexamethasone either alone ( control group ) or in combination with daratumumab ( daratumumab group ) . The primary end point was progression-free survival . RESULTS At a median follow-up of 13.5 months in a protocol -specified interim analysis , 169 events of disease progression or death were observed ( in 53 of 286 patients [ 18.5 % ] in the daratumumab group vs. 116 of 283 [ 41.0 % ] in the control group ; hazard ratio , 0.37 ; 95 % confidence interval [ CI ] , 0.27 to 0.52 ; P<0.001 by stratified log-rank test ) . The Kaplan-Meier rate of progression-free survival at 12 months was 83.2 % ( 95 % CI , 78.3 to 87.2 ) in the daratumumab group , as compared with 60.1 % ( 95 % CI , 54.0 to 65.7 ) in the control group . A significantly higher rate of overall response was observed in the daratumumab group than in the control group ( 92.9 % vs. 76.4 % , P<0.001 ) , as was a higher rate of complete response or better ( 43.1 % vs. 19.2 % , P<0.001 ) . In the daratumumab group , 22.4 % of the patients had results below the threshold for minimal residual disease ( 1 tumor cell per 105 white cells ) , as compared with 4.6 % of those in the control group ( P<0.001 ) ; results below the threshold for minimal residual disease were associated with improved outcomes . The most common adverse events of grade 3 or 4 during treatment were neutropenia ( in 51.9 % of the patients in the daratumumab group vs. 37.0 % of those in the control group ) , thrombocytopenia ( in 12.7 % vs. 13.5 % ) , and anemia ( in 12.4 % vs. 19.6 % ) . Daratumumab-associated infusion-related reactions occurred in 47.7 % of the patients and were mostly of grade 1 or 2 . CONCLUSIONS The addition of daratumumab to lenalidomide and dexamethasone significantly lengthened progression-free survival among patients with relapsed or refractory multiple myeloma . Daratumumab was associated with infusion-related reactions and a higher rate of neutropenia than the control therapy . ( Funded by Janssen Research and Development ; POLLUX Clinical Trials.gov number , NCT02076009 . ) BACKGROUND Panobinostat is a potent oral pan-deacetylase inhibitor that in pre clinical studies has synergistic anti-myeloma activity when combined with bortezomib and dexamethasone . We aim ed to compare panobinostat , bortezomib , and dexamethasone with placebo , bortezomib , and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma . METHODS PANORAMA1 is a multicentre , r and omised , placebo-controlled , double-blind phase 3 trial of patients with relapsed or relapsed and refractory multiple myeloma who have received between one and three previous treatment regimens . Patients were r and omly assigned ( 1:1 ) via an interactive web-based and voice response system , stratified by number of previous treatment lines and by previous use of bortezomib , to receive 21 day cycles of placebo or panobinostat ( 20 mg ; on days 1 , 3 , 5 , 8 , 10 , 12 , orally ) , both in combination with bortezomib ( 1·3 mg/m(2 ) on days 1 , 4 , 8 , 11 , intravenously ) and dexamethasone ( 20 mg on days 1 , 2 , 4 , 5 , 8 , 9 , 11 , 12 , orally ) . Patients , physicians , and the investigators who did the data analysis were masked to treatment allocation ; crossover was not permitted . The primary endpoint was progression-free survival ( in accordance with modified European Group for Blood and Marrow Transplantation criteria and based on investigators ' assessment ) and was analysed by intention to treat . The study is ongoing , but no longer recruiting , and is registered at Clinical Trials.gov , number NCT01023308 . FINDINGS 768 patients were enrolled between Jan 21 , 2010 , and Feb 29 , 2012 , with 387 r and omly assigned to panobinostat , bortezomib , and dexamethasone and 381 to placebo , bortezomib , and dexamethasone . Median follow-up was 6·47 months ( IQR 1·81 - 13·47 ) in the panobinostat group and 5·59 months ( 2·14 - 11·30 ) in the placebo group . Median progression-free survival was significantly longer in the panobinostat group than in the placebo group ( 11·99 months [ 95 % CI 10·33 - 12·94 ] vs 8·08 months [ 7·56 - 9·23 ] ; hazard ratio [ HR ] 0·63 , 95 % CI 0·52 - 0·76 ; p<0·0001 ) . Overall survival data are not yet mature , although at the time of this analysis , median overall survival was 33·64 months ( 95 % CI 31·34-not estimable ) for the panobinostat group and 30·39 months ( 26·87-not estimable ) for the placebo group ( HR 0·87 , 95 % CI 0·69 - 1·10 ; p=0·26 ) . The proportion of patients achieving an overall response did not differ between treatment groups ( 235 [ 60·7 % , 95 % CI 55·7 - 65·6 ] for panobinostat vs 208 [ 54·6 % , 49·4 - 59·7 ] for placebo ; p=0·09 ) ; however , the proportion of patients with a complete or near complete response was significantly higher in the panobinostat group than in the placebo group ( 107 [ 27·6 % , 95 % CI 23·2 - 32·4 ] vs 60 [ 15·7 % , 12·2 - 19·8 ] ; p=0·00006 ) . Minimal responses were noted in 23 ( 6 % ) patients in the panobinostat group and in 42 ( 11 % ) in the placebo group . Median duration of response ( partial response or better ) was 13·14 months ( 95 % CI 11·76 - 14·92 ) in the panobinostat group and 10·87 months ( 9·23 - 11·76 ) in the placebo group , and median time to response ( partial response or better ) was 1·51 months ( 1·41 - 1·64 ) in the panobinostat group and 2·00 months ( 1·61 - 2·79 ) in the placebo group . Serious adverse events were reported in 228 ( 60 % ) of 381 patients in the panobinostat group and 157 ( 42 % ) of 377 patients in the placebo group . Common grade 3 - 4 laboratory abnormalities and adverse events ( irrespective of association with study drug ) included thrombocytopenia ( 256 [ 67 % ] in the panobinostat group vs 118 [ 31 % ] in the placebo group ) , lymphopenia ( 202 [ 53 % ] vs 150 [ 40 % ] ) , diarrhoea ( 97 [ 26 % ] vs 30 [ 8 % ] ) , asthenia or fatigue ( 91 [ 24 % ] vs 45 [ 12 % ] ) , and peripheral neuropathy ( 67 [ 18 % ] vs 55 [ 15 % ] ) . INTERPRETATION Our results suggest that panobinostat could be a useful addition to the treatment armamentarium for patients with relapsed or relapsed and refractory multiple myeloma . Longer follow up will be necessary to determine whether there is any effect on overall survival . FUNDING Novartis Pharmaceuticals BACKGROUND Multiple myeloma cells uniformly overexpress CD38 . We studied daratumumab , a CD38-targeting , human IgG1κ monoclonal antibody , in a phase 1 - 2 trial involving patients with relapsed myeloma or relapsed myeloma that was refractory to two or more prior lines of therapy . METHODS In part 1 , the dose-escalation phase , we administered daratumumab at doses of 0.005 to 24 mg per kilogram of body weight . In part 2 , the dose-expansion phase , 30 patients received 8 mg per kilogram of daratumumab and 42 received 16 mg per kilogram , administered once weekly ( 8 doses ) , twice monthly ( 8 doses ) , and monthly for up to 24 months . End points included safety , efficacy , and pharmacokinetics . RESULTS No maximum tolerated dose was identified in part 1 . In part 2 , the median time since diagnosis was 5.7 years . Patients had received a median of four prior treatments ; 79 % of the patients had disease that was refractory to the last therapy received ( 64 % had disease refractory to proteasome inhibitors and immunomodulatory drugs and 64 % had disease refractory to bortezomib and lenalidomide ) , and 76 % had received autologous stem-cell transplants . Infusion-related reactions in part 2 were mild ( 71 % of patients had an event of any grade , and 1 % had an event of grade 3 ) , with no dose-dependent adverse events . The most common adverse events of grade 3 or 4 ( in ≥ 5 % of patients ) were pneumonia and thrombocytopenia . The overall response rate was 36 % in the cohort that received 16 mg per kilogram ( 15 patients had a partial response or better , including 2 with a complete response and 2 with a very good partial response ) and 10 % in the cohort that received 8 mg per kilogram ( 3 had a partial response ) . In the cohort that received 16 mg per kilogram , the median progression-free survival was 5.6 months ( 95 % confidence interval [ CI ] , 4.2 to 8.1 ) , and 65 % ( 95 % CI , 28 to 86 ) of the patients who had a response did not have progression at 12 months . CONCLUSIONS Daratumumab monotherapy had a favorable safety profile and encouraging efficacy in patients with heavily pretreated and refractory myeloma . ( Funded by Janssen Research and Development and Genmab ; Clinical Trials.gov number , NCT00574288 . ) BACKGROUND Bortezomib with dexamethasone is a st and ard treatment option for relapsed or refractory multiple myeloma . Carfilzomib with dexamethasone has shown promising activity in patients in this disease setting . The aim of this study was to compare the combination of carfilzomib and dexamethasone with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma . METHODS In this r and omised , phase 3 , open-label , multicentre study , patients with relapsed or refractory multiple myeloma who had one to three previous treatments were r and omly assigned ( 1:1 ) using a blocked r and omisation scheme ( block size of four ) to receive carfilzomib with dexamethasone ( carfilzomib group ) or bortezomib with dexamethasone ( bortezomib group ) . R and omisation was stratified by previous proteasome inhibitor therapy , previous lines of treatment , International Staging System stage , and planned route of bortezomib administration if r and omly assigned to bortezomib with dexamethasone . Patients received treatment until progression with carfilzomib ( 20 mg/m(2 ) on days 1 and 2 of cycle 1 ; 56 mg/m(2 ) thereafter ; 30 min intravenous infusion ) and dexamethasone ( 20 mg oral or intravenous infusion ) or bortezomib ( 1·3 mg/m(2 ) ; intravenous bolus or subcutaneous injection ) and dexamethasone ( 20 mg oral or intravenous infusion ) . The primary endpoint was progression-free survival in the intention-to-treat population . All participants who received at least one dose of study drug were included in the safety analyses . The study is ongoing but not enrolling participants ; results for the interim analysis of the primary endpoint are presented . The trial is registered at Clinical Trials.gov , number NCT01568866 . FINDINGS Between June 20 , 2012 , and June 30 , 2014 , 929 patients were r and omly assigned ( 464 to the carfilzomib group ; 465 to the bortezomib group ) . Median follow-up was 11·9 months ( IQR 9·3 - 16·1 ) in the carfilzomib group and 11·1 months ( 8·2 - 14·3 ) in the bortezomib group . Median progression-free survival was 18·7 months ( 95 % CI 15·6-not estimable ) in the carfilzomib group versus 9·4 months ( 8·4 - 10·4 ) in the bortezomib group at a preplanned interim analysis ( hazard ratio [ HR ] 0·53 [ 95 % CI 0·44 - 0·65 ] ; p<0·0001 ) . On- study death due to adverse events occurred in 18 ( 4 % ) of 464 patients in the carfilzomib group and in 16 ( 3 % ) of 465 patients in the bortezomib group . Serious adverse events were reported in 224 ( 48 % ) of 463 patients in the carfilzomib group and in 162 ( 36 % ) of 456 patients in the bortezomib group . The most frequent grade 3 or higher adverse events were anaemia ( 67 [ 14 % ] of 463 patients in the carfilzomib group vs 45 [ 10 % ] of 456 patients in the bortezomib group ) , hypertension ( 41 [ 9 % ] vs 12 [ 3 % ] ) , thrombocytopenia ( 39 [ 8 % ] vs 43 [ 9 % ] ) , and pneumonia ( 32 [ 7 % ] vs 36 [ 8 % ] ) . INTERPRETATION For patients with relapsed or refractory multiple myeloma , carfilzomib with dexamethasone could be considered in cases in which bortezomib with dexamethasone is a potential treatment option . FUNDING Onyx Pharmaceuticals , Inc. , an Amgen subsidiary BACKGROUND Elotuzumab , an immunostimulatory monoclonal antibody targeting signalling lymphocytic activation molecule ( SLAM ) family member 7 ( SLAMF7 ) , selectively kills SLAMF7-expressing myeloma cells through direct activation and engagement of the innate immune system , and thus might have clinical benefit in the treatment of myeloma . In phase 1 of this phase 1b-2 study , 82 % of patients with relapsed multiple myeloma who were given elotuzumab plus lenalidomide and dexamethasone achieved an overall response . Here we report the final phase 2 results . METHODS We did this r and omised , multicentre , open-label , dose-escalation study ( 1703 ) at 17 hospitals in the USA , Canada , France , and Germany . Patients aged at least 18 years with confirmed , relapsed multiple myeloma , Eastern Cooperative Oncology Group performance status 0 - 2 , and one to three previous therapies but no previous lenalidomide were eligible for phase 2 . We r and omly assigned patients ( 1:1 ) to either 10 mg/kg or 20 mg/kg intravenous elotuzumab plus oral lenalidomide ( 25 mg ) and dexamethasone ( 40 mg ) . We stratified patients on the basis of the number of previous therapies ( one versus two or three ) , and status of previous treatment with immunomodulatory drugs ( yes or no ) , and used permuted block r and omisation with a block size of four . Treatment was given in 28-day cycles until disease progression or unacceptable toxic effects occurred ( elotuzumab was given on days 1 , 8 , 15 , and 22 for cycles 1 to 2 and days 1 and 15 for subsequent cycles ; lenalidomide was given on days 1 - 21 and dexamethasone once per week ) . The primary endpoint was the proportion of patients who achieved an objective response according to International Myeloma Working Group criteria . Primary analyses were done in the intention-to-treat population , and safety was analysed in all patients who received at least one dose of study drugs . This study is registered with Clinical Trials.gov , number NCT00742560 . FINDINGS Between Jan 4 , 2010 , and Dec 21 , 2010 , we recruited and r and omly assigned 73 patients to elotuzumab ( 36 to 10 mg/kg , 37 to 20 mg/kg ) . At data cutoff ( Jan 16 , 2014 ) , 13 patients remained on treatment ( six on 10 mg/kg , seven on 20 mg/kg ) . 61 ( 84 % ) patients achieved an objective response ( 33 [ 92 % ] with 10 mg/kg , 28 [ 76 % ] with 20 mg/kg ) ; 31 ( 42 % ) a very good partial response ( 17 [ 47 % ] with 10 mg/kg , 14 [ 38 % ] with 20 mg/kg ) ; and 20 ( 27 % ) a partial response ( 10 [ 28 % ] with 10 mg/kg , 10 [ 27 % ] with 20 mg/kg ) . The most common treatment-emergent adverse events of any grade were diarrhoea ( 48 [ 66 % ] ) , muscle spasms ( 45 [ 62 % ] ) , and fatigue ( 41 [ 56 % ] ) . 57 ( 78 % ) patients had grade 3 - 4 events , the most common of which were lymphopenia ( 15 [ 21 % ] ) and neutropenia ( 14 [ 19 % ] ) . Three deaths occurred , none related to the study drugs . INTERPRETATION Elotuzumab combined with lenalidomide and dexamethasone in patients with relapsed multiple myeloma showed acceptable safety and efficacy that seems better than that previously noted with lenalidomide and dexamethasone only . Phase 3 trials are in progress . FUNDING Bristol-Myers Squibb , AbbVie Biotherapeutics This multicenter , first-in-human study evaluated the safety , tolerability , and pharmacokinetic and pharmacodynamic properties of the anti-CS1 monoclonal antibody elotuzumab . A st and ard 3 + 3 design was used to determine maximum tolerated dose ; dose-limiting toxicities were assessed during cycle 1 . Thirty-five patients with relapsed/refractory multiple myeloma were treated with intravenous elotuzumab at doses ranging from 0.5 to 20 mg/kg every 2 weeks . Patients who achieved at least stable disease after 4 treatments could receive another 4 treatments . No maximum tolerated dose was identified up to the maximum planned dose of 20 mg/kg . The most common adverse events , regardless of attribution , were cough , headache , back pain , fever , and chills . Adverse events were generally mild to moderate in severity , and adverse events attributed to study medication were primarily infusion-related . Plasma elotuzumab levels and terminal half-life increased with dose whereas clearance decreased , suggesting target-mediated clearance . CS1 on bone marrow-derived plasma cells was reliably saturated ( ≥ 95 % ) at the 10-mg/kg and 20-mg/kg dose levels . Using the European Group for Bone and Marrow Transplantation myeloma response criteria , 9 patients ( 26.5 % ) had stable disease . In summary , elotuzumab was generally well tolerated in this population , justifying further exploration of this agent in combination regimens CD38 , a type II transmembrane glycoprotein highly expressed in hematological malignancies including multiple myeloma ( MM ) , represents a promising target for mAb-based immunotherapy . In this study , we describe the cytotoxic mechanisms of action of daratumumab , a novel , high-affinity , therapeutic human mAb against a unique CD38 epitope . Daratumumab induced potent Ab-dependent cellular cytotoxicity in CD38-expressing lymphoma- and MM-derived cell lines as well as in patient MM cells , both with autologous and allogeneic effector cells . Daratumumab stood out from other CD38 mAbs in its strong ability to induce complement-dependent cytotoxicity in patient MM cells . Importantly , daratumumab-induced Ab-dependent cellular cytotoxicity and complement-dependent cytotoxicity were not affected by the presence of bone marrow stromal cells , indicating that daratumumab can effectively kill MM tumor cells in a tumor-preserving bone marrow microenvironment . In vivo , daratumumab was highly active and interrupted xenograft tumor growth at low dosing . Collectively , our results show the versatility of daratumumab to effectively kill CD38-expressing tumor cells , including patient MM cells , via diverse cytotoxic mechanisms . These findings support clinical development of daratumumab for the treatment of CD38-positive MM tumors BACKGROUND New treatment options are needed for patients with multiple myeloma that is refractory to proteasome inhibitors and immunomodulatory drugs . We assessed daratumumab , a novel CD38-targeted monoclonal antibody , in patients with refractory multiple myeloma . METHODS In this open-label , multicentre , phase 2 trial done in Canada , Spain , and the USA , patients ( age ≥18 years ) with multiple myeloma who were previously treated with at least three lines of therapy ( including proteasome inhibitors and immunomodulatory drugs ) , or were refractory to both proteasome inhibitors and immunomodulatory drugs , were r and omly allocated in a 1:1 ratio to receive intravenous daratumumab 8 mg/kg or 16 mg/kg in part 1 stage 1 of the study , to decide the dose for further assessment in part 2 . Patients received 8 mg/kg every 4 weeks , or 16 mg/kg per week for 8 weeks ( cycles 1 and 2 ) , then every 2 weeks for 16 weeks ( cycles 3 - 6 ) , and then every 4 weeks thereafter ( cycle 7 and higher ) . The allocation schedule was computer-generated and r and omisation , with permuted blocks , was done central ly with an interactive web response system . In part 1 stage 2 and part 2 , patients received 16 mg/kg dosed as in part 1 stage 1 . The primary endpoint was overall response rate ( partial response [ PR ] + very good PR + complete response [ CR ] + stringent CR ) . All patients who received at least one dose of daratumumab were included in the analysis . The trial is registered with Clinical Trials.gov , number NCT01985126 . FINDINGS The study is ongoing . In part 1 stage 1 of the study , 18 patients were r and omly allocated to the 8 mg/kg group and 16 to the 16 mg/kg group . Findings are reported for the 106 patients who received daratumumab 16 mg/kg in parts 1 and 2 . Patients received a median of five previous lines of therapy ( range 2 - 14 ) . 85 ( 80 % ) patients had previously received autologous stem cell transplantation , 101 ( 95 % ) were refractory to the most recent proteasome inhibitors and immunomodulatory drugs used , and 103 ( 97 % ) were refractory to the last line of therapy . Overall responses were noted in 31 patients ( 29.2 % , 95 % CI 20.8 - 38.9)-three ( 2.8 % , 0.6 - 8.0 ) had a stringent CR , ten ( 9.4 % , 4.6 - 16.7 ) had a very good PR , and 18 ( 17.0 % , 10.4 - 25.5 ) had a PR . The median time to first response was 1.0 month ( range 0.9 - 5.6 ) . Median duration of response was 7.4 months ( 95 % CI 5.5-not estimable ) and progression-free survival was 3.7 months ( 95 % CI 2.8 - 4.6 ) . The 12-month overall survival was 64.8 % ( 95 % CI 51.2 - 75.5 ) and , at a subsequent cutoff , median overall survival was 17.5 months ( 95 % CI 13.7-not estimable ) . Daratumumab was well tolerated ; fatigue ( 42 [ 40 % ] patients ) and anaemia ( 35 [ 33 % ] ) of any grade were the most common adverse events . No drug-related adverse events led to treatment discontinuation . INTERPRETATION Daratumumab monotherapy showed encouraging efficacy in heavily pretreated and refractory patients with multiple myeloma , with a favourable safety profile in this population of patients . FUNDING Janssen Research & Development BACKGROUND Elotuzumab , an immunostimulatory monoclonal antibody targeting signaling lymphocytic activation molecule F7 ( SLAMF7 ) , showed activity in combination with lenalidomide and dexamethasone in a phase 1b-2 study in patients with relapsed or refractory multiple myeloma . METHODS In this phase 3 study , we r and omly assigned patients to receive either elotuzumab plus lenalidomide and dexamethasone ( elotuzumab group ) or lenalidomide and dexamethasone alone ( control group ) . Co primary end points were progression-free survival and the overall response rate . Final results for the co primary end points are reported on the basis of a planned interim analysis of progression-free survival . RESULTS Overall , 321 patients were assigned to the elotuzumab group and 325 to the control group . After a median follow-up of 24.5 months , the rate of progression-free survival at 1 year in the elotuzumab group was 68 % , as compared with 57 % in the control group ; at 2 years , the rates were 41 % and 27 % , respectively . Median progression-free survival in the elotuzumab group was 19.4 months , versus 14.9 months in the control group ( hazard ratio for progression or death in the elotuzumab group , 0.70 ; 95 % confidence interval , 0.57 to 0.85 ; P<0.001 ) . The overall response rate in the elotuzumab group was 79 % , versus 66 % in the control group ( P<0.001 ) . Common grade 3 or 4 adverse events in the two groups were lymphocytopenia , neutropenia , fatigue , and pneumonia . Infusion reactions occurred in 33 patients ( 10 % ) in the elotuzumab group and were grade 1 or 2 in 29 patients . CONCLUSIONS Patients with relapsed or refractory multiple myeloma who received a combination of elotuzumab , lenalidomide , and dexamethasone had a significant relative reduction of 30 % in the risk of disease progression or death . ( Funded by Bristol-Myers Squibb and AbbVie Biotherapeutics ; ELOQUENT-2 Clinical Trials.gov number , NCT01239797 . ) PURPOSE To evaluate the maximum-tolerated dose ( MTD ) , safety , and efficacy of elotuzumab in combination with bortezomib in patients with relapsed or relapsed and refractory multiple myeloma ( MM ) . PATIENTS AND METHODS Elotuzumab ( 2.5 , 5.0 , 10 , or 20 mg/kg intravenously [ IV ] ) and bortezomib ( 1.3 mg/m(2 ) IV ) were administered on days 1 and 11 and days 1 , 4 , 8 , and 11 , respectively , in 21-day cycles by using a 3 + 3 dose-escalation design . Patients with stable disease or better after four cycles could continue treatment until disease progression or unexpected toxicity . Responses were assessed during each cycle by using European Group for Blood and Marrow Transplantation ( EBMT ) criteria . RESULTS Twenty-eight patients with a median of two prior therapies were enrolled ; three patients each received 2.5 , 5.0 , and 10 mg/kg of elotuzumab and 19 received 20 mg/kg ( six during dose escalation and 13 during an expansion phase ) . No dose-limiting toxicities were observed during cycle 1 of the dose-escalation phase , and the MTD was not reached up to the maximum planned dose of 20 mg/kg . The most frequent grade 3 to 4 adverse events ( AEs ) were lymphopenia ( 25 % ) and fatigue ( 14 % ) . Two elotuzumab-related serious AEs of chest pain and gastroenteritis occurred in one patient . An objective response ( a partial response or better ) was observed in 13 ( 48 % ) of 27 evaluable patients and in two ( 67 % ) of three patients refractory to bortezomib . Median time to progression was 9.46 months . CONCLUSION The combination of elotuzumab and bortezomib was generally well-tolerated and showed encouraging activity in patients with relapsed/refractory MM BACKGROUND Lenalidomide plus dexamethasone is a reference treatment for relapsed multiple myeloma . The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple myeloma . METHODS We r and omly assigned 792 patients with relapsed multiple myeloma to carfilzomib with lenalidomide and dexamethasone ( carfilzomib group ) or lenalidomide and dexamethasone alone ( control group ) . The primary end point was progression-free survival . RESULTS Progression-free survival was significantly improved with carfilzomib ( median , 26.3 months , vs. 17.6 months in the control group ; hazard ratio for progression or death , 0.69 ; 95 % confidence interval [ CI ] , 0.57 to 0.83 ; P=0.0001 ) . The median overall survival was not reached in either group at the interim analysis . The Kaplan-Meier 24-month overall survival rates were 73.3 % and 65.0 % in the carfilzomib and control groups , respectively ( hazard ratio for death , 0.79 ; 95 % CI , 0.63 to 0.99 ; P=0.04 ) . The rates of overall response ( partial response or better ) were 87.1 % and 66.7 % in the carfilzomib and control groups , respectively ( P<0.001 ; 31.8 % and 9.3 % of patients in the respective groups had a complete response or better ; 14.1 % and 4.3 % had a stringent complete response ) . Adverse events of grade 3 or higher were reported in 83.7 % and 80.7 % of patients in the carfilzomib and control groups , respectively ; 15.3 % and 17.7 % of patients discontinued treatment owing to adverse events . Patients in the carfilzomib group reported superior health-related quality of life . CONCLUSIONS In patients with relapsed multiple myeloma , the addition of carfilzomib to lenalidomide and dexamethasone result ed in significantly improved progression-free survival at the interim analysis and had a favorable risk-benefit profile . ( Funded by Onyx Pharmaceuticals ; Clinical Trials.gov number , NCT01080391 . ) BACKGROUND Ixazomib is an oral proteasome inhibitor that is currently being studied for the treatment of multiple myeloma . METHODS In this double-blind , placebo-controlled , phase 3 trial , we r and omly assigned 722 patients who had relapsed , refractory , or relapsed and refractory multiple myeloma to receive ixazomib plus lenalidomide-dexamethasone ( ixazomib group ) or placebo plus lenalidomide-dexamethasone ( placebo group ) . The primary end point was progression-free survival . RESULTS Progression-free survival was significantly longer in the ixazomib group than in the placebo group at a median follow-up of 14.7 months ( median progression-free survival , 20.6 months vs. 14.7 months ; hazard ratio for disease progression or death in the ixazomib group , 0.74 ; P=0.01 ) ; a benefit with respect to progression-free survival was observed with the ixazomib regimen , as compared with the placebo regimen , in all prespecified patient subgroups , including in patients with high-risk cytogenetic abnormalities . The overall rates of response were 78 % in the ixazomib group and 72 % in the placebo group , and the corresponding rates of complete response plus very good partial response were 48 % and 39 % . The median time to response was 1.1 months in the ixazomib group and 1.9 months in the placebo group , and the corresponding median duration of response was 20.5 months and 15.0 months . At a median follow-up of approximately 23 months , the median overall survival has not been reached in either study group , and follow-up is ongoing . The rates of serious adverse events were similar in the two study groups ( 47 % in the ixazomib group and 49 % in the placebo group ) , as were the rates of death during the study period ( 4 % and 6 % , respectively ) ; adverse events of at least grade 3 severity occurred in 74 % and 69 % of the patients , respectively . Thrombocytopenia of grade 3 and grade 4 severity occurred more frequently in the ixazomib group ( 12 % and 7 % of the patients , respectively ) than in the placebo group ( 5 % and 4 % of the patients , respectively ) . Rash occurred more frequently in the ixazomib group than in the placebo group ( 36 % vs. 23 % of the patients ) , as did gastrointestinal adverse events , which were predominantly low grade . The incidence of peripheral neuropathy was 27 % in the ixazomib group and 22 % in the placebo group ( grade 3 events occurred in 2 % of the patients in each study group ) . Patient-reported quality of life was similar in the two study groups . CONCLUSIONS The addition of ixazomib to a regimen of lenalidomide and dexamethasone was associated with significantly longer progression-free survival ; the additional toxic effects with this all-oral regimen were limited . ( Funded by Millennium Pharmaceuticals ; TOURMALINE-MM1 Clinical Trials.gov number , NCT01564537 . ) BACKGROUND Daratumumab , a human IgGκ monoclonal antibody that targets CD38 , induces direct and indirect antimyeloma activity and has shown substantial efficacy as monotherapy in heavily pretreated patients with multiple myeloma , as well as in combination with bortezomib in patients with newly diagnosed multiple myeloma . METHODS In this phase 3 trial , we r and omly assigned 498 patients with relapsed or relapsed and refractory multiple myeloma to receive bortezomib ( 1.3 mg per square meter of body-surface area ) and dexamethasone ( 20 mg ) alone ( control group ) or in combination with daratumumab ( 16 mg per kilogram of body weight ) ( daratumumab group ) . The primary end point was progression-free survival . RESULTS A prespecified interim analysis showed that the rate of progression-free survival was significantly higher in the daratumumab group than in the control group ; the 12-month rate of progression-free survival was 60.7 % in the daratumumab group versus 26.9 % in the control group . After a median follow-up period of 7.4 months , the median progression-free survival was not reached in the daratumumab group and was 7.2 months in the control group ( hazard ratio for progression or death with daratumumab vs. control , 0.39 ; 95 % confidence interval , 0.28 to 0.53 ; P<0.001 ) . The rate of overall response was higher in the daratumumab group than in the control group ( 82.9 % vs. 63.2 % , P<0.001 ) , as were the rates of very good partial response or better ( 59.2 % vs. 29.1 % , P<0.001 ) and complete response or better ( 19.2 % vs. 9.0 % , P=0.001 ) . Three of the most common grade 3 or 4 adverse events reported in the daratumumab group and the control group were thrombocytopenia ( 45.3 % and 32.9 % , respectively ) , anemia ( 14.4 % and 16.0 % , respectively ) , and neutropenia ( 12.8 % and 4.2 % , respectively ) . Infusion-related reactions that were associated with daratumumab treatment were reported in 45.3 % of the patients in the daratumumab group ; these reactions were mostly grade 1 or 2 ( grade 3 in 8.6 % of the patients ) , and in 98.2 % of these patients , they occurred during the first infusion . CONCLUSIONS Among patients with relapsed or relapsed and refractory multiple myeloma , daratumumab in combination with bortezomib and dexamethasone result ed in significantly longer progression-free survival than bortezomib and dexamethasone alone and was associated with infusion-related reactions and higher rates of thrombocytopenia and neutropenia than bortezomib and dexamethasone alone . ( Funded by Janssen Research and Development ; Clinical Trials.gov number , NCT02136134 . ) Daratumumab targets CD38-expressing myeloma cells through a variety of immune-mediated mechanisms ( complement-dependent cytotoxicity , antibody-dependent cell-mediated cytotoxicity , and antibody-dependent cellular phagocytosis ) and direct apoptosis with crosslinking . These mechanisms may also target nonplasma cells that express CD38 , which prompted evaluation of daratumumab 's effects on CD38-positive immune sub population s. Peripheral blood ( PB ) and bone marrow ( BM ) from patients with relapsed/refractory myeloma from 2 daratumumab monotherapy studies were analyzed before and during therapy and at relapse . Regulatory B cells and myeloid-derived suppressor cells , previously shown to express CD38 , were evaluated for immunosuppressive activity and daratumumab sensitivity in the myeloma setting . A novel sub population of regulatory T cells ( Tregs ) expressing CD38 was identified . These Tregs were more immunosuppressive in vitro than CD38-negative Tregs and were reduced in daratumumab-treated patients . In parallel , daratumumab induced robust increases in helper and cytotoxic T-cell absolute counts . In PB and BM , daratumumab induced significant increases in CD8(+):CD4(+ ) and CD8(+):Treg ratios , and increased memory T cells while decreasing naïve T cells . The majority of patients demonstrated these broad T-cell changes , although patients with a partial response or better showed greater maximum effector and helper T-cell increases , elevated antiviral and alloreactive functional responses , and significantly greater increases in T-cell clonality as measured by T-cell receptor ( TCR ) sequencing . Increased TCR clonality positively correlated with increased CD8(+ ) PB T-cell counts . Depletion of CD38(+ ) immunosuppressive cells , which is associated with an increase in T-helper cells , cytotoxic T cells , T-cell functional response , and TCR clonality , represents possible additional mechanisms of action for daratumumab and deserves further exploration |
911 | 25,681,408 | Conclusions : Our results found a beneficial effect for strength/resistance and coordination/stabilisation exercise programs over other interventions in the treatment of chronic low back pain and that cardiorespiratory and combined exercise programs are ineffective | Objective : To determine , for adults with chronic low back pain , which exercise interventions are the most effective at reducing pain compared to other treatments . | Background The evidence that exercise intervention is effective for treatment of chronic low back pain comes from trials that are not placebo-controlled . Objective The purpose of this study was to investigate the efficacy of motor control exercise for people with chronic low back pain . Design This was a r and omized , placebo-controlled trial . Setting The study was conducted in an outpatient physical therapy department in Australia . Patients The participants were 154 patients with chronic low back pain of more than 12 weeks ’ duration . Intervention Twelve sessions of motor control exercise ( ie , exercises design ed to improve function of specific muscles of the low back region and the control of posture and movement ) or placebo ( ie , detuned ultrasound therapy and detuned short-wave therapy ) were conducted over 8 weeks . Measurements Primary outcomes were pain intensity , activity ( measured by the Patient-Specific Functional Scale ) , and patient 's global impression of recovery measured at 2 months . Secondary outcomes were pain ; activity ( measured by the Patient-Specific Functional Scale ) ; patient 's global impression of recovery measured at 6 and 12 months ; activity limitation ( measured by the Rol and -Morris Disability Question naire ) at 2 , 6 , and 12 months ; and risk of persistent or recurrent pain at 12 months . Results The exercise intervention improved activity and patient 's global impression of recovery but did not clearly reduce pain at 2 months . The mean effect of exercise on activity ( measured by the Patient-Specific Functional Scale ) was 1.1 points ( 95 % confidence interval [CI]=0.3 to 1.8 ) , the mean effect on global impression of recovery was 1.5 points ( 95 % CI=0.4 to 2.5 ) , and the mean effect on pain was 0.9 points ( 95 % CI=−0.01 to 1.8 ) , all measured on 11-point scales . Secondary outcomes also favored motor control exercise . Limitation Clinicians could not be blinded to the intervention they provided . Conclusions Motor control exercise produced short-term improvements in global impression of recovery and activity , but not pain , for people with chronic low back pain . Most of the effects observed in the short term were maintained at the 6- and 12-month follow-ups OBJECTIVE To compare the effects of 4 months of isolated lumbar resistance exercise and total body resistance exercise on walking performance in obese , older adults with chronic low back pain . A secondary analysis examined whether responsiveness to training modulated walking improvement . DESIGN R and omized , controlled trial . SETTING Research laboratory affiliated with tertiary care facility . METHODS AND INTERVENTION Participants ( N = 49 ; 60 - 85 years ) were r and omized into a 4-month resistance exercise intervention ( TOTRX ) , lumbar extensor exercise intervention ( LEXT ) , or a control group ( CON ) . MAIN OUTCOME MEASUREMENTS Walking performance , maximal low back strength and leg strength , and average resting and low back pain severity score ( from an 11-point numerical pain rating scale ; NRSpain ) were collected at baseline and month 4 . RESULTS The TOTRX and LEXT improved lumbar extensor strength relative to CON , and the TOTRX ( P < .05 ) . NRSpain scores at month 4 were lowest in the TOTRX group compared with the LEXT and CON groups , respectively ( 2.0 ± 1.7 points vs 3.7 ± 2.6 points and 4.6 ± 2.4 points ; P < .006 ) . A total of 53 % and 67 % of participants in the TOTRX and LEXT groups were responders who made lumbar extensor strength gains that achieved ≥20 % greater than baseline values . Although the TOTRX demonstrated the greatest improvement in walking endurance among the intervention groups , this did not reach significance ( 10.1 ± 12.2 % improvement in TOTRX vs 7.4 ± 30.0 % LEXT and -1.7 ± 17.4 % CON ; P = .11 ) . Gait speed increased most in the TOTRX ( 9.0 ± 13.5 % ) compared with the LEXT and CON groups ( P < .05 ) . The change in lumbar extensor strength explained 10.6 % of the variance of the regression model for the change in walking endurance ( P = .024 ) . CONCLUSIONS The use of LEXT and TOTRX produced similar modest improvements in patients ' walking endurance . Lumbar extensor strength gain compared with leg strength gain is a moderate but important contributor to walking endurance in obese older adults with chronic low back pain . Responders to resistance exercise programs ( event those with only lumbar extension exercise ) who make at least a 20 % improvement in strength can expect better improvement in walking endurance than those who do not achieve this strength improvement Background The treatment of non-specific chronic low back pain is often based on three different models regarding the development and maintenance of pain and especially functional limitations : the deconditioning model , the cognitive behavioral model and the biopsychosocial model . There is evidence that rehabilitation of patients with chronic low back pain is more effective than no treatment , but information is lacking about the differential effectiveness of different kinds of rehabilitation . A direct comparison of a physical , a cognitive-behavioral treatment and a combination of both has never been carried out so far . Methods The effectiveness of active physical , cognitive-behavioral and combined treatment for chronic non-specific low back pain compared with a waiting list control group was determined by performing a r and omized controlled trial in three rehabilitation centers . Two hundred and twenty three patients were r and omized , using concealed block r and omization to one of the following treatments , which they attended three times a week for 10 weeks : Active Physical Treatment ( APT ) , Cognitive-Behavioral Treatment ( CBT ) , Combined Treatment of APT and CBT ( CT ) , or Waiting List ( WL ) . The outcome variables were self-reported functional limitations , patient 's main complaints , pain , mood , self-rated treatment effectiveness , treatment satisfaction and physical performance including walking , st and ing up , reaching forward , stair climbing and lifting . Assessment s were carried out by blinded research assistants at baseline and immediately post-treatment . The data were analyzed using the intention-to-treat principle . Results For 212 patients , data were available for analysis . After treatment , significant reductions were observed in functional limitations , patient 's main complaints and pain intensity for all three active treatments compared to the WL . Also , the self-rated treatment effectiveness and satisfaction appeared to be higher in the three active treatments . Several physical performance tasks improved in APT and CT but not in CBT . No clinical ly relevant differences were found between the CT and APT , or between CT and CBT . Conclusion All three active treatments were effective in comparison to no treatment , but no clinical ly relevant differences between the combined and the single component treatments were found Objectives Although motor control exercises have been shown to be effective in the management of low back pain ( LBP ) the mechanism of action is unclear . The current study investigated the relationship between the ability to recruit transversus abdominis and clinical outcomes of participants in a clinical trial . Methods Ultrasonography was used to assess the ability to recruit transversus abdominis in a nested design : a sample of 34 participants with chronic LBP was recruited from participants in a r and omised controlled trial comparing the efficacy of motor control exercise , general exercise and spinal manipulative therapy . Perceived recovery , function , disability and pain were also assessed . Results Participants with chronic LBP receiving motor control exercise had a greater improvement in recruitment of transversus abdominis ( 7.8 % ) than participants receiving general exercise ( 4.9 % reduction ) or spinal manipulative therapy ( 3.7 % reduction ) . The effect of motor control exercise on pain reduction was greater in participants who had a poor ability to recruit transversus abdominis at baseline . There was a significant , moderate correlation between improved recruitment of transversus abdominis and a reduction in disability ( r = −0.35 ; 95 % CI 0.02 to 0.62 ) . Conclusion These data provide some support for the hypothesised mechanism of action of motor control exercise and suggest that the treatment may be more effective in those with a poor ability to recruit transversus abdominis OBJECTIVE To determine if the use of an isokinetic device for trunk exercise is more effective than st and ard physiotherapy in promoting motor disinhibition for patients with chronic low back pain . POPULATION chronic low back pain out patients who are treated in a Rheumatology or PM & R unit within an academic hospital . METHODOLOGY This is a prospect i ve , controlled , r and omized study , with two groups of treatment : one treated with isokinetic techniques and the other with st and ard physiotherapy , six sessions for each treatment during 2 weeks . Outcome measures include pain ( VSA ) , trunk mobility ( Schöber index , distance from fingers to floor ) , muscle extensibility and muscle strength ( Biering-Sorensen and Shirado-Ito test ) , and functional capacity ( Quebec scale ) . RESULTS Seventeen subjects were enrolled . The results suggest that both isokinetic exercise and physiotherapy result in improved range of motion , extensibility , muscle strength , and pain , without any significant superiority of one technique over the other . However , each technique has specific advantage . DISCUSSION Despite method ologic limitations , this study shows that isokinetic exercise is not better than physiotherapy in reversing motor inhibition in chronic low back pain . Our results are consistent with those of other studies in the literature , with regard to the absence of established overall superiority of one exercise technique or program over the other in this population , and with regard to partial benefits of specific exercise techniques . CONCLUSION The non-specific benefit of one technique indicates that further studies are needed to evaluate the benefit of combining exercise techniques in chronic low back pain , in order to address the multiple factors involved in this pathology Study Design . R and omized , single blind , controlled trial . Objective . To determine the efficacy of 2 components of musculoskeletal physiotherapy on chronic low back disorder . Summary of Background Data . Musculoskeletal physiotherapy encompasses many treatment methods , however , manual therapy and exercises to rehabilitate spinal stabilization are the most frequently used . Despite their popularity , scant evidence supports their use on subjects with chronic low back disorder . Methods . A total of 346 subjects were r and omized to manual therapy , a 10-week spinal stabilization rehabilitation program , or a minimal intervention control group . Data were collected at baseline , and 3 , 6 , 12 , and 24 months after intervention . Outcome measures recorded intensity of low back pain , disability , h and icap , medication , and quality of life . There were 4 main variables combined in a primary component analysis to form a single outcome measure ( i.e. , a measure of dysfunction ) . Results . The results indicated statistically significant improvements in favor of the spinal stabilization group at the 6-month stage in pain ( 65.9 % reduction in symptoms ) and dysfunction ( combined mean reduction of 134 , st and ard error 23.84 ) , and at the 1-year stage in medication ( 34.3 % reduction in medication ) , dysfunction ( combined mean reduction of 134 , st and ard error 18.2 ) , and disability ( mean difference in change 15.71 Oswestry Disability Index , 95 % confidence interval 19.3–10.01 ) . Conclusions . As a component of musculoskeletal physiotherapy , the spinal stabilization program is more effective than manually applied therapy or an education booklet in treating chronic low back disorder over time . Both manual therapy and the spinal stabilization program are significantly effective in pain reduction in comparison to an active control . To our knowledge and up until now , this result has not been shown in patients with chronic low back disorder OBJECTIVE To develop a clinical prediction rule to predict treatment response to a stabilization exercise program for patients with low back pain ( LBP ) . DESIGN A prospect i ve , cohort study of patients with nonradicular LBP referred to physical therapy ( PT ) . SETTING Outpatient PT clinics . PARTICIPANTS Fifty-four patients with nonradicular LBP . INTERVENTION A st and ardized stabilization exercise program . MAIN OUTCOME MEASURE Treatment response ( success or failure ) was categorized based on changes in the Oswestry Disability Question naire scores after 8 weeks . RESULTS Eighteen subjects were categorized as treatment successes , 15 as treatment failures , and 21 as somewhat improved . After using regression analyses to determine the association between st and ardized examination variables and treatment response status , preliminary clinical prediction rules were developed for predicting success ( positive likelihood ratio [ LR ] , 4.0 ) and failure ( negative LR , .18 ) . The most important variables were age , straight-leg raise , prone instability test , aberrant motions , lumbar hypermobility , and fear-avoidance beliefs . CONCLUSIONS It appears that the response to a stabilization exercise program in patients with LBP can be predicted from variables collected from the clinical examination . The prediction rules could be used to determine whether patients with LBP are likely to benefit from stabilization exercises The application of single motor unit biofeedback training ( SMUBT ) techniques was compared to traditional therapies in treating chronic low back pain ( CLBP ) . Thirty-six volunteers ( who experienced daily pain for 7 years in the T8 to S1 area ) were r and omly assigned to one of three treatments ; SMUBT , relaxation training , or an educational program . The pain level and electromyographic activity of all subjects were assessed by a person blind to the treatment ; before , immediately after , and 90 days after treatment . The SMUBT group reported immediately decreased pain which was maintained at 90 days , the relaxation group showed no changes , while the education group reported decreased pain at 90 days . The EMG results showed decreased amplitude and bilateral differences for the SMUBT and education groups . A 4-year follow-up revealed the SMUBT group remained symptom free . Implication s and discussion of the results concludes the paper Context Yoga combines exercise with achieving a state of mental focus through breathing . In the United States , 1 million people practice yoga for low back pain . Contribution The authors recruited patients who had a recent primary care visit for low back pain and r and omly assigned 101 to yoga or conventional exercise or a self-care book . Patients in the yoga and exercise groups reported good adherence at 26 weeks . Compared with self-care , symptoms were milder and function was better with yoga . The exercise group had intermediate outcomes . Symptoms improved between 12 and 26 weeks only with yoga . Implication s Yoga was a more effective treatment for low back pain than a self-care book . The Editors Most treatments for chronic low back pain have modest efficacy at best ( 1 ) . Exercise is one of the few proven treatments for chronic low back pain ; however , its effects are often small , and no form has been shown to be clearly better than another ( 2 - 5 ) . Yoga , which often couples physical exercise with breathing , is a popular alternative form of mindbody therapy . An estimated 14 million Americans practice d yoga in 2002 ( 6 ) , including more than 1 million who used it as a treatment for back pain ( 7 , 8) . Yoga may benefit patients with back pain simply because it involves exercise or because of its effects on mental focus . We found no published studies in western biomedical literature that evaluated yoga for chronic low back pain ; therefore , we design ed a clinical trial to evaluate its effectiveness and safety for this condition . Methods Study Design and Setting This r and omized , controlled trial compared the effects of yoga classes with conventional exercise classes and with a self-care book in patients with low back pain that persisted for at least 12 weeks . The study was conducted at Group Health Cooperative , a nonprofit , integrated health care system with approximately 500000 enrollees in Washington State and Idaho . The Group Health Cooperative institutional review board approved the study protocol , and all study participants gave oral informed consent before the eligibility screening and written consent before the baseline interview and r and omization . Patients Patients from Group Health Cooperative were recruited for 12-week sessions of classes that were conducted between June and December 2003 . We mailed letters describing the study to 6913 patients between 20 and 64 years of age who had visited a primary care provider for treatment of back pain 3 to 15 months before the study ( according to electronic visit records ) . We also advertised the study in the health plan 's consumer magazine . Patients were informed that we were comparing 3 approaches for the relief of back pain and that each was design ed to help reduce the negative effects of low back pain on people 's lives . A research assistant telephoned patients who returned statements of interest to assess their eligibility . After we received their signed informed consent forms , eligible patients were telephoned again for collection of baseline data and r and omization to treatment . We excluded individuals whose back pain was complicated ( for example , sciatica , previous back surgery , or diagnosed spinal stenosis ) , potentially attributable to specific underlying diseases or conditions ( for example , pregnancy , metastatic cancer , spondylolisthesis , fractured bones , or dislocated joints ) , or minimal ( rating of less than 3 on a bothersomeness scale of 0 to 10 ) . We also excluded individuals who were currently receiving other back pain treatments or had participated in yoga or exercise training for back pain in the past year , those with a possible disincentive to improve ( such as patients receiving workers ' compensation or those involved in litigation ) , and those with unstable medical or severe psychiatric conditions or dementia . Patients who had contraindications ( for example , symptoms consistent with severe disk disease ) or schedules that precluded class participation , those who were unwilling to practice at home , or those who could not speak or underst and English were also excluded . R and omization Protocol Participants were r and omly assigned to participate in yoga or exercise classes or to receive the self-care book . We r and omly generated treatment assignments for each class series by using a computer program with block sizes of 6 or 9 . A research er who was not involved in patient recruitment or r and omization placed the assignments in opaque , sequentially numbered envelopes , which were stored in a locked filing cabinet until needed for r and omization . Interventions The yoga and exercise classes developed specifically for this study consisted of 12 weekly 75-minute classes design ed to benefit people with chronic low back pain . In addition to attending classes held at Group Health facilities , participants were asked to practice daily at home . Participants received h and outs that described home practice s , and yoga participants received auditory compact discs to guide them through the sequence of postures with the appropriate mental focus ( examples of postures are shown in the Appendix Figure ) . Study participants retained access to all medical care provided by their insurance plan . Appendix Figure . Yoga postures Yoga We chose to use viniyoga , a therapeutically oriented style of yoga that emphasizes safety and is relatively easy to learn . Our class instructor and a senior teacher of viniyoga , who has + written a book about its therapeutic uses ( 9 ) , design ed the yoga intervention for patients with back pain who did not have previous yoga experience . Although all the sessions emphasized use of postures and breathing for managing low back symptoms , each had a specific focus : relaxation ; strength-building , flexibility , and large-muscle movement ; asymmetric poses ; strengthening the hip muscles ; lateral bending ; integration ; and customizing a personal practice . The postures were selected from a core of 17 relatively simple postures , some with adaptations ( Appendix Table ) , and the sequence of the postures in each class was performed according to the rudiments of viniyoga ( 9 ) . Each class included a question - and -answer period , an initial and final breathing exercise , 5 to 12 postures , and a guided deep relaxation . Most postures were not held but were repeated 3 or 6 times . Exercise Because we could not identify a clearly superior form of therapeutic exercise for low back pain from the literature , a physical therapist design ed a 12-session class series that was 1 ) different from what most participants would have probably experienced in previous physical therapy sessions ( to maximize adherence ) and 2 ) similar to the yoga classes in number and length . We included a short educational talk that provided information on proper body mechanics , the benefits of exercise and realistic goal setting , and overcoming common barriers to developing an exercise routine ( for example , fear ) . Each session began with the educational talk ; feedback from the previous week ; simple warm-ups to increase heart rate ; and repetitions of a series of 7 aerobic exercises and 10 strengthening exercises that emphasized leg , hip , abdominal , and back muscles . Over the course of the 12-week series , the number of repetitions of each aerobic and strength exercise increased from 8 to 30 in increments of 2 . The strengthening exercises were followed by 12 stretches for the same muscle groups ; each stretch was held for 30 seconds . Classes ended with a short , unguided period of deep , slow breathing . Self-Care Book Participants were mailed a copy of The Back Pain Helpbook ( 10 ) , an evidence -based book that emphasized such self-care strategies as adoption of a comprehensive fitness and strength program , appropriate lifestyle modification , and guidelines for managing flare-ups . Although we did not provide any instructions for using the book , many of the chapters concluded with specific action items . Outcome Measures Interviewers who were masked to the treatment assignments conducted telephone interviews at baseline and at 6 , 12 , and 26 weeks after r and omization . The baseline interview collected information regarding sociodemographic characteristics , back pain history , and the participant 's level of knowledge about yoga and exercise . Participants were asked to describe their current pain and to rate their expectations for each intervention . The primary outcomes were back-related dysfunction and symptoms , and the primary time point of interest was 12 weeks . We used the modified Rol and Disability Scale ( 11 ) to measure patient dysfunction by totaling the number of positive responses to 23 questions about limitations of daily activities that might arise from back pain . This scale has been found to be valid , reliable , and sensitive to change ( 12 - 14 ) ; research ers estimate that the minimum clinical ly significant difference on the Rol and scale ranges from 2 to 3 points ( 13 , 15 ) . Participants rated how bothersome their back pain had been during the previous week on an 11-point scale , in which 0 represented not at all bothersome and 10 represented extremely bothersome ; a similar measure demonstrated substantial construct validity in earlier research ( 13 ) . Estimates of the minimum clinical ly significant difference on the bothersomeness scale were approximately 1.5 points ( 16 , 17 ) . Secondary outcome measures were general health status , which we assessed by conducting the Short Form-36 Health Survey ( 18 ) ; degree of restricted activity as determined by patient responses to 3 questions ( 19 ) ; and medication use . After all outcomes data were collected , we asked questions related to specific interventions ( for example , Did you practice at home ? ) . At the 12-week interview , we asked class participants about any pain or substantial discomfort they experienced as a result of the classes . We assessed adherence to the home practice recommendations by asking class participants to complete weekly home practice logs and by asking about home practice during the follow-up OBJECTIVE To evaluate a progressive fitness programme for patients with chronic low back pain . DESIGN Single blind r and omised controlled trial . Assessment s were carried out before and after treatment by an observer blinded to the study and included a battery of vali date d measures . All patients were followed up by postal question naire six months after treatment . SETTING Physiotherapy department of orthopaedic hospital . SUBJECTS 81 patients with chronic low back pain referred from orthopaedic consultants for physiotherapy . The patients were r and omly allocated to a fitness programme or control group . INTERVENTION Both groups were taught specific exercises to carry out at home and referred to a back-school for education in back care . Patients allocated to the fitness class attended eight exercise classes over four weeks in addition to the home programme and backschool . RESULTS Significant differences between the groups were shown in the changes before and after treatment in scores on the Oswestry low back pain disability index ( P < 0.005 ) , pain reports ( sensory P < 0.05 and affective P < 0.005 ) , self efficacy reports ( P < 0.05 ) , and walking distance ( P < 0.005 ) . No significant differences between the groups were found by the general health question naire or question naire on pain locus of control . A benefit of about 6 percentage points on the disability index was maintained by patients in the fitness group at six months . CONCLUSION There is a role for supervised fitness programmes in the management of moderately disabled patients with chronic low back pain . Further clinical trials , however , need to be established in other centres to confirm these findings [ Purpose ] The purpose of this study was to investigate the effects of a Nintendo Wii exercise program on chronic work-related LBP compared with stability exercise . [ Methods ] Twenty-four workers participated in this study . All of the participants were diagnosed with chronic LBP by a physician . Participants were r and omly assigned to three groups : a control group ( CG ) , lumbar stabilization exercise group ( LSE ) , and Nintendo Wii exercise group ( NWE ) . Participants were treated 3 times a week for 8 weeks . Each session lasted 30 minutes . [ Results ] The results demonstrated that exercise programs improved significantly physical functions related to LBP . In health-related QOL , the Nintendo Wii exercise program significantly improved both the mental and physical health composites , but other groups had significant improvement only in the physical health composite . [ Conclusion ] The Nintendo Wii exercise program could be a biopsychosocial intervention for work-related LBP in factory workers Study Design . R and omized parallel-group comparative trial with a 6-month follow-up period . Objective . To compare , in chronic low back pain patients , the effectiveness of a functional restoration program , including intensive physical training , occupational therapy , and psychological support to an active individual therapy consisting of 3 hours physical therapy per week during 5 weeks . Summary of Background Data . Controlled studies conducted in the United States showed a benefit of functional restoration in patients with low back pain , especially on return to work . R and omized Canadian and European trials had less favorable results . In France , there has been up to now no r and omized study . Controlled studies suggested a positive effect of functional restoration programs . Methods . Eighty-six patients with low back pain were r and omized to either the functional restoration ( 44 patients ) or the active individual therapy ( 42 patients ) program . One person in each group never started the program . Two patients did not complete the functional restoration program , and one was lost to follow-up at 6 months . The mean number of sick-leave days in the 2 previous years was 6 months . Results . After adjustment on the variable ≪ workplace enrolled in an ergonomic program ≫ , the mean number of sick-leave days was significantly lower in the functional restoration group . Physical criteria and treatment appreciation were also better . There was no significant difference in the intensity of pain , the quality of life and functional indexes , the psychological characteristics , the number of contacts with the medical system , and the drug intake . Conclusions . This study demonstrates the effectiveness of a functional restoration program on important outcome measures , such as sick leave , in a country that has a social system that protects people facing difficultiesat work [ Purpose ] This study aim ed to identify the effects of the CORE exercise program on pain and active range of motion ( AROM ) in patients with chronic low back pain . [ Subjects and Methods ] Thirty subjects with chronic low back pain were r and omly allocated to two groups : the CORE group ( n = 15 ) and the control group ( n = 15 ) . The CORE group performed the CORE exercise program for 30 minutes a day , 3 times a week , for 4 weeks , while the control group did not perform any exercise . The visual analog scale ( VAS ) and an algometer were used to measure pain , and pain-free AROM in the trunk was measured before and after the intervention . [ Results ] The CORE group showed significantly decreased VAS scores at rest and during movement and had a significantly increased pressure pain threshold in the quadratus lumborum and AROM in the trunk compared with those in the control group . [ Conclusion ] This study demonstrated that the CORE exercise program is effective in decreasing pain and increasing AROM in patients with chronic low back pain . Thus , the CORE exercise program can be used to manage pain and AROM in patients with chronic low back pain Low back pain is a significant public health problem and one of the most commonly reported reasons for the use of Complementary Alternative Medicine . A r and omized control trial was conducted in subjects with non‐specific chronic low back pain comparing Iyengar yoga therapy to an educational control group . Both programs were 16 weeks long . Subjects were primarily self‐referred and screened by primary care physicians for study of inclusion /exclusion criteria . The primary outcome for the study was functional disability . Secondary outcomes including present pain intensity , pain medication usage , pain‐related attitudes and behaviors , and spinal range of motion were measured before and after the interventions . Subjects had low back pain for 11.2±1.54 years and 48 % used pain medication . Overall , subjects presented with less pain and lower functional disability than subjects in other published intervention studies for chronic low back pain . Of the 60 subjects enrolled , 42 ( 70 % ) completed the study . Multivariate analyses of outcomes in the categories of medical , functional , psychological and behavioral factors indicated that significant differences between groups existed in functional and medical outcomes but not for the psychological or behavioral outcomes . Univariate analyses of medical and functional outcomes revealed significant reductions in pain intensity ( 64 % ) , functional disability ( 77 % ) and pain medication usage ( 88 % ) in the yoga group at the post and 3‐month follow‐up assessment s. These preliminary data indicate that the majority of self‐referred persons with mild chronic low back pain will comply to and report improvement on medical and functional pain‐related outcomes from Iyengar yoga therapy QUESTION Is eight weeks of high-intensity strengthening of the isolated lumbar extensors more effective than low-intensity strengthening or no strengthening ? Are any gains maintained 16 weeks later ? DESIGN R and omised , three-arm trial with concealed allocation , assessor blinding , and intention-to-treat- analysis . Participants in the waiting list control group were r and omised again , after the first 8 weeks , to either the high-intensity or the low-intensity strengthening program . PARTICIPANTS Sixty-five army personnel with non-specific chronic low back pain . INTERVENTION The high-intensity training group received 10 sessions of 15 to 20 repetitions for the isolated lumbar extensor muscles . The low-intensity training group received a nonprogressive , low-intensity resistance protocol . OUTCOME MEASURES Primary outcomes were global perceived effect and disability . Secondary outcomes were health-related quality of life , fear of movement/(re-)injury , and isometric lumbar extensor muscle strength . Measures were taken before and after the training and 16 weeks later . RESULTS At eight weeks , SF-36 overall score was on average 7 % ( 95 % CI 1 to 13 ) greater in the high-intensity training group compared with the low-intensity training group and the waiting list control group , and self-assessed decrease of back symptoms was on average 39 % ( 95 % CI 14 to 64 ) greater in the high-intensity training group compared with the waiting list control group . There was no difference in improvement between the groups for any other outcome at 8 weeks or 24 weeks . CONCLUSIONS Although some beneficial effects were found , the results of this high-intensity strengthening program of the isolated lumbar extensor muscles do not clearly support the generally-cl aim ed beneficial influence of exercise for chronic non-specific low back pain Kell , RT , Risi , AD , and Barden , JM . The response of persons with chronic nonspecific low back pain to three different volumes of periodized musculoskeletal rehabilitation . J Strength Cond Res 25(4 ) : 1052 - 1064 , 2011-Chronic nonspecific low back pain ( CLBP ) is a common musculoskeletal health issue associated with pain and disability reduced quality of life ( QoL ) . Pain initiates a fear-avoidance cycle , which needs to be broken if rehabilitation is to work . To break this cycle , exercise must be gradual and focused on strengthening the weakened musculature . Recently , periodized resistance training was effectively used as a musculoskeletal rehabilitation for adults with CLBP . The purpose of this study was to determine if the volume of periodized musculoskeletal rehabilitation ( PMR ) influences strength , pain , disability , and QoL in untrained persons . Subjects ( n = 240 ) were age and sex matched , with attempts made to match on strength and pain , and r and omly assigned to groups after baseline testing : ( a ) 4 days per week ( 4D ; n = 60 ) , ( b ) 3 days per week ( 3D ; n = 60 ) ( c ) , 2 days per week ( 2D ; n = 60 ) training volume or control ( C ; n = 60 ) with no training . The PMR program progressively overloaded muscle groups , with mean training volumes of 4D ( 1,563 repetitions [ reps ] per week ) , 3D ( 1,344 reps per week ) , and 2D ( 564 reps per week ) . Three weeks of familiarization and 13 weeks of PMR were employed . The 4D training volume significantly ( p ≤ 0.05 ) outperformed all other training volumes by weeks 9 and 13 . However , all training volumes made significant ( p ≤ 0.05 ) improvements in strength , pain , disability , and QoL across time . The effect sizes ( ESs ) associated with the group means of the outcome measures ranged from moderate to strong , with the 4D training volume consistently demonstrating the largest ESs . The 4D training volume is most effective at treating CLBP . Periodization can not only be applied to athlete training but also to the rehabilitation setting Study Design . Prospect i ve case series with historical controls ( normative data ) . Objectives . To compare the aerobic fitness level of patients with chronic low back pain ( CLBP ) with healthy controls matched for gender , age , and level of sport activity and to evaluate the association of the difference in aerobic fitness level with pain intensity , duration and degree of disability , fear of injury , and level of activity during work , including household and leisure time . Summary and Background Data . Controversy exists whether patients with CLBP have a lower level of aerobic fitness and whether this level may partly depend on the patients ’ activity level . Methods . A total of 108 CLBP patients completed question naires regarding pain , disability , fear of injury , and activity level and performed a modified Åstr and submaximal cycling test . The maximum oxygen consumption ( VO2max ) was calculated and compared with normative data . Multiple linear regression analysis was performed with the difference of the level of aerobic fitness as dependent variable . Results . VO2max could be calculated in 78 % of the patients . Both men and women with CLBP had significant lower VO2max than the healthy referents ( 10 mL/kg LBM • min−1 and 5.6 mL/kg LBM • min−1 respectively , P < 0.001 ) , and this difference was significantly greater in men ( P = 0.03 ) . Multiple regression analysis showed that the level of aerobic fitness was not associated with the presumed variables . The patients who stopped the test prematurely were older ( P = 0.02 ) and more disabled ( P = 0.01 ) . Conclusion . CLBP patients , especially men , seem to have a reduced aerobic fitness level compared with the normative population . No explanatory factor for that loss could be identified OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity BACKGROUND Psychological interventions targeting maladaptive pain behaviors and depressive symptoms are commonly used in the management of chronic pain . OBJECTIVE To compare the effectiveness of psychotherapy , based on client-centered therapy , and exercise for patients with chronic nonspecific low back pain ( LBP ) . SETTING Outpatient physiotherapy and psychotherapy departments within a Brazilian academic institution . DESIGN Thirty-three patients with chronic nonspecific LBP were recruited and r and omized to receive client-centered therapy ( N = 16 ) or exercise ( N = 17 ) for 9 weeks . OUTCOME MEASURES AND DATA ANALYSIS : Pain and disability were measured at baseline , 9 weeks , and 6 months by a 10-cm visual analog scale and by the Brazilian Rol and -Morris Question naire , respectively . Depression was measured at baseline and 9 weeks by the Beck Depression Inventory . Multiple regression analyses with baseline scores as covariates were used to determine the effects of treatment on outcomes . RESULTS For all outcomes at each time point , the exercise group showed greater improvements than psychotherapy . The difference between groups was statistically and clinical ly significant for disability at 9 weeks ( -4.9 points , 95 % CI -9.08 to -0.72 ) . CONCLUSIONS This was the first study to investigate the effects of client-centered therapy and exercise for patients with chronic LBP . Our results showed that client-centered therapy is less effective than exercise in reducing disability at short term A number of treatments are widely prescribed for chronic back pain , but few have been rigorously evaluated . We examined the effectiveness of transcutaneous electrical nerve stimulation ( TENS ) , a program of stretching exercises , or a combination of both for low back pain . Patients with chronic low back pain ( median duration , 4.1 years ) were r and omly assigned to receive daily treatment with TENS ( n = 36 ) , sham TENS ( n = 36 ) , TENS plus a program of exercises ( n = 37 ) , or sham TENS plus exercises ( n = 36 ) . After one month no clinical ly or statistically significant treatment effect of TENS was found on any of 11 indicators of outcome measuring pain , function , and back flexion ; there was no interactive effect of TENS with exercise . Overall improvement in pain indicators was 47 percent with TENS and 42 percent with sham TENS ( P not significant ) . The 95 percent confidence intervals for group differences excluded a major clinical benefit of TENS for most outcomes . By contrast , after one month patients in the exercise groups had significant improvement in self-rated pain scores , reduction in the frequency of pain , and greater levels of activity as compared with patients in the groups that did not exercise . The mean reported improvement in pain scores was 52 percent in the exercise groups and 37 percent in the nonexercise groups ( P = 0.02 ) . Two months after the active intervention , however , most patients had discontinued the exercises , and the initial improvements were gone . We conclude that for patients with chronic low back pain , treatment with TENS is no more effective than treatment with a placebo , and TENS adds no apparent benefit to that of exercise alone In recent times lumbar stabilisation programmes , targeting the local stabilisers in the lumbar region , have increased in popularity in the treatment of chronic low back pain ( CLBP ) yet their effectiveness in enhancing quality of life remains unclear . The objective of this pilot study was to examine the effectiveness of a programme of lumbar stabilisation exercises in improving quality of life and functional outcomes in patients with CLBP . Forty-one patients with CLBP who volunteered to take part in the study were r and omly assigned to a treatment group ( n=20 ) or a control group ( n=21 ) . The treatment group underwent a 10-week lumbar stabilisation programme whilst the control group received no intervention . The Rol and Disability Question naire , Oswestry Disability Question naire and the SF-36 survey were administered to subjects in both groups at baseline and follow-up . Significant improvements were seen in all measures in the treatment group whereas control subjects demonstrated either no change or a significant worsening ( P<0.05 ) . These results suggest that a programme of lumbar stabilisation is effective in improving quality of life and functional outcome in patients with CLBP . In jüngster Zeit haben lumbale Stabilisationsprogramme , die auf die lokalen Stabilisatoren des Lumbalbereichs abzielen , bei der Beh and lung von chronischen Schmerzen i m unteren Rückenbereich an Popularität gewonnen , dabei bleibt deren Effektivität i m Hinblick auf die Verbesserung der Lebensqualität unklar . Das Ziel dieser Pilotstudie war die Untersuchung der Wirksamkeit eines Programms mit Übungen zur lumbalen Stabilisation hinsichtlich der Verbesserung der Lebensqualität und der funktionellen Outcomes bei Patienten mit CLBP . 41 freiwillige Studienteilnehmer mit chronischen Schmerzen i m unteren Rückenbereich wurden in r and omisierter Form einer Beh and lungsgruppe ( n=20 ) oder einer Vergleichsgruppe ( n=21 ) zugeordnet . Die Beh and lungsgruppe absolvierte ein 10-wöchiges Programm zur lumbalen Stabilisierung während die Vergleichsgruppe keine Beh and lung erhielt . Zu Studienbeginn und bei der Kontrolluntersuchung wurde in beiden Gruppen der Rol and Disability Question naire , der Oswestry Disability Question naire und der SF-36-Fragebogen ausgefüllt . In der Beh and lungsgruppe zeigten sich bei allen Messungen signifikante Verbesserungen , während in der Vergleichsgruppe die Patienten entweder keine Veränderung oder eine signifikante Verschlechterung aufwiesen ( P<0.05 ) . Diese Ergebnisse legen den Schluss nahe , dass ein Programm zur lumbalen Stabilisation bei der Verbesserung der Lebensqualität und des funktionalen Outcomes bei Patienten mit chronischen Schmerzen i m unteren Rückenbereich wirksam ist . En los últimos años ha aumentado la popularidad de los programas de estabilización lumbar , dirigidos a estabilizar a nivel local la región lumbar , para el tratamiento del dolor lumbar crónico ( DLC ) , pero su eficacia para mejorar la calidad de vida todavía no está clara . El objetivo de este estudio piloto era examinar la eficacia de un programa de ejercicios de estabilización lumbar para mejorar la calidad de vida y los result ados funcionales en pacientes con DLC . Se asignó aleatoriamente a 41 pacientes con DLC que aceptaron participar voluntariamente en el estudio a un grupo de tratamiento ( n=20 ) o a un grupo control ( n=21 ) . El grupo de tratamiento participó en un programa de estabilización lumbar de 10 semanas de duración , mientras que el grupo control no recibió ninguna intervención . Los sujetos de ambos grupos cumplimentaron el Cuestionario de discapacidad de Rol and , el Cuestionario de discapacidad de Oswestry y el cuestionario SF-36 en el periodo basal y en el periodo de seguimiento . Se observaron mejoras significativas de todos los parámetros en el grupo de tratamiento , mientras que en los sujetos del grupo control los parámetros no variaron o empeoraron significativamente ( P<0.05 ) . Estos result ados indican que un programa de estabilización lumbar es eficaz para mejorar la calidad de vida y el result ado funcional en los pacientes con DLC . Récemment , les programmes de rééducation active du rachis lombaire qui visent les muscles assurant la stabilité dans la région lombaire ont acquis une certaine popularité dans le traitement de la lombalgie chronique alors que leur efficacité en termes d'amélioration de la qualité de vie reste à établir . La présente étude pilote avait pour but d'évaluer l'efficacité d'un programme d'exercices de rééducation lombaire sur la qualité de vie et sue la capacité fonctionnelle chez des patients souffrant de lombalgie chronique . Au total , 41 patients lombalgiques chroniques , qui avaient accepté de participer à l'étude , ont été répartis par r and omisation entre deux groupes , do nt l'un était traité ( n=20 ) et l'autre était le groupe témoin ( n=21 ) . Un programme de rééducation lombaire de 10 semaines était mis en place dans le groupe traité , aucune intervention n'étant réalisée dans le groupe témoin . Les outils d'évaluation de l'incapacité fonctionnelle que sont le Rol and Disability Question naire et l'Oswestry Disability Question naire ainsi que l'échelle de qualité de vie SF-36 ont été utilisés chez les patients des deux groupes lors de l'évaluation initiale et pour lors du suivi . Il a été observé des améliorations importantes de toutes les mesures dans le groupe traité , t and is que le groupe témoin ne voyait aucune modification ou bien présentait une aggravation significative ( P<0.05 ) . Ces résultats semblent indiquer qu'un programme de rééducation musculaire du rachis lombaire permet une amélioration de la qualité de vie et des capacités fonctionnelles chez les patients lombalgiques chroniques Kell , RT , and Asmundson , GJG . A comparison of two forms of periodized exercise rehabilitation programs in the management of chronic nonspecific low-back pain . J Strength Cond Res 23(2 ) : 513 - 523 , 2009-The purpose of this study was to determine the influence of 2 different periodized exercise rehabilitation programs ( resistance training [ RT ] and aerobic training [ AT ] ) on musculoskeletal health , body composition , pain , disability , and quality of life ( QOL ) in chronic ( ≥3 months ; ≥3 d·wk−1 ) nonspecific low-back pain ( CLBP ) persons . Twenty-seven CLBP subjects were r and omly assigned to 1 of 3 groups , 1 ) RT ( n = 9 ) , 2 ) AT ( n = 9 ) , or 3 ) control ( C ; n = 9 ) . Subjects were tested at baseline and at weeks 8 and 16 of training . Intensity and volume were periodized in the training groups . Significance was set at p ≤ 0.05 . No significant differences were noted among the groups at baseline . The RT group significantly decreased body fat percent from baseline to week 8 and from baseline to week 16 , whereas the AT group significantly decreased body fat percent and body mass from baseline to week 16 . The RT group significantly improved most musculoskeletal fitness , pain , disability , and QOL outcomes from baseline to week 8 , baseline to week 16 , and weeks 8 to 16 . However , the AT group showed significant improvements in flexibility from baseline to week 8 and in cardiorespiratory and peak leg power from baseline to week 8 and baseline to week 16 . The AT groups showed no significant improvements in pain , disability , or QOL . The primary finding was that periodized RT was successful at improving many fitness , pain , disability , and QOL outcome measures , whereas AT was not . This study indicates that whole-body periodized RT can be used by training and conditioning personnel in the rehabilitation of those clients suffering with CLBP OBJECTIVE To evaluate a specific workplace intervention for the management of chronic lower back pain among employees working in assembly positions in the automotive industry . DESIGN R and omized controlled trial . SETTING On site at the workplace of a French automotive manufacturer . PARTICIPANTS Subjects ( N=75 volunteers ) were recruited on site and r and omly assigned to either an experimental group ( n=37 ) or a control group ( n=38 ) . INTERVENTION The experimental group followed a supervised 60-minute session , 3 times per week , of muscle strengthening , flexibility , and endurance training during 2 months . The control group received no direct intervention . Evaluation took place at baseline , 2 months , and 6 months . MAIN OUTCOME MEASURES Pain related parameters were evaluated using vali date d question naires and scales translated into French ( Quebec Back Pain Disability Scale , Rolan Morris Disability Question naire , Dallas Pain Question naire , and the Tampa Scale for Kinesiophobia ) . Perceived pain intensity was evaluated using the numerical rating scale , and physical outcome measures were evaluated using specific indicators ( flexibility , Biering-Sorensen Test , Shirado test ) . The multivariate analysis of variance , t test , and Wilcoxon signed-rank test were used for statistical analysis . RESULTS We observed a significant beneficial effect ( P<.025 ) for the experimental group at 2 and 6 months in pain parameters , specific flexibility , and in back functions , and a significant improvement at 6 months in the control group for the perceived pain intensity , anterior flexion , flexibility of quadriceps , and Dallas Pain Question naire 's work recreational score . An increase in the practice of physical activity outside the workplace was noted in both groups at 2 months but persisted at 6 months for the experimental group . CONCLUSIONS This study reinforces the multiple health benefits of physical activity and physical therapy modalities in the workplace by assisting individuals at risk who have chronic LBP OBJECTIVE To determine the effectiveness of a special form of exercise therapy ( ' Cesar therapy ' ) on self reported recovery and improvement of posture amongst patients with chronic aspecific lower back pain . DESIGN Prospect i ve r and omized controlled and blinded investigation . METHOD After informed consent had been obtained , patients with chronic aspecific lower back pain were given , on a r and omized basis , either an exercise therapy ( experimental group , n = 112 ) or a st and ard treatment by their general practitioner ( control group , n = 110 ) . Outcome measures were self reported recovery of back pain and improvement of posture ( thoracic and lumbar spine , pelvis ) . Self reported recovery was determined by means of a dichotomized 7-point scale ( question naire ) . Posture was measured qualitatively by a panel of 11 Cesar therapists ( blinded ) and quantitatively by an optical-electronic posture recording system ( Vicon ) . Measurements were taken at baseline ( pre-r and omization ) and at 3 , 6 and 12 months after r and omization . RESULTS Three months after r and omization , patients who were treated according to Cesar therapy , reported an improvement in their back symptoms ( 80 % ) significantly more often than the control group ( 47 % ) . In both groups , however , only small improvements in posture were found . The judgement of the Cesar panel exhibited a significant difference between the two groups , with respect to the spine , in favour of Cesar therapy . Differences between the groups were still present 6 months after r and omization , but could no longer be detected at 12 months after r and omization . CONCLUSION Cesar therapy was significantly more effective than st and ard treatment among patients with chronic lower back pain for a period of 6 months after r and omization STUDY DESIGN A r and omized study comparing the results of active rehabilitation and passive control treatment in patients with chronic low back pain with follow-up at 6 months and 1 year . OBJECTIVES To study the efficacy of active rehabilitation on pain , self-experienced disability , and lumbar fatigability . SUMMARY OF BACKGROUND DATA Exercises in an outpatient setting are widely used for the treatment of chronic low back pain . The efficacy of the active rehabilitation approach has been documented in r and omized control studies , but these studies have seldom been focused on lumbar fatigability , which is now recognized as a frequent problem among patients with chronic low back pain . METHODS Fifty-nine middle-aged patients ( 37 men and 22 women ) with nonspecific chronic low back pain were r and omly assigned to 12 weeks ' active rehabilitation or to a passive control treatment ( massage , thermal therapy ) . Pain and disability index , low back pain intensity ( visual analog scale , 100 mm ) , and the objective ly assessed lumbar muscle fatigability ( spectral electromyogram , mean power frequency slope [ MPFSLOPE ] ) in a new 90-second submaximal isoinertial back endurance test were recorded before and after the interventions and at 6-month and 1-year follow-up visits . RESULTS Results of repeated measures multivariate analysis of variance indicated that back pain intensity ( visual analog scale ) and functional disability ( pain and disability index score ) decreased , and lumbar endurance ( MPFSLOPE ) improved significantly more ( P < 0.05 ) in the active rehabilitation group than in the passive control treatment group , when measured at a 1-year follow-up examination . The group difference in visual analog scale and pain and disability index changes became even more significant at the end of 1 year . The change in lumbar endurance was significantly greater in the active rehabilitation group than in the passive control treatment group at the 6-month follow-up , but not at the 1-year follow-up . CONCLUSIONS The active progressive treatment program was more successful in reducing pain and self-experienced disability and also in improving lumbar endurance than was the passive control treatment . However , the group difference in lumbar endurance tended to diminish at the 1-year follow-up Background and Purpose Given the complex nature of chronic pain , the effects of high-intensity aerobic exercise on pain , disability , psychological strain , and serum cortisol concentrations in people with chronic low back pain were investigated . Subjects Twenty subjects receiving primary health care were r and omly allocated into exercise and control groups . Methods Subjects in the exercise group received a 12-week , high-intensity aerobic exercise program . Subjects in the control group received 12 weeks of passive modalities without any form of physical activity . Results Data analysis identified reductions in pain ( 41 % , t10=8.51 , P<.001 ) , disability ( 31 % , t10=7.32 , P<.001 ) , and psychological strain ( 35 % , t10=7.09 , P<.001 ) in subjects in the exercise group and no changes in subjects in the control group . High-intensity exercise failed to influence serum cortisol concentrations . Discussion and Conclusion Regular high-intensity aerobic exercise alleviated pain , disability , and psychological strain in subjects with chronic low back pain but did not improve serum cortisol concentrations Study Design . A multicenter , r and omized , single‐blinded controlled trial with 1‐year follow‐up . Objectives . To evaluate the efficiency of progressively grade d medical exercise therapy , conventional physiotherapy , and self‐exercise by walking in patients with chronic low back pain . Summary and Background Data . Varieties of medical exercise therapy and conventional physiotherapy are considered to reduce symptoms , improve function , and decrease sickness absence , but this opinion is controversial . Methods . Patients with chronic low back pain or radicular pain sick‐listed for more than 8 weeks and less than 52 weeks ( Sickness Certificate II ) were included . The treatment lasted 3 months ( 36 treatments ) . Pain intensity , functional ability , patient satisfaction , return to work , number of days on sick leave , and costs were recorded . Results . Of the 208 patients included in this study , 71 were r and omly assigned to medical exercise therapy , 67 to conventional physiotherapy , and 70 to self‐exercise . Thirty‐three ( 15.8 % ) patients dropped out during the treatment period . No difference was observed between the medical exercise therapy and conventional physiotherapy groups , but both were significantly better than self‐exercise group . Patient satisfaction was highest for medical exercise therapy . Return to work rates were equal for all 3 intervention groups at assessment 15 months after therapy was started , with 123 patients were back to work . In terms of costs for days on sick leave , the medical exercise therapy group saved 906,732 Norwegian Kroner ( NOK ) ( $ 122,531.00 ) , and the conventional physiotherapy group saved NOK 1,882,560 ( $ 254,200.00 ) , compared with the self‐exercise group . Conclusions . The efficiency of medical exercise therapy and conventional physiotherapy is shown . Leaving patients with chronic low back pain untampered poses a risk of worsening the disability , result ing in longer periods of sick leave OBJECTIVES To examine the relative efficacy of three active therapies for patients with chronic low back pain . METHODS One hundred and forty-eight subjects with chronic low back pain were r and omized to receive , twice weekly for 3 months , ( i ) active physiotherapy , ( ii ) muscle reconditioning on training devices , or ( ii ) low-impact aerobics . Question naires were administered to assess pain intensity , pain frequency and disability before and after therapy and at 6 and 12 months of follow-up . RESULTS One hundred and thirty-two of the 148 patients ( 89 % ) completed the therapy programmes and 127 of the 148 ( 86 % ) returned a question naire at all four time-points . The three treatments were equally efficacious in significantly reducing pain intensity and frequency for up to 1 yr after therapy . However , the groups differed with respect to the temporal changes in self-rated disability over the study period ( P=0.03 ) : all groups showed a similar reduction after therapy , but for the physiotherapy group disability increased again during the first 6 months of follow-up whilst the other two groups showed a further decline . In all groups the values then remained stable up to the 12-month follow-up . The larger group size and minimal infrastructure required for low-impact aerobics rendered it considerably less expensive to administer than the other two programmes . CONCLUSIONS The introduction of low-impact aerobic exercise programmes for patients with chronic low back pain may reduce the enormous costs associated with its treatment OBJECTIVE The aim of this study was to investigate the effect of active non-weight-bearing ( NWB ) group exercising on women with non specific chronic low back pain ( NSCLBP ) . METHODS Forty females with NSCLBP were assigned in a r and omized control longitudinal single blinded pilot study . 20 of them were assigned to a NWB bi-weekly group exercise class and 20 females were included in the control group . The exercises involved the entire lumbo-pelvic spine aim ed at improving lumbar mobility/flexibility and stability . Pain intensity ( VAS ) , back specific disability ( Roll and Morris question naire-RMQ ) , and lumbar flexion and extension ranges of motion measurements were taken prior to intervention ( t(0 ) ) , immediately following 4 weeks of intervention ( t(1 ) ) and 8 weeks later ( t(fu ) ) . Reliability trials were conducted on 10 females . Non-parametric tests were used for statistical significance ( p < 0.05 ) . RESULTS The following significant changes in outcome measures were indicated at t(1 ) compared with t(0 ) and control group ( p < 0.001 ) : an increase in lumbar flexion and extension ( mean difference = 9.26 ◦ ( + 54 % ) for flexion and 5.95 ◦ for extension(+98 % ) ) ; reduction in VAS score ( mean difference = 2.32 ( + 58 % ) ) and RMQ score ( mean difference = 4.9 ( −34 % ) ) . All changes remained significant at t(fu ) . At t(0 ) , lumbar flexion was correlated with extension ( r = 0.547 ) and VAS ( r = −0.581),whereas the RMQ score correlated with VAS score ( r = 0.599 ) and negatively with lumbar extension ( r = −0.665 ) . At t(1),lumbar flexion correlated with extension ( r = 0.664 ) and negatively with RMQ score ( r = −0.54 ) . At t(fu ) , changes in VAS score were negatively correlated with changes in lumbar flexion ( r = −0.522 ) , while changes in lumbar flexion correlated with extension ( r = 0.58 ) . CONCLUSIONS A functional program of NWB group exercising improves functional , painful status , lumbar flexion and extension ranges of motion in women suffering from NSCLBP BACKGROUND AND PURPOSE Improving functional performance in patients with chronic low back pain is of primary importance . The purpose of this study was to examine the effects of 2 proprioceptive neuromuscular facilitation ( PNF ) programs on trunk muscle endurance , flexibility , and functional performance in subjects with chronic low back pain ( CLBP ) . SUBJECTS Eighty-six women ( 40.2+/-11.9 [ mean+/-SD ] years of age ) who had complaints of CLBP were r and omly assigned to 3 groups : rhythmic stabilization training , combination of isotonic exercises , and control . METHODS Subjects trained with each program for 4 weeks with the aim of improving trunk stability and strength . Static and dynamic trunk muscle endurance and lumbar mobility were measured before , at the end of , and 4 and 8 weeks after training . Disability and back pain intensity also were measured with the Oswestry Index . RESULTS Multivariate analysis of variance indicated that both training groups demonstrated significant improvements in lumbar mobility ( 8.6%-24.1 % ) , static and dynamic muscle endurance ( 23.6%-81 % ) , and Oswestry Index ( 29.3%-31.8 % ) measurements . DISCUSSION AND CONCLUSION Static and dynamic PNF programs may be appropriate for improving short-term trunk muscle endurance and trunk mobility in people with CLBP INTRODUCTION A dynamometer employing a stabilization procedure ( lumbar extension machine , MedX , Ocala , FL ) is effective in improving strength and reducing symptoms of low back pain ( LBP ) , and research ers have hypothesized that this effectiveness is due to the pelvic stabilization . However , effects of the dynamometer with and without pelvic stabilization on LBP have not been compared : This was the aim of the present study . METHODS Forty-two chronic LBP patients were r and omly assigned to a lumbar extension training with pelvic stabilization group ( STAB ; n=15 ) , a lumbar extension without pelvic stabilization group ( NO-STAB ; n=15 ) and a control group ( n=12 ) . STAB and NO-STAB participants completed one weekly session of dynamic variable resistance exercise ( one set of 8 - 12 repetitions to fatigue ) on the lumbar extension machine ( with or without pelvic stabilization ) for 12 weeks . Pre- and post-test measures of self-reported LBP ( 101-point visual analog scale ; pre-test mean of 25 ) , related disability ( Oswestry disability index ; pre-test mean of 34 ) and lumbar strength were taken . RESULTS After the exercise program , the STAB group increased significantly in lumbar strength at all joint angles , and decreased significantly in visual analogue and Oswestry scores . However , there were no significant changes in these variables in the NO-STAB and control groups . DISCUSSION Isolated lumbar extension exercise is very effective in reducing LBP in chronic patients . However , when the pelvis is not stabilized , otherwise identical exercises appear ineffective in reducing LBP Objectives : The aim of this study on persons with nonspecific chronic low back pain was to evaluate the effect of a multimodal physical therapy program with or without the addition of deep-water running on pain , physical disability , and general health . Design : A r and omized controlled trial involving 46 subjects with nonspecific chronic low back pain were treated three times a week for 15 wks . Each group received 60 mins of multimodal physical therapy program ( an individualized exercise program ; manual therapy ; and back care , pain education , and information on an active lifestyle ) , whereas one group performed additional 20-min sessions of deep-water running at an individual workload of the aerobic threshold . Results : Both interventions result ed in significant improvements in pain , disability , and physical health . The mean change in pain , disability , and physical health state were −36.1 ± 25.1 mm on the visual analog scale , −3.0 ± 4.8 points for the Rol and Morris Question naire , and 10.6 ± 12.9 points for the Short Form-12 for the physical therapy plus deep-water running group and −34.1 ± 26.0 mm on the visual analog scale , −1.6 ± 1.5 points for the Rol and Morris Question naire , and 8.9 ± 13.0 points for the Short Form-12 for the physical therapy alone group . Conclusions : Pain , disability , health status , muscle strength and endurance , and lumbar range of motion significantly improved in both groups . The addition of a deep-water running program at an individual workload of the aerobic threshold to the multimodal physical therapy program produced a significant improvement in pain in patients with nonspecific chronic low back pain , but this was not significantly different when compared with multimodal physical therapy program alone . Disability , health status , muscle strength and endurance , and lumbar range of motion significantly improved to a similar level in both intervention groups Study Design . Pragmatic , r and omized , assessor blinded , clinical trial with economic analysis . Objective . To compare the effectiveness and cost-effectiveness of three kinds of physiotherapy commonly used to reduce disability in chronic low back pain . Summary of Background Data . Physiotherapy reduces disability in chronic back pain , but there are several forms of physiotherapy and it is unclear which is most effective or cost effective . Methods . A total of 212 patients referred to physiotherapy with chronic low back pain were r and omized to receive usual outpatient physiotherapy , spinal stabilization classes , or physiotherapist-led pain management classes . Primary outcome was Rol and Disability Question naire score 18 months from baseline ; secondary measures were pain , health-related quality of life , and time off work . Healthcare costs associated with low back pain and quality -adjusted life years ( QALYs ) were also measured . Results . A total of 71 participants were assigned to usual outpatient physiotherapy , 72 to spinal stabilization , and 69 to physiotherapist-led pain management . A total of 160 ( 75 % ) provided follow-up data at 18 months , showing similar improvements with all interventions : mean ( 95 % confidence intervals ) Rol and Disability Question naire score improved from 11.1 ( 9.6–12.6 ) to 6.9 ( 5.3–8.4 ) with usual outpatient physiotherapy , 12.8 ( 11.4−14.2 ) to 6.8 ( 4.9–8.6 ) with spinal stabilization , and 11.5 ( 9.8–13.1 ) to 6.5 ( 4.5–8.6 ) following pain management classes . Pain , quality of life , and time off work also improved within all groups with no between-group differences . Mean ( SD ) healthcare costs and QALY gain were £ 474 ( 840 ) and 0.99 ( 0.27 ) for individual physiotherapy , £ 379 ( 1040 ) and 0.90 ( 0.37 ) for spinal stabilization , and £ 165 ( 202 ) and 1.00 ( 0.28 ) for pain management . Conclusions . For chronic low back pain , all three physiotherapy regimens improved disability and other relevant health outcomes , regardless of their content . Physiotherapist-led pain management classes offer a cost-effective alternative to usual outpatient physiotherapy and are associated with less healthcare use . A more widespread adoption of physiotherapist-led pain management could result in considerable cost savings for healthcare providers Study Design . R and omized controlled trial . Objective . To compare the effects of full range of motion ( ROM ) and limited ROM isolated lumbar extension exercise upon full ROM lumbar extension strength , ROM , perceived pain , and disability . Summary of Background Data . Limited ROM is common in chronic low back pain as is lumbar extensor deconditioning . Limited ROM exercise is a common prescription but is yet to be empirically tested . Methods . Males ( n = 21 ) and females ( n = 17 ) with nonspecific chronic low back pain were initially recruited . Participants were r and omized to either a full ROM ( FullROM ) or limited ROM ( LimROM ) training group or a control group . A total of 24 participants ( males : n = 14 , females : n = 10 ) completed the study and were included in analysis . The intervention lasted 12 weeks . FullROM and LimROM groups completed isolated lumbar extension resistance training once per week , performing one set of exercise at 80 % of their maximal tested functional torque to failure . FullROM group trained through a full ROM . LimROM group trained through the mid 50 % of their full ROM . Full ROM isolated lumbar extension strength , lumbar and st and ing ROM ( Schobers test ) , perceived pain ( visual analogue scale ) , and disability ( Revised Oswestry Disability Index ) were measured pre- and postintervention . Results . FullROM and LimROM significantly improved in full ROM lumbar extension strength , perceived pain , and disability compared with the control group . No changes occurred in lumbar or st and ing ROM . No significant differences were found between either FullROM or LimROM for any outcome measure . Changes in perceived pain and disability met minimal clinical ly important change values for FullROM ( visual analogue scale , −30.3 + 25.76 mm and Oswestry Disability Index , −18.2 + 6.63 patients ) and LimROM ( visual analogue scale , −16.29 + 10.97 mm and Oswestry Disability Index , −12 + 5.16 patients ) . Conclusion . The results suggest that both FullROM and LimROM are equally effective in increasing full ROM lumbar extension strength and producing clinical ly meaningful improvement in perceived pain and disability . Level of Evidence : |
912 | 28,862,313 | No judgement could be made on which protocol is " best " for measuring VO2max in persons after stroke due to lack of high- quality studies on the measurement properties of the cardiopulmonary exercise test | OBJECTIVE To systematic ally review and critically appraise the literature on measurement properties of cardiopulmonary exercise test protocol s for measuring aerobic capacity , VO2max , in persons after stroke . | Background and Purpose — Despite the importance of exercise training in mitigating cardiovascular risk , the development of exercise programs for people poststroke has been limited by lack of feasibility data concerning cardiopulmonary exercise testing ( CPET ) to inform the exercise prescription . Therefore , we examined the feasibility of CPETs for developing an exercise prescription in people ≥3 months poststroke . Methods — CPET results from 98 consecutively enrolled patients poststroke with motor impairments and 98 age- and sex-matched patients with coronary artery disease were examined at baseline and after 6 months of exercise training . Results — The proportion of patients with stroke and coronary artery disease attaining an intensity sufficient for prescribing exercise at baseline was 68.4 % versus 82.7 % , respectively ( P=0.02 ) and 84.7 % versus 83.8 % ( P=0.9 ) at 6 months . Women were less likely than men poststroke to achieve a sufficient intensity at baseline ( 40 % versus 80.9 % , P<0.001 ) but not at 6 months ( 78.3 % versus 87.1 , P=0.3 ) . A clinical ly relevant abnormality occurred in 11.2 % of stroke and 12.2 % of patients with coronary artery disease on baseline CPETs ( P=0.8 ) and 10.6 % of stroke and 5.9 % of patients with coronary artery disease on the 6-month CPET ( P=0.4 ) . No serious cardiovascular events occurred during 349 CPETs . Conclusions — Most patients after stroke achieved a level of exertion during the CPET sufficient to inform an exercise prescription . At least 1 of 10 patients poststroke developed a clinical ly relevant abnormality on baseline and postprogram CPETs with no serious cardiovascular events . These data support the feasibility and safety of CPETs for prescribing exercise poststroke . Strategies to improve use of baseline CPETs for women poststroke require further investigation This study evaluated the feasibility , safety , and findings from a protocol for exercise-bicycle ergometry in subacute-stroke survivors . Of 117 eligible c and i date s , 14 could not perform the test and 3 discontinued because of cardiac safety criteria . In the 100 completed tests , peak heart rate was 116 + /- 19.1 beats/min ; peak VO(2 ) was 11.4 + /- 3.7 ml x kg x min(-1 ) , peak METs were 3.3 + /- 0.91 , exercise duration was 5.1 + /- 2.84 min , and Borg score was 14 + /- 2.6 . Among 71 tests , anaerobic threshold was achieved in 3.0 + /- 1.7 min with a VO(2 ) of 8.6 + /- 1.7 ml x kg x min(-1 ) . After screening , this protocol is feasible and safe in subacute-stroke survivors with mild to moderate deficits . These stroke survivors have severely limited functional exercise capacity . Research and clinical practice in stroke rehabilitation should incorporate more comprehensive evaluation and treatment of endurance limitations Abstract Purpose : The majority of post-stroke individuals suffer from low exercise capacity as a secondary reaction to immobility . The aim of this study was to prove the concept of feedback-controlled robotics-assisted treadmill exercise ( RATE ) to assess aerobic capacity and guide cardiovascular exercise in severely impaired individuals early after stroke . Method : Subjects underwent constant load and incremental exercise testing using a human-in-the-loop feedback system within a robotics-assisted exoskeleton ( Lokomat , Hocoma AG , CH ) . Inclusion criteria were : stroke onset ≤8 weeks , stable medical condition , non-ambulatory status , moderate motor control of the lower limbs and appropriate cognitive function . Outcome measures included oxygen uptake kinetics , peak oxygen uptake ( VO2peak ) , gas exchange threshold ( GET ) , peak heart rate ( HRpeak ) , peak work rate ( Ppeak ) and accuracy of reaching target work rate ( P-RMSE ) . Results : Three subjects ( 18–42 d post-stroke ) were included . Oxygen uptake kinetics during constant load ranged from 42.0 to 60.2 s. Incremental exercise testing showed : VO2peak range 19.7–28.8 ml/min/kg , GET range 11.6–12.7 ml/min/kg , and HRpeak range 115–161 bpm . Ppeak range was 55.2–110.9 W and P-RMSE range was 3.8–7.5 W. Conclusions : The concept of feedback-controlled RATE for assessment of aerobic capacity and guidance of cardiovascular exercise is feasible . Further research is warranted to vali date the method on a larger scale . Implication s for Rehabilitation Aerobic capacity is seriously reduced in post-stroke individuals as a secondary reaction to immobility . Robotics-assisted walking devices may have substantial clinical relevance regarding assessment and improvement of aerobic capacity early after stroke . Feedback-controlled robotics-assisted treadmill exercise represents a new concept for cardiovascular assessment and intervention protocol s for severely impaired individuals BACKGROUND AND PURPOSE Rehabilitation care after stroke is highly variable and increasingly shorter in duration . The effect of therapeutic exercise on impairments and functional limitations after stroke is not clear . The objective of this study was to determine whether a structured , progressive , physiologically based exercise program for subacute stroke produces gains greater than those attributable to spontaneous recovery and usual care . METHODS This r and omized , controlled , single-blind clinical trial was conducted in a metropolitan area and 17 participating healthcare institutions . We included persons with stroke who were living in the community . One hundred patients ( mean age , 70 years ; mean Orpington score , 3.4 ) consented and were r and omized from a screened sample of 582 . Ninety-two subjects completed the trial . Intervention was a structured , progressive , physiologically based , therapist-supervised , in-home program of thirty-six 90-minute sessions over 12 weeks targeting flexibility , strength , balance , endurance , and upper-extremity function . Main outcome measures were postintervention strength ( ankle and knee isometric peak torque , grip strength ) , upper- and lower-extremity motor control ( Fugl Meyer ) , balance ( Berg and functional reach ) , endurance ( peak aerobic capacity and exercise duration ) , upper-extremity function ( Wolf Motor Function Test ) , and mobility ( timed 10-m walk and 6-minute walk distance ) . RESULTS In the intention-to-treat multivariate analysis of variance testing the overall effect , the intervention produced greater gains than usual care ( Wilk 's lambda=0.64 , P=0.0056 ) . Both intervention and usual care groups improved in strength , balance , upper- and lower-extremity motor control , upper-extremity function , and gait velocity . Gains for the intervention group exceeded those in the usual care group in balance , endurance , peak aerobic capacity , and mobility . Upper-extremity gains exceeded those in the usual care group only in patients with higher baseline function . CONCLUSIONS This structured , progressive program of therapeutic exercise in persons who had completed acute rehabilitation services produced gains in endurance , balance , and mobility beyond those attributable to spontaneous recovery and usual care Background The test – retest reliability for multiple cardiopulmonary exercise test ( CPX ) variables has not been compared in a single study and the influence of different diseases on test – retest reliability has not been examined . We investigated different measures of test – retest reliability for multiple variables and compared them by category of cardiac or respiratory disease . Methods Patients with chronic obstructive airways disease ( n = 24 ) , heart failure ( n = 43 ) , or severe mitral valve disease ( n = 26 ) were recruited into a prospect i ve study . Each patient underwent two bicycle ergometer tests ; the first , a familiarization test , with a 10 W/min ramp , and the second a personalized ramp based on the results of the familiarization test to elicit maximal effort within 8–10 min . Intraclass correlation coefficients ( ICC ) and coefficients of variation between the two tests were calculated . Influence of potential modifiers was assessed using repeated measures analysis of variance . Results Peak VO2 ( ICC 0.95 , 95 % CI 0.94–0.97 ) , oxygen uptake efficiency slope ( ICC 0.93 , 95 % CI 0.90–0.95 ) , O2 pulse ( ICC 0.96 , 95 % CI 0.94–0.97 ) , and the VE/VCO2 ratio at the nadir ( ICC 0.92 , 95 % CI 0.89–0.95 ) all showed excellent test – retest reliability , with within-subject coefficients of variation < 0.12 . VO2 at the anaerobic threshold ( ICC 0.84 , 95 % CI 0.78–0.89 ) and the VE/VCO2 slope ( ICC 0.88 , 95 % CI 0.79–0.93 ) showed good test – retest reliability , although inferior to peak VO2 . Age , gender , body mass index , disease aetiology , protocol change , and intertest interval did not affect the reliability of most variables . Conclusions CPX showed high test – retest reliability ; certain variables such as peak VO2 and oxygen uptake efficiency slope outperform others . These results identify which variables are most suitable for serial testing of patients with three common disease aetiologies owing to their superior reproducibility Objectives For the measurement of patient-reported outcomes , such as ( health-related ) quality of life , often many measurement instruments exist that intend to measure the same construct . To facilitate instrument selection , our aim was to develop a highly sensitive search filter for finding studies on measurement properties of measurement instruments in PubMed and a more precise search filter that needs less abstract s to be screened , but at a higher risk of missing relevant studies . Methods A r and om sample of 10,000 PubMed records ( 01 - 01 - 1990 to 31 - 12 - 2006 ) was used as a gold st and ard . Studies on measurement properties were identified using an exclusion filter and h and search ing . Search terms were selected from the relevant records in the gold st and ard as well as from 100 systematic review s of measurement properties and combined based on sensitivity and precision . The performance of the filters was tested in the gold st and ard as well as in two validation sets , by calculating sensitivity , precision , specificity , and number needed to read . Results We identified 116 studies on measurement properties in the gold st and ard . The sensitive search filter was able to retrieve 113 of these 116 studies ( sensitivity 97.4 % , precision 4.4 % ) . The precise search filter had a sensitivity of 93.1 % and a precision of 9.4 % . Both filters performed very well in the validation sets . Conclusion The use of these search filters will contribute to evidence -based selection of measurement instruments in all medical fields The assessment of functional capacity reflects the ability to perform activities of daily living that require sustained aerobic metabolism . The integrated efforts and health of the pulmonary , cardiovascular , and skeletal muscle systems dictate an individual ’s functional capacity . Numerous investigations have demonstrated that the assessment of functional capacity provides important diagnostic and prognostic information in a wide variety of clinical and research setting s. This scientific statement , an up date of the previously published American Heart Association ( AHA ) document,1 highlights the major clinical and research applications of functional capacity assessment . For a comprehensive review of exercise testing , the reader is referred to the American College of Cardiology (ACC)/AHA Guidelines for Exercise Testing.2,3 Functional capacity is the ability of an individual to perform aerobic work as defined by the maximal oxygen uptake ( Vo2max ) , that is , the product of cardiac output and arteriovenous oxygen ( a−Vo2 ) difference at physical exhaustion , as shown in the following equation : ! [Formula][1 ] Where HR indicates heart rate and SV indicates stroke volume . Because Vo2max typically is achieved by exercise that involves only about half of the total body musculature , it is generally believed that Vo2max is limited by maximal cardiac output rather than peripheral factors.4 Although Vo2max is measured in liters of oxygen per minute , it usually is expressed in milliliters of oxygen per kilogram of body weight per minute to facilitate intersubject comparisons . In addition , functional capacity , particularly when estimated from the work rate achieved rather than directly measured Vo , is frequently expressed in metabolic equivalents ( METs ) , with 1 MET representing the resting energy expenditure ( ≈3.5 mL O2 · kg−1 · min−1 ) . In this instance , functional capacity is commonly expressed clinical ly as a multiple of the resting metabolic rate . Vo2max … [ 1 ] : Background Exercise testing devices for evaluating cardiopulmonary fitness in patients with severe disability after stroke are lacking , but we have adapted a robotics-assisted tilt table ( RATT ) for cardiopulmonary exercise testing ( CPET ) . Using the RATT in a sample of patients after stroke , this study aim ed to investigate test-retest reliability and repeatability of CPET and to prospect ively investigate changes in cardiopulmonary outcomes over a period of four weeks . Methods Stroke patients with all degrees of disability underwent 3 separate CPET sessions : 2 tests at baseline ( TB1 and TB2 ) and 1 test at follow up ( TF ) . TB1 and TB2 were at least 24 h apart . TB2 and TF were 4 weeks apart . A RATT equipped with force sensors in the thigh cuffs , a work rate estimation algorithm and a real-time visual feedback system was used to guide the patients ’ exercise work rate during CPET . Test-retest reliability and repeatability of CPET variables were analysed using paired t-tests , the intraclass correlation coefficient ( ICC ) , the coefficient of variation ( CoV ) , and Bl and and Altman limits of agreement . Changes in cardiopulmonary fitness during four weeks were analysed using paired t-tests . Results Seventeen sub-acute and chronic stroke patients ( age 62.7 ± 10.4 years [ mean ± SD ] ; 8 females ) completed the test sessions . The median time post stroke was 350 days . There were 4 severely disabled , 1 moderately disabled and 12 mildly disabled patients . For test-retest , there were no statistically significant differences between TB1 and TB2 for most CPET variables . Peak oxygen uptake , peak heart rate , peak work rate and oxygen uptake at the ventilatory anaerobic threshold ( VAT ) and respiratory compensation point ( RCP ) showed good to excellent test-retest reliability ( ICC 0.65–0.94 ) . For all CPET variables , CoV was 4.1–14.5 % . The mean difference was close to zero in most of the CPET variables . There were no significant changes in most cardiopulmonary performance parameters during the 4-week period ( TB2 vs TF ) . Conclusions These findings provide the first evidence of test-retest reliability and repeatability of the principal CPET variables using the novel RATT system and testing methodology , and high success rates in identification of VAT and RCP : good to excellent test-retest reliability and repeatability were found for all submaximal and maximal CPET variables . Reliability and repeatability of the main CPET parameters in stroke patients on the RATT were comparable to previous findings in stroke patients using st and ard exercise testing devices . The RATT has potential to be used as an alternative exercise testing device in patients who have limitations for use of st and ard exercise testing devices BACKGROUND Existing reference values for clinical exercise testing have been derived from small nonr and om sample s , lacking women and older individuals and some with poor or no maximal end criteria . The objective was to study the cardiorespiratory response during maximal exercise in a representative predominantly Caucasian sample of men and women . METHODS Nine hundred four r and omly sample d men and women , 20 to 85 years old , exercised on a treadmill to exhaustion . Oxygen uptake ( V.O2 ) , heart rate ( HR ) , BP , blood lactate concentration , and ventilatory variables were measured . RESULTS Seven hundred fifty-nine participants met the criteria for an acceptable maximal V.O2 ( V.O2max ) based on a respiratory exchange ratio≥1.10 or a Borg score≥17 . In the 20- to 29-year-old age group , V.O2max ( mL/kg/min ) was 40.3 ( ±7.1 ) in women and 48.6 ( ±9.6 ) in men . A linear decline ( 8 % per decade ) was observed after age 30 years in both sexes . Maximal HR decreased with age by ±6.3 beats/min per decade . The maximal oxygen pulse was 33 % lower in women and decreased significantly with age in both sexes by 5 % and 3 % per decade for women and men , respectively . Women 's maximal ventilation was 66 % that of men and decreased with age after 40 to 49 years in both sexes . Breathing reserve was higher and blood lactate was lower in women than in men . CONCLUSIONS This study establishes reference values for V.O2max ( absolute , relative to body weight and fat-free weight ) , maximal HR , oxygen pulse , BP , ventilation , breathing reserve , respiratory exchange ratio , and blood lactate concentration during maximal exercise on treadmill in a large population Abstract Objective : To determine the physiological and functional responses from high aerobic intensity treadmill walking in 4 x 4-minute intervals in people with chronic stroke and to evaluate the feasibility of this mode of training . Method : This was a baseline control trial with 1 year follow-up in an outpatient rehabilitation setting at a university hospital . Eight people with chronic stroke participated in and completed the study . Their mean age was 48.9 ( ± 10.6 ) years . We tested uphill treadmill walking in 4 x 4-minute work periods at an intensity between 85 % and 95 % of peak heart rate from initial maximal treadmill testing . There were 3-minute active breaks between the intervals . The main outcome measures were peak oxygen uptake ( VO2peak ) and walking economy ( Cw ) . Overall compliance and adverse events determine the feasibility . Results : VO2peak increased from 2.32 ( ± 0.44 ) to 2.60 ( ± 0.55 ) L • min–1 post training ( P = .003 ) . Walking economy ( Cw ) improved from 1.12 ( ± 0.15 ) to 1.04 ( ± 0.18 ) L • min–1 ( P = .043 ) . At 1 year follow-up , VO2peak was 2.59 ( ±0.58 ) L • min –1 and was not significantly different from posttraining measurement ( P = 1.00 ) . Cw was 1.19 ( ± 0.15 ) L • min–1 at 1 year follow-up and thus was worse than post training ( P = .023 ) . Functional improvements were found in the 6-minute walk test ( 6MWT ) ( P = .020 ) , 10-meter walk test ( 10MWT ) ( P = .032 ) , and Timed Up and Go test ( TUG ) ( P = .002 ) at post tests . Conclusions : High aerobic intensity interval treadmill walking significantly increased VO2peak and improved Cw in these subjects . The training was feasible and may have important implication s for cardiovascular health and future rehabilitation programs in this population OBJECTIVE To establish the test-retest reliability and concurrent validity with maximum oxygen consumption ( VO2max ) for 3 submaximal exercise tests in persons with chronic stroke : ( 1 ) submaximal treadmill test , ( 2 ) submaximal cycle ergometer test , and ( 3 ) 6-minute walk test ( 6MWT ) . DESIGN Prospect i ve study using a convenience sample . SETTING Free-st and ing tertiary rehabilitation center . PARTICIPANTS A volunteer sample of 12 community-dwelling individuals who had a stroke with moderate motor deficits . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Heart rate , blood pressure , and oxygen consumption ( VO2 ) were assessed during the exercise tests . RESULTS Test-retest reliability was good to excellent for the exercise tests ( maximal and submaximal tests ) . VO2 for all submaximal measures related to VO2max ( r range , .66-.80 ) . Neither the 6MWT distance , self-selected gait speed , nor hemodynamic measures related to VO2max . CONCLUSION The VO2 measures of the submaximal exercise tests had excellent reliability and good concurrent validity with VO2max . Submaximal exercise tests may be a method by which to monitor the effects of interventions after a screening test ( eg , symptom-limited grade d exercise test , dobutamine stress echocardiograph ) BACKGROUND AND PURPOSE Coronary artery disease is prevalent in stroke patients and is an important factor affecting rehabilitation and health outcomes . However , the presence of neurological deficits in gait and balance has discouraged systematic application of exercise testing and prescription in the stroke population . We evaluated a novel grade d treadmill stress test in paretic stroke patients and tested floor walking as a predictor of adequate neurological function to perform the treadmill test . METHODS Patients ( n = 31 ) with residual paretic gait deficits after ischemic stroke were evaluated with grade d treadmill at gait velocities individualized to functional mobility observed during an initial zero-incline treadmill tolerance test . RESULTS Most patients ( 30/31 ) tolerated testing , achieving mean heart rates of 129 + /- 14 beats per minute ( mean + /- SD ) , representing 84 + /- 10 % of maximal age-predicted heart rate . Evidence for asymptomatic myocardial ischemia was found in 29 % of those without known coronary artery disease . Exercise termination was more often due to generalized fatigue than cardiopulmonary intolerance ( 23/31 versus 4/31 ; P < .0001 ) or hemiparetic leg fatigue ( 1/31 ; P < .0001 ) . Floor walking across a wide range of velocities ( 0.25 to 2.5 mph ) demonstrated a strong linear relation with treadmill velocities ( n = 24 ; r = 80 ; P < .0001 ) ; all patients floor walking at > or = 0.5 mph had adequate neuromotor function to perform the exercise test . CONCLUSIONS These findings suggest that grade d treadmill exercise testing , with proper safety pre caution s , can be used to assess cardiopulmonary function in paretic stroke patients . A simple floor-walking test predicts adequate neurological function to perform the exercise test . Exercise capacity is most limited by generalized fatigue and not by the paretic limb , supporting a rationale for endurance training in this population OBJECTIVE To compare oxygen consumption during walking with body weight support ( BWS ) with oxygen consumption during unsupported treadmill walking . DESIGN Patient and reference group . Comparisons between two walking conditions within each group . SETTING Research laboratory of a university hospital . PARTICIPANTS Nonr and om convenience sample of 9 hemiparetic and 9 healthy subjects , mean age of 56 and 57 years , respectively . INTERVENTIONS The subjects walked on a treadmill with 0 % and 30 % BWS at their self-selected and maximum walking speeds . The trials were performed twice . MAIN OUTCOME MEASURES Ventilatory oxygen uptake ( VO2 ) and heart rate were measured by computerized breath-by-breath analysis and electrocardiography . RESULTS VO2 was lower during walking with 30 % BWS than during unsupported walking . At self-selected speed the Wilcoxon 's signed rank p values were < .01 for both patients and reference group ; at maximum velocity , p values were p < .02 for the patients and p < .05 for the reference group . Patients ' heart rates were lower when they walked with 30 % BWS than at 0 % BWS , at both self-selected and maximum walking speeds ( p < .05 and p < .02 , respectively ) . CONCLUSIONS The 30 % body weight supported condition requires less oxygen consumption than full weight bearing . Treadmill training with BWS can be tolerated by patients with cardiovascular problems The purpose of this study was to evaluate the feasibility and exercise capacity of cycle ergometry exercise testing and exercise performance in patients with post-acute stroke . Nineteen male patients ( mean age , 62.7 + /- 9.2 years ) with a post stroke interval of 9.9 + /- 2.0 days underwent symptom- limited cardiopulmonary exercise testing . Peak exercise capacity was measured by open-circuit spirometry during st and ard upright ergometer cycling . The mean peak oxygen uptake was 11.8 mL/kg/min , peak heart rate with age-predicted maximal heart rate was 67.9 + /- 3.4 % , and peak oxygen pulse was 7.5 mL/beat . The anaerobic threshold was achieved with a mean peak oxygen uptake of 73.4 % . Mean peak minute ventilation was 42.1 L/min , and ventilatory reserve was 48.1 + /- 16.8 % . Our findings confirm that cycle ergometry exercise testing is feasible and exercise capacity is compromised in post-acute stroke survivors within 2 weeks after stroke . Respiratory impairments do not appear to contribute to the reduced exercise capacity post stroke BACKGROUND AND PURPOSE In hemiparetic individuals , low endurance to exercise may compound the increased energy cost of movement and contribute to poor rehabilitation outcomes . The purpose of this investigation was to describe how hemiparetic stroke patients responded to intense exercise and aerobic training . METHODS Forty-two subjects were r and omly assigned to an exercise training group or to a control group . Treatments were given three times per week for 10 weeks in similar laboratory setting s. Baseline and posttest measurements were made of maximal oxygen consumption , heart rate , workload , exercise time , resting and submaximal blood pressures , and sensorimotor function . RESULTS Only experimental subjects showed significant improvement in maximal oxygen consumption , workload , and exercise time . Improvement in sensorimotor function was significantly related to the improvement in aerobic capacity . After treatment , experimental subjects showed significantly lower systolic blood pressure at submaximal workloads during the grade d exercise test . CONCLUSIONS We conclude that hemiparetic stroke patients may improve their aerobic capacity and submaximal exercise systolic blood pressure response with training . Sensorimotor improvement is related to the improvement in aerobic capacity OBJECTIVE To assess the test-retest reliability of cardiopulmonary measurements during peak effort and submaximal treadmill walking tests in older patients with gait-impaired chronic hemiparetic stroke . DESIGN Nonr and omized test-retest . SETTING Hospital geriatric research stress testing laboratory . PARTICIPANTS Fifty-three subjects ( 44 men , 9 women ; mean age , 65+/-8y ) with chronic hemiparetic gait after remote ( > 6mo ) ischemic stroke . Patients had mild to moderate chronic hemiparetic gait deficits , making h and rail support necessary during treadmill walking . INTERVENTIONS Peak effort and submaximal effort treadmill walking tests were conducted and then repeated on a separate day at least a week later . Main outcome measures Reliability coefficients ( r ) were calculated for heart rate , systolic blood pressure ( SBP ) , oxygen consumption ( Vo(2 ) [ L/min ] ) , Vo(2 ) ( mL.kg(-1).min(-1 ) ) , respiratory exchange ratio ( RER ) , rate-pressure product ( RPP ) , and oxygen pulse during peak effort testing . The reliability coefficients for all but SBP and RPP data were calculated from the submaximal tests . RESULTS Heart rate ( r=.87 ) , Vo(2)peak ( L/min ) ( r=.92 ) , Vo(2)peak ( mL.kg(-1).min(-1 ) ) ( r=.92 ) , and oxygen pulse ( r=93 ) were highly reliable parameters during maximal testing in this population . Submaximal testing produced highly reliable results for V.o(2 ) ( L/min ) ( r=.89 ) and oxygen pulse ( r=.85 ) . All cardiopulmonary measures except RER had a reliability coefficient greater than.80 during submaximal testing in this population . CONCLUSION Our study provides the first evidence that peak effort treadmill testing provides highly reliable oxygen consumption measures in chronic hemiparetic stroke patients using minimal h and rail support . The submaximal tests were at or near the threshold level of reliability for the 2 most important measures of V.o(2 ) ( L/min ) and V.o(2 ) ( mL.kg(-1).min(-1 ) ) ( r=.89 , r=.84 , respectively ) , with the remaining measures falling above.70 |
913 | 22,548,983 | In the second and third trimesters , AL was not associated with increased adverse pregnancy outcomes as compared with quinine or sulphadoxine-pyrimethamine , showed improved tolerability relative to quinine , and its efficacy was non-inferior to quinine .
There is evidence to suggest that the pharmacokinetics of anti-malarial drugs may change in pregnancy , although the impact on efficacy and safety needs to be studied further , especially since the majority of studies report high cure rates and adequate tolerability . | Malaria during pregnancy , particularly Plasmodium falciparum malaria , has been linked to increased morbidity and mortality , which must be reduced by both preventive measures and effective case management .
The World Health Organization ( WHO ) recommends artemisinin-based combination therapy ( ACT ) to treat uncomplicated falciparum malaria during the second and third trimesters of pregnancy , and quinine plus clindamycin during the first trimester .
However , the national policies of many African countries currently recommend quinine throughout pregnancy .
Therefore , the aim of this article is to provide a summary of the available data on the safety and efficacy of artemether-lumefantrine ( AL ) in pregnancy . | The efficacy of artemether and artemether followed by mefloquine was evaluated in 45 pregnant women with drug resistant Plasmodium falciparum malaria during the second and third trimesters . There was prompt clinical response to both treatment regimens . The parasite and fever clearance times and the cure rate were similar in both groups . Except for the correlation between initial parasite density and fever clearance time in the artemether-mefloquine group , there was no correlation between initial parasite density and parasite or fever clearance times in the two groups . Similarly , there was no correlation between parasite and fever clearance . Both treatment regimens were well tolerated . All newborn babies of the participating women were normal at birth . Physical and neurodevelopmental assessment of the newborn babies followed up for a period varying between 6 and 36 months were within normal limits . Artemether alone or with mefloquine are effective and do not produce undue deleterious effects in pregnant patients with drug-resistant falciparum malaria during the second and third trimesters BACKGROUND Adherence to antimalarial drug regimens is improved by simple dosing . If the fixed antimalarial drug combination artemether-lumefantrine ( AL ) could be given once daily , this should improve adherence and thus effectiveness and lower the risk of selecting for resistance . METHODS In an open r and omized study , 43 patients with uncomplicated falciparum malaria were given equivalent doses of AL with 200 ml flavoured milk either as the conventional twice-daily regimen or as a single daily dose for 3 days . The primary end point was a comparison of the areas under the plasma lumefantrine concentration-time curves ( AUC ) . Secondary end points were the day 42 polymerase chain reaction (PCR)-adjusted cure rates and the tolerability profiles . RESULTS Lumefantrine pharmacokinetic profiles were obtained for 36 patients . The AUC((0 - ->infinity ) ) of the once-daily regimen was 30 % lower than that in the conventional regimen ( P = 0.011 ) with a median ( range ) value of 306 ( 114 - 5781 ) microg/ml h , compared with 432 ( 308 - 992 ) microg/ml h. There was no significant difference in the peak plasma concentrations reached . PCR-adjusted cure rate estimates at day 42 of follow-up were 94 % ( 95 % CI : 84 - 100 ) in the six-dose arm and 85 % ( 70 - 100 ) in the three-dose arm ( P = 0.3 ) . CONCLUSION Artemether-lumefantrine efficacy is reduced by once-daily dosing , because absorption of lumefantrine is dose limited . At currently recommended doses , this antimalarial should be given twice daily in a 3-day regimen , with food containing fat Background To date no comparative trials have been done , to our knowledge , of fixed-dose artemisinin combination therapies ( ACTs ) for the treatment of Plasmodium falciparum malaria in pregnancy . Evidence on the safety and efficacy of ACTs in pregnancy is needed as these drugs are being used increasingly throughout the malaria-affected world . The objective of this study was to compare the efficacy , tolerability , and safety of artemether-lumefantrine , the most widely used fixed ACT , with 7 d artesunate monotherapy in the second and third trimesters of pregnancy . Methods and Findings An open-label r and omised controlled trial comparing directly observed treatment with artemether-lumefantrine 3 d ( AL ) or artesunate monotherapy 7 d ( AS7 ) was conducted in Karen women in the border area of northwestern Thail and who had uncomplicated P. falciparum malaria in the second and third trimesters of pregnancy . The primary endpoint was efficacy defined as the P. falciparum PCR-adjusted cure rates assessed at delivery or by day 42 if this occurred later than delivery , as estimated by Kaplan-Meier survival analysis . Infants were assessed at birth and followed until 1 y of life . Blood sampling was performed to characterise the pharmacokinetics of lumefantrine in pregnancy . Both regimens were very well tolerated . The cure rates ( 95 % confidence interval ) for the intention to treat ( ITT ) population were : AS7 89.2 % ( 82.3%–96.1 % ) and AL 82.0 % ( 74.8%–89.3 % ) , p = 0.054 ( ITT ) ; and AS7 89.7 % ( 82.6%–96.8 % ) and AL 81.2 % ( 73.6%–88.8 % ) , p = 0.031 ( per- protocol population ) . One-third of the PCR-confirmed recrudescent cases occurred after 42 d of follow-up . Birth outcomes and infant ( up to age 1 y ) outcomes did not differ significantly between the two groups . The pharmacokinetic study indicated that low concentrations of artemether and lumefantrine were the main contributors to the poor efficacy of AL . Conclusion The current st and ard six-dose artemether-lumefantrine regimen was well tolerated and safe in pregnant Karen women with uncomplicated falciparum malaria , but efficacy was inferior to 7 d artesunate monotherapy and was unsatisfactory for general deployment in this geographic area . Reduced efficacy probably results from low drug concentrations in later pregnancy . A longer or more frequent AL dose regimen may be needed to treat pregnant women effectively and should now be evaluated . Parasitological endpoints in clinical trials of any antimalarial drug treatment in pregnancy should be extended to delivery or day 42 if it comes later . Trial Registration : Current Controlled Trials IS RCT Background Safety data regarding exposure to artemisinin-based combination therapy in pregnancy are limited . This prospect i ve cohort study conducted in Zambia evaluated the safety of artemether-lumefantrine ( AL ) in pregnant women with malaria . Methods Pregnant women attending antenatal clinics were assigned to groups based on the drug used to treat their most recent malaria episode ( AL vs. sulphadoxine-pyrimethamine , SP ) . Safety was assessed using st and ard and pregnancy-specific parameters . Post-delivery follow-up was six weeks for mothers and 12 months for live births . Primary outcome was perinatal mortality ( stillbirth or neonatal death within seven days after birth ) . Results Data from 1,001 pregnant women ( AL n = 495 ; SP n = 506 ) and 933 newborns ( AL n = 466 ; SP n = 467 ) showed : perinatal mortality ( AL 4.2 % ; SP 5.0 % ) , comprised of early neonatal mortality ( each group 2.3 % ) , stillbirths ( AL 1.9 % ; SP 2.7 % ) ; preterm deliveries ( AL 14.1 % ; SP 17.4 % of foetuses ) ; and gestational age-adjusted low birth weight ( AL 9.0 % ; SP 7.7 % ) . Infant birth defect incidence was 1.8 % AL and 1.6 % SP , excluding umbilical hernia . Abortions prior to antenatal care could not be determined : abortion occurred in 4.5 % of women treated with AL during their first trimester ; none were reported in the 133 women exposed to SP and /or quinine during their first trimester . Overall development ( including neurological assessment ) was similar in both groups . Conclusions These data suggest that exposure to AL in pregnancy , including first trimester , is not associated with particular safety risks in terms of perinatal mortality , malformations , or developmental impairment . However , more data are required on AL use during the first trimester Background . There is some consensus that malaria in pregnancy may negatively affect infant 's mortality and malaria morbidity , but there is less evidence concerning the factors involved . Methods . A total of 1030 Mozambican pregnant women were enrolled in a r and omized , placebo-controlled trial of intermittent preventive treatment with sulfadoxine-pyrimethamine , and their infants were followed up throughout infancy . Overall mortality and malaria morbidity rates were recorded . The association of maternal and fetal risk factors with infant mortality and malaria morbidity was assessed . Results . There were 58 infant deaths among 997 live-born infants . The risk of dying during infancy was increased among infants born to women with acute placental infection ( odds ratio [ OR ] , 5.08 [ 95 % confidence interval ( CI ) , 1.77–14.53 ) ] , parasitemia in cord blood ( OR , 19.31 [ 95 % CI , 4.44–84.02 ] ) , low birth weight ( OR , 2.82 [ 95 % CI , 1.27–6.28 ] ) or prematurity ( OR , 3.19 [ 95 % CI , 1.14–8.95 ] ) . Infants born to women who had clinical malaria during pregnancy ( OR , 1.96 [ 95 % CI , 1.13–3.41 ] ) or acute placental infection ( OR , 4.63 [ 95 % CI , 2.10–10.24 ] ) had an increased risk of clinical malaria during infancy . Conclusions . Malaria infection at the end of pregnancy and maternal clinical malaria negatively impact survival and malaria morbidity in infancy . Effective clinical management and prevention of malaria in pregnancy may improve infant 's health and survival Background Prompt use of an effective anti-malarial drug is essential for controlling malaria and its adverse effects in pregnancy . The World Health Organization recommends an artemisinin-based combination therapy as the first-line treatment of uncomplicated malaria in the second and third trimesters of pregnancy . The study objective was to determine the degree to which presumed episodes of uncomplicated symptomatic malaria in pregnancy were treated with a recommended anti-malarial regimen in a region of Ug and a. Methods Utilizing a population -based r and om sample , we interviewed women living in Jinja , Ug and a who had been pregnant in the past year . Results Self-reported malaria during the index pregnancy was reported among 67 % ( n = 334 ) of the 500 participants . Among the 637 self-reported episodes of malaria , an anti-malarial drug was used for treatment in 85 % of the episodes . Use of a currently recommended treatment in the first trimester was uncommon ( 5.6 % ) . A contraindicated anti-malarial drug ( sulphadoxine-pyrimethamine and /or artemether-lumefantrine ) was involved in 70 % of first trimester episodes . Recommended anti-malarials were used according to the guidelines in only 30.1 % of all second and third trimester episodes . Conclusions Self-reported malaria was extremely common in this population and adherence to treatment guidelines for the management of malaria in pregnancy was poor . Use of artemether-lumefantrine combined with non-recommended anti-malarials was common practice . Overuse of anti-malarial drugs , especially ones that are no longer recommended , undermines malaria control efforts by fueling the spread of drug resistance and delaying appropriate treatment of non-malarial febrile illnesses . Improved diagnostic capacity is essential to ultimately improving the management of malaria-like symptoms during pregnancy and appropriate use of currently available anti-malarials Background Maternal mortality is a major health problem concentrated in re source -poor regions . Accurate data on its causes using rigorous methods is lacking , but is essential to guide policy-makers and health professionals to reduce this intolerable burden . The aim of this study was to accurately describe the causes of maternal death in order to contribute to its reduction , in one of the regions of the world with the highest maternal mortality ratios . Methods and Findings We conducted a prospect i ve study between October 2002 and December 2004 on the causes of maternal death in a tertiary-level referral hospital in Maputo , Mozambique , using complete autopsies with histological examination . HIV detection was done by virologic and serologic tests , and malaria was diagnosed by histological and parasitological examination . During 26 mo there were 179 maternal deaths , of which 139 ( 77.6 % ) had a complete autopsy and formed the basis of this analysis . Of those with test results , 65 women ( 52.8 % ) were HIV-positive . Obstetric complications accounted for 38.2 % of deaths ; haemorrhage was the most frequent cause ( 16.6 % ) . Nonobstetric conditions accounted for 56.1 % of deaths ; HIV/AIDS , pyogenic bronchopneumonia , severe malaria , and pyogenic meningitis were the most common causes ( 12.9 % , 12.2 % , 10.1 % and 7.2 % respectively ) . Mycobacterial infection was found in 12 ( 8.6 % ) maternal deaths . Conclusions In this tertiary hospital in Mozambique , infectious diseases accounted for at least half of all maternal deaths , even though effective treatment is available for the four leading causes , HIV/AIDS , pyogenic bronchopneumonia , severe malaria , and pyogenic meningitis . These observations highlight the need to implement effective and available prevention tools , such as intermittent preventive treatment and insecticide-treated bed-nets for malaria , antiretroviral drugs for HIV/AIDS , or vaccines and effective antibiotics for pneumococcal and meningococcal diseases . Deaths due to obstetric causes represent a failure of health-care systems and require urgent improvement The emergence and spread of multidrug-resistant Plasmodium falciparum compromises the treatment of malaria , especially during pregnancy , where the choice of antimalarials is already limited . Artesunate ( n=528 ) or artemether ( n=11 ) was used to treat 539 episodes of acute P. falciparum malaria in 461 pregnant women , including 44 first-trimester episodes . Most patients ( 310 [ 57.5 % ] ) received re-treatments after earlier treatment with quinine or mefloquine . By use of survival analysis , the cumulative artemisinin failure rate for primary infections was 6.6 % ( 95 % confidence interval , 1.0 - 12.3 ) , compared with the re-treatment failure rate of 21.7 % ( 95 % confidence interval , 15.4 - 28.0 ; P=.004 ) . The artemisinins were well tolerated with no evidence of adverse effects . Birth outcomes did not differ significantly to community rates for abortion , stillbirth , congenital abnormality , and mean gestation at delivery . These results are reassuring , but further information about the safety of these valuable antimalarials in pregnancy is needed Background The World Health Organization endorses the use of artemisinin-based combination therapy for treatment of acute uncomplicated falciparum malaria in the second and third trimesters of pregnancy . However , the effects of pregnancy on the pharmacokinetics of artemisinin derivatives , such as artesunate ( AS ) , are poorly understood . In this analysis , the population pharmacokinetics of oral AS , and its active metabolite dihydroartemisinin ( DHA ) , were studied in pregnant and non-pregnant women at the Kingasani Maternity Clinic in the DRC . Methods Data were obtained from 26 pregnant women in the second ( 22 - 26 weeks ) or the third ( 32 - 36 weeks ) trimester of pregnancy and from 25 non-pregnant female controls . All subjects received 200 mg AS . Plasma AS and DHA were measured using a vali date d LC-MS method . Estimates for pharmacokinetic and variability parameters were obtained through nonlinear mixed effects modelling . Results A simultaneous parent-metabolite model was developed consisting of mixed zero-order , lagged first-order absorption of AS , a one-compartment model for AS , and a one-compartment model for DHA . Complete conversion of AS to DHA was assumed . The model displayed satisfactory goodness-of-fit , stability , and predictive ability . Apparent clearance ( CL/F ) and volume of distribution ( V/F ) estimates , with 95 % bootstrap confidence intervals , were as follows : 195 L ( 139 - 285 L ) for AS V/F , 895 L/h ( 788 - 1045 L/h ) for AS CL/F , 91.4 L ( 78.5 - 109 L ) for DHA V/F , and 64.0 L/h ( 55.1 - 75.2 L/h ) for DHA CL/F. The effect of pregnancy on DHA CL/F was determined to be significant , with a pregnancy-associated increase in DHA CL/F of 42.3 % ( 19.7 - 72.3 % ) . Conclusions In this analysis , pharmacokinetic modelling suggests that pregnant women have accelerated DHA clearance compared to non-pregnant women receiving orally administered AS . These findings , in conjunction with a previous non-compartmental analysis of the modelled data , provide further evidence that higher AS doses would be required to maintain similar DHA levels in pregnant women as achieved in non-pregnant controls BACKGROUND Malaria in pregnancy is associated with maternal and fetal morbidity and mortality . In 2006 , WHO recommended use of artemisinin-based combination treatments during the second or third trimesters , but data on efficacy and safety in Africa were scarce . We aim ed to assess whether artemether-lumefantrine was at least as efficacious as oral quinine for the treatment of uncomplicated falciparum malaria during the second and third trimesters of pregnancy in Mbarara , Ug and a. METHODS We did an open-label , r and omised , non-inferiority trial between October , 2006 , and May , 2009 , at the antenatal clinics of the Mbarara University of Science and Technology Hospital in Ug and a. Pregnant women were r and omly assigned ( 1:1 ) by computer generated sequence to receive either quinine hydrochloride or artemether-lumefantrine , and were followed up weekly until delivery . Our primary endpoint was cure rate at day 42 , confirmed by PCR . The non-inferiority margin was a difference in cure rate of 5 % . Analysis of efficacy was for all r and omised patients without study deviations that could have affected the efficacy outcome . This study was registered with Clinical Trials.gov , number NCT00495508 . FINDINGS 304 women were r and omly assigned , 152 to each treatment group . By day 42 , 16 patients were lost to follow-up and 25 were excluded from the analysis . At day 42 , 137 ( 99.3 % ) of 138 patients taking artemether-lumefantrine and 122 ( 97.6 % ) of 125 taking quinine were cured-difference 1.7 % ( lower limit of 95 % CI -0.9 ) . There were 290 adverse events in the quinine group and 141 in the artemether-lumefantrine group . INTERPRETATION Artemisinin derivatives are not inferior to oral quinine for the treatment of uncomplicated malaria in pregnancy and might be preferable on the basis of safety and efficacy . FUNDING Médecins Sans Frontières and the European Commission ABSTRACT The objective of this study was to conduct a prospect i ve population pharmacokinetic and pharmacodynamic evaluation of lumefantrine during blinded comparisons of artemether-lumefantrine treatment regimens in uncomplicated multidrug-resistant falciparum malaria . Three combination regimens containing an average adult lumefantrine dose of 1,920 mg over 3 days ( four doses ) ( regimen A ) or 2,780 mg over 3 or 5 days ( six doses ) ( regimen B or C , respectively ) were given to 266 Thai patients . Detailed observations were obtained for 51 hospitalized adults , and sparse data were collected for 215 patients of all ages in a community setting . The population absorption half-life of lumefantrine was 4.5 h. The model-based median ( 5th and 95th percentiles ) peak plasma lumefantrine concentrations were 6.2 ( 0.25 and 14.8 ) μg/ml after regimen A , 9.0 ( 1.1 and 19.8 ) μg/ml after regimen B , and 8 ( 1.4 and 17.4 ) μg/ml after regimen C. During acute malaria , there was marked variability in the fraction of drug absorbed by patients ( coefficient of variation , 150 % ) . The fraction increased considerably and variability fell with clinical recovery , largely because food intake was resumed ; taking a normal meal close to drug administration increased oral bioavailability by 108 % ( 90 % confidence interval , 64 to 164 ) ( P , 0.0001 ) . The higher-dose regimens ( B and C ) gave 60 and 100 % higher areas under the concentration-time curves ( AUC ) , respectively , and thus longer duration s for which plasma lumefantrine concentrations exceeded the putative in vivo MIC of 280 μg/ml ( median for regimen B , 252 h ; that for regimen C , 298 h ; that for regimen A , 204 h [ P , 0.0001 ] ) and higher cure rates . Lumefantrine oral bioavailability is very dependent on food and is consequently poor in acute malaria but improves markedly with recovery . The high cure rates with the two six-dose regimens result ed from increased AUC and increased time at which lumefantrine concentrations were above the in vivo MIC Plasmodium falciparum malaria is increasing world-wide , as is resistance to the available antimalarials . On the Thai-Burmese border this problem is most acute in pregnant women , as options for their treatment are even more restricted because of the unknown effects of antimalarials on the foetus . Presented here are the results of descriptive , clinical , drug studies on quinine , mefloquine and artemisinin derivatives for P. falciparum in pregnant women . Mefloquine and quinine have high failure rates for primary and recrudescent infections . Artemisinin-based treatments in pregnant women have proved safe , tolerable and efficacious . However , r and omized drug studies with these drugs and other new antimalarials are required to define the true safety and efficacy of these drugs in pregnant women Forty-two healthy Caucasian subjects were r and omized in a double-blind , parallel three-group study ( 14 subjects per group ) to investigate potential electrocardiographic and pharmacokinetic interactions between the antimalarials artemether-lumefantrine ( six-dose regimen of Riamet over 3 days ) and quinine ( 2-h intravenous infusion of 10 mg/kg body weight , not exceeding 600 mg in total , 2 h after the last dose of Riamet ) . The study medications were all safe and well tolerated after all treatments . Neither the pharmacokinetics of lumefantrine nor the pharmacokinetics of quinine was influenced by the presence of the other drug . Plasma levels of artemether and dihydroartemisinin appeared to be lower following the combined treatment Riamet + quinine , but this was not considered to be clinical ly relevant . Riamet alone had no effect on QTc interval . Infusion of quinine alone caused a transient prolongation of QTc interval , which was consistent with the known cardiotoxicity of quinine , with this effect being slightly but significantly greater when quinine was infused after Riamet . It would thus appear that the inherent risk of QTc prolongation of IV quinine was enhanced by prior administration of Riamet . However , these occasional QTc prolongations , which were small in magnitude and not correlated with plasma concentrations of any of the compounds , were not considered to be of clinical importance . In conclusion , overlapping therapy with artemether-lumefantrine and IV quinine in the treatment of patients with complicated or multidrug-resistant Plasmodium falciparum malaria may result in a modest increased risk of QTc prolongation , but this is far outweighed by the potential therapeutic benefit BACKGROUND The six-dose regimen of artemether-lumefantrine is effective and is among combination therapies prioritised to replace antimalarials that no longer work in Africa . However , its effectiveness has not been assessed in the field , and could be compromised by poor adherence , incorrect timing of doses , and insufficient intake of fatty foods with every dose . Our aim , therefore , was to assess the effectiveness of artemether-lumefantrine prescribed under routine outpatient conditions , compared with its efficacy when given under supervision to in patients with acute uncomplicated falciparum malaria . METHODS We did a r and omised trial to compare the efficacy , safety , and pharmacokinetics of artemether-lumefantrine when given in a supervised ( all doses observed with fatty-food intake ; n=313 ) or unsupervised ( first dose supervised followed by outpatient treatment with nutritional advice ; n=644 ) setting to patients of all ages ( weight > 10 kg ) with acute , uncomplicated falciparum malaria in Mbarara , Ug and a. Our primary endpoint was 28 day , PCR-adjusted , parasitological cure rate . Analysis was by intention to treat and evaluability analysis . FINDINGS 38 patients were lost to follow-up and one withdrew consent . Day-28 cure rates were 97.7 % ( 296 of 303 ) and 98.0 % ( 603 of 615 ) in the supervised and unsupervised groups , respectively . We recorded 15 non-severe , drug-related adverse events , all of which resolved . INTERPRETATION Artemether-lumefantrine has a high cure rate irrespective of whether given under supervision with food or under conditions of routine clinic practice . If used as first-line treatment , artemether-lumefantrine could make a substantial contribution to malaria control in Africa , though cost is an issue Summary Background The effects of malaria and its treatment in the first trimester of pregnancy remain an area of concern . We aim ed to assess the outcome of malaria-exposed and malaria-unexposed first-trimester pregnancies of women from the Thai – Burmese border and compare outcomes after chloroquine-based , quinine-based , or artemisinin-based treatments . Methods We analysed all antenatal records of women in the first trimester of pregnancy attending Shoklo Malaria Research Unit antenatal clinics from May 12 , 1986 , to Oct 31 , 2010 . Women without malaria in pregnancy were compared with those who had a single episode of malaria in the first trimester . The association between malaria and miscarriage was estimated using multivariable logistic regression . Findings Of 48 426 pregnant women , 17 613 ( 36 % ) met the inclusion criteria : 16 668 ( 95 % ) had no malaria during the pregnancy and 945 ( 5 % ) had a single episode in the first trimester . The odds of miscarriage increased in women with asymptomatic malaria ( adjusted odds ratio 2·70 , 95 % CI 2·04–3·59 ) and symptomatic malaria ( 3·99 , 3·10–5·13 ) , and were similar for Plasmodium falciparum and Plasmodium vivax . Other risk factors for miscarriage included smoking , maternal age , previous miscarriage , and non-malaria febrile illness . In women with malaria , additional risk factors for miscarriage included severe or hyperparasitaemic malaria ( adjusted odds ratio 3·63 , 95 % CI 1·15–11·46 ) and parasitaemia ( 1·49 , 1·25–1·78 for each ten-fold increase in parasitaemia ) . Higher gestational age at the time of infection was protective ( adjusted odds ratio 0·86 , 95 % CI 0·81–0·91 ) . The risk of miscarriage was similar for women treated with chloroquine ( 92 [ 26 % ] of 354 ) , quinine ( 95 [ 27 % ) of 355 ) , or artesunate ( 20 [ 31 % ] of 64 ; p=0·71 ) . Adverse effects related to antimalarial treatment were not observed . Interpretation A single episode of falciparum or vivax malaria in the first trimester of pregnancy can cause miscarriage . No additional toxic effects associated with artesunate treatment occurred in early pregnancy . Prospect i ve studies should now be done to assess the safety and efficacy of artemisinin combination treatments in early pregnancy . Funding Wellcome Trust and Bill & Melinda Gates Foundation ABSTRACT Artemether-lumefantrine has become one of the most widely used antimalarial drugs in the world . The objective of this study was to determine the population pharmacokinetic properties of lumefantrine in pregnant women with uncomplicated multidrug-resistant Plasmodium falciparum malaria on the northwestern border of Thail and . Burmese and Karen women ( n = 103 ) with P. falciparum malaria and in the second and third trimesters of pregnancy were treated with artemether-lumefantrine ( 80/480 mg ) twice daily for 3 days . All patients provided five capillary plasma sample s for drug quantification , and the collection times were r and omly distributed over 14 days . The concentration-time profiles of lumefantrine were assessed by nonlinear mixed-effects modeling . The treatment failure rate ( PCR-confirmed recrudescent infections at delivery ) was high ; 16.5 % ( 95 % confidence interval , 9.9 to 25.1 ) . The population pharmacokinetics of lumefantrine were described well by a two-compartment open model with first-order absorption and elimination . The final model included interindividual variability in all pharmacokinetic parameters and a linear covariate relationship between the estimated gestational age and the central volume of distribution . A high proportion of all women ( 40 % , 41/103 ) had day 7 capillary plasma concentrations of < 355 ng/ml ( which corresponds to approximately < 280 ng/ml in venous plasma ) , a threshold previously associated with an increased risk of therapeutic failure in nonpregnant patients in this area . Predictive modeling suggests that a twice-daily regimen given for 5 days would be preferable in later pregnancy . In conclusion , altered pharmacokinetic properties of lumefantrine contribute to the high rates of failure of artemether-lumefantrine treatment in later pregnancy . Dose optimization is urgently needed The efficacy-safety and pharmacokinetics of the six-dose regimen of artemether-lumefantrine ( Coartem/Riamet ; Novartis Pharma AG , Basel , Switzerl and ) were assessed in a r and omized trial in 219 patients ( > or = 12 years old ) with acute , uncomplicated Plasmodium falciparum malaria in Thail and . One hundred and sixty-four patients received artemether-lumefantrine and 55 received the st and ard treatment combination of mefloquine-artesunate . Both drugs induced rapid clearance of parasites and malaria symptoms . The 28-day cure rates were 95.5 % ( 90 % confidence interval [ CI ] = 91.7 , 97.9 % ) for artemether-lumefantrine and 100 % ( 90 % CI = 94.5 , 100 % ) for mefloquine-artesunate . This high-dose regimen of artemether-lumefantrine was very well tolerated , with very good compliance . The most frequent adverse events were headache , dizziness , nausea , abdominal pain , dyspepsia , vomiting , and skin rash . Overall , only 2 % of patients in both groups showed QTc prolongations but without any cardiac complication , and no differences were seen between patients with and without measurable baseline plasma levels of quinine or mefloquine . Plasma levels of artemether , dihydroartemisinin , and lumefantrine were consistent with historical data for the same dose regimen , and were higher , particularly for lumefantrine , than those previously observed with the four-dose regimen , explaining the greater efficacy of the six-dose regimen in a drug-resistant setting . These results confirm the excellent safety and efficacy of the six-dose regimen of artemether-lumefantrine in the treatment of multidrug-resistant P. falciparum malaria Forty-two healthy subjects were r and omized in a parallel three-group design trial to investigate potential electrocardiographic and pharmacokinetic interactions between the new antimalarial co-artemether , a combination of artemether and lumefantrine ( both of which are predominantly metabolized through CYP3A4 ) , and mefloquine , another antimalarial described as a substrate ( and possible inhibitor ) of CYP3A4 . Subjects were assigned to one of the three possible treatment groups ( i.e. , co-artemether alone or mefloquine alone or the combination of both ) . The dosage was 1000 mg mefloquine ( divided into three doses over 12 h ) followed 12 h later by six applications of co-artemether ( 40 mg artemether+480 mg lumefantrine each ) over 60 h. The study medications were generally well tolerated after all treatments . Concomitant administration with mefloquine caused statistically significant lower ( around 30 - 40 % ) plasma concentrations of lumefantrine than when co-artemether was administered alone . Even if important , this decrease in lumefantrine exposure was considered unlikely to impact clinical efficacy given the wide therapeutic index of co-artemether and the usual high variability in lumefantrine plasma levels , mostly and more importantly influenced by food intake . However , patients should be encouraged to eat at dosing times to compensate for this decreased bioavailability . The pharmacokinetics of artemether , DHA or mefloquine were not affected . Artemether concentrations significantly decreased over doses , independently of mefloquine co-administration , while DHA concentrations slightly ( not significantly ) increased . Therefore , no clinical ly relevant risks due to pharmacokinetic drug-drug interaction are expected at the enzymatic level following co-administration of co-artemether with CYP3A4 substrates with similar affinity to that of mefloquine |
914 | 24,785,615 | : Health care providers should be aware that women who are obese when they become pregnant are more likely to experience elevated antenatal and postpartum depression symptoms than normal-weight women , with intermediate risks for overweight women | OBJECTIVE : To evaluate the prevalence and risk of antenatal and postpartum mental disorders among obese and overweight women . | Associations between salivary cortisol and maternal psychological distress and well-being were examined prospect ively on 112 women with normally progressing , singleton pregnancies between 24 and 38 weeks gestation . At each of 5 visits , conducted in 3-week intervals , women provided a saliva sample and completed question naires measuring trait anxiety , depressive symptoms , pregnancy-specific hassles and uplifts , and psychological well-being . Maternal salivary cortisol was unrelated to psychological measures with the exception of minor associations detected with measures of anxiety and depressive symptoms between 30 and 32 weeks only . Findings indicate that self-reported maternal psychological distress and well-being are not associated with significant variation in maternal salivary cortisol levels during the second half of gestation . This suggests that studies that measure psychological factors in pregnancy but do not measure maternal cortisol should exercise caution in assuming activation of the maternal hypothalamic – pituitary – adrenal axis is the mechanism through which maternal psychological factors are transduced to the fetus Study goals were to distinguish between maternal risk factors for fetal versus infant mortality , and to identify which maternal characteristics contributed the greatest risk of mortality overall . This case – control retrospective study abstract ed data on more than forty maternal characteristics from 261 prenatal and delivery records : all 26 fetal deaths , all 40 infant deaths and 195 r and omly selected surviving births in a high-mortality Healthy Start community . Bivariate and multivariate analyses were conducted . The fetal-mortality population was significantly more likely than the infant-mortality population to have no insurance ( P = .047 ) , inadequate prenatal care ( P = .039 ) and previous fetal death ( P = .021 ) . Comparing the combined mortality population with the surviving sample , two tiers of risk emerged : Rare-but-lethal risks , including no prenatal care ( P < .001 ) and Child-Protective-Service involvement ( P = .001 ) , and common- and -dangerous risks , including inadequate maternal weight gain ( OR = 13.55 ) , drug or alcohol abuse ( OR = 8.67 ) , obesity ( OR = 2.77 ) and anemia ( OR = 3.61 ) . Both fetal and infant mortality groups must be considered when identifying maternal risks . Inadequate prenatal weight gain , obesity and anemia contribute as much to feto-infant mortality as substance abuse . Public health efforts to improve maternal nutrition and healthy weight should be redoubled This study investigates the relationship between adverse pregnancy outcomes in high-risk African American women in Washington , DC and sociodemographic risk factors , behavioral risk factors , and the most common and interrelated medical conditions occurring during pregnancy : diabetes , hypertension , preeclampsia , and Body Mass Index ( BMI ) . Data are from a r and omized controlled trial conducted in 6 prenatal clinics . Women in their 1st or 2nd trimester were screened for behavioral risks ( smoking , environmental tobacco smoke exposure , depression , and intimate partner violence ) and demographic eligibility . 1,044 were eligible , interviewed and followed through their pregnancies . Classification and Regression Trees ( CART ) methodology was used to : ( 1 ) explore the relationship between medical and behavioral risks ( reported at enrollment ) , sociodemographic factors and pregnancy outcomes ; ( 2 ) identify the relative importance of various predictors of adverse pregnancy outcomes ; and ( 3 ) characterize women at the highest risk of poor pregnancy outcomes . The strongest predictors of poor outcomes were prepregnancy BMI , preconceptional diabetes , employment status , intimate partner violence , and depression . In CART analysis , preeclampsia was the first splitter for low birthweight ; preconceptional diabetes was the first splitter for preterm birth ( PTB ) and neonatal intensive care admission ; BMI was the first splitter for very PTB , large for gestational age , Cesarean section and perinatal death ; employment was the first splitter for miscarriage . Preconceptional factors strongly influence pregnancy outcomes . For many of these women , the high risks they brought into pregnancy were more likely to impact their pregnancy outcomes than events during pregnancy Background Body image satisfaction in pregnancy may have an important influence on maternal biopsychosocial outcomes . Purpose This study aims to examine the mediating influence of trimesters 2 and 3 body image satisfaction on trimesters 2 and 3 depressive symptoms , exercise behavior , and gestational weight gain . Methods Pregnant women ( N = 151 ; mean age = 30 ) prospect ively completed study measures via mail during their 1st , 2nd , and 3rd trimesters . Results As predicted , trimesters 2 and 3 body image satisfaction mediated the relationship between trimester 1 body image satisfaction and trimester 2 depressive symptoms and the relationship between trimester 2 body image satisfaction and trimester 3 depressive symptoms . In contrast to the hypothesis , no mediation was observed for the relationship between body image satisfaction and exercise behavior or gestational weight gain . Conclusions These preliminary findings demonstrate that body image satisfaction is an important psychological determinant of depressive symptoms in pregnancy . Promoting healthy body image may be a non-pharmacological strategy that offers protective effects against depressive symptoms during pregnancy OBJECTIVE To identify and describe dietary patterns in a cohort of pregnant women , and investigate whether dietary patterns during pregnancy are related to postpartum depression ( PPD ) . DESIGN The study uses data from the prospect i ve mother-child cohort ' Rhea ' study . Pregnant women completed an FFQ in mid-pregnancy and the Edinburg Postpartum Depression Scale ( EPDS ) at 8 - 10 weeks postpartum . Dietary patterns during pregnancy ( ' health conscious ' , ' Western ' ) were identified using principal component analysis . Associations between dietary patterns categorized in tertiles and PPD symptoms were investigated by multivariable regression models after adjusting for confounders . SETTING Heraklion , Crete , Greece , 2007 - 2010 . SUBJECTS A total of 529 women , participating in the ' Rhea ' cohort . RESULTS High adherence to a ' health conscious ' diet , characterized by vegetables , fruit , pulses , nuts , dairy products , fish and olive oil , was associated with lower EPDS scores ( highest v. lowest tertile : β-coefficient = -1·75 , P = 0·02 ) . Women in the second ( relative risk ( RR ) = 0·52 , 95 % CI 0·30 , 0·92 ) or third tertile ( RR = 0·51 , 95 % CI 0·25 , 1·05 ) of the ' health conscious ' dietary pattern were about 50 % less likely to have high levels of PPD symptoms ( EPDS ≥ 13 ) compared with those in the lowest tertile . CONCLUSIONS This is the first prospect i ve study showing that a healthy diet during pregnancy is associated with reduced risk for PPD . Additional longitudinal studies and trials are needed to confirm these findings BACKGROUND The impact of prenatal depression on pregnancy outcomes is largely unknown . METHODS We conducted a population -based prospect i ve cohort study among pregnant women of the Kaiser Permanente Medical Care Program to examine the impact of prenatal depression on the risk of preterm delivery . We interviewed pregnant women in their early pregnancy . Women 's depressive symptoms were ascertained using the st and ard Center for Epidemiological Studies Depression Scale ( CESD ) . The presence of significant prenatal depressive symptoms and severe depressive symptoms was determined by CESD scores > or = 16 and > or = 22 , respectively . RESULTS Among the 791 participants who answered CESD questions and delivered a live birth , after controlling for potential confounders using the Cox proportional hazard regression , women with CESD scores > or = 16 had almost twice the risk of preterm delivery compared with women without depressive symptoms : adjusted hazard ratio ( aHR ) = 1.9 , 95 % confidence interval ( CI ) 1.0 - 3.7 . The risk of preterm delivery increased with increasing severity of depression : aHR = 1.6 ( CI 0.7 - 3.6 ) for CESD 16 - 21 and aHR = 2.2 ( CI 1.1 - 4.7 ) for CESD > or = 22 . The risk of preterm delivery associated with prenatal depression appears to be exacerbated by low educational level , a history of fertility problems and the presence of obesity and stressful events . The observed associations were not confounded by the use of antidepressants , although some of the associations did not reach statistical significance . CONCLUSIONS Our findings show that pregnant women with depressive symptoms are at increased risk of preterm delivery and , in addition , provide preliminary evidence that social and reproductive risk factors as well as obesity and stressful events may exacerbate the effect OBJECTIVE We assessed the relation between prepregnancy body mass index ( BMI ) and the likelihood of major depressive disorder ( MDD ) during pregnancy and tested whether this association was modified by gestational weight gain . METHOD Women ( N = 242 ) were enrolled at < 20 weeks gestation into a prospect i ve cohort study . Diagnosis of MDD was made with the Structured Clinical Interview for DSM-IV at 20 , 30 , and 36 weeks gestation . Gestational weight gain was compared with the 1990 Institute of Medicine weight gain recommendations . To assess the independent association between prepregnancy BMI and the odds of MDD , MDD at each time point was used as the dependent measure in a multivariable longitudinal logistic regression model employing generalized estimating equations . The data were collected from 2003 - 2007 . RESULTS There was a strong , positive dose-response association between prepregnancy BMI and the likelihood of MDD ( P = .002 ) . Compared with a BMI of 18 , the adjusted odds ratios ( 95 % confidence interval ) for BMI s of 23 , 28 , and 33 were 1.4 ( 1.1 to 1.7 ) , 1.9 ( 1.3 to 2.9 ) , and 2.6 ( 1.4 to 4.3 ) , respectively . Gestational weight gain significantly modified this effect . Among women with weight gains within and above the 1990 Institute of Medicine recommendations , pregravid overweight was associated with a greater likelihood of MDD . In contrast , all women with weight gains below recommended levels had an elevated odds of depression regardless of their pregravid BMI ( P < .05 ) . CONCLUSIONS Because pregravid overweight , poor gestational weight gain , and MDD all pose substantial risks for fetal development and birth outcomes , health care providers should monitor depression levels in these women to facilitate appropriate depression intervention OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity BACKGROUND An ecological analysis found that the docosahexaenoic acid content in mother 's milk and seafood intake were inversely correlated with postpartum depression . This prospect i ve study investigated the relationship of consumption of selected high-fat foods and specific types of fatty acids with the risk of postpartum depression . METHOD The subjects were 865 Japanese women . Dietary data were obtained from a self-administered diet history question naire during pregnancy . The Edinburgh Postnatal Depression Scale ( EPDS ) was used for the evaluation of postpartum depression . Adjustment was made for age , gestation , parity , cigarette smoking , family structure , family income , education , changes in diet in the previous month , season when data at baseline were collected , body mass index , time of delivery before the second survey , medical problems in pregnancy , baby 's sex and baby 's birthweight . RESULTS The percentage of women with high depression scores was 14.0 % . No evident dose-response associations were observed between intake of fish , meat , eggs , dairy products , total fat , saturated fatty acids , monounsaturated fatty acids , n-3 polyunsaturated fatty acids , n-6 polyunsaturated fatty acids , linoleic acid , alpha-linolenic acid , arachidonic acid , eicosapentaenoic acid or docosahexaenoic acid and the ratio of n-3 to n-6 polyunsaturated fatty acids and the risk of postpartum depression . However , there was an inverted J-shaped relationship between intake of n-3 polyunsaturated fatty acids and docosahexaenoic acid and the risk of postpartum depression . CONCLUSIONS This study failed to substantiate a clear inverse relationship between fish and n-3 polyunsaturated fatty acid intake and postpartum depression . Further investigations are needed to determine whether fish and n-3 polyunsaturated fatty acid consumption is preventive against postpartum depression Antenatal depression is associated with small-for-gestational age , but few studies have examined associations with weight during childhood . Similarly , few studies address whether antenatal and postpartum depression differentially affect child weight . Among 838 mother-child dyads in Project Viva , a prospect i ve cohort study , we examined relationships of antenatal and postpartum depression with child weight and adiposity . We assessed maternal depression at mid-pregnancy and 6 months postpartum with the Edinburgh Postnatal Depression Scale ( score > or = 13 indicating probable depression ) . We assessed child outcomes at age 3 years : body mass index ( BMI ) z-score , weight-for-height z-score , sum of subscapular ( SS ) and triceps ( TR ) skinfold thickness ( SS + TR ) for overall adiposity , and SS : TR ratio for central adiposity . Sixty-nine ( 8.2 % ) women experienced antenatal depression and 59 ( 7.0 % ) postpartum depression . Mean ( SD ) outcomes at age 3 were : BMI z-score , 0.45 ( 1.01 ) ; SS + TR , 16.72 ( 4.03 ) mm ; SS : TR , 0.64 ( 0.15 ) . In multivariable models , antenatal depression was associated with lower child BMI z-score ( -0.24 [ 95 % confidence interval : -0.49 , 0.00 ] ) , but higher SS : TR ( 0.05 [ 0.01 , 0.09 ] ) . There was no evidence of a dose-response relationship between antenatal depression and these outcomes . Postpartum depression was associated with higher SS + TR ( 1.14 [ 0.11 , 2.18 ] ) . In conclusion , whereas antenatal depression was associated with smaller size and central adiposity at age 3 years , postpartum depression was associated with higher overall adiposity Many women of reproductive age from developing countries have poor nutritional status , and the prevalence of depression during pregnancy is high . The objective of the present study was to assess the prevalence of antenatal depressive symptoms in early pregnancy , and to identify the demographic and nutritional factors associated with these symptoms in a sample of urban South Indian pregnant women . This cross-sectional study was the baseline assessment of a prospect i ve r and omized controlled trial of vitamin B12 supplementation in urban pregnant south Indian women between the ages of 18 and 40 years ( www . clinical trials.gov : NCT00641862 ) . 365 women in their first trimester of pregnancy were screened for depressive symptoms at an urban clinic in Karnataka , South India , using the Kessler Psychological Distress Scale ( K-10 ) . Nutritional , clinical and biochemical factors were also assessed . Mean ( SD ) age of the cohort was 22.6 ( 3.7 ) years and mean ( SD ) BMI was 20.4 ( 3.3 ) kg/m2 . 121 ( 33 % ) of the women in the 1st trimester had symptoms consistent with depression ( K-10 score > 6 ) . In multivariate log binomial regression analysis , presence of antenatal depressive symptoms in the first trimester were positively associated with vomiting , prevalence ratio ( PR ) = 1.54 ( 95 % CI 1.10 , 2.16 ) and negatively with anemia , PR = 0.67 ( 95 % CI 0.47 , 0.96 ) . Nutrient intakes , serum vitamin B12 , methylmalonic acid , homocysteine and red cell folate levels were not associated with measures of depression . Antenatal depressive symptoms in early pregnancy are highly prevalent in urban Indian women and are more common in women with vomiting and without anemia . In this cross-sectional data , blood concentrations of vitamin B12 and folate were not associated with depressive symptoms . The relationship between nutritional status and depressive symptoms may require larger and longitudinal studies OBJECTIVES To advance the underst and ing of the relationship between maternal perinatal depression and child overweight , we used appropriate methodology to account for missing data ; incorporated three exposure time points ; and included adequate covariate adjustment in a large , sociodemographically diverse sample . STUDY DESIGN AND SETTING We used data from 6,782 mother-child pairs in a prospect i ve population -based study . Maternal depression was assessed with the Brief Symptom Inventory at midpregnancy and 2 and 6 months postpartum . Child height and weight were measured at 36 months of age and converted to body mass index ( BMI ) z-scores . We compared the complete-case and multiple imputation ( MI ) analyses . RESULTS Fully adjusted complete-case models showed a positive association between depression at 2 months postpartum and child BMI z-score ( β=0.19 [ 95 % confidence interval (CI)=0.03 , 0.36 ] ; n=1,732 ) , and no association between prenatal depression or 6-month postpartum depression and child BMI . Using MI ( n=6,782 ) , there was no association between perinatal depression and child BMI at any time point . CONCLUSIONS Our study adds evidence that postpartum depression is not associated with child growth across the population in high-income countries . Our results highlight the importance of appropriate h and ling of missing data , adequate covariate control , and the value of study ing the conditions that have produced conflicting evidence regarding perinatal depression and child weight OBJECTIVE To determine the trajectory of postpartum weight changes and to examine associations between weight change in the first 6 weeks postpartum and demographic , clinical , psychosocial , and behavioral variables . DESIGN Prospect i ve , longitudinal design . SETTING Community hospital and university research setting . PARTICIPANTS 26 low-income women ( 9 White , 8 Black , and 9 Hispanic ) with uncomplicated term pregnancies . MAIN OUTCOME MEASURE Body mass index measured weekly . RESULTS Among White women , body mass index decreased significantly for the first 3 weeks of the postpartum period . Black women experienced a significant reduction in body mass index for only the first 2 postpartum weeks . Similarly , the postpartum body mass index decreased for the first 2 weeks for Hispanic women . Prepregnancy body mass index and gestational weight gain each had a significant positive effect on postpartum body mass index . Perception of social support at 4 weeks had a significant positive effect on postpartum body mass index in Black women . CONCLUSIONS The trajectory of weight change was nonlinear with large initial weight losses during the first 2 to 3 weeks postpartum followed by weight plateaus for the remainder of the first 6 weeks postpartum Observational studies suggest association between low concentrations of omega-3 family fatty acids and greater risk for post-partum depression ( PPD ) . The objective was to investigate the effect of unbalanced dietary intake of omega-6/omega-3 ratio > 9:1 in the prevalence for PPD . The study comprises a prospect i ve cohort with four waves of follow-up during pregnancy and one following delivery . PPD was evaluated according to the Edinburgh Post-partum Depression Scale ( PPD ≥ 11 ) in 106 puerperae between 2005 and 2007 , in Rio de Janeiro , Brazil . Independent variables included socio-demographic , obstetric , pre-pregnancy body mass index ( BMI ) and dietary intake data , which were obtained by means of a food frequency question naire in the first trimester of pregnancy . Statistical analysis involved calculation of PPD prevalence and multivariate Poisson regression with robust variance . PPD prevalence amounted to 26.4 % [ n = 28 ; confidence interval ( CI ) 95 % : 18.0 - 34.8 ] , and higher prevalences of PPD were observed in women who consumed an omega-6/omega-3 ratio > 9:1 ( 60.0 % ) and in those with pre-pregnancy BMI < 18.5 kg/m(2 ) ( 66.7 % ) . These variables held as factors associated to PPD in the multivariate model , elevating the chances of occurrence of the outcome in 2.50 ( CI 95 % : 1.21 - 5.14 ) and 4.01 times ( CI 95 % : 1.96 - 8.20 ) , respectively . Analyses were adjusted for age , schooling , pre-pregnancy BMI , lipids consumption and time elapsed since delivery . It verified an association between omega-6/omega-3 ratio above 9:1 , the levels recommended by the Institute of Medicine , and the prevalence of PPD . These results add to the evidence regarding the importance of omega-6 and omega-3 fatty acids in the regulation of mental health mechanisms BACKGROUND Intimate partner violence affects 1 in 4 women at some stage in their lives . Exposure to violence has short- and long-term consequences for women themselves and their children . The objective of this study was to examine associations between fear of an intimate partner and maternal physical and psychological morbidity in early pregnancy . METHOD This paper reports baseline measures from a prospect i ve pregnancy cohort study of 1,507 nulliparous women recruited at six public hospitals in Melbourne , Australia . RESULTS The study showed that 18.7 percent ( 280/1,497 ) of women reported being afraid of an intimate partner at some stage in their lives ; 3.1 percent ( 47/1,497 ) were afraid in early pregnancy and 15.6 percent ( 233/1,497 ) had been afraid before but not during the current pregnancy . Compared with women who had never been afraid of an intimate partner , women who reported being afraid of an intimate partner in early pregnancy ( < or = 24 wk gestation ) were at increased risk of urinary incontinence ( adjusted OR = 1.64 , 95 % CI 0.9 - 3.1 ) , fecal incontinence ( adjusted OR = 3.32 , 95 % CI 1.2 - 9.2 ) , vaginal bleeding ( adjusted OR = 2.84 , 95 % CI 1.5 - 5.5 ) , anxiety ( adjusted OR = 10.22 , 95 % CI 5.0 - 21.2 ) , and depression ( adjusted OR = 4.43 , 95 % CI 2.1 - 9.7 ) . Women afraid of an intimate partner before but not during pregnancy experienced a similar pattern of morbidity . CONCLUSIONS Women afraid of an intimate partner both before and during pregnancy have poorer physical and psychological health in early pregnancy ABSTRACT Objective : This paper presents a longitudinal analysis of behavioral and psychosocial correlates of weight trends during the first postpartum year . Data are derived from the Austin New Mothers Study ( ANMS ) , a longitudinal study of a low-income , tri-ethnic sample of postpartum women that incorporated serial assessment of weight and behavioral and psychosocial variables . Method : Postpartum body mass index ( BMI ) was measured prospect ively ( post-delivery , 6 weeks , and 3 , 6 , and 12 months postpartum ) . The analytic sample consisted of 382 White , African American , and Hispanic women receiving maternity care funded by Medicaid who had at least three measured postpartum weights . Behavioral and psychosocial variables included energy intakes , fat intakes , physical activity , health-related lifestyle , smoking , breastfeeding , contraception , depressive symptoms , emotional eating , body image , and weight-related distress . Results : Using hierarchical linear modeling to incorporate baseline only and time-varying effects , significant associations with postpartum BMI were found for the following variables : ethnicity ( p = .001 ) , time of weight measurement ( p < .001 ) , the interaction of ethnicity and time ( p = .005 ) , prepregnant BMI ( p < .001 ) , gestational weight gain ( p < .001 ) , weight-related distress ( p < .001 ) , and energy intakes ( p = .005 ) . After adjusting for covariates , ethnic groups displayed differing trends in postpartum BMI result ing in White women having significantly lower BMI s at 12 months postpartum compared to ethnic minority women ( p 's < .01 ) . Conclusion : Behavioral and psychosocial variables contribute to a fuller underst and ing of BMI status of low-income women during the first postpartum year Women with gestational diabetes mellitus ( GDM ) have a substantial risk of subsequently developing type 2 diabetes . This risk may be mitigated by engaging in healthy eating , physical activity , and weight loss when indicated . Since postpartum depressive symptoms may impair a woman ’s ability to engage in lifestyle changes , we sought to identify factors associated with depressive symptoms in the early postpartum period among women with recent GDM . The participants are part of the baseline cohort of the TEAM GDM ( Taking Early Action for Mothers with Gestational Diabetes Mellitus ) study , a one-year r and omized trial of a lifestyle intervention program for women with a recent history of GDM , conducted in Boston , Massachusetts between June 2010 and September 2012 . We administered the Edinburgh Postnatal Depression Scale ( EPDS ) at 4–15 weeks postpartum to women whose most recent pregnancy was complicated by GDM ( confirmed by laboratory data or medical record review ) . An EPDS score ≥9 indicated depressive symptoms . We measured height and thyroid stimulating hormone , and administered a question naire to collect demographic data and information about breastfeeding and sleep . We calculated body mass index ( BMI ) using self-reported pre-pregnancy weight and measured height . We review ed medical records to obtain data about medical history , including history of depression , mode of delivery , and insulin use during pregnancy . We conducted bivariable analyses to identify correlates of postpartum depressive symptoms , and then modeled the odds of postpartum depressive symptoms using multivariable logistic regression . Our study included 71 women ( mean age 33 years ± 5 ; 59 % White , 28 % African-American , 13 % Asian , with 21 % identifying as Hispanic ; mean pre-pregnancy BMI 30 kg/m2 ± 6 ) . Thirty-four percent of the women scored ≥9 on the EPDS at the postpartum visit . In the best fit model , factors associated with depressive symptoms at 6 weeks postpartum included cesarean delivery ( aOR 4.32 , 95 % CI 1.46 , 13.99 ) and gestational weight gain ( aOR 1.21 [ 1.02 , 1.46 ] , for each additional 5 lbs gained ) . Use of insulin during pregnancy , breastfeeding , personal history of depression , and lack of a partner were not retained in the model . Identifying factors associated with postpartum depression in women with GDM is important since depression may interfere with lifestyle change efforts in the postpartum period . In this study , cesarean delivery and greater gestational weight gain were correlated with postpartum depressive symptoms among women with recent GDM ( Clinical trials.gov NCT01158131 ) BACKGROUND Although maternal perinatal mental illnesses commonly present to and are primarily treated in general practice , few population -based estimates of this burden exist , and the most affected socioeconomic groups of pregnant women remain unclear . AIM To provide estimates of maternal depression , anxiety and serious mental illness ( SMI ) in UK general practice and quantify impacts of socioeconomic deprivation . DESIGN AND SETTING Cross-sectional analysis of prospect ively recorded general practice records from a UK-wide data base . METHOD A pregnancy ending in live birth was r and omly selected for every woman of childbearing age , 1994 - 2009 . Prevalence and diagnostic overlap of mental illnesses were calculated using a combination of medical diagnoses and psychotropic drug prescriptions . Socioeconomic deprivation was assessed using multivariate logistic regression , adjusting for calendar period and pregnancy history . RESULTS Among 116 457 women , 5.1 % presented with antenatal depression and 13.3 % with postnatal depression . Equivalent figures for anxiety were 2.6 % and 3.7 % and for SMI 1/1000 and 2/1000 women . Socioeconomic deprivation increased the risk of all mental illnesses , although this was more marked in older women . Those age 35 - 45 years in the most deprived group had 2.63 times the odds of antenatal depression ( 95 % confidence interval [ CI ] = 2.22 to 3.13 ) compared with the least deprived ; in women aged 15 - 25 years the increased odds associated with deprivation was more modest ( odds ratio = 1.35 , 95 % CI = 1.07 to 1.70 ) . Similar patterns were found for anxiety and SMI . CONCLUSION Strong socioeconomic inequalities in perinatal mental illness persist with increasing maternal age . Targeting detection and effective interventions to high-risk women may reduce inequity and avoid substantial psychiatric morbidity Objective : This report describes associations between body mass index ( BMI ; kg/m2 ) , eating attitudes , and affective symptoms across pregnancy and the postpartum period in a sample of 64 women . Methods : As part of a larger study , women were recruited during pregnancy and followed prospect ively to 14 months postpartum . Measures included self-reported prepregnancy and 4-month postpartum BMI as well as pregnancy , 4-month , and 14-month postpartum eating attitudes ( EAT ) , depressive symptoms ( CES-D ) , and anxiety symptoms ( STAI ) . Results : During pregnancy , symptoms of depression or anxiety were not significantly correlated with concurrent eating attitudes or measures of BMI . However , at 14 months postpartum , measures of eating attitudes and both depression and anxiety symptoms were associated . Measures of BMI were associated with depressive and anxiety symptoms at both 4 and 14 months postpartum . Four-month eating attitudes and BMI predicted 14-month postpartum depressive symptoms , beyond pregnancy , and 4-month postpartum measures of affective symptoms . Results suggested that overweight women were at risk for elevated anxiety at 4 months and depressive symptoms at both 4 and 14 months postpartum . Conclusions : These results provide evidence for a significant , albeit moderate , relationship between BMI , eating attitudes , and symptoms of depression and anxiety in the postpartum period that are not present during pregnancy PURPOSE This study examined the associations among maternal depression , measured in several ways , psychiatric medication use in pregnancy , and preterm delivery ( PTD ) . METHODS Data were collected from 3,019 women enrolled in the Pregnancy Outcomes and Community Health Study ( 1998 - 2004 ) , a prospect i ve study of pregnant women in five Michigan communities . Information on depressive symptoms , history of depression , and psychiatric medication use was ascertained through interviews at mid-pregnancy . These variables and other relevant covariates were incorporated into regression models with a binary outcome , that is , term ( > or = 37 weeks ' gestation ) as referent and PTD ( < 37 weeks ' gestation ) . A second set of models used a multicategory outcome , namely , term as the referent and PTD further subdivided by gestational weeks and clinical circumstances . MAIN FINDINGS The odds of overall PTD was increased among women who used psychiatric medication during pregnancy and had either elevated levels of depressive symptoms at mid-pregnancy ( adjusted odds ratio [ AOR ] , 2.0 ; 95 % confidence interval [ CI ] , 1.1 - 3.6 ) or a history of depression before pregnancy ( AOR , 1.6 ; 95 % CI , 1.1 - 2.5 ) . The combination of psychiatric medication use in pregnancy and depression , before pregnancy , or within pregnancy was most strongly linked to a medically indicated delivery before 35 weeks ' gestation ( AOR , 2.9 and 3.6 , respectively ) . CONCLUSIONS There are at least two plausible explanations for these findings . First , psychiatric medication use in pregnancy may pose an excess risk of PTD . Second , medication use may be an indicator of depressive symptom severity , which is a direct or indirect ( i.e. , alters behavior ) contributing factor to PTD Objective : Lifestyle intervention could help obese pregnant women to limit their weight gain during pregnancy and improve their psychological comfort , but has not yet been evaluated in r and omized controlled trials . We evaluated whether a targeted antenatal lifestyle intervention programme for obese pregnant women influences gestational weight gain ( GWG ) and levels of anxiety or depressed mood . Design and subjects : This study used a longitudinal interventional design . Of the 235 eligible obese pregnant women , 205 ( mean age ( years ) : 29±4.5 ; body mass index ( BMI , kg m−2 ) : 34.7±4.6 ) were r and omized to a control group , a brochure group receiving written information on healthy lifestyle and an experimental group receiving an additional four antenatal lifestyle intervention sessions by a midwife trained in motivational lifestyle intervention . Anxiety ( State and Trait Anxiety Inventory ) and feelings of depression ( Edinburgh Depression Scale ) were measured during the first , second and third trimesters of pregnancy . Socio-demographical , behavioural , psychological and medical variables were used for controlling and correcting outcome variables . Results : We found a significant reduction of GWG in the brochure ( 9.5 kg ) and lifestyle intervention ( 10.6 kg ) group compared with normal care group ( 13.5 kg ) ( P=0.007 ) . Furthermore , levels of anxiety significantly decreased in the lifestyle intervention group and increased in the normal care group during pregnancy ( P=0.02 ) ; no differences were demonstrated in the brochure group . Pre-pregnancy BMI was positively related to levels of anxiety . Obese pregnant women who stopped smoking recently showed a significant higher GWG ( β=3.04 ; P=0.01 ) ; those with concurrent gestational diabetes mellitus ( GDM ) ( β=3.54 ; P=0.03 ) and those who consumed alcohol on a regular base ( β=3.69 ; P=0.04 ) showed significant higher levels of state anxiety . No differences in depressed mood or obstetrical/neonatal outcomes were observed between the three groups . Conclusions : A targeted lifestyle intervention programme based on the principles of motivational interviewing reduces GWG and levels of anxiety in obese pregnant women |
915 | 22,511,006 | There is evidence that surgery is of benefit if undertaken early before the patient deteriorates . | BACKGROUND AND PURPOSE By 2010 there had been 14 published trials of surgery for intracerebral hemorrhage reported in systematic review s or to the authors , but the role and timing of operative intervention remain controversial and the practice continues to be haphazard .
This study attempted to obtain individual patient data from each of the 13 studies published since 1985 to better define groups of patients that might benefit from surgery . | Background and Purpose — Treatment of intracerebral hematoma ( ICH ) is controversial . An advantage of neurosurgical intervention over conservative treatment of ICH has not been established . Recent reports suggest a favorable effect of stereotactic blood clot removal after liquefaction by means of a plasminogen activator . The SICHPA trial was aim ed at investigating the efficacy of this treatment . Methods — A stereotactically placed catheter was used to instill urokinase to liquefy and drain the ICH in 6-hour intervals over 48 hours . From 1996 to 1999 , 13 centers entered 71 patients into the study . Patients were r and omized into a surgical group ( n=36 ) and a nonsurgical group ( n=35 ) . Admission criteria were the following : age > 45 years , spontaneous supratentorial ICH , Glasgow Eye Motor score ranging from 2 to 10 , ICH volume > 10 cm3 , and treatment within 72 hours . The primary end point was death at 6 months . As secondary end points , ICH volume reduction and overall outcome measured by the modified Rankin scale were chosen . The trial was prematurely stopped as a result of slow patient accrual . Results — Seventy patients were analyzed . Overall mortality at day 180 after stroke was 57 % ; this included 20 of 36 patients ( 56 % ) in the surgical group and 20 of 34 patients ( 59 % ) in the nonsurgical group . A significant ICH volume reduction was achieved by the intervention ( 10 % to 20 % , P < 0.05 ) . Logistic regression analysis indicated the possibility of efficacy for surgical treatment ( odds ratio , 0.23 ; 95 % confidence interval , 0.05 to 1.20;P = 0.08 ) . The odds ratio of mortality combined with modified Rankin scale score 5 at 180 days was also not statistically significant ( odds ratio , 0.52 ; 95 % confidence interval , 1.2 to 2.3;P = 0.38 ) . Conclusions — Stereotactic aspiration can be performed safely and in a relatively uniform manner ; it leads to a modest reduction of 18 mL of hematoma reduction over 7 days when compared with control , which has a 7-mL reduction , and therefore may improve prognosis The purpose of this study was to judge the clinical value of minimally invasive stereotactic puncture and thrombolysis therapy ( MISPTT ) for acute intracerebral hemorrhage ( ICH ) . A r and omized control clinical trial was undertaken . According to the enrollment criteria , 122 acute ICH cases were analyzed , of which 64 cases received MISPTT ( MISPTT group , MG ) and 58 cases received conventional craniotomy ( CC group , CG ) . The Glasgow coma scale ( GCS ) scores , postoperative complications ( PC ) , and rebleeding incidences were compared . Moreover , 1 year postoperation , the long-term outcomes of patients with regard to hematoma volume ( HV ) < 50 mL and HV ≥50 mL were judged , respectively , by the Glasgow outcome scale ( GOS ) , Barthel index ( BI ) , modified Rankin Scale ( mRS ) , and case fatality ( CF ) . MG patients showed obvious amelioration in GCS score compared with that of CG patients . The total incidence of PC in MG decreased compared with that of CG . The incidences of rebleeding in MG and CG were 9.4 and 17.2 % , respectively ( P = 0.243 ) . There were no obvious differences between the CFs of MG and CG ( 17.2 and 25.9 % , respectively , P = 0.199 ) . The GOS , BI , and mRS representing long-term outcome for both HV < 50 mL and HV ≥50 mL in MG were ameliorated significantly greater than that in CG patients ( all P < 0.05 ) . These data suggest that there are advantages with MISPTT not only in trauma and safety , but the MISPTT group had fewer complications and a trend toward improved short-term and long-term outcomes Background Within the spectrum of spontaneous intracerebral haemorrhage there are some patients with large or space occupying haemorrhage who require surgery for neurological deterioration and others with small haematomas who should be managed conservatively . There is equipoise about the management of patients between these two extremes . In particular there is some evidence that patients with lobar haematomas and no intraventricular haemorrhage might benefit from haematoma evacuation . The STICH II study will establish whether a policy of earlier surgical evacuation of the haematoma in selected patients will improve outcome compared to a policy of initial conservative treatment . Methods / Design an international multicentre r and omised parallel group trial . Only patients for whom the treating neurosurgeon is in equipoise about the benefits of early craniotomy compared to initial conservative treatment are eligible . All patients must have a CT scan confirming spontaneous lobar intracerebral haemorrhage ( ≤1 cm from the cortex surface of the brain and 10 - 100 ml in volume ) . Any clotting or coagulation problems must be corrected and r and omisation must take place within 48 hours of ictus . With 600 patients , the study will be able to demonstrate a 12 % benefit from surgery ( 2p < 0.05 ) with 80 % power . Stratified r and omisation is undertaken using a central 24 hour r and omisation service accessed by telephone or web . Patients r and omised to early surgery should have the operation within 12 hours . Information about the status ( Glasgow Coma Score and focal signs ) of all patients through the first five days of their trial progress is also collected in addition to another CT scan at about five days ( + /- 2 days ) . Outcome is measured at six months via a postal question naire to the patient . Primary outcome is death or severe disability defined using a prognosis based 8 point Glasgow Outcome Scale . Secondary outcomes include : Mortality , Rankin , Barthel , EuroQol , and Survival . Trial Registration IS RCT N : IS RCT BACKGROUND Spontaneous supratentorial intracerebral haemorrhage accounts for 20 % of all stroke-related sudden neurological deficits , has the highest morbidity and mortality of all stroke , and the role of surgery remains controversial . We undertook a prospect i ve r and omised trial to compare early surgery with initial conservative treatment for patients with intracerebral haemorrhage . METHODS A parallel-group trial design was used . Early surgery combined haematoma evacuation ( within 24 h of r and omisation ) with medical treatment . Initial conservative treatment used medical treatment , although later evacuation was allowed if necessary . We used the eight-point Glasgow outcome scale obtained by postal question naires sent directly to patients at 6 months follow-up as the primary outcome measure . We divided the patients into good and poor prognosis groups on the basis of their clinical status at r and omisation . For the good prognosis group , a favourable outcome was defined as good recovery or moderate disability on the Glasgow outcome scale . For the poor prognosis group , a favourable outcome also included the upper level of severe disability . Analysis was by intention to treat . FINDINGS 1033 patients from 83 centres in 27 countries were r and omised to early surgery ( 503 ) or initial conservative treatment ( 530 ) . At 6 months , 51 patients were lost to follow-up , and 17 were alive with unknown status . Of 468 patients r and omised to early surgery , 122 ( 26 % ) had a favourable outcome compared with 118 ( 24 % ) of 496 r and omised to initial conservative treatment ( odds ratio 0.89 [ 95 % CI 0.66 - 1.19 ] , p=0.414 ) ; absolute benefit 2.3 % ( -3.2 to 7.7 ) , relative benefit 10 % ( -13 to 33 ) . INTERPRETATION Patients with spontaneous supratentorial intracerebral haemorrhage in neurosurgical units show no overall benefit from early surgery when compared with initial conservative treatment Objective : To perform a single-center pilot investigation of early hematoma removal in patients with intracerebral hemorrhage ( ICH ) . Background : Considerable debate remains regarding the utility of surgical clot evacuation for ICH . Methods : This was a prospect i ve trial of open craniotomy within 12 hours of ICH symptom onset versus best medical therapy . Patients were eligible if they had a nontraumatic ICH > 9 mL with significant neurologic impairment and were prepared for surgery within 12 hours of symptom onset . The study included a prospect i ve registry of patients and a r and omized trial . Results : The registry group included 34 medical and seven surgical patients . The surgical group had larger hemorrhages ( median , 96 mL ) and a lower Glasgow Coma Scale ( GCS ) score ( median , 10 ) compared with the medical group ( 33 mL ; GCS score , 13 ) . Six-month mortality was less in the medical group ( 36 % ) compared with the surgical group ( 54 % ) . In the r and omized series , median ICH volumes were similar in the surgical group ( n = 17 ; 49 mL ) compared with the medical group ( n = 17 ; 44 mL ) . Median GCS score was also similar ( medical , 10 ; surgical , 11 ) . Mortality was lower in the surgical group ( 6 % ) compared with the medical group ( 24 % ) at 1 month , but similar at 6 months ( surgical group , 17 % ; medical group , 24 % ) . Conclusion : A trial of early surgery for ICH is feasible . This study represents the largest prospect i ve , r and omized series of surgery for ICH . A modest early mortality benefit for surgery is possible , but long-term benefit for surgery was not established in this single-center pilot investigation St and ards of scientific reporting have evolved from the very beginning of scientific reporting . Virtually all journals now publish instructions for authors and most medical journals adhere to certain st and ards of publication . Such st and ards have been promoted by international groups such as the International Committee of Medical Journal Editors ( ICMJE ) and Committee on Publication Ethics ( COPE ) . The ICMJE has published general st and ards for crafting scientific articles : the “ Uniform Requirements for Manuscripts Su bmi tted to Biomedical Journals : Writing and Editing for Biomedical Publication ” [ 7 ] . These guidelines include suggestions not only for manuscript preparation , but also guidelines for ethical issues related to publishing . COPE , however , focuses on ethical issues [ 1 ] . CORR adheres to these guidelines ; authors may find links to these guidelines in our online Instructions for Authors . Such guidelines , as important as they are , lack sufficient detail to ensure all important information is included . Therefore , in addition to these general guidelines for preparing a manuscript , numerous international groups have published guidelines to ensure various sorts of studies contain all essential information . These include the CONSORT ( Consoli date d St and ards of Reporting Trials ) guidelines for r and omized trials [ 2 , 3 , 8 ] , QUORUM ( Quality of Reporting of Meta-analyses ) [ 6 ] and MOOSE ( Meta- analysis Of Observational Studies in Epidemiology ) [ 13 ] for meta-analyses , and STROBE ( Strengthening the Reporting of Observational Studies in Epidemiology ) for various sorts of observational studies ( the majority of clinical studies in surgical disciplines ) [ 12 , 15 ] . In essence , these guidelines tell investigators and authors what information is required to ensure readers ( and review ers ) can properly evaluate the study . Despite these st and ards , most reports of clinical studies lack such critical information . I suspect this is less by intent than lack of awareness of what information is required . In addition , although many journals , including CORR require a Level of Evidence [ 5 , 10 , 16 ] for studies involving patients , most clinical articles published in surgical journals have a relatively low level ; prospect i ve , r and omized trials are uncommon ( and often impractical ) , and even sufficiently large retrospective cohort studies to control for confounding variables may be unachievable for many conditions or treatments in single institutions . In the absence of high levels of evidence , systematic review s [ 9 , 11 , 17 ] and meta-analyses [ 4 ] have become increasingly common . My search of PubMed for articles limited to meta- analysis yielded 276 articles from 1950–1989 , 2116 from 1990–1994 , 3736 from 1995–1999 , 7920 from 2000–2004 , and 9313 from 2005 to 2009 . Most of these analyses undoubtedly collected information from lower level studies , thereby incurring the limitations of the individual studies . Virtually all systematic and meta-analyses we have recently published noted missing and variably reported data . In contrast to medical disciplines , surgical disciplines do not have the advantage of being able to conduct tightly design ed prospect i ve , r and omized , blinded , controlled trials . ( A PubMed search limited to r and omized controlled trials suggested The Journal of Bone and Joint Surgery and CORR had together published 556 RCTs and although I did not individually check these for quality , they reflect a small fraction of the articles both journals publish . ) For the foreseeable future , most of our information will arise from observational studies rather than prospect i ve trials . In this setting , it is especially important that each article contain all relevant information for future systematic review s and meta-analyses . The STROBE guidelines [ 12 ] provide authors with lists of critical information for reporting three sorts of observational studies : cohort ( longitudinal studies typically reporting outcomes of treatment in one or more cohorts ) , case-control ( studies identifying factors in outcomes ) , and cross-sectional studies ( studies to identify prevalence of factors or characteristics in a population at a single time ) . CORR now requires authors to adhere to CONSORT guidelines for r and omized clinical trials , QUORUM guidelines for meta-analyses , and STROBE guidelines for observational clinical studies . Authors will be able to download from our Instructions to Authors convenient templates for the various sorts of articles we publish ; these templates contain the information required . In addition , we request authors read and follow the guidelines in the Cochrane H and book for Systematic Review s of Interventions 4.2.6 [ 14 ] . Adherence to these st and ards will enhance our ability to answer key clinical questions in more definitive ways than we have in the past , and to answer more questions Hypertensive putaminal hemorrhage remains a major cause of hemorrhagic stroke carrying extremely high morbidity . Considerable controversy remains regarding the optimal form of therapy . Between 1983 and 1989 we conducted a prospect i ve r and omized trial with three treatment strategies : best medical management , best medical management plus intracranial pressure monitoring , and surgical evacuation . Only patients with significant deficit harboring a putaminal hematoma at least 3.0 cm in diameter were entered . The study was interrupted after 21 patients had been studied ( 9 , best medical management ; 4 , intracranial pressure monitoring ; and 8 , surgical evacuation ) . No differences were found among groups for age , admission blood pressure , and time interval between onset of symptoms and arrival at hospital . None of the subjects were capable of returning to prestroke activity . Fifteen ( 71 % ) died or remained vegetative at 6 months , and only 4 ( 19 % ) were capable of independent life at home . Of the 9 patients in the best medical management arm , 7 were dead or vegetative . In the surgical group , 4 patients died and only 2 were capable of independent life . These results suggest that current medical and neurosurgical therapies remain ineffective in preventing the devastating neurologic consequences of hypertensive putaminal hemorrhage OBJECT Stereotactic evacuation of hematoma has been reported to reduce the incidence of mortality and to improve functional outcome in patients with spontaneous putaminal hemorrhage . Stereotactic evacuation of hematoma has not been widely accepted as a st and ard therapy , however , because its effect on functional outcome has been regarded as marginal and there have been no r and omized trials with sufficient statistical power to quantify the benefits of this procedure . The authors reassessed the value of stereotactic evacuation of hematoma by analyzing its impact on activities of living during the chronic period following spontaneous putaminal hemorrhage in a r and omized study . METHODS Four hundred ninety patients were entered into the study . The severity of their hemorrhages was grade d neurologically on admission ( neurological grade s : 1 , eyes are open ; 2 , eyes are closed but open to weak stimuli ; 3 , eyes are closed but open to strong stimuli ; 4 , eyes do not open but extremities move to stimuli ; and 5 , eyes do not open and extremities do not move to stimuli ) . Patients with Grade 2 and those with Grade 3 were r and omized into two groups with different treatment protocol s ( Group I , stereotactic evacuation of the hematoma ; and Group II , conservative treatment ) . Patients assigned neurological Grade 4 or 5 were excluded from the study because a large-scale retrospective study in Japan revealed that surgical treatment in patients assigned to these neurological grade s does not improve functional outcome . Among the 490 patients , 242 were r and omized strictly . This patient population comprised 148 men and 94 women ranging in age from 38 to 80 years ( mean 60.5 years ) . Compared with Group II , Group I treatment result ed in a lower mortality rate and better recovery to functional independence in patients with neurological Grade 3 . In patients with Grade 2 , Group I treatment contributed to a better recovery of functional outcome and a lower mortality rate , but the difference was not significant . Multivariate analysis confirmed that stereotactic evacuation of the hematoma was contributory to a better recovery in functional outcome . CONCLUSIONS Stereotactic evacuation of hematoma is clearly of value in selected patients with spontaneous putuminal hemorrhage , whose eyes are closed but will open in response to strong stimuli ( neurological Grade 3 ) on admission Background : A modest benefit was previously demonstrated for hematoma evacuation within 12 hours of intracerebral hemorrhage onset . Perhaps surgery within 4 hours would further improve outcome . Methods : Adult patients with spontaneous supratentorial intracerebral hemorrhage were prospect ively enrolled . Craniotomy and clot evacuation were commenced within 4 hours of symptom onset in all cases . Mortality and functional outcome were assessed at 6 months . This group of patients was compared with patients treated within 12 hours of symptom onset using the same surgical and medical protocol s. Results : The study was stopped after a planned interim analysis of 11 patients in the 4-hour surgery arm . Median time to surgery was 180 minutes ; median hematoma volume was 40 mL ; median baseline NIH Stroke Scale score was 19 and Glasgow Coma Scale score was 12 . Six-month mortality was 36 % and median Barthel score was 75 in survivors . Postoperative rebleeding occurred in four patients , three of whom died . A relationship between postoperative rebleeding and mortality was apparent ( p = 0.03 ) . Rebleeding occurred in 40 % of the patients treated within 4 hours , compared with 12 % of the patients treated within 12 hours ( p = 0.11 ) . There was a clear correlation between improved outcome and smaller postsurgical hematoma volume ( p = 0.04 ) . Conclusions : Surgical hematoma evacuation within 4 hours of symptom onset is complicated by rebleeding , indicating difficulty with hemostasis . Maximum removal of blood remains a predictor of good outcome BACKGROUND Treatment of primary SICH is still controversial . The aim of this study was to investigate the effectiveness of craniotomy and early hematoma evacuation vs nonoperative management in patients with SICH . METHODS A prospect i ve r and omized study of craniotomy and early hematoma removal vs best medical management was performed in 108 patients with primary SICH . Surgical or medical treatment was initiated within 8 hours post ictus . Principal eligibility criterium was the presence of neurologic impairment associated with a spontaneous subcortical or putaminal hemorrhage bigger than 30 mL. Outcomes were assessed at 1 year post ictus . RESULTS Analysis of outcome revealed a significantly higher percentage of GOS scores higher than 3 for the surgical patients , compared with those of the conservative group ( 33 % and 9 % , respectively ; P < .05 ) . By contrast , the mortality rates between operated and conservatively managed patients did not differ significantly . The main prognostic variables were the initial neurologic status , hematoma volume , and location . Stratifications of these parameters and analysis showed that the positive effect of surgery on the quality of survival was statistically not valid for patients with GCS scores lower than 8 or ICH volumes 80 mL or higher at the time of enrollment . CONCLUSIONS The study demonstrates that surgical patients with subcortical or putaminal hematomas showed better functional results than their conservatively treated counterparts . However , early ICH evacuation failed to improve the survival rates , as compared with best medical management A controlled r and omized study of endoscopic evacuation versus medical treatment was performed in 100 patients with spontaneous supratentorial intracerebral ( subcortical , putaminal , and thalamic ) hematomas . Patients with aneurysms , arteriovenous malformations , brain tumors , or head injuries were excluded . Criteria for inclusion were as follows : patients ' age between 30 and 80 years ; a hematoma volume of more than 10 cu cm ; the presence of neurological or consciousness impairment ; the appropriateness of surgery from a medical and anesthesiological point of view ; and the initiation of treatment within 48 hours after hemorrhage . The criteria of r and omization were the location , size , and side of the hematoma as well as the patient 's age , state of consciousness , and history of hypertension . Evaluation of outcome was performed 6 months after hemorrhage . Surgical patients with subcortical hematomas showed a significantly lower mortality rate ( 30 % ) than their medically treated counterparts ( 70 % , p less than 0.05 ) . Moreover , 40 % of these patients had a good outcome with no or only a minimal deficit versus 25 % in the medically treated group ; the difference was statistically significant for operated patients with no postoperative deficit ( p less than 0.01 ) . Surgical patients with hematomas smaller than 50 cu cm made a significantly better functional recovery than did patients of the medically treated group , but had a comparable mortality rate . By contrast , patients with larger hematomas showed significantly lower mortality rates after operation but had no better functional recovery than the medically treated group . This effect from surgery was limited to patients in a preoperatively alert or somnolent state ; stuporous or comatose patients had no better outcome after surgery . The outcome of surgical patients with putaminal or thalamic hemorrhage was no better than for those with medical treatment ; however , there was a trend toward better quality of survival and chance of survival in the operated group INTRODUCTION Brain hemorrhage is the most frequent fatal form of stroke and has the highest level of morbidity of any stroke subtype . For patients with both intracerebral hemorrhage and intraventricular hemorrhage ( IVH ) , expected mortality is 50 - 80 % . No vali date d , efficacious treatment exists for humans , but animal models demonstrate substantial physiologic and functional benefits associated with rapid , near-complete removal of blood from either the ventricle or intracerebral location ( i.e. , approximately 80 % removal over 48 h ) . The purpose of the CLEAR-IVH trial ( Parts A and B ) is to evaluate safety and efficacy of using multiple injections of low-dose rt-PA to accelerate lysis and evacuation of IVH . METHODS Patients enrolled in the trial receive an injection of 1.0 mg rtPA through an external ventricular drain every 8 h up to 12 doses , or until clot reduction or clinical endpoint is met . CT scans are taken daily to monitor clot resolution and check for unexpected bleeding events . In a previous dose-finding study where the safety profile ( symptomatic rebleeding ) was 0 % , 1 mg rt-PA every 8 h was determined the appropriate dose . RESULTS Comprehensive analyses of 36 patients in the recently completed CLEAR-IVH Part B are currently being conducted . Adverse events are within safety limits , including 30-day mortality , 8 % ; symptomatic re-bleeding , 8 % ; and bacterial ventriculitis , 0 % . CONCLUSION Preliminary analyses show that use of low-dose rt-PA can be safely administered to stable IVH clots and may increase lysis rates INTRODUCTION Compared to ischemic stroke , intracerebral hemorrhage ( ICH ) is easily and rapidly identified , occurs in younger patients , and produces relatively small initial injury to cerebral tissues -- all factors suggesting that interventional amelioration is possible . Investigations from the last decade established that extent of ICH-mediated brain injury relates directly to blood clot volume and duration of blood exposure to brain tissue . Using minimally-invasive surgery plus recombinant tissue plasminogen activator ( rtPA ) , MISTIE investigators explored aggressive avenues to treat ICH . METHODS We investigated the difference between surgical intervention plus rtPA and st and ard medical management for ICH . Subjects in both groups were medically managed according to st and ard ICU protocol s. Subjects r and omized to surgery underwent stereotactic catheter placement and clot aspiration . Injections of rtPA were then given through hematoma catheter every 8 h , up to 9 doses , or until a clot-reduction endpoint . After each injection the system was flushed with sterile saline and closed for 60 min before opening to spontaneous drainage . RESULTS Average aspiration of clots for all patients r and omized to surgery plus rtPA was 20 % of mean initial clot size . After acute treatment phase ( aspiration plus rtPA ) , clot was reduced an average of 46 % . Recorded adverse events were within safety limits , including 30-day mortality , 8 % ; symptomatic re-bleeding , 8 % ; and bacterial ventriculitis , 0 % . Patients r and omized to medical management showed 4 % clot resolution in a similar time window . Preliminary analysis indicates that clot resolution rates are greatly dependent on catheter placement . Location of ICH also affects efficacy of aggressive treatment of ICH . CONCLUSION There is tentative indication that minimally-invasive surgery plus rtPA shows greater clot resolution than traditional medical management Background and purpose s To evaluate the effects of minimally invasive craniopuncture therapy compared with conservative treatment in treating intracerebral hemorrhage ( 25 - 40 ml ) in the basal ganglion . Methods A multicenter , r and omized control clinical trial comprised 465 cases of hemorrhage in the basal ganglion from 42 hospitals in China . Three hundred and seventy-seven patients with hemorrhage were r and omly assigned to receive minimally invasive craniopuncture therapy ( n = 195 ) or conservative control treatment ( n = 182 ) . The main indices of evaluation were the degree of neurological impairment at the 14th day after treatment , activities of daily living at the end of the 3rd month and the case fatality within 3 months . Results Improvement of neurological function in the minimally invasive craniopuncture group was significantly better than that in the control group at the 14th day ( χ2 = 7 93 , P = 0 02 ) . At the end of the 3rd month , there was a significant difference between the two groups in activities of daily living score ( χ2 = 2313 , P<0·001 ) . The proportion of dependent survival patients ( modified Rankin scale > 2 ) in the craniopuncture group ( 40·9 % ) was significantly lower than that in the conservative group ( 63·0 % ) at the end of the 3rd month ( χ2 = 16·95 , P<0·01 ) . There was no significant difference in the cumulative fatality rates within three months between the two groups [ 6·7 % ( 13/195 ) in the craniopuncture group and 8·8 % ( 16/182 ) in the conservative group ] . Conclusions This minimally invasive craniopuncture technique can improve the independent survival of patients with small basal ganglion hemorrhage . It is a safe and practical technique in treating cerebral hemorrhage In a prospect i ve study , 52 patients with a spontaneous supratentorial intracerebral hematoma ( ICH ) were r and omly assigned to receive emergency surgery or conservative treatment within 48 hours after the bleed . Patients with a decreased level of consciousness and /or a severe neurological deficit were admitted to the study . The overall mortality rate at 6 months was 42 % : 10 ( 38 % ) of the 26 patients in the conservative group and 12 ( 46 % ) of the 26 in the surgical group . Six ( 20 % ) of the 30 survivors at 6 months were able to conduct their activities of daily living independently : five ( 31 % ) of the 16 patients in the conservative group and one ( 7 % ) of the 14 in the operative group . These differences are not statistically significant . The mortality rate of semicomatose or stuporous patients ( Glasgow Coma Scale score 7 to 10 ) was statistically significantly lower in the surgical group ( none of the four patients ) than in the conservative group ( four of five patients ) ( p less than 0.05 ) ; however , all surviving patients in this subgroup were severely disabled . The study suggests that surgical treatment of this category of patients with ICH does not offer any definite advantage over conservative treatment . In semicomatose or stuporous patients , surgery may improve the length of survival , but the quality of life remains poor |
916 | 17,253,470 | There was a small but statistically significant 6 % decrease in subjective symptoms after a single dose of decongestant compared with placebo .
This was supported by a significant decrease in nasal airways resistance .
With repeated doses , nasal decongestants produce a very small statistical benefit of 4 % over three to five days , again supported by a decrease in nasal airways resistance .
A single oral dose of nasal decongestant in the common cold is modestly effective for the short term relief of congestion in adults , and these drugs also provide benefit in some individuals after regular use over three to five days . | BACKGROUND The common cold is a major and recurrent cause of morbidity , on average affecting children and adults two or more times each year .
Nasal congestion is its commonest symptom and many therapies are marketed for its relief .
There is no meta- analysis of controlled clinical trials on the effects of nasal decongestants in the common cold .
OBJECTIVES To assess the efficacy of nasal decongestants at reducing the symptom of nasal congestion in adults and children with the common cold and to identify possible adverse effects associated with their use . | The effects of oral administration of a lozenge containing 11 mg (-)-menthol on nasal resistance to airflow ( NAR ) and nasal sensation of airflow in 62 subjects suffering from nasal congestion associated with naturally acquired common cold infection have been studied . NAR was measured by posterior rhinomanometry and nasal sensation of airflow by means of a visual analogue scale ( VAS ) . The effects of the lozenge were compared with a c and y placebo lozenge in a double blind r and omized trial . NAR showed a significant increase ( P less than 0.05 ) in both the menthol and placebo groups over the 2 h experiment with no difference between the groups at any time . The VAS scores showed significant changes of subjective improvement in nasal sensation of airflow ( P less than 0.001 ) in the menthol-treated group 10 min after dosing whereas the placebo group showed no change . It is concluded that dosing with 11 mg menthol in subjects with common cold has no effect on NAR as measured by posterior rhinomanometry but causes a marked change in nasal sensation of airflow with a subjective sensation of nasal decongestion Background Pseudoephedrine ( 60 mg ) is widely used as an oral decongestant taken in tablet or syrup formulations every 4–6 hours for the treatment of nasal congestion associated with common cold and allergy . However , there are relatively few studies in the literature that have used objective measures of nasal airway resistance ( NAR ) to assess the efficacy of pseudoephedrine , and most studies use only a single dose of medication . The present study has the aims of study ing the safety and efficacy of a new pseudoephedrine formulation after single and multiple doses in patients with URTI . Methods The study was a double-blind , r and omized , parallel-group , placebo-controlled trial conducted over three study days at a single center . Patients suffering from nasal congestion associated with common cold were recruited and total NAR was measured by the technique of posterior rhinomanometry . NAR and subjective scores of nasal congestion were measured at baseline and after dosing with study medication , every hour over a four-hour period on day 1 after a single dose , and on day 3 after multiple doses of medication . Subjective scores of congestion/stuffiness were also made as a summary score at the end of each day of treatment . Results Two hundred and thirty-eight patients with nasal congestion associated with acute upper respiratory tract infection ( URTI ) , mean age 20 years , were recruited to the study and received treatment . After a single dose on day 1 the pseudoephedrine group had a statistically significant lower area under the NAR curve than placebo ( p = 0.006 ) for the primary efficacy variable area under the NAR curve from 0–3 hours ( NAR AUC 0–3h ) , and similarly for the secondary efficacy variable NAR AUC 0–4h ( p = 0.001 ) . On day three after multiple doses , the pseudoephedrine group had a statistically significant lower NAR AUC 0–3h and AUC 0–4h than placebo ( p < 0.001 ) , On day 1 , the pseudoephedrine group had significantly lower subjective scores for congestion than placebo visual analog scale ( VAS ) AUC 0–3h ( p = 0.029 ) and similarly for VAS AUC 0–4h ( p = 0.021 ) . On day 3 , the differences in subjective scores were not significantly different . The mean decrease from baseline of the summary score for congestion/stuffiness over the duration of the study was greater in the pseudoephedrine group compared to the placebo group ( p = 0.016 ) . On average , heart rate was between two and four beats per minute greater in the pseudoephedrine group compared to placebo . Five adverse events were reported in both treatment groups and these were deemed to be unrelated to treatment . Conclusion The results demonstrate that pseudoephedrine is a safe and effective treatment for nasal congestion associated with URTI . The results from the laboratory study on day 1 demonstrate by both objective and subjective measures of nasal congestion that a single dose of 60 mg pseudoephedrine is superior to placebo treatment . Support for the decongestant efficacy of multiple doses of pseudoephedrine is provided by objective measures on day 3 and subjective measures made over three days , but not by the VAS scores on day 3 OBJECTIVE Nasal inhalation of steam has been proposed as treatment of viral colds on the assumption that increased intranasal temperature will inhibit replication of rhinovirus ( RV ) . The effect of steam inhalation on RV shedding by infected volunteers was examined in this study . DESIGN R and omized controlled trial . Volunteers experimentally infected with RV were treated with machine-generated humidified air , which was either hot ( active ) or at room temperature ( placebo ) . Viral shedding was assessed over the 4 days following treatment . SETTING Local hotel . PARTICIPANTS Twenty volunteers from the university community who were susceptible to the challenge virus . INTERVENTION Two 30-minute intranasal treatments , the first at 24 hours after inoculation and the second at 48 hours . The temperature of active vapor was 42 degrees C to 44 degrees C and of placebo vapor was 22 degrees C. MAIN OUTCOME MEASURES Viral titers in nasal washings on each of 5 days following inoculation . RESULTS Mean viral titers prior to the first treatment were 10(1.7 ) tissue culture infectious doses per milliliter in the active group and 10(1.5 ) in the placebo group . Mean titers for the next 4 days were 10(1.7 ) , and 10(1.7 ) , 10(1.2 ) , and 10(0.9)/mL in the active group and 10(1.8 ) , 10(1.9 ) , 10(1.6 ) , and 10(0.7)/mL in the placebo group ( no significant difference ) . The proportion of volunteers who shed virus on each day was also similar in the two groups . CONCLUSION Two nasal inhalation treatments with steam had no effect on viral shedding in volunteers with experimental RV colds A total of 466 healthy adults from four different regions of Engl and entered a double-blind , r and omised trial to test the effectiveness of an antihistamine ( triprolidine ) and a decongestant ( pseudoephedrine ) , alone or in combination , in relieving symptoms of the common cold . During the study 199 subjects reported a total of 243 colds . Subjects recorded the severity of 12 symptoms during treatment and noted separately the severity of a further seven symptoms that represented unwanted effects of treatment or served as an index of suggestibility . They were then asked about their overall improvement in symptoms during treatment and whether they thought they had taken placebo . Sneezing , nasal obstruction , and overall response to treatment were significantly improved ( p < 0.01 ) with psuedoephedrine or pseudoephedrine and triprolidine compared with placebo The effectiveness of orally administered pseudoephedrine in patients with acute or chronic nonsuppurative rhinitis was evaluated under double-blind conditions . Intranasally administered ephedrine which was given to all patients at the end of this study served as the positive control . Marked nasal decongestant effects of a single oral dose of pseudoephedrine ( 60 mg tablet ) , as determined by a modified passive anterior , rhinometrie technique occurred within 30 minutes and were maintained for at least four hours . The mean nasal decongestant response ( Δ% of baseline ) of 57.2 % was associated with a mean peak , plasma pseudoephedrine level of 274 ng/ml . In addition , the maximum response to oral pseudoephedrine treatment was equivalent to the response produced by ephedrine nasal spray . These results suggest that pseudoephedrine is an orally effective nasal decongestant We tested the hypothesis that antihistamine-decongestant combinations cause no clinical ly significant relief of the symptoms of upper respiratory tract infections in young children by r and omly assigning 96 children to one of three treatment groups : antihistamine-decongestant , placebo , and no treatment . There were no differences among the three study groups in the proportion of children considered " better " overall by the parent 48 hours after the initial assessment ( drug , 67 % ; placebo , 71 % ; no treatment , 57 % ; p = 0.53 ) . There were no differences among groups in individual or composite symptom score changes . Two thirds of parents whose children were eligible for the drug trial believed that their child needed medicine for cold symptoms . In the proportion of parents believing that their child needed medicine , there was no difference between those who consented to participate and those who refused . Parents who wanted medicine at the initial visit reported more improvement at follow-up , regardless of whether the child received drug , placebo , or no treatment . We conclude that there is no clinical ly significant improvement in symptoms of upper respiratory tract infection , including no significant placebo effect , in young children for whom an antihistamine-decongestant is prescribed A placebo-controlled double-blind r and omized trial was carried out to assess the efficacy of pseudoephedrine in relieving nasal congestion in the common cold . Fifty-four previously healthy persons who had a common cold for at least 5 days or less at the start of the study with moderate to severe nasal congestion were recruited , 52 completed the trial . Following a single dose of oral pseudoephedrine ( 60 mg capsule ) or placebo , symptoms of congestion improved significantly compared with placebo at times 60 , 90 , 120 , and 150 min after the dose . Total nasal minimum cross-sectional area and nasal volume measured by acoustic rhinometry increased significantly compared to placebo ( P = 0.018 and P = 0.003 , respectively ) after the dose . There was no significant change in nasal area as measured by active posterior rhinomanometry after pseudoephedrine compared to placebo . We conclude that in the acute common cold , a single 60 mg dose of pseudoephedrine produces significant increases in the dimensions of the nasal cavity compared to placebo and this is associated with a reduction in the symptom of congestion The aim of the trial was to examine the effectiveness of an oral decongestant in common cold . Thirty subjects with naturally acquired colds got a 100 mg sustained release tablet containing norephedrine on one day and a placebo tablet on another day in double blind design . Changes in nasal patency were assessed by rhinomanometry , measurement of nasal expiratory peak flow , and a self- assessment test , and the number of sneezes and of nose blowings were recorded in a 10 hours period after medication . Rhinomanometry , but not peak flow measurements showed a significant difference ( p less than 0.02 ) two hours after medication , and the self- assessment of nasal blockage showed that the effect lasted for the entire 10 hours observation period ( p less than 0.01 ) . Nasal respiration was reestablished in half of the blocked noses . There was no effect on number of sneezes and nose blowings . In conclusion , oral norephedrine has a moderate decongestant effect , which may justify its use in adults with common colds . This symptom amelioration must be balanced against cost of therapy and risk of side effects . A prevention of otitis media and of sinusitis has not been documented in the literature A VARIETY of drugs and drug formulations have been developed for the symptomatic relief of engorged mucous membranes which accompany coryza and upper respiratory infections . Existing objective techniques for measuring duration of drug effect include the determination of urinary excretion patterns1or blood levels2following drug administration . However , these are measurements of drug levels only inferentially related to therapeutic responses . Direct determinations of nasal airflow have been used occasionally to compare the effectiveness of formulations , and some of these rhinometric techniques have been review ed by Aviado,3Stoksted,4 and McLaurin.5,6The technique that we have developed is essentially a modification of that reported by McLaurin , dependent only upon a pressure transducer and a direct writing recorder . St and ard airflow measurements depend upon variations of pressure drop relative to a st and ard external pressure , an oxygen tank , for example . For our method we have eliminated the external pressure st and The utility of an anterior rhinomanometric method for the assessment of decongestant drug activity is illustrated with representative clinical data . Controlled studies employing topical nasal spray , nasal inhaler , and oral syrup formulations were conducted under single- or double-blind conditions in patients with allergic or coryzal rhinitis . The method provided an objective means to distinguish active from placebo ( vehicle ) treatments and to discriminate differences in decongestant activity between two active formulations . Furthermore , objective ly determined increases in nasal patency paralleled the patients ' subjective perception of improved airflow . In conclusion , this rhinomanometric methodology provided objective confirmation of drug activity with orally-administered , inhaled , and topically-applied decongestant drug formulations The aim of this study was to investigate the efficacy of pseudoephedrine as a nasal decongestant . Patients with nasal congestion associated with common cold received two doses of medication separated by 4 hours , either 60 mg pseudoephedrine ( n = 20 ) , or placebo ( n = 20 ) . Unilateral nasal airflow was measured over a 7-hour period to record the spontaneous changes in nasal airflow associated with the nasal cycle . Minimum ( F MIN ) and maximum ( F MAX ) unilateral nasal airflows were defined as the minimum and maximum nasal airflow values for each nasal passage recorded during the 7-hour period of the study . There was no significant difference in F MAX between the two treatment groups yet there was a significant difference in F MIN ( p < 0.05 ) . No difference in total nasal airflow ( TNAF ) between treatment groups was found , either before or after treatment ( p > 0.05 ) . The results demonstrate that ( TNAF ) is not as sensitive a measure of decongestion as F MIN . The findings of this study show that pseudoephedrine had no effect on the decongestion phase of the nasal cycle , but did significantly limit the congestion phase . The decongestant action may be explained by the sympathomimetic supplementing the natural sympathetic nervous activity to the nasal blood vessels OBJECTIVE The objective of the two pharmacokinetic studies reported here was to compare the relative bioavailability of an ibuprofen/pseudoephedrine modified-release capsule with each of the active ingredients given alone as st and ard formulations . STUDY DESIGN Evaluation of two open , r and omised , cross-over studies , one single dose and one multiple dose , in healthy male volunteers . METHODS Healthy volunteers were r and omised in a cross-over design to single or multiple doses of a combination of ibuprofen ( 600 mg ) plus pseudoephedrine ( 90 mg ) in a slow-release formulation and the individual active products alone as st and ard formulations ; ibuprofen 400 mg , pseudoephedrine 60 mg . RESULTS The single-dose study demonstrated that the bioavailabilities of ibuprofen and pseudoephedrine achieved with the slow-release formulation were not significantly different from those with st and ard tablets of each ingredient alone . In addition , mean plasma levels of ibuprofen predictive of clinical efficacy were achieved within 0.5 - 1 h and lasted for 10 - 12 h thereafter . The time required to reach clinical ly effective blood levels of pseudoephedrine was longer , starting at approximately 2 h. However , the plasma levels predicted that the clinical effect would then last for at least a further 12 h. Trough levels from the multiple-dose study showed that clinical ly relevant analgesic and decongestant plasma levels were maintained for 24 h during twice-daily dosing . The slow-release formulation was well tolerated with only mild adverse events . CONCLUSIONS Blood levels would predict that the present slow-release formulation of ibuprofen plus pseudoephedrine should offer reliable day and night control of cold and flu and sinus symptoms and be associated with a favourable safety profile Assessing the quality of r and omized controlled trials ( RCTs ) is important and relatively new . Quality gives us an estimate of the likelihood that the results are a valid estimate of the truth . We present an annotated bibliography of scales and checklists developed to assess quality . Twenty-five scales and nine checklists have been developed to assess quality . The checklists are most useful in providing investigators with guidelines as to what information should be included in reporting RCTs . The scales give readers a quantitative index of the likelihood that the reported methodology and results are free of bias . There are several shortcomings with these scales . Future scale development is likely to be most beneficial if questions common to all trials are assessed , if the scale is easy to use , and if it is developed with sufficient rigor BACKGROUND Little data exist on the cause and treatment of subfacial pain and pressure and other discomfort attributed to the paranasal sinuses that develop early during the course of the common cold . The purpose of this study was to determine the efficacy of the combination of pseudoephedrine hydrochloride with acetaminophen for the treatment of early symptoms during colds , which are attributed by the patient to the sinuses . METHODS Four hundred thirty subjects ( 216 , pseudoephedrine and acetaminophen recipients ; 214 , placebo recipients ) with cold symptoms of 48 hours or less who reported overall " sinus " symptoms of at least moderate severity were enrolled in this r and omized double-blind placebo-controlled 2-dose study . Self-reported symptoms were scored ( 0 to 4 , absent to severe ) before and at 2 hours after the first and second doses . The 2 primary were measured 2 hours after the second dose were the overall sinus symptom assessment and a weighted composite assessment of sinus pressure , pain , and congestion ( sinus symptoms ) . RESULTS Compared with baseline , 2 hours after the second dose , the mean + /- SEM overall sinus symptom assessment score had decreased by 1.30 + /- 0 . 06 in the pseudoephedrine and acetaminophen-treated subjects compared with 0.93 + /- 0.06 in the placebo-treated subjects ( P < or = .029 ) . The mean + /- SEM weighted average of sinus symptoms 2 hours after the second dose of study medication had decreased by 1.14 + /- 0.06 in the pseudoephedrine and acetaminophen-treated subjects compared with 0.84 + /- 0.06 in the placebo-treated subjects ( P < or = .029 ) . Reductions in similar magnitude were also observed for each of the individual sinus symptoms , and headache and rhinorrhea . Nervousness occurred in 4 % of the pseudoephedrine and acetaminophen recipients compared with 0 % of placebo recipients ( P = .007 ) . CONCLUSION Our results suggest that pseudoephedrine plus acetaminophen is effective for relief of symptoms attributable to the paranasal sinuses that may develop early in the course of a cold . Arch Fam Med . 2000;9:979 - Background Single-dose studies indicate that pseudoephedrine ( PSE ) provides moderate relief for congestion in coryza , but there is a lack of repeated-dose studies . Methods Two hundred sixteen subjects participated in this double-blind , r and omized placebo-controlled trial over 3 days . Measurements included posterior rhinomanometry , acoustic rhinometry , and subjective measures of congestion using a categorical scale and visual analog scale ( VAS ) . Treatment was with one 60-mg PSE tablet four times daily or matching placebo . Results After the first dose , PSE relative to placebo consistently showed small improvements for all objective assessment s of nasal congestion . The prespecified primary efficacy outcome ( day 1 nasal airway resistance area under the curve ) was not significantly different between groups . PSE produced a 5.5 % ( p = 0.031 ) increase in total nasal volume for 0.5–3 hours after dosing . A pooled analysis of days 1 and 3 data showed a VAS score decrease of 7.0 % ( p = 0.072 ) for the 0.5- to 3-hour period on PSE . Conclusion PSE showed small but nonsignificant improvements in objective assessment s of nasal congestion relative to placebo after a single dose The pathogenesis of symptoms of the common cold and their optimal treatment are incompletely understood . To evaluate the role of an oral alpha agonist alone and in combination with a nonsteroidal anti-inflammatory drug in the treatment of experimental rhinovirus colds , 58 subjects were r and omized to receive pseudoephedrine 60 mg alone , pseudoephedrine 60 mg plus ibuprofen 200 mg , or placebo , four times daily for 4 1/2 days beginning 30 hours after intranasal rhinovirus inoculation under double-blind conditions . The frequencies of infection , colds occurrence , and viral shedding did not differ significantly between the groups . Total symptom scores were reduced by 59 % by pseudoephedrine plus ibuprofen ( p less than 0.05 ) and 48 % by pseudoephedrine alone compared with placebo . Nasal symptom scores tended to be lower in recipients of pseudoephedrine plus ibuprofen compared with pseudoephedrine alone ( p = 0.09 ) , but other parameters showed no significant treatment differences between the groups . Rhinorrhea , as determined by nasal secretion weights , was significantly reduced in both treatment groups compared to placebo . Nasal patency measurements tended to show the greatest improvement in recipients of pseudoephedrine plus ibuprofen . Therapy was clinical ly well tolerated . The results suggest that an oral alpha agonist is effective in modifying certain manifestations of experimental rhinovirus infection and that the addition of a nonsteroidal anti-inflammatory drug may provide additional benefit in nasal symptoms and patency . Studies involving large numbers of patients with natural colds are needed to determine the clinical significance of these findings A rhinomanometric technique was used to evaluate the nasal decongestant effect of a single dose of Day Nurse ® over a 4-hour post-dosing period in human volunteers suffering from nasal congestion due to a common cold . A significant improvement in nasal congestion was obtained at the 1 hour , 2 hour , 3 Hour and 4 hour post-dosing interval , from initial values compared to a placebo group . The study therefore demonstrated by an objective technique that Day Nurse ® provides relief of nasal congestion and related symptoms in cold sufferers By means of anterior rhinomanometry , the decongestant effect of topically applied phenylpropanolamine ( PPA ) was evaluated in 40 patients with nasal obstruction . A dose-response relation was obtained for 0.5 , 2.5 and 5.0 % PPA solution , with the maximum effect ( 40 % decongestion ) found with the 2.5 % solution . The decongestant effect was comparable to that induced by physical exercise ( 50 % decongestion ) . It is concluded that PPA nose-drops are effective and offer an attractive alternative to some of the commonly used nasal decongestants OBJECTIVE To determine whether an antihistamine-decongestant combination ( ADC ) is superior to placebo in temporarily relieving symptoms of upper respiratory tract infection ( URI ) in preschool children . DESIGN R and omized , double-blind , placebo-controlled trial . SETTING Four pediatric offices in the Seattle , Wash , area . PARTICIPANTS Children 6 months through 5 years of age with a URI of less than 7 days ' duration . METHODS Children were r and omly assigned to receive an ADC ( brompheniramine maleate-phenylpropanolamine hydrochloride ) or placebo as needed for URI symptoms . Two hours after each dose of study medication , changes in the child 's runny nose , nasal congestion , cough , and sleep status were assessed by means of a st and ardized question naire . RESULTS A total of 175 responses were recorded for 59 patients . There were no statistically significant differences in symptom improvement between the ADC and the placebo group ( runny nose , p = 0.48 ; nasal congestion , p = 0.94 ; cough , p = 0.66 ) . However , the proportion of children asleep 2 hours after receiving the ADC was significantly higher than the proportion receiving placebo ( 46.6 % vs 26.5 % ; p = 0.01 ) . Results were unchanged after control for the correlated nature of repeated responses , age , symptom duration , use of acetaminophen , time that the medication was given , and parental desire for medication . CONCLUSIONS The ADC was equivalent to placebo in providing temporary relief of URI symptoms in preschool children . However , the ADC did have significantly greater sedative effects than did placebo |
917 | 29,755,216 | Software apps as exergames developed for use at home and community activity centers may minimize health disparities and increase QoL for HF patients | Background : Complementary and alternative medicine is a rapidly growing area of biomedical inquiry .
Yoga has emerged in the forefront of holistic medical care due to its long history of linking physical , mental , and spiritual well-being .
Research in yoga therapy ( YT ) has associated improved cardiovascular and quality of life ( QoL ) outcomes for the special needs of heart failure ( HF ) patients .
Aim : The aim of this study is to review yoga intervention studies on HF patients , discuss proposed mechanisms , and examine yoga 's effect on physiological systems that have potential benefits for HF patients .
Second , to recommend future research directions to find the most effective delivery methods of yoga to medically stable HF patients . | Background Type 2 diabetes is a major health problem in many countries including India . Yoga may be an effective type 2 diabetes prevention strategy in India , particularly given its cultural familiarity . Methods This was a parallel , r and omized controlled pilot study to collect feasibility and preliminary efficacy data on yoga for diabetes risk factors among people at high risk of diabetes . Primary outcomes included : changes in BMI , waist circumference , fasting blood glucose , postpr and ial blood glucose , insulin , insulin resistance , blood pressure , and cholesterol . We also looked at measures of psychological well-being including changes in depression , anxiety , positive and negative affect and perceived stress . Forty-one participants with elevated fasting blood glucose in Bangalore , India were r and omized to either yoga ( n = 21 ) or a walking control ( n = 20 ) . Participants were asked to either attend yoga classes or complete monitored walking 3–6 days per week for eight weeks . R and omization and allocation was performed using computer-generated r and om numbers and group assignments delivered in sealed , opaque envelopes generated by off-site study staff . Data were analyzed based on intention to treat . Results This study was feasible in terms of recruitment , retention and adherence . In addition , yoga participants had significantly greater reductions in weight , waist circumference and BMI versus control ( weight −0.8 ± 2.1 vs. 1.4 ± 3.6 , p = 0.02 ; waist circumference −4.2 ± 4.8 vs. 0.7 ± 4.2 , p < 0.01 ; BMI −0.2 ± 0.8 vs. 0.6 ± 1.6 , p = 0.05 ) . There were no between group differences in fasting blood glucose , postpr and ial blood glucose , insulin resistance or any other factors related to diabetes risk or psychological well-being . There were significant reductions in systolic and diastolic blood pressure , total cholesterol , anxiety , depression , negative affect and perceived stress in both the yoga intervention and walking control over the course of the study . Conclusion Among Indians with elevated fasting blood glucose , we found that participation in an 8-week yoga intervention was feasible and result ed in greater weight loss and reduction in waist circumference when compared to a walking control . Yoga offers a promising lifestyle intervention for decreasing weight-related type 2 diabetes risk factors and potentially increasing psychological well-being . Trial registration Clinical Trials.gov Identified NCT00090506 Background Heart failure ( HF ) and chronic obstructive pulmonary disease ( COPD ) are highly prevalent and associated with a large symptom burden , that is compounded in a dual HF- COPD diagnosis . Yoga has potential benefit for symptom relief ; however functional impairment hinders access to usual yoga classes . We developed a Tele-Yoga intervention and evaluated it in a controlled pilot trial . This paper reports on the appropriateness and acceptability of the intervention and the evaluation design . Methods A controlled , non-r and omised trial was conducted of an 8-week Tele-Yoga intervention versus an educational control ( information leaflets mailed to participants with one phone call a week ) . Biweekly one-hour Tele-Yoga classes were implemented via multipoint videoconferencing that connected participants to live classes via an Internet connection to their televisions . Semi-structured qualitative interviews were conducted with participants post study exit to explore reasons for and experiences of participating , including views of study outcome measures and physiological tests . Transcribed interviews were analysed using thematic content analysis . Results Fifteen people participated in the pilot study ( 7 in the intervention group , 8 in the control ) . Of these , 12 participants were interviewed , 6 in each group , mean age 71.2 years ( SD 10.09 ) ; 3 were male . Themes are reported in the following categories : acceptability and appropriateness of the intervention , potential active ingredients of the intervention , acceptability and appropriateness of the control , participation in the research , and acceptability of the testing procedures . The intervention was acceptable and appropriate : the intervention group reported enjoying yoga and valuing the home-based aspect and participants described a high symptom burden and social isolation . However , technological problems result ed in poor video-streaming quality for some participants . Potential active ingredients included physical postures , breathing exercises and guidance in relaxation and meditation . The educational control intervention was acceptable and appropriate , with participants reporting little effect on their well-being and no impact on mechanisms hypothesised to explain yoga ’s effectiveness . The question naires and home physiological testing were acceptable to participants . Conclusions Tele-Yoga is an acceptable and appropriate intervention in people with HF and COPD and further research is warranted to refine the technology used in its delivery . Findings provide guidance for research ers working in tele- interventions , yoga , and similar population s . Trial registration Clinical Trials.gov Identifier : NCT02078739 ( 4 March 2014 ) Background — Exercise training reduces the symptoms of chronic heart failure . Which exercise intensity yields maximal beneficial adaptations is controversial . Furthermore , the incidence of chronic heart failure increases with advanced age ; it has been reported that 88 % and 49 % of patients with a first diagnosis of chronic heart failure are > 65 and > 80 years old , respectively . Despite this , most previous studies have excluded patients with an age > 70 years . Our objective was to compare training programs with moderate versus high exercise intensity with regard to variables associated with cardiovascular function and prognosis in patients with postinfa rct ion heart failure . Methods and Results — Twenty-seven patients with stable postinfa rct ion heart failure who were undergoing optimal medical treatment , including & bgr;-blockers and angiotensin-converting enzyme inhibitors ( aged 75.5±11.1 years ; left ventricular [ LV ] ejection fraction 29 % ; & OV0312;o2peak 13 mL · kg−1 · min−1 ) were r and omized to either moderate continuous training ( 70 % of highest measured heart rate , ie , peak heart rate ) or aerobic interval training ( 95 % of peak heart rate ) 3 times per week for 12 weeks or to a control group that received st and ard advice regarding physical activity . & OV0312;o2peak increased more with aerobic interval training than moderate continuous training ( 46 % versus 14 % , P<0.001 ) and was associated with reverse LV remodeling . LV end-diastolic and end-systolic volumes declined with aerobic interval training only , by 18 % and 25 % , respectively ; LV ejection fraction increased 35 % , and pro-brain natriuretic peptide decreased 40 % . Improvement in brachial artery flow-mediated dilation ( endothelial function ) was greater with aerobic interval training , and mitochondrial function in lateral vastus muscle increased with aerobic interval training only . The MacNew global score for quality of life in cardiovascular disease increased in both exercise groups . No changes occurred in the control group . Conclusions — Exercise intensity was an important factor for reversing LV remodeling and improving aerobic capacity , endothelial function , and quality of life in patients with postinfa rct ion heart failure . These findings may have important implication s for exercise training in rehabilitation programs and future studies AIMS The purpose of this study was to evaluate whether yoga training in addition to st and ard medical therapy can improve cardiac function and reduce N terminal pro B-type natriuretic peptide ( NT pro BNP ) in heart failure ( HF ) . METHODS 130 patients were recruited and r and omized into two groups : Control Group ( CG ) ( n = 65 ) , Yoga Group ( YG ) . In YG , 44 patients and in CG , 48 patients completed the study . Cardiac function using left ventricular ejection fraction ( LVEF ) , myocardial performance index ( Tei index ) , and NT pro BNP , a biomarker of HF , was assessed at baseline and after 12 weeks . RESULT Improvement in LVEF , Tei index , and NT pro BNP were statistically significant in both the groups . Furthermore , when the changes in before and after 12 weeks were in percentage , LVEF increased 36.88 % in the YG and 16.9 % in the CG , Tei index was reduced 27.87 % in the YG and 2.79 % in the CG , NT pro BNP was reduced 63.75 % in the YG and 10.77 % in the CG . The between group comparisons from pre to post 12 weeks were significant for YG improvements ( LVEF , P < 0.01 , Tei index , P < 0.01 , NT pro BNP , P < 0.01 ) . CONCLUSION These results indicate that the addition of yoga therapy to st and ard medical therapy for HF patients has a markedly better effect on cardiac function and reduced myocardial stress measured using NT pro BNP in patients with stable HF BACKGROUND Despite recent advances in pharmacologic and device therapy , morbidity and mortality from heart failure ( HF ) remain high . Yoga combines physical and breathing exercises that may benefit patients with HF . We hypothesized that an 8-week regimen of yoga in addition to st and ard medical therapy would improve exercise capacity , inflammatory markers , and quality of life ( QoL ) in patients with HF . METHODS AND RESULTS New York Heart Association Class I-III HF patients were r and omized to yoga treatment ( YT ) or st and ard medical therapy ( MT ) . Measurements included a grade d exercise test ( GXT ) to V O(2Peak ) and the following serum biomarkers : interleukin-6 ( IL-6 ) , high-sensitivity C-reactive protein ( hsCRP ) , and extracellular superoxide dismutase ( EC-SOD ) . The Minnesota Living with Heart Failure Question naire ( MLHFQ ) was administered to assess changes in QoL. A total of 19 patients were enrolled after the initial screening . Of the 19 patients , 9 were r and omized to YT and 10 to MT . Patients had a mean EF of 25 % . GXT time and V O(2Peak ) were significantly improved in the YT versus MT groups ( + 18 % in the YT and -7.5 % in MT ; P = .03 vs. control and + 17 in YT and -7.1 in MT ; P = .02 , respectively ) . There were statistically significant reductions in serum levels of IL-6 and hsCRP and an increase in EC-SOD in the YT group ( all P < .005 vs. MT ) . MLHFQ scores improved by 25.7 % in the YT group and by 2.9 % in the MT group . CONCLUSIONS Yoga improved exercise tolerance and positively affected levels of inflammatory markers in patients with HF , and there was also a trend toward improvements in CONTEXT Guidelines recommend that exercise training be considered for medically stable out patients with heart failure . Previous studies have not had adequate statistical power to measure the effects of exercise training on clinical outcomes . OBJECTIVE To test the efficacy and safety of exercise training among patients with heart failure . DESIGN , SETTING , AND PATIENTS Multicenter , r and omized controlled trial of 2331 medically stable out patients with heart failure and reduced ejection fraction . Participants in Heart Failure : A Controlled Trial Investigating Outcomes of Exercise Training ( HF-ACTION ) were r and omized from April 2003 through February 2007 at 82 centers within the United States , Canada , and France ; median follow-up was 30 months . INTERVENTIONS Usual care plus aerobic exercise training , consisting of 36 supervised sessions followed by home-based training , or usual care alone . MAIN OUTCOME MEASURES Composite primary end point of all-cause mortality or hospitalization and prespecified secondary end points of all-cause mortality , cardiovascular mortality or cardiovascular hospitalization , and cardiovascular mortality or heart failure hospitalization . RESULTS The median age was 59 years , 28 % were women , and 37 % had New York Heart Association class III or IV symptoms . Heart failure etiology was ischemic in 51 % , and median left ventricular ejection fraction was 25 % . Exercise adherence decreased from a median of 95 minutes per week during months 4 through 6 of follow-up to 74 minutes per week during months 10 through 12 . A total of 759 patients ( 65 % ) in the exercise training group died or were hospitalized compared with 796 patients ( 68 % ) in the usual care group ( hazard ratio [ HR ] , 0.93 [ 95 % confidence interval { CI } , 0.84 - 1.02 ] ; P = .13 ) . There were nonsignificant reductions in the exercise training group for mortality ( 189 patients [ 16 % ] in the exercise training group vs 198 patients [ 17 % ] in the usual care group ; HR , 0.96 [ 95 % CI , 0.79 - 1.17 ] ; P = .70 ) , cardiovascular mortality or cardiovascular hospitalization ( 632 [ 55 % ] in the exercise training group vs 677 [ 58 % ] in the usual care group ; HR , 0.92 [ 95 % CI , 0.83 - 1.03 ] ; P = .14 ) , and cardiovascular mortality or heart failure hospitalization ( 344 [ 30 % ] in the exercise training group vs 393 [ 34 % ] in the usual care group ; HR , 0.87 [ 95 % CI , 0.75 - 1.00 ] ; P = .06 ) . In prespecified supplementary analyses adjusting for highly prognostic baseline characteristics , the HRs were 0.89 ( 95 % CI , 0.81 - 0.99 ; P = .03 ) for all-cause mortality or hospitalization , 0.91 ( 95 % CI , 0.82 - 1.01 ; P = .09 ) for cardiovascular mortality or cardiovascular hospitalization , and 0.85 ( 95 % CI , 0.74 - 0.99 ; P = .03 ) for cardiovascular mortality or heart failure hospitalization . Other adverse events were similar between the groups . CONCLUSIONS In the protocol -specified primary analysis , exercise training result ed in nonsignificant reductions in the primary end point of all-cause mortality or hospitalization and in key secondary clinical end points . After adjustment for highly prognostic predictors of the primary end point , exercise training was associated with modest significant reductions for both all-cause mortality or hospitalization and cardiovascular mortality or heart failure hospitalization . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00047437 Background Little is known about the metabolic and heart rate responses to a typical hatha yoga session . The purpose s of this study were 1 ) to determine whether a typical yoga practice using various postures meets the current recommendations for levels of physical activity required to improve and maintain health and cardiovascular fitness ; 2 ) to determine the reliability of metabolic costs of yoga across sessions ; 3 ) to compare the metabolic costs of yoga practice to those of treadmill walking . Methods In this observational study , 20 intermediate-to-advanced level yoga practitioners , age 31.4 ± 8.3 years , performed an exercise routine inside a human respiratory chamber ( indirect calorimeter ) while wearing heart rate monitors . The exercise routine consisted of 30 minutes of sitting , 56 minutes of beginner-level hatha yoga administered by video , and 10 minutes of treadmill walking at 3.2 and 4.8 kph each . Measures were mean oxygen consumption ( VO2 ) , heart rate ( HR ) , percentage predicted maximal heart rate ( % MHR ) , metabolic equivalents ( METs ) , and energy expenditure ( kcal ) . Seven subjects repeated the protocol so that measurement reliability could be established . Results Mean values across the entire yoga session for VO2 , HR , % MHR , METs , and energy/min were 0.6 L/kg/min ; 93.2 beats/min ; 49.4 % ; 2.5 ; and 3.2 kcal/min ; respectively . Results of the ICCs ( 2,1 ) for mean values across the entire yoga session for kcal , METs , and % MHR were 0.979 and 0.973 , and 0.865 , respectively . Conclusion Metabolic costs of yoga averaged across the entire session represent low levels of physical activity , are similar to walking on a treadmill at 3.2 kph , and do not meet recommendations for levels of physical activity for improving or maintaining health or cardiovascular fitness . Yoga practice incorporating sun salutation postures exceeding the minimum bout of 10 minutes may contribute some portion of sufficiently intense physical activity to improve cardio-respiratory fitness in unfit or sedentary individuals . The measurement of energy expenditure across yoga sessions is highly reliable BACKGROUND The number of African American ( AA ) patients living with heart failure ( HF ) has been increasing , especially among the economically disadvantaged . Yoga therapy has been found to improve physical and psychological parameters among healthy individuals , but its effect in patients with HF remains unknown . The purpose of this study was to examine the effects of yoga therapy on cardiovascular endurance ( VO2peak ) , flexibility , quality of life ( QoL ) , and inflammatory markers on medically stable HF patients . METHODS Forty patients ( 38 AA , 1 Asian , and 1 Caucasian ) with systolic or diastolic HF were r and omized to the yoga group ( YG , n = 21 ) or the control group ( CG , n = 19 ) . All patients were asked to follow a home walk program . Premeasurement and postmeasurement included a treadmill stress test to peak exertion , flexibility , interleukin-6 ( IL-6 ) , C-reactive protein ( CRP ) , and extracellular superoxide dismutase ( EC-SOD ) . QoL was assessed by the Minnesota Living with Heart Failure Question naire ( MLwHFQ ) . RESULTS The statistical analyses ( assessed by ANOVA and t-tests ) were significant for favorable changes in the YG , compared with those in the CG , for flexibility ( P = 0.012 ) , treadmill time ( P = 0.002 ) , VO2peak ( P = 0.003 ) , and the biomarkers ( IL-6 , P = 0.004 ; CRP , P = 0.016 ; and EC-SOD , P = 0.012 ) . Within the YG , pretest to posttest scores for the total ( P = 0.02 ) and physical subscales ( P < 0.001 ) of the MLwHFQ were improved . CONCLUSIONS Yoga therapy offered additional benefits to the st and ard medical care of predominantly AA HF patients by improving cardiovascular endurance , QoL , inflammatory markers , and flexibility Background —It is well established that a depressed baroreflex sensitivity may adversely influence the prognosis in patients with chronic heart failure ( CHF ) and in those with previous myocardial infa rct ion . Methods and Results —We tested whether a slow breathing rate ( 6 breaths/min ) could modify the baroreflex sensitivity in 81 patients with stable ( 2 weeks ) CHF ( age , 58±1 years ; NYHA classes I [ 6 patients ] , II [ 33 ] , III [ 27 ] , and IV [ 15 ] ) and in 21 controls . Slow breathing induced highly significant increases in baroreflex sensitivity , both in controls ( from 9.4±0.7 to 13.8±1.0 ms/mm Hg , P < 0.0025 ) and in CHF patients ( from 5.0±0.3 to 6.1±0.5 ms/mm Hg , P < 0.0025 ) , which correlated with the value obtained during spontaneous breathing ( r = + 0.202 , P = 0.047 ) . In addition , systolic and diastolic blood pressure decreased in CHF patients ( systolic , from 117±3 to 110±4 mm Hg , P = 0.009 ; diastolic , from 62±1 to 59±1 mm Hg , P = 0.02 ) . Conclusions —These data suggest that in patients with CHF , slow breathing , in addition to improving oxygen saturation and exercise tolerance as has been previously shown , may be beneficial by increasing baroreflex sensitivity OBJECTIVE Several studies suggest that yoga can decrease oxidative stress . However reports are scanty regarding whether yoga training can improve the glutathione level of individual . This study is design ed to appraise the role of yoga in maintaining glutathione ( reduced and oxidized ) levels and antioxidant status . STUDY DESIGN This study was conducted on healthy male volunteers from the Indian Navy , who were divided into two groups -- a yoga ( n = 30 ) group and a control ( n = 21 ) group . The yoga group was trained in yoga for 6 months . The yoga schedule consisted of prayers , asana , pranayama , and meditation . The control group practice d routine physical training exercise for 6 months . Blood sample s were collected when the volunteers were in fasting condition before and after completion of 6-month training period . Reduced and oxidized glutathione , glutathione reductase activity and total antioxidant status ( TAS ) were estimated . RESULTS Reduced glutathione level increased significantly ( p < 0.05 ) in the yoga group after completion of training . Glutathione reductase activity increased significantly in the control group ( p < 0.05 ) . TAS increased significantly ( p < 0.001 ) in the yoga group and decreased significantly ( p < 0.001 ) in the control group . CONCLUSIONS Regular practice of yoga can maintain or improve antioxidant level of the body . The clinical relevance is that yoga practice can be used to maintain the antioxidant defense system under stressful conditions of training as observed in the case of soldiers and athletes Background —Blacks have disproportionately high rates of cardiovascular disease . Psychosocial stress may contribute to this disparity . Previous trials on stress reduction with the Transcendental Meditation ( TM ) program have reported improvements in cardiovascular disease risk factors , surrogate end points , and mortality in blacks and other population s. Methods and Results —This was a r and omized , controlled trial of 201 black men and women with coronary heart disease who were r and omized to the TM program or health education . The primary end point was the composite of all-cause mortality , myocardial infa rct ion , or stroke . Secondary end points included the composite of cardiovascular mortality , revascularizations , and cardiovascular hospitalizations ; blood pressure ; psychosocial stress factors ; and lifestyle behaviors . During an average follow-up of 5.4 years , there was a 48 % risk reduction in the primary end point in the TM group ( hazard ratio , 0.52 ; 95 % confidence interval , 0.29–0.92 ; P=0.025 ) . The TM group also showed a 24 % risk reduction in the secondary end point ( hazard ratio , 0.76 ; 95 % confidence interval , 0.51–0.1.13 ; P=0.17 ) . There were reductions of 4.9 mmHg in systolic blood pressure ( 95 % confidence interval −8.3 to –1.5 mmHg ; P=0.01 ) and anger expression ( P<0.05 for all scales ) . Adherence was associated with survival . Conclusions —A selected mind – body intervention , the TM program , significantly reduced risk for mortality , myocardial infa rct ion , and stroke in coronary heart disease patients . These changes were associated with lower blood pressure and psychosocial stress factors . Therefore , this practice may be clinical ly useful in the secondary prevention of cardiovascular disease . Clinical Trial Registration —URL : www . clinical trials.gov Unique identifier : NCT01299935 Background : Ejection fraction promotion in heart failure patients reduces mortalities and limitations . Objectives : This study was to investigate the effect of exercise on ejection fraction of chronic heart failure patients . Patients and Methods : The present study was conducted on patients with chronic heart failure . 66 patients were divided r and omly into two experimental and control groups of 33 each . The subjects were male and female . The patients in experimental group followed an exercise program three sessions per week for 24 weeks . Echocardiography and quality of life question naire were used to gather data . The data were analyzed by SPSS 18 through pair and independent t-test . Results : The results indicated a significant difference in left ventricular diameter ( LV-ESD , LV-EDD ) and ejection fraction at the end of exercise program in experimental group and 24 weeks after in control group . There was a significant difference in quality of life in physical performance , activity limitation following physical problems , energy and fatigue , social performance , physical pain , and public health ( P < 0.05 for all ) between two groups . Conclusions : Exercise program increases ejection fraction and quality of life in chronic heart failure patients , associated with management of disease by health team Background Adherence to the Heart Failure Society of America ( HFSA ) 2010 guidelines recommending 30 minutes of supervised moderate intensity exercise five days per week is difficult for patients with heart failure ( HF ) . Innovative programs are needed to assist HF patients to adhere to long-term exercise . The objective of this prospect i ve r and omized two-group repeated measures experimental design is to determine the efficacy of a behavioral exercise training intervention on long-term adherence to exercise at 18 months in patients with heart failure . Methods / Design A sample size of 246 subjects with heart failure will be recruited over a 3 year period . All subjects receive a cardiopulmonary exercise test and 9 supervised exercise training sessions during a 3 week run-in period prior to r and omization . Subjects completing at least 6 of 9 training sessions are r and omized to the HEART Camp Intervention group ( HC ) or to a st and ard care ( SC ) exercise group . The HC intervention group receives cognitive-behavioral strategies that address the intervention components of knowledge , attitudes , self-efficacy , behavioral self-management skills and social support . The SC group is provided access to the exercise facility and regular facility staff for the 18 month study period . The primary aim is to evaluate the effect of HEART Camp on adherence to exercise , with our central hypothesis that the HC group will have significantly better adherence to exercise at 18 months . Secondary aims include evaluating which components of the HEART Camp intervention mediate the effects of the intervention on adherence ; evaluating the effect of HEART Camp on specific health outcomes ; exploring selected demographic variables ( race , gender , age ) as potential moderators of the effect of the HEART Camp intervention on adherence ; and exploring the perceptions and experiences that context ualize exercise adherence . Discussion The HEART Camp intervention is the first to test a multi-component intervention design ed to improve long-term adherence to exercise behavior in patients with HF . Improving long-term adherence to exercise is the logical first step to ensure the required dose of exercise that is necessary to realize beneficial health outcomes and reduce costs in this burdensome chronic illness . Trial registration Clincaltrials.gov NCT01658670 Acute inflammation is accompanied from its outset by the release of specialized pro-resolving mediators ( SPMs ) , including resolvins , that orchestrate the resolution of local inflammation . We showed earlier that , in rats with subcutaneous inflammation of the back induced by carrageenan , stretching for 10 min twice daily reduced inflammation and improved pain , 2 weeks after carrageenan injection . In this study , we hypothesized that stretching of connective tissue activates local pro-resolving mechanisms within the tissue in the acute phase of inflammation . In rats injected with carrageenan and r and omized to stretch versus no stretch for 48 h , stretching reduced inflammatory lesion thickness and neutrophil count , and increased resolvin ( RvD1 ) concentrations within lesions . Furthermore , subcutaneous resolvin injection mimicked the effect of stretching . In ex vivo experiments , stretching of connective tissue reduced the migration of neutrophils and increased tissue RvD1 concentration . These results demonstrate a direct mechanical impact of stretching on inflammation-regulation mechanisms within connective tissue BACKGROUND Congestive heart failure ( CHF ) is highly prevalent and the most costly cardiovascular illness in the United States . Yoga is known to be effective in lowering stress , lessening depression , and increasing physical fitness and may be used as an adjuvant management program for CHF patients . PRIMARY STUDY OBJECTIVE To determine the feasibility of a yoga intervention program among a multiethnic CHF population living in underserved neighborhoods . METHODS Uncontrolled intervention trial . SETTING Kaiser Permanente Medical Centers , Richmond and Oakl and , California . PARTICIPANTS 14 CHF patients ( 7 female ) , mean age 64 ( SD=6.4 ) years , and 62 % African-American . INTERVENTION Eight-week , 2x/week , 1-hr yoga classes that included meditation , breathing exercises , gentle yoga poses , and relaxation . PRIMARY OUTCOME MEASURES The intervention feasibility was measured by recruitment rates , participant retention and adherence . Body weight and self-reported depression and quality of life were measured before and after the intervention . RESULTS Among the 14 patients enrolled , 13 completed the intervention . Of those who completed the trial , 92 % attended at least 50 % of the classes . There was a significant reduction in weight ( -3.5 lb , p=0.01 ) and improvement in the severity of depression ( p<0.05 ) , as well as a trend toward increased quality of life ( p=08 ) . No adverse events were observed . CONCLUSIONS This pilot trial demonstrates that it is feasible for patients with CHF to incorporate yoga into their lifestyle . Yoga may help with routine disease management , prevention of fluid retention , and improvement of depression and quality of life . A larger trial is needed to confirm efficacy and to determine the long-term effects on other important outcomes , such as hospital re-admission rates or prognostic biomarkers BACKGROUND Despite reported benefits of exercising for chronic heart failure patients , limited data are available on quality of life and the effects of different modes of training . This study assessed the effects of local endurance training with knee extensor muscles on exercise tolerance and health-related quality of life in male patients with moderate , chronic heart failure . METHODS AND RESULTS Twenty-one patients ( mean age , 60 years ; range , 43 - 73 years ) in New York Heart Association functional classes II-III ( ejection fraction , 28 + /- 11 % ) were r and omized to two training groups and one control group . Both training groups performed the same relative quantity of dynamic work with knee extensor muscles 3 days a week for 8 weeks . However , the quantity of muscle mass trained at one time and , consequently , the load on the integrated circulation differed between the groups ( two- and one-leg training ) . Exercise capacity and perceived quality of life were assessed before and after the training or control period . Exercise tolerance increased ( P < .01 ) in both training groups with significantly ( P < .01 ) better improvement in submaximal exercise capacity in the two-leg group . There was no improvement in the control group . Coping capacity did not differ from the reference range and did not change during the study . Global health-related quality of life was depressed at baseline . Training improved ( P < .05 ) health-related quality of life . Compared with the control group , the improvement of health-related quality of life subscales was more pronounced in the two-leg training group ( P < .02-.005 ) as compared to the one-leg training group ( not significant to P < .05 ) . CONCLUSIONS Local muscle endurance training has beneficial effects on exercise tolerance and health-related quality of life in patients with moderate , chronic heart failure . As two-leg training showed a tendency toward better improvement in submaximal exercise capacity and in quality of life than one-leg training , the effects on quality of life appear to be exercise-related in addition to a possible placebo-related effect . Also , the effect appears to be related to the extent of muscle trained at one time Shavasan is known to enhance one 's ability to combat stressful situations . The present study was planned to determine if shavasan could modulate the physiological response to stress induced by cold pressor test ( CPT ) and the possible mechanisms involved . Ten normal adults were taught shavasan and practice d the same for a total duration of seven days . RR interval variation ( RRIV ) , deep breathing difference ( DBD ) , and heart rate , blood pressure & rate-pressure-product ( RPP ) response to CPT were measured before and immediately after shavasan . Shavasan produced a significant increase in DBD and an appreciable but statistically insignificant increase in RRIV suggesting an enhanced parasympathetic activity . Significant blunting of cold pressor-induced increase in heart rate , blood pressure and RPP by shavasan was seen during and even five minutes after CPT suggesting that shavasan reduces the load on the heart by blunting the sympathetic response . It is concluded that shavasan can enhance one 's ability to withst and stress induced by CPT and this ability can be achieved even with seven days of shavasan training Background : Lung functions are found to be impaired in coronary artery disease ( CAD ) , congestive heart failure , left ventricular dysfunction , and after cardiac surgery . Diffusion capacity progressively worsens as the severity of CAD increases due to reduction in lung tissue participating in gas exchange . Aims and Objectives : Pranayama breathing exercises and yogic postures may play an impressive role in improving cardio-respiratory efficiency and facilitating gas diffusion at the alveolo-capillary membrane . This study was done to see the effect of yoga regimen on lung functions particularly diffusion capacity in CAD patients . Material s and Methods : A total of 80 stable CAD patients below 65 years of age of both sexes were selected and r and omized into two groups of 40 each . Group I CAD patients were given yoga regimen for 3 months which consisted of yogic postures , pranayama breathing exercises , dietary modification , and holistic teaching along with their conventional medicine while Group II CAD patients were put only on conventional medicine . Lung functions including diffusion capacity were recorded thrice in both the groups : 0 day as baseline , 22nd day and on 90th day by using computerized MS medisoft Cardio-respiratory Instrument , HYP’AIR Compact model of cardio-respiratory testing machine was manufactured by P K Morgan , India . The recorded parameters were statistically analyzed by repeated measures ANOVA followed by Tukey 's test in both the groups . Cardiovascular parameters were also compared before and after intervention in both the groups . Results : Statistically significant improvements were seen in slow vital capacity , forced vital capacity , peak expiratory flow rate , maximum voluntary ventilation , and diffusion factor/ transfer factor of lung for carbon monoxide after 3 months of yoga regimen in Group I. Forced expiratory volume in 1st sec ( FEV1 ) , and FEV1 % also showed a trend toward improvement although not statistically significant . HR , SBP and DBP also showed significant improvement in Group-I patients who followed yoga regimen . Conclusions : Yoga regimen was found to improve lung functions and diffusion capacity in CAD patients besides improving cardiovascular functions . Thus , it can be used as a complimentary or adjunct therapy along with the conventional medicine for their treatment and rehabilitation The purpose of this investigation was to test the effectiveness of an adherence facilitation intervention consisting of goal setting , graphic feedback , and provider guidance to support adherence to home exercise in a sample of patients with heart failure who had completed a supervised exercise program . The sample consisted of 13 patients with an ejection fraction of 40 % or less who were r and omly assigned to either the exercise only group ( n=6 ) or the exercise with adherence facilitation group ( n=7 ) . The format of the intervention was graphic depiction of each patient 's exercise goals in comparison to each patient 's exercise participation . Graphs were mailed at 3-week intervals for 12 weeks . Results indicate that patients who received the intervention demonstrated higher exercise adherence and greater confidence in continuing to exercise in the future . The adherence facilitation intervention may be helpful to heart failure patients in adapting to a program of home exercise . (c)2002 CHF , BACKGROUND AND OBJECTIVE It is well known that a hall mark of heart failure is adverse changes in autonomic function . Elevated blood pressure is a powerful predictor of congestive heart failure and other Cardiovascular Disease ( CVD ) outcomes . In this study , we planned to examine the effects of a 12 week yoga therapy on blood pressure , heart rate , heart rate variability , and rate pressure product ( RPP ) . METHODS Out of 130 heart failure patients recruited for the study , 65 patients were r and omly selected to receive 12 week yoga therapy along with st and ard medical therapy ( yoga group ) . Other patients ( n=65 ) received only st and ard medical therapy ( control group ) . Heart rate , blood pressure , cardiac autonomic function ( by short-term heart-rate variability analysis ) and myocardial oxygen consumption ( by RPP ) were assessed before and after 12 weeks . In the yoga group , 44 patients and in the control group , 48 patients completed the study . RESULTS There was a significant decrease in heart rate , blood pressure and RPP in yoga group compared to control group . Also , LFnu and LF-HF ratio decreased significantly and HFnu increased significantly in yoga group compared to control group . CONCLUSION Twelve-week yoga therapy significantly improved the parasympathetic activity and decreased the sympathetic activity in heart failure patients ( NYHA I&II ) On the basis of medical officers diagnosis , thirty three ( N = 33 ) hypertensives , aged 35 - 65 years , from Govt . General Hospital , Pondicherry , were examined with four variables viz , systolic and diastolic blood pressure , pulse rate and body weight . The subjects were r and omly assigned into three groups . The exp . group-I underwent selected yoga practice s , exp . group-II received medical treatment by the physician of the said hospital and the control group did not participate in any of the treatment stimuli . Yoga imparted in the morning and in the evening with 1 hr/session . day-1 for a total period of 11-weeks . Medical treatment comprised drug intake every day for the whole experimental period . The result of pre-post test with ANCOVA revealed that both the treatment stimuli ( i.e. , yoga and drug ) were effective in controlling the variables of hypertension BACKGROUND Measuring adherence to exercise is important to clinicians and research ers because inadequate adherence can adversely affect the effectiveness of an exercise program and cloud the relationship between exercise and clinical outcomes . Hence , assessment strategies for adherence to exercise , as with assessment strategies for other outcomes , must have demonstrated validity if they are to be employed with confidence . We conducted this study to determine the validity of pedometers as a measure of exercise adherence to a home-based walking program in heart failure patients . METHODS AND RESULTS Exercise adherence was measured using pedometers in 38 patients ( 74 % men ) age 54.1 + /- 11.7 years who participated in a 12-month home-based walking program . A comparison of functional status as measured by the 6-minute walk distance and peak oxygen uptake ( VO2 max ) at 6 months into the exercise training program was made between 2 groups of participants who were thought to represent adherers and nonadherers : participants who demonstrated > or = 10 % change in pedometer scores ( n = 20 ) and those who showed no change in pedometer scores ( n = 18 ) from baseline to 6 months . Patients who showed improvements in their pedometer scores over 6 months had better functional status at 6 months ( 6-minute walk distance 1718 + /- 46 versus 1012 + /- 25 meters , F = 5.699 , P = .022 ; VO 2 max 17 + /- 0.7 versus 10 + /- 0.5 units , F = 7.162 , P = .011 ) when compared with patients whose pedometers reflected minimal change in distance walked ( ie , < or = 10 % ) . CONCLUSION Pedometers are inexpensive and readily available to both clinicians and research ers . The results of this study suggest that they may be a valid indicator of exercise adherence in heart failure patients who participate in a home-based walking program Background : Some sociodemographic and psychological variables such as patients ’ belief about illness are associated with attendance at cardiac rehabilitation . Exploration of patients ’ beliefs about treatment regarding cardiac rehabilitation has been limited to qualitative studies ; their role in relation to attendance at cardiac rehabilitation after acute myocardial infa rct ion ( AMI ) remains speculative . Objectives : To develop a valid and reliable measure of patients ’ beliefs regarding cardiac rehabilitation and to ascertain the relationship between such beliefs and attendance . Design : A prospect i ve question naire-based study . Setting : Coronary care unit of a London teaching hospital . Patients : 130 patients with AMI ; 104 ( 83 % ) men ; mean age 58.4 ( st and ard deviation ( SD ) 10.7 ) years . Interventions : Patients completed a 26-item question naire consisting of statements pertaining to beliefs about cardiac rehabilitation . Main outcome measures : Cardiac rehabilitation attendance ; beliefs of patients about cardiac rehabilitation . Results : Four subscales pertaining to patients ’ beliefs about cardiac rehabilitation were produced , accounting for 65.3 % of the attendance variance : perceived necessity of cardiac rehabilitation ( α = 0.71 ) , concerns about exercise ( α = 0.79 ) , practical barriers ( α = 0.70 ) and perceived personal suitability ( α = 0.74 ) . Patients who attended were more likely to believe that cardiac rehabilitation was necessary and to underst and its role compared with non-attenders ( 17.7 ( SD 2.7 ) v 16.9 ( SD 3.0 ) , p = 0.029 ) . Patients who thought cardiac rehabilitation was suitable for a younger , more active person were less likely to attend ( 5.6 ( SD 1.9 ) v 4.6 ( SD 1.7 ) , p = 0.007 ) . Patients who expressed concerns about exercise or who reported practical barriers to attendance were less likely to attend , although these did not reach statistical significance . Conclusion : Beliefs about cardiac rehabilitation can be quantified and differ between attenders and non-attenders of cardiac rehabilitation Abstract A wakeful hypometabolic state may be induced by simple , non-cultic mental techniques or by traditional meditational practice s. The hypometabolic state seems to represent an integrated hypothalamic response ( " relaxation response " ) which is consistent with a state of decreased sympathetic-nervous-system activity . A prospect i ve investigation was design ed to test whether regular elicitation of the relaxation response might lower blood-pressures in hypertensive patients who were maintained on constant antihypertensive therapy . Fourteen people were investigated . During the control period of 5.6 weeks , blood-pressures did not change significantly from day to day and averaged 145.6 mm . Hg systolic and 91.9 mm . Hg diastolic . During the experimental period of 20 weeks , systolic blood-pressures decreased to 135.0 mm . Hg ( BACKGROUND The Support , Education , and Research in Chronic Heart Failure ( SEARCH ) study was design ed to assess the impact of a mindfulness-based psychoeducational intervention on clinical outcomes , depression , and quality of life in patients with chronic heart failure ( CHF ) . Although research has shown that psychosocial factors including depression are important risk factors for adverse events in patients with CHF , no large clinical trials have investigated the efficacy of psychosocial interventions to reduce these factors in this population . METHODS This was a prospect i ve cohort study of 208 adults with left ventricular ejection fraction < or = 40 % and CHF geographically assigned to treatment or control groups with follow-up at 3 , 6 , and 12 months . Treatment groups met weekly for 8 consecutive weeks for training in mindfulness meditation , coping skills , and support group discussion . RESULTS Subjects had a mean age of 61 years , left ventricular ejection fraction 26 % , and median New York Heart Association class II . The majority were treated with angiotensin-converting enzyme inhibitors ( 80 % ) and beta-blockers ( 86 % ) . At baseline , patients in the treatment group had more severe CHF with higher New York Heart Association class ( P = .0209 ) and more severe psychological distress ( Center of Epidemiology - Depression , Profile of Mood States ; P < .05 ) . When compared with controls , treatment result ed in lower anxiety ( Profile of Mood States , P = .003 ) , depression ( Center of Epidemiology - Depression , P = .05 ) , improved symptoms ( Kansas City Cardiomyopathy Question naire symptom scale , P = .033 ) and clinical scores ( Kansas City Cardiomyopathy Question naire clinical score , P = .024 ) over time . There were no treatment effects on death/rehospitalization at 1 year . CONCLUSIONS An 8-week mindfulness-based psychoeducational intervention reduced anxiety and depression ; this effect was attenuated at 1 year . Importantly , the intervention led to significantly better symptoms of CHF at 12 months compared to control subjects . Our results suggest that interventions of this type might have a role in optimal therapy for CHF |
918 | 21,281,917 | Traditional open rotator cuff repairs using tranosseous bone tunnels had the advantage of reapproximating the rotator cuff tendon solidly onto the greater tuberosity | Rotator cuff tears are a ubiquitous cause of shoulder pain and disability .
Full thickness rotator cuff tears are present in 19 - 21 % of the general population , and their prevalence increases with age .
The incidence of this problem is exacerbated by the ever advancing age of our patient population .
Thankfully , with advances in arthroscopic rotator cuff repair , this has become a treatable problem with low morbidity , few complications , and good success .
Although patients can do well in the face of a persistent or recurrent rotator cuff tear after arthroscopic repair , several studies have documented better subjective and objective results when the rotator cuff tear has been documented to heal . | Aim This experimental study aim ed to compare the load-to-failure rate and stiffness of single- versus double-row suture techniques for repairing rotator cuff lesions using two different suture material s. Additionally , the mode of failure of each repair was evaluated . Method In 32 sheep shoulders , a st and ardized tear of the infraspinatus tendon was created . Then , n = 8 specimen were r and omized to four repair methods : ( 1 ) Double-row Anchor Ethibond ® coupled with polyester sutures , USP No. 2 ; ( 2 ) Double-Row Anchor HiFi ® with polyblend polyethylene sutures , USP No. 2 ; ( 3 ) Single-Row Anchor Ethibond ® coupled with braided polyester sutures , USP No. 2 ; and ( 4 ) Single-Row Anchor HiFi ® with braided polyblend polyethylene sutures , USP No. 2 . Arthroscopic Mason – Allen stitches were placed ( single-row ) and combined with medial horizontal mattress stitches ( double-row ) . All specimens were loaded to failure at a constant displacement rate on a material testing machine . Results Group 4 showed lowest load-to-failure result with 155.7 ± 31.1 N compared to group 1 ( 293.4 ± 16.1 N ) and group 2 ( 397.7 ± 7.4 N ) ( P < 0.001 ) . Stiffness was highest in group 2 ( 162 ± 7.3 N/mm ) and lowest in group 4 ( 84.4 ± 19.9 mm ) ( P < 0.001 ) . In group 4 , the main cause of failure was due to the suture cutting through the tendon ( n = 6 ) , a failure case observed in only n = 1 specimen in group 2 ( P < 0.001 ) . Conclusions A double-row technique combined with arthroscopic Mason-Allen/horizontal mattress stitches provides high initial failure strength and may minimize the risk of the polyethylene sutures cutting through the tendon in rotator cuff repair when a single load force is used Background Recurrent defects after open and arthroscopic rotator cuff repair are common . Double-row repair techniques may improve initial fixation and quality of rotator cuff repair . Purpose To evaluate the load to failure , cyclic displacement , and anatomical footprint of 4 arthroscopic rotator cuff repair techniques . Hypothesis Double-row suture anchor repair would have superior structural properties and would create a larger footprint compared to single-row repair . Study Design Controlled laboratory study . Methods Twenty fresh-frozen cadaveric shoulders were r and omly assigned to 4 arthroscopic repair techniques . The repair was performed as either a single-row technique or 1 of 3 double-row techniques : diamond , mattress double anchor , or modified mattress double anchor . Angle of loading , anchor type , bone mineral density , anchor distribution , angle of anchor insertion , arthroscopic technique , and suture type and size were all controlled . Footprint length and width were quantified before and after repair . Displacement with cyclic loading and load to failure were determined . Results There were no differences in load to failure and displacement with cyclic loading between the single-row repair and each double-row repair . All repair groups demonstrated load to failure greater than 250 N. A significantly greater supraspinatus footprint width was seen with double-row techniques compared to single-row repair . Conclusions The single-row repair technique was similar to the double-row techniques in load to failure , cyclic displacement , and gap formation . The double-row anchor repairs consistently restored a larger footprint than did the single-row method . Clinical Relevance The arthroscopic techniques studied have strong structural properties that approached the reported performance of open repair techniques . Double-row techniques provide a larger footprint width ; although not addressed by this study , such a factor may improve the biological quality of repair The aim of the study was to evaluate the time zero contact pressure over a defined rotator cuff footprint using different repair and stitch techniques in an established sheep model . Forty fresh-frozen sheep shoulders were r and omly assigned to five repair groups : single-row repair using simple stitches ( SRA-s ) , single-row repair using horizontal mattress stitches ( SRA-m ) , and single-row repair using arthroscopic Mason-Allen stitches ( SRA-ama ) . Double-row repair was either performed with a combination of simple and horizontal mattress stitches ( DRA-sm ) or with arthroscopic Mason-Allen/horizontal mattress stitches ( DRA-amam ) . Investigations were performed using a pressure-sensitive film system . The average contact pressure and pressure pattern were measured for each group . Contact pressure was lowest in SRA-m followed by SRA-s . SRA-ama showed highest contact pressure of all single-row treatment groups ( P < 0.05 ) . DRA-amam presented the highest overall contact pressure ( P < 0.05 ) , whereas DRA-sm exerted contact pressure equal to that of SRA-ama . Both double-row techniques showed the most exp and ed pressure pattern . Average contact pressures for the more complex single- and double-row techniques utilizing arthroscopic Mason-Allen stitches were greater than were those of the repair techniques utilizing simple and horizontal mattress stitches . However , the contact pattern between the anchors could be increased by using the double-row technique , result ing in more footprint coverage compared to patterns utilizing the single-row techniques . These results support the use of the more complex arthroscopic Mason-Allen stitches and may improve the environment for healing of the repaired rotator cuff tendon The purpose of this study was to identify potential predictors of function and tendon healing after arthroscopic rotator cuff repair that will enable the orthopaedic surgeon to determine which patients can expect a successful outcome . Between 2003 and 2005 , the Arthroscopic Rotator Cuff Registry was established to collect demographic , intraoperative , functional outcome , and ultrasound data prospect ively on all patients who underwent primary arthroscopic rotator cuff repair . At total of 193 patients met the study criteria , and 127 ( 65.8 % ) completed the 2-year follow-up . The most significant independent factors affecting ultrasound outcome were age ( odds ratio [ OR ] , 1.08 ; 95 % confidence interval [ CI ] , 1.02 - 1.14 ; P = .006 ) and tear size ( OR , 2.29 ; 95 % CI , 1.55 - 3.38 ; P < .001 ) . After adjustment for age and tear size , the intraoperative factors found to be significantly associated with a tendon defect were concomitant biceps procedures ( OR , 11.39 ; 95 % CI , 2.90 - 44.69 ; P < .001 ) and acromioclavicular joint procedures ( OR , 3.85 ; 95 % CI , 1.46 - 10.12 ; P = .006 ) . In contrast to the ultrasound data , the functional outcome variables , such as satisfaction ( OR , 3.92 ; 95 % CI , 2.00 - 7.68 ; P < .001 ) and strength ( OR , 10.05 ; 95 % CI , 1.61 - 62.77 ; P = .01 ) , had a greater role in predicting an American Shoulder and Elbow Surgeons score greater than 90 . The progression from a single-tendon rotator cuff tear to a multiple-tendon tear with associated pathology increased the likelihood of tendon defect by at least 9 times , and therefore , earlier surgical intervention for isolated , single-tendon rotator cuff tears could optimize the likelihood of ultrasound healing and an excellent functional outcome PURPOSE The purpose of this study was to determine biomechanical differences in cyclic elongation and ultimate strength between double-row rotator cuff repair and single-row repair for partial rotator cuff repairs . METHODS We r and omly assigned 18 immature bovine specimens ( aged 12 to 16 weeks ) to 3 repair groups ( 6 per group ) . A 1 x 2-cm defect was created at the infraspinatus tendon insertion site . Two suture anchors were implanted 1 cm apart at the anatomic insertion area for the lateral row . Two suture anchors were implanted 1 cm medial to the lateral row and 1 cm apart from each other for the medial row . Repair groups were constructed as follows : single-row repair with double-loaded suture anchors ( group 1 ) , double-row repair with single-loaded medial row and double-loaded lateral row ( group 2 ) , and double-row repair with single-loaded medial row and single-loaded lateral row ( group 3 ) . Specimens were cyclically loaded from 10 N to 90 N for 500 cycles and then loaded at 0.5 mm/s to failure . Data for cyclic elongation , with loads at 3 mm , 5 mm , and 10 mm , were analyzed via a 1-way analysis of variance ( P < .05 ) . RESULTS There were no significant differences for peak elongation after cyclic loading between groups . There were no significant differences between repair groups for loads at 3 mm , 5 mm , and 10 mm of elongation . Constructs typically failed by knot slippage ( 83 % ) , with a single sample having tendon-suture failure ( 17 % ) . CONCLUSIONS Double-row repair did not show a biomechanical advantage compared with single-row repair . With this result in mind , the theoretic advantage of a potentially larger footprint must be balanced against the added surgical time , complexity , and cost of double-row repair . CLINICAL RELEVANCE Arthroscopic surgeons should choose the best form of fixation for a given patient , without undue emphasis on single-row repair versus double-row repair . The clinical and biologic impact of footprint restoration was not addressed in this study The aim of the study was to evaluate the time zero mechanical properties of single- versus double-row configuration for rotator cuff repair in an animal model with consideration of the stitch technique and suture material . Thirty-two fresh-frozen sheep shoulders were r and omly assigned to four repair groups : suture anchor single-row repair coupled with ( 1 ) braided , nonabsorbable polyester suture sized USP No. 2 ( SRAE ) or ( 2 ) braided polyblend polyethylene suture sized No. 2 ( SRAH ) . The double-row repair was coupled with ( 3 ) USP No. 2 ( DRAE ) or ( 4 ) braided polyblend polyethylene suture No. 2 ( DRAH ) . Arthroscopic Mason – Allen stitches were used ( single-row ) and combined with medial horizontal mattress stitches ( double-row ) . Shoulders were cyclically loaded from 10 to 180 N. Displacement to gap formation of 5- and 10-mm at the repair site , cycles to failure , and the mode of failure were determined . The ultimate tensile strength was verified in specimens that resisted to 3,000 cycles . DRAE and DRAH had a lower frequency of 5- ( P = 0.135 ) and 10-mm gap formation ( P = 0.135 ) . All DRAE and DRAH resisted 3,000 cycles while only three SRAE and one SRAH resisted 3,000 cycles ( P < 0.001 ) . The ultimate tensile strength in double-row specimens was significantly higher than in others ( P < 0.001 ) . There was no significant variation in using different suture material ( P > 0.05 ) . Double-row suture anchor repair with arthroscopic Mason – Allen/medial mattress stitches provides initial strength superior to single-row repair with arthroscopic Mason – Allen stitches under isometric cyclic loading as well as under ultimate loading conditions . Our results support the concept of double-row fixation with arthroscopic Mason – Allen/medial mattress stitches in rotator cuff tears with improvement of initial fixation strength and ultimate tensile load . Use of new polyblend polyethylene suture material seems not to increase the initial biomechanical aspects of the repair construct The reported functional results of rotator cuff repair performed arthroscopically have been good . Only little is known about the cuff integrity after arthroscopic repair and how it influences the outcome . The aim of the study is to set a baseline of what rate of healing response respectively re-tears to expect and how cuff integrity alters the outcome . Fifty-three consecutive patients with an isolated supraspinatus tendon tear were arthroscopically operated and their tendons repaired . All pre- and postoperative data were prospect ively collected . At a minimum follow-up after 24 months ( average 26.4 months ) , the integrity of the cuff was evaluated by an open magnetic resonance imaging and the patients ’ function and satisfaction were documented and grade d to the sex- and age-related Constant-score also using a dynamometer for strength testing . The re-tear rate was 24.5 % with 13 non-healed tendons . The Constant-score of all patients improved significantly . The scores of the patients with a re-tear were significantly lower than those of the patient with an intact cuff . That was due to a less good performance in strength testing . The other categories of the Constant-score did not show any differences . The age of the patients with a re-tear was significantly higher . With the exception of age , we did not find any negative prognostic factor for a re-tear , and with the exception of re-tear no other factor influenced the Constant-score . Arthroscopic supraspinatus tendon repair yields a re-tear rate of 25 % which is comparable with the results of open or mini/open repair . Cuff integrity influences postoperative strength and Constant-score . Patients older than 65 years show a higher re-tear rate . Therapeutic Level IV is the level of evidence Thirty chronic rotator cuff tears were repaired consecutively and evaluated prospect ively using a precise anatomic description of the tear that included the rotator interval , the Constant functional score , and an assessment of the tendon state and the atrophy of the supraspinatus muscle by preoperative and postoperative magnetic resonance imaging . Early correlations ( mean followup , 21.1 months ) attempted to define predictive factors of the final outcome of the repair , physical factors indicative of final tendon state , and postoperative evolution of supraspinatus atrophy . Magnetic resonance imaging oblique sagittal views showed that supraspinatus atrophy correlated with the sagittal and coronal extent of the tear and represented a strong predictive factor of postoperative retearing . At followup , 15 ( 50 % ) cuffs were continuous and thick , seven ( 23 % ) were continuous but thin , and six ( 20 % ) were retorn . Two ( 7 % ) cuffs had been repaired only partly . In the group with a persistent tear , flexion strength and differential Constant score were correlated with the final tendon state with no excellent or good results , and with less than 4 kg of strength . Supraspinatus atrophy improved in 18 of the 22 postoperative continuous cuffs , but never decreased in persistent tears , although there was pain relief and functional gain BACKGROUND Recent studies have shown that arthroscopic rotator cuff repairs can have higher rates of failure than do open repairs . Current methods of rotator cuff repair have been limited to single-row fixation of simple and horizontal stitches , which is very different from open repairs . The objective of this study was to compare the initial cyclic loading and load-to-failure properties of double-row fixation with those of three commonly used single-row techniques . METHODS Ten paired human supraspinatus tendons were split in half , yielding four tendons per cadaver . The bone mineral content at the greater tuberosity was assessed . Four stitch configurations ( two-simple , massive cuff , arthroscopic Mason-Allen , and double-row fixation ) were r and omized and tested on each set of tendons . Specimens were cyclically loaded between 5 and 100 N at 0.25 Hz for fifty cycles and then loaded to failure under displacement control at 1 mm/sec . Conditioning elongation , peak-to-peak elongation , ultimate tensile load , and stiffness were measured with use of a three-dimensional tracking system and compared , and the failure type ( suture or anchor pull-out ) was recorded . RESULTS No significant differences were found among the stitches with respect to conditioning elongation . The mean peak-to-peak elongation ( and st and ard error of the mean ) was significantly lower for the massive cuff ( 1.1 + /- 0.1 mm ) and double-row stitches ( 1.1 + /- 0.1 mm ) than for the arthroscopic Mason-Allen stitch ( 1.5 + /- 0.2 mm ) ( p < 0.05 ) . The ultimate tensile load was significantly higher for double-row fixation ( 287 + /- 24 N ) than for all of the single-row fixations ( p < 0.05 ) . Additionally , the massive cuff stitch ( 250 + /- 21 N ) was found to have a significantly higher ultimate tensile load than the two-simple ( 191 + /- 18 N ) and arthroscopic Mason-Allen ( 212 + /- 21 N ) stitches ( p < 0.05 ) . No significant differences in stiffness were found among the stitches . Failure mechanisms were similar for all stitches . Rotator cuff repairs in the anterior half of the greater tuberosity had a significantly lower peak-to-peak elongation and higher ultimate tensile strength than did repairs on the posterior half . CONCLUSIONS In this in vitro cadaver study , double-row fixation had a significantly higher ultimate tensile load than the three types of single-row fixation stitches . Of the single-row fixations , the massive cuff stitch had cyclic and load-to-failure characteristics similar to the double-row fixation . Anterior repairs of the supraspinatus tendon had significantly stronger biomechanical behavior than posterior repairs BACKGROUND The reported rate of failure after arthroscopic rotator cuff repair has varied widely . The influence of the repair technique on the failure rates and functional outcomes after open or arthroscopic rotator cuff repair remains controversial . The purpose of the present study was to evaluate the functional and anatomic results of arthroscopic rotator cuff repairs performed with the double-row suture anchor technique on the basis of computed tomography or magnetic resonance imaging arthrography in order to determine the postoperative integrity of the repairs . METHODS A prospect i ve series of 105 consecutive shoulders undergoing arthroscopic double-row rotator cuff repair of the supraspinatus or a combination of the supraspinatus and infraspinatus were evaluated at a minimum of two years after surgery . The evaluation included a routine history and physical examination as well as determination of the preoperative and postoperative strength , pain , range of motion , and Constant scores . All shoulders had a preoperative and postoperative computed tomography arthrogram ( 103 shoulders ) or magnetic resonance imaging arthrogram ( two shoulders ) . RESULTS There were thirty-six small rotator cuff tears , forty-seven large isolated supraspinatus or combined supraspinatus and infraspinatus tendon tears , and twenty-two massive rotator cuff tears . The mean Constant score ( and st and ard deviation ) was 43.2 + /- 15.1 points ( range , 8 to 83 points ) preoperatively and 80.1 + /- 11.1 points ( range , 46 to 100 points ) postoperatively . Twelve of the 105 repairs failed . Intact rotator cuff repairs were associated with significantly increased strength and active range of motion . CONCLUSIONS Arthroscopic repair of a rotator cuff tear with use of the double-row suture anchor technique results in a much lower rate of failure than has previously been reported in association with either open or arthroscopic repair methods . Patients with an intact rotator cuff repair have better pain relief than those with a failed repair . After repair , large and massive rotator cuff tears result in more postoperative weakness than small tears do Rotator cuff repair via transosseous tunnels can improve footprint contact area and pressure when compared with suture anchor techniques . A double-row technique has been used clinical ly to improve footprint coverage by a repaired tendon . We hypothesized that a transosseous-equivalent rotator cuff repair via tendon suture bridges would demonstrate improved pressurized contact between the tendon and tuberosity when compared with a double-row technique . In 6 fresh-frozen human shoulders , a transosseous-equivalent rotator cuff repair was performed : a suture limb from each of 2 medial anchors was bridged over the tendon and fixed laterally with an interference screw ( 4 suture bridges ) . In 6 of the contralateral specimens , two types of repair were performed r and omly in each specimen : ( 1 ) a double-row repair and ( 2 ) a transosseous-equivalent repair with a single screw ( 2 suture bridges ) . For all repairs , pressure-sensitive film was placed at the tendon-footprint interface , and software was used to obtain measurements . The mean pressurized contact area between the tendon and insertion was significantly greater for the 4-suture bridge technique ( 124.2 + /- 16.3 mm2 , 77.6 % footprint ) compared with both the double-row ( 63.3 + /- 28.5 mm2 , 39.6 % footprint ) and 2-suture bridge ( 99.7 + /- 22.0 mm2 , 62.3 % footprint ) techniques ( P < .05 ) . The mean interface pressure exerted over the footprint by the tendon was greater for the 4-suture bridge technique ( 0.27 + /- 0.04 MPa ) than for the double-row technique ( 0.19 + /- 0.01 MPa ) ( P = .002 ) . The transosseous-equivalent rotator cuff repair technique can improve pressurized contact area and mean pressure between the tendon and footprint when compared with a double-row technique . A transosseous-equivalent technique , using suture bridges , may help optimize the healing biology at a repaired rotator cuff insertion PURPOSE Arthroscopic rotator cuff repair produces equally good clinical results compared with open or mini-open repair . However , there are concerns about whether the same repair integrity can be achieved . The purpose of our study was to compare clinical and structural results of arthroscopic and mini-open rotator cuff repair . METHODS Nineteen patients who had arthroscopic rotator cuff repair ( mean follow-up , 25.0 months ) were matched for age , gender , and duration of symptoms with nineteen patients who had mini-open repair ( mean follow-up , 17.6 months ) . We compared preoperative and follow-up Constant scores , as well as early range of motion after 6 weeks and 3 months . All patients were examined with the same magnetic resonance imaging system at follow-up to evaluate cuff integrity . RESULTS There was no difference in clinical and structural outcome . The overall Constant score improved from 53.8 to 83.9 in the arthroscopic group and from 53.5 to 83.7 in the mini-open group . Early range of motion did not differ significantly at 6 weeks or 3 months postoperatively . The number of retears was 6 ( 31.6 % ) in the arthroscopic group and 7 ( 36.8 % ) in the mini-open group . This difference was not statistically significant ( P = .7358 ) . Although smaller retears had no influence on the clinical result , more retracted retears correlated with lower abduction strength regardless of the repair method . CONCLUSIONS In isolated supraspinatus tears arthroscopic rotator cuff repair produces excellent clinical results and equivalent tendon integrity compared with mini-open repair . LEVEL OF EVIDENCE Level III , retrospective therapeutic comparative study PURPOSE The purpose of this study was to compare the clinical outcome of arthroscopic rotator cuff repair with single-row and double-row techniques . METHODS Eighty patients with a full-thickness rotator cuff tear underwent arthroscopic repair with suture anchors . They were divided into 2 groups of 40 patients according to repair technique : single row ( group 1 ) or double row ( group 2 ) . Results were evaluated by use of the Disabilities of the Arm , Shoulder and H and ( DASH ) and Work-DASH self-administered question naires , normalized Constant score , and muscle strength measurement . On analyzing the results at a 2-year follow-up , we considered the following independent variables : baseline scores ; age ; gender ; dominance ; location , shape , and area of cuff tear ; tendon retraction ; fatty degeneration ; treatment of biceps tendon ; and rotator cuff repair technique ( anchors or anchors and side to side ) . Univariate and multivariate statistical analyses were performed to determine which variables were independently associated with the outcome . Significance was set at P < .05 . RESULTS Of the patients , 8 ( 10 % ) were lost to follow-up . Comparison between groups did not show significant differences for each variable considered . Overall , according to the results , the mean DASH scores were 15.4 + /- 15.6 points in group 1 and 12.7 + /- 10.1 points in group 2 ; the mean Work-DASH scores were 16.0 + /- 22.0 points and 9.6 + /- 13.3 points , respectively ; and the mean Constant scores were 100.5 + /- 17.8 points and 104.9 + /- 21.8 points , respectively . Muscle strength was 12.7 + /- 5.7 lb in group 1 and 12.9 + /- 7.0 lb in group 2 . Univariate and multivariate analysis showed that only age , gender , and baseline strength significantly and independently influenced the outcome . Differences between groups 1 and 2 were not significant . CONCLUSIONS At short-term follow-up , arthroscopic rotator cuff repair with the double-row technique showed no significant difference in clinical outcome compared with single-row repair . LEVEL OF EVIDENCE Level I , high- quality r and omized controlled trial with no statistically significant differences but narrow confidence intervals BACKGROUND The reported rate of failure after arthroscopic rotator cuff repair has varied widely . The influence of the repair technique on the failure rates and functional outcomes after open or arthroscopic rotator cuff repair remains controversial . The purpose of the present study was to evaluate the functional and anatomic results of arthroscopic rotator cuff repairs performed with the double-row suture anchor technique on the basis of computed tomography or magnetic resonance imaging arthrography in order to determine the postoperative integrity of the repairs . METHODS A prospect i ve series of 105 consecutive shoulders undergoing arthroscopic double-row rotator cuff repair of the supraspinatus or a combination of the supraspinatus and infraspinatus were evaluated at a minimum of two years after surgery . The evaluation included a routine history and physical examination as well as determination of the preoperative and postoperative strength , pain , range of motion , and Constant scores . All shoulders had a preoperative and postoperative computed tomography arthrogram ( 103 shoulders ) or magnetic resonance imaging arthrogram ( two shoulders ) . RESULTS There were thirty-six small rotator cuff tears , forty-seven large isolated supraspinatus or combined supraspinatus and infraspinatus tendon tears , and twenty-two massive rotator cuff tears . The mean Constant score ( and st and ard deviation ) was 43.2+/-15.1 points ( range , 8 to 83 points ) preoperatively and 80.1+/-11.1 points ( range , 46 to 100 points ) postoperatively . Twelve of the 105 repairs failed . Intact rotator cuff repairs were associated with significantly increased strength and active range of motion . CONCLUSIONS Arthroscopic repair of a rotator cuff tear with use of the double-row suture anchor technique results in a much lower rate of failure than has previously been reported in association with either open or arthroscopic repair methods . Patients with an intact rotator cuff repair have better pain relief than those with a failed repair . After repair , large and massive rotator cuff tears result in more postoperative weakness than small tears do PURPOSE The purpose of this study was to compare the initial mechanical strength of 3 rotator cuff repair techniques . METHODS A total of 30 fresh-frozen cadaveric shoulders were prepared , and full-thickness supraspinatus tears were created . Specimens were r and omized and placed into 3 groups : ( 1 ) transosseous suture technique ( group I : TOS , n = 10 , 6F/4 M ) , ( 2 ) single-row suture anchor fixation ( group II : SRSA , n = 10 , 6F/4 M ) , and ( 3 ) double-row suture anchor fixation ( group III : DRSA , n = 10 , 6F/4 M ) . Each specimen underwent cyclic load testing from 5 N to 180 N at a rate of 33 mm/sec . The test was stopped when complete failure ( repair site gap of 10 mm ) or a total of 5,000 cycles was attained . RESULTS Group I ( TOS ) failed at an average of 75.3 + /- 22.49 cycles , and group II ( SRSA ) at an average of 798.3 + /- 73.28 cycles ; group III ( DRSA ) had no failures because all sample s were stopped when 5,000 cycles had been completed . Fixation strength of the DRSA technique proved to be significantly greater than that of SRSA ( P < .001 ) , and both suture anchor groups were significantly stronger than the TOS group ( P < .001 ) . CONCLUSIONS Suture anchor repairs were significantly stronger than transosseous repairs . Furthermore , double-row suture anchor fixation was significantly stronger than was single-row repair . Therefore , double-row fixation may be superior to other techniques in that it provides a substantially stronger repair that could lead to improved biologic healing . CLINICAL RELEVANCE A high incidence of incomplete healing occurs in rotator cuff repair . Use of double-row fixation may help the clinician to address some deficiencies in current methods by increasing the strength of the repair , potentially leading to improved healing rates Arthroscopic rotator cuff repair ( RCR ) has been reported to have good clinical results but high retear rates by ultrasound . We prospect ively assessed postoperative cuff integrity and outcome after arthroscopic RCR ( 40 patients ) and compared these results with open RCR ( 32 patients ) . Evaluation preoperatively and at 1 year included a physical examination and magnetic resonance imaging . American Shoulder and Elbow Surgeons and Constant scores improved significantly in both groups ( P < .0001 ) . Overall , 69 % of repairs in the open group and 53 % in the arthroscopic group were intact by magnetic resonance imaging . Of tears less than 3 cm in size , 74 % in the open group and 84 % in the arthroscopic group were intact . Of tears greater than 3 cm in size , 62 % in the open group and 24 % in the arthroscopic group were intact ( P < .036 ) . In the arthroscopic group , patients with an intact cuff had significantly greater strength of elevation ( P = .01 ) and external rotation ( P = .02 ) . We conclude that open and arthroscopic RCRs have similar clinical outcomes . Cuff integrity is comparable for small tears , but large tears have twice the retear rate after arthroscopic repair BACKGROUND The retear rate following rotator cuff repair is variable . Recent biomechanical studies have demonstrated that double-row tendon-to-bone fixation excels in initial fixation strength and footprint coverage compared with the single-row or transosseous fixation methods . This study was design ed to report the repair integrity and clinical outcome following arthroscopic double-row rotator cuff repair . METHODS A consecutive series of 106 patients with full-thickness rotator cuff tears underwent arthroscopic double-row rotator cuff repair with use of suture anchors and were followed prospect ively . Twenty patients lacked complete follow-up data or were lost to follow-up . The eighty-six study subjects included fifty-two men and thirty-four women , with an average age of 60.5 years . There were twenty-six small , thirty medium , twenty-two large , and eight massive tears . Clinical outcomes were evaluated at an average of thirty-one months . Repair integrity was estimated with use of magnetic resonance imaging , which was performed , on the average , fourteen months postoperatively , and was classified into five categories , with type I indicating sufficient thickness with homogeneously low intensity ; type II , sufficient thickness with partial high intensity ; type III , insufficient thickness without discontinuity ; type IV , the presence of a minor discontinuity ; and type V , the presence of a major discontinuity . RESULTS The average clinical outcome scores all improved significantly at the time of the final follow-up ( p < 0.01 ) . At a mean of fourteen months postoperatively , magnetic resonance imaging revealed that thirty-seven shoulders had a type-I repair ; twenty-one , a type-II repair ; thirteen , a type-III repair ; eight , a type-IV repair ; and seven , a type-V repair . The overall rate of retears ( types IV and V ) was 17 % . The retear rate was 5 % for small-to-medium tears , while it was 40 % for large and massive tears . The shoulders with a type-V repair demonstrated significantly inferior functional outcome in terms of overall scores and strength compared with the other types of repairs ( p < 0.01 ) . CONCLUSIONS Arthroscopic double-row repair can result in improved repair integrity compared with open or miniopen repair methods . However , the retear rate for shoulders with large and massive tears remains higher than that for smaller tears , and shoulders with large repair defects ( type V ) demonstrate significantly inferior functional outcomes |
919 | 18,574,359 | Review of the published studies reveals that no one procedure or set of predictor variables is sufficient to identify CPP at-risk for opioid misuse or abuse .
Strong predictors include a personal history of illicit drug and alcohol abuse . | BACKGROUND Opioids can provide relief for people with chronic pain .
However , a minority may develop aberrant drug behaviors .
A critical issue is identifying " at-risk " patients .
OBJECTIVE To synthesize the evidence of published strategies for identifying at-risk patients to guide clinicians ' decisions and practice s for prescribing opioid treatment for chronic pain patients ( CPP ) .
There is a scarcity of evidence regarding characteristics that predict aberrant behavior before beginning long-term opioids . | Background Opioid misuse can complicate chronic pain management , and the non-medical use of opioids is a growing public health problem . The incidence and risk factors for opioid misuse in patients with chronic pain , however , have not been well characterized . We conducted a prospect i ve cohort study to determine the one-year incidence and predictors of opioid misuse among patients enrolled in a chronic pain disease management program within an academic internal medicine practice . Methods One-hundred and ninety-six opioid-treated patients with chronic , non-cancer pain of at least three months duration were monitored for opioid misuse at pre-defined intervals . Opioid misuse was defined as : 1 . Negative urine toxicological screen ( UTS ) for prescribed opioids ; 2 . UTS positive for opioids or controlled substances not prescribed by our practice ; 3 . Evidence of procurement of opioids from multiple providers ; 4 . Diversion of opioids ; 5 . Prescription forgery ; or 6 . Stimulants ( cocaine or amphetamines ) on UTS . Results The mean patient age was 52 years , 55 % were male , and 75 % were white . Sixty-two of 196 ( 32 % ) patients committed opioid misuse . Detection of cocaine or amphetamines on UTS was the most common form of misuse ( 40.3 % of misusers ) . In bivariate analysis , misusers were more likely than non-misusers to be younger ( 48 years vs 54 years , p < 0.001 ) , male ( 59.6 % vs. 38 % ; p = 0.023 ) , have past alcohol abuse ( 44 % vs 23 % ; p = 0.004 ) , past cocaine abuse ( 68 % vs 21 % ; p < 0.001 ) , or have a previous drug or DUI conviction ( 40 % vs 11 % ; p < 0.001 % ) . In multivariate analyses , age , past cocaine abuse ( OR , 4.3 ) , drug or DUI conviction ( OR , 2.6 ) , and a past alcohol abuse ( OR , 2.6 ) persisted as predictors of misuse . Race , income , education , depression score , disability score , pain score , and literacy were not associated with misuse . No relationship between pain scores and misuse emerged . Conclusion Opioid misuse occurred frequently in chronic pain patients in a pain management program within an academic primary care practice . Patients with a history of alcohol or cocaine abuse and alcohol or drug related convictions should be carefully evaluated and followed for signs of misuse if opioids are prescribed . Structured monitoring for opioid misuse can potentially ensure the appropriate use of opioids in chronic pain management and mitigate adverse public health effects of diversion A r and om sample of 1,200 employees of a steel manufacturing plant were r and omly assigned to four different self-report methods of assessing illicit drug use : 1 ) Individual interview in the workplace , 2 ) group-administered question naire in the workplace , 3 ) telephone interview , and 4 ) individual interview off the worksite . Urine specimens were collected and analyzed on all 928 subjects participating in the study , and hair analysis was conducted on 307 of the subjects . Although self-reports produced the highest drug use prevalence rate , analyses combining the results of the three assessment methods showed that the actual prevalence rate was approximately 50 % higher than the estimate produced by self-reports . The group-administered question naire condition produced prevalence rates that were roughly half those of the other self-report methods . The findings cast doubt on the validity of self-reports as a means of estimating drug use prevalence and suggest the need for multiple assessment methods Objective To examine the incidence of abnormal urine toxicology screening among chronic pain patients prescribed opioids for their pain and to relate these results to patient descriptors and type , number , and dose of prescribed opioids . Methods A retrospective analysis of data from 470 patients who had urine screening at a pain management program in an urban teaching hospital was performed . Urine sample s were analyzed using gas chromatography-mass spectrometry . Patients were categorized as having urine screens that were “ normal ” ( expected findings based on their prescribed drugs ) or abnormal . Abnormal findings were those of ( 1 ) absence of a prescribed opioid , ( 2 ) presence of an additional nonprescribed controlled substance , ( 3 ) detection of an illicit substance , and ( 4 ) an adulterated urine sample . Results Forty-five percent of the patients were found to have abnormal urine screens . Twenty percent were categorized as having an illicit substance in their urine . Illicit substances and additional drugs were found more frequently in younger patients than in older patients ( P<0.001 ) . No other variables were found to predict abnormal urine screen results . Discussion These results confirm past findings that r and om urine toxicology screens among patients prescribed opioids for pain reveal a high incidence of abnormal findings . Common patient descriptors , and number , type , and dose of prescribed opioids were found to be poor predictors of abnormal results This study introduces the Addiction Behaviors Checklist ( ABC ) , which is a brief ( 20-item ) instrument design ed to track behaviors characteristic of addiction related to prescription opioid medications in chronic pain population s. Items are focused on observable behaviors noted both during and between clinic visits . One hundred thirty-six consecutive veterans in a multidisciplinary Veterans Affairs Chronic Pain Clinic who were receiving long-term opioid medication treatment were included in this study . This study represents one of the first to follow a sample of chronic pain patients on opioid therapy over time , using a structured assessment tool to evaluate and track behaviors suggestive of addiction . Interrater reliability and concurrent validity data are presented , as well as a cut-off score for use in determining inappropriate medication use . The psychometric findings support the ABC as a viable assessment tool that can increase a provider 's confidence in determinations of appropriate vs. inappropriate opioid use & NA ; Prescribing long‐term opioids for patients with chronic pain is controversial . The primary purpose of this study was to examine physicians ' beliefs about and prescribing of the long‐term use of opioids in the treatment of chronic pain patients . Concerns about regulatory pressure and appropriateness of education regarding opioids were also examined . The design was a stratified r and om sample . In the United States , 6962 physicians were r and omly selected from two states in each of five regions of the country ( Northeast , Midwest , Southeast , Southwest , and Pacific ) . Physicians from seven medical specialties ( Family Practice , Internal Medicine , Physical Medicine and Rehabilitation , Rheumatology , Orthopedic Surgery , Neurosurgery , and Neurology ) were surveyed and 1912 ( 27.46 % ) responded . A survey consisting of questions regarding years of practice , number of chronic pain patients treated , frequency of prescribing long‐term opioids , concerns about opioids , goals of treatment , beliefs about education regarding opioids , and concerns about regulatory pressures was used . Based on the physicians who responded , it appears that prescription of long‐term opioids is relatively wide‐spread . Differences were noted by region , specialty , and the requirement for the use of multiple prescriptions for schedule II drugs . Physicians in the Midwestern United States were the least likely to prescribe the long‐term use of opioids . Rheumatologists and general practitioners were significantly more likely to prescribe long‐term opioids than were surgeons , neurologists , or physiatrists and were more likely to emphasize the importance of symptom improvement as an appropriate goal even in the absence of functional improvements . The majority of the respondents expressed relatively little concern about tolerance , dependence , and addiction as impediments to prescribing opioids . Physicians from states requiring multiple prescriptions reported that this legal requirement had little impact on their practice Abstract OBJECTIVES : To define the spectrum of chronic noncancer pain treated with opioid medications in 2 primary care setting s , and the prevalence of psychiatric comorbidity in this patient population . We also sought to determine the proportion of patients who manifested prescription opioid abuse behaviors and the factors associated with these behaviors . DESIGN : A retrospective cohort study . SETTING : A VA primary care clinic and an urban hospital-based primary care center ( PCC ) located in the northeastern United States . PATIENTS : A r and om sample of VA patients ( n=50 ) and all PCC patients ( n=48 ) with chronic noncancer pain who received 6 or more months of opioid prescriptions during a 1-year period ( April 1 , 1997 through March 31 , 1998 ) and were not on methadone maintenance . MEASUREMENTS : Information regarding patients ’ type of chronic pain disorder , demographic , medical , and psychiatric status , and the presence of prescription opioid abuse behaviors was obtained by medical record review . MAIN RESULTS : Low back pain was the most common disorder accounting for 44 % and 25 % of all chronic pain diagnoses in the VA and PCC sample s , respectively , followed by injury-related ( 10 % and 13 % ) , diabetic neuropathy ( 8 % and 10 % ) , degenerative joint disease ( 16 % and 13 % ) , spinal stenosis ( 10 % and 4 % ) , headache ( 4 % and 13 % ) and other chronic pain disorders ( 8 % and 22 % ) . The median duration of pain was 10 years ( range 3 to 50 years ) in the VA and 13 years in the PCC sample ( range 1 to 49 years ) . Among VA and PCC patients , the lifetime prevalence rates of psychiatric comorbidities were : depressive disorder ( 44 % and 54 % ) , anxiety disorder ( 20 % and 21 % ) , alcohol abuse/dependence ( 46 % and 31 % ) , and narcotic abuse/dependence ( 18 % and 38 % ) . Prescription opioid abusive behaviors were recorded for 24 % of VA and 31 % of PCC patients . A lifetime history of a substance use disorder ( adjusted odds ratio [ OR ] , 3.8 ; 95 % confidence interval [ CI ] , 1.4 to 10.8 ) and age ( adjusted OR , 0.94 ; 95 % CI , 0.89 to 0.99 ) were independent predictors of prescription opioid abuse behavior . CONCLUSIONS : A broad spectrum of chronic noncancer pain disorders are treated with opioid medications in primary care setting s. The lifetime prevalence of psychiatric comorbidity was substantial in our study population . A significant minority of patients manifested prescription opioid abusive behaviors , and a lifetime history of a substance use disorder and decreasing age were associated with prescription opioid abuse behavior . Prospect i ve studies are needed to determine the potential benefits as well as risks associated with opioid use for chronic noncancer pain in primary care OBJECTIVE To provide clinicians with a brief screening tool to predict accurately which individuals may develop aberrant behaviors when prescribed opioids for chronic pain . DESIGN One hundred and eighty-five consecutive new patients treated in one pain clinic took the self-administered Opioid Risk Tool ( ORT ) . The ORT measured the following risk factors associated in scientific literature with substance abuse : personal and family history of substance abuse ; age ; history of preadolescent sexual abuse ; and certain psychological diseases . Patients received scores of 0 - 3 ( low risk ) , 4 - 7 ( moderate risk ) , or > or= 8 ( high risk ) , indicating the probability of their displaying opioid-related aberrant behaviors . All patients were monitored for aberrant behaviors for 12 months after their initial visits . RESULTS For those patients with a risk category of low , 17 out of 18 ( 94.4 % ) did not display an aberrant behavior . For those patients with a risk category of high , 40 out of 44 ( 90.9 % ) did display an aberrant behavior . The authors used the c statistic to vali date the ORT , because it simultaneously assesses sensitivity and specificity . The ORT displayed excellent discrimination for both the male ( c = 0.82 ) and the female ( c = 0.85 ) prognostic models . CONCLUSION In a preliminary study , among patients prescribed opioids for chronic pain , the ORT exhibited a high degree of sensitivity and specificity for determining which individuals are at risk for opioid-related , aberrant behaviors . Further studies in a variety of pain and nonpain setting s are needed to determine the ORT 's universal applicability Assessing for the presence of addiction in the chronic pain patient receiving chronic opioid analgesia is a challenging clinical task . This paper presents a recently developed screening tool for addictive disease in chronic pain patients , and pilot efficacy data describing its ability to do so . In a small sample of patients ( n = 52 ) referred from a multidisciplinary pain center for " problematic " medication use , responses to the screening question naire were compared between patients who met combined diagnostic criteria for a substance use disorder and those who did not , as assessed by a trained addiction medicine specialist . Responses of addicted patients significantly differed from those of nonaddicted patients on multiple screening items , with the two groups easily differentiated by total question naire score . Further , three key screening indicators were identified as excellent predictors for the presence of addictive disease in this sample of chronic pain patients OBJECTIVES Opiates are commonly used to treat patients with chronic nonmalignant pain . There is much controversy over the definition , incidence , and risk factors of prescription opiate abuse in chronic pain treatment . The present study , done at the Seattle VA Medical Center , was design ed to create opiate abuse criteria , test inter-rater reliability of the criteria , apply the criteria to a group of chronic pain patients , and correlate the risk of opiate abuse with the results of alcohol and drug testing . DESIGN / OUTCOME MEASURES A committee of experienced pain providers design ed a five-point prescription opiate abuse checklist based on DSM-III-R parameters . The criteria were then applied to patients enrolled in the pain clinic . The reliability of the criteria were determined using two providers who were familiar with every patient in the clinic . Drug , alcohol , and psychosocial testing were correlated with the risk of opiate abuse . RESULTS A total of 19 % ( 76/403 ) of all pain clinic patients were using chronic opiates . Thirty-four percent ( 26/76 ) met one , and 27.6 % ( 21/76 ) met three or more of the abuse criteria . The criteria had an inter-rater reliability of > 0.9 . There were no differences between chronic opiate users ( n = 76 ) and opiate abusers ( n = 21 ) for a history of drug or alcohol abuse or on psychosocial testing . CONCLUSIONS Prescription opiate abuse criteria for use in patients with chronic nonmalignant pain were design ed . The criteria had good reliability and can be applied during normal clinic interactions . The percentage of chronic opiate users who become opiate abusers in pain treatment is within the range reported by others . Past opiate or alcohol abuse or psychosocial testing on clinic admission failed to predict who would become an opiate abuser . The criteria can be used to identify patients who will subsequently require more intensive treatment or intervention or can be used as an outcome to measure to test the effectiveness of treatment strategies |
920 | 28,478,618 | In conclusion , RA was associated with higher primary patency rates of AVF and improved local blood flow in comparison to LA ; however , both procedures were comparable in terms of primary failure rates and postoperative complications . | There is a consensus in the literature that regional anesthesia ( RA ) improves local hemodynamic parameters in comparison to local anesthesia ( LA ) during arteriovenous fistula ( AVF ) surgical construction .
However , the effects of both techniques on fistula patency and failure rates are still controversial .
The aim of this meta- analysis is to synthesize evidence from published r and omized trials and observational studies regarding the safety and efficacy of RA versus LA in AVF surgical construction . | BACKGROUND As the number of patients aged > /=65 years starting haemodialysis ( HD ) continues to increase , more patients are at risk of falls , functional decline and cognitive impairment . In an earlier prospect i ve cohort study , we showed that 44 % of elderly HD patients had more than one fall within a 1-year period . The objective of this study was to assess whether falls remained predictive of increased mortality risk even after controlling for age , comorbidity , dialysis vintage and laboratory variables . METHODS Using a prospect i ve , cohort study design , patients aged > /=65 years and on chronic HD during the period April 2002 - 2003 were recruited . Patients were followed biweekly , and falls occurring within the first year were recorded . Outcome data were collected until death , study end ( 30 December 2006 ) , transplantation or transfer to another dialysis centre . RESULTS A total of 162 patients were followed for a median of 32.7 months ( quartiles 14 - 57 ) . In a univariate Cox model with a time-dependent variable for falls status , survival was worse amongst fallers compared to non-fallers ( HR 2.13 , 95 % CI 1.32 - 3.45 ; P = 0.002 ) . After adjustment for age , dialysis vintage , comorbidity and laboratory variables , falls were a significant predictor of mortality ( HR 1.78 , 95 % CI 1.07 - 2.98 , P = 0.03 ) . Exclusion of falls associated with concurrent illnesses did not alter the results ( HR 1.63 , CI 1.02 - 2.28 P = 0.05 ) . CONCLUSIONS We conclude that the occurrence of more than one accidental fall in a community-dwelling HD patient aged > /=65 years is associated with an independent increased risk of death . As fall interventions are effective , screening HD patients for falls may be a simple measure of clinical importance The goal of the study was to compare effectiveness of regional and local anesthesia in dialysis arterio-venous fistula ( AVF ) operations . It was a prospect i ve , r and omized study . 103 patients with end stage renal disease underwent AVF operations on upper limb . The patients have been r and omly divided in two groups . Group I : 49 patients in whom the operations have been done under the local anesthesia ; and Group II : 54 patients in whom the operation has been performed under the vertical infraclavicular block . Duplex sonography evaluation of upper arm vessels was performed pre-operatively and at 1 , 3 and 6 months postoperatively . Following parameters were measured on duplex scan : vessel diameter , blood flow rates ( PSV and EDV ) , resistive index ( RI ) and pulsatility index ( PI ) . Significantly less number of patients with regional anesthesia required additional perioperative analgesics as compared with the local anesthesia group . Time to postoperative pain initiation , need for postoperative pain killers was significantly better in Group II as compared with the Group I. Duration of operation was significantly less in regional as compared with local anesthesia . Postoperative PSV and EDVs were negatively correlated with patient age . The fistula maturation time was positively correlated with age . The vein diameter , postoperative PSV and EDV have been significantly increased in Group I as compared with Group II . The postoperative PI has significantly increased and RI has significantly decreased in Group I as compared with Group II . The total number of dialysis punctures was higher in regional as compared with the local anesthesia . Regional anesthesia provides significantly better analgesia as compared with the local anesthesia in AVF operations . It significantly improves the duplex sonography parameters after AVF formation . It can be a method of choice for some forms of fistulas Purpose Assessment of the effectiveness of Brachial Plexus Block ( BPB ) via axillary approach compared to regional anesthesia for arteriovenous fistula surgery in patients affected by end-stage renal disease . Methods We compared forty patients r and omly divided into two groups . Group A underwent BPB procedure with 15 mL ropivacaine 1 % and 10 mL of saline ( 0.9 % NaCl ) via axillary approach . Group B received local anesthesia with lidocaine 2 % . The forearm blood vessels were assessed by Doppler ultrasonography before and after the intervention . Results BPB performed on Group A was associated with a considerable venous dilation and a significant decrease ( 48.7 % , P<.05 ) in pulsatility index ( PI ) measured by Doppler ultrasound . In Group B , PI and venous dilation remained unaltered in the postoperative phase . No complications such as thrombosis or occlusion were encountered among patients who underwent BPB . Conclusions The axillary-approached BPB was more advantageous than local anesthesia . Its effectiveness was because of venous dilation and the decrease in the PI , consequent to the reduction in peripheral resistances and the increase in local blood flow , thus offering an ideal background for fistula creation and short-term patency BACKGROUND Central venous catheters ( CVC ) are a potential source of bacteraemia and have been associated with increased mortality in haemodialysis patients . We aim ed to investigate the relationships between haemodialysis vascular access , taking into account changes in vascular access type during patients ' lives , and cause specific mortality risk in a national cohort of dialysis patients . METHODS Prospect i ve cohort study including all patients receiving haemodialysis in Scotl and at annual cross sectional surveys in 2009 , 2010 and 2011 . Data were collected through the Scottish Renal Registry and by a structured review of case records following death . Cox proportional hazards regression and multivariable logistic regression were used to model survival and risk of death from septicaemia respectively . RESULTS Of a cohort of 2666 patients , 873 ( 32 % ) died during follow-up . After case-mix adjustment , patients using only tunnelled CVC during follow-up had a higher risk of all cause mortality across all strata of prior renal replacement therapy exposure [ adjusted hazard ratio ( HR ) : 1.83 - 2.08 ] . Case-mix adjusted risks of cardiovascular death ( adjusted HR : 2.20 - 2.95 ) and infection-related death ( adjusted HR : 3.10 - 3.63 ) were also higher in this group . Patients using tunnelled CVCs during follow-up and prior to death had 6.9-fold higher odds of death from septicaemia compared with those using only arteriovenous fistulae or grafts . CONCLUSION Compared with an arteriovenous fistula or graft , sustained use of tunnelled CVCs for vascular access is associated with higher risks of all-cause , cardiovascular and infection-related mortality Background An arteriovenous fistula is the optimal form of vascular access in patients with end-stage renal failure requiring haemodialysis . Unfortunately , approximately one-third of fistulae fail at an early stage . Different anaesthetic techniques can influence factors associated with fistula success , such as intraoperative blood flow and venous diameter . A regional anaesthetic brachial plexus block results in vasodilatation and improved short- and long-term fistula flow compared to the infiltration of local anaesthetic alone . This , however , has not yet been shown in a large trial to influence long-term fistula patency , the ultimate clinical measure of success . The aim of this study is to compare whether a regional anaesthetic block , compared to local anaesthetic infiltration , can improve long-term fistula patency . Methods This study is an observer-blinded , r and omised controlled trial . Patients scheduled to undergo creation of either brachial or radial arteriovenous fistulae will receive a study information sheet , and consent will be obtained in keeping with the Declaration of Helsinki . Patients will be r and omised to receive either : ( i ) an ultrasound guided brachial plexus block using lignocaine with adrenaline and levobupivicaine , or ( ii ) local anaesthetic infiltration with lignocaine and levobupivicaine . A total of 126 patients will be recruited . The primary outcome is fistula primary patency at three months . Secondary outcomes include primary patency at 1 and 12 months , secondary patency and fistula flow at 1 , 3 and 12 months , flow on first haemodialysis , procedural pain , patient satisfaction , change in cephalic vein diameter pre- and post-anaesthetic , change in radial or brachial artery flow pre- and post-anaesthetic , alteration of the surgical plan after anaesthesia as guided by vascular mapping with ultrasound , and fistula infection requiring antibiotics . Conclusions No large r and omised controlled trial has examined the influence of brachial plexus block compared with local anaesthetic infiltration on the long-term patency of arteriovenous fistulae . If the performance of brachial plexus block increases fistulae patency , this will have significant clinical and financial benefits as the number of patients able to commence haemodialysis when planned should increase , and the number of “ redo ” or revision procedures should be reduced . Trial registration This study has been approved by the West of Scotl and Research Ethics Committee 5 ( reference no. 12/WS/0199 ) and is registered with the Clinical Trials.gov data base ( reference no. NCT01706354 ) The use of ultrasound reduces the onset time , improves the quality of sensory block , and minimizes the risks associated with the supraclavicular approach for brachial plexus and stellate ganglion blockade . The present study was design ed to evaluate whether ultrasound also facilitates the approach for 3-in-1 blocks . Forty patients ( ASA physical status II or III ) undergoing hip surgery after trauma were r and omly assigned to two groups . In the ultrasound ( US ) group , 20 mL bupivacaine 0.5 % was administered under US guidance , whereas in the control group , the same amount and concentration of local anesthetic was administered with the assistance of a nerve stimulator ( NS ) . After US- or NS-based identification of the femoral nerve , the local anesthetic solution was administered , and the distribution of the local anesthetic solution was visualized and recorded on videotape in the US group . The quality and the onset of the sensory block was assessed by using the pinprick test in the central sensory region of each of the three nerves and compared with the same stimulation on the contralateral leg every 10 min for 60 min . The rating was performed using a scale from 100 % ( uncompromised sensibility ) to 0 % ( no sensory sensation ) . Heart rate , noninvasive blood pressure , and oxygen saturation were measured at short intervals for 60 min . The onset of sensory blockade was significantly shorter in Group US compared with Group NS ( US 16 + /- 14 min , NS 27 + /- 16 min , P < 0.05 ) . The quality of the sensory block after injection of the local anesthetic was also significantly better in Group US compared with Group NS ( US 15 % + /- 10 % of initial value , NS 27 % + /- 14 % of initial value , P < 0.05 ) . A good analgesic effect was achieved in 95 % of the patients in the US group and in 85 % of the patients in the NS group . In the US group , visualization of the cannula tip , the femoral nerve , the major vessels , and the local anesthetic spread was possible in 85 % of patients . Incidental arterial puncture ( n = 3 ) was observed only in the NS group . We conclude that an US-guided approach for 3-in-1 block reduces the onset time , improves the quality of the sensory block and minimizes the risks associated with this regional anesthetic technique . Implication s : The onset time and the quality of a regional anesthetic technique for the lower extremity is improved by ultrasonographic nerve identification compared with older techniques . ( Anesth Analg 1997;85:854 - 7 OBJECTIVE To reduce the onset of 0.5 % bupivacaine by adding 2 % lidocaine with 0.5 % bupivacaine for ultrasound-guided and double stimulation technique at musculocutaneous and radial nerve for infraclavicular brachial plexus block . DESIGN Prospect i ve r and omized double-blinded , controlled trial study . MATERIAL AND METHOD 90 patients undergoing creation of arteriovenous fistula under ultrasound-guided infraclavicular brachial plexus block were r and omized into 2 groups . Gr B ( 46 patients ) received 0.5 % bupivacaine 30 mL and Gr BL ( 44 patients ) received mixture of 0.5 % bupivacaine 20 mL and 2 % lidocaine 10 mL. The onset of sensory block were assessed by response to pinprick ( grading : 0 = no sensation , 1 = hypoesthesia , and 2 = normal sensation ) . Rescue analgesia during the operation , duration of sensory and motor blockade were recorded . Surgeon and patient satisfactions are also evaluated using 6-point scale ( 0 = dissatisfied to 5 = very satisfied ) . RESULTS There were no significant difference in the onset time of either group . Duration of sensory and motor block was not different . Surgeons ' and patients ' satisfaction were also not significantly different between the groups . CONCLUSION Mixing 2 % lidocaine with 0.5 % bupivacaine to the final concentration of 0.67%for lidocaine and 0.33 % for bupivacaine does not reduce the onset of ultrasound-guided infraclavicular brachial plexus block BACKGROUND The most recent Kidney Disease Outcomes Quality Initiative ( KDOQI ) guidelines recommend that the order of preference for arteriovenous fistula ( AVF ) placement is the radial-cephalic primary AVF , followed by the secondary brachiocephalic ( BC ) and , if either of these is not viable , then brachiobasilic ( BB ) AVF should be fashioned . However , there is limited prospect i ve data comparing technical and clinical outcomes of these two approaches . The purpose of our study was to compare outcome , patency , and complication rates in these two autogenous upper arm AV accesses . METHODS Between December 2003 and and January 2007 , patients ( 61 male , 39 female ) who have lost more distal AVFs were enrolled in the study . After preoperative duplex mapping , patients with patent both basilic and cephalic veins greater than 3 mm of diameter were r and omized into BCAVF and BBAVF groups , each group consisting of 50 patients . All procedures were performed under local anesthesia as one-stage procedures . Follow-up data were prospect ively collected . Kaplan-Meier analysis was used to calculate primary and secondary patency rates . Univariate and multivariate Cox-regression analysis was used to find risks for the occurrence of thrombosis . RESULTS Baseline demographics , clinical characteristics , and preoperative history dialysis access were comparable between groups with the exception of the fact that mean caliber of the basilic veins were larger ( 4.51 + /- 0.93 mm vs 3.90 + /- 0.1 mm ; P = .002 ) . The mean duration of operation was significantly shorter in the BC group compared with the BB group ( P < .001 ) . There was no significant difference in the thirty day mortality , wound complications , 24 hour thrombosis , postoperative hemorrhage , maturation , and time to maturation between the groups . Mean follow-up was 43.2 + /- 1.8 months . Primary patency at 1 and 3 years of follow-up was 87 % and 81 % for the BC group and 86 % and 73 % for the BB group ( P = .7 ) Secondary patency at one and three year follow-up was 87 % and 70 % for the BC group and 88 % and 71 % for the BB group , respectively ( P = .8 ) . Twenty-eight patients ( 28 % ) in the BC ( 18 patients ) and BB ( 10 patients ) group died with a patent fistula during the follow-up period ( P = .18 ) . Multivariate analysis revealed that use of dominant arm increased the risk of fistula failure . CONCLUSION We conclude that brachiobasilic and brachiocephalic AVF are equally effective alternatives ; however , a longer and dem and ing operation with BB AVF construction should be considered OBJECTIVE Brachial plexus block offers several advantages when creating vascular access for hemodialysis . However , no controlled studies have directly evaluated arteriovenous fistula ( AVF ) blood flow in patients anesthetized by this method . We compared the effects of ultrasound-guided , infraclavicular brachial plexus block and local infiltration anesthesia on blood flow in the radial artery and AVF during the early and late postoperative periods . METHODS Sixty patients were r and omly assigned to an experimental group , which received infraclavicular brachial plexus block ( IB ) , or to a control ( C ) group that received local infiltration anesthesia . Blood flow in the distal radial artery was measured before and after IB or infiltration anesthesia . AVF flow during the early and late postoperative period was evaluated using duplex ultrasound imaging . The rates of primary fistula failure were also compared . RESULTS After anesthesia , preoperative radial arterial flow was 56 ± 8.6 mL/min in group IB vs 40.7 ± 6.11 mL/min in group C ( P < .0001 ) . Blood flow in the fistula , measured in mL/min at 3 hours , 7 days , and 8 weeks postoperatively , was also greater in group 1B vs group C , respectively , at 69.6 ± 7.9 vs 44.8 ± 13.8 ( P < .001 ) , 210.6 ± 30.9 vs 129 ± 36.1 ( P < .001 ) , and 680.6 ± 96.7 vs 405.3 ± 76.2 ( P < 0.001 ) . CONCLUSION When used for AVF access surgery , infraclavicular brachial plexus block provides higher blood flow in the radial artery and AVF than is achieved with infiltration anesthesia Both , regional and local anesthesia are used for dialysis arterio-venous fistula ( AVF ) formation in end-stage renal disease patients . There are no prospect i ve , r and omized clinical trials comparing effectiveness of these types of anesthesia in these patients . It was a prospect i ve , r and omized study . 103 patients with ESRD underwent dialysis AVF operations on upper limb . The patients have been r and omly divided in two groups . Group I : 49 patients in whom the operations have been done under the local anesthesia ; and Group II : 54 patients in whom the operation has been performed under the vertical infraclavicular block . Radio-Cefalic , Brachio-Cefalic and Brachio-Basilic(I stage transposition ) fistulas have been created in all patients .Influence of the type of anesthesia on intra- and postoperative pain has been evaluated and compared between the groups . The mean follow-up was 359.5 days in Group I and 340.5 days in Group II (p-NS).The mean patients age was 59.7±13.1 years and 60.1±14 years in local and regional anesthesia groups , respectively ( p = NS ) . For the whole group , significantly less number of patients with regional anesthesia required additional perioperative analgesics as compared with the local anesthesia group ( p=0.0363 ) . Time to postoperative pain initiation was significantly higher in Group II ( 2.3 hours ) as compared with the Group I ( 1.7 hours , p=0.0477 ) . The need for postoperative pain killers was significantly less in regional as compared with the local anesthesia ( p=0.0318 ) . Duration of operation was significantly less in regional ( 67.5 min . ) as compared with local anesthesia ( 134.7 min . p=0.0007 ) group . This difference has been detected in Brachio-Cefalic and Brachio-Basilic fistulas ( p=0.0257 and 0.001 , respectively ) but not in Radio-Cefalic one . No anesthesia related complications have been detected . Insufficiency of regional anesthesia has been identified in 3 cases (5.5%).In 5 patients from regional anesthesia group ( 9.4 % ) as a result of vasodilation have made more simplified operation . Regional anesthesia provides significantly betterperiperativeanalgesiaas compared with the local anesthesia in AVF operations . It can change the tactic of surgery , significantly decreases the operation time and should be a method of choice for some forms AVF operations The National Kidney Foundation 's Dialysis Outcomes Quality Initiative recommends an ideal 3- to 4-month arteriovenous fistula ( AVF ) maturation period prior to cannulation . This recommendation may be misinterpreted by practicing nephrologists to mean that they should wait 3 months before performing a clinical assessment of the AVF . Such a delay in evaluating AVF maturity results in unnecessarily prolonged catheter use in dialysis patients whose ultimately unsatisfactory fistula could already have been diagnosed and modified at a much earlier point . Clinical assessment at 1 month can detect the common etiologies for nonmaturity , including stenosis in the vein adjacent to the anastomosis and accessory vein diversion of flow from the main fistula vein . Duplex ultrasound provides additional information in selected cases . Early evaluation allows for early fistulography for problems and potentially early cannulation for adequately maturing fistulas . Prospect i ve trials of early AVF clinical assessment at 1 month should be performed Durable vascular access for hemodialysis remains a critical issue in end-stage renal disease patients . Creation of an autogenous arteriovenous ( AV ) fistula in the most distal location of the nondominant extremity is the preferred technique and provides superior patency over an AV graft . Others have shown that regional anesthesia in the form of axillary block results in the dilatation of the native veins and allows for their increased utilization in creating AV fistulae . We report on 26 patients undergoing creation of a vascular access for hemodialysis . Regional anesthesia consisting of axillary nerve block was used in all cases . All surgical plans with regard to the site and type of access were made based on the physical exam and ultrasound vein measurements taken prior to surgery . On the day of surgery patients were reevaluated with venous ultrasound using tourniquet before and after administration of the regional block . The previously determined operative plan either remained unchanged or was modified depending on the venous dilatation noted after administration of regional block . Among 26 patients , average vein diameter increased from 0.29 + /- 0.12 cm to 0.34 + /- 0.11 cm ( P = 0.008 ) . Twenty-one of 26 patients had no modification in operative plan ( group 1 ) . Five had some modification of the original operative plan ( group 2 ) : AV graft to a brachial vein transposition ( n = 2 ) , AV graft to a Cimino fistula ( n = 2 ) , and brachiocephalic to a Cimino ( n = 1 ) . The average follow-up for all patients was 82.6 + /- 75.6 days and did not differ between the groups . There was one failure in a patient from group 1 , and there was no significant difference in the patency rate between study groups ( P = 0.29 ) . Following regional nerve block , operative plans in patients undergoing AV access surgery were modified in 29.4 % of patients undergoing creation of an AV access for hemodialysis ; either from graft to fistula creation or from the proximal to more distal fistula site . The routine use of regional anesthesia as well as intraoperative ultrasound during AV access surgery can lead to improved site selection and increased opportunity for AV fistula creation The development of steal syndrome distal to an arteriovenous fistula ( AVF ) created for hemodialysis access remains a significant clinical problem . This study was undertaken to determine the role of intraoperative noninvasive testing in the prediction and management of steal syndrome following arteriovenous fistula creation . First , in order to determine a threshold digital/brachial index ( DBI ) for patients at risk for steal syndrome , we performed a retrospective review of patients who had had the DBI measured and who developed symptoms ( steal syndrome ) following AVF creation . This was followed by a prospect i ve evaluation of the ability of the DBI to predict which patients undergoing AVF surgery would develop steal syndrome . A DBI of < 0.6 identifies a patient at risk for steal syndrome . Intraoperative DBI can not be used to predict which patient will develop steal syndrome ; however , if revision is indicated , the DBI should be increased to > 0.6 . Failure to accomplish this puts the patient at risk for continued steal syndrome Background and Objectives . The present study was performed at the Crystal Clinic Surgery Center , an outpatient free-st and ing surgicenter specializing in orthopedic surgery , to determine the incidence of both neurologic and vascular sequelae associated with exclusive use of a transarterial approach to axillary brachial plexus block in order to assess the technique 's safety and efficacy . Methods . The prospect i ve consecutive study involved 1,000 adult patients scheduled for surgery using axillary brachial plexus block . The transarterial approach was performed on all patients using a medium-bevel 24-gauge Jelco 1 - 5-inch needle . Data tabulated included the incidence of neurovascular complications and the outcome of successful axillary brachial plexus anesthesia . Results . Two patients presented with a sensory paresthesia ( 0.2 % ) in the distribution of the ulnar nerve and the musculocutaneous nerve that most likely occurred during supplementation of an incomplete block . Three patients presented with upper-arm myalgias ( 0.3 % ) related to tourniquet injury . After the operation , two patients developed reflex sympathetic dystrophy , which responded to stellate ganglion blocks . Vascular complications , including transient arterial spasm in 10 of 996 ( 1 % ) , unintentional intravascular injection in 2 of 996 ( 0.2 % ) , and small ( 0 - 2 cm ) hematoma formation in 2 of 996 ( 0.2 % ) , were recognized but did not require any intervention other than close observation . The study revealed a complete block in 88.8 % of cases , an incomplete block requiring supplemental local anesthesia in 10 % of cases , and a complete block failure in 1.2 % . Conclusions . This study demonstrated the safety and efficacy of the transarterial technique in achieving brachial plexus block Background and objective Patients with end-stage chronic renal failure are at risk of developing several serious postanaesthetic complications . Many anaesthesiologists perform brachial plexus anaesthesia with high doses of local anaesthetic in order to achieve an extensive blockade of the upper limb . Brachial plexus block is a suitable technique for anaesthesia for creation , repair or removal of vascular access for haemodialysis . The aim of this study was to measure mepivacaine plasma concentrations after axillary block with 650 mg plain mepivacaine in patients with end-stage chronic renal failure . Methods Mepivacaine plasma concentrations were assessed throughout a 150-min period , in 10 patients after axillary block with 650 mg plain mepivacaine ( 600 mg for axillary block and 50 mg for supplementation ) . Results Mepivacaine plasma concentrations expressed in µg mL−1 as medians and their ranges were : 1.69 ( 1.23–7.78 ) at 5 min , 5.61 ( 4.36–8.19 ) at 30 min , 8.28 ( 3.83–11.21 ) at 60 min , 7.93 ( 5.63–11.1 ) at 90 min and 6.49 ( 5.56–8.35 ) at 150 min without any symptoms of toxicity . Conclusions Brachial plexus anaesthesia with 650 mg plain mepivacaine did not result in serious systemic toxicity in these patients despite the high mepivacaine plasma concentrations found We used color Doppler ultrasonography to prospect ively study the effects of supraclavicular brachial plexus block ( BPB ) on blood flow and vein diameter in patients undergoing arteriovenous access surgery . BPB might produce a sympathectomy-like effect that could have a role in improving patencty . Thirty-one consecutive patients who underwent arteriovenous access surgery with BPB were studied prospect ively , in addition to 5 patients with BPB having other operations and 5 patients undergoing general anesthesia for elective surgery . Vessel diameter and pulsatility index ( PI ) were among the parameters measured . Mean PI decreased from 6.18 + /- 1.67 before the block to 3.92 + /- 1.75 at 10 min after initiation of the block ( p = 0.001 ) . Basilic vein diameter increased from 6.28 + /- 0.86 mm ( range 4.85 to 7.30 ) before the block to 7.83 + /- 1.52 mm ( range 5.80 to 12.14 ) 10 min after the block ( p = 0.03 ) . In the general anesthesia control group the PI decreased , but returned to preanesthetic levels immediately after the patients reached the recovery room . In the nonaccess BPB group the PI remained low after the block for at least 5 h. Brachial plexus block causes significant venous dilation and a significant decrease in the pulsatility index . This appears to be due to a beneficial sympathectomy-like effect of the block that might prevent early failure and improve patency in vascular access surgery |
921 | 23,440,846 | We found little innovation in the behavioral interventions .
Since some of these studies were conducted , improvements in HIV treatment have influenced the fertility intentions of HIV-positive people . | BACKGROUND Contraception services can help meet the family planning goals of women living with HIV as well as prevent mother-to-child transmission .
Due to the increased availability of antiretroviral therapy , survival has improved for people living with HIV , and more HIV-positive women may desire to have a child or another child .
This review examines behavioral interventions to improve contraceptive use , for family planning , among women who are HIV-positive .
OBJECTIVES We systematic ally review ed studies that examined behavioral interventions for HIV-positive women that were intended to inform contraceptive choice , encourage contraceptive use , or promote adherence to a contraceptive regimen . | This study examined whether a culturally adapted version of a previously evaluated efficacious HIV prevention program reduced sexual risk behaviors of youth living with HIV ( YLH ) in Ug and a. YLH , 14 to 21 years , were r and omized to intervention ( N = 50 ) or control ( N = 50 ) conditions . Significantly more YLH in the intervention used condoms consistently and decreased their number of sexual partners in comparison to the control condition . Western interventions can be culturally adapted to retain efficacy in reducing the sexual risk behavior of YLH Background Long-acting reversible contraceptives ( LARCs ) and sterilisation are the most cost-effective methods of contraception but are rarely used in sub-Saharan Africa partly due to limited access . Study design HIV-positive pregnant women attending two urban clinics in Rw and a were followed prospect ively in a perinatal HIV transmission cohort study . Women attending one clinic were referred to public family planning ( FP ) services for all contraceptive methods ( Site A ) and women attending the other clinic ( Site B ) were offered implants and intrauterine devices ( IUDs ) on-site . Results Fifty three percent of the pregnant women reported an intention to use a LARC or to be sterilised after delivery . The uptake of implants was significantly higher at Site B ( 38 % ) than at Site A ( 6 % ) . The IUD uptake was extremely low at both sites ( 2 % ) . Twenty-eight of the 39 women at Site B who had intended to start using a LARC actually did so as compared to only one of 23 at Site A. Conclusion When access to LARC was provided , a substantial number of HIV-positive women started using hormonal implants , but not IUDs , in the postpartum period . HIV and FP services should consider improving access to implants to reduce the number of unintended pregnancies Objective : To evaluate a multipronged approach to promote dual contraceptive use by women within heterosexual HIV-1-serodiscordant partnerships . Methods : For 213 HIV-1-serodiscordant couples in Thika , Kenya , participating in an HIV-1 prevention clinical trial , contraceptive promotion was initiated through a multipronged intervention that included staff training , couples family planning sessions , and free provision of hormonal contraception on-site . Contraceptive use and pregnancy incidence were compared between two time periods ( before versus after June 2007 , when the intervention was initiated ) and between Thika and other Kenyan trial sites ( Eldoret , Kisumu , and Nairobi ) . Generalized estimating equations and And ersen – Gill proportional hazards modeling were used . Results : Nonbarrier contraceptive use increased after implementation of the intervention : from 31.5 to 64.7 % of visits among HIV-1-seropositive women [ odds ratio 4.0 , 95 % confidence interval ( CI ) 3.0–5.3 ] and from 28.6 to 46.7 % of visits among HIV-1-seronegative women ( odds ratio 2.2 , 95 % CI 1.4–3.5 ) . In comparison , at the other Kenyan sites , where the intervention was not implemented , contraceptive use changed minimally , from 15.6 to 22.3 % of visits for HIV-1-seropositive women and from 13.6 to 12.7 % among HIV-1-seronegative women . Self-reported condom use remained high during follow-up . Pregnancy incidence at the Thika was significantly lower after compared with before June 2007 ( hazard ratio 0.2 , 95 % CI 0.1–0.6 ) and was approximately half that at other Kenyan sites during the intervention period ( hazard ratio 0.5 , 95 % CI 0.3–0.8 ) . Conclusion : A multipronged family planning intervention can lead to high nonbarrier contraceptive uptake and reduced pregnancy incidence among women in HIV-1-serodiscordant partnerships 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 |
922 | 25,908,428 | Short-term results of the surgical treatment of people with AIS demonstrate the ability of surgery to improve various outcome measures .
MAIN RESULTS We did not identify any evidence comparing surgical to non-surgical interventions for AIS with severe curves of over 45 degrees . | BACKGROUND Adolescent idiopathic scoliosis ( AIS ) is a three-dimensional deformity of the spine .
While AIS can progress during growth and cause a surface deformity , it is usually not symptomatic .
However , if the final spinal curvature surpasses a certain critical threshold , the risk of health problems and curve progression is increased .
Interventions for the prevention of AIS progression include scoliosis-specific exercises , bracing , and surgery .
The main aims of all types of interventions are to correct the deformity and prevent further deterioration of the curve and to restore trunk asymmetry and balance , while minimising morbidity and pain , allowing return to full function .
Surgery is normally recommended for curvatures exceeding 40 to 50 degrees to stop curvature progression with a view to achieving better truncal balance and cosmesis .
However there is a clear paucity of information on long-term follow-up of surgical treatment of people with AIS .
OBJECTIVES To examine the impact of surgical versus non-surgical interventions in people with AIS who have severe curves of over 45 degrees , with a focus on trunk balance , progression of scoliosis , cosmetic issues , quality of life , disability , psychological issues , back pain , and adverse effects , at both the short term ( a few months ) and the long term ( over 20 years ) . | Study Design . A consecutive series of female patients with adolescent idiopathic scoliosis treated between 1968 and 1977 , either with distraction and fusion using Harrington rods ( n = 145 ) or with a brace ( n = 122 ) , were followed for at least 20 years after completion of the treatment . Objectives . To determine the long-term outcomes of childbearing and sexual life in women treated for adolescent idiopathic scoliosis , as compared with matched control subjects who did not have scoliosis . Summary of Background Data . The effect of pregnancy on curve progression is not established , and results are contradictory . Few reports exist on the social life ( marriage , childbearing , and sexual function ) of formerly treated individuals with scoliosis . Methods . In this study , 136 surgically treated women ( 94 % ) and 111 brace-treated women ( 91 % ) completed the Scoliosis Research Society (SRS)/MODEM ’s question naire concerning childbearing and sexual life as a part of an unbiased personal follow-up examination . Of these , 129 surgically treated and 105 brace-treated women also underwent a radiographic examination . The Cobb method was used to measure curve size in present and earlier examinations . An age-matched control group of 90 women was r and omly selected and subjected to the same examinations . Results . The mean age for all the groups was 40 years . Of the surgically treated and brace-treated women , 85 % were or had been married , as compared with 82 % of the control women . In the total cohort , 628 pregnancies had occurred . No significant mean difference existed between the groups in the number of children born ( 1.8 for the surgically treated , 1.9 for the brace-treated , and 2 for the control women ) ( P = 0.25 ) . The patients in the brace-treated group had a significantly higher mean age at first pregnancy ( 28 years ) than the control subjects ( 25.9 years ) ( P = 0.011 ) , whereas the age for the surgically treated women ( 26.6 years ) did not differ significantly from that for the brace-treated women . There were no significant differences between the groups in rates for low back pain ( 35 % for the surgically treated , 43 % for the brace-treated , and 28 % for the control group ) or for cesarean section ( 19 % for the surgically treated , 14 % for the brace-treated , and 18 % for the control group ) during the first pregnancy . The rate of vacuum extraction s was higher in the surgically treated group ( 16 % ) than in thecontrol group ( 5 % ) ( P = 0.036 ) or the brace-treated group(8 % ) . Limitation of sexual function from the back was admitted by 33 % of the surgically treated , 28 % of the brace-treated , and 15 % of the control women : surgically treated vs control subjects ( P = 0.0042 ) , brace-treated vs control subjects ( P = 0.026 ) , and brace-treated vs surgically treated subjects ( P = 0.57 , a nonsignificant difference ) . These limitations were largely because of difficulties participating physically in activities or self-consciousness about appearance . Pain was a minor reason for limitation . There was no correlation between progression of the major or lumbar curve and number of pregnancies , or between curve progression and age at first pregnancy . Conclusions . Patients treated for adolescent idiopathic scoliosis appeared to function well with regard to marital status and number of children . The scoliotic curve did not seem to increase as a result of childbearing . Minor problems occurred during pregnancy and delivery . Some patients , however , experienced a slight negative effect in their sexual life AIM Bracing is considered to be effective in the treatment of adolescent idiopathic scoliosis . The concept prevailing today includes an asymmetrical construction , mainly using a mechanical three-point system . We developed the new Sforzesco brace , based on the SPoRT concept ( Symmetric , Patient-oriented , Rigid , Three-dimensional , active ) . The aim of this study is to verify the results of this concept and brace , compared to three-point classical systems . METHODS We performed a prospect i ve , pair-controlled study . It was possible to match 15 patients , out of the first 18 consecutively treated with the Sforzesco brace ( Group SPoRT ) , with previous patients treated with the Lyon brace ( Group LY ) . SPoRT included 14.2+/-1.7 year old patients , with 47+/-7 degrees Cobb worst curves , and 11+/-4 degrees Bunnell ; LY included 13.6+/-1.6 year old patients , with 43+/-7 degrees Cobb and 12+/-5 degrees Bunnell . The brace had to be worn 23 h per day and patients were evaluated after 6 months both clinical ly and radiographically ( without the brace ) . Appropriate statistics were used . RESULTS At the baseline there were slight differences between the groups , with SPoRT worse than LY . All radiographic and clinical parameters decreased significantly with treatment in both groups , apart from thoracic Cobb degrees in LY . SPoRT had better results than LY ( P<0.05 ) radiographically ( worst curve -10+/-5 degrees vs -5+/-7 degrees , all curves -8+/-7 degrees vs -6+/-7 degrees ) , for sagittal profile ( distance from plumbline : T12 -6+/-9 mm vs + 2+/-8 and L3 -7+/-12 vs 0+/-10 ) and aesthetics of the shoulders ( 9 improved and 6 unchanged vs 5 and 8) and waists ( 10 improved and 5 unchanged vs 5 and 8) . Finally , clinical results in terms of patient recovery were better in SPoRT than LY ( 12 improved and 3 unchanged vs 8 and 5 ) . CONCLUSION When a new treatment is introduced , it is not possible to wait years ( end of therapy ) before verifying its utility , and in scoliosis bracing a short term study already gives very important clues . This study confirms the immediate efficacy of brace treatment ( even in such high degree cases ) whatever the brace concept used , with only 2 ( out of 30 ) progressed curves . In SPoRT we had no progressions , and obtained a statistically significant 80 % better radiographic results than LY in the worst scoliosis curve , and 40 % in the average of all curves , as well as improved aesthetics and sagittal profile ( that is crucial in scoliosis bracing ) . The Sforzesco brace should be used , and the SPoRT concept explored in the long term to verify if the classical three-point system should be totally ( or partially ) ab and oned Background Studies investigating the outcome of conservative scoliosis treatment differ widely with respect to the inclusion criteria used . This study has been performed to investigate the possibility to find useful inclusion criteria for future prospect i ve studies on physiotherapy ( PT ) . Material s and methods A PubMed search for outcome papers on PT was performed in order to detect study design s and inclusion criteria used . Results Real outcome papers ( start of treatment in immature sample s/end results after the end of growth ; controlled studies in adults with scoliosis with a follow-up of more than 5 years ) have not been found . Some papers investigated mid-term effects of exercises , most were retrospective , few prospect i ve and many included patient sample s with question able treatment indications . Conclusion There is no outcome paper on PT in scoliosis with a patient sample at risk for being progressive in adults or in adolescents followed from premenarchial status until skeletal maturity . However , papers on bracing are more frequently found and bracing can be regarded as evidence -based in the conservative management and rehabilitation of idiopathic scoliosis in adolescents Abstract . No results on long-term outcome in terms of health-related quality of life ( HRQL ) have previously been presented for patients treated for adolescent idiopathic scoliosis . A consecutive series of patients with adolescent idiopathic scoliosis , treated between 1968 and 1977 before the age of 21 , either with distraction and fusion using Harrington rods [ surgical treatment group ( ST ) , n=156 ; 145 females and 11 males ] or with a brace [ brace treatment group ( BT ) , n=127 ; 122 females and 5 males ] were followed at least 20 years after completion of the treatment . Ninety-four percent of ST and 91 % of BT patients filled in a question naire comprising the SF-36 , Psychological General Well-Being Index ( PGWB ) , Oswestry Disability Back Pain Question naire , parts of SRS/MODEM 'S question naire and study -specific questions concerning the treatment , as a part of an unbiased personal follow-up examination including radiography and clinical examination . An age- and sex-matched control group of 100 persons was r and omly selected and subjected to the same examinations . The results showed no differences in terms of sociodemographic data between the groups . Both ST and BT patients had a slightly , but significantly , reduced physical function using the SF-36 subscales , SF-36/Physical Component Summary ( PCS ) score as well as the Oswestry Disability Back Pain Question naire compared to the controls . Neither the mental subscales and the Mental Component Summary ( MCS ) score of SF-36 nor the PGWB index showed any significant difference between the groups . Forty-nine percent of ST , 34 % of BT and 15 % of controls admitted limitation of social activities due to their back [ P<0.001 ST vs controls , P=0.0010 BT vs controls , and n.s . ( P=0.024 ) ST vs BT ] , mostly due to difficulties with physical participation in activities or self-consciousness about appearance . Pain was a minor reason for limitation . No correlation was found between the outcome scores and curve size after treatment , curve type , total treatment time or age at completed treatment . Patients treated for adolescent idiopathic scoliosis were found to have approximately the same HRQL as the general population . A minority of the patients ( 4 % ) had a severely decreased psychological well-being , and a few ( 1.5 % ) were severely physically disabled due to the back Background Studies investigating the outcome of conservative scoliosis treatment differ widely with respect to the inclusion criteria used [ 1 ] . While the application of the SRS criteria for studies on bracing seem useful , there are no inclusion criteria for the investigation of physiotherapy alone . This study has been performed to investigate the possibility of useful inclusion criteria for future prospect i ve studies on physiotherapy ( PT ) BACKGROUND CONTEXT Evidence demonstrating the biomechanical effects of the Hueter-Volkmann principle on vertebral body growth in spinal deformities is lacking . Bracing a scoliotic curve should , in theory , unload the growth plates on the concave side of the vertebral bodies near the curve 's apex . Growth stimulation , leading to structural remodeling of the vertebral bodies , on the curve 's concave side may explain the improvement or lack of curve progression , as measured by Cobb angles , reported with successful brace management of adolescent idiopathic scoliosis ( AIS ) . PURPOSE To determine whether brace treatment stimulated asymmetric chondrogenesis in the apical three vertebral bodies . STUDY DESIGN A prospect i ve cohort of patients with AIS receiving brace treatment were followed from the initiation of brace treatment until skeletal maturity . Patients were then retrospectively divided into those with and without radiographic progression . This post hoc analysis was included to determine risk factors for curve progression . PATIENT SAMPLE Forty-one skeletally immature patients with AIS meeting criteria for brace treatment were followed until skeletal maturity . All patients were treated with thoracolumbosacral orthotics ( TLSOs ) . OUTCOME MEASURES The positional derotation of the TLSO on the spine was measured by comparing the initial radiograph with the first radiograph in a brace . The long-term structural changes of the vertebral bodies were determined by comparing the initial and final radiographs . Differences in initial radiographic parameters between the groups of patients with AIS with and without curve progression indicated predictive factors for successful brace treatment . METHODS Initial radiographic measurements were compared with those observed in a brace and those observed at final follow-up . The same analysis was retrospectively repeated comparing patients with AIS with and without radiographic progression . RESULTS Cobb measurements ( p=.0001 ) and concave-to-convex height ratios of the apical three vertebral bodies improved when the brace was initially applied ( p=.0035 ) . Structural remodeling or a rotational correction of the apical three vertebral bodies was appreciated only in patients with flexible curves ( p=.01 ) . CONCLUSION Brace application results in immediate positional derotations of the spine in patients with AIS . These positional derotations were maintained only in patients with flexible curves , at final follow-up . Brace treatment was not recommended in patients whose curves did not correct at least 20 % in a TLSO A prospect i ve study was carried out of the incidence and natural history of adolescent idiopathic scoliosis in 26,947 students . Data were obtained on 1,122 students with idiopathic scoliosis . The incidence of idiopathic scoliosis was 4.5 per cent . The female-to-male ratio was 1.25:1.0 over-all , but the ratio varied directly with the severity of the curve -- that is , 1:1 for curves of 6 to 10 degrees , and 5.4:1 for curves of more than 20 degrees . Progression of the curve was determined by a two-year follow-up of 603 patients . Progression was observed in 6.8 per cent of the students and in 15.4 per cent of the skeletally immature girls with scoliosis of more than 10 degrees at the initial examination . In 20 per cent of the skeletally immature children with curves of 20 degrees at the initial examination , there was no progression . Spontaneous improvement of the curve occurred in 3 per cent and was seen more frequently in curves milder than 11 degrees . Treatment was required in 2.75 students per 1,000 screened Background The effectiveness of orthotic treatment continues to be controversial in international medical literature due to differences in the reported results and conclusions of various studies . Heterogeneity of the sample s has been suggested as a reason for conflicting results . Besides the obvious theoretical differences between the brace concepts , the variability in the technical factors can also explain the contradictory results between same brace types . This paper will investigate the degree of variability among responses of scoliosis specialists from the Brace Study Ground of the International Society on Scoliosis Orthopedic and Rehabilitation Treatment SOSORT . Ultimately , this information could be a foundation for establishing a consensus and framework for future prospect i ve controlled studies . Methods A preliminary question naire on the topic of ' brace action ' relative to the theory of three-dimensional scoliosis correction and brace treatment was developed and circulated to specialists interested in the conservative treatment of adolescent idiopathic scoliosis . A particular case was presented ( main thoracic curve with minor lumbar ) . Several key points emerged and were used to develop a second question naire which was discussed and full filed after the SOSORT consensus meeting ( Milano , Italy , January 2005 ) . Results Twenty-one question naires were completed . The Chêneau brace was the most frequently recommended . The importance of the three point system mechanism was stressed . Options about proper pad placement on the thoracic convexity were divided 50 % for the pad reaching or involving the apical vertebra and 50 % for the pad acting caudal to the apical vertebra . There was agreement about the direction of the vector force , 85 % selecting a ' dorso lateral to ventro medial ' direction but about the shape of the pad to produce such a force . Principles related to three-dimensional correction achieved high consensus ( 80%–85 % ) , but suggested methods of correction were quite diverse . Conclusion This study reveals that among participating SOSORT specialists there continues to be a strongly held and conflicting if not a contentious opinion regarding brace design and treatment . If the goal of a ' treatment consensus ' is realistic and achievable , significantly more effort will be required to reconcile these differences OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity Study Design . A Cochrane systematic review . Objective . To evaluate the efficacy of bracing for adolescents with AIS versus no treatment or other treatments , on quality of life , disability , pulmonary disorders , progression of the curve , psychological , and cosmetic issues . Summary of Background Data . Idiopathic scoliosis is a three-dimensional deformity of the spine . The most common form is diagnosed in adolescence . Although adolescent idiopathic scoliosis ( AIS ) can progress during growth and cause a surface deformity , it is usually not symptomatic . Methods . We search ed CENTRAL , MEDLINE , EMBASE , five other data bases , and two trials registers up to February 2015 . We also checked reference lists and h and search ed grey literature . R and omized controlled trials ( RCTs ) and prospect i ve controlled cohort studies comparing braces with no treatment , other treatment , surgery , and different types of braces for adolescent with AIS . We used st and ard method ological procedures expected by the Cochrane Collaboration . Results . We included seven studies . Five were planned as RCTs , two as prospect i ve controlled clinical trials . One RCT failed completely , another was continued as an observational study . There was very low quality evidence from one small RCT that quality of life ( QoL ) during treatment did not differ significantly between rigid bracing and observation . Conclusion . Two studies showed that bracing did not change QoL during treatment , and QoL , back pain psychological and cosmetic issues in the long term ( 16 years . ) All articles showed that bracing prevented curve progression . The high rate of failure of RCTs demonstrates the huge difficulties in performing RCTs in a field where parents reject r and omization of their children . Level of Evidence : Study Design . A consecutive series of patients with adolescent idiopathic scoliosis ( AIS ) , treated between 1968 and 1977 before 21 years of age with either distraction and fusion using Harrington rods ( ST , n = 156 ; 145 females and 11 males ) or with brace ( BT , n = 127 ; 122 females and 5 males ) , were followed at least 20 years after completion of the treatment . Objectives . To determine the long-term outcome in terms of spinal mobility and muscle strength and its possible correlations to present back pain and function in patients surgically or brace treated for AIS . Summary of Background Data . Few reports on long-term outcome on these variables have previously been presented for this group of patients . Methods . A total of 135 ( 87 % ) of ST and 102 ( 80 % ) of BT patients underwent a complete examination by two unbiased observers incl . evaluation of lumbar muscle endurance and spinal mobility , curve size ( Cobb method ) , vali date d question naires in terms of general and disease-specific quality of life aspects , as well as present back function and pain . An age- and sex-matched control group of 100 persons was r and omly selected and subjected to the same examinations . Results . For both ST and BT groups , lumbar spinal motion as well as muscle endurance were significantly decreased compared with controls . For ST patients , better lumbar extensor and flexor muscle endurance or lumbar spinal mobility correlated with a better physical function . The length of fusion into the lumbar spine correlated inversely with lumbar range of motion , but the finger-floor distance was not affected . BT patients with reduced lumbar spinal mobility experienced lumbar back pain more often than controls . Conclusions . For both brace treated and surgically treated AIS patients , spinal mobility and muscle endurance were reduced more than 20 years after completed treatment . The physical function was not severely restricted STUDY DESIGN A group of 102 brace-treated adolescents , aged 10 - 19 years with spine deformities participated in a cross-sectional study . OBJECTIVES To determine the effect of various types of orthoses on self-perceived health status . SUMMARY OF BACKGROUND DATA Spinal orthosis is an effective means of controlling progressive scoliosis , but bracing has shown a considerable impact on several aspects of adolescent functioning . METHODS Skeletally immature patients with spine deformities ( 75 % with idiopathic scoliosis ) who visited consecutively for routine biannual follow-up evaluations of orthotic treatment were studied . Twenty-five patients used the Milwaukee brace , 30 the Boston brace , 13 the thoracolumbosacral orthosis ( TLSO ) , and 34 the Charleston bending orthosis . Patients completed the Quality of Life Profile for Spine Deformities ( QLPSD ) , a specific instrument that measures quality of life in five areas labeled psychosocial functioning , sleep disturbances , back pain , body image , and back flexibility . Higher QLPSD scores mean a high level of impairment of quality of life . RESULTS Milwaukee brace-treated patients scored significantly higher than Boston brace-treated and TLSO-braced patients and patients with Charleston bending orthosis in the overall QLPSD score ( mean + /- SD , 53.60 + /- 13.26 vs. 45.65 + /- 12.81 and 42.79 + /- 12.99 , respectively ) and in back flexibility and psychosocial functioning . Other quality -of-life-related variables selected in multivariate analysis were the Risser sign , clinical diagnosis , duration of brace treatment , and degrees of correction . CONCLUSION In cases of different orthoses of proven similar effectiveness in controlling the scoliotic curves , the use of bracing with the lowest impact on the quality of life should be recommended Study Design . Prospect i ve , sequential enrollment . Objective . We report the development and testing of the Spinal Appearance Question naire ( SAQ ) for reliability , validity , and responsiveness in patients with idiopathic scoliosis . Summary of Background Data . The SAQ was design ed to measure patients ’ and their parents ’ perception of their spinal deformity ’s appearance using st and ardized drawings and questions . This study was design ed to test the instrument ’s psychometric properties . Methods . The SAQ was administered as a test-retest to idiopathic scoliosis patients and parents for reliability and initial validity assessment ( Group I ) . It was then administered to patients before surgery and 1 year after surgery ( Group II ) for responsiveness and further validity testing . Finally , both the SAQ and SRS instruments were administered to adolescent idiopathic patients before surgery and 1 year after surgery ( Group III ) for comparison of the 2 instruments . Results . Group I : The individual scale items had good to excellent reliability ( Spearman ’s rho , 0.57–0.99 ) and high internal scale consistency ( Cronbach ’s alpha > 0.7 ) . The mean scale scores differentiated between curves greater than 30 ° and lesser curves ( P < 0.01 ) . Surgery improved scores compared with those with “ surgery recommended . ” Group II : The domains correlated with clinical and radiographic aspects of the deformity before surgery . All of the domains showed significant difference after surgery ( P < 0.0001 ) and large effect size for all domains except for the patient chest domain . Group III : Both the SAQ and the SRS instruments had significant improvement in all of their domains except for the SRS Activity scale . The relative efficiency of the SAQ domains to the SRS appearance domain ( the most responsive SRS domain ) was greater for 5 SAQ domains . Conclusion . The SAQ is reliable , responsive to curve improvement , and shows strong evidence of validity . It provides more detail than the SRS in the appearance domain , and provides explanation of spinal deformity ’s concerns and improvements STUDY DESIGN This study is a follow-up investigation for a consecutive series of patients with adolescent idiopathic scoliosis treated between 1968 and 1977 . In this series , 156 patients underwent surgery with distraction and fusion using Harrington rods , and 127 were treated with brace . OBJECTIVES To determine the long-term outcome in terms of radiologic findings and curve progression at least 20 years after completion of the treatment . SUMMARY OF BACKGROUND DATA Radiologic appearance is important in comparing the outcome of different treatment options and in evaluating clinical results . Earlier studies have shown a slight increase of the Cobb angle in brace-treated patients with time , but not in fused patients . METHODS Of 283 patients , 252 attended a clinical and radiologic follow-up assessment by an unbiased observer ( 91 % of the surgically treated and 87 % of the brace-treated patients ) . This evaluation included chart review s , vali date d question naires , clinical examination , and full-length st and ing frontal and lateral roentgenographs . Curve size was measured by the Cobb method on anteroposterior roentgenograms as well as by sagittal contour and balance on lateral films . The occurrence of any degenerative changes or other complications was noted . An age- and gender-matched control group of 100 individuals was r and omly selected and subjected to the same examinations . RESULTS The mean follow-up times were 23 years for surgically treated group and 22 years for brace-treated group . The deterioration of the curves was 3.5 degrees for all the surgically treated curves and 7.9 degrees for all the brace-treated curves ( P < 0.001 ) . Five patients , all brace-treated , had a curve increase of 20 degrees or more . The overall complication rate after surgery was low : Pseudarthrosis occurred in three patients , and flat back syndrome developed in four patients . Eight of the patients treated with fusion ( 5.1 % ) had undergone some additional curve-related surgical procedure . The lumbar lordosis was less in the surgically treated than in the brace-treated patients or the control group ( mean , 33 degrees vs 45 degrees and 44 degrees , respectively ) . Both surgically treated and brace-treated patients had more degenerative disc changes than the control participants ( P < 0.001 ) , but no significant differences were found between the scoliosis groups . No statistically significant difference in terms of radiographically detectable degenerative changes in the unfused lumbar discs was found between patients fused below L3 or those fused to L3 and above ( P = 0.22 ) . A study on intra- and interobserver measurements of kyphosis , lordosis , and sagittal vertical axis on two films for each patient demonstrated that the repeatability of measuring sagittal plumbline on two different lateral radiographs , with patients moving between radiograms , was unreliable for comparison . CONCLUSIONS Although more than 20 years had passed since completion of the treatment , most of the curves did not increase . The surgical complication rate was low . Degenerative disc changes were more common in both patient groups than in the control group STUDY DESIGN This was a prospect i ve study of two cohort groups of patients ( one group receiving anterior instrumentation and the other posterior instrumentation ) receiving treatment for thoracic idiopathic scoliosis . OBJECTIVE To present the 2-year postoperative results of a prospect i ve multicenter study comparing the use of anterior instrumentation with that of posterior multisegmented hook instrumentation for the correction of adolescent thoracic idiopathic scoliosis . SUMMARY OF BACKGROUND DATA Despite reports of satisfactory results , problems have been reported with posterior systems , including worsening of the lumbar curve after surgery and failure to correct hypokyphosis . Theoretically , the advantages of anterior instrumentation include prevention of lumbar curve decompensation by shortening the convexity of the thoracic curve . In addition , by removing the disc , better correction of thoracic hypokyphosis could be obtained . METHODS Seventy-eight patients who underwent an anterior spinal fusion using flexible threaded rods and nuts ( Harms-MOSS instrumentation , De Puy-Motech-Acromed , Clevel and , OH ) were analyzed and compared with 100 patients who underwent posterior spinal fusion with multisegmented hook systems . Parameters of comparison included coronal and sagittal correction , balance , distal lumbar fusion levels , and complication . All patients had idiopathic thoracic curves of King Types II to V. The average age at surgery was 14 years in each group , the average preoperative curve 57 degrees , and the minimum duration of follow-up for all patients 24 months . All data were collected prospect ively and analyzed via Epl into statistical analysis ( Centers of Disease Control , Atlanta , GA ) . RESULTS Average coronal correction of the main thoracic curve was 58 % in the anterior group and 59 % in the posterior group ( P = 0.92 ) . Analysis of sagittal contour showed that the posterior systems failed to correct a preoperative hypokyphosis ( sagittal T5 to T12 less than 20 degrees ) in 60 % of cases , whereas 81 % were normal postoperatively in the anterior group . However , hyperkyphosis ( sagittal T5 to T12 greater than 40 degrees ) occurred after surgery in 40 % of the anterior group when the preoperative kyphosis was greater than 20 degrees . Postoperative coronal balance was equal in both groups . An average of 2.5 ( range , 0 - 6 ) distal fusion levels were saved using the anterior spinal instrumentation according to the criteria used for determining posterior fusion levels in this study . Selective fusion of the thoracic curve ( distal fusion level T11 , T12 , L1 ) was performed in 76 of 78 patients ( 97 % ) in the anterior group as compared with only 18 of 100 ( 18 % ) in the posterior group . Surgically confirmed pseudarthrosis occurred in 4 of 78 patients ( 5 % ) in the anterior group and in 1 of 100 patients ( 1 % ) in the posterior group ( P = 0.10 ) . Loss of correction greater than 10 degrees occurred in 18 of 78 patients ( 23 % ) in the anterior group and in 12 of 100 patients ( 12 % ) in the posterior group ( P = 0.01 ) . Implant breakage occurred in 24 patients ( 31 % ) of the anterior group and in only 1 patient ( 1 % ) of the posterior group . CONCLUSIONS 1 ) Coronal correction and balance were equal in both the anterior and posterior groups , even though the anterior group had the majority of curves ( 97 % ) fused short or to L1 , whereas only 18 % were fused short or to L1 in the posterior group . 2 ) In the anterior group there was a better correction of sagittal profile in those with a preoperative hypokyphosis less than 20 degrees . However , hyperkyphosis ( with a mean of 54 degrees ) occurred in 40 % of those in the anterior group with a preoperative kyphosis of more than 20 degrees . 3 ) An average of 2.5 lumbar levels can be saved with anterior fusion and instrumentation according to the criteria used for choosing posterior fusion levels in this study . 4 ) Using the 3.2-mm flexible rod in this study , loss of correction , pseudarthrosis , and rod breakage were unacceptably Ventral derotation spondylodesis , according to Zielke , achieves good results in operative treatment of idiopathic thoracic scolioses . Corrections of scoliotic major and secondary curve as well as derotation of the spine are reliably performed . The high rate of rod fractures with subsequent correction loss as well as a proportionate kyphogenic effect represents a problem . By keeping to the correcting principle , anterior double-rod instrumentation ( Halm-Zielke Instrumentation ) is to be stable in a similar way as posterior double-rod systems . Thus , it is done to facilitate brace-free postoperative care and to prevent excessive kyphotic pattern of the spine . In this prospect i ve study , we retrospectively collected data . We performed radiological follow-up of two groups of patients with idiopathic thoracic scoliosis ( King II , III and IV ) undergoing an operation with posterior approach ( USS instrumentation , posterior group , n=104 ) in 1997 and 1998 or being corrected with an anterior fusion ( Halm-Zielke instrumentation , anterior group , n=37 ) between 2000 and 2001 . Mean age of all patients for operation was 15±4 years . Follow-up was performed after 4±2 years on average . Preoperative measurements of the major and secondary curve , the lateral profile , rotation and frontal balance ( C7 to S1 ) did not show any significant differences apart from a more severe scoliotic curve in the lumbar spine for the anterior group with appropriately higher lumbar rotation . During follow-up we noticed similar corrections of the thoracic major and lumbar curve in both groups ranging from 49 to 56 % . In case of hypokyphotic ( T4–T12≤20 ° ) scoliosis a kyphogenic effect on the thoracic spine was achieved with both surgical methods . Hyperkyphotic ( T4–T12≥40 ° ) scolioses were flattened by posterior spinal fusion ; the effect of anterior spinal fusion was not significant . Correction of thoracic and lumbar rotation in the anterior group by 37 or 30 % was more significant than in the posterior group by 27 or 20 % . There was no impact of anterior technique on the balance of the spine whereas the latter shifted by an average of 7 mm to the left in the posterior group . The number of fused segments was significantly smaller in the anterior group with 7±1 vertebral bodies ( posterior , 11±1 vertebral bodies ) . Rates of complication were identical with 11 or 12 % in both groups during follow-up . Anterior and posterior double-rod instrumentations result in comparable corrections for idiopathic thoracic scoliosis of the major and secondary curve . In case of posterior technique , however , four vertebral bodies less were integrated in spondylodesis on average . Balance of the spine did not change after anterior spondylodesis ; however , it declined by using the posterior technique . Augmentation of the anterior threaded rod combined with a solid second rod significantly decreases the rate of implant breakages and reliably reduces consecutive correction losses Study Design . A multicenter study of the outcomes of the surgical treatment of adolescent idiopathic scoliosis using the Scoliosis Research Society Question naire ( SRS 24 ) . Objective . To evaluate the patient based outcome of the surgical treatment of adolescent idiopathic scoliosis . Summary of Background Data . A paucity of information exists with respect to patient measures of outcome regarding the surgical treatment of adolescent idiopathic scoliosis . To our knowledge , no prospect i ve outcome study on this topic thus far exists . Methods . Using the SRS 24 question naire , seven scoliosis centers agreed to prospect ively assess outcome for surgically treated patients with adolescent idiopathic scoliosis . Data were collected before surgery and at 24 months after surgery . Data were analyzed using paired and independent sample s t test for all seven SRS 24 question naire domains ( Pain , General Self-Image , Postoperative Self-Image , Postoperative Function , Function From Back Condition , General Level of Activity , and Satisfaction ) using Statistical Package for Social Science . The domains were analyzed with respect to the total cohort , gender , curve magnitude , and type of surgery using independent- sample s t tests . Results . A total of 242 patients were included in our analysis . A baseline preoperative pain level of 3.68 of 5 was found . This improved to 4.63 after surgery , representing an improvement of 0.95 points . Surgical intervention was associated with improving outcome when compared with preoperative status . Pain , General Self-Image , Function From Back Condition , and Level of Activity all demonstrated statistically significant improvement as compared with preoperative status ( P < 0 . 001 ) . Overall , patients were highly satisfied with the results of surgery . Conclusion . Preoperative pain exists in our adolescent scoliosis population . Pain scores were improved in our study population at the 2-year postsurgical follow-up . Statistically significant improvements were likewise seen in the General Self-Image , Function From Back Condition , and Level of Activity domains . The present study demonstrates the ability of surgery to improve the outcome of patients afflicted with adolescent idiopathic scoliosis STUDY DESIGN A consecutive series of patients with adolescent idiopathic scoliosis and brace-treated ( BT ) between 1968 and 1977 before age 21 years ( BT : n = 127 ; 122 females and 5 males ) were followed-up at least 20 years after completion of the treatment . OBJECTIVES To determine the long-term outcome in terms of back pain and function in patients BT for adolescent idiopathic scoliosis . SUMMARY OF BACKGROUND DATA Few reports on long-term outcome of back pain and function have previously been presented for consecutive groups of these patients . MATERIAL S AND METHODS One hundred ten ( 87 % ) BT patients were reexamined as part of an unbiased personal follow-up . This included a clinical examination , evaluation of curve size ( Cobb method ) , and degenerative findings in full st and ing frontal and lateral radiographs . Vali date d question naires in terms of general and disease-specific quality -of-life aspects as well as present back and pain symptoms were used . One hundred nine had complete follow-up . An age- and sex-matched control group of 100 persons was r and omly selected and subjected to the same examinations . RESULTS The deterioration of the curves was a mean of 7.9 degrees for all curves , excluding the only patient who underwent operation after 4 years ( increase = 27 degrees ) . The patients had significantly more degenerative disc changes than the controls . Lumbar and thoracic back pain , although mild ( 2.7 on visual analogue scale ) , was significantly more frequent among the patients than the controls ( 75 vs. 47 % , P = 0.0050 and 35.8 vs. 22.0 % , P = 0.033 , respectively ) . Only 24 % of the patients admitted daily pain and analgesics were sparsely used . The patients had a slightly , but significantly , worse back function as measured by the Oswestry Disability Index ( 9.2 vs. 4.8 , P = 0.0012 ) and general function score ( 7.7 vs. 4.2 , P = 0.0006 ) , but general health-related quality of life was not affected . No differences could be seen in sociodemographic variables between the groups , except for having ever been on sick leave because of the back ( 38 % vs. 19 % , P = 0.0036 ) . Furthermore , no differences could be found between patients with different curve types ( single thoracic , n = 50 ; lumbar , n = 19 ; double curves , n = 40 ) . No correlation could be found between pain and its localization and curve size , an increase of at least 10 degrees since end of treatment , curve type , degenerative changes on any of the two lowest lumbar disc levels , body mass index , or smoking . CONCLUSIONS More than 20 years after brace treatment for AIS , minimal pain and no dysfunction occurred compared with normal controls . Compared with surgically treated patients with a mean end result similar to this group , no significant differences were found except that BT patients experience more affective components of their pain |
923 | 17,897,515 | With GEE modelling , the reporting quality had a strong association with trial size , publication year , trial location and funding source , but not with the results and type of primary outcome . | OBJECTIVE Several studies have shown that the quality of reports of r and omized controlled trials ( RCTs ) in medicine is variable and often poor , whereas the quality of those in surgery is unknown .
We aim ed to assess the quality of reports of RCTs in coronary artery bypass grafting ( CABG ) surgery when comparing off- and on-pump techniques . | OBJECTIVES Cardiopulmonary bypass ( CPB ) is widely regarded as an important contributor to renal failure , a well recognized complication following coronary artery surgery ( coronary artery bypass grafting ( CABG ) ) . Anecdotally off-pump coronary surgery ( OPCAB ) is considered renoprotective . We examine the extent of renal glomerular and tubular injury in low-risk patients undergoing either OPCAB or on-pump coronary artery bypass ( ONCAB ) . METHODS Forty low-risk patients with normal preoperative cardiac and renal functions awaiting elective CABG were prospect ively r and omized into those undergoing OPCAB ( n=20 ) and ONCAB ( n=20 ) . Glomerular and tubular injury were measured respectively by urinary excretion of microalbumin and retinol binding protein ( RBP ) indexed to creatinine ( Cr ) . Daily measurements were taken from admission to postoperative day 5 . Fluid balance , serum Cr and blood urea were also monitored . RESULTS No mortality or renal complication were observed . Both groups had similar demographic makeup , Parsonnet score , functional status and extent of coronary revascularization ( 2.1+/-1.0 vs. 2.5+/-0.7 grafts ; P=0.08 ) . Serum Cr and blood urea remained normal in both groups throughout the study . A significant and similar rise in urinary RBP : Cr occurred in both groups peaking on day 1 ( 3183+/-2534 vs. 4035+/-4079 ; P=0.43 ) before reapproximating baseline levels . These trends were also observed with urinary microalbumin : Cr ( 5.05+/-2.66 vs. 6.77+/-5.76 ; P=0.22 ) . Group B patients had a significantly more negative fluid balance on postoperative day 2 ( -183+/-1118 vs. 637+/-847 ml ; P=0.03 ) . CONCLUSIONS Although renal complication or serum markers of kidney dysfunction were absent , sensitive indicators revealed significant and similar injury to renal tubules and glomeruli following either OPCAB or ONCAB . These results suggest that avoidance of CPB does not offer additional renoprotection to patients at low risk of perioperative renal insult during CABG BACKGROUND Pulmonary dysfunction is still a major problem in coronary artery bypass grafting ( CABG ) . The purpose of this r and omized study was to determine the effect of different CABG techniques on pulmonary function . METHODS Fifty eight patients with severe obstructive pulmonary disease had elective isolated coronary surgery . The surgical methods for the patients with chronic obstructive pulmonary disease ( COPD ) were st and ard CABG in 18 patients ( group 1 ) , beating heart surgery in 19 patients ( group 2 ) , and minimally invasive direct coronary artery bypass grafting ( MIDCABG ) in 21 patients ( group 3 ) . RESULTS The earliest extubation time was from group 3 ( p < 0.001 ) . The average stay in the intensive care unit was significantly longer in group 1 ( 2.6 + /- 1.5 days ) than in groups 2 ( 1.4 + /- 0.8 days ) and 3 ( 1.1 + /- 0.8 days ) ( p < 0.05 ) . The most prevalent respiratory morbidity was atelectasis that developed in 6 patients from group 1 , in 2 patients from group 2 , and in 3 patients from group 3 . Forced expiratory volumes in 1 second ( FEV1 ) obtained in the second postoperative month were significantly lower than preoperative values only in group 1 ( p < 0.05 ) . Forced vital capacity ( FVC ) values were significantly lower than the preoperative values in all three groups ( p < 0.05 ) . CONCLUSIONS Off-pump bypass surgical procedures are more advantageous than on-pump methods for patients with COPD . These patients can be operated on using the beating heart technique or by using MIDCABG to prevent side effects of CPB on pulmonary function and effects of sternotomy BACKGROUND Coronary artery bypass surgery with cardiopulmonary bypass carries a significant risk of perioperative brain injury . At least 1 % to 5 % will suffer a stroke , and at 3-months postoperatively approximately 30 % are reported to have cognitive impairment assessed by neuropsychologic testing . In off-pump surgery cardiopulmonary bypass is not used and instrumentation on the ascending aorta is reduced . The main aim of this study was to assess if off-pump surgery reduces intraoperative cerebral embolization . METHODS This was a prospect i ve and r and omized study of two comparable groups with regard to age , sex , years of education , preoperative cognitive functioning , and surgical characteristics . Fifty-two patients ( 29 off-pump ) were monitored by the use of transcranial Doppler ultrasound for cerebral microembolization during surgery . Preoperative and postoperative clinical , cerebral magnetic resonance imaging , and neuropsychologic examinations were also carried out . RESULTS There was a significant reduction in the number of cerebral microemboli during off-pump compared with on-pump surgery ( 16.3 [ range 0 to 131 ] versus 90.0 [ range 15 to 274 ] , p < 0.0001 ) . No significant difference with regard to the incidence of neuropsychologic performance ( decline in 29 % off-pump , 35 % on-pump ) or neuroradiologic findings at 3 months was found , and there was no association between the number of cerebral microemboli and cognitive outcome . CONCLUSIONS This study clearly demonstrates that off-pump surgery leads to a reduction in intraoperative cerebral microembolization . A significant reduction in the number of off-pump patients with cognitive decline or ischemic brain lesions on cerebral magnetic resonance imaging could not be demonstrated in this relatively small patient population BACKGROUND Although no r and omised controlled trial has assessed the midterm effects of coronary-artery bypass surgery on the beating heart , this technique is being used in more and more patients . We did two r and omised trials to compare the short-term morbidity associated with off-pump and on-pump myocardial revascularisation . Our aim was to pool the results to assess midterm outcomes . METHODS From March , 1997 , to November , 1999 , we r and omly allocated 200 patients to off-pump and 201 to on-pump coronary surgery . In Beating Heart Against Cardioplegic Arrest Study ( BHACAS ) 1 , we excluded patients who had had myocardial infa rct ion in the past month or who required grafting of the circumflex artery distal to the first obtuse marginal branch . In BHACAS 2 , we included such patients . Primary outcomes were all-cause mortality and cardiac-related events at midterm follow-up ( 1 - 3 years ) . Analysis was by intention to treat . FINDINGS Analyses of combined data from both trials showed the following risk differences with off-pump compared with on-pump surgery : atrial fibrillation -25 % ( 95 % CI -33 % to -16 % ) ; chest infection -12 % ( -19 % to -5 % ) ; inotropic requirement -18 % ( -25 % to -10 % ) ; transfusion of red blood cells -31 % ( -41 to -21 ) ; and hospital stay longer than 7 days -13 % ( -21 to -5 ) . Mean follow-up was 25 0 months ( SD 9.1 ) for BHACAS 1 and 13.7 months ( 5 5 ) for BHACAS 2 . Four ( 2 % ) of 200 patients in the off-pump groups died from any cause , compared with seven ( 3 % ) of 201 in the on-pump group ( hazard ratio 0.57 , 95 % CI 0.17 - 1.96 ) . 33 ( 17 % ) of 200 patients in the off-pump group died or had a cardiac-related event , compared with 42 ( 21 % ) of 201 in the on-pump group ( 0.78 , 0 49 - 1.22 ) . INTERPRETATION Off-pump coronary surgery significantly lowers in-hospital morbidity without compromising outcome in the first 1 - 3 years after surgery compared with conventional on-pump coronary surgery BACKGROUND We investigated whether off-pump coronary artery bypass ( OPCAB ) surgery should be the procedure of choice in total arterial myocardial revascularization with composite grafts . METHODS We prospect ively enrolled 176 patients undergoing total arterial myocardial revascularization and assigned them at r and om to one of two groups : group 1 was composed of 88 patients undergoing coronary surgery with cardiopulmonary bypass ( CPB ) ; group 2 consisted of 88 patients receiving the OPCAB procedure . We excluded from this study patients with significant risk factors for CPB-related morbidity . Composite arterial grafts in Y-T shape were realized in three different configurations according to patients ' characteristics , coronary anatomy , and target stenosis . RESULTS There were no significant differences between the two groups in terms of preoperative characteristics and risk factors ( Euroscore : group 1 = 6.1 + /- 3.5 , group 2 = 6.6 + /- 3.8 ) . Mean number of anastomoses was similar in both groups ( group 1 = 2.8 + /- 0.8 , group 2 = 2.7 + /- 0.5 ) whereas mean mechanical ventilation time ( group 1 = 23 + /- 9 hours , group 2 = 9 + /- 4 hours ) , intensive care unit stay ( group 1 = 43 + /- 6 hours , group 2 = 22 + /- 8 hours ) , and postoperative stay ( group 1 = 7 + /- 3 days , group 2 = 5 + /- 2 days ) were significantly reduced in group 2 . Early mortality was 2.3 % in group 1 and 3.4 % in group 2 ( p = not significant ) . Major postoperative complications occurred similarly in the two groups ( atrial fibrillation : group 1 = 35.2 % , group 2 = 21.6 % ; myocardial infa rct ion : group 1 = 2.2 % , group 2 = 1.1 % ; stroke : group 1 = 2.2 % , group 2 = 0 % ; abdominal infa rct ion : group 1 = 3.4 % , group 2 = 0 % ) . At follow-up ( mean , 15 + /- 12 months ) no significant differences were observed in terms of survival free of any cardiac-related event ( group 1 = 94.3 % , group 2 = 96.5 % ; p = not significant ) . CONCLUSIONS Off-pump coronary artery surgery could be successfully used for total arterial grafting without compromising the completeness of revascularization . Avoidance of CPB significantly decreased mechanical ventilation support and length of intensive care unit and postoperative stay ; however in the absence of risk factors for cardiopulmonary bypass , off-pump coronary artery surgery did not improve early and midterm clinical outcome BACKGROUND The interpretation of the results of r and omized controlled trials ( RCTs ) has traditionally emphasized statistical significance rather than clinical importance . Our aim was to assess the quality of reporting of factors related to clinical importance in a sample of published RCTs . METHODS A r and om sample of 27 ( of a total of 266 ) RCTs published in 5 major medical journals over a 1-year period were review ed by 4 independent review ers for factors considered important in the interpretation of the clinical importance of study results : identification of a clearly defined primary outcome , reporting of the expected difference between groups used in the calculation of sample size ( the delta value ) and whether it was based on the minimal clinical ly important difference of the intervention , the statistical significance of the results , presentation of pertinent confidence intervals , and the authors ' interpretation of the clinical importance of the results . RESULTS Twenty-two of 27 ( 81 % ) articles explicitly reported a single primary outcome . Of the 20 articles that included a sample size calculation , 18 ( 90 % ) reported a delta value . Two of the 18 ( 11 % ) articles explicitly stated that the delta value was chosen to reflect the minimal clinical ly important difference of the intervention . For the primary outcomes , confidence intervals surrounding the point estimates of the efficacy of the interventions were reported in 11 of 27 ( 41 % ) studies . The study results were interpreted from the perspective of clinical importance in 20 of 27 ( 74 % ) of the articles . Of these 20 reports , 5 ( 25 % ) provided justification for their clinical interpretation of the results . INTERPRETATION Authors of RCTs published in major general medical and internal medicine journals do not consistently provide their own interpretation of the clinical importance of their results , and they often do not provide sufficient information to allow readers to make their own interpretation BACKGROUND There is increased interest in coronary artery bypass grafting ( CABG ) without cardiopulmonary bypass ( CPB ) , although the preservation of the myocardium under such circumstances has not been properly investigated . The aim of this r and omized study was to compare the changes in myocardial metabolism during CABG with and without CPB . METHODS Myocardial energy metabolism and tissue injury during CABG was monitored in a series of 22 patients ( 11 with and 11 without CPB ) . RESULTS The maximum myocardial lactate production was significantly higher ( p = 0.02 ) in the group operated with CPB ( 0.56 mmol/L ) than without it ( 0.17 mmol/L ) . A similar phenomenon was seen in the transcardiac pH differences ( 0.085 and 0.034 with and without CPB , p = 0.007 ) . The postoperative peak values of creatine kinase-MB mass ( 15.1 vs 6.3 microg/L ) and troponin I ( 13.8 vs 5.2 microg/L ) were significantly higher ( p < 0.001 and p = 0.008 ) with than without CPB . CONCLUSIONS CABG on a beating heart is associated with better myocardial energy preservation and less myocardial damage compared with conventional CABG with CPB and intermittent ante grade mild hypothermic blood cardioplegia Background Atrial fibrillation ( AF ) increases the morbidity of CABG . The pathophysiology is uncertain , and its prevention remains suboptimal . This prospect i ve , r and omized study was design ed to define the role of cardiopulmonary bypass ( CPB ) and cardioplegic arrest in the pathogenesis of this complication . Methods and Results Two hundred patients were prospect ively r and omized to ( 1 ) on-pump conventional surgery [ ( 100 patients , 79 men , mean age 63 ( 40 to 77 ) years ) ] with normothermic CPB and cardioplegic arrest of the heart or ( 2 ) off-pump surgery [ ( 100 patients , 82 men , mean age 63 ( 38 to 86 ) years ) ] on the beating heart . Heart rate and rhythm were continuously monitored with an automated arrhythmia detector during the first 72 hours after surgery . Thereafter , routine clinical observation was performed and continuous monitoring restarted in the case of arrhythmia . The association of perioperative factors with AF was investigated by univariate analysis . Significant variables were then included into a stepwise logistic regression model to ascertain their independent influence on the occurrence of AF . There were no significant baseline differences between groups . Thirty-nine patients in the on-pump group and 8 patients in the off-pump group had postoperative sustained AF ( P = 0.001 ) . Univariate analysis showed that CPB inclusive of cardioplegic arrest , postoperative inotropic support , intubation time , chest infection , and hospital length of stay were predictors of AF ( all P < 0.05 ) . However , stepwise multivariate regression analysis identified CPB inclusive of cardioplegic arrest as the only independent predictor of postoperative AF ( OR 7.4 ; CI 3.4 to 17.9 ) . Conclusions CPB inclusive of cardioplegic arrest is the main independent predictor of postoperative AF in patients undergoing coronary revascularization CONTEXT Coronary artery bypass graft ( CABG ) surgery is associated with a decline in cognitive function , which has largely been attributed to the use of cardiopulmonary bypass ( on-pump procedures ) . Cardiac stabilizers facilitate CABG surgery without use of cardiopulmonary bypass ( off-pump procedures ) and should reduce the cognitive decline associated with on-pump procedures . OBJECTIVE To compare the effect of CABG surgery with ( on-pump ) and without ( off-pump ) cardiopulmonary bypass on cognitive outcome . DESIGN AND SETTING R and omized controlled trial conducted in the Netherl and s of CABG surgery patients enrolled from March 1998 through August 2000 , with 3- and 12-month follow-up . PARTICIPANTS AND INTERVENTION Patients scheduled for their first CABG surgery ( mean age , 61 years ; n = 281 ) were r and omly assigned to off-pump surgery ( n = 142 ) or on-pump surgery ( n = 139 ) . MAIN OUTCOME MEASURES Cognitive outcome at 3 and 12 months , which was determined by psychologists ( blinded for r and omization ) who administered 10 neuropsychological tests before and after surgery . Quality of life , stroke rate , and all-cause mortality at 3 and 12 months were secondary outcome measures . RESULTS Cognitive outcome could be determined at 3 months in 248 patients . Cognitive decline occurred in 21 % in the off-pump group and 29 % in the on-pump group ( relative risk [ RR ] , 0.65 ; 95 % confidence interval [ CI ] , 0.36 - 1.16 ; P = .15 ) . The overall st and ardized change score ( ie , improvement of cognitive performance ) was 0.19 in the off-pump vs 0.13 in the on-pump group ( P = .03 ) . At 12 months , cognitive decline occurred in 30.8 % in the off-pump group and 33.6 % in the on-pump group ( RR , 0.88 ; 95 % CI , 0.52 - 1.49 ; P = .69 ) . The overall st and ardized change score was 0.19 in the off-pump vs 0.12 in the on-pump group ( P = .09 ) . No statistically significant differences were observed between the on-pump and off-pump groups in quality of life , stroke rate , or all-cause mortality at 3 and 12 months . CONCLUSION Patients who received their first CABG surgery without cardiopulmonary bypass had improved cognitive outcomes 3 months after the procedure , but the effects were limited and became negligible at 12 months Objective . The aim of this prospect i ve , r and omized study was to investigate the impact of coronary artery bypass grafting ( CABG ) on peripheral monocytes and to evaluate the additional effect of cardiopulmonary bypass ( CPB ) . Design . Twenty patients admitted for elective CABG were r and omized to either on-pump ( ONCAB , n=9 ) or off-pump ( OFFCAB , n=11 ) surgery and blood sample s were drawn before , during and 24 h after the operation . The total number of monocytes and the proportion of the more mature CD16+/CD14 + monocytes were measured . Expression of activation markers ( CD11b , CD35 and CD62L ) and oxidative burst were determined using flow cytometry on both resting and in vitro stimulated cells . Serum concentrations of soluble CD14 and monocytes/macrophage chemotactic protein 1 ( MCP-1 ) were analysed . Results . During surgery there was a selective decrease in the proportion of CD16+/CD14 + monocytes compared to total monocytes . These had returned to preoperative values 24 h after surgery while the total number of monocytes had increased more than 100 % . Intracellular production of oxygen free radical H2O2 was increased in the ONCAB group during surgery compared to OFFCAB . Monocyte expression and in vitro mobilization of complement receptors , CD11b and CD35 , were similar in both study groups during and after surgery as was the expression of CD62L . Serum levels of MCP-1 decreased during surgery as did soluble CD14 , both with increased levels again the day after surgery . Conclusion . It is concluded that the circulating monocyte population is activated during and as a consequence of CABG . There were few apparent additional effects of CPB found in this study . In this setting the inflammation caused by the surgery procedure per se probably surpasses the impact of the CPB on circulating blood monocytes OBJECTIVES S100 protein has been used as a marker for cerebral injury . Studies have reported lower levels in off-pump coronary artery surgery ( CABG ) compared to on-pump surgery . However , most of these are flawed as S100 from extracerebral sources was included ( e.g. blood from cardiotomy suckers ) . Microemboli ( high-intensity transient signals or HITS ) during CABG have been implicated as a cause of postoperative neurocognitive dysfunction . The aim of this study was to compare the number of HITS during on-pump and off-pump CABG , measure S100 accurately by excluding extracerebral sources , and assess whether any changes in S100 were related to HITS . METHODS Thirty-five patients admitted for CABG were r and omised to on-pump ( n=20 ) or off-pump ( n=15 ) surgery . Bilateral transcranial Doppler ultrasonography was performed on the middle cerebral artery to detect HITS . S100 was measured preoperatively , at termination of bypass in on-pump surgery , at completion of anastomoses in off-pump surgery , and 48 h postoperatively . A cell saver was used instead of cardiotomy suction in the on-pump group in order to limit extracerebral contamination of the S100 assay . RESULTS The number of HITS was 2016+/-1897 during on-pump and 16+/-21 during off-pump surgery ( P<0.0001 ) . In on-pump surgery S100 increased from 0.05+/-0.03 to 0.50+/-0.28 microg/l ( P<0.0001 ) at termination of bypass . In off-pump surgery S100 increased from 0.08+/-0.05 to 0.35+/-0.20 microg/l ( P<0.0001 ) at completion of anastomoses . The mean intraoperative S100 in the on-pump group was 1.6 times greater compared to that in the off-pump group ( 95 % CI 0.88 - 2.8 ; P=0.01 ) . There was no evidence of a relationship between S100 and HITS in both groups . By 48 h S100 decreased to 0.22+/-0.14 microg/l in the on-pump and 0.21+/-0.09 microg/l in the off-pump group ( P<0.0001 , compared to the preoperative value ) . CONCLUSIONS We have demonstrated a significantly higher number of cerebral microemboli in patients undergoing on-pump compared to off-pump CABG . By limiting contamination from extracerebral sources , we have shown S100 beta levels during on-pump CABG one and a half times greater than that in off-pump , although this did not reach statistical significance . In addition , we have shown no correlation between S100 beta and the total microemboli count , possibly because of the small numbers in this study Background —There is biochemical evidence that off-pump coronary artery bypass grafting ( OPCABG ) reduces myocardial injury compared with the use of cardiopulmonary bypass ( ONCABG ) , but the functional significance of this is uncertain . We hypothesized that OPCABG surgery would result in reduced postoperative reversible ( stunning ) and irreversible myocardial injury , as assessed by cardiovascular MRI ( CMRI ) . Methods and Results —In a single-center r and omized trial , 60 patients undergoing multivessel total arterial revascularization were r and omly assigned : 30 to OPCABG and 30 to ONCABG . Patients underwent preoperative and early postoperative cine MRI for assessment of global left ventricular function , and contrast-enhanced CMRI for assessment of irreversible myocardial injury . Serial troponin I measurements were obtained perioperatively and correlated with the CMRI findings . The mean preoperative cardiac index was similar in the 2 surgical groups ( 2.9±0.7 ONCABG ; 2.9±0.8 OPCABG ; P = 0.9 ) . After surgery , the cardiac index was significantly higher in the OPCABG group ( 2.7±0.6 ONCABG ; 3.2±0.8 OPCABG ; P = 0.04 ) . New irreversible myocardial injury was similar in incidence ( 36 % ONCABG ; 44 % OPCABG ; P = 0.8 ) and magnitude ( 6.3±3.6 g ONCABG ; 6.8±4.0 g OPCABG ; P = 0.9 ) across the 2 groups . The median area-under-the-curve ( AUC ) troponin I values were significantly larger in the ONCABG group ( 182 versus 135 & mgr;g/L ; P = 0.02 ) . There was a moderate correlation between the troponin I AUC values and mean mass of new myocardial hyperenhancement ( r2=0.4 ; P = 0.008 ) . Conclusions —OPCABG results in significantly better left ventricular function early after surgery but does not reduce the incidence or extent of irreversible myocardial injury Background —There is increasing evidence that cardiopulmonary bypass ( CPB ) may be responsible for the morbidity associated with coronary artery bypass grafting ( CABG ) surgery . Recent developments in cardiac stabilization devices have made CABG without CPB feasible . However , there is conflicting evidence to date from published trials comparing outcomes between CABG performed with and without CPB , with some trials indicating an advantage to the avoidance of CPB and others showing little benefit . Methods and Results —In a single-center r and omized trial , 300 patients requiring CABG surgery at a single institution were prospect ively r and omized to have the procedure performed with CPB ( n=150 ) or on the beating heart ( n=150 ) . Exclusion criteria for the trial included emergency procedure , concomitant major cardiac procedures , ejection fraction < 30 % , and reoperation . In-hospital outcomes were analyzed on an intention-to-treat basis . A mean of 3.0±0.9 grafts were performed in the CPB group compared with 2.8±0.9 grafts in the beating-heart group ( P = 0.06 ) . There were no significant differences between the CPB group and the beating-heart group in mortality ( 0.7 % versus 1.3 % ; P = 1.0 ) , transfusion ( 8.7 % versus 9.3 % ) , perioperative myocardial infa rct ion ( 0.7 % versus 2.7 % ; P = 0.37 ) , permanent stroke ( 0 % versus 1.3 % ; P = 0.50 ) , new atrial fibrillation ( 32 % versus 25 % ; P = 0.20 ) , and deep sternal wound infection ( 0.7 % versus 0 % ; P = 1.0 ) . The mean time to extubation was 4 hours , the mean stay in the intensive care unit was 22 hours , and the median length of hospitalization was 5 days in both groups ( P = NS ) . Conclusions —In contrast to published trials , we were unable to demonstrate any advantage with CABG performed without CPB in terms of patient morbidity . Excellent results can be obtained with either surgical approach OBJECTIVE This study investigated whether the activation of coagulation , fibrinolysis , and endothelium occurring during the first postoperative month after on-pump coronary artery bypass surgery differs from that after off-pump coronary artery bypass grafting . METHODS Thirty-five patients c and i date s to coronary surgery were r and omized to undergo on-pump ( n = 18 ) or off-pump ( n = 17 ) coronary artery bypass grafting . Blood sample s were collected before the intervention and to 1 month after surgery . RESULTS Prothrombin fragment F1.2 , thrombin-antithrombin complex , and D-dimer increased after surgery and were persistently higher than preoperative values as late as 30 postoperative days in both on- and off-pump groups ; higher levels of these variables were detected after on-pump surgery relative to off-pump surgery only at the time point after termination of cardiopulmonary bypass ( fragment F1.2 and thrombin-antithrombin complex ) or from bypass end to 8 postoperative days ( D-dimer ) . Fibrinogen levels decreased after surgery and then increased in parallel in both groups to 8 days after surgery . The von Willebr and factor level increased postoperatively in both groups and returned to baseline 30 days after surgery ; it was higher after on-pump surgery from bypass end to 8 postoperative days . Soluble vascular cell adhesion molecule 1 was increased significantly from baseline in both groups 30 days after surgery , with no difference between groups . CONCLUSION Patients undergoing off-pump surgery showed protection against activation of coagulation and fibrinolysis and against endothelial injury only during the intraoperative period ; this was followed by the development of a prothrombotic pattern comparable to that of patients undergoing on-pump surgery lasting at least as late as 30 days after surgery OBJECTIVE By maintaining native coronary blood flow in on-pump beating heart surgery ( OnP-BH ) and comparing with OPCAB strategy pump-related effects on myocardial injury and cardiac dysfunction could be specifically differentiated from ischemia/reperfusion-related consequences of surgical coronary revascularization . METHODS In a r and omized- prospect i ve design , 40 elective patients with normal EF and three vessels coronary artery disease ( left main disease excluded ) were assigned to OPCAB or OnP-BH surgery . Before coronary occlusion and 1 , 30 , 60 , and 90 min after reperfusion with the LIMA graft , coronary sinus ( CS ) blood was sample d to determine intraoperative myocardial ischemia ( pH , lactate , pO2 ) and oxidative stress ( malondialdehyde , MDA ) . Additionally to CS blood arterial blood was analyzed 4 , 12 , and 24 h postoperatively to determine myocardial necrosis ( CK-MB , cardiac troponin I ) , myocardial dysfunction ( NT-proBNP ) and inflammation ( C-reactive protein ) . RESULTS Groups were identical with regards to age and gender ( OPCAB 63.0+/-6.0 versus OnP-BH 65.3+/-3.9 y , 20 % female patients ) . Number of grafts were 3.0+/-0.5 in OPCAB versus 2.9+/-0.3 in OnP-BH ( n.s . ) with 44 versus 34 % bilateral IMAs and 56 versus 50 % complete arterial revascularization . Regarding ischemia , intraoperatively only lactate values increased significantly in the OnP-BH group . Significantly higher CK-MB and troponin I levels were found from LIMA-LAD flow release onwards to 4 h postoperatively in the OnP-BH group . NT-proBNP levels were significantly higher in the OnP-BH group during the entire study period . CRP levels were higher in the OnP-BH group 12 and 24 h postoperatively . CONCLUSIONS In this r and omized study on routine coronary patients with normal ventricular function , OPCAB revealed less myocardial injury than OnP-BH . These findings implicate that CPB slightly affects the myocardium INTRODUCTION The aim of this study was to determine if coronary artery bypass graft ( CABG ) surgery performed utilizing the Octopus II stabilizing system provides myocardial and cerebral protection comparable to traditional CABG surgery utilizing cardiopulmonary bypass ( CPB ) . METHODS Elective patients requiring surgery for double or triple vessel disease were r and omized to receive either conventional CABG with CPB ( n = 14 ) or OPCAB using the Octopus II stabilizing system ( n = 12 ) , after receiving institutional approval and written consent . Exclusion criteria included previous cardiac surgery , recent myocardial infa rct ion , and previous cerebrovascular disease . Troponin T ( TnT ) was measured preoperatively and at 2 , 4 , 6 , 8 , 10 , 12 , 24 , and 72 hours after initiation of grafting . Neuropsychological assessment s ( 10 measures ) were performed in the week prior to surgery , one week , and six months after surgery . RESULTS Troponin T release was reduced in the OPCAB patients at all time points ( repeated measures ANOVA p = 0.043 ) , reaching significance at 8 , 10 and 12 hours ( p = 0.033 , 0.038 , 0.019 ) . Other factors ( composite clinical end point ( prolonged LOS or ICU stay or 30-day mortality ) , infa rct ion , and intubation time ) did not show any significant differences between the two groups . The incidence of neuropsychological deficits was not different between the two groups at both seven-day and six-month follow-up assessment s. CONCLUSIONS Decreased TnT release suggests a myocardial benefit for the OPCAB procedure . A neuropsychological benefit remains to be demonstrated BACKGROUND Cardiopulmonary bypass ( CPB ) is associated with a systemic stress hormonal response , which can lead to changes in hemodynamics and organ perfusion . We examined perioperative stress hormone release in low-risk patients undergoing coronary artery bypass grafting with and without cardiopulmonary bypass . METHODS Fifty-two patients undergoing primary coronary artery bypass grafting by the same surgeon were r and omly assigned into either on-pump ( n = 26 ) or off-pump ( n = 26 ) groups . The on-pump coronary artery bypass grafting group underwent mildly hypothermic ( 35 degrees C ) pulsatile cardiopulmonary bypass with arterial line filtration . Arterial blood sample s were collected preoperatively , at the end of operation , and at 1 , 6 , and 24 hours postoperatively . Plasma levels of vasopressin and cortisol were measured using radioimmunoassay . Anesthetic management was st and ardized . RESULTS Both groups had similar demographic makeup and extent of revascularization ( on-pump coronary artery bypass grafting , 2.8 + /- 1.0 grafts versus off-pump coronary artery bypass grafting , 2.4 + /- 0.9 grafts ; p = 0.20 ) . No mortality or major morbidity was observed and there were no crossovers . The cardiopulmonary bypass and aortic cross-clamp times in the on-pump coronary artery bypass grafting group were 63 + /- 24 and 33 + /- 11 minutes , respectively . In both groups there was a similar and significant rise in cortisol and vasopressin levels in the early postoperative phase , with a partial recovery toward baseline values observed at 24 hours postoperatively . Repeated measures analysis of covariance showed no significant difference between the groups with time for both hormones ( cortisol , p = 0.40 ; vasopressin , p = 0.30 ) . CONCLUSIONS Despite the avoidance of cardiopulmonary bypass , off-pump coronary artery bypass grafting surgery triggers a systemic stress hormone response that is comparable to conventional surgical revascularization . The neurohormonal environment during beating-heart surgery should be further explored BACKGROUND This study investigated whether off-pump coronary bypass graft operations on the beating heart under normothermic conditions reduces the systemic oxidative stress and inflammatory reaction seen in patients operated under cardiopulmonary bypass ( CPB ) . METHODS A cardiac stabilizer ( Octopus Tissue Stabilizer ; Medtronic Inc , Minneapolis , MN ) was used to perform the coronary anastomoses on the normothermic beating heart with or without CPB . Serial blood sample s were taken at various intervals . Plasma was analyzed for several oxidative stress and inflammatory markers . RESULTS Significant increases from prior anesthesia values of lipid hydroperoxides ( 190 % at 4 hours ) , protein carbonyls ( 250 % at 0.5 hours ) and nitrotyrosine ( 510 % at 0.5 hours ) were seen in the CPB group , but they were abolished or significantly reduced in the off-pump group . Complement C3a and elastase levels were rapidly increased upon the institution of CPB , and this was followed by increases in IL-8 , TNF-alpha , and sE-selectin . In contrast , the rise of these factors was blunted in patients operated without CPB . CONCLUSIONS Off-pump coronary bypass graft operation on a beating heart significantly reduces oxidative stress and suppresses the inflammatory reaction associated with the use of CPB Clinicians are presented with problems that require evidence . R and omized controlled trials ( RCTs ) are considered the optimal study design for evaluating the effect of a new medical or surgical intervention . Surgical RCTs are carried out less often than RCTs of medical interventions , partly because using RCTs to evaluate surgical or interventional procedures is difficult and dem and s special consideration of issues such as blinding and the effects of surgeon factor , learning curve and differences in preor postprocedural care . Despite these obstacles , RCTs are becoming more common as surgeons in many specialties become acquainted with the proper methodology for health research . The mere description of a study as “ r and omized ” does not allow clinicians to infer validity — to base inferences on the accuracy of the results drawn from the sample of patients studied ( internal validity ) or the generalizability of these results to other setting s ( external validity ) . The purpose of this article is to review , within a framework of a critical appraisal of surgical RCTs , strategies to interpret the results and the issues to consider when applying these results to a clinical practice setting . A clinical scenario will be used to illustrate how surgeons might retrieve and evaluate evidence BACKGROUND AND PURPOSE Several studies have shown that the quality of reporting of trials throughout medicine is variable and often poor . We report on the quality of the final reports of r and omized controlled trials ( RCTs ) of drug therapies assessed in acute stroke . METHODS English- language reports published up to the end of 1996 relating to completed RCTs in acute stroke were identified from electronic search es of the Cochrane Stroke Review Group data base of stroke trials and the Cochrane Controlled Trials Register ( CD-ROM issue 1 , 1997 , of the Cochrane Library ) . Report quality was assessed with the 33 criteria of the CONSORT statement and 53 additional factors relevant to acute stroke or trials in general . Trial quality was also assessed with a 7-point scale . RESULTS Up to 1996 , 114 RCTs were published which involved 20 536 patients ( median , 80 ; range , 16 to 1267 per trial ) ; 39 ( 35.5 % ) of these were published in Stroke . The median total report quality was 40/86 ( range , 15 to 61 ) for all criteria and 19/33 ( range , 9 to 29 ) for the CONSORT criteria alone . Although adequate information was given in the introduction and discussion sections of most reports , insufficient details were given on methods , assignment of patients to treatment groups , statistical analyses , the prevalence of risk factors , and assessment of outcomes . Report quality has improved between 1956 and 1996 ( Spearman correlation coefficient [ rs ] , 0.575 ; 95 % confidence interval [ CI ] , 0 . 439 to 0.685 ) and was superior in large trials ( rs=0.434 ; 95 % CI , 0 . 274 to 0.571 ) . Although report quality was related to trial quality ( rs=0.675 ; 95 % CI , 0.563 to 0.763 ) , it was not related to journal impact factor ( rs=0.170 ; 95 % CI , -0.015 to 0.344 ) . Trials with a positive outcome tended to be less well reported than those with a neutral or negative outcome ( rs=-0.192 ; 95 % CI , -0.351 to -0.011 ) . CONCLUSIONS The overall quality of study reports for parallel group RCTs in acute stroke is poor but appears to be improving with time and in parallel with an increase in trial size . Reports often lack detailed information on the methods of r and omization , concealment of allocation , and statistical analysis , all factors which can , if undertaken poorly , affect trial results and validity . It is vital that future trials are adequately reported ; we believe that authors should follow the CONSORT guidelines and that referees and editors should ensure this happens BACKGROUND The effect of cardiopulmonary bypass ( CPB ) on the level of anaesthetic depth has not been studied previously in a r and omized way . METHODS We assessed the effect of CPB on the propofol needed to maintain a fixed bispectral index score , and on the recovery from anaesthesia in 22 patients undergoing coronary artery bypass graft surgery with CPB ( on-pump ) compared with 18 patients operated on without CPB ( off-pump ) . Anaesthesia was induced and maintained with propofol and alfentanil . Throughout the procedure , the infusion rate of propofol was adjusted to keep the BIS value at 40 + /- 5 . RESULTS With the off-pump technique , the duration of surgery and anaesthetic administration were significantly greater . The need for propofol in proportion to time was exactly the same in both groups . During anaesthesia and the first 3 h thereafter , the BIS recordings were similar in both groups . No differences were detected in the time to awakening or tracheal extubation . CONCLUSIONS CPB does not affect propofol requirements or immediate postoperative recovery compared with the off-pump technique Background —The use of cardiopulmonary bypass during coronary artery bypass surgery ( CABG ) has been associated with substantial morbidity . The recent introduction of cardiac stabilizers facilitates CABG without cardiopulmonary bypass ( off-pump CABG ) , but it is unknown whether cardiac outcome after off-pump surgery is similar to that for the on-pump procedure . Methods and Results —In a multicenter trial , 281 patients ( mean age 61 years , SD 9 years ) were r and omly assigned to off-pump or on-pump CABG . In-hospital results and cardiac outcome and quality of life after 1 month are presented . Cardiac outcome was defined as survival free of stroke , myocardial infa rct ion , and coronary reintervention . The mean numbers of distal anastomoses per patient were 2.4 ( SD 1.0 ) and 2.6 ( SD 1.1 ) in the off-pump and on-pump groups , respectively . Completeness of revascularization was similar in both groups . Blood products were needed during 3 % of the off-pump procedures and 13 % of the on-pump procedures ( P < 0.01 ) . Release of creatine kinase muscle-brain isoenzyme was 41 % less in the off-pump group ( P < 0.01 ) . Otherwise , no differences in complications were found postoperatively . Off-pump patients were discharged 1 day earlier . At 1 month , operative mortality was zero in both groups , and quality of life had improved similarly . In both groups , 4 % of the patients had recurrent angina . The proportions of patients surviving free of cardiovascular events were 93.0 % in the off-pump group and 94.2 % in the on-pump group ( P = 0.66 ) . Conclusions —In selected patients , off-pump CABG is safe and yields a short-term cardiac outcome comparable to that of on-pump CABG OBJECTIVE In order to evaluate the traumatic effects of median sternotomy and cardiopulmonary bypass ( CPB ) in conventional and minimally invasive coronary artery bypass grafting , inflammatory response was studied in a prospect i ve r and omized trial in patients referred to single-vessel coronary artery bypass grafting . METHODS Four surgical techniques were compared : group 1 , median sternotomy with CPB in ten patients ( eight male , two female ; aged 59.6+/-11.0 years ( mean+/-SD ) ) ; group 2 , median sternotomy and off-pump in ten patients ( seven male , three female ; aged 65.1+/-10.0 years ) ; group 3 , minithoracotomy with CPB in ten patients ( seven male , three female , aged 61.2+/-10.4 years ) ; group 4 , minithoracotomy and off-pump in ten patients ( nine male , one female , aged 62.9+/-9.8 years ) . All patients received a left internal mammary artery graft to the left anterior descending artery ( LAD ) . Clinical data , perioperative values of cytokines and cardiac enzymes were monitored . RESULTS There were no major complications . Troponin-T and creatine kinase isoenzyme MB ( CK-MB ) levels were significantly higher in CPB procedures ( P<0.0056 ; multivariate general linear model ) . Interleukin-6 ( IL-6 ) levels were significantly higher in minithoracotomy procedures . Interleukin-1 ( IL-1 ) was significantly increased in all patients compared with the preoperative values . CONCLUSIONS The use of CPB is combined with higher levels of troponin-T and CK-MB as signs of myocardial damage . Surgical access was identified as a trigger of inflammatory response , as minithoracotomy is related to higher levels of IL-6 . IL-1 increased in all procedures and this occurred independently of the surgical access or the use of CPB , which points out a potential relationship between inflammatory response and anesthesia . Neither CPB nor surgical access influenced the clinical outcome in the treatment of coronary artery single-vessel bypass grafting OBJECTIVE On-pump beating heart coronary artery surgery provides the opportunity to examine the isolated effect of cardiopulmonary bypass . This prospect i ve r and omized study compares the early clinical outcomes and inflammatory response of patients undergoing elective on-pump and off-pump beating heart coronary artery bypass grafting . METHOD AND PATIENTS Thirty-seven consecutive patients undergoing elective coronary artery bypass grafting were recruited from a pool of 73 patients , with 19 patients r and omized to on-pump beating heart surgery and 18 patients to off-pump coronary bypass surgery . Intraoperative events and postoperative outcomes were recorded . Plasma levels of interleukin-6 , interleukin-8 , and interleukin-10 , tumor necrosis factor-alpha , and vascular cell adhesion molecule-1 were measured before the operation , intraoperatively , after the operation , and 4 , 24 , and 48 hours thereafter . RESULTS There was no significant difference in clinical outcomes between the 2 groups . The operating time was longer and consumption of platelets was greater for the on-pump beating heart group . There was no postoperative mortality or major complication in either group . There was significant elevation in the levels of interleukin-6 , interleukin-8 , and interleukin-10 and tumor necrosis factor-alpha during and immediately after the operations in the on-pump beating heart group when compared with the off-pump group . Levels of interleukin-8 ( P = .01 ) and tumor necrosis factor-alpha ( P = .0004 ) remained significantly elevated 4 hours after the operation in the on-pump beating heart group . The level of vascular adhesion molecule dropped significantly during the operation but was elevated 4 hours ( P = .026 ) after the operation in the on-pump beating heart group . CONCLUSION The use of cardiopulmonary bypass alone without global myocardial ischemia secondary to aortic crossclamping and cardioplegic cardiac arrest can trigger intense inflammatory responses Abstract Objective . To assess the number and quality of the reporting of r and omised controlled trials ( RCTs ) published in Intensive Care Medicine . Design . Systematic revision . Setting R and omised controlled trials published in Intensive Care Medicine . Study selection . All RCTs published in this journal from its birth to December 2000 identified by MEDLINE and our own research . Measurements and results . The Jadad scale and the individual assessment of key method ological components , namely the r and omisation process , blinding and reporting and h and ling of loss to follow-up , were used to evaluate the quality of reporting . Other information was extracted regarding the design characteristics and the analytical approach . 173 RCTs , 63 % of which were from European countries , were analysed . Adequately reported RCTs according to a Jadad scale score of more than 2 were 44 ( 25.4 % ) . Analysis of individual method ological components revealed a variable percentage of adequate reporting ranging from 3.5 % for r and omisation to 10.4 % for blinding and to 49.1 % for loss to follow-up . Sample sizes were small with a median of 30 patients and rationale for its estimation was reported in 7.5 % . Despite this , 81.5 % of RCTs reported statistically significant results , suggesting that the treatment effects were strong or that a publication bias existed or that the uncertainty principle was not fulfilled . Conclusions . R and omised controlled trials offer the best evidence of the efficacy of medical interventions , provided that high st and ards of transparent reporting are used . More resolute attention to the method ological quality of reporting and adherence to recently published guidelines ( CONSORT II ) may help to achieve this result OBJECTIVE In this study , we test the hypothesis that off-pump coronary bypass surgery might result in less lymphocyte activation than on-pump coronary surgery . We also study the behavior of lymphocyte activation markers during and after surgery . BACKGROUND Coronary artery bypass surgery is known to be associated with changes of inflammatory mediators , immune function , and early phase lymphocyte activation , which could cause postoperative lymphopenia and lymphocyte unresponsiveness . METHODS We studied lymphocyte activation response in 28 patients r and omized to off-pump ( n = 13 ) or on-pump ( n = 15 ) coronary artery bypass surgery . Expression of CD25 , CD26 , CD69 , and DR on T ( CD3 + ) and B ( CD19 + ) lymphocytes on peripheral blood was assessed through flow cytometry . RESULTS The response of T lymphocytes and their activation markers , as well as B lymphocytes and their activation markers , was similar after on- and off-pump surgery . Overall , T lymphocytes decreased to the lowest level 9 h after surgery and tended to increase later . For B lymphocytes , there was early reduction with increase on the 1st postoperative day . There was early activation of CD69 + and late activation of CD25 + on T lymphocytes . For B lymphocytes , there was early activation of CD69 + and late activation of DR+ . CONCLUSIONS ( 1 ) Compared to on-pump cardiopulmonary bypass , off-pump surgery does not reduce lymphocyte activation . ( 2 ) Coronary bypass surgery causes the early activation of lymphocytes , as evidence d by the increased expression of lymphocyte activation markers OBJECTIVE Retrospective comparisons of selected patients undergoing off-pump versus conventional on-pump coronary artery bypass grafting have yielded inconsistent results and raised concerns about completeness of revascularization in off-pump coronary artery bypass grafting . METHODS Two hundred unselected patients referred for elective primary coronary artery bypass grafting were r and omly assigned to undergo off-pump coronary artery bypass grafting with an Octopus tissue stabilizer ( Medtronic , Inc , Minneapolis , Minn ) or conventional coronary artery bypass grafting with cardiopulmonary bypass by a single surgeon . Revascularization intent determined before r and om assignment was compared with the revascularization performed . All management followed strict , unbiased , criteria -driven protocol s. Patients and nonoperative care providers were blinded to surgical group . RESULTS Baseline characteristics were similar . The number of grafts performed per patient ( mean + /- SD 3.39 + /- 1.04 for off-pump coronary artery bypass grafting , 3.40 + /- 1.08 for conventional coronary artery bypass grafting ) and the index of completeness of revascularization ( number of grafts performed/number of grafts intended , 1.00 + /- 0.18 for off-pump coronary artery bypass grafting , 1.01 + /- 0.09 for conventional coronary artery bypass grafting ) were similar . Likewise , the index of completeness of revascularization was similar between groups for the lateral wall . Combined hospital and 30-day mortalities and stroke rates were similar . Postoperative myocardial serum enzyme measures were significantly lower after off-pump coronary artery bypass grafting , suggesting less myocardial injury . Adjusted postoperative thromboelastogram indices , fibrinogen , international normalized ratio , and platelet levels all showed significantly less coagulopathy after off-pump coronary artery bypass grafting . Patients undergoing off-pump coronary artery bypass grafting received fewer units of blood , were more likely to avoid transfusion altogether , and had a higher hematocrit at discharge . Cardiopulmonary bypass was an independent predictor of transfusion ( odds ratio 2.42 , P = .0073 ) by multivariate analysis . More patients undergoing off-pump coronary artery bypass grafting were extubated in the operating room and within 4 hours . Postoperative length of stay ( in days ) was shorter for off-pump coronary artery bypass grafting ( 5.1 + /- 6.5 for off-pump coronary artery bypass grafting , 6.1 + /- 8.2 for conventional coronary artery bypass grafting , P = .005 by Wilcoxon test ) . One patient ( in the conventional coronary artery bypass grafting group ) required angioplasty for graft closure within 30 days . CONCLUSIONS When compared with conventional coronary artery bypass grafting with cardiopulmonary bypass , off-pump coronary artery bypass grafting achieved similar completeness of revascularization , similar in-hospital and 30-day outcomes , shorter length of stay , reduced transfusion requirement , and less myocardial injury OBJECTIVE The objectives are 2-fold : ( 1 ) . to serially determine endothelin ( ET ) levels in arterial vascular compartments in patients undergoing coronary artery bypass surgery using either cardiopulmonary bypass or off-pump techniques , and ( 2 ) . to define potential relationships between endothelial levels and specific perioperative parameters of patient recovery . METHODS In a prospect i ve , r and omized study , endothelin plasma content was measured from patients undergoing coronary artery bypass grafting using either off-pump techniques ( OPCAB group , n = 25 ) or conventional cardiopulmonary bypass ( CPB group , n = 25 ) before surgery , before and after coronary artery anastomosis , and 6 and 24 hours postoperatively . Specific indices of patient recovery including pulmonary artery pressures , ventilation requirement , and hospital stay were documented for patients in both study groups . RESULTS Postoperative systemic arterial ET levels were significantly increased by 200 % in the CPB group and 50 % in the OPCAB group . ET levels remained significantly higher in the CPB group relative to the OPCAB group throughout the postoperative period of observation ( p < 0.05 ) . Pulmonary artery pressures , ventilation requirement , and hospital stay were significantly increased in patients in the CPB group . CONCLUSIONS Postoperative ET levels were higher in patients who underwent CPB for coronary artery bypass surgery . Increased ET in the postoperative period may contribute to a more complex recovery from coronary artery bypass surgery in patients undergoing cardiopulmonary bypass Coronary artery bypass graft ( CABG ) surgery with cardiopulmonary bypass ( CPB ) can produce a higher incidence of neuropsychological complications than other types of highly invasive noncardiac vascular surgery . Cognitive complications most likely arise from either embolization or hypoxia . An alternative surgical procedure has been developed that allows CABG to be performed without stopping the heart ( " off-pump " CABG , or OPCABG ) . This study examined the neuropsychological performance of patients undergoing OPCABG , hypothesizing that patients undergoing OPCABG would show fewer cognitive deficits than patients whose hearts were stopped . A 1-hr neuropsychological battery was administered preoperatively to 43 patients before prospect i ve r and omization to either CPB CABG or OPCABG , and again to 34 of those patients 2 to 3 months postoperatively by an examiner blind to surgical condition . Neuropsychological status did not change 2.5 months postsurgically in either OPCABG or CABG groups . However , both groups showed dramatic presurgical cognitive deficits in multiple domains , particularly verbal memory and psychomotor speed . This corroborates previous research suggesting that patients requiring CABG surgery may evidence significant presurgical cognitive deficits as a result of existing vascular disease BACKGROUND Off-pump coronary artery bypass surgery is becoming increasingly popular despite the lack of sufficient evidence from r and omized trials . The aim of our prospect i ve , r and omized , single-center study was to examine the role of off-pump revascularization among nonselected patients . METHODS A total of 400 consecutive nonselected patients ( mean age 63 years ) scheduled for isolated coronary revascularization were r and omized by a cardiologist into two groups : A ( on-pump ) and B ( off-pump ) . The cardiac surgeon was allowed to change the operative technique at any time after r and omization . The only exclusion criterion was an emergency procedure . The primary end point was any of the following within 30 days : death , myocardial infa rct ion , stroke , or new renal failure requiring hemodialysis . The study was analyzed on the intention-to-treat principle . RESULTS The primary end point occurred in 4.9 % of patients in group A versus 2.9 % in group B ( not significant ) . Mortality was 1.1 % in group A versus 2.0 % in group B ( not significant ) . Preoperative crossover occurred in 5.4 % of patients in each group ( not significant ) . Intraoperative conversion was necessary in 9.8 % of patients in group B versus 1.1 % of patients in group A ( p < 0.001 ) . Group B patients had fewer distal anastomoses ( 2.3 versus 2.7 in group A ; p < 0.001 ) , less blood loss ( 560 versus 680 mL ; p < 0.001 ) , lower postoperative creatine kinase MB levels ( 0.15 versus 0.56 microkat/L ; p < 0.001 ) and lower total hospital costs ( 3,451 versus 4,387 ; p < 0.001 ) . CONCLUSIONS In our study off-pump technique was applicable in 85 % of nonselected patients and is at least as clinical ly safe and effective as on-pump surgery BACKGROUND Cardiopulmonary bypass seems to be a major cause for both intraoperative microemboli and cerebral hypoperfusion . This study investigates high intensive transient signals ( HITS ) in transcranial Doppler ultrasound ( TCD ) and serum levels of the neurobiochemical marker protein S-100 in patients who underwent coronary artery bypass operation without cardiopulmonary bypass ( off-pump CABG ) in comparison with the conventional procedure using cardiopulmonary bypass ( CPB ) . The results are related to the neuropsychologic outcome in both surgical groups . METHODS Forty patients were r and omized in 2 groups ( 20 conventional and 20 off-pump CABG ) . Neurocognitive status was assessed preoperatively and postoperatively . Venous serum levels of S-100 protein were measured before and after coronary operation , HITS were measured in the middle cerebral artery during the operation . RESULTS The median value of HITS was 394.5 ( 0 to 2217 ) in the conventional versus 11 ( 0 to 50 ) in the off-pump group , p less than 0.0001 . Postoperative S-100 serum levels were : 3.76 ( 0.13 to 11.2 ) microg/L ( conventional ) versus 0.13 ( 0.04 to 1.01 ) microg/L ( off-pump ) , p less than 0.0001 . Postoperative cognitive testing showed significantly different results with a postoperative impairment of 90 % of the patients in the conventional group versus no impairment in the off-pump group . CONCLUSIONS Cognitive impairment seems to be strongly associated to CPB and the occurrence of micro-emboli . The off-pump technique appears to be promising in order to eliminate the source of these neuropyschologic impairments following CABG operation BACKGROUND The Consoli date d St and ards for Reporting Trials ( CONSORT ) are recommendations for improving the quality of reports of r and omized controlled trials ( RCTs ) . OBJECTIVE To determine the extent to which clinical pharmacology journals implement specific CONSORT recommendations . DESIGN AND SETTING Analysis of RCTs published between May 2002 and May 2003 in four clinical pharmacology journals . MAIN OUTCOME MEASURES Proportion of RCTs that published a participant flow diagram and that reported on r and omization and restriction methods , allocation concealment , blinding , intention-to-treat analysis , ethical considerations , adverse events and source of funding . RESULTS Of 482 clinical trials , 193 were RCTs . Healthy participants were involved in 129 [ 66.8 % , 95 % confidence interval ( CI ) 59.9 , 73.1 ] trials , patients who required treatment in 61 ( 31.6 % , 95 % CI 25.4 , 38.4 ) trials and both in three ( 1.6 % , 95 % CI 0.5 , 4.4 ) trials . The following items were infrequently reported : sequence generation ( 17 % ) , allocation concealment ( 3 % ) , use of restriction ( 16 % ) , description of blinding ( 26 % ) , and flow diagrams of study participants ( 2 % ) . In contrast , the following areas were often reported : use of intention-to-treat analysis ( 79 % ) , description of withdrawals ( 92.2 % ) and description of adverse events ( 71 % ) , ethics review ( 94 % ) and informed consent ( 95 % ) . Sources of funding were reported in 56 % of studies . CONCLUSION The use of the selected CONSORT items is limited in these journals , possibly as many items may not be relevant to the types of studies published in clinical pharmacology journals . Further efforts are required to determine the applicability of CONSORT to RCTs in clinical pharmacology ABSTRACT Cardiopulmonary bypass ( CPB ) and operative trauma are associated with increased expression of pro‐ inflammatory mediators . We determined the relative contribution of CPB on activation of cytokines and adhesion molecules in patients undergoing coronary revascularization by comparing them with patients receiving off‐pump coronary artery bypass grafting ( OPCAB ) . Twenty‐six patients were assigned to either the OPCAB procedure using a suction device and regular sternotomy ( n = 13 ) , or were treated conventionally using extracorporeal circulation , blood cardioplegia , and hypothermic arrest ( 29 ° C‐31 ° C ; n = 13 ) . Systemic levels of TNF‐&agr ; and the soluble adhesion molecules P‐selectin and intracellular adhesion molecule 1 ( ICAM‐1 ) were assayed . Immunohistochemistry was used to account for cardiac‐specific expression of adhesion molecules in interventricular endomyocardial sections . Both systemic and endomyocardial expres‐ sion of adhesion molecules were lower in the OPCAB group . Coronary revascularization with CPB result ed in a significant higher expression of TNF‐&agr ; , which was associated with P‐selectin and ICAM‐1 expression . This was accompanied with higher catecholamine requirement in the CPB group in the early postoperative period . Despite comparable surgical trauma , the OPCAB procedure without the use of CPB and cardioplegic arrest significantly reduces systemic and cardiac adhesion molecule expression and catecholamine requirement . Since the clinical course in the early postoperative period was comparable , larger trials are required to select the appropria te patient who benefits most from one or the other treatment regime OBJECTIVE The subset of patients most likely to benefit from off-pump coronary artery bypass grafting ( CABG ) remains a controversial issue , but the technique has been proposed to decrease postoperative mortality and morbidity . Th e objective of this study was to compare off-pump to onpump CABG in patients with known risk factors for mortality and morbidity . METHODS Between October 2001 and September 2002 , 65 high-risk patients were prospect ively r and omized to undergo off-pump or o n-pump CABG . Recruited patients had at least 3 of the following criteria : age greater than 65 years , high blood pressure , diabetes , serum creatinine greater than 133 mol/L , left ventricular ejection fraction lower than 45 % , chronic pulmonary diseas e , unstable angina , congestive heart failure , repeat CABG , anemia , and carotid atherosclerosis . Hospital mortality and morbidity were the primary end-points of the study . RESULTS Six patients ( 9 % ) crossed over from the original r and omized group . Twenty-eight patients averaging 70 + /- 8 years of age underwent 3 + /- 1 grafts off pump , and 37 patients averaging 70 + /- 6 years of age underwent 3.4 + /- 1 grafts on pump . Revascularization was considered complete in 21 ( 7 5 % ) of off-pump patients compared to 33 ( 89 % ) of onpump patients ( P = .1 ) . There were no hospital deaths in off-pump patients , and 2 patients ( 5 % ) undergoing onpump CABG died early following surgery ( P = .2 ) . Two offpump ( 7 % ) compared to 11 on-pump ( 30 % ) of patients presented composite end-points including death , neurological injury , renal failure , respiratory failure , and operative myocardial infa rct ion after CABG ( P = .02 ) . CONCLUSION The present study suggests that off-pump CABG , when technically feasible , significantly reduces morbidity following surgery in a group of high-risk patients Abstract INTRODUCTION : Evidence -based medicine relies on reproducible , high- quality reporting in the literature . Previous evaluations , which have assessed 11 basic elements of design and analysis in top impact clinical journals ( both nonsurgical and surgical ) , have demonstrated that the reporting quality is less than perfect , although improving . The current study evaluates the quality of reporting in Diseases of the Colon and Rectum and other clinical ly related journals to identify specific areas where future improvements may be made . METHODS : Two independent evaluators assessed all r and omized , controlled trials published in Diseases of the Colon and Rectum in the years 1990 , 1995 , and 2000 . Additional assessment s for 2000 were performed on all r and omized , controlled trials published in Annals of Surgery , Archives of Surgery , and Gastroenterology . The frequency of reporting of 11 explicitly defined , traditionally important , basic elements of design and analysis were determined . These elements included reporting of eligibility criteria , admission before allocation , r and omization ( and method ) , blinded assessment ( patient and observer ) , complications , loss to follow-up , statistical approach and tests , and power calculation . RESULTS : Interobserver reliability was strong ( kappa , 0.76 ) . The number of r and omized , controlled trials published in Diseases of the Colon and Rectum increased from 5 ( in 1990 ) to 13 ( in 1995 ) to 17 ( in 2000 ) . Of the 1990 r and omized , controlled trials , an average of 60 percent of the 11 basic elements were reported . Of the 1995 r and omized , controlled trials , 72 percent of the items were reported ( P = 0.05 ) , whereas of the 2000 r and omized , controlled trials , 77 percent of the 11 items were reported ( P < 0.002 vs. 1990 ) . The best-reported items were eligibility criteria , discussion of statistical tests , and accounting for all patients lost to follow-up . Only 11 percent of the 2000 r and omized , controlled trials reported statistical power calculations . For the other journals that were evaluated , 72 to 88 percent of items were reported , with eligibility criterion being the best consistently reported item and power calculation being the worst . CONCLUSIONS : For Diseases of the Colon and Rectum , the number of r and omized , controlled trials and the quality of reporting is improving . However , although certain research st and ards are reported adequately , others are not . The calculation of statistical power is clearly important when interpreting r and omized , controlled trial results ( whether differences are reported or not ) , yet only 11 percent of studies contained this information . Improving the reporting of this single item would likely lead to improving the overall quality of clinical studies in colorectal surgery . Improved reporting might be best facilitated by having authors adhere to a list of explicitly determined elements that should be included . Ko CY , Sack J , Chang JT , Fink A. Reporting r and omized , controlled trials : where quality of reporting may be improved . Dis Colon Rectum 2002;45:443–447 The methodology of r and omized control trials ( RCTs ) of the primary treatment of early breast cancer has been review ed using a quantitative method . Sixty-three RCTs comparing various treatment modalities tested on over 34,000 patients and reported in 119 papers were evaluated according to a st and ardized scoring system . A percentage score was developed to assess the internal validity of a study ( referring to the quality of its design and execution ) and its external validity ( referring to presentation of information required to determine its generalizability ) . An overall score was also calculated as the combination of the two . The mean overall score for the 63 RCTs was 50 % ( 95 % confidence interval [ CI ] = 46 % to 54 % ) with small and nonstatistically significant differences between types of trial . The most common method ologic deficiencies encountered in these studies were related to the r and omization process ( only 27 of the 63 RCTs adopted a truly blinded procedure ) , the h and ling of withdrawals ( only 26 RCTs included all patients in the analyses ) , the description of the follow-up schedule ( only 12 RCTs reported adequately ) , the report of side effects ( adequate information given in 33 RCTs ) , and the description of the patient population ( satisfactory in 29 RCTs ) . Telephone calls to the principal investigators improved the quality scores by seven points on a scale of 100 , indicating that some of the deficiencies lay in reporting rather than performance . There was evidence that quality has improved over time and that the increasing tendency of involving a biostatistician in the research team was positively associated with the improvement of the internal validity but not with the external BACKGROUND Right ventricular assist devices ( RVADs ) have been proposed to improve exposure of the coronary arteries in off-pump surgery . In this study we investigated the impact of the A-Med RVAD on inflammatory response and organ function in patients undergoing coronary artery bypass grafting . METHODS Sixty patients were prospect ively r and omized to conventional surgery with cardiopulmonary bypass ( CPB ) and cardioplegic arrest , beating heart surgery ( off-pump ) , or beating heart surgery with the RVAD . Serial blood sample s were collected postoperatively , for analysis of inflammatory markers , troponin I , protein S100 , and free hemoglobin . Renal tubular function was assessed by measuring urine N-acetyl-glucosaminidase activity . RESULTS No hospital deaths or major postoperative complications occurred in the study population . Interleukin-6 , interleukin-8 , C3a , and troponin I levels after surgery were significantly higher in the CPB group compared with the off-pump and RVAD groups . Free hemoglobin levels immediately after the operation , peak and total S100 levels , and N-acetyl-glucosaminidase activity were also significantly higher in the CPB group . CONCLUSIONS Off-pump coronary revascularization , with or without RVAD , reduces inflammatory response , myocardial , neurologic , and renal injury , and decreases hemolysis when compared with conventional surgery with CPB and cardioplegic arrest BACKGROUND The feasibility of complete revascularization on the beating heart without cardiopulmonary bypass ( CPB ) as compared with the st and ard operation with CPB in elective low-risk patients with multivessel disease has not been clearly demonstrated in a prospect i ve trial . METHODS Eighty selected low-risk patients were enrolled . In preoperative study with coronary angiography , the decision was made whether complete revascularization without CPB could be performed . Patients were r and omly assigned to receive CABG either with ( n = 40 ) or without CPB ( n = 40 ) . R and omization criteria were age , sex , and left ventricular ejection fraction . Completeness of revascularization as well as short- and mid-term clinical outcome in a 13.4 + /- 6.5 month follow-up period were monitored . RESULTS Twenty-six of 40 ( 65 % ) patients undergoing CABG without CPB underwent complete revascularization . In 5 of these patients ( 12.5 % ) suitable vessels were discarded for technical reasons and 9 patients ( 22.5 % ) were switched to CABG with CPB owing to the deeply intramyocardial course of target vessels ( n = 5 ) or to hemodynamic instability ( n = 4 ) . In the group of patients operated on with CPB , 34 of 40 patients ( 85 % ) received complete revascularization . In 6 patients ( 15 % ) suitable vessels were discarded for technical reasons . Mean number of bypass grafts was 3.1 + /- 0.8 with CPB and 2.6 + /- 0.5 without CPB ( p = 0.043 ) . Clinical outcome and hospital stay were comparable in both groups . No patient died during the study period . No myocardial infa rct ion was observed . Three patients undergoing CABG without CPB underwent successful PTCA 3 months after surgery . CONCLUSIONS CABG without the use of CPB is effective for complete revascularization in the majority of selected low-risk patients . Nevertheless , it has to be stated that the rate of incomplete revascularization in this early series of CABG without CPB is higher , and compromises the basic principle of complete revascularization Abstract Objective : To assess neurocognitive impairment after the off-pump and on-pump techniques for coronary artery bypass graft surgery in patients with triple vessel disease . Design : R and omised controlled trial . Setting : University Hospital of Wales , Cardiff . Participants : 60 patients undergoing coronary artery bypass graft surgery for triple vessel disease prospect ively r and omised to the off-pump or on-pump technique . Main outcome measures : Change in scores in nine st and ard neuropsychometric tests administered preoperatively and at 1 and 10 weeks postoperatively . Results : The on-pump group showed a significantly greater deterioration in scores for two and three tests at 1 week and 10 weeks postoperatively , respectively , than the off-pump group . The on-pump group also showed a significantly higher incidence of major deterioration in one of the tests both 1 week and 10 weeks postoperatively . The incidence of neurocognitive impairment at 1 week postoperatively was 27 % ( 8 out of 30 ) in the off-pump group and 63 % ( 19 out of 30 ) in the on-pump group ( P=0.004 ) ; and at 10 weeks postoperatively was 10 % ( 3 out of 30 ) in the off-pump group and 40 % ( 12 out of 30 ) in the on-pump group ( P=0.017 ) . Conclusion : Off-pump coronary artery bypass graft surgery results in less neurocognitive impairment than the on-pump technique Abstract Background : Off-pump coronary artery bypass surgery has emerged as an alternative technique to traditional onpump surgery . The aim of this r and omized study was to compare perioperative morbidity and mortality and intraoperative and short-term graft patency in off-pump and on-pump coronary artery bypass grafting . Methods : One hundred twenty patients were r and omized for coronary revascularization with or without cardiopulmonary bypass . In all patients grafts and anastomoses were monitored with transit time Doppler ultrasonography and angiography . Angiography was repeated 3 months after the procedure in 115 of the patients . Results : Angiography 3 months postoperatively revealed that internal mammary artery patency was 98 % in both groups . Vein graft patency was 83 % in the off-pump group and 91 % in the on-pump group , a difference that was not statistically significant . One perioperative death was recorded in each group . Two strokes were recorded in the on-pump group , none in the off-pump group . Conclusion : In this prospect i ve , controlled study , perioperative and short-term outcome of off-pump coronary surgery equaled that of on-pump surgery Abstract Objective To determine whether poor reporting of methods in r and omised controlled trials reflects on poor methods . Design Observational study . Setting Reports of r and omised controlled trials conducted by the Radiation Therapy Oncology Group since its establishment in 1968 . Participants The Radiation Therapy Oncology Group . Outcome measures Content of reports compared with the design features described in the protocol s for all r and omised controlled trials . Results The method ological quality of 56 r and omised controlled trials was better than reported . Adequate allocation concealment was achieved in all trials but reported in only 42 % of papers . An intention to treat analysis was done in 83 % of trials but reported in only 69 % of papers . The sample size calculation was performed in 76 % of the studies , but reported in only 16 % of papers . End points were clearly defined and α and βerrors were prespecified in 76 % and 74 % of the trials , respectively , but only reported in 10 % of the papers . The one exception was the description of drop outs , where the frequency of reporting was similar to that contained in the original statistical files of the Radiation Therapy Oncology Group . Conclusions The reporting of method ological aspects of r and omised controlled trials does not necessarily reflect the conduct of the trial . Review ing research protocol s and contacting trialists for more information may improve quality assessment BACKGROUND This prospect i ve r and omized study aim ed to compare beating and arrested heart revascularization in patients undergoing first elective coronary artery bypass graft , with cardiac troponin I release used to evaluate myocardial injury . METHODS Seventy patients were r and omly assigned to a beating or arrested heart revascularization group . Cardiac troponin I concentrations were measured in serial venous blood sample s drawn preoperatively in both groups : after aortic unclamping at 6 , 9 , 12 , and 24 hours in the arrested heart group and after the last anastomosis at 6 , 9 , 12 , and 24 hours in the beating heart group . Analysis of covariance with repeated measures was performed to test the effect of group and time on cardiac troponin I concentration . RESULTS The total amount of cardiac troponin I released was higher in the arrested heart revascularization group than in the beating heart revascularization group ( 8.25 + /- 6.16 vs 3.18 + /- 4.75 microg , p < 0.0001 ) . Cardiac troponin I concentrations were significantly higher in the arrested heart group at hours 6 , 9 , 12 , and 24 than in the beating heart group ( p < 0.0001 ) . CONCLUSIONS The lower release of cardiac troponin I in the beating heart revascularization group indicates that conventional coronary artery bypass graft with cardioplegic arrest causes more damage to the heart than off-pump myocardial revascularization Background —Previous r and omized comparisons of off-pump and on-pump coronary artery bypass grafting ( CABG ) have yielded controversial results about the cardiac and neurological events and graft patency . In addition , these r and omized studies were composed of CABG with a few arterial grafts . We performed a prospect i ve r and omized controlled study to compare off-pump and on-pump CABG with multiple arterial grafts . Methods and Results —Between July , 2002 , and September , 2004 , 167 consecutive unselected patients referred for elective primary CABG were r and omly assigned to undergo multiple arterial off-pump CABG ( n=81 ) or on-pump CABG ( n=86 ) . The clinical outcomes and S-100 protein , neuron-specific enolase , and maximum creatine kinase-MB levels were compared . Early graft patency was examined within 3 weeks after the operation by angiography . The number of grafts performed per patient ( 3.5±1.0 for off-pump CABG and 3.6±0.9 for on-pump CABG ) and the number of arterial grafts performed per patient ( 3.3±1.0 for off-pump CABG and 3.4±0.9 for on-pump CABG ) were similar . Completeness of revascularization ( completed grafts/planned grafts ) was 98 % in both procedures . There were no hospital deaths in either group . The operation time was significantly ( P<0.001 ) shorter in the off-pump group than in the on-pump group ( 267±60 minutes versus 307±59 minutes ) . The incidence of perioperative complications was similar . The frequency of no need for transfusion was higher in the off-pump group than in the on-pump group ( 80 % versus 55 % , P<0.001 ) . The S-100 protein levels at the admission into the intensive care unit were significantly ( P<0.001 ) lower in the off-pump group than in the on-pump group ( 0.20±0.11 ng/mL versus 0.34±0.22 ng/mL ) . The neuron-specific enolase levels at the intensive care unit admission were significantly ( P<0.001 ) lower in the off-pump group than in the on-pump group ( 10.4±9.0 ng/mL versus 16.9±6.9 ng/mL ) . Maximum creatine kinase-MB levels were significantly ( P=0.046 ) lower in the off-pump group than in the on-pump group ( 17.1±16.7 IU/L versus 21.5±10.6 IU/L ) . The overall early graft patency rate with or without stenosis was the same ( 98 % ) in both groups , but the rate without stenosis was slightly worse in the off-pump group ( 93 % ) than in the on-pump group ( 96 % ) ( P=0.093 ) . The stenosis-free patency rate in the right coronary area was significantly ( P=0.028 ) worse in the off-pump CABG group ( 90 % ) than in the on-pump group ( 99 % ) . Conclusions —Off-pump CABG with multiple arterial grafts was as safe as the conventional on-pump CABG , with similar completeness of revascularization and early graft patency BACKGROUND Coronary artery bypass grafting ( CABG ) surgery is associated with systemic inflammation . Activation of neutrophils is a crucial step in inflammation and results in neutrophil sequestration within the tissues . One of the potential advantages of performing off-pump coronary artery bypass ( OPCAB ) surgery is the attenuation of the systemic inflammatory response . This prospect i ve r and omized study compares neutrophil activation in patients undergoing OPCAB versus those undergoing CABG with cardiopulmonary bypass ( CPB ) . METHODS Twenty patients undergoing primary isolated CABG were r and omly divided prospect ively into 2 groups : 1 group underwent CABG with CPB , and the other group underwent OPCAB . Central venous blood sample s were obtained before skin incision and at 15 minutes , 60 minutes , 2 hours , 5 hours , and 24 hours following the initiation of CPB or application of the stabilization device . Differential white cell counts were measured with routine laboratory techniques . CD11b surface expression on neutrophils was measured by flow cytometry . Interleukin 8 levels in the plasma were measured by enzyme-linked immunosorbent assays . RESULTS The 2 groups were matched with respect to preoperative and operative characteristics . White cell and neutrophil counts rose in both groups following the operation but were significantly higher in the OPCAB group at 5 hours ( P < .001 and P = .002 , respectively ) . Interleukin 8 concentrations were significantly higher in the CPB group at 5 hours following the initiation of CPB ( P = .034 ) . CD11b levels were significantly higher in the CPB group at 60 minutes ( P = .002 ) . CONCLUSION This prospect i ve r and omized study demonstrates that the activation of circulating neutrophils as measured by CD11b expression is lower following OPCAB than in CPB . Although OPCAB is associated with significantly higher neutrophil counts , these neutrophils exhibit fewer activation markers . The lower postoperative neutrophil counts occurring in the CPB group may be explained by the activation and consequent sequestration of the neutrophils in the CPB circuit and tissues OBJECTIVE The aim of this prospect i ve , r and omised study was to investigate the influence of extracorporeal circulation on the inflammatory response , our hypothesis being that off pump coronary artery bypass grafting ( OFFCAB ) procedures would generate less activation than on pump procedures ( ONCAB ) . METHODS Patients admitted for elective CABG were r and omised to either ONCAB or OFFCAB surgery and blood sample s were taken during and up to 24 h after the operation . We measured complement factors C5a and the terminal complement complex ( TCC , C59-b ) , and the interleukins IL-6 and IL-8 . Leukocytes were studied for cellular counts and adhesion molecules ( CD11b , CD35 and CD62L ) by flow cytometry . We included a combination of activity markers with different aspects of neutrophil function and combined these with in vitro activation . RESULTS The complement factors C5a and TCC showed a more rapid ( P=0.02 , P<0.001 ) and TCC a more profound ( P<0.001 ) increase in the ONCAB group than in the OFFCAB group during the operation , after that there were no inter-group differences . Cellular markers , cell counts and interleukin levels were activated by surgery but with no difference between groups . CONCLUSION This prospect i ve , r and omised study showed less complement activation in low risk OFFCAB , compared to ONCAB patients BACKGROUND We sought to investigate the effect of multiple coronary artery bypass grafting ( CABG ) with or without cardiopulmonary bypass ( CPB ) on the perioperative inflammatory response . METHODS Sixty patients undergoing CABG were r and omly assigned to one of two groups : ( A ) on pump with conventional CPB and cardioplegic arrest , and ( B ) off pump on the beating heart . Serum sample s were collected for estimation of neutrophil elastase , interleukin 8 ( IL-8 ) , C3a , and C5a preoperatively and at 1 , 4 , 12 , and 24 hours postoperatively . Furthermore , white blood cell ( WBC ) , neutrophil , and monocyte counts were carried out preoperatively and at 1 , 12 , 36 and 60 hours postoperatively . Overall incidence of infection and perioperative clinical outcome were also recorded . RESULTS The groups were similar in terms of age , weight , gender ratio , extent of coronary disease , left ventricular function , and number of grafts per patient . Neutrophil elastase concentration peaked early after CPB in the on-pump group , with a decline with time . Repeated- measures analysis of variance between groups and comparisons at each time point ( modified Bonferroni ) showed elastase concentrations were significantly higher in the on-pump than the off-pump group ( both p < 0.0001 ) . IL-8 increased significantly after surgery in the on-pump group , with no decline during the observation period ( p = 0.01 vs off pump ) . C3a and C5a rose early after surgery in both groups when compared with baseline values . Postoperative WBC , neutrophil , and monocyte counts were significantly higher in the on-pump than the off-pump group ( p < 0.01 ) . Finally , the incidence of postoperative overall infections was significantly higher in the on-pump group ( p < 0.0001 vs off pump ) . CONCLUSIONS CABG on the beating heart is associated with a significant reduction in inflammatory response and postoperative infection when compared with conventional revascularization with CPB and cardioplegic arrest BACKGROUND To evaluate hospital mortality and morbidity after myocardial revascularization in a prospect i ve and multicenter study , comparing on-pump versus off-pump in a special subset of patients with lesions in the left descending artery , alone or associated with the right coronary artery . METHODS A multicenter prospect i ve r and omized study was performed . One hundred and sixty selected low-risk patients were enrolled ; 80 patients were operated on-pump ( coronary artery bypass grafting [ CABG ] , group I ) and 80 patients were operated off-pump ( off-pump coronary artery bypass [ OPCAB ] , group II ) . One hundred and five were male and ages ranged from 39 to 70 years old ; mean 58.81 + /- 9.31 and median 59 . Preoperative clinical characteristics were similar in both groups ; only previous myocardial infa rct ion was higher in the OPCAB group . Patients with severe left ventricular dysfunction ( FE < /= 35 % ) , renal failure and lesions of the circumflex artery and its branches were excluded , as well as patients with significant comorbidities that were inappropriate for r and omization because we selected them for OPCAB procedures . RESULTS Hospital mortality was 2.5 % , three patients ( 3.7 % ) in group I ( on-pump ) and one patient ( 1.2 % ) in group II ( off-pump ) ( ns ) . The number of grafts per patients in group I was 1.81 + /- 0.6 , and 1.77 + /- 0.68 in group II ( p = 0.833 ) . There was no difference in the total operation time 205.10 + /- 54.30 minutes in group I and 189.50 + /- 55.44 in group II ( ns ) . Six patients ( 7.5 % ) had myocardial infa rct ion in group I and three ( 3.7 % ) in group II ( ns ) . Bleeding in the postoperative period was 680.50 + /- 434.1 mL in the on-pump group and 678.6 + /- 357.0 mL in the off-pump group ( ns ) . Three patients ( 3.7 % ) presented transient neurologic dysfunction in group I and six patients ( 7.5 % ) in group II ( ns ) . Intensive care stay was 2.4 + /- 1.0 days in the CABG and 2.3 + /- 0.98 days in the OPCAB group ( ns ) . CONCLUSIONS We did not find any statistical difference in hospital mortality and morbidity using on-pump or off-pump techniques for low-risk patients OBJECTIVES Our purpose was to establish whether coronary revascularization on the beating heart without cardiopulmonary bypass is less harmful to the brain than conventional surgery with cardiopulmonary bypass as indicated by measures of cognitive function or by changes in serum concentrations of S-100 protein , a recognized biochemical marker of cerebral injury . METHODS We conducted a prospect i ve r and omized trial in which the assessors of the outcome measures were blind to the treatment received . Sixty patients without known neurologic abnormality , undergoing coronary revascularization , were prospect ively r and omized to 1 of 2 groups : ( 1 ) cardiopulmonary bypass ( 32 degrees C-34 degrees C ) and cardioplegic arrest ( on pump ) with intermittent ante grade warm blood cardioplegia or ( 2 ) surgery on the beating heart ( off pump ) . Neuropsychologic performance was assessed before and 12 weeks after the operation . Serum S-100 protein concentration was measured at intervals up to 24 hours after the operation . RESULTS The groups had similar preoperative characteristics . There were no deaths or major neurologic complications in either group , nor was there any difference between groups in the chosen index of neurologic deterioration . Serum S-100 protein concentrations were higher in the on-pump group at 30 minutes , but any such difference between groups had disappeared 4 hours later . The extent of the changes in S-100 protein was unrelated to the index of neuropsychologic deterioration . CONCLUSIONS The changes in S-100 protein concentration suggest that the brain and /or blood-brain barrier may be more adversely affected during coronary artery surgery with cardiopulmonary bypass than during surgery on the beating heart , but that this may not be reflected in detectable neuropsychologic deterioration at 12 weeks OBJECTIVE Coronary artery bypass grafting on the beating heart through median sternotomy is a relatively new treatment , which allows multiple revascularization without the use of cardiopulmonary bypass . A prospect i ve r and omized study was design ed to investigate the effect of coronary bypass with or without cardiopulmonary bypass on postoperative blood loss and transfusion requirement . METHODS Two hundred patients with coronary artery disease were prospect ively r and omized to ( 1 ) on-pump treatment with conventional cardiopulmonary bypass and cardioplegic arrest and ( 2 ) off-pump treatment on the beating heart . Postoperative blood loss identified as total chest tube drainage , transfusion requirement , and related costs together with hematologic indices and clotting profiles were analyzed . RESULTS There was no difference between the groups with respect to preoperative and intraoperative patient variables . The mean ratio of postoperative blood loss and 95 % confidence interval between groups was 1.64 and 1.39 to 1.94 , respectively , suggesting on average a postoperative blood loss 1.6 times higher in the on-pump group compared with the off-pump group . Seventy-seven patients in the off-pump group required no blood transfusion compared with only 48 in the on-pump group ( P < .01 ) . Furthermore , less than 5 % of patients in the on-pump group required fresh frozen plasma and platelet transfusion compared with 30 % and 25 % , respectively , in the on-pump group ( both P < .05 ) . Mean transfusion cost per patient was higher in the on-pump compared with that in the off-pump group ( $ 184.8 + /- $ 35.2 vs $ 21.47 + /- $ 6.9 , P < .01 ) . CONCLUSIONS Coronary artery bypass grafting on the beating heart is associated with a significant reduction in postoperative blood loss , transfusion requirement , and transfusion-related cost when compared with conventional revascularization with cardiopulmonary bypass and cardioplegic arrest BACKGROUND Cardiac operations using extracorporeal circulation bear a risk of cerebral complications . The aim of our study was to investigate if off-pump operations without heart-lung machines can reduce cerebral injury . METHODS S100 , a protein specific for cerebral tissue , was used as a marker for cerebral impairment in 108 r and omized patients undergoing coronary bypass operation : 67 patients ( group A ) were operated on with extracorporeal circulation and cardioplegic cardiac arrest , and 41 patients ( group B ) underwent off-pump beating heart revascularization . Both groups were similar regarding age , sex , ejection fraction , and number of anastomoses . S100 levels were measured from induction of anesthesia until 24 hours after the operation . RESULTS Data collection was 100 % complete . There was no in-hospital death . Nonfatal myocardial infa rct ions occurred in 2 patients in group A , and 1 patient in group B required resternotomy for bleeding . There was no neurologic deficit in either group . S100 levels increased only slightly in the off-pump patients ( group B ) , whereas in group A there was a sharp rise in S100 concentration during extracorporeal circulation , only returning to baseline 6 hours after the end of the operation . Peak S100 levels were four times higher in group A than in group B ( 2.1 microg/L versus 0.5 microg/L ; p < 001 ) . CONCLUSIONS The results of our study suggest that perioperative cerebral impairment is reduced in cardiac operations without the use of extracorporeal circulation . Further large-scale studies are needed to show whether this result is reflected by fewer neurologic deficits Background . Coronary artery bypass grafting ( CABG ) with cardiopulmonary bypass ( CPB ) has the risk of renal dysfunction . The cause of renal dysfunction after CPB is multifactorial , such as nonpulsatile flow , renal hypoperfusion , hypothermia , and duration of CPB . This study compared off-pump technique with on-pump technique on renal function in patients who underwent CABG . Methods . Sixty patients with normal preoperative renal functions undergoing CABG were r and omly assigned to conventional revascularization with CPB ( on-pump ) or beating heart revascularization ( off-pump ) . Renal functions were assessed up to 10 days postoperatively . Results . Creatinine clearance was found to be significantly higher in the off-pump group than in the on-pump group ( p < .05 ) . The off-pump group had significantly less increase in creatinine levels when compared with the on-pump group ( p < .05 ) . The free water clearance values decreased similarly in both groups ; however , the recovery was more prompt in the off-pump group ( p < .05 ) . No significant differences were found in the prevalence of postoperative hemodialysis . Conclusion . The off-pump technique may provide a positive contribution and sufficient protection on postoperative renal functions in patients undergoing CABG BACKGROUND / PURPOSE Reports of clinical trials often lack adequate descriptions of design and analysis ; recent attention has focused on improving this omission so readers can properly assess the strength of the findings and draw their own conclusions . Similar analysis of study design and method ologic st and ards associated with quality reporting has not been carried out for pediatric surgery journals . METHODS All studies ( n = 642 ) published in 1998 in Journal of Pediatric Surgery ( JPS ) and Pediatric Surgery International ( PSI ) , were review ed for demographic data and study design . The frequency of reporting of 11 basic elements of design and analysis was evaluated in r and omized clinical trials ( RCT ) , nonr and omized clinical trials ( N RCT ) , and retrospective cohorts ( RC ) from JPS by consensus of 2 assessors . RESULTS Of the 642 studies , 17 % of articles ( 111 of 642 ) were classified as clinical studies . Sixty-three were comparative studies and consisted of RC ( n = 48 ) , N RCT ( n = 12 ) , and RCT ( n = 3 ) . Two-thirds of articles published were either case reports or case series ( 431 of 642 ) , and 16 % were basic science articles . Demographic analysis showed a wide range of topics addressed , 4 authors per article , and multiple country of origin of authors . More than 66 % of all RCT in JPS reported on eligibility criteria , admission before allocation , r and om allocation , method of r and omization , patients ' blindness to treatment , treatment complications , statistical analyses , statistical methods , loss to follow-up , and statistical methods ; 2 elements of design and analysis , however , were poorly reported : blind assessment of outcome ( 33 % ) and power ( 17 % ) . CONCLUSIONS There were few r and omized , controlled trials in pediatric surgery journals , and further attention should be given to evaluate the causal factors . Nine elements of quality reporting were well reported ; however , 2 others were poorly reported ; this may improve if editors of pediatric surgical journals provide authors with guidelines on how to report clinical trial design and analysis BACKGROUND Off-pump coronary artery bypass grafting surgery reduces the intraoperative cerebral embolic load and may therefore cause less brain injury . The main aim of this study was to compare off-pump and on-pump surgery with regard to the frequency of new postoperative cerebral ischemic lesions and the prevalence of postoperative cognitive impairment . We also assessed whether preoperative cerebral ischemic injury predicts the risk for cognitive dysfunction after surgery . METHODS One hundred twenty patients with ischemic coronary artery disease were prospect ively r and omized to undergo off-pump or on-pump surgery . A detailed neuropsychological assessment and a cerebral magnetic resonance imaging examination were performed on the day before and at 3 months postoperatively . The neuropsychological assessment was repeated at 12 months . RESULTS There was no significant ( p = 0.17 ) difference between off-pump ( 8.2 % ) and on-pump ( 17.3 % ) surgery with regard to new postoperative cerebral lesions . The prevalence of cognitive impairment after surgery was also similar in the two groups ( 3 months : off-pump 20.4 % , on-pump 23.1 % , p = 0.74 ; 12 months : off-pump 24.1 % , on-pump 23.1 % , p = 0.90 ) . The degree of preoperative cerebral ischemic injury was significantly associated with cognitive dysfunction after on-pump ( p = 0.02 ) but not after off-pump ( p = 0.22 ) surgery . None of the patients with normal preoperative radiologic findings were found to have cognitive impairment at 3 months postoperatively ( p = 0.04 ) . CONCLUSIONS Long-term cognitive function and magnetic resonance imaging evidence of brain injury were similar after off-pump and on-pump coronary artery bypass grafting surgery . Preoperative cerebral magnetic resonance imaging can be used to predict the risk for cognitive dysfunction after coronary artery bypass grafting surgery |
924 | 25,411,862 | RESULTS Across modalities , the existing evidence suggests that technology-assisted psychological interventions are efficacious for improving self-management of chronic pain in adults .
All modalities have been shown to provide benefit and no clearly superior modality has emerged . | OBJECTIVES The use of technology to provide chronic pain self-management interventions has increased in the recent years .
Individual studies have primarily focused on a single technology-assisted modality and direct comparisons of different technology-assisted modalities are rare .
Thus , little is known about the relative strengths and weaknesses of each technology-assisted modality .
MATERIAL S AND METHODS This article is a systematic review of technology-assisted self-management interventions for chronic nonheadache , noncancer pain in adults . | Summary Use of the Chronic Pain Management Program was associated with significant decreases in pain‐related , functional , and mental health outcomes and an increase in pain knowledge . Abstract Internet‐based educational and therapeutic programs ( e‐health applications ) are becoming increasingly popular for a variety of psychological and physical disorders . We tested the efficacy of an online Chronic Pain Management Program , a comprehensive , fully self‐directed and self‐paced system that integrates social networking features and self‐management tools into an interactive learning environment . Of 305 adult participants ( 196 women , 109 men ) , a total of 162 individuals with chronic pain were r and omly assigned unsupervised access to the program for approximately 6 weeks ; 143 were assigned to the wait‐listed control group with treatment as usual . A comprehensive assessment was administered before the study and approximately 7 and 14 weeks thereafter . All recruitment , data collection , and participant involvement took place online . Participation was fully self‐paced , permitting the evaluation of program effectiveness under real‐world conditions . Intent‐to‐treat analysis that used linear growth models was used as the primary analytic tool . Results indicated that program utilization was associated with significant decreases in pain severity , pain‐related interference and emotional burden , perceived disability , catastrophizing , and pain‐induced fear . Further , program use led to significant declines in depression , anxiety , and stress . Finally , as compared to the wait‐listed control group , the experimental group displayed a significant increase in knowledge about the principles of chronic pain and its management . Study limitations are considered , including the recognition that not all persons with chronic pain are necessarily good c and i date s for self‐initiated , self‐paced , interactive learning Objective The aim of this study was to compare 2 self-help-based interventions ; a coping-oriented approach , applied relaxation ( AR ) and an acceptance-oriented approach , acceptance and commitment therapy ( ACT ) , for persons with chronic pain . Method This study is a r and omized control trial ( N=90 ) with a mixed between-within participants design with repeated measures . Interventions in both conditions comprised an initial face-to-face session , a 7-week manual-based self-help intervention including weekly therapist telephone support and a concluding face-to-face session . Outcome measures included satisfaction with life , depression , anxiety , acceptance of chronic pain , level of function , and pain intensity . Effects were measured at preintervention and postintervention and at 6 and 12 months after the end of intervention . Results The results show that the ACT condition increased their level of acceptance significantly compared with the AR condition . There was also a marginally significant interaction effect regarding satisfaction with life in which the ACT condition had improved in comparison to the AR condition . Further , the ACT condition reported a higher level of function and decreased pain intensity compared with the AR condition . Both conditions improved significantly regarding depression and anxiety . Conclusions A manual-based self-help intervention with weekly therapist support in an ACT format adds value to the treatment repertoire for persons suffering with chronic pain Background Patients with knee and /or hip osteoarthritis ( OA ) are less physically active than the general population , while the benefits of physical activity ( PA ) have been well documented . Based on the behavioral grade d activity treatment , we developed a Web-based intervention to improve PA levels in patients with knee and /or hip OA , entitled “ Join2move ” . The Join2move intervention is a self-paced 9-week PA program in which the patient ’s favorite recreational activity is gradually increased in a time-contingent way . Objective The aim of the study was to investigate whether a fully automated Web-based PA intervention in patients with knee and /or hip OA would result in improved levels of PA , physical function , and self-perceived effect compared with a waiting list control group . Methods The study design was a two-armed r and omized controlled trial which was not blinded . Volunteers were recruited via articles in newspapers and health-related websites . Eligibility criteria for participants were : ( 1 ) aged 50 - 75 years , ( 2 ) self-reported knee and /or hip OA , ( 3 ) self-reported inactivity ( 30 minutes of moderate PA , 5 times or less per week ) , ( 4 ) no face-to-face consultation with a health care provider other than general practitioners , for OA in the last 6 months , ( 5 ) ability to access the Internet weekly , and ( 6 ) no contra-indications to exercise without supervision . Baseline , 3-month , and 12-month follow-up data were collected through online question naires . Primary outcomes were PA , physical function , and self-perceived effect . In a subgroup of participants , PA was measured objective ly using accelerometers . Secondary outcomes were pain , fatigue , anxiety , depression , symptoms , quality of life , self-efficacy , pain coping , and locus of control . Results Of the 581 interested respondents , 199 eligible participants were r and omly assigned to the intervention ( n=100 ) or waiting list control group ( n=99 ) . Response rates of question naires were 84.4 % ( 168/199 ) after 3 months and 75.4 % ( 150/199 ) after 12 months . In this study , 94.0 % ( 94/100 ) of participants actually started the program , and 46.0 % ( 46/100 ) reached the adherence threshold of 6 out of 9 modules completed . At 3 months , participants in the intervention group reported a significantly improved physical function status ( difference=6.5 points , 95 % CI 1.8 - 11.2 ) and a positive self-perceived effect ( OR 10.7 , 95 % CI 4.3 - 26.4 ) compared with the control group . No effect was found for self-reported PA . After 12 months , the intervention group showed higher levels of subjective ( difference=21.2 points , 95 % CI 3.6 - 38.9 ) and objective PA ( difference=24 minutes , 95 % CI 0.5 - 46.8 ) compared with the control group . After 12 months , no effect was found for physical function ( difference=5 points , 95 % CI −1.0 to 11.0 ) and self-perceived effect ( OR 1.2 , 95 % CI 0.6 - 2.4 ) . For several secondary endpoints , the intervention group demonstrated improvements in favor of the intervention group . Conclusions Join2move result ed in changes in the desired direction for several primary and secondary outcomes . Given the benefits and its self-help format , Join2move could be a component in the effort to enhance PA in sedentary patients with knee and /or hip OA . Trial Registration The Netherl and s National Trial Register : NTR2483 ; http://www.trialregister.nl/trialreg/admin/ rct view.asp?TC=2483 ( Archived by WebCite at http://www.webcitation.org/67NqS6Beq ) Background It is estimated that 30 % of adults in the United States experience daily chronic pain . This results in a significant burden on the health care system , in particular primary care , and on the workplace . Chronic pain management with cognitive-behavioral psychological treatment is effective in reducing pain intensity and interference , health-related quality of life , mood , and return to work . However , the population of individuals with chronic pain far exceeds the population of therapists that can provide this care face-to-face . The use of tailored , Web-based interventions for the management of chronic pain could address limitations to access by virtue of its unlimited scalability . Objective To examine the effects of a tailored Web-based chronic pain management program on subjective pain , activity and work interference , quality of life and health , and stress . Methods Eligible participants accessed the online pain management program and informed consent via participating employer or health care benefit systems ; program participants who completed baseline , 1- , and 6-month assessment s were included in the study . Of the 645 participants , the mean age was 56.16 years ( SD 12.83 ) , most were female ( 447/645 , 69.3 % ) , and white ( 505/641 , 78.8 % ) . Frequent pain complaints were joint ( 249/645 , 38.6 % ) , back ( 218/645 , 33.8 % ) , and osteoarthritis ( 174/654 , 27.0 % ) . The online pain management program used evidence -based theories of cognitive behavioral intervention , motivational enhancement , and health behavior change to address self-management , coping , medical adherence , social support , comorbidities , and productivity . The program content was individually tailored on several relevant participant variables . Results Both pain intensity ( mean 5.30 , SD 2.46 ) , and unpleasantness ( mean 5.43 , SD 2.52 ) decreased significantly from baseline to 1-month ( mean 4.16 , SD 2.69 and mean 4.24 , 2.81 , respectively ) and 6-month ( mean 3.78 , SD 2.79 and mean 3.78 , SD 2.79 , respectively ) assessment s ( P<.001 ) . The magnitude of the 6-month effects were large . Trends for decreases in pain interference ( 36.8 % reported moderate or enormous interference ) reached significance at 6 months ( 28.9 % , P<.001 ) . The percentage of the sample reporting fair or poor quality of life decreased significantly from 20.6 % at baseline to 16.5 % at 6 months ( P=.006 ) . Conclusions Results suggest that the tailored online chronic pain management program showed promising effects on pain at 1 and 6 months posttreatment and quality of life at 6 months posttreatment in this naturalistic study . Further research is warranted to determine the significance and magnitude of the intervention ’s effects in a r and omized controlled trial BACKGROUND total knee arthroplasty is an effective means for relieving the symptoms associated with degenerative arthritis of the knee . Rehabilitation is a necessary adjunct to surgery and is important in regaining optimum function . Access to high- quality rehabilitation services is not always possible , especially for those who live in rural or remote areas . The aim of this study was to evaluate the equivalence of an Internet-based telerehabilitation program compared with conventional outpatient physical therapy for patients who have had a total knee arthroplasty . METHODS this investigation was a single-blinded , prospect i ve , r and omized , controlled noninferiority trial . Sixty-five participants were r and omized to receive a six-week program of outpatient physical therapy either in the conventional manner or by means of an Internet-based telerehabilitation program . The primary outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) measured at baseline and six weeks by a blinded independent assessor . Secondary outcomes included the Patient-Specific Functional Scale , the timed up- and -go test , pain intensity , knee flexion and extension , quadriceps muscle strength , limb girth measurements , and an assessment of gait . Noninferiority was assessed through the comparison of group differences with a noninferiority margin and with linear mixed model statistics . RESULTS baseline characteristics between groups were similar , and all participants had significant improvement on all outcome measures with the intervention ( p < 0.01 for all ) . After the six-week intervention , participants in the telerehabilitation group achieved outcomes comparable to those of the conventional rehabilitation group with regard to flexion and extension range of motion , muscle strength , limb girth , pain , timed up- and -go test , quality of life , and clinical gait and WOMAC scores . Better outcomes for the Patient-Specific Functional Scale and the stiffness subscale of the WOMAC were found in the telerehabilitation group ( p < 0.05 ) . The telerehabilitation intervention was well received by participants , who reported a high level of satisfaction with this novel technology . CONCLUSIONS the outcomes achieved via telerehabilitation at six weeks following total knee arthroplasty were comparable with those after conventional rehabilitation . LEVEL OF EVIDENCE therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence Background Chronic pain , especially back pain , is a prevalent condition that is associated with disability , poor health status , anxiety and depression , decreased quality of life , and increased health services use and costs . Current evidence suggests that exercise is an effective strategy for managing chronic pain . However , there are few clinical programs that use generally available tools and a relatively low-cost approach to help patients with chronic back pain initiate and maintain an exercise program . Objective The objective of the study was to determine whether a pedometer-based , Internet-mediated intervention can reduce chronic back pain-related disability . Methods A parallel group r and omized controlled trial was conducted with 1:1 allocation to the intervention or usual care group . 229 veterans with nonspecific chronic back pain were recruited from one Department of Veterans Affairs ( VA ) health care system . Participants r and omized to the intervention received an uploading pedometer and had access to a website that provided automated walking goals , feedback , motivational messages , and social support through an e-community ( n=111 ) . Usual care participants ( n=118 ) also received the uploading pedometer but did not receive the automated feedback or have access to the website . The primary outcome was measured using the Rol and Morris Disability Question naire ( RDQ ) at 6 months ( secondary ) and 12 months ( primary ) with a difference in mean scores of at least 2 considered clinical ly meaningful . Both a complete case and all case analysis , using linear mixed effects models , were conducted to assess differences between study groups at both time points . Results Baseline mean RDQ scores were greater than 9 in both groups . Primary outcome data were provided by approximately 90 % of intervention and usual care participants at both 6 and 12 months . At 6 months , average RDQ scores were 7.2 for intervention participants compared to 9.2 for usual care , an adjusted difference of 1.6 ( 95 % CI 0.3 - 2.8 , P=.02 ) for the complete case analysis and 1.2 ( 95 % CI -0.09 to 2.5 , P=.07 ) for the all case analysis . A post hoc analysis of patients with baseline RDQ scores ≥4 revealed even larger adjusted differences between groups at 6 months but at 12 months the differences were no longer statistically significant . Conclusions Intervention participants , compared with those receiving usual care , reported a greater decrease in back pain-related disability in the 6 months following study enrollment . Between-group differences were especially prominent for patients reporting greater baseline levels of disability but did not persist over 12 months . Primarily , automated interventions may be an efficient way to assist patients with managing chronic back pain ; additional support may be needed to ensure continuing improvements . Trial Registration Clinical Trials.gov NCT00694018 ; http:// clinical trials.gov/ct2/show/NCT00694018 ( Archived by WebCite at http://www.webcitation.org/6IsG4Y90E ) OBJECTIVE The effects of treatment counseling or symptom monitoring telephone intervention strategies on the health outcomes of patients with rheumatoid arthritis ( RA ) or osteoarthritis ( OA ) , compared with usual care , were assessed . METHODS A 3-group , r and omized , controlled 9-month trial was conducted incorporating 405 patients with RA or OA and using the Arthritis Impact Measurement Scales ( AIMS 2 ) as the outcome measure . RESULTS Analyses of covariance showed that the AIMS 2 total health status of the treatment counseling group ( effect size = 33 , P < 0.01 ) , but not the symptom monitoring group ( effect size = 0.21 , P = 0.10 ) , was significantly improved , compared with usual care , for both RA and OA patients . The specific types of benefits differed significantly between RA and OA patients . The mean number of medical visits by OA patients in the treatment counseling group was also significantly reduced ( P < 0.01 ) . CONCLUSION Telephone contact using the treatment counseling strategy produced significant , but different , health status benefits for RA and OA patients . The symptom monitoring strategy produced modest benefits UNLABELLED This paper examines whether a telephone-based , automated maintenance enhancement program can help to reduce opioid and nonsteroidal anti-inflamatory drugs ( NSAID ) analgesic use in patients with chronic pain . Following 11 weeks of group cognitive-behavioral therapy ( CBT ) , 51 subjects with chronic musculoskeletal pain were r and omized to 1 of 2 study groups . Twenty-six subjects participated in 4 months of a Therapeutic Interactive Voice Response ( TIVR ) program in addition to st and ard follow-up care , while a control group of 25 subjects received st and ard follow-up care only . TIVR is an automated , telephone-based tool developed for the maintenance and enhancement of CBT skills . Opioid analgesic use decreased in the experimental group in both follow-ups : 4 and 8 months postCBT . In addition , at 8-month follow-up , 21 % of the TIVR subjects had discontinued the use of opioid analgesics , 23 % had discontinued NSAIDS , and 10 % had discontinued antidepressant medications . In contrast , the control group showed increases in opioid and NSAIDS use . Analysis of covariance ( ANCOVA ) revealed significant between-group differences in opioid analgesic use at 8-month follow up ( P = .004 ) . We have previously demonstrated the efficacy of TIVR to decrease pain and improve coping ; this analysis demonstrates that the use of TIVR may also result in concurrent reductions in opioid analgesic and NSAID medications use . PERSPECTIVE This article demonstrates that the Therapeutic Interactive Voice Response maintenance enhancement program can help to reduce opioid analgesic use in patients with chronic pain . This automated maintenance enhancement program could potentially assist patients not only to decrease pain and improve coping , but also to diminish the likelihood of opioid dependence & NA ; This paper reports the development of a scale for assessing the quality of reports of r and omised controlled trials for psychological treatments . The Delphi method was used in which a panel of 15–12 experts generated statements relating to treatment and design components of trials . After three rounds , statements with high consensus agreement were review ed by a second expert panel and rewritten as a scale . Evidence to support the reliability and validity of the scale is reported . Three expert and five novice raters assessed sets of 31 and 25 published trials to establish scale reliability ( ICC ranges from 0.91 to 0.41 for experts and novices , respectively ) and item reliability ( Kappa and inter‐rater agreement ) . The total scale score discriminated between trials globally judged as good and poor by experts , and trial quality was shown to be a function of year of publication . Uses for the scale are suggested We conducted a pilot study of a nurse-run telephone self-management programme for elderly people with osteoarthritis ( OA ) . Thirty-two subjects , aged 60 years or more , with a diagnosis of OA were recruited from two hospital rheumatology clinics and were r and omized to a control or intervention group . The intervention group received six weekly mailings of OA health education modules , a relaxation audio-tape and six weekly 45 min follow-up telephone self-management sessions . There was a 100 % compliance rate in the intervention group , and all subjects completed baseline and three-month interviews ; one subject in each group was lost to six-month follow-up . There were no significant differences in self-management between the control and intervention groups . However , at three months there were improvements in the intervention group ( relative to baseline ) on some outcome measures . The results suggest that the telephone may be a useful tool for reinforcing health-promoting activities for patients & NA ; Both pharmacological and non‐pharmacological interventions have demonstrated efficacy in the management of fibromyalgia ( FM ) . Non‐pharmacological interventions however are far less likely to be used in clinical setting s , in part due to limited access . This manuscript presents the findings of a r and omized controlled trail of an Internet‐based exercise and behavioral self‐management program for FM design ed for use in the context of a routine clinical care . 118 individuals with FM were r and omly assigned to either ( a ) st and ard care or ( b ) st and ard care plus access to a Web‐Enhanced Behavioral Self‐Management program ( WEB‐SM ) grounded in cognitive and behavioral pain management principles . Individuals were assessed at baseline and again at 6 months for primary endpoints : reduction of pain and an improvement in physical functioning . Secondary outcomes included fatigue , sleep , anxiety and depressive symptoms , and a patient global impression of improvement . Individuals assigned to the WEB‐SM condition reported significantly greater improvement in pain , physical functioning , and overall global improvement . Exercise and relaxation techniques were the most commonly used skills throughout the 6 month period . A no‐contact , Internet‐based , self‐management intervention demonstrated efficacy on key outcomes for FM . While not everyone is expected to benefit from this approach , this study demonstrated that non‐pharmacological interventions can be efficiently integrated into routine clinical practice with positive outcomes Background A large proportion of patients with knee and /or hip osteoarthritis ( OA ) do not meet the recommended levels of physical activity ( PA ) . Therefore , we developed a web-based intervention that provides a tailored PA program for patients with knee and /or hip OA , entitled Join2move . The intervention incorporates core principles of the behaviour grade d activity theory ( BGA ) . The aim of this study was to investigate the preliminary effectiveness , feasibility and acceptability of Join2move in patients with knee and /or hip OA . Methods A non-r and omized pilot study was performed among patients with knee and /or hip OA . Primary outcomes were PA ( SQUASH Question naire ) , physical function ( HOOS and KOOS question naires ) and self-perceived effect ( 7-point Likert scale ) . Baseline , 6 and 12 week follow-up data were collected via online question naires . To assess feasibility and acceptability , program usage ( modules completed ) and user satisfaction ( SUS question naire ) were measured as secondary outcomes . Participants from the pilot study were invited to be interviewed . The interviews focused on users ’ experiences with Join2move . Besides the pilot study we performed two usability tests to determine the feasibility and acceptability of Join2move . In the first usability test , software experts evaluated the website from a list of usability concepts . In the second test , users were asked to verbalize thoughts during the execution of multiple tasks . Results Twenty OA patients with knee and /or hip OA between 50 and 80 years of age participated in the pilot study . After six weeks , pain scores increased from 5.3 to 6.6 ( p=0.04 ) . After 12 weeks this difference disappeared ( p=0.5 ) . Overall , users were enthusiastic about Join2move . In particular , performing exercise at one 's own pace without time or travel restrictions was cited as convenient . However , some minor flaws were observed . Users perceived some difficulties in completing the entire introduction module and rated the inability to edit and undo actions as annoying . Conclusions This paper outlines the preliminary effectiveness , feasibility and acceptability of a web-based PA intervention . Preliminary results from the pilot study revealed that PA scores increased , although differences were not statistically significant . Interviews and usability tests suggest that the intervention is feasible and acceptable in promoting PA in patients with knee and /or hip OA . The intervention was easy to use and the satisfaction with the program was high . Trial registration The Netherl and s National Trial Register . Trial number : & NA ; We developed Therapeutic Interactive Voice Response ( TIVR ) as an automated , telephone‐based tool for maintenance enhancement following group cognitive – behavioral therapy ( CBT ) for chronic pain . TIVR has four components : a daily self‐monitoring question naire , a didactic review of coping skills , pre‐recorded behavioral rehearsals of coping skills , and monthly personalized feedback messages from the CBT therapist based on a review of the patient ’s daily reports . The first three components are pre‐recorded and all four can be accessed remotely by patients via touch‐tone telephone on dem and . Following 11 weeks of group CBT , 51 subjects with chronic musculoskeletal pain were r and omized to one of two study groups . Twenty‐six subjects participated in 4 months of TIVR , while a control group of 25 subjects received st and ard care only . The TIVR group showed maximum improvement over baseline at the 8‐month follow‐up for seven of the eight outcome measures ; improvement was found to be significant for all outcomes ( p ⩽ .001 ) . Between‐group analysis of covariance ( ANCOVA ) revealed significantly greater improvement for the experimental group at both 4‐ and 8‐month follow‐ups for most of the outcomes . Results demonstrate that TIVR can be used to decrease pain , improve coping and decrease likelihood of relapse into pain behavior . Preliminary analysis of medication usage suggests that the superior outcome of the TIVR group was unlikely to be a consequence of differential medication use BACKGROUND Given the high health care utilization , limited evidence for the effectiveness of back pain interventions , and the proliferation of e-mail health discussion groups , this study seeks to determine if the Internet can be used to improve health status and health care utilization for people with chronic back pain . METHODS R and omized controlled trial . Participants included 580 people from 49 states with chronic back pain having at least 1 outpatient visit in the past year , no " red-flag " symptoms , and access to e-mail . Major exclusion criteria included continuous back pain for more than 90 days causing major activity intolerance and /or receiving disability payments . INTERVENTION Closed , moderated , e-mail discussion group . Participants also received a book and videotape about back pain . Controls received a subscription to a non-health-related magazine of their choice . MAIN OUTCOME MEASURES Pain , disability , role function , health distress , and health care utilization . RESULTS At 1-year treatment , subjects compared with controls demonstrated improvements in pain ( P = .045 ) , disability ( P = .02 ) , role function ( P = .007 ) , and health distress ( P = .001 ) . Physician visits for the past 6 months declined by 1.5 visits for the treatment group and by 0.65 visits for the control group ( P = .07 ) . Mean hospital days declined nearly 0.20 days for the treated group vs and increased 0.04 days for the control group ( P = .24 ) . CONCLUSIONS An e-mail discussion group can positively affect health status and possibly health care utilization . It may have a place in the treatment of chronic recurrent back pain Objective To evaluate the effectiveness of an Acceptance Commitment Therapy based self-help book for people with chronic pain . Method This was a r and omized 2 group study design . Over a 6-week period , 6 participants read the self-help book and completed exercises from it with weekly telephone support whereas 8 others formed a wait-list control group . Subsequently , 5 of the wait-list participants completed the intervention . Participants completed preintervention and postintervention question naires for acceptance , values illness , quality of life , satisfaction with life , depression , anxiety , and pain . Initial outcome data were collected for 8 control participants and 6 intervention participants . Including the wait-list controls , a total of 11 participants completed preintervention and postintervention measures . Whilst completing the self-help intervention , each week participants ' rated the content of the book according to reading level and usefulness , and their comprehension of the content was also assessed . Results Compared with controls , participants who completed the book showed improved quality of life and decreased anxiety . When data from all the treatment participants were pooled , those who completed the intervention showed statistically significant improvements ( with large effect sizes ) for acceptance , quality of life , satisfaction with life , and values illness . Medium effect sizes were found for improvements in pain ratings . Conclusions These findings support the hypothesis that using the self-help book , with minimal therapist contact adds value to the lives of people who experience chronic pain OBJECTIVE To determine whether an interactive self-management Website for people with chronic back pain would significantly improve emotional management , coping , self-efficacy to manage pain , pain levels , and physical functioning compared with st and ard text-based material s. DESIGN The study utilized a pretest-posttest r and omized controlled design comparing Website ( painACTION-Back Pain ) and control ( text-based material ) conditions at baseline and at 1- , 3 , and 6-month follow-ups . PARTICIPANTS Two hundred and nine people with chronic back pain were recruited through dissemination of study information online and at a pain treatment clinic . The 6-month follow-up rates for the Website and control groups were 73 % and 84 % , respectively . MEASUREMENTS Measures were based on the recommendations of the Initiative on Methods , Measurement , and Pain Assessment in Clinical Trials and included measures of pain intensity , physical functioning , emotional functioning , coping , self-efficacy , fear-avoidance , perceived improvement with treatment , self-efficacy , and catastrophizing . RESULTS Compared with controls , painACTION-Back Pain participants reported significantly : 1 ) lower stress ; 2 ) increased coping self-statements ; and 3 ) greater use of social support . Comparisons between groups suggested clinical ly significant differences in current pain intensity , depression , anxiety , stress , and global ratings of improvement . Among participants recruited online , those using the Website reported significantly : 1 ) lower " worst " pain ; 2 ) lower " average " pain ; and 3 ) increased coping self-statements , compared with controls . Participants recruited through the pain clinic evidence d no such differences . CONCLUSIONS An online self-management program for people with chronic back pain can lead to improvements in stress , coping , and social support , and produce clinical ly significant differences in pain , depression , anxiety , and global rates of improvement OBJECTIVE To determine the efficacy of an Internet-based Arthritis Self-Management Program ( ASMP ) as a re source for arthritis patients unable or unwilling to attend small-group ASMPs , which have proven effective in changing health-related behaviors and improving health status measures . METHODS R and omized intervention participants were compared with usual care controls at 6 months and 1 year using repeated- measures analyses of variance . Patients with rheumatoid arthritis , osteoarthritis , or fibromyalgia and Internet and e-mail access ( n = 855 ) were r and omized to an intervention ( n = 433 ) or usual care control ( n = 422 ) group . Measures included 6 health status variables ( pain , fatigue , activity limitation , health distress , disability , and self-reported global health ) , 4 health behaviors ( aerobic exercise , stretching and strengthening exercise , practice of stress management , and communication with physicians ) , 5 utilization variables ( physician visits , emergency room visits , chiropractic visits , physical therapist visits , and nights in hospital ) , and self-efficacy . RESULTS At 1 year , the intervention group significantly improved in 4 of 6 health status measures and self-efficacy . No significant differences in health behaviors or health care utilization were found . CONCLUSION The Internet-based ASMP proved effective in improving health status measures at 1 year and is a viable alternative to the small-group ASMP Summary Objective : To illustrate the development and pilot evaluation of a website design ed to enhance self-management of chronic low back pain for the Italian-speaking population of Switzerl and . Methods : 20 patients affected by chronic low back pain used a website – specifically created for the project – for a period of five months , under the monitoring of a team of health professionals . Evaluation was carried out by means of a telephone question naire administered at baseline and at the end of the intervention , and intermediate online user-testing performed in the fourth month of the intervention . A control group of 15 patients was created to assist the evaluation . Results : Compared to the control group , results from the pilot evaluation suggest a decrease in the intensity of back pain in people with access to the website ; an increase in physical activity ; a reduction in both medical consultation and the use of painkillers , and a gain in declarative and procedural knowledge . This coincides with a general positive assessment of the website . Conclusion : The study supports the need to test the proposed approach on a wider scale PURPOSE Pain , a common reason for visits to primary care physicians , is often not well managed . The objective of this study was to determine the effectiveness of pain management interventions suitable for primary care physicians . METHODS Patients from 14 rural primary care practice s ( 47 physicians ) who reported diverse pain problems with ( n = 644 ) or without ( n = 693 ) psychosocial problems were r and omized to usual-care or intervention groups . All patients in the intervention group received information tailored to their problems and concerns ( INFO ) . These patients ’ physicians received feedback about their patients ’ problems and concerns ( FEED ) . A nurse-educator ( NE ) telephoned patients with pain and psychosocial problems to teach problem-solving strategies and basic pain management skills . Outcomes were assessed with the Medical Outcomes Study 36-Item Short-Form and the Functional Interference Estimate at baseline , 6 months , and 12 months . RESULTS Patients with pain and psychosocial problems r and omized to INFOFEED+NE significantly improved on the bodily pain ( P = .011 ) , role physical ( P = .025 ) , vitality ( P < .001 ) , role emotional ( P = .048 ) , and the Functional Interference Estimate ( P = .027 ) scales compared with usual-care patients at 6 months . These improvements were maintained at the 12-month assessment even though these patients had received , on average , only 3 telephone calls . Compared with usual-care patients , at 6 months patients who received INFOFEED alone experienced minimal improvements that were not sustained at the 12-month assessment . CONCLUSIONS For patients with pain and psychosocial problems , telephone-based assistance result ed in significant , sustained benefit in pain and psychosocial problems UNLABELLED The Self-care Pain Management Project assessed the feasibility and efficacy of delivering online mind-body self-care techniques to 78 adults aged 55 and older with chronic pain . To assess feasibility , the study monitored use of the intervention and documented participant satisfaction . A r and omized trial with intervention ( n = 41 ) and waiting list comparison groups ( n = 37 ) was used to assess changes in pain intensity , limitations due to pain , pain self-efficacy , depression , anxiety , and awareness of responses to pain from baseline to follow-up at 6 weeks . There were statistically significant results for between-group difference in awareness of responses to pain , improvements in pain intensity and pain interference for both groups , and increases in confidence with using nonmedical self-care techniques to manage pain for the intervention group . Reductions in mean pain scores reported by the intervention group at log on and log off also suggest that the intervention may have an immediate impact on reducing pain . Findings document the feasibility of a relatively short-term , online mind-body pain management intervention that can have benefits for participants . The characteristics of those who volunteered for an online self-care pain management intervention also have implication s for identifying target population s for such interventions . PERSPECTIVE This article documents the outcomes of an Internet-based self-care pain management intervention that focused on mind-body exercises . The study suggests that the Internet can be an efficient mode for delivering self-care education to older adults with chronic pain and has potential benefits that complement clinical care Objectives : Evaluate the effectiveness of an online self-management programme ( EPP Online ) for Engl and residents with long-term conditions . Methods : A prospect i ve longitudinal study . Data were collected online at baseline , 6 and 12 months . The intervention was an asynchronous 6-week chronic-disease self-management programme offered online . We measured seven health status measures ( health distress , self-rated health , illness intrusiveness , disability , fatigue , pain and shortness of breath ) , four behaviours ( aerobic exercise , stretching exercise , stress management and communications with physician ) , and five utilization measures ( GP visits , pharmacy visits , PT/OT visits , emergency visits and hospitalizations ) . We also measured self-efficacy and satisfaction with the health care system . Results : A total of 568 completed baseline data : 546 ( 81 % ) completed 6 months and 443 ( 78 % ) completed 1 year . Significant improvements ( p<0.01 ) were found at 6 months for all variables except self-rated health , disability , stretching , hospitalizations and nights in hospital . At 12 months only decrease in disability , nights in hospital and hospitalizations were not significant with reduction in visits to emergency departments being marginally significant ( p = 0.012 ) . Both self-efficacy and satisfaction with the health care system improved significantly . Discussion : The peer-led online programme conditions appears to decrease symptoms , improve health behaviours , self-efficacy and satisfaction with the health care system and reducing health care utilization up to 1 year OBJECTIVE The purpose was to examine whether or not participation in an e-mail discussion group would affect use of selected complementary and alternative medicine ( CAM ) modalities during an Internet-based , 1-year r and omized , controlled trial on back pain management . METHODS Intervention subjects ( n = 190 ) participated in a closed , moderated e-mail discussion group ; control subjects ( n = 231 ) received usual care . At 1 year , we compared CAM use over the previous 6-month period during which intervention subjects had had interactive discussion s about them . Differences in CAM use between groups were compared using Chi-square and t-tests . RESULTS Subjects did not differ statistically between groups ( p > 0.05 ) . They were Caucasian ( approximately 91 % ) , male ( approximately 60 % ) , in their mid-40s , well educated , had approximately 13 years back pain duration , a disability level approximately 10 ( Rol and -Morris scale : 0 - 23 ; 23 = worst ) , and > 80 % had used the Internet for greater than a year before the r and omized trial . During the study period , only small proportions in either group had initiated use of glucosamine ( 13 % versus 8 % ) , chiropractic services ( 5 % versus 4 % ) , acupuncture ( 3 % , both ) , yoga ( 6 % versus 4 % ) , or magnets ( 6 % , both ) . CONCLUSION Results suggest that participation in interactive discussion s over the Internet about these CAM modalities may not affect their use Abstract The purpose of this study was to investigate the effects of an Internet‐based cognitive‐behavioral intervention with telephone support for chronic back pain . Participants who met the criteria for chronic back pain ( N=56 ) were r and omly assigned to either an Internet‐based cognitive behavioral self‐help treatment or to a waiting‐list control condition . The study period lasted 8 weeks and consisted of 1 week of self‐monitoring prior to the intervention , 6 weeks of intervention , and 1 week of post‐intervention assessment . Treatment consisted of education , cognitive skill acquisition , behavioral rehearsal , generalization and maintenance . The dropout rate was 9 % ( N=5 ) . Results showed statistically significant improvements in catastrophizing , control over pain and ability to decrease pain . Some improvement was found in both the control group and the treatment group . A follow‐up of 3 months after treatment termination was completed in 92 % ( N=47 ) of the participants who completed the treatment intervention . Follow‐up results showed that some improvement was maintained . Findings indicate that Internet‐based self‐help with telephone support , based on established psychological treatment methods , holds promise as an effective approach for treating disability in association with pain OBJECTIVE In order to maintain treatment gains achieved during multidisciplinary treatments for chronic back pain , patients are challenged to implement the behavioral changes they learned during treatment into their daily life . Offering support during the critical time after treatment conclusion helps patients deal with relapses , provides them with practical advice and social support , and helps to master this transfer . As in-person offerings are not always feasible , innovative concepts are needed to enable hospitals to provide aftercare to their patients . SUBJECTS AND METHODS An Internet-based aftercare intervention following multidisciplinary therapy for back pain was constructed , implemented , and evaluated . The aftercare program comprised two modules : ( 1 ) an individualized self-monitoring module and ( 2 ) a weekly , 90-min chat session moderated by a therapist whom participants already knew from treatment . A r and omized controlled trial ( n=75 ) was conducted that compared the post-treatment symptom developments of program participants with symptom developments of controls ( treatment as usual [ TAU ] ) . RESULTS The program was proven to be feasible and well accepted by participants ; on average , 68.2 % of the participants rated the previous chat session as helpful . Intention-to-treat analyses demonstrated significant effects on post-treatment courses of disability . The largest effects were found for pain-related disability : for TAU participants , disability increased an average of 1.25 scale points ( Rol and -Morris Question naire ) per 100 days ; for program participants , disability decreased an average of 0.39 scale points ( p<0.01 ) . CONCLUSIONS The aftercare intervention was shown to be feasible and well accepted . Its efficacy should be tested with a larger-scale r and omized controlled trial Background : Efforts to enhance patient-physician communication may improve management of underdiagnosed chronic conditions . Patient internet portals offer an efficient venue for coaching patients to discuss chronic conditions with their primary care physicians ( PCP ) . Objectives : We sought to test the effectiveness of an internet portal-based coaching intervention to promote patient-PCP discussion about chronic conditions . Research Design : We conducted a r and omized trial of a nurse coach intervention conducted entirely through a patient internet-portal . Subjects : Two hundred forty-one patients who were registered portal users with scheduled PCP appointments were screened through the portal for 3 target conditions , depression , chronic pain , mobility difficulty , and r and omized to intervention and control groups . Measures : One-week and 3-month patient surveys assessed visit experiences , target conditions , and quality of life ; chart abstract ions assessed diagnosis and management during PCP visit . Results : Similar high percentages of intervention ( 85 % ) and control ( 80 % ) participants reported discussing their screened condition during their PCP visit . More intervention than control patients reported their PCP gave them specific advice about their health ( 94 % vs. 84 % ; P = 0.03 ) and referred them to a specialist ( 51 % vs. 28 % ; P = 0.002 ) . Intervention participants reported somewhat higher satisfaction than controls ( P = 0.07 ) . Results showed no differences in detection or management of screened conditions , symptom ratings , and quality of life between groups . Conclusions : Internet portal-based coaching produced some possible benefits in care for chronic conditions but without significantly changing patient outcomes . Limited sample sizes may have contributed to insignificant findings . Further research should explore ways internet portals may improve patient outcomes in primary care . Clinical Trials.gov registration NCT00130416 Purpose : Arthritis self‐efficacy ( ASE ) characterizes individuals ' confidence in managing their arthritis . This study 's purpose was to examine the effects of a telephone intervention on ASE , depression , pain , and fatigue in older adults with arthritis . Methods : Eighty‐five elders with arthritis were r and omly assigned to the intervention or control group . Participants in both groups : ( a ) completed baseline assessment s of ASE , depression , pain , and fatigue ; ( b ) received written information on arthritis management ; and ( c ) received individualized action plans for achieving their own arthritis management goal over the 6‐week study . Participants in the intervention group received a telephone intervention including instruction on managing arthritis and encouragement to pursue their goal . In the sixth week the assessment tools were re‐administered . Quantitative and qualitative data analysis methods were employed . Results : Quantitative analyses showed a significant increase in ASE and a significant reduction in depression and pain over time for both groups . Qualitative analyses revealed several themes related to benefits of telephone intervention . Conclusion : Study results suggest that minimal intervention ( ie , written information , goal ‐ setting , and action plans ) may produce positive changes in ASE , depression , and pain in some older adults with arthritis . Furthermore , telephone intervention may assist older patients in managing their arthritis BACKGROUND The clinical impact of telephone-delivered cognitive behavioral therapy ( TCBT ) , exercise , or a combined intervention in primary care patients with chronic widespread pain ( CWP ) is unclear . METHODS A total of 442 patients with CWP ( meeting the American College of Rheumatology criteria ) were r and omized to receive 6 months of TCBT , grade d exercise , combined intervention , or treatment as usual ( TAU ) . The primary outcome , using a 7-point patient global assessment scale of change in health since trial enrollment ( range : very much worse to very much better ) , was assessed at baseline and 6 months ( intervention end ) and 9 months after r and omization . A positive outcome was defined as " much better " or " very much better . " Data were analyzed using logistic regression according to the intention-to-treat principle . RESULTS The percentages reporting a positive outcome at 6 and 9 months , respectively , were TAU group , 8 % and 8 % ; TCBT group , 30 % and 33 % ; exercise group , 35 % and 24 % ; and combined intervention group , 37 % and 37 % ( P < .001 ) . After adjustment for age , sex , center , and baseline predictors of outcome , active interventions improved outcome compared with TAU : TCBT ( 6 months : odds ratio [ OR ] , 5.0 [ 95 % CI , 2.0 - 12.5 ] ; 9 months : OR , 5.4 [ 95 % CI , 2.3 - 12.8 ] ) , exercise ( 6 months : OR , 6.1 [ 95 % CI , 2.5 - 15.1 ] ; 9 months : OR , 3.6 [ 95 % CI , 1.5 - 8.5 ] ) , and combined intervention ( 6 months : OR , 7.1 [ 95 % CI , 2.9 - 17.2 ] ; 9 months : OR , 6.2 [ 95 % CI , 2.7 - 14.4 ] ) . At 6 and 9 months , combined intervention was associated with improvements in the 36-Item Short Form Health Question naire physical component score and a reduction in passive coping strategies . Conclusions on cost-effectiveness were sensitive to missing data . CONCLUSION TCBT was associated with substantial , statistically significant , and sustained improvements in patient global assessment . TRIAL REGISTRATION clinical trials.gov Identifier : IS RCT N67013851 This study investigated the effectiveness of telephone-delivered cognitive-behavioral therapy ( T-CBT ) in the management of chronic pain with older military veterans enrolled in VA primary -care clinics . We conducted a r and omized clinical trial comparing T-CBT with telephone-delivered pain education ( T-EDU ) . A total of 98 military veterans with chronic pain were enrolled in the study and r and omized into one of two treatment conditions . Study participants were recruited from primary -care clinics at an urban VA medical center and affiliated VA community-based outpatient clinics ( CBOCs ) . Pain management outcomes were measured at midtreatment ( 10 weeks ) , posttreatment ( 20 weeks ) , 3-month follow-up ( 32 weeks ) , and 6-month follow-up ( 46 weeks ) . No significant differences were found between the two treatment groups on any of the outcome measures . Both treatment groups reported small but significant increases in level of physical and mental health , and reductions in pain and depressive symptoms . Improvements in all primary outcome measures were mediated by reductions in catastrophizing . Telephone-delivered CBT and EDU warrant further study as easily accessible interventions for rural-living older individuals with chronic pain This study investigates utilization of the Internet in the rehabilitation of people on long-term sick leave with chronic pain and /or burnout . Fifty-five people were r and omly assigned to two groups : a treatment group ( n=27 ) that participated in a rehabilitation course over the Internet and a waiting list group ( n=28 ) . The goals were to improve participants ' health and increase quality of life , and , for those who were not on permanent disability pensions , to increase work capacity , if possible . A 20-week program , based on 19 films on different themes , was supplemented with written material and a Socratic dialogue over the Internet . Upon completion of the rehabilitation course , statistically significant improvements were observed in the treatment group in comparison to the waiting list group , for variables such as depression , pain , vitality , social function , performance problems involving work or other activities due to physical illness and the presence of stress symptoms . Thirteen of 23 individuals ( 57 % ) also increased their work capacity . The number needed to treat regarding recovering from anxiety and depression was 2 . For increased work capacity , the number needed to treat was 3 . Rehabilitation of people on long-term sick leave carried out over the Internet is a good complement to other rehabilitation programs . Die vorliegende Studie befasst sich mit der Nutzung des Internets bei der Rehabilitation von Langzeitkranken mit chronischen Schmerzen und/oder Burnout-Syndrom . Zwei Gruppen wurden insgesamt 55 Studienteilnehmer r and omisiert zugeordnet , d. h. einer Therapiegruppe ( n=27 ) , die an einem Internet-basierten Reha-Kurs teilnahm , und einer Wartelistengruppe ( n=28 ) . Die Ziele waren die gesundheitliche Verbesserung der Teilnehmer und die Steigerung der Lebensqualität und – für diejenigen , die nicht permanent eine Erwerbsunfähigkeitsrente bezogen – nach Möglichkeit eine Steigerung der Arbeitsleistung . Ein 20-Wochen-Programm auf der Grundlage von 19 Filmen zu unterschiedlichen Themen wurde durch schriftliches Material und einen sokratischen Dialog per Internet ergänzt . Nach Beendigung des Reha-Kurses wurden in der Therapiegruppe verglichen mit der Wartelistengruppe statistisch signifikante Verbesserungen bei Variablen wie Depression , Schmerzen , Lebenskraft , gesellschaftliche Funktion , Leistungsprobleme bei der Arbeit oder and eren Aktivitäten infolge von körperlicher Krankheit und das Vorh and ensein von Stresssymptomen beobachtet . Dreizehn von 23 Teilnehmern ( 57 % ) steigerten zudem ihre Arbeitsleistung . Wegen der Rekonvaleszenz von Angstgefühlen und Depression mussten insgesamt zwei Teilnehmer beh and elt werden , bei der Steigerung der Arbeitsleistung lag die Zahl bei drei . Mit einer Internet-basierten Rehabilitation von Langzeitkranken lassen sich and ere Reha-Programme gut ergänzen . Este estudio investiga la utilización de Internet en la rehabilitación de individuos con ausencia prolongada al trabajo por enfermedad , por padecer dolor crónico o el síndrome del desgaste profesional , o ambos . Se distribuyeron a 55 individuos al azar en dos grupos : un grupo de tratamiento ( n=27 ) , quienes participaron en un curso de rehabilitación impartido mediante Internet , y un grupo en lista de espera ( n=28 ) . Los objetivos fueron mejorar la salud y calidad de vida de los participantes y , para aquellos que no estaban percibiendo pensión de invalidez permanente , aumentar la capacidad de trabajo , de ser posible . Se aplicó un programa de 20 semanas , por Internet , en el que se emplearon 19 películas sobre diferentes temas , complementadas con material es escritos y un diálogo socrático . Al terminar el curso de rehabilitación se hallaron mejorías estadísticamente significativas en el grupo sometido a tratamiento , a diferencia del grupo en la lista de espera , en relación con variables tales como la depresión , el dolor , la vitalidad , la función social , problemas de rendimiento en el trabajo o al realizar otras actividades debido a la presencia de enfermedades orgánicas , y la presencia de síntomas de estrés . Trece de los 23 individuos ( 57 % ) mejoraron su capacidad de trabajo . De estas personas , 2 recibieron el tratamiento como alivio a la ansiedad y depresión que padecían ; y 3 para mejorar su capacidad de trabajo . La rehabilitación de individuos con ausencia prolongada al trabajo por enfermedad , mediante Internet , es un buen complemento al resto de los programas de rehabilitación empleados . Cette étude s'intéresse à l'utilisation de l'Internet pour la rééducation des individus en congé maladie de longue durée souffrant de douleurs chroniques et/ou d'épuisement . Cinquante-cinq personnes ont été réparties de manière aléatoire dans deux groupes ; un groupe de traitement ( n=27 ) , qui a participé au stage de rééducation sur Internet , et un groupe sur liste d'attente ( n=28 ) . Les objectifs étaient d'améliorer la santé et la qualité de vie des participants et , pour les individus ne bénéficiant pas de pensions d'invalidité permanentes , d'accroître la capacité de travail dans la mesure du possible . Un programme sur 20 semaines , reposant sur 19 films consacrés à des thèmes différents , a été complété par des matériaux écrits et un dialogue socratique via l'Internet . À la fin du stage de rééducation , des améliorations statistiquement significatives ont été observées chez le groupe de traitement par rapport au groupe sur liste d'attente , notamment pour les variables comme la dépression , la douleur , la vitalité , la fonction sociale , les problèmes de performances dus à la maladie physique et impliquant le travail ou d'autres activités , et la présence de symptômes de stress . Treize des 23 participants ( 57 % ) ont également augmenté leur capacité de travail . Le nombre d'individus à traiter pour des problèmes d'anxiété et de dépression était de 2 . Pour l'augmentation de la capacité de travail , le nombre à traiter était de 3 . La rééducation des individus en congé maladie de longue durée via l'Internet constitue un bon complément aux autres programmes de rééducation BACKGROUND Osteoarthritis is a leading cause of pain and disability , and self-management behaviors for osteoarthritis are underutilized . OBJECTIVE To examine the effectiveness of a telephone-based self-management intervention for hip or knee osteoarthritis in a primary care setting . DESIGN R and omized clinical trial with equal assignment to osteoarthritis self-management , health education ( attention control ) , and usual care control groups . ( Clinical Trials.gov registration number : NCT00288912 ) SETTING Primary care clinics in a Veterans Affairs Medical Center . PATIENTS 515 patients with symptomatic hip or knee osteoarthritis . INTERVENTION The osteoarthritis self-management intervention involved educational material s and 12 monthly telephone calls to support individualized goals and action plans . The health education intervention involved nonosteoarthritis educational material s and 12 monthly telephone calls related to general health screening topics . MEASUREMENTS The primary outcome was score on the Arthritis Impact Measurement Scales-2 pain subscale ( range , 0 to 10 ) . Pain was also assessed with a 10-cm visual analog scale . Measurements were collected at baseline and 12 months . RESULTS 461 participants ( 90 % ) completed the 12-month assessment . The mean Arthritis Impact Measurement Scales-2 pain score in the osteoarthritis self-management group was 0.4 point lower ( 95 % CI , -0.8 to 0.1 point ; P = 0.105 ) than in the usual care group and 0.6 point lower ( CI , -1.0 to -0.2 point ; P = 0.007 ) than in the health education group at 12 months . The mean visual analog scale pain score in the osteoarthritis self-management group was 1.1 points lower ( CI , -1.6 to -0.6 point ; P < 0.001 ) than in the usual care group and 1.0 point lower ( CI , -1.5 to -0.5 point ; P < 0.001 ) than in the health education group . Health care use did not differ across the groups . LIMITATION The study was conducted at 1 Veterans Affairs Medical Center , and the sample consisted primarily of men . CONCLUSION A telephone-based osteoarthritis self-management program produced moderate improvements in pain , particularly compared with a health education control group . PRIMARY FUNDING SOURCE U.S. Department of Veterans Affairs Health Services Research and Development Service & NA ; Examination of a clinician‐guided Internet‐delivered cognitive behaviour therapy program for chronic pain found significant improvements in disability , anxiety , depression , and average pain ratings . & NA ; The present study evaluated the efficacy of a clinician‐guided Internet‐delivered cognitive behaviour therapy ( iCBT ) program , the Pain Course , to reduce disability , anxiety , and depression associated with chronic pain . Sixty‐three adults with chronic pain were r and omised to either a Treatment Group or waitlist Control Group . Treatment consisted of 5 iCBT‐based lessons , homework tasks , additional re sources , weekly e‐mail or telephone contact from a Clinical Psychologist , and automated e‐mails . Twenty‐nine of 31 Treatment Group participants completed the 5 lessons during the 8‐week program , and posttreatment and 3‐month follow‐up data were collected from 30/31 and 29/31 participants , respectively . Treatment Group participants obtained significantly greater improvements than Control Group participants in levels of disability , anxiety , depression , and average pain levels at posttreatment . These improvements corresponded to small to large between‐groups effect sizes ( Cohen ’s d ) at posttreatment for disability ( d = .88 ) , anxiety ( d = .38 ) , depression ( d = .66 ) , and average pain ( d = .64 ) , respectively . These outcomes were sustained at follow‐up and participants rated the program as highly acceptable . Overall , the clinician spent a total mean time of 81.54 minutes ( SD 30.91 minutes ) contacting participants during the program . The results appear better than those reported in iCBT studies to date and provide support for the potential of clinician‐guided iCBT in the treatment of disability , anxiety , and depression for people with chronic pain Background and Purpose Fear of movement is a risk factor for poor postoperative outcomes in patients following spine surgery . The purpose s of this case series were : ( 1 ) to describe the effects of a cognitive-behavioral – based physical therapy ( CBPT ) intervention in patients with high fear of movement following lumbar spine surgery and ( 2 ) to assess the feasibility of physical therapists delivering cognitive-behavioral techniques over the telephone . Case Description Eight patients who underwent surgery for a lumbar degenerative condition completed the 6-session CBPT intervention . The intervention included empirically supported behavioral self-management , problem solving , and cognitive restructuring and relaxation strategies and was conducted in person and then weekly over the phone . Patient-reported outcomes of pain and disability were assessed at baseline ( 6 weeks after surgery ) , postintervention ( 3 months after surgery ) , and at follow-up ( 6 months after surgery ) . Performance-based outcomes were tested at baseline and postintervention . The outcome measures were the Brief Pain Inventory , Oswestry Disability Index , 5-Chair St and Test , and 10-Meter Walk Test . Outcomes Seven of the patients demonstrated a clinical ly significant reduction in pain , and all 8 of the patients had a clinical ly significant reduction in disability at 6-month follow-up . Improvement on the performance-based tests also was noted postintervention , with 5 patients demonstrating clinical ly meaningful change on the 10-Meter Walk Test . Discussion The findings suggest that physical therapists can feasibly implement cognitive-behavioral skills over the telephone and may positively affect outcomes after spine surgery . However , a r and omized clinical trial is needed to confirm the results of this case series and the efficacy of the CBPT intervention . Clinical implication s include broadening the availability of well-accepted cognitive-behavioral strategies by exp and ing implementation to physical therapists and through a telephone delivery model |
925 | 29,989,042 | Overall , the studies suggest that water carriage is associated with negative aspects of the water carriers ' health .
There is moderate quantitative and strong qualitative evidence that water carriage is associated with pain , fatigue , perinatal health problems and violence against vulnerable people , and inconclusive evidence of an association with stress or self-reported mental health and general health status . | Introduction The work of carrying water falls mainly on women and children , particularly in sub-Saharan Africa and rural areas .
While concerns have been raised , how water carriage is associated with health of the water carrier is not clear .
The aim of this review is to summarise evidence on whether , and how , water carriage is associated with the water carrier 's health . | Objective A focus on bacterial contamination has limited many studies of water service delivery in slums , with diarrheal illness being the presumed outcome of interest . We conducted a mixed methods study in a slum of 12,000 people in Mumbai , India to measure deficiencies in a broader array of water service delivery indicators and their adverse life impacts on the slum ’s residents . Methods Six focus group discussion s and 40 individual qualitative interviews were conducted using purpose ful sampling . Quantitative data on water indicators — quantity , access , price , reliability , and equity — were collected via a structured survey of 521 households selected using population -based r and om sampling . Results In addition to negatively affecting health , the qualitative findings reveal that water service delivery failures have a constellation of other adverse life impacts — on household economy , employment , education , quality of life , social cohesion , and people ’s sense of political inclusion . In a multivariate logistic regression analysis , price of water is the factor most strongly associated with use of inadequate water quantity ( ≤20 liters per capita per day ) . Water service delivery failures and their adverse impacts vary based on whether households fetch water or have informal water vendors deliver it to their homes . Conclusions Deficiencies in water service delivery are associated with many non-health-related adverse impacts on slum households . Failure to evaluate non-health outcomes may underestimate the deprivation result ing from inadequate water service delivery . Based on these findings , we outline a multidimensional definition of household “ water poverty ” that encourages policymakers and research ers to look beyond evaluation of water quality and health . Use of multidimensional water metrics by governments , slum communities , and research ers may help to ensure that water supplies are design ed to advance a broad array of health , economic , and social outcomes for the urban poor Background People living with HIV/AIDS have substantially greater need for water , sanitation , and hygiene . Encouraging hygiene education for People Living with HIV/AIDS in home based care services and additional support for the provision of water , sanitation , and hygiene services is recommended . Methods A cross-sectional study was carried during 2009 to assess water , sanitation status and hygiene practice s and associated factors among People Living with HIV/AIDS in home based care services in Gondar city of Ethiopia . A systematic r and om sampling was used to select study subjects from 900 Home Based Care clients of People Living HIV/AIDS in Gondar city . Data was collected from 296 People Living with HIV/AIDS from two NGO ’s in the city . For in-depth interview , four different categories were participated . Logistic regression and thematic framework analysis were performed for quantitative and qualitative part respectively . Results Two hundred ninety four subjects ( 72.8 % ( 214 ) females and 27.2 % ( 80 ) males ) were studied . The mean age was 35.8 ± 8.7 years . In the study , 42.9 % ( 126 ) of the households have unimproved water status , 67 % ( 197 ) of the households have unimproved sanitation status , and 51.7 % ( 152 ) of the households have poor hygienic practice . Diarrhoea with water status ; educational status and latrine availability with sanitation status ; and h and washing device availability and economical reasons for the affordability of soap with hygienic practice were significantly associated . Economical reasons and hygiene education were factors that affect water , sanitation , and hygienic practice . Stigma and discrimination were minimized as a factor in the study area . Conclusions There is high burden of water , sanitation and hygiene in people living HIV/AIDS in home based care services . Encouraging hygiene education for people living HIVAIDS in home based care services and additional support for the provision of water , sanitation , and hygiene services is recommended Background Governments , multinational organisations , and charities have commenced the distribution of sanitary products to address current deficits in girls ’ menstrual management . The few effectiveness studies conducted have focused on health and education outcomes but have failed to provide quantitative assessment of girls ’ preferences , experiences of absorbents , and comfort . Objectives of the study were , first , to quantitatively describe girls ’ experiences with , and ratings of reliability and acceptability of different menstrual absorbents . Second , to compare ratings of freely-provided reusable pads ( AFRIpads ) to other existing methods of menstrual management . Finally , to assess differences in self-reported freedom of activity during menses according to menstrual absorbent . Methods Cross-sectional , secondary analysis of data from the final survey of a controlled trial of reusable sanitary pad and puberty education provision was undertaken . Participants were 205 menstruating schoolgirls from eight schools in rural Ug and a. 72 girls who reported using the intervention-provided reusable pads were compared to those using existing improvised methods ( predominately new or old cloth ) . Results Schoolgirls using reusable pads provided significantly higher ratings of perceived absorbent reliability across activities , less difficulties changing absorbents , and less disgust with cleaning absorbents . There were no significant differences in reports of outside garment soiling ( OR 1.00 95%CI 0.51–1.99 ) , or odour ( 0.84 95%CI 0.40–1.74 ) during the last menstrual period . When girls were asked if menstruation caused them to miss daily activities there were no differences between those using reusable pads and those using other existing methods . However , when asked about activities avoided during menstruation , those using reusable pads participated less in physical sports , working in the field , fetching water , and cooking . Conclusions Reusable pads were rated favourably . This translated into some benefits for self-reported involvement in daily activities , although reports of actual soiling and missing activities due to menstruation did not differ . More research is needed comparing the impact of menstrual absorbents on girls ’ daily activities , and validating outcome measures for menstrual management research The lifting and carrying of loads in agriculture on small l and holdings are unavoidable . Rural communities often lack access to appropriate technologies which may result in various health hazards . The objective was to study gender participation in agricultural activities involving manual material h and ling tasks , to assess MSDs experienced in various MMH tasks and to evaluate traditional method and design ed technology . The study was conducted on 100 agricultural workers . Data on gender participation in MMH tasks in household , animal husb and ry and agriculture and result ing MSDs was gathered . Pre and post assessment of technology intervention was done for NIOSH Lifting Index , QEC , and RPE . The results revealed greater susceptibility of females to musculoskeletal problems in most of the household and animal husb and ry tasks . The h and trucks design ed were pushing type with power grasp h and le . The respondents were advised to carry 5 kg of weight per lift instead of lifting more weight in one lift/minute while filling the h and truck . By decreasing the weight and increasing the number of lifts per minute the respondents were seen falling in green zone indicating significant reduction in NIOSH lifting index . QEC scores concluded that for filling the h and truck 5 kg of weight should be carried to keep the exposure level low This paper examines the impact of water fetching by women and the quality of water during periods of water scarcity on the health of women in the Kumasi metropolitan area . A sample of 210 women drawn using systematic r and om procedure is used for the study . Formal interview is the main instrument used . The survey has established that income , quality of water , hours spent fetching water during scarcity and age are the main factors influencing women 's health in the metropolis during water scarcity . In both the core and periphery , the water-related problem influencing health is hours spent fetching water during scarcity . An empirical model on water needs and women 's health has emerged from the survey . Recommendations have been made on strategies to ensure regular volume of surface water , effective management of scarce water re sources with the participation of women , and ensuring gender equity in domestic services The use of self-assessed health status ( SAHS ) as a measure of health is common in empirical research . We analyse a unique Australian survey in which a r and om sub- sample of respondents answer a st and ard self-assessed health question twice-before and after an additional set of health related questions . A total of 28 % of respondents change their reported health status . Response reliability is related to age , income and occupation . We also compare the responses of these individuals to other respondents who are queried only once , to isolate effects of question order and mode of administration We used a community engagement approach to develop a One Health profile of an agro-pastoralist population at the interface of wildlife areas in eastern South Africa . Representatives from 262 r and omly-selected households participated in an in-person , cross-sectional survey . Questions were design ed to ascertain the participants ' knowledge , attitudes , and practice s with regard to human health , domestic animal health , and natural re sources including wildlife and water . Surveys were conducted within four selected villages by a team of trained surveyors and translators over four weeks in July-August 2013 . Questions were a combination of multiple choice ( single answer ) , multiple selection , open-ended , and Likert scale . The study found that nearly three-quarters of all households surveyed reported owning at least one animal ( 55 % owned chickens , 31 % dogs , 25 % cattle , 16 % goats , 9 % cats , and 5 % pigs ) . Among the animal-owning respondents , health concerns identified included dissatisfaction with government-run cattle dip facilities ( 97 % ) and frequent morbidity and mortality of chickens that had clinical signs consistent with Newcastle disease ( 49 % ) . Sixty-one percent of participants believed that diseases of animals could be transmitted to humans . Ninety-six percent of respondents desired greater knowledge about animal diseases . With regard to human health issues , the primary barrier to health care access was related to transportation to/from the community health clinics . Environmental health issues revealed by the survey included disparities by village in drinking water reliability and frequent domiciliary rodent sightings positively associated with increased household size and chicken ownership . Attitudes towards conservation were generally favorable ; however , the community demonstrated a strong preference for a dichotomous approach to wildlife management , one that separated wildlife from humans . Due to the location of the community , which neighbors the Great Limpopo Transfrontier Conservation Area , and the livestock-dependent lifestyle of the re source -poor inhabitants , a One Health approach that takes into consideration the interconnectedness of human , animal , and environmental health is necessary . The community profile described in this study provides a foundation for health research and planning initiatives that are driven by community engagement and consider the multitude of factors affecting health at the human-domestic animal-wildlife interface . Furthermore , it allows for the determination and quantification of the linkages between human , animal , and environmental health OBJECT The Hoffmann sign is commonly used in clinical practice to assess cervical spine disease . It is unknown whether the sign correlates with the severity of myelopathy , and no consensus exists regarding the significance of a positive sign in asymptomatic individuals . METHODS In a retrospective review of cervical spine surgeries for myelopathy due to cervical spondylosis , ossification of the posterior longitudinal ligament , or disc herniation performed at a tertiary center , the authors compiled data on the presence of hyperreflexia , the Hoffmann and Babinski signs , and modified Japanese Orthopaedic Association ( mJOA ) scale scores . Then , in a prospect i ve evaluation , new patients with lumbar spine complaints were examined for the presence of a Hoffmann sign , and , if present , a cervical MR imaging study was assessed for cord compression . RESULTS Of the 225 surgically treated patients , a Hoffmann sign occurred in 68 % , hyperreflexia in 60 % , and a Babinski sign in 33 % . In patients with milder disability ( mJOA Scores 14 - 16 ) , the Hoffmann sign was present in 46 % , whereas a Babinski sign occurred in 10 % ; in those with severe myelopathy and mJOA scores of < or = 10 , the Hoffmann sign was present in 81 % and the Babinski sign in 83 % . Of 290 patients presenting exclusively with lumbar spine-related complaints , 36 ( 12 % ) had a positive Hoffmann sign . Magnetic resonance imaging demonstrated spinal cord compression in 91 % when the sign was present bilaterally and 50 % when positive unilaterally . CONCLUSIONS In patients surgically treated for cervical myelopathy , the Hoffmann sign is more prevalent and more likely to be seen in individuals with less severe neurological deficits than the Babinski sign . In patients with lumbar symptoms , a bilateral Hoffmann sign was a highly sensitive marker for occult cervical cord compression , whereas a unilateral Hoffmann sign correlated with similar disease in about one-half of patients |
926 | 29,990,615 | The findings show that involving the target community in developing culturally appropriate interventions appears to be important in their acceptability , delivery and uptake .
Using community-based participation in intervention planning , evaluation and research appears to produce culturally and linguistically tailored interventions that address core values , attitudes , beliefs and norms , and encourage participation in PA .
Furthermore , the use of community health workers and underpinning the interventions with a psychological theory show promise in increasing PA uptake . | OBJECTIVES To identify interventions aim ed at increasing physical activity ( PA ) levels among South Asian ( SA ) adults and identify the specific changes in the content and delivery mode of interventions design ed to increase PA levels among SA people aged ≥18 years . | High prevalence of type 2 diabetes ( T2D ) is seen in some immigrant groups in Western countries , particularly in those from the Indian subcontinent . Our aims were to increase the physical activity ( PA ) level in a group of Pakistani immigrant men , and to see whether any increase was associated with reduced serum glucose and insulin concentrations . The intervention was developed in collaboration with the Pakistani community . It used a social cognitive theory framework and consisted of structured supervised group exercises , group lectures , individual counselling and telephone follow-up . One- hundred and fifty physically inactive Pakistani immigrant men living in Oslo , Norway , were r and omised to either a control group or an intervention group . The 5-month intervention focused on increasing levels of PA , which were assessed by use of accelerometer ( Actigraph MTI 7164 ) recordings . Risk of diabetes was assessed by serum glucose and insulin concentrations determined in a fasted state , and after an oral glucose tolerance test ( OGTT ) . ANCOVA was used to assess differences between groups . There was a mean difference in PA between the two groups of 49 counts per minute per day , representing a 15 % ( 95 % CI = 8.7–21.2 ; P = 0.01 ) higher increase in total PA level in the intervention group than in the control group . Insulin values taken 2 h after an OGTT were reduced in the intervention group by 27 % ( 95 % CI = 18.9–35.0 ; P = 0.02 ) more than those in the control group . There were no differences in fasting or postpr and ial glucose values between the groups at the follow-up test . This type of intervention can increase PA and reduce serum insulin in Pakistani immigrant men , thereby presumably reducing their risk of T2D OBJECTIVES To investigate the acceptability and feasibility of using short message services ( SMS ) via cell phones to ensure adherence to management prescriptions by diabetic patients . METHODS Type 2 diabetic patients with 5 or more years of diabetes and having HbA1c between 7.0 % to 10 % were r and omized to the control arm ( n = 105 ) to receive st and ard care and to the intervention arm ( SMS , n = 110 ) . Messages in English on principles of diabetes management were sent once in 3 days , the contents and frequencies varied as per the patients ' preferences . The study duration was 1 year . All participants were advised to report for quarterly clinic visits . A comparative assessment of the clinical , biochemical and anthropometric outcomes was made among the groups at the annual visit . RESULTS Annual review was possible in 71 % of intervention group and 63 % of control group . SMS was acceptable to the patients and the median number requested was 2 per week . HbA1c and plasma lipids improved significantly in the SMS group . CONCLUSIONS The pilot study showed that frequent communication via SMS was acceptable to diabetic patients and it helped to improve the health outcomes Migrant mortality does not conform to a single pattern of convergence towards prevalence rates in the host population . To underst and better how migrant mortality develops , it is necessary to further investigate how the underlying behavioural determinants change following migration . We studied whether the prevalence of behavioural risk factors over two generations of Turkish and Moroccan migrants converge towards the prevalence rates in the Dutch population . From a r and om sample from the population register of Amsterdam , 291 Moroccan and 505 Turkish migrants , aged 15–30 , participated in a structured interview that included questions on smoking , alcohol consumption , physical inactivity and weight/height . Data from the Dutch population were available from Statistics Netherl and s. By calculating age-adjusted Odds Ratio ’s , prevalence rates among both generations were compared with prevalence rates in the host population for men and women separately . We found indications of convergence across generations towards the prevalence rates in the host population for smoking in Turkish men , for overweight in Turkish and Moroccan women and for physical inactivity in Turkish women . Alcohol consumption , however , remained low in all subgroups and did not converge towards the higher rates in the host population . In addition , we found a reversed trend among Turkish women regarding smoking : the second generation smoked significantly more , while the first generation did not differ from ethnic Dutch . In general , behavioural risk factors in two generations of non-Western migrants in the Netherl and s seem to converge towards the prevalence rates in the Dutch population . However , some subgroups and risk factors showed a different pattern This study used an experimental , pretest-posttest control group repeated measures design to evaluate the effectiveness of a community-based culturally appropriate lifestyle intervention program to reduce the risk for type 2 diabetes ( T2DM ) among Gujarati Asian Indians ( AIs ) in an urban community in the US . Participants included 70 adult AIs in the greater Houston metropolitan area . The primary outcomes were reduction in weight and hemoglobin A1c ( HbA1c ) and improvement in physical activity . Participants were screened for risk factors and r and omly assigned to a 12-week group-based lifestyle intervention program ( n = 34 ) or a control group ( n = 36 ) that received st and ard print material on diabetes prevention . Participants also completed clinical measures and self-reported question naires about physical activity , social , and lifestyle habits at 0 , 3 , and 6 months . No significant baseline differences were noted between groups . While a significant decline in weight and increase in physical activity was observed in all participants , the intervention group lowered their HbA1c ( p < 0.0005 ) and waist circumference ( p = 0.04 ) significantly as compared to the control group . Findings demonstrated that participation in a culturally tailored , lifestyle intervention program in a community setting can effectively reduce weight , waist circumference , and HbA1c among Gujarati AIs living in the US Type 2 diabetes is extremely common in South Asians , e.g. in men from Pakistani and Indian population s it is about three times as likely as in the general population in Engl and , despite similarities in body mass index . Lifestyle interventions reduce the incidence of diabetes . Trials in Europe and North America have not , however , reported on the impact on South Asian population s separately or provided the details of their cross-cultural adaptation processes . Prevention of diabetes and obesity in South Asians ( PODOSA ) is a r and omized , controlled trial in Scotl and of an adapted , lifestyle intervention aim ed at reducing weight and increasing physical activity to reduce type 2 diabetes in Indians and Pakistanis . The trial was adapted from the Finnish Diabetes Prevention Study . We describe , reflect on and discuss the following key issues : The core adaptations to the trial design , particularly the delivery of the intervention in homes by dietitians rather than in clinics . The use of both a multilingual panel and professional translators to help translate and /or develop material s. The processes and challenges of phonetic translation . How intervention re sources were adapted , modified , newly developed and translated into Urdu and Gurmukhi ( written Punjabi ) . The insights gained in PODOSA ( including time pressures on investigators , imperfections in the adaptation process , the power of verbal rather than written information , the utilization of English and the mother-tongue language s simultaneously by participants and the costs ) might help the research community , given the challenge of health promotion in multi-ethnic , urban societies Background To our knowledge , no studies have aim ed at improving the PA level in south Asian immigrant men residing in Western countries , and few studies have considered the relevance of SCT constructs to the PA behaviour of this group in the long term . The observed low physical activity ( PA ) level among south Asian immigrants in Western countries may partly explain the high prevalence of cardiovascular diseases ( CVD ) and type 2 diabetes ( T2D ) in this group . We have shown previously in a r and omised controlled trial , the Physical Activity and Minority Health study ( PAMH ) that a social cognitive based intervention can beneficially influence PA level and subsequently reduce waist circumference and insulin resistance in the short-term . In an extended follow-up of the PAMH study : we aim ed 1 ) to determine if the intervention produced long-term positive effects on PA level six months after intervention ( follow-up 2 ( FU2 ) ) , and 2 ) to identify the social cognitive mediators of any intervention effects . Methods Physically inactive Pakistani immigrant men ( n = 150 ) who were free of CVD and T2D were r and omly assigned to a five months PA intervention or a control group . Six months after the intervention ended , we telephoned all those who attended FU1 and invited them for a second follow-up test ( FU2 ) ( n = 133 ) . PA was measured using ActiGraph accelerometers . Statistical differences between groups were determined by use of ANCOVA . Results Significant differences ( baseline to FU2 ) between the groups were found for all PA variables ( e.g. , total PA level , sedentary time , PA intensity ) . Support from family and outcome expectancies increased more in the intervention group compared with the control group . Self-efficacy did not differ significantly between groups . Conclusions Our results show that a multi component PA programme can increase PA over the short and long term in a group of immigrant Pakistani men . However , we could not identify the factors that mediated these changes in PA . Protocol ID07112001326 , NCT ID : BACKGROUND Type 2 diabetes can often be prevented by lifestyle modification ; however , successful lifestyle intervention programmes are labour intensive . Mobile phone messaging is an inexpensive alternative way to deliver educational and motivational advice about lifestyle modification . We aim ed to assess whether mobile phone messaging that encouraged lifestyle change could reduce incident type 2 diabetes in Indian Asian men with impaired glucose tolerance . METHODS We did a prospect i ve , parallel-group , r and omised controlled trial between Aug 10 , 2009 , and Nov 30 , 2012 , at ten sites in southeast India . Working Indian men ( aged 35 - 55 years ) with impaired glucose tolerance were r and omly assigned ( 1:1 ) with a computer-generated r and omisation sequence to a mobile phone messaging intervention or st and ard care ( control group ) . Participants in the intervention group received frequent mobile phone messages compared with controls who received st and ard lifestyle modification advice at baseline only . Field staff and participants were , by necessity , not masked to study group assignment , but allocation was concealed from laboratory personnel as well as principal and co-investigators . The primary outcome was incidence of type 2 diabetes , analysed by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00819455 . RESULTS We assessed 8741 participants for eligibility . 537 patients were r and omly assigned to either the mobile phone messaging intervention ( n=271 ) or st and ard care ( n=266 ) . The cumulative incidence of type 2 diabetes was lower in those who received mobile phone messages than in controls : 50 ( 18 % ) participants in the intervention group developed type 2 diabetes compared with 73 ( 27 % ) in the control group ( hazard ratio 0·64 , 95 % CI 0·45 - 0·92 ; p=0·015 ) . The number needed to treat to prevent one case of type 2 diabetes was 11 ( 95 % CI 6 - 55 ) . One patient in the control group died suddenly at the end of the first year . We recorded no other serious adverse events . INTERPRETATION Mobile phone messaging is an effective and acceptable method to deliver advice and support towards lifestyle modification to prevent type 2 diabetes in men at high risk . FUNDING The UK India Education and Research Initiative , the World Diabetes Foundation Background In low/middle income countries like India , diabetes is prevalent and health care access limited . Most adults have a mobile phone , creating potential for mHealth interventions to improve public health . To examine the feasibility and initial evidence of effectiveness of mDiabetes , a text messaging program to improve diabetes risk behaviors , a global nonprofit organization ( Arogya World ) implemented mDiabetes among one million Indian adults . Objective A prospect i ve , parallel cohort design was applied to examine whether mDiabetes improved fruit , vegetable , and fat intakes and exercise . Methods Intervention participants were r and omly selected from the one million Nokia subscribers who elected to opt in to mDiabetes . Control group participants were r and omly selected from non-Nokia mobile phone subscribers . mDiabetes participants received 56 text messages in their choice of 12 language s over 6 months ; control participants received no contact . Messages were design ed to motivate improvement in diabetes risk behaviors and increase awareness about the causes and complications of diabetes . Participant health behaviors ( exercise and fruit , vegetable , and fat intake ) were assessed between 2012 and 2013 via telephone surveys by blinded assessors at baseline and 6 months later . Data were cleaned and analyzed in 2014 and 2015 . Results 982 participants in the intervention group and 943 in the control group consented to take the phone survey at baselne . At the end of the 6-month period , 611 ( 62.22 % ) in the intervention and 632 ( 67.02 % ) in the control group completed the follow-up telephone survey . Participants receiving texts demonstrated greater improvement in a health behavior composite score over 6 months , compared with those who received no messages F(1 , 1238 ) = 30.181 , P<.001 , 95 % CI , 0.251 - 0.531 . Fewer intervention participants demonstrated health behavior decline compared with controls . Improved fruit , vegetable , and fat consumption ( P<.01 ) but not exercise were observed in those receiving messages , as compared with controls . Conclusions A text messaging intervention was feasible and showed initial evidence of effectiveness in improving diabetes-related health behaviors , demonstrating the potential to facilitate population -level behavior change in a low/middle income country . Trial Registration Australian New Zeal and Clinical Trials Registry ( ACTRN ) : 12615000423516 ; https://www.anzctr.org.au/Trial/ Registration /Trial Review .aspx?id=367946&is Review = true ( Archived by WebCite at http://www.webcitation.org/6j5ptaJgF OBJECTIVE To determine the effect of mobile phone intervention on HbA1c in type-2 Diabetes Mellitus ( DM ) patients living in rural areas of Pakistan . STUDY DESIGN R and omized controlled trial . PLACE AND DURATION OF STUDY Department of Endocrinology , Liaquat National Hospital , Karachi , from December 2013 to June 2014 . METHODOLOGY A total of 440 patients in intervention and control groups were enrolled . All patients between 18 - 70 years of age , residing in rural areas of Pakistan , HbA1c ³ 8.0 % and having personal functional mobile phone were included . The intervention group patients were called directly on mobile phone after every 15 days for a period of 4 months . They were asked about the self-monitoring blood glucose , intake of medications , physical activity , healthy eating and were physically examined after 4 months . However , the control group was examined initially and after 4 months physically in the clinic and there were no mobile phone contacts with these patients . RESULTS Patients in intervention group showed improvement ( p < 0.001 ) in following diet plan from 17.3 % at baseline to 43.6 % at endline , however , the control group showed insignificant increase ( p=0.522 ) from 13.6 % at baseline to 15.9 % at endline . Intervention group ( RR = 2.71 , 95 % CI = 1.18 - 6.40 ) showed significant positive association with normalization of HbA1c levels . The relationship was adjusted for age , gender , socio-economic status , ethnicity , education , hypertension , medication , BMI , diet , LDL levels and physical activity . Dietary restriction and low LDL levels also showed significant associations with reduced HbA1c levels on multivariate analysis . CONCLUSION Mobile phone technology in rural areas of Pakistan was helpful in lowering HbA1c levels in intervention group through direct communication with the diabetic patients . Lowering LDL and following diabetic diet plan can reduce HbA1c in these patients and help in preventing future complications BACKGROUND The susceptibility to type 2 diabetes of people of south Asian descent is established , but there is little trial-based evidence for interventions to tackle this problem . We assessed a weight control and physical activity intervention in south Asian individuals in the UK . METHODS We did this non-blinded trial in two National Health Service ( NHS ) regions in Scotl and ( UK ) . Between July 1 , 2007 , and Oct 31 , 2009 , we recruited men and women of Indian and Pakistani origin , aged 35 years or older , with waist circumference 90 cm or greater in men or 80 cm or greater in women , and with impaired glucose tolerance or impaired fasting glucose determined by oral glucose tolerance test . Families were r and omised ( using a r and om number generator program , with permuted blocks of r and om size , stratified by location [ Edinburgh or Glasgow ] , ethnic group [ Indian or Pakistani ] , and number of participants in the family [ one vs more than one ] ) to intervention or control . Participants in the same family were not r and omised separately . The intervention group received 15 visits from a dietitian over 3 years and the control group received four visits in the same period . The primary outcome was weight change at 3 years . Analysis was by modified intention to treat , excluding participants who died or were lost to follow-up . We used linear regression models to provide mean differences in baseline-adjusted weight at 3 years . This trial is registered , number IS RCT N25729565 . FINDINGS Of 1319 people who were screened with an oral glucose tolerance test , 196 ( 15 % ) had impaired glucose tolerance or impaired fasting glucose and 171 entered the trial . Participants were in 156 family clusters that were r and omised ( 78 families with 85 participants were allocated to intervention ; 78 families with 86 participants were allocated to control ) . 167 ( 98 % ) participants in 152 families completed the trial . Mean weight loss in the intervention group was 1.13 kg ( SD 4.12 ) , compared with a mean weight gain of 0.51 kg ( 3.65 ) in the control group , an adjusted mean difference of -1.64 kg ( 95 % CI -2.83 to -0.44 ) . INTERPRETATION Modest , medium-term changes in weight are achievable as a component of lifestyle-change strategies , which might control or prevent adiposity-related diseases . FUNDING National Prevention Research Initiative , NHS Research and Development ; NHS National Services Scotl and ; NHS Health Scotl and |
927 | 30,315,905 | Several main categories emerged : Attentional variables appear to be of importance to both performance and learning , motivational factors and mood have been implicated as moderate predictors of success , while personality factors have mixed findings .
Attention , motivation , mood and other factors affect neurofeedback success .
Attention is consistently found to be crucial for efficient neurofeedback learning .
Mood and Motivation are moderate predictors of neurofeedback success . | & NA ; Real‐time functional magnetic resonance imaging (fMRI)‐based neurofeedback represents the latest applied behavioural neuroscience methodology developed to train participants in the self‐regulation of brain regions or networks .
However , as with previous biofeedback approaches which rely on electroencephalography ( EEG ) or related approaches such as brain‐machine interface technology ( BCI ) , individual success rates vary significantly , and some participants never learn to control their brain responses at all .
Given that these approaches are often being developed for eventual use in a clinical setting ( albeit there is also significant interest in using NF for neuro‐enhancement in typical population s ) , this represents a significant hurdle which requires more research .
Here we present the findings of a systematic review which focused on how psychological variables contribute to learning outcomes in fMRI‐based neurofeedback . | Many patients show no or incomplete responses to current pharmacological or psychological therapies for depression . Here we explored the feasibility of a new brain self-regulation technique that integrates psychological and neurobiological approaches through neurofeedback with functional magnetic resonance imaging ( fMRI ) . In a proof-of-concept study , eight patients with depression learned to upregulate brain areas involved in the generation of positive emotions ( such as the ventrolateral prefrontal cortex ( VLPFC ) and insula ) during four neurofeedback sessions . Their clinical symptoms , as assessed with the 17-item Hamilton Rating Scale for Depression ( HDRS ) , improved significantly . A control group that underwent a training procedure with the same cognitive strategies but without neurofeedback did not improve clinical ly . R and omised blinded clinical trials are now needed to exclude possible placebo effects and to determine whether fMRI-based neurofeedback might become a useful adjunct to current therapies for depression For most people , adolescence is synonymous with emotional turmoil and it has been shown that early difficulties with emotion regulation can lead to persistent problems for some people . This suggests that intervention during development might reduce long-term negative consequences for those individuals . Recent research has highlighted the suitability of real-time fMRI-based neurofeedback ( NF ) in training emotion regulation ( ER ) networks in adults . However , its usefulness in directly influencing plasticity in the maturing ER networks remains unclear . Here , we used NF to teach a group of 17 7–16 year-olds to up-regulate the bilateral insula , a key ER region . We found that all participants learned to increase activation during the up-regulation trials in comparison to the down-regulation trials . Importantly , a subsequent Granger causality analysis of Granger information flow within the wider ER network found that during up-regulation trials , bottom-up driven Granger information flow increased from the amygdala to the bilateral insula and from the left insula to the mid-cingulate cortex , supplementary motor area and the inferior parietal lobe . This was reversed during the down-regulation trials , where we observed an increase in top-down driven Granger information flow to the bilateral insula from mid-cingulate cortex , pre- central gyrus and inferior parietal lobule . This suggests that : 1 ) NF training had a differential effect on up-regulation vs down-regulation network connections , and that 2 ) our training was not only superficially concentrated on surface effects but also relevant with regards to the underlying neurocognitive bases . Together these findings highlight the feasibility of using NF in children and adolescents and its possible use for shaping key social cognitive networks during development If an individual can learn to directly control activation of localized regions within the brain , this approach might provide control over the neurophysiological mechanisms that mediate behavior and cognition and could potentially provide a different route for treating disease . Control over the endogenous pain modulatory system is a particularly important target because it could enable a unique mechanism for clinical control over pain . Here , we found that by using real-time functional MRI ( rtfMRI ) to guide training , subjects were able to learn to control activation in the rostral anterior cingulate cortex ( rACC ) , a region putatively involved in pain perception and regulation . When subjects deliberately induced increases or decreases in rACC fMRI activation , there was a corresponding change in the perception of pain caused by an applied noxious thermal stimulus . Control experiments demonstrated that this effect was not observed after similar training conducted without rtfMRI information , or using rtfMRI information derived from a different brain region , or sham rtfMRI information derived previously from a different subject . Chronic pain patients were also trained to control activation in rACC and reported decreases in the ongoing level of chronic pain after training . These findings show that individuals can gain voluntary control over activation in a specific brain region given appropriate training , that voluntary control over activation in rACC leads to control over pain perception , and that these effects were powerful enough to impact severe , chronic clinical pain Real‐time functional magnetic resonance imaging ( rtfMRI ) is a novel technique that has allowed subjects to achieve self‐regulation of circumscribed brain regions . Despite its anticipated therapeutic benefits , there is no report on successful application of this technique in psychiatric population s. The objectives of the present study were to train schizophrenia patients to achieve volitional control of bilateral anterior insula cortex on multiple days , and to explore the effect of learned self‐regulation on face emotion recognition ( an extensively studied deficit in schizophrenia ) and on brain network connectivity . Nine patients with schizophrenia were trained to regulate the hemodynamic response in bilateral anterior insula with contingent rtfMRI neurofeedback , through a 2‐weeks training . At the end of the training stage , patients performed a face emotion recognition task to explore behavioral effects of learned self‐regulation . A learning effect in self‐regulation was found for bilateral anterior insula , which persisted through the training . Following successful self‐regulation , patients recognized disgust faces more accurately and happy faces less accurately . Improvements in disgust recognition were correlated with levels of self‐activation of right insula . RtfMRI training led to an increase in the number of the incoming and outgoing effective connections of the anterior insula . This study shows for the first time that patients with schizophrenia can learn volitional brain regulation by rtfMRI feedback training leading to changes in the perception of emotions and modulations of the brain network connectivity . These findings open the door for further studies of rtfMRI in severely ill psychiatric population s , and possible therapeutic applications . Hum Brain Mapp , 2013 . © 2011 Wiley Periodicals , OBJECTIVE This study examined the effect of motivation as a possible psychological influencing variable on P300 amplitude and performance in a brain-computer interface ( BCI ) controlled by event-related potentials ( ERP ) . METHODS Participants were instructed to copy spell a sentence by attending to cells of a r and omly flashing 7 * 7 matrix . Motivation was manipulated by monetary reward . In two experimental groups participants received 25 ( N=11 ) or 50 ( N=11 ) Euro cent for each correctly selected character ; the control group ( N=11 ) was not rewarded . BCI performance was defined as the overall percentage of correctly selected characters ( correct response rate = CRR ) . RESULTS Participants performed at an average of 99 % . At electrode location Cz the P300 amplitude was positively correlated to self-rated motivation . The P300 amplitude of the most motivated participants was significantly higher than that of the least motivated participants . Highly motivated participants were able to communicate correctly faster with the ERP-BCI than less motivated participants . CONCLUSIONS Motivation modulates the P300 amplitude in an ERP-BCI . SIGNIFICANCE Motivation may contribute to variance in BCI performance and should be monitored in BCI setting Sixteen subjects naive to biofeedback learned lateralised interhemispheric control of slow cortical potentials ( SCPs ) across electrode sites F3-F4 during three sessions of visual electroencephalograph ( EEG ) biofeedback . Subjects were required to generate slow negativity shifts either towards the left or the right hemisphere in sixty pseudor and omly ordered trials per session . Group 1 ( n = 8) were told to use emotional strategies in the task ( positive emotions for left hemisphere activation , negative emotion for right hemisphere activation ) , group 2 received no guidance . Both groups received feedback in the form of an on-screen rocket-ship , initially central ly placed , which rose to indicate an increase in left hemisphere negativity ( relative to the right hemisphere ) and fell to indicate an increase in right hemisphere negativity ( relative to the left hemisphere ) . A 2 x 3 x 3 x 2 ANOVA ( group x session x block x trial ) showed no performance differences between the strategy and no strategy groups . Both groups learned to produce correct direction shifts in the final third of each session during both trial types ( P < 0.001 ) . The no strategy group showed a particularly strong within session learning effect ( P < 0.0037 ) with poor performance in the early part of the sessions , and strong shifts at the end . Subjects high on withdrawal showed stronger rightward shifts in keeping with right hemisphere involvement in behavioural withdrawal . This is the first demonstration of self regulation of interhemispheric frontal asymmetry |
928 | 19,692,157 | Compared with calcium-based agents , lanthanum significantly decreased end-of-treatment serum calcium and calcium-phosphorus product levels , but with similar end-of-treatment phosphorus levels .
Effects of calcium acetate on biochemical end points were similar to those of calcium carbonate .
Existing data are insufficient to conclude for a differential impact of any phosphate binder on cardiovascular mortality or other patient-level outcome .
Currently , there are insufficient data to establish the comparative superiority of non-calcium-binding agents over calcium-containing phosphate binders for such important patient-level outcomes as all-cause mortality and cardiovascular end points . | BACKGROUND Phosphate binders are widely used to control serum phosphorus levels in patients with chronic kidney disease ( CKD ) .
We analyzed the effects of phosphate binders on biochemical and patient-level end points in patients with CKD . | The objective of the study was to evaluate the phosphate-binding efficacy , side effects , and cost of therapy of calcium ketoglutarate granulate as compared with calcium carbonate tablets in patients on chronic hemodialysis . The study design used was a r and omized , crossover open trial , and the main outcome measurements were plasma ionized calcium levels , plasma phosphate levels , plasma intact parathyroid hormone ( PTH ) levels , requirements for supplemental aluminum-aminoacetate therapy , patient tolerance , and cost of therapy . Nineteen patients on chronic hemodialysis were treated with a dialysate calcium concentration of 1.25 mmol/L and a fixed alfacalcidol dose for at least 2 months . All had previously tolerated therapy with calcium carbonate . Of the 19 patients included , 10 completed both treatment arms . After 12 weeks of therapy , the mean ( + /-SEM ) plasma ionized calcium level was significantly lower in the ketoglutarate arm compared with the calcium carbonate arm ( 4.8+/-0.1 mg/dL v 5.2+/-0.1 mg/dL ; P = 0.004 ) , whereas the mean plasma phosphate ( 4.5+/-0.3 mg/dL v 5.1+/-0.1 mg/dL ) and PTH levels ( 266+/-125 pg/mL v 301+/-148 pg/mL ) did not differ significantly between the two treatment arms . Supplemental aluminum-aminoacetate was not required during calcium ketoglutarate treatment , while two patients needed this supplement when treated with calcium carbonate . Five of 17 ( 29 % ) patients were withdrawn from calcium ketoglutarate therapy within 1 to 2 weeks due to intolerance ( anorexia , vomiting , diarrhea , general uneasiness ) , whereas the remaining 12 patients did not experience any side effects at all . The five patients with calcium ketoglutarate intolerance all had pre-existing gastrointestinal symptoms ; four of them had received treatment with cimetidine or omeprazol before inclusion into the study . Calculations based on median doses after 12 weeks showed that the cost of the therapy in Denmark was 10 times higher for calcium ketoglutarate compared with calcium carbonate ( US$ 6.00/d v US$ 0.65/d ) . Calcium ketoglutarate may be an effective and safe alternative to treatment with aluminum-containing phosphate binders in patients on hemodialysis who are intolerant of calcium carbonate or acetate because of hypercalcemia . However , care must be exercised when dealing with patients with pre-existing gastrointestinal discomfort . Due to the high cost of the therapy , calcium ketoglutarate should be used only for selected patients Background —Aortic pulse wave velocity ( PWV ) is a predictor of mortality in patients with end-stage renal failure ( ESRF ) . The PWV is partly dependent on blood pressure ( BP ) , and a decrease in BP can attenuate the stiffness . Whether the changes in PWV in response to decreases in BP can predict mortality in ESRF patients has never been investigated . Methods and Results —One hundred fifty ESRF patients ( aged 52±16 years ) were monitored for 51±38 months . From entry until the end of follow-up , the changes of PWV in response to decreased BP were measured ultrasonographically . BP was controlled by adjustment of “ dry weight ” and , when necessary , with ACE inhibitors , calcium antagonists , and /or & bgr;-blockers , in combination if necessary . Fifty-nine deaths occurred , including 40 cardiovascular and 19 noncardiovascular events . Cox analyses demonstrated that independent of BP changes , the predictors of all-cause and cardiovascular mortality were as follows : absence of PWV decrease in response to BP decrease , increased left ventricular mass , age , and preexisting cardiovascular disease . Survival was positively associated with ACE inhibitor use . After adjustment for all confounding factors , the risk ratio for the absence of PWV decrease was 2.59 ( 95 % CI 1.51 to 4.43 ) for all-cause mortality and 2.35 ( 95 % CI 1.23 to 4.41 ) for cardiovascular mortality . The risk ratio for ACE inhibitor use was 0.19 ( 95 % CI 0.14 to 0.43 ) for all-cause mortality and 0.18 ( 95 % CI 0.06 to 0.55 ) for cardiovascular mortality . Conclusions —These results indicate that in ESRF patients , the insensitivity of PWV to decreased BP is an independent predictor of mortality and that use of ACE inhibitors has a favorable effect on survival that is independent of BP changes We conducted a r and omized unblinded parallel clinical trial to compare the effectiveness , side effects and tolerance between calcium acetate ( CA ) and calcium carbonate ( CC ) in 80 stable chronic hemodialysis patients selected on the basis of their acceptable control of serum phosphorus ( P ) levels with aluminum hydroxide ( AH ) . All patients were dialyzed against the same calcium dialyzate ( 1.62 mmol/l ) . The serum analytical tests included : calcium corrected to total protein , P , PTH ( intact molecule ) and bicarbonate . The study was divided into the following periods : P0 : baseline measurements ; P1 : washout ( withdrawal of AH for 15 days ) ; P2 : r and om allocation to CA and CC treatment at doses equivalent to 75 mEq of elemental calcium , stratified according to previous doses of AH ( 2 months ) ; P3 : adjustment of doses until control P ( 2 months ) . CA was poorly tolerated in 7 patients and CC in 2 ( NS ) . The changes in serum P levels between P0 and P2 periods were lower in the CA group ( 1.73 + /- 0.25 vs. 1.80 + /- 0.50 mmol/l ; p = 0.26 ) than in the CC group ( 1.77 + /- 0.35 vs. 1.93 + /- 0.48 mmol/l ; p = 0.03 , paired t test ) . Serum calcium was hardly modified by CA ( 2.42 + /- 0.20 vs. 2.47 + /- 0.17 mmol/l ; NS ) while in the CC group , it rose significantly ( 2.40 + /- 0.12 vs. 2.55 + /- 0.22 mmol/l ; p = 0.0004 ) . There were no differences in the control of PTH or bicarbonate . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Calcium-based phosphate binders may induce tissue calcification , and little is known about their effects on bone density . We compared the effects of a calcium with a non-calcium phosphate binder on both arterial calcification and bone density measured by computed tomography . METHODS Seventy-two adult haemodialysis patients were r and omized to treatment with calcium carbonate ( CC ) or sevelamer ( SEV ) for 2 years . Electron beam CT scans were performed at baseline and at 6 , 12 and 24 months . Serum phosphorus , calcium , calcium x phosphorus product and intact parathyroid hormone ( iPTH ) were measured and other routine laboratory tests were also carried out . RESULTS The average calcium x phosphorus product was similar in the two treatment groups . However , patients receiving CC had significantly lower average iPTH ( P<0.01 ) , were more likely to have hypercalcaemic episodes ( P = 0.03 ) and had significantly greater increases in coronary artery ( CC median 484 , P<0.0001 , SEV median 37 , P = 0.3118 , between-group P = 0.0178 ) and aortic ( CC median 610 , P = 0.0003 , SEV median 0 , P = 0.5966 , between-group P = 0.0039 ) calcification scores . The CC group also had a significant decrease in trabecular bone density ( CC median -6 % , P = 0.0049 , SEV median + 3 % , P = 0.0296 , between-group P = 0.0025 ) . However , there was no significant difference in cortical bone density between the two groups . CONCLUSIONS This 2 year study shows that calcium carbonate use is continuously associated with progressive arterial calcification in haemodialysis patients . In addition , it suggests that it is also associated with decreased trabecular bone density . However , this latter finding requires confirmation by a study specifically devoted to this issue AIMS High serum phosphorus levels are a common problem in patients receiving long-term dialysis treatment . Lanthanum carbonate ( Fosrenol ) is a new non-aluminum , non-calcium phosphate binder developed for the treatment of hyperphosphatemia in patients with end-stage renal disease ( ESRD ) . We report data from a recent trial , which , for the first time , assessed the efficacy and tolerability of lanthanum carbonate treatment , compared with placebo , in Chinese patients with ESRD . PATIENTS AND METHODS Following a one- to three-week washout phase and a four-week , open-label lanthanum carbonate dose-titration phase , male and female hemodialysis patients were r and omized ( 1:1 ) to receive either lanthanum carbonate or placebo for four weeks . The primary efficacy parameter of the study was the control of serum phosphorus levels ( < or = 1.8 mmol/l [ < or = 5.6 mg/dl ] ) . Secondary endpoints included the profile of serum phosphorus during titration and parathyroid hormone , calcium , and calcium x phosphorus ( Ca x P ) product levels . The safety and tolerability of lanthanum carbonate were assessed by monitoring adverse events throughout the study . RESULTS Mean serum phosphorus level at the end of washout was 2.5 + /- 0.5 mmol/l ( 7.7 + /- 1.5 mg/dl ; n=73 ) , and there was no evidence of a difference in levels between the treatment groups pre-r and omization . At the end of the study , lanthanum carbonate-treated patients had significantly lower phosphorus levels ( 1.6 + /- 0.5 mmol/l [ 5.1 + /- 1.5 mg/dl ] ; n=30 ) than those receiving placebo ( 2.3 + /- 0.4 mmol/l [ 7.2 + /- 1.3 mg/dl ] ; n=31 ; p < 0.001 ) . In addition , a significantly higher proportion of patients receiving lanthanum carbonate had controlled serum phosphorus levels ( 60 % ) compared with the placebo group ( 10 % ; p < 0.001 ) . Ca x P product levels were also significantly lower in the lanthanum carbonate group at the end of r and omized treatment ( p < 0.001 ) . Lanthanum carbonate was well tolerated ; only one serious adverse event was reported , which was unrelated to treatment . CONCLUSIONS Lanthanum carbonate was shown to be an effective and well-tolerated phosphate binder for the treatment of hyperphosphatemia in Chinese patients with ESRD . This finding supports the results of previous US and European studies , which have also shown that lanthanum carbonate treatment effectively controls serum phosphorus levels BACKGROUND Sevelamer hydrochloride is a recently approved calcium- and aluminium-free phosphate binder . A r and omized study comparing sevelamer and calcium acetate was performed to assess the control of hyperphosphatemia in hemodialysis patients . METHODS Administration of phosphate binders was discontinued during a two-week washout period . The patients were then r and omized to receive sevelamer or calcium acetate . The laboratory tests were performed monthly for 34 weeks . RESULTS There was a statistically significant decrease of serum phosphorus in both sevelamer and calcium acetate treatments . In addition , sevelamer improved the lipid profile . CONCLUSION This study confirms that sevelamer is effective at lowering serum phosphorus in hemodialysis patients and that it has several striking properties that could be beneficial in atherosclerosis in dialysis patients Since dietary restrictions and phosphorus removal by haemodialysis ( HD ) are not sufficient to control serum phosphate ( s-phosphate ) levels in dialysis patients the use of oral phosphate binders is m and atory . Calcium ketoglutarate ( CaKE ) is an analogue of glutamic acid exerting phosphate binding properties . Therefore we compared this substance to calcium acetate ( CaAC ) in a 24-weeks open cross-over trial in 28 maintenance HD patients . Medications and HD prescriptions were kept unchanged during the trial . Following 2 weeks of withdrawal of phosphate binders , patients were r and omly assigned to one of the calcium salts for 12 weeks ; after a second withdrawal of 2 weeks , all patients were shifted to the other treatment for another 12 weeks . All patients received equimolar doses of CaKE and CaAC with respect to the amount of prescribed elemental calcium . Treatment with CaAC and CaKE significantly reduced s-phosphate levels after 4 weeks ( CaAC 1.95+/-0.6 vs. 2.4+/-0.53 mmol/l , P = 0.004 ; CaKE 1.95+/-0.4 vs. 2.47+/-0.63 mmol/l , P = 0.0001 ) reaching a virtually stable plateau over the remaining observation time without significant differences between the groups . The incidence of hypercalcaemia defined as a serum calcium level > or = 2.8 mmol/l was significantly higher in CaAC than in CaKE treated patients ( n = 8 vs. n = 1 , P = 0.03 ) . There were no significant differences in serum intact parathyroid hormone ( PTH ) bicarbonate , albumin or calcitriol levels between the groups after 12 weeks treatment . We conclude that CaKE is as effective as CaAC for treatment of hyperphosphataemia in chronic HD patients and may be particularly helpful in patients who are prone to develop hypercalcaemia CONTEXT Hyperphosphatemia has an important role in the development of bone and mineral abnormalities in end-stage renal disease ( ESRD ) . OBJECTIVE To compare the phosphorus binding power and the hypercalcemic effect of calcium acetate and calcium carbonate in hemodialysis patients . TYPE OF STUDY Crossover , r and omized , double-blind study . PLACE A private hospital dialysis center . PARTICIPANTS Fifty-two patients who were undergoing regular hemodialysis three times a week ( [ Ca++ ] dialysate = 3.5 mEq/L ) . PROCEDURES Half of the patients were started on 5.6 g/day of calcium acetate and , after a 2 week washout period , received 6.2 g/day of calcium carbonate . The other half followed an inverse protocol . MAIN MEASUREMENTS Clinical interviews were conducted 3 times a week to monitor for side effects . Determinations of serum urea , calcium , phosphorus , hematocrit , Kt/V and blood gas analysis were obtained before and after each treatment . RESULTS Twenty-three patients completed the study . A significant increase in calcium plasma levels was only observed after treatment with calcium carbonate [ 9.34 mg/dl ( SD 0.91 ) vs. 9.91 mg/dl ( SD 0.79 ) , P < 0.01 ] . The drop in phosphorus levels was substantial and significant for both salts [ 5.64 mg/dl ( SD 1.54 ) vs. 4.60 mg/dl ( SD 1.32 ) , P < 0.01 and 5.89 mg/dl ( SD 1.71 ) vs. 4.56 mg/dl ( SD 1.57 ) , P < 0.01 , for calcium acetate and calcium carbonate respectively ] . The percentage reduction in serum phosphorus ( at the end of the study ) per milliequivalent of salt administered per day tended to be higher with calcium acetate but statistical significance was not found . CONCLUSION Calcium acetate can be a good alternative to calcium carbonate in the h and ling of hyperphosphatemia in ESRD patients . When calcium acetate is used , control of hyperphosphatemia can be achieved with a lower administration of calcium , perhaps with a lower risk of hypercalcemia OBJECTIVE Current phosphate binders used in hemodialysis patients include calcium-based binders that result in frequent hypercalcemia . The use of a calcium- and aluminum-free phosphate-binding polymer in hemodialysis ( sevelamer ) disclosed efficacy in the short and long-term studies . However , due to race differences we performed a short-term study on the Saudi hemodialysis patients and compared sevelamer with a st and ard calcium-based phosphate binder . METHODS An open-label , r and omized , cross-over study was performed to evaluate the safety and effectiveness of sevelamer hydrochloride in controlling hyperphosphatemia in hemodialysis patients . After a 2-week phosphate binder washout period , stable hemodialysis patients were given either sevelamer or calcium carbonate , and the dosages were titrated to achieve phosphate control over an 8-week period . After a 2-week washout period , patients crossed over to the alternate agent for 8 weeks . Twenty patients from the Dialysis Unit of King Fahd Hospital , Jeddah , Kingdom of Saudi Arabia , were recruited for the study between March 2003 and June 2003 . RESULTS There was a similar decrease in serum phosphate values over the course of the study with both sevelamer ( -3.3 + /-2.2 mg/dL ) and calcium carbonate ( -3.9 + /-2.8 mg/dL ) . Fifty-two percent of patients developed serum calcium greater than 2.75 mmol/L ( 11.0 mg/dL ) while receiving calcium carbonate versus 26 % of patients receiving sevelamer ( p<0.05 ) . The incidence of hypercalcemia for sevelamer was not different from the incidence of hypercalcemia during the washout period . Patients treated with sevelamer also sustained a 13 % mean decrease in serum cholesterol levels . CONCLUSION Sevelamer was effective in controlling hyperphosphatemia without result ing in an increase in the incidence of hypercalcemia seen with calcium carbonate . This agent appears quite effective in the treatment of hyperphosphatemia in hemodialysis patients , and its usage may be advantageous in the treatment of dialysis patients The risk of death in hemodialysis patients treated with calcium-containing phosphate binders or sevelamer is not known . We assessed all-cause mortality in 127 patients new to hemodialysis assigned to calcium-containing binders or sevelamer after a median follow-up of 44 months from r and omization . This was a predetermined secondary end point of a r and omized clinical trial design ed to assess progression of coronary artery calcium ( CAC ) scores in the two treatment arms . Thirty-four deaths occurred during the follow-up period : 23 in subjects r and omized to calcium-containing phosphate binders and 11 in subjects r and omized to sevelamer . Baseline CAC score was a significant predictor of mortality after adjustment for age , race , gender , and diabetes with increased mortality proportional to baseline score ( P=0.002 ) . Mortality was borderline significantly lower in subjects r and omized to sevelamer ( 5.3/100 patient years , confidence interval ( CI ) ( 2.2 - 8.5 ) compared to those r and omized to calcium-containing binders ( 10.6/100 patient years , CI 6.3 - 14.9 ) ( P=0.05 ) . The greater risk of death for patients treated with calcium-containing phosphate binders persisted after full multivariable adjustment ( P=0.016 , hazard ratio 3.1 , CI 1.23 - 7.61 ) . In subjects new to hemodialysis baseline CAC score was a significant predictor of all-cause mortality . Treatment with sevelamer was associated with a significant survival benefit as compared to the use of calcium-containing phosphate binders Disturbances of mineral metabolism are associated with significant morbidity and mortality in patients with chronic kidney disease . Unfortunately , some of the treatments for these disturbances also have been found to be associated with morbidity . More recently , there is increasing evidence in the form of prospect i ve , r and omized trials that the use of calcium-based phosphate binders contributes to progressive coronary artery and aorta calcification compared with the non-calcium-containing binder sevelamer . Moreover , there is compelling biologic plausibility that hyperphosphatemia and excess exogenous calcium administration can accelerate vascular calcification . Unfortunately , there is no bedside test that can determine whether there is a dose of calcium salts ( either as maintenance or as cumulative dose ) that can be administered safely , and , unfortunately , the serum calcium concentration does not reflect calcium balance . Therefore , calcium-based phosphate binders should be avoided in many , if not most , patients who are undergoing dialysis BACKGROUND Patients affected by end-stage renal disease ( ESRD ) demonstrate a very high cardiovascular risk mediated by traditional cardiovascular risk factors as well as abnormal mineral metabolism and a state of chronic inflammation . Sevelamer is a nonabsorbable non-calcium-based hydrogel with potential antiatherosclerotic properties . METHOD AND RESULTS One hundred eight patients undergoing maintenance hemodialysis were r and omized to sevelamer or calcium acetate as treatment for hyperphosphatemia . A coronary artery calcium score , as a measure of plaque burden , was calculated at baseline and 1 year , along with serial measurements of serum lipoproteins , beta2-microglobulin , and high-sensitivity C-reactive protein ( hs-CRP ) . At 1 year , coronary artery calcium score progressed significantly from baseline in calcium acetate-treated subjects ( P < .001 ) but not in sevelamer-treated patients ( P = NS ) . Total cholesterol ( P < .0001 ) , low-density lipoprotein cholesterol ( P < .0001 ) , apolipoprotein B ( P < .0001 ) , beta2-microglobulin ( P = .018 ) , and hs-CRP ( P < .002 ) decreased , and high-density lipoprotein increased significantly ( P = .036 ) from baseline in the sevelamer-treated subjects but not in subjects treated with calcium acetate despite the more frequent use of statins in the latter group ( 46 % vs 22 % , P < .05 ) . The changes in total and low-density lipoprotein cholesterol , apolipoprotein B , and hs-CRP were significantly different between treatment groups ( all P < .01 ) . CONCLUSIONS Sevelamer leads to favorable changes in lipids and inflammatory markers with potentially useful antiatherogenic effects in hemodialysis patients BACKGROUND Lanthanum carbonate ( LC ) has been proposed as a new phosphate binder . Presented here are the results from one centre that participated in a multicentre trial to assess the effect of treatment with LC and calcium carbonate ( CC ) on the evolution of renal osteodystrophy in dialysis patients . Bone biopsies were performed at baseline , after 1 year of treatment and after a further 2-year follow-up period to assess the lanthanum concentration in bone and plasma . METHODS Twenty new dialysis patients were r and omized to receive LC ( median dose 1250 mg ) for 1 year ( n = 10 ) , followed by 2 years of CC treatment or CC ( n = 10 ) during the whole study period ( 3 years ) . RESULTS After 36 weeks of treatment , steady state was reached with plasma lanthanum levels varying around 0.6 ng/ml . Six weeks after cessation of 1 year of treatment , the plasma lanthanum levels declined to a value of 0.17 + /- 0.12 ng/ml ( P < 0.05 ) and after 2 years to 0.09 + /- 0.03 ng/ml . Plasma and bone lanthanum levels did not correlate with the average lanthanum dose at any time point . The mean bone concentration in patients receiving LC increased from 0.05 + /- 0.03 to 2.3 + /- 1.6 microg/g ( P < 0.05 ) after 1 year and slightly decreased at the end of the study to 1.9 + /- 1.6 microg/g ( P < 0.05 ) . CONCLUSIONS Bone deposition after 1 year of treatment with LC is low ( highest concentration : 5.5 microg/g ) . There is a slow release of lanthanum from its bone deposits 2 years after the discontinuation of the treatment and no association with aluminium-like bone toxicity BACKGROUND Inadequate phosphorus control is associated with increased morbidity and mortality in patients with CKD stage 5 . Although phosphate binders are often used in patients on peritoneal dialysis ( PD ) , no large r and omized controlled studies evaluating their use solely in this population have previously been reported . METHODS In this multicentre , open-label study , adult patients on PD with serum phosphorus > 5.5 mg/dl were r and omized ( 2:1 ) to 12 weeks of treatment with sevelamer hydrochloride or calcium acetate . Doses were titrated to achieve serum phosphorus of 3.0 - 5.5 mg/dl . Changes in serum phosphorus , calcium , intact parathyroid hormone ( iPTH ) , lipids and plasma biomarkers were assessed . RESULTS A total of 253 patients were screened , 143 of whom were r and omized ( sevelamer hydrochloride , n = 97 ; calcium acetate , n = 46 ) . Treatment groups were well balanced with regard to baseline demographics . Serum phosphorus levels were significantly reduced after 12 weeks with both sevelamer hydrochloride and calcium acetate ( P < 0.001 ) . Serum PTH was also reduced in both groups while serum calcium increased in the calcium acetate group ( P = 0.001 ) but not in the sevelamer hydrochloride group . Sevelamer hydrochloride was also associated with decreases in total cholesterol , low-density lipoprotein cholesterol and uric acid and an increase in bone-specific alkaline phosphatase ( all P < 0.001 versus baseline ) . Both treatments were well tolerated and safety profiles were consistent with previous reports in haemodialysis patients . Hypercalcaemia was experienced by more calcium acetate-treated patients ( 18 versus 2 % ; P = 0.001 ) . CONCLUSIONS In summary , sevelamer hydrochloride provides a reduction in serum phosphorus compared to that obtained with calcium-based binders in PD patients . The effects of sevelamer hydrochloride appear similar in both PD and haemodialysis population Hyperphosphataemia plays a key role in the pathogenesis of renal osteodystrophy , and phosphate-binding agents are required in many chronic dialysis patients . Aluminium hydroxide and calcium carbonate are well-established phosphate binders , but their use is associated with toxicity or poor efficacy . Calcium acetate is known to be a potent phosphate binder , and has recently been used successfully in chronic dialysis patients . In this r and omized cross-over trial in 31 chronic haemodialysis patients , equimolar doses of calcium acetate and calcium carbonate were administered for 6 weeks each . Compliance was estimated from tablet counts , and biochemical parameters were measured at the end of each treatment period . Of the 31 patients 23 completed both treatment arms ; of the remainder , three withdrew due to adverse symptoms , hypercalcaemia necessitated treatment withdrawal in two , and three died . Non-compliance was significantly higher with acetate ( 18.3 % tablets not taken ) than with carbonate ( 8.7 % ) . Serum phosphate was significantly lower after treatment with acetate ( 1.51 mmol/l ) than with carbonate ( 1.80 ) , as was the Ca x PO4 product ( 3.59 vs 4.18 respectively ) and PTH ( 17.8 vs 25.4 pmol/l respectively ) . Serum calcium was significantly higher after acetate therapy ( 2.40 vs 2.32 mmol/l ) . No significant difference was found for sodium , potassium , bicarbonate , urea , creatinine , and haemoglobin . This study confirms that the treatment of hyperphosphataemia is more effective with calcium acetate than with calcium carbonate . For the first time an associated beneficial effect on secondary hyperparathyroidism has also been demonstrated . Patient tolerability of calcium acetate was considerably poorer , probably due in part to tablet formulation and bulkiness , as well as possible direct gastrointestinal effects of the acetate salt BACKGROUND Cardiovascular disease is frequent and severe in patients with end-stage renal disease . Disorders of mineral metabolism may contribute by promoting cardiovascular calcification . METHODS We conducted a r and omized clinical trial comparing sevelamer , a non-absorbed polymer , with calcium-based phosphate binders in 200 hemodialysis patients . Study outcomes included the targeted concentrations of serum phosphorus , calcium , and intact parathyroid hormone ( PTH ) , and calcification of the coronary arteries and thoracic aorta using a calcification score derived from electron beam tomography . RESULTS Sevelamer and calcium provided equivalent control of serum phosphorus ( end-of- study values 5.1 + /- 1.2 and 5.1 + /- 1.4 mg/dL , respectively , P = 0.33 ) . Serum calcium concentration was significantly higher in the calcium-treated group ( P = 0.002 ) , and hypercalcemia was more common ( 16 % vs. 5 % with sevelamer , P = 0.04 ) . More subjects in the calcium group had end-of- study intact PTH below the target of 150 to 300 pg/mL ( 57 % vs. 30 % , P = 0.001 ) . At study completion , the median absolute calcium score in the coronary arteries and aorta increased significantly in the calcium treated subjects but not in the sevelamer-treated subjects ( coronary arteries 36.6 vs. 0 , P = 0.03 and aorta 75.1 vs. 0 , P = 0.01 , respectively ) . The median percent change in coronary artery ( 25 % vs. 6 % , P = 0.02 ) and aortic ( 28 % vs. 5 % , P = 0.02 ) calcium score also was significantly greater with calcium than with sevelamer . CONCLUSIONS Compared with calcium-based phosphate binders , sevelamer is less likely to cause hypercalcemia , low levels of PTH , and progressive coronary and aortic calcification in hemodialysis patients BACKGROUND AND OBJECTIVES Management of hyperphosphatemia , a predictor of mortality in chronic kidney disease , is challenging . Nonadherence to dietary phosphate binders , in part , contributes to uncontrolled serum phosphorus levels . This phase IIIb trial assessed the efficacy of increased dosages ( 3000 to 4500 mg/d ) of reformulated lanthanum carbonate ( 500- , 750- , and 1000-mg tablets ) in nonresponders to dosages of up to 3000 mg/d . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS This 8-wk study with a 4-mo open-label extension enrolled 513 patients who were undergoing maintenance hemodialysis . Patients who achieved serum phosphorus control at week 4 with < or=3000 mg/d lanthanum carbonate entered cohort A ; nonresponders were r and omly assigned to receive 3000 , 3750 , or 4500 mg/d ( cohort B ) . The primary outcome measure was the control rate for predialysis serum phosphorus levels at the end of week 8 , among patients in cohort B. RESULTS At the end of week 4 , 54 % of patients achieved serum phosphorus control at dosages < or=3000 mg/d administered as one tablet per meal . Among patients who entered cohort B , control rates of 25 , 38 , and 32 % for patients who were r and omly assigned to 3000 , 3750 , or 4500 mg/d lanthanum carbonate , respectively , were achieved , with no increase in adverse events . Patients and physicians reported significantly higher levels of satisfaction with reformulated lanthanum carbonate compared with previous phosphate binders , partly because of reduced tablet burden with higher dosage strengths . Physicians and patients also expressed a preference for lanthanum carbonate over previous medication . CONCLUSIONS Reformulated lanthanum carbonate is an effective phosphate binder that may reduce daily tablet burden Calcium acetate has many characteristics of an ideal phosphorus binder . It is a readily soluble salt that avidly binds phosphorus in vitro at pH 5 and above . One-dose/one-meal balance studies show it to be more potent than calcium carbonate or calcium citrate . We studied chronic ( 3-month ) phosphorus binding with calcium acetate in 91 hyperphosphatemic dialysis patients at four different centers . All phosphorus binders were stopped for 2 weeks . Calcium acetate at an initial dose of 8.11 mmol ( 325 mg Ca2 + ) per meal was then used as the only phosphorus binder . Dose was adjusted to attempt control of predialysis phosphorus level less than 1.78 mmol/L ( 5.5 mg/100 mL ) . Final calcium acetate dose was 14.6 mmol ( 586 mg ) Ca2 + per meal . Sixteen patients developed mild transient hypercalcemia ( mean , 2.84 mmol/L [ 11.4 mg/dL ] . Initial phosphorus values in mmol/L ( mg/dL ) were 2.39 ( 7.4 ) ; at 1 month , 1.91 ( 5.9 ) ; and at 3 months , 1.68 ( 5.2 ) . Initial calcium values in mmol/L ( mg/dL ) were 2.22 ( 8.9 ) ; at 1 month , 2.37 ( 9.5 ) ; and at 3 months , 2.42 ( 9.7 ) . Initial aluminum values in mumol/L ( micrograms/L ) were 2.99 ( 80.7 ) ; and at 3 months were 2.54 ( 68.4 ) . Initial C-terminal parathyroid hormone ( C-PTH ) values in ng/mL were 14.6 ; at 1 month , 11.9 ; and at 3 months , 13.2 . Sixty-nine patients then entered a double-blind study . Phosphorus binders were stopped for 1 week . Calcium acetate ( at a dose established in a prior study ) or placebo was then administered for 2 weeks . Next , patients were crossed to the opposite regimen for 2 weeks . Initial phosphorus was 2.36 mmol/L ( 7.3 mg/100 mL ) and calcium 2.22 mmol/L ( 8.9 mg/100 mL ) . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Lanthanum carbonate is a highly effective phosphate binder with significant potential as a treatment for hyperphosphatemia in patients with end-stage renal disease ( ESRD ) . Here , the results of a placebo-controlled , dose-ranging study are presented . METHODS 196 patients ( > or = 18 years ) receiving hemodialysis for at least 6 months entered a 1- to 3-week , single-blind , placebo run-in phase . Of these , 145 patients were r and omized to a double-blind phase in which they received placebo or lanthanum carbonate in daily lanthanum doses of 225 , 675 , 1,350 or 2,250 mg for 6 weeks . Serum levels of phosphorus , calcium and parathyroid hormone , and adverse events were monitored throughout the study . RESULTS The intent-to-treat analysis ( n = 144 ) showed significant dose-related reductions in serum phosphorus at lanthanum doses of 675 , 1,350 and 2,250 mg . After 6 weeks of treatment , phosphorus levels were significantly lower in the lanthanum groups receiving 1,350 mg/day and 2,250 mg/day , compared with the placebo group ( respective changes from r and omization : -0.95 + /- 1.39 mg/dl ( -0.31 + /- 0.45 mmol/l ) , -1.13 + /- 2.01 mg/dl ( -0.36 + /- 0.65 mmol/l ) , 0.75 + /- 1.47 mg/dl ( 0.24 + /- 0.47 mmol/l ) , p < 0.001 ) . Significant reductions in serum phosphorus , compared with placebo , occurred in the lanthanum 1,350 mg/day group from the second week of treatment and in the 2,250 mg/day group from the first week of treatment . Adverse events were mainly gastrointestinal ( e.g. nausea and vomiting ) . Treatment-related adverse events occurred in 39 % of patients treated with lanthanum carbonate and 44 % of the placebo group . CONCLUSION Lanthanum carbonate is an effective and well-tolerated agent for the short-term treatment of hyperphosphatemia in patients with ESRD BACKGROUND Abnormalities in serum calcium , phosphorus , and parathyroid hormone ( PTH ) concentrations are common in patients with chronic kidney disease and have been associated with increased morbidity and mortality . No clinical trials have been conducted to clearly identify categories of calcium , phosphorus , and PTH levels associated with the lowest mortality risk . Current clinical practice guidelines are based largely on expert opinions , and clinical ly relevant differences exist among guidelines across countries . We sought to describe international trends in calcium , phosphorus , and PTH levels during 10 years and identify mortality risk categories in the Dialysis Outcomes and Practice Patterns Study ( DOPPS ) , an international study of hemodialysis practice s and associated outcomes . STUDY DESIGN Prospect i ve cohort study . PARTICIPANTS 25,588 patients with end-stage renal disease on hemodialysis therapy for longer than 180 days at 925 facilities in DOPPS I ( 1996 - 2001 ) , DOPPS II ( 2002 - 2004 ) , or DOPPS III ( 2005 - 2007 ) . PREDICTORS Serum calcium , albumin-corrected calcium ( Ca(Alb ) ) , phosphorus , and PTH levels . OUTCOMES Adjusted hazard ratios for all-cause and cardiovascular mortality calculated using Cox models . RESULTS Distributions of mineral metabolism markers differed across DOPPS countries and phases , with lower calcium and phosphorus levels observed in the most recent phase of DOPPS . Survival models identified categories with the lowest mortality risk for calcium ( 8.6 to 10.0 mg/dL ) , Ca(Alb ) ( 7.6 to 9.5 mg/dL ) , phosphorus ( 3.6 to 5.0 mg/dL ) , and PTH ( 101 to 300 pg/mL ) . The greatest risk of mortality was found for calcium or Ca(Alb ) levels greater than 10.0 mg/dL , phosphorus levels greater than 7.0 mg/dL , and PTH levels greater than 600 pg/mL and in patients with combinations of high-risk categories of calcium , phosphorus , and PTH . LIMITATIONS Because of the observational nature of DOPPS , this study can only indicate an association between mineral metabolism categories and mortality . CONCLUSIONS Our results provide important information about mineral metabolism trends in hemodialysis patients in 12 countries during a decade . The risk categories identified in the DOPPS cohort may be relevant to efforts at international harmonization of existing clinical guidelines for mineral metabolism AIMS To investigate the evolution of renal osteodystrophy in patients on maintenance dialysis , treated with lanthanum carbonate ( LC ) vs. st and ard phosphate-binder therapy ( Stx ) . MATERIAL S AND METHODS This was a 2-year , r and omized , prospect i ve , open-label study during which patients on dialysis received LC titrated to a maximum of 3,000 mg/day or their previous phosphate binder treatment with the aim to achieve target phosphorus levels of < or = 5.9 mg/dl . Paired bone biopsy sample s for histomorphometric analysis were available at baseline and 1 year ( LC 32 , Stx 33 ) , and at baseline and 2 years ( LC 32 , Stx 24 ) . RESULTS With similar phosphorus control , Stx was associated with numerically higher serum calcium levels at most visits . Results of osteocalcin and bone-specific alkaline phosphatase in LC patients were higher throughout the study and correlated with parameters of bone formation ; however , the differences were not significant . Histological changes in bone turnover and volume were analyzed with respect to normal ranges . There was an improvement in bone turnover in the LC group , which was significant in the 1-year group , and an improvement in bone volume which was significant in the 2-year group . No significant changes in bone turnover or bone volume were observed in the Stx groups . In the 2-year LC group , 1 patient had osteomalacia at baseline and end of therapy , and a mineralization defect developed in 2 other patients . Several possible factors for a mineralization defect were present in these patients , but no single cause could be clearly identified . Histomorphometric parameters of bone , including formation and mineralization , did not correlate with bone lanthanum . No mineralization defect was observed in the Stx groups . CONCLUSION These findings show that similar phosphorus control with Stx and LC results in higher bone turnover after 1 year and higher bone volume after 2 years with LC BACKGROUND The efficacy of lanthanum carbonate as a phosphate binder for the treatment of hyperphosphatemia has been reported , but not from a double-blind , comparator-controlled comparative study . METHODS The safety and efficacy of lanthanum carbonate and calcium carbonate on serum phosphate and calcium levels in Japanese hemodialysis patients were assessed by a r and omized , double-blind , comparator-controlled , parallel group , multicenter study . This study is the first study using a r and omized , double-blind method to compare lanthanum carbonate and calcium carbonate as phosphate binders . RESULTS In the double-blind phase , the changes in the serum phosphate level were similar in the lanthanum carbonate and calcium carbonate groups . The differences in the corrected serum calcium level or the calcium x phosphate products between the 2 groups were not statistically significant . However , the mean change in the corrected serum calcium level from baseline to the last outpatient visit was significantly lower in the lanthanum carbonate group than in the calcium carbonate group . The incidence of hypercalcemia in the lanthanum carbonate group was also significantly lower than in the calcium carbonate group . CONCLUSION Both compounds show similar efficacy on the serum phosphate level in patients undergoing hemodialysis when the dose is managed in a dose-variable and double-blind manner . However , lanthanum carbonate is superior in terms of lowering the incidence of hypercalcemia A prospect i ve , r and omized open-label trial of sevelamer hydrochloride with or without calcium carbonate ( CC ) involved 86 hemodialysis patients in Japan . The dosage of CC was fixed at 3.0 g/day for the 12-week study . After the first 4 weeks all subjects were changed from CC to sevelamer 3.0 g/day for another 4 weeks , then allocated r and omly to three groups for the final 4 weeks : group A , sevelamer 6.0 g/day ; group B , sevelamer 3.0 g/day and CC 3.0 g/day ; group C , CC 3.0 g/day . The target serum phosphorous concentration (P)=5.5 mg/dL and the corrected calcium concentration ( Ca ) was 9.0 - 10.0 mg/dL. Of the 86 patients , 62 finished the study without a change of dosage and their data were analyzed ( group A , N=16 ; group B , N=26 ; group C , N=20 ) . At week 8 compared with week 4 , the concentration of P increased from 5.7+/-1.4 to 6.4+/-1.7 mg/dL in group A , and decreased significantly in groups B and C , and in group B compared with groups A and C ; groups A and C had similar concentrations at week 8 . The Ca concentration decreased significantly from 9.7+/-1.0 to 9.1+/-0.7 mg/dL after the change to sevelamer . At week 8 Ca was not significantly changed in group A , whereas a significant increase occurred in groups B and C. Side-effects with sevelamer administration occurred in 34 of the 86 patients and 24 dropped out of the study , with a high frequency in group A ( 13/29 ; 44.8 % ) . In conclusion , there was an additive effect of sevelamer for the treatment of hyperphosphatemia with CC . The combination therapy was better tolerated and showed higher patient compliance than CC or sevelamer monotherapy OBJECTIVE We have previously shown sevelamer hydrochloride ( RenaGel ) to be an effective and well-tolerated treatment for hyperphosphatemia in hemodialysis patients . PATIENTS AND METHODS We performed a r and omized clinical trial to compare the efficacy of RenaGel alone and RenaGel with calcium , using the serum phosphorus concentration and intact parathyroid hormone ( PTH ) as the principal outcomes of interest . Calcium ( 900 mg elemental ) was provided as a once-nightly dose on an empty stomach . 71 patients were r and omized and included in the intent-to-treat population ; 55 completed the 16-week study period ( 2 weeks washout , 12 weeks treatment , 2 weeks washout ) . 49 % of subjects were taking vitamin D metabolites . RESULTS Serum phosphorus and PTH rose significantly when patients stopped their phosphate binders during both washout periods . RenaGel and RenaGel with calcium were equally effective at reducing serum phosphorus ( mean change -2.4 mg/dL vs. -2.3 mg/dL ) . RenaGel with calcium was associated with a small increase in serum calcium ( mean change 0.3 mg/dL vs. 0.0 mg/dL in RenaGel group , P = 0.09 ) that was not statistically significant . During the treatment phase , the reduction in PTH tended to be greater in the RenaGel with calcium group ( median change -67.0 vs. -22.5 pg/mL in RenaGel group , P = 0.07 ) . Non-users of vitamin D metabolites treated with RenaGel with calcium experienced a significant decrease in PTH ( median change -114.5 vs. -22 pg/mL in RenaGel group , P = 0.006 ) . Adverse events were seen with equal frequency in both groups , being generally mild in intensity , and rarely attributable to the drugs . CONCLUSION We conclude that RenaGel and RenaGel with calcium are similarly effective in the treatment of ESRD-related hyperphosphatemia . Provision of supplemental calcium or metabolites of vitamin D with RenaGel may enhance control of hyperparathyroidism BACKGROUND Statins reduce the incidence of cardiovascular events in patients at high cardiovascular risk . However , a benefit of statins in such patients who are undergoing hemodialysis has not been proved . METHODS We conducted an international , multicenter , r and omized , double-blind , prospect i ve trial involving 2776 patients , 50 to 80 years of age , who were undergoing maintenance hemodialysis . We r and omly assigned patients to receive rosuvastatin , 10 mg daily , or placebo . The combined primary end point was death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . Secondary end points included death from all causes and individual cardiac and vascular events . RESULTS After 3 months , the mean reduction in low-density lipoprotein ( LDL ) cholesterol levels was 43 % in patients receiving rosuvastatin , from a mean baseline level of 100 mg per deciliter ( 2.6 mmol per liter ) . During a median follow-up period of 3.8 years , 396 patients in the rosuvastatin group and 408 patients in the placebo group reached the primary end point ( 9.2 and 9.5 events per 100 patient-years , respectively ; hazard ratio for the combined end point in the rosuvastatin group vs. the placebo group , 0.96 ; 95 % confidence interval [ CI ] , 0.84 to 1.11 ; P=0.59 ) . Rosuvastatin had no effect on individual components of the primary end point . There was also no significant effect on all-cause mortality ( 13.5 vs. 14.0 events per 100 patient-years ; hazard ratio , 0.96 ; 95 % CI , 0.86 to 1.07 ; P=0.51 ) . CONCLUSIONS In patients undergoing hemodialysis , the initiation of treatment with rosuvastatin lowered the LDL cholesterol level but had no significant effect on the composite primary end point of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . ( Clinical Trials.gov number , NCT00240331 . The purpose of this study was to evaluate the effect of high-dose oral calcium on biochemical indices of bone formation , bone bisphosphonate clearance ( BBC ) and bone mineral content ( BMC ) of the distal forearm in patients undergoing hemodialysis . Eighteen patients agreed to participate and were r and omized in a double-blind manner to receive either 2 g elemental calcium/day ( n = 9 ) or placebo ( n = 9 ) for 6 months . Previous treatment with aluminum-containing phosphate binders was continued unchanged throughout the study . In the placebo group , serum alkaline phosphatase and osteocalcin tended to increase by 8.0 and 10.2 % , respectively , while BBC changed significantly by 49.5 % ( p < 0.05 ) . In the calcium group the opposite was observed with small decreases in alakline phosphatase and osteocalcin by 8.2 and 11.0 % , respectively , and no change in BBC . BMC decreased by 5.0 % in the placebo group , but increased by 5.2 % in the calcium group , result ing in a difference of 10.2 % ( p < 0.05 ) . The present study demonstrates that high-dose oral calcium tends to reduce bone turnover and seems able to prevent bone loss in hemodialyzed patients Dietary phosphate restriction and the oral administration of calcium and aluminum salts have been the principal means of controlling hyperphosphatemia in individuals with end-stage renal disease over the past decade . Although relatively well-tolerated , a large fraction of patients treated with calcium develop hypercalcemia , particularly when administered concurrently with calcitriol , despite a lowering of the dialysate calcium concentration . We evaluated the efficacy of cross-linked poly[allylamine hydrochloride ] ( RenaGel ; Geltex Pharmaceuticals , Waltham , MA ) , a nonabsorbable calcium- and aluminum-free phosphate binder , in a r and omized , placebo-controlled , double-blind trial of 36 maintenance hemodialysis patients followed over an 8-week period . RenaGel was found to be as effective as calcium carbonate or acetate as a phosphate binder . The reduction in serum phosphorus was significantly greater after 2 weeks of treatment with RenaGel ( 6.6 + /- 2.1 mg/dL to 5.4 + /- 1.5 mg/dL ) compared with placebo ( 7.0 + /- 2.1 mg/dL to 7.2 + /- 2.4 mg/dL ; P = 0.037 ) . There was no significant change in serum calcium concentration in either treatment group . The total serum cholesterol and low-density lipoprotein cholesterol fraction were significantly reduced in RenaGel-treated patients compared with placebo-treated patients ( P = 0.013 and P = 0.003 , respectively ) without a concomitant reduction in high-density lipoprotein cholesterol ( P = 0.93 ) . There was no difference among recipients of RenaGel and placebo in terms of adverse events . RenaGel is a safe and effective alternative to oral calcium for the management of hyperphosphatemia in end-stage renal disease INTRODUCTION The hyperphosphatemia , hypocalcemia and low calcitriol levels are pathogenic factors for secondary hyperparathyroidism in chronic renal failure . The phosphorus control is essential to prevent secondary hyperparathyroidism . There are not comparatives studies to test the efficacy of control of phosphorus binders in predialysis patients . AIM To compare the efficacy of calcium carbonate vs calcium acetate as phosphate binder in predialysis patients . MATERIAL AND METHODS The present study includes 28 patients with chronic renal failure ( mean clearance of creatinine 21 ml/min ) . Patients were separated into two groups : Group 1 : ( n = 14 ) received calcium carbonate 2,500 mg/day ( 1,000 mg of calcium ) ; Group 2 : ( n = 14 ) receives calcium acetate 1,000 mg ( 254 mg of calcium ) . Calcium and phosphorus were determined every 4 months ; i-PTH , alkaline phosphatase and clearance of creatinine were determined every six months . RESULTS Both groups were comparable regarding age , renal function , calcium , phosphorus , alkaline phosphatase and i-PTH on basal situation and the end of study were not different . The serum calcium increased , not significantly , in the calcium carbonate group ( group 1 ) [ from 9.2 to 9.8 mg/dl ( p = 0.05 ) ] , however it was not modified in the calcium acetate group ( group 2 ) . The serum phosphorus decreased significantly ( p < 0.05 ) in both groups , independently of the calcium levels . Alkaline phosphatase and i-PTH not was modified during the study period . CONCLUSIONS 1 ) Both calcium carbonate and calcium acetate are similarly effective as phosphate binder . 2 ) The carbonate group required four fold greater doses of calcium that acetate group . 3 ) The calcium acetate has less hypercalcemic effect than calcium carbonate BACKGROUND Previous clinical trials showed that progression of coronary artery calcification ( CAC ) may be slower in hemodialysis patients treated with sevelamer than those treated with calcium-based phosphate binders . Because sevelamer decreases low-density lipoprotein cholesterol ( LDL-C ) levels , we hypothesized that intensive lowering of LDL-C levels with atorvastatin in hemodialysis patients treated with calcium acetate would result in CAC progression rates similar to those in sevelamer-treated patients . STUDY DESIGN R and omized , controlled , open-label , noninferiority trial with an upper bound for the noninferiority margin of 1.8 . SETTING & PARTICIPANTS 203 prevalent hemodialysis patients at 26 dialysis centers with serum phosphorus levels greater than 5.5 mg/dL , LDL-C levels greater than 80 mg/dL , and baseline CAC scores of 30 to 7,000 units assessed by means of electron-beam computed tomography . INTERVENTIONS 103 patients were r and omly assigned to calcium acetate , and 100 patients to sevelamer for 12 months to achieve phosphorus levels of 3.5 to 5.5 mg/dL. Atorvastatin was added to achieve serum LDL-C levels less than 70 mg/dL in both groups . OUTCOMES & MEASUREMENTS The primary end point was change in CAC score assessed by means of electron-beam computed tomography . RESULTS After 12 months , mean serum LDL-C levels decreased to 68.8 + /- 22.0 mg/dL in the calcium-acetate group and 62.4 + /- 23.0 mg/dL in the sevelamer group ( P = 0.3 ) . Geometric mean increases in CAC scores were 35 % in the calcium-acetate group and 39 % in the sevelamer group , with a covariate-adjusted calcium acetate-sevelamer ratio of 0.994 ( 95 % confidence interval , 0.851 to 1.161 ) . LIMITATIONS Treatment assignment was not blinded . The 1.8 a priori margin is large , CAC is a surrogate outcome , duration of treatment was short , and dropout rate was high . CONCLUSIONS With intensive lowering of LDL-C levels for 1 year , hemodialysis patients treated with either calcium acetate or sevelamer experienced similar progression of CAC The first reported double-blind cross-over comparison between the phosphorus binders calcium carbonate and calcium acetate was undertaken in 15 stable patients on chronic maintenance haemodialysis . Detailed registration of diet and analysis of the protein catabolic rate suggested an unchanged phosphorus intake during the study . It was found that predialytic serum phosphate concentration was significantly decreased by 0.11 mmol/l ( 0.34 mg/dl ) ( P = 0.021 , 95 % confidence limits 0.02 - 0.21 mmol/l ; 0.06 - 0.65 mg/dl ) during calcium acetate treatment . The calcium phosphate product was insignificantly decreased during treatment with calcium acetate whereas we could not exclude the possibility that calcium concentration had increased UNLABELLED We performed a post hoc analysis of a 52-week r and omized trial conducted in adult hemodialysis patients that compared the effects of calcium-based phosphate binders and sevelamer , a nonabsorbable polymer , on parameters of mineral metabolism and vascular calcification by electron beam tomography . In this analysis , we evaluated the relative effects of calcium and sevelamer on thoracic vertebral attenuation by CT and markers of bone turnover . Subjects r and omized to calcium salts experienced a significant reduction in trabecular bone attenuation and a trend toward reduction in cortical bone attenuation , in association with higher concentrations of serum calcium , lower concentrations of PTH , and reduced total and bone-specific alkaline phosphatase . INTRODUCTION In patients with chronic kidney disease , hyperphosphatemia is associated with osteodystrophy , vascular and soft tissue calcification , and mortality . Calcium-based phosphate binders are commonly prescribed to reduce intestinal phosphate absorption and to attenuate secondary hyperparathyroidism . Clinicians and investigators have presumed that , in hemodialysis patients , calcium exerts beneficial effects on bone . MATERIAL S AND METHODS We performed a post hoc analysis of a 52-week r and omized trial conducted in adult hemodialysis patients that compared the effects of calcium-based phosphate binders and sevelamer , a nonabsorbable polymer , on parameters of mineral metabolism and vascular calcification by electron beam tomography . In this analysis , we evaluated the relative effects of calcium and sevelamer on thoracic vertebral attenuation by CT and markers of bone turnover . RESULTS AND CONCLUSIONS The average serum phosphorus and calcium x phosphorus products were similar for both groups , although the average serum calcium concentration was significantly higher in the calcium-treated group . Compared with sevelamer-treated subjects , calcium-treated subjects showed a decrease in thoracic vertebral trabecular bone attenuation ( p = 0.01 ) and a trend toward decreased cortical bone attenuation . More than 30 % of calcium-treated subjects experienced a 10 % or more decrease in trabecular and cortical bone attenuation . On study , sevelamer-treated subjects had higher concentrations of total and bone-specific alkaline phosphatase , osteocalcin , and PTH ( p < 0.001 ) . When used to correct hyperphosphatemia , calcium salts lead to a reduction in thoracic trabecular and cortical bone attenuation . Calcium salts may paradoxically decrease BMD in hemodialysis patients A comparative study of long-term haemodialysis patients investigated the effects of calcium acetate and calcium carbonate on concentrations of serum phosphate , calcium , and parathyroid hormone . It was demonstrated that both substances led to a significant decrease in phosphate and serum parathyroid hormone . Administration of calcium acetate reduced the serum phosphate concentration in 7 weeks from an initial value of 2.08 + /- 0.53 mmol/l to 1.51 + /- 0.39 mmol/l ( P less than 0.01 ) . Following a 1-week wash-out period , calcium carbonate reduced the serum phosphate concentration in the same patients from 1.99 + /- 0.62 mmol/l to 1.34 + /- 0.40 mmol/l ( P less than 0.01 ) . Of particular significance , however , is the fact that in relation to daily elementary calcium intake , calcium acetate was a considerably more effective binder of intestinal phosphate than calcium carbonate . During administration of calcium acetate only 1.02 g of elementary calcium were required daily in order to reduce the serum phosphate concentration . The same patients , however , required 1.88 g of elementary calcium during calcium carbonate therapy . Complementary studies investigated the influence of an accompanying calcitriol medication . In this instance , too , calcium acetate was shown to be more effective ; although the patients developed hypercalcaemia with calcium acetate , this happened more often with calcium carbonate . In summary it can be said that daily calcium loading of the uraemic organism under calcium acetate therapy is reduced by nearly half as compared to calcium carbonate therapy , and that this can be achieved with the same effective decrease of the serum phosphate concentration Current phosphate binders used in hemodialysis patients include calcium-based binders that result in frequent hypercalcemia and aluminum-based binders that result in total body aluminum accumulation over time . This investigation describes the use of a calcium- and aluminum-free phosphate-binding polymer in hemodialysis patients and compares it with a st and ard calcium-based phosphate binder . An open-label , r and omized , crossover study was performed to evaluate the safety and effectiveness of sevelamer hydrochloride in controlling hyperphosphatemia in hemodialysis patients . After a 2-week phosphate binder washout period , stable hemodialysis patients were administered either sevelamer or calcium acetate , and the dosages were titrated upward to achieve improved phosphate control over an 8-week period . After a 2-week washout period , patients crossed over to the alternate agent for 8 weeks . Eighty-four patients from eight centers participated in the study . There was a similar decrease in serum phosphate values over the course of the study with both sevelamer ( -2.0 + /- 2.3 mg/dL ) and calcium acetate ( -2.1 + /- 1.9 mg/dL ) . Twenty-two percent of patients developed a serum calcium greater than 11.0 mg/dL while receiving calcium acetate , versus 5 % of patients receiving sevelamer ( P < 0.01 ) . The incidence of hypercalcemia for sevelamer was not different from the incidence of hypercalcemia during the washout period . Patients treated with sevelamer also sustained a 24 % mean decrease in serum low-density lipoprotein cholesterol levels . Sevelamer was effective in controlling hyperphosphatemia without result ing in an increase in the incidence of hypercalcemia seen with calcium acetate . This agent appears quite effective in the treatment of hyperphosphatemia in hemodialysis patients , and its usage may be advantageous in the treatment of dialysis patients Background / Aims : Hyperphosphatemia is an important clinical consequence of renal failure , and its multiple adverse systemic effects are associated with significantly increased risks of morbidity and mortality in dialysis patients . Existing oral phosphate binders have not permitted control of serum phosphate within currently accepted guidelines . This study compares lanthanum carbonate with calcium carbonate for control of serum phosphate in hemodialysis patients . Methods : In this European multicentre study , 800 patients were r and omised to receive either lanthanum or calcium carbonate and the dose titrated over 5 weeks to achieve control of serum phosphate . Serum levels of phosphate , calcium and parathryoid hormone were followed over the following 20 weeks . Results : Around 65 % of patients in each group achieved phosphate control , but in the calcium carbonate group this was at the expense of significant hypercalcemia ( 20.2 % of patients vs. 0.4 % ) . Consequently , calcium x phosphate product tended to be better controlled in the lanthanum group . Conclusion : This 6-month study demonstrates that serum phosphate control with lanthanum carbonate ( 750–3,000 mg/day ) is similar to that seen with calcium carbonate ( 1,500–9,000 mg/day ) , but with a significantly reduced incidence of hypercalcemia . Lanthanum carbonate is well tolerated and may be more effective in reducing calcium x phosphate product than calcium carbonate Disturbances in mineral metabolism play a central role in the development of renal bone disease . In a 54-wk , r and omized , open-label study , 119 hemodialysis patients were enrolled to compare the effects of sevelamer hydrochloride and calcium carbonate on bone . Biopsy-proven adynamic bone disease was the most frequent bone abnormality at baseline ( 59 % ) . Serum phosphorus , calcium , and intact parathyroid hormone were well controlled in both groups , although calcium was consistently lower and intact parathyroid hormone higher among patients who were r and omly assigned to sevelamer . Compared with baseline values , there were no changes in mineralization lag time or measures of bone turnover ( e.g. , activation frequency ) after 1 yr in either group . Osteoid thickness significantly increased in both groups , but there was no significant difference between them . Bone formation rate per bone surface , however , significantly increased from baseline only in the sevelamer group ( P = 0.019 ) . In addition , of those with abnormal microarchitecture at baseline ( i.e. , trabecular separation ) , seven of 10 in the sevelamer group normalized after 1 yr compared with zero of three in the calcium group . In summary , sevelamer result ed in no statistically significant changes in bone turnover or mineralization compared with calcium carbonate , but bone formation increased and trabecular architecture improved with sevelamer . Further studies are required to assess whether these changes affect clinical outcomes , such as rates of fracture BACKGROUND Lanthanum carbonate is a novel , non-calcium , non-aluminum phosphate binder under evaluation for the treatment of hyperphosphatemia in end-stage renal disease ( ESRD ) patients receiving either hemodialysis or continuous ambulatory peritoneal dialysis . METHODS This 16-week study assessed the control of serum phosphorus with lanthanum carbonate , and its effects on serum calcium , calcium x phosphorus product , and parathyroid hormone ( PTH ) . Hemodialysis patients > or = 18 years old entered into a 1- to 3-week washout period during which serum phosphorus levels rose to > 5.9 mg/dL ( 1.90 mmol/L ) . In total , 126 patients were titrated with lanthanum carbonate at doses containing 375 , 750 , 1,500 , 2,250 , or 3,000 mg/d elemental lanthanum , given in divided doses with meals over a 6-week period , to achieve serum levels < or = 5.9 mg/dL. By the end of dose titration , 11/126 ( 9 % ) patients received < or = 750 mg/d of lanthanum , 25 ( 20 % ) received 1,500 mg/d , 37 ( 29 % ) received 2,250 mg/d , and 53 ( 42 % ) received 3,000 mg/d . Following titration , patients were r and omized to receive either lanthanum carbonate or placebo during a 4-week , double-blind maintenance phase . RESULTS At the study endpoint , the mean difference in serum phosphorus between the lanthanum carbonate and placebo treatment arms was 1.91 mg/dL ( 0.62 mmol/L ) ( P < 0.0001 ) . Calcium x phosphorus product ( P < 0.0001 ) and serum PTH levels ( P < 0.01 ) were also significantly lower with lanthanum carbonate versus placebo . The incidence of drug-related adverse events was similar between placebo- and lanthanum carbonate-treated patients . CONCLUSION Lanthanum carbonate is an effective and well-tolerated agent for the treatment of hyperphosphatemia in patients with ESRD BACKGROUND Lanthanum carbonate ( LC ) ( Fosrenol ) is a novel new treatment for hyperphosphatemia . In this phase III , open-label study , we compared the effects of LC and calcium carbonate ( CC ) on the evolution of renal osteodystrophy ( ROD ) in dialysis patients . METHODS Ninety-eight patients were r and omized to LC ( N = 49 ) or CC ( N = 49 ) . Bone biopsies were taken at baseline and after one year of treatment . Acceptable paired biopsies were available for static and dynamic histomorphometry studies in 33 LC and 30 CC patients . Blood sample s were taken at regular intervals for biochemical analysis and adverse events were monitored . RESULTS LC was well tolerated and serum phosphate levels were well controlled in both treatment groups . The incidence of hypercalcemia was lower in the LC group ( 6 % vs. 49 % for CC ) . At baseline , subtypes of ROD were similarly distributed in both groups , with mixed ROD being most common . At one-year follow-up in the LC group , 5 of 7 patients with baseline low bone turnover ( either adynamic bone or osteomalacia ) , and 4 of 5 patients with baseline hyperparathyroidism , had evolved toward a normalization of their bone turnover . Only one lanthanum-treated patient evolved toward adynamic bone compared with 6 patients in the CC group . In the LC group , the number of patients having either adynamic bone , osteomalacia , or hyperpara decreased overall from 12 ( 36 % ) at baseline to 6 ( 18 % ) , while in the calcium group , the number of patients with these types of ROD increased from 13 ( 43 % ) to 16 ( 53 % ) . CONCLUSION LC is a poorly absorbed , well-tolerated , and efficient phosphate binder . LC-treated dialysis patients show almost no evolution toward low bone turnover over one year ( unlike CC-treated patients ) , nor do they experience any aluminum-like effects on bone |
929 | 32,206,899 | In-hospital factors relating to assessment , imaging and thrombolysis administration also contributed . | This review examined factors that delay thrombolysis and what management strategies are currently employed to minimise this delay , with the aim of suggesting future directions to overcome bottlenecks in treatment delivery . | Background — The effectiveness of specific systems changes to reduce DTN ( door-to-needle ) time has not been fully evaluated . We analyzed the impact of 4 specific DTN time reduction strategies implemented prospect ively in a staggered fashion . Methods and Results — The HASTE ( Hurry Acute Stroke Treatment and Evaluation ) project was implemented in 3 phases at a single academic medical center . In HASTE I ( June 6 , 2012 to June 5 , 2013 ) , baseline performance was analyzed . In HASTE II ( June 6 , 2013 to January 24 , 2015 ) , 3 changes were implemented : ( 1 ) a STAT stroke protocol to prenotify the stroke team about incoming stroke patients ; ( 2 ) administering alteplase at the computed tomography ( CT ) scanner ; and ( 3 ) registering the patient as unknown to allow immediate order entry . In HASTE III ( January 25 , 2015 to June 29 , 2015 ) , we implemented a process to bring the patient directly to CT on the emergency medical services stretcher . Log-transformed DTN time was modeled . Data from 350 consecutive alteplase-treated patients were analyzed . Multivariable regression showed the following factors to be significant : giving alteplase in the CT ( 32 % decrease in DTN time , 95 % confidence interval [ CI ] 38%–55 % ) , stretcher to CT ( 30 % decrease in DTN time , 95 % CI 16%–42 % ) , patient registered as unknown ( 12 % decrease in DTN time , 95 % CI 3%–20 % ) , STAT stroke protocol ( 11 % decrease in DTN time , 95 % CI 1%–20 % ) , and stroke severity ( National Institutes of Health Stroke Scale score 6–8 : 19 % decrease in DTN time , 95 % CI 6%–31 % ; National Institutes of Health Stroke Scale score > 8 : 27 % decrease in DTN time , 95 % CI 17%–37 % ) . Conclusions — Taking the patient to CT on the emergency medical services stretcher , registering the patient as unknown , STAT stroke protocol , and administering alteplase in CT are associated with lower DTN time Background and Purpose Use of thrombolysis and acute treatments for cerebral infa rct ion may require that acute stroke be treated as a medical emergency . To assess the factors influencing the time to admission in acute stroke , we conducted a prospect i ve study of all such patients admitted to the hospitals in Leicester , UK , over a 12-month period . Methods Factors assessed were age , sex , time of stroke onset , stroke severity , home circumstances , and routes of admission . Initial between-group comparisons were made with the Mann-Whitney U test . The individual contribution of each of these variables was assessed with multiple linear regression analysis . Results An accurate time of stroke onset was identified in 374 ( 70 % ) of 535 registered patients ( median age 77 [ range , 29–98 ] years ; 332 men , 203 women ) . Median time from onset to admission was 6 hours , with 25 % of the patients arriving in less than 2.5 hours and 75 % in less than 11.5 hours . Multiple regression confirmed that only admission through the bed allocation bureau ( p<0.001 ) , living alone ( p<0.001 ) , and nocturnal onset ( p=0.003 ) prolonged delay time . Despite patients over 70 years of age taking a median of 7 hours from onset to admission compared with 4 hours for those under age 70 ( p<0.001 ) , the effect of age appeared to be dependent on these three factors . Age , sex , level of consciousness , rural domicile , and place of admission did not influence the delay time independently . Conclusions We have identified some of the factors affecting the hospital admission delay time for stroke . With the possible advent of effective early treatments for stroke , these factors will need to be addressed Background and Purpose — Faster treatment with intravenous tissue-type plasminogen activator ( tPA ) is likely to improve outcomes . Optimizing prehospital triage by mobile stroke units ( MSUs ) may speed treatment times . The Benefits of Stroke Treatment Delivered Using a Mobile Stroke Unit ( BEST-MSU ) study was launched in May 2014 using the first MSU in the United States to compare stroke management using an MSU versus st and ard management ( SM ) . Herein , we describe the results of the prespecified , nonr and omized run-in phase design ed to obtain preliminary data on study logistics . Methods — The run-in phase consisted of 8 MSU weeks when all-patient care occurred on the MSU and 2 SM weeks when the MSU nurse met personnel on scene or at the emergency department to ensure comparability with MSU patients . Telemedicine was independently performed in 9 MSU cases . Results — Of 130 alerts , 24 MSU and 2 SM patients were enrolled . Twelve of 24 MSU patients received tPA on board ; 4 were treated within 60 minutes of last seen normal , and 4 went on to endovascular treatment . There were no hemorrhagic complications . Four had primary intracerebral hemorrhage . Agreement on tPA eligibility between the onsite and telemedicine physician was 90 % . Conclusions — The run-in phase provided a tPA treatment rate of 1.5 patients per week , assured us that treatment within 60 minutes of onset is possible , and enabled enrollment of patients on SM weeks . We also recognized the opportunity to assess the effect of the MSU on endovascular treatment and intracerebral hemorrhage . Challenges include the need to control biased patient selection on MSU versus SM weeks and establish inter-rater agreement for tPA treatment using telemedicine Background and Purpose — Enrollment in acute stroke trials at a stroke center with multiple study protocol s may delay the initiation of intravenous thrombolytics in patients who present within 3 hours of symptom onset . Methods — We studied all patients presenting with acute ischemic stroke over the past 3.5 years who qualified for thrombolysis within 3 hours of symptom onset . We collected demographics , baseline National Institutes of Health Stroke Scale scores , CT findings , and arrival-to-treatment times and compared patients treated with intravenous thrombolytics in a clinical trial with patients who received st and ard of care intravenous tissue plasminogen activator . Results — Of 290 treated patients , 19 were enrolled in prelytic studies , 46 were enrolled in postlytic studies , and 225 were treated with st and ard intravenous tissue plasminogen activator . There was no significant difference in age , gender , National Institutes of Health Stroke Scale score , admission glucose , or changes on CT . There was no difference in onset-to-arrival time or arrival-to-treatment time between patients enrolled in clinical studies and those who received st and ard treatment . However , among study patients , prelytic r and omization led to a significantly longer arrival-to-treatment time by 13 minutes ( P=0.028 ) . Conclusion — We found that trials requiring prethrombolytic r and omization can lead to a delay in the initiation of treatment . Future studies are needed to determine if such a delay is clinical ly significant and can be shortened by improved enrollment strategies Background and Purpose — Thrombolysis for treatment of acute ischemic stroke should be administered as fast as possible after symptom onset . The aim of this study was to examine , in our tertiary care center , the time intervals preceding intra-arterial thrombolysis in order to accelerate and optimize the management of acute strokes . Methods — Between January 1 , 2000 , and April 30 , 2002 , 597 patients with acute stroke were admitted to our stroke center . One hundred forty-eight patients underwent diagnostic arteriography , and 100 ( 16.8 % ) received intra-arterial thrombolysis . For all patients , we prospect ively recorded and analyzed the time of symptom onset , admission , CT and /or MRI scan , diagnostic arteriography , and , if performed , intra-arterial thrombolysis . Results — The mean time to arrival in the emergency department was 99 minutes for patients who were admitted directly ( Bern patients ) , 127 minutes for those who were referred from community hospitals without a CT scanner ( non-Bern/−CT patients ) , and 210 minutes for patients from hospitals with imaging facilities ( non-Bern/+CT patients ) . The mean delay from symptom onset to treatment was 234 minutes for Bern patients , 269 minutes for non-Bern/−CT patients , and 302 minutes for non-Bern/+CT patients . The patients from the last group needed longer to receive intra-arterial thrombolysis than did patients who were admitted directly ( P = 0.002 ) or who were transferred from a hospital without a CT scanner ( P = 0.03 ) . Conclusions — This prospect i ve study indicates that direct referral without prior imaging at community hospitals shortens the time until intra-arterial thrombolysis . In addition , our in-hospital delay preceding intra-arterial thrombolysis is longer than the delays reported for intravenous thrombolysis and indicates potential for improvement Background Intravenous thrombolysis ( IVT ) with ( recombinant ) tissue plasminogen activator is an effective treatment in acute ischemic stroke . However , IVT is contraindicated when blood pressure is above 185/110 mmHg , because of an increased risk on symptomatic intracranial hemorrhage . In current Dutch clinical practice , two distinct strategies are used in this situation . The active strategy comprises lowering blood pressure with antihypertensive agents below these thresholds to allow start of IVT . In the conservative strategy , IVT is administered only when blood pressure drops spontaneously below protocol led thresholds . A retrospective analysis in two recent stroke trials showed a non-significant signal towards better functional outcome in the active group ; robust evidence for either strategy , however , is lacking . We hypothesize that ( I ) the active strategy leads to a better functional outcome three months after acute ischemic stroke . Secondary hypotheses are that this effect occurs despite ( II ) increasing the number of symptomatic intracranial hemorrhages , and could be attributable to ( III ) a higher rate of IVT treatments and ( IV ) a shorter door-to-needle time . Methods and design The TRUTH is a prospect i ve , observational , cluster-based , parallel group follow-up study ; in which participating centers continue their current local treatment guidelines . Outcomes of patients admitted to centers with an active will be compared to those admitted to centers with a conservative strategy . The primary outcome is functional outcome on the modified Rankin Scale at three months . Secondary outcomes are symptomatic intracranial hemorrhage , IVT treatment and door-to-needle time . We based our sample size estimate on an ordinal analysis of the mRS with the “ proportional odds ” model . With the aforementioned signal observed in a recent retrospective study in these patients as an estimate of the effect size and with alpha 0 · 05 , this analysis would have an 80 % power with a total number of 600 patients . Corrections for expected imbalance in group size and clustering effects result ed in a sample size of 1235 patients . Discussion The TRUTH is the first large prospect i ve study specifically study ing IVT-c and i date s with elevated blood pressure , and has the potential to change clinical practice and optimize acute stroke care in these patients BACKGROUND The time from symptom onset to seeking medical assistance ( decision delay ) accounts for a proportion of prehospital delay in acute stroke . The aims of this study were to identify factors related to decision delay and calling the emergency medical services ( EMS ) as the first medical contact . METHODS Data were prospect ively collected from 350 patients with acute stroke or transient ischemic attack . Data on decision delay , prehospital delay , types of first medical contact , and previous stroke knowledge were recorded . Multivariable logistic regression analyses were conducted to identify factors related to decision delay of 1 hour or less and calling the EMS as the first medical contact . RESULTS The median decision delay was 2.0 hours . Decision delay accounted for 62.3 % of prehospital delay ( median value ) . Moderate ( National Institutes of Health Stroke Scale [ NIHSS ] score 8 - 16 ; odds ratio [ OR ] 4.16 [ 95 % confidence interval 1.86 - 9.30 ] ) or severe symptoms ( NIHSS score ≥ 17 ; OR 10.38 [ 2.70 - 39.90 ] ) and living together ( OR 1.84 [ 1.02 - 3.43 ] ) were associated with decision delay of 1 hour or less . Moderate ( OR 6.31 [ 2.79 - 14.29 ] ) or severe symptoms ( OR 8.44 [ 2.64 - 26.98 ] ) were associated with calling the EMS as the first medical contact . Previous stroke knowledge did not affect an early decision or EMS use . CONCLUSIONS The decision to seek medical assistance in acute stroke accounts for more than half of the prehospital delay . Severity of symptoms and living together are related to an early decision ( ≤1 hour ) . Previous stroke knowledge does not affect decision delay or EMS use Rationale Mobile stroke units speed treatment for acute ischemic stroke , thereby possibly improving outcomes . Aim To compare mobile stroke unit and st and ard management clinical outcomes , healthcare utilization , and cost-effectiveness in tissue plasminogen activator-eligible acute ischemic stroke patients calling 911 . Sample size 693 . Eighty percent power with 0.05 type I error rate to detect a difference of 0.09 in mean utility-weighted modified Rankin scale between groups . Design Phase III , multicenter , prospect i ve cluster-r and omized ( mobile stroke unit versus st and ard management weeks ) comparative effectiveness study in tissue plasminogen activator-eligible patients . Outcomes Primary : Ninety-day mean utility-weighted modified Rankin scale . Co primary : cost-effectiveness based on EQ5D quality of life and one year poststroke costs . Analysis Two- sample t-test and linear regression adjusting for covariates ; incremental cost-effectiveness ratio and net benefit regression . Results As of March 2017 , 288 tissue plasminogen activator-eligible patients have been enrolled ( 173 in the mobile stroke unit arm and 115 in the st and ard management arm ) . Two new centers start in early 2017 with target end of recruitment September 2019 . Conclusion This is the first r and omized study to test for disability , healthcare utilization , and cost-effectiveness of a mobile stroke unit . The progress of the study suggests that it is feasible . Management of tissue plasminogen activator eligible acute ischemic stroke patients by a mobile stroke unit could potentially result in less disability and healthcare utilization , and be cost effective . Mobile stroke units are very costly . This trial may determine if the fixed cost can be justified by a reduction in disability and healthcare utilization . Clinical Trial Registration NCT02190500 Background and Purpose — Clinical triage scales for prehospital recognition of large vessel occlusion ( LVO ) are limited by low specificity when applied by paramedics . We created the 3-step ambulance clinical triage for acute stroke treatment ( ACT-FAST ) as the first algorithmic LVO identification tool , design ed to improve specificity by recognizing only severe clinical syndromes and optimizing paramedic usability and reliability . Methods — The ACT-FAST algorithm consists of ( 1 ) unilateral arm drift to stretcher < 10 seconds , ( 2 ) severe language deficit ( if right arm is weak ) or gaze deviation/hemineglect assessed by simple shoulder tap test ( if left arm is weak ) , and ( 3 ) eligibility and stroke mimic screen . ACT-FAST examination steps were retrospectively vali date d , and then prospect ively vali date d by paramedics transporting culturally and linguistically diverse patients with suspected stroke in the emergency department , for the identification of internal carotid or proximal middle cerebral artery occlusion . The diagnostic performance of the full ACT-FAST algorithm was then vali date d for patients accepted for thrombectomy . Results — In retrospective ( n=565 ) and prospect i ve paramedic ( n=104 ) validation , ACT-FAST displayed higher overall accuracy and specificity , when compared with existing LVO triage scales . Agreement of ACT-FAST between paramedics and doctors was excellent ( & kgr;=0.91 ; 95 % confidence interval , 0.79–1.0 ) . The full ACT-FAST algorithm ( n=60 ) assessed by paramedics showed high overall accuracy ( 91.7 % ) , sensitivity ( 85.7 % ) , specificity ( 93.5 % ) , and positive predictive value ( 80 % ) for recognition of endovascular-eligible LVO . Conclusions — The 3-step ACT-FAST algorithm shows higher specificity and reliability than existing scales for clinical LVO recognition , despite requiring just 2 examination steps . The inclusion of an eligibility step allowed recognition of endovascular-eligible patients with high accuracy . Using a sequential algorithmic approach eliminates scoring confusion and reduces assessment time . Future studies will test whether field application of ACT-FAST by paramedics to bypass suspected patients with LVO directly to endovascular-capable centers can reduce delays to endovascular thrombectomy Objective : To test the transferability of the Helsinki stroke thrombolysis model that achieved a median 20-minute door-to-needle time ( DNT ) to an Australian health care setting . Methods : The existing “ code stroke ” model at the Royal Melbourne Hospital was evaluated and restructured to include key components of the Helsinki model : 1 ) ambulance prenotification with patient details alerting the stroke team to meet the patient on arrival ; 2 ) patients transferred directly from triage onto the CT table on the ambulance stretcher ; and 3 ) tissue plasminogen activator ( tPA ) delivered in CT immediately after imaging . We analyzed our prospect i ve , consecutive tPA registry for effects of these protocol changes on our DNT after implementation during business hours ( 8 am to 5 pm Monday – Friday ) from May 2012 . Results : There were 48 patients treated with tPA in the 8 months after the protocol change . Compared with 85 patients treated in 2011 , the median ( interquartile range ) DNT was reduced from 61 ( 43–75 ) minutes to 46 ( 24–79 ) minutes ( p = 0.040 ) . All of the effect came from the change in the in-hours DNT , down from 43 ( 33–59 ) to 25 ( 19–48 ) minutes ( p = 0.009 ) , whereas the out-of-hours delays remain unchanged , from 67 ( 55–82 ) to 62 ( 44–95 ) minutes ( p = 0.835 ) . Conclusion : We demonstrated rapid transferability of an optimized tPA protocol to a different health care setting . With the cooperation of ambulance , emergency , and stroke teams , we succeeded in the absence of a dedicated neurologic emergency department or electronic patient records , which are features of the Finnish system . The next challenge is providing the same service out-of-hours BACKGROUND Many studies have examined the timeliness of thrombolysis for acute ischemic stroke , but less is known about door-to-imaging time . We conducted a prospect i ve cohort study to assess the timing of neuroimaging among patients with suspected acute stroke in the province of Ontario , Canada , and to examine factors associated with delays in neuroimaging . METHODS We included all patients 18 years and older with suspected acute stroke seen at hospitals with neuroimaging capacity within the Ontario Stroke Registry between Apr. 1 , 2010 , and Mar. 31 , 2011 . We used a hierarchical , multivariable Cox proportional hazards model to evaluate the association between patient and hospital factors and the likelihood of receiving timely neuroimaging ( ≤ 25 min ) after arrival in the emergency department . RESULTS A total of 13 250 patients presented to an emergency department with stroke-like symptoms during the study period . Of the 3984 who arrived within 4 hours after symptom onset , 1087 ( 27.3 % ) had timely neuroimaging . The factors independently associated with an increased likelihood of timely neuroimaging were less time from symptom onset to presentation , more severe stroke , male sex , no history of stroke or transient ischemic attack , arrival to hospital from a setting other than home and presentation to a design ated stroke centre or an urban hospital . INTERPRETATION A minority of patients with stroke-like symptoms who presented within the 4-hour thrombolytic treatment window received timely neuroimaging . Neuroimaging delays were influenced by various patient and hospital factors , some of which are modifiable Background and Purpose — Early initiated treatment of stroke increases the chances of a good recovery . This r and omized controlled study evaluates how an increased priority level for patients with stroke , from level 2 to 1 , from the Emergency Medical Communication Center influences thrombolysis frequency , time to stroke unit , and whether other medical emergencies reported negative consequences . Methods — Patients aged 18 to 85 years in Stockholm , Sweden , with symptoms of stroke within 6 hours were r and omized from the Emergency Medical Communication Center or emergency medical services to an intervention group , priority level 1 , immediate call of an ambulance , or to a control group with st and ard priority level , that is , priority level 2 ( within 30 minutes ) . Before study start , an educational program on identification of stroke and importance of early initiated treatment was directed to all medical dispatchers and ambulance and emergency department personnel . Results — During 2008 , 942 patients were r and omized of which 53 % ( n=496 ) had a final stroke/transient ischemic attack diagnosis . Patients in the Emergency Medical Communication Center r and omized intervention group reached the stroke unit 26 minutes earlier than the control group ( P<0.001 ) after the emergency call . Thrombolysis was given to 24 % of the patients in the intervention group compared with 10 % of the control subjects ( P<0.001 ) . The higher priority level showed no negative effect on other critical ill patients requiring priority level 1 prehospital attention . Conclusion — This r and omized study shows negligible harm to other medical emergencies , a significant increase in thrombolysis frequency , and a shorter time to the stroke unit for patients with stroke up grade d to priority level 1 from the Emergency Medical Communication Center and through the acute chain of stroke care BACKGROUND Only 2 - 5 % of patients who have a stroke receive thrombolytic treatment , mainly because of delay in reaching the hospital . We aim ed to assess the efficacy of a new approach of diagnosis and treatment starting at the emergency site , rather than after hospital arrival , in reducing delay in stroke therapy . METHODS We did a r and omised single-centre controlled trial to compare the time from alarm ( emergency call ) to therapy decision between mobile stroke unit ( MSU ) and hospital intervention . For inclusion in our study patients needed to be aged 18 - 80 years and have one or more stroke symptoms that started within the previous 2·5 h. In accordance with our week-wise r and omisation plan , patients received either prehospital stroke treatment in a specialised ambulance ( equipped with a CT scanner , point-of-care laboratory , and telemedicine connection ) or optimised conventional hospital-based stroke treatment ( control group ) with a 7 day follow-up . Allocation was not masked from patients and investigators . Our primary endpoint was time from alarm to therapy decision , which was analysed with the Mann-Whitney U test . Our secondary endpoints included times from alarm to end of CT and to end of laboratory analysis , number of patients receiving intravenous thrombolysis , time from alarm to intravenous thrombolysis , and neurological outcome . We also assessed safety endpoints . This study is registered with Clinical Trials.gov , number NCT00153036 . FINDINGS We stopped the trial after our planned interim analysis at 100 of 200 planned patients ( 53 in the prehospital stroke treatment group , 47 in the control group ) , because we had met our prespecified criteria for study termination . Prehospital stroke treatment reduced the median time from alarm to therapy decision substantially : 35 min ( IQR 31 - 39 ) versus 76 min ( 63 - 94 ) , p<0·0001 ; median difference 41 min ( 95 % CI 36 - 48 min ) . We also detected similar gains regarding times from alarm to end of CT , and alarm to end of laboratory analysis , and to intravenous thrombolysis for eligible ischaemic stroke patients , although there was no substantial difference in number of patients who received intravenous thrombolysis or in neurological outcome . Safety endpoints seemed similar across the groups . INTERPRETATION For patients with suspected stroke , treatment by the MSU substantially reduced median time from alarm to therapy decision . The MSU strategy offers a potential solution to the medical problem of the arrival of most stroke patients at the hospital too late for treatment . FUNDING Ministry of Health of the Saarl and , Germany , the Werner-Jackstädt Foundation , the Else-Kröner-Fresenius Foundation , and the Rettungsstiftung Saar Background and Purpose — Emergency department ( ED ) crowding occurs when dem and s for ED care exceed the supply of available re sources . Prior studies have shown that ED crowding is associated with a delay in provision of critical ED services , but the impact of ED crowding on acute stroke care has not been extensively studied . Methods — We conducted a retrospective study of patients who presented to the ED with acute stroke symptoms ( ischemic stroke , transient ischemic attack , intracerebral hemorrhage ) at 2 hospitals . All patients with active stroke symptoms who presented within 3 hours were included and a r and om sample of patients with symptoms > 3 hours was used for comparison . The association between ED crowding measures ( waiting room number , ED occupancy , number of admitted patients , and total patient hours ) and time to head CT order , completion , and interpretation , and time to administration of thrombolysis was determined . Results — Of 253 patients presenting with acute stroke symptoms ≤3 hours from symptom onset , 52 ( 21 % ) received thrombolysis . A r and om comparison group of 253 patients with symptoms > 3 hours was identified . There was no significant association between ED crowding and delays in CT timing or thrombolysis in patients with symptoms ≤3 hours . Several measures of ED crowding were associated with prolonged times to CT order and completion in patients with symptoms > 3 hours . Conclusions — ED crowding was not associated with care delays in thrombolysis-eligible patients with stroke . However , those with symptoms > 3 hours do experience CT delays at higher levels of ED crowding Background : Stroke units and thrombolysis are evidence based treatments for stroke patients . Few studies have prospect ively assessed the success of , and obstacles to implementation of such strategies in patients admitted to district general hospitals . Objective : To document delays in admissions of acute stroke patients to hospital , failures in accessing a stroke unit and the clinical impact of missed opportunities for intervention in acute stroke patients . Design , setting and methods : Prospect i ve observational study in a district general hospital in Northern Irel and . Delays , demographic details , risk factors , stroke severity and classification were recorded prospect ively in all stroke patients admitted to a district general hospital from 22 March 2004 until 21 March 2005 . Using established numbers needed to treat to prevent disability or death , the clinical impact of the lost opportunities was determined . Results : Of 171 acute stroke patients 115 ( 67 % ) spent some or all of their hospital stay in a stroke unit . Less severe strokes , living alone and attending a general practitioner all independently delayed hospital admission . Nineteen ( 12.5 % ) ischaemic stroke patients would have been eligible for intravenous thrombolysis treatment . Admitting all patients to the stroke unit would have gained independence for two patients , allowed two more patients to live at home , and prevented one death . Failure to thrombolyse eligible acute ischaemic stroke patients result ed in six patients having more disability , two of whom may have lost their independence . Conclusions : Improved stroke unit access is required in this district general hospital . Reorganisation of acute stroke services should allow thrombolysis for acute ischaemic stroke in most district general hospitals INTRODUCTION Intravenous tissue plasminogen activator ( tPA ) within 3 hours of stroke onset is a licensed proven therapy for ischaemic stroke , with recent trial data showing benefit up to 4.5 hours . We previously published in this journal data of a survey conducted in 2004 showing only 9 % of ischaemic stroke patients presenting to the Singapore General Hospital ( SGH ) arrived within 2 hours of onset . We aim ed to determine whether the problem of delayed hospital arrival persists in 2009 and to establish the impact of widening the time window for intravenous tPA to 4.5 hours . MATERIAL S AND METHODS We prospect ively surveyed consecutive ischaemic stroke patients admitted to the SGH from 9th March to 30th April 2009 . Patients and /or relatives were interviewed with a st and ardised form similar to the 2004 survey . RESULTS Among the 146 ischaemic stroke patients surveyed ( median age 67 years , 59 % male , median NIHSS score 2 ) , 6 % presented to SGH within 2 hours and 15 % within 3.5 hours of onset . Median time from stroke onset to hospital arrival was 1245 minutes ( 20.75 hours ) . Pre-hospital consultation was significantly associated with hospital arrival after 2 hours from onset . Main reasons cited for delay were not realising the gravity of symptoms ( 31 % ) and not recognising them as stroke ( 27 % ) . CONCLUSION Delayed arrival to SGH following acute ischaemic stroke remains a problem in 2009 . This confirms the lack of stroke awareness in Singapore and highlights the need for public stroke education . Furthermore , these data confirm that widening the time window for intravenous tPA treatment to 4.5 hours at SGH will increase its utilisation Background and Purpose — Successful acute stroke intervention depends on early hospital presentation . Our study aim ed to examine the extent of and factors associated with prehospital delays after acute stroke in Taiwan , where people are new to thrombolytic therapy for stroke . Methods — Data were prospect ively collected from 196 patients admitted with acute stroke who presented to the emergency department ( ED ) of the study hospital within 48 hours of symptom onset before intravenous recombinant tissue plasminogen activator was approved . Prehospital delay was defined as time from symptom onset to the ED arrival . Univariate and multivariable regression analyses were conducted to evaluate factors influencing delay in ED presentation and delay in decision to seek medical help . Results — The median interval between symptom onset and decision to seek medical contact was 90 minutes ; the median interval between symptom onset and ED arrival was 335 minutes . The time from symptom onset to first call for medical help accounted for 45 % ( 95 % confidence interval , 41 to 50 ) of the prehospital delay . Advanced age delayed the decision to seek medical help , whereas stroke severity reduced the risk for this delay . Conclusions — The time interval between symptom onset and the decision to call for medical care is far from optimal and is the underlying cause of prolonged prehospital delay . Educational efforts to reduce extent of delay are urgently needed Recombinant tissue plasminogen activator ( rtPA ) reduces the combined endpoint of death and disability if given within three hours of onset of ischaemic stroke . However few patients receive rtPA , with delays in in-hospital evaluation and treatment being key barriers to therapy . The Austin Hospital Acute Stroke Team ( AST ) was introduced with the aim of improving the speed of assessment and management of acute stroke patients presenting to the emergency department . We sought to assess the effect of the AST on number of eligible patients receiving rtPA and assessment times within our already active stroke service . Data were obtained prospect ively for all AST calls during the period from 17 January 2005 - -31 December 2005 . Information recorded included : demographics , time of call , clinical features , diagnosis and any treatment with rtPA . Information prospect ively acquired from patients receiving stroke thrombolysis the previous year was also analysed . There were 663 stroke unit admissions and 224 AST calls during the study period . 53 % of calls occurred within working hours and 68 % had a final diagnosis of stroke . Twenty-seven patients received treatment with rtPA ( 12 % of calls ) , whereas only ten patients received rtPA in 2004 . The most common reason for not treating was mild or rapidly resolving deficit . Onset-needle time and door-needle times significantly improved following introduction of the AST . Thus , we conclude that the introduction of the AST emergency call system has increased the number of eligible patients receiving rtPA . Improved onset-needle and door-needle times are achievable by this team approach Background Urgent assessment is essential after stroke . Several countries have had public education campaigns , based on the FAST ( Face-Arm-Speech-Time ) test to reduce delays in seeking attention . However , the impact of these campaigns on patient behavior is uncertain . Methods We prospect ively determined patient behavior after incident major stroke ( NIHSS > 3 ) in a UK population based study ( Oxford Vascular Study ) before ( 2002–2008 ) and after ( 2009–2013 ) introduction of the FAST TV-campaign and assessed any sustained impact of campaign continuation . Results Among 668 consecutive patients with major stroke , medical attention was sought by a byst and er in 553 ( 89·6 % ) . Patients were more likely to present directly to emergency services ( OR = 2·18 , 95%CI:1·54–3·09 , P < 0·0001 ) after the campaign and to arrive at hospital within 3 h ( OR = 2·18 , 1·55–3·06 , P < 0·0001 ) . Median [ IQR ] time to seeking attention fell from 53 [ 15–265 ] to 31 [ 7–120 ] minutes ( P = 0·005 ) and median time to hospital arrival from 185 [ 88–885 ] to 119 [ 78–256 ] minutes ( P < 0·0001 ) . On time-series analysis improvements in hospital arrival within 3 h and use of emergency medical services were significantly associated to initiation of the campaign ( aOR = 3·11 , 1·53–6·29 , P = 0·002 ; and 2·22 , 1·05–4·67 , P = 0·036 , respectively ) , independent of trend , age , sex , ethnicity , educational level , social class , prior stroke and stroke severity , and have been sustained to 2013 . Conclusion Delays to seeking and receiving medical attention after major stroke in the UK . fell strikingly in 2009 , coinciding with the start of the FAST TV campaign . That medical attention was sought by a byst and er in nearly 90 % of cases illustrates the importance of mass-media public education rather than focused programs in high-risk groups for major stroke IMPORTANCE The effectiveness of intravenous thrombolysis in acute ischemic stroke is time dependent . The effects are likely to be highest if the time from symptom onset to treatment is within 60 minutes , termed the golden hour . OBJECTIVE To determine the achievable rate of golden hour thrombolysis in prehospital care and its effect on outcome . DESIGN , SETTING , AND PARTICIPANTS The prospect i ve controlled Prehospital Acute Neurological Treatment and Optimization of Medical Care in Stroke study was conducted in Berlin , Germany , within an established infrastructure for stroke care . Weeks were r and omized according to the availability of a specialized ambulance ( stroke emergency mobile unit ( STEMO ) from May 1 , 2011 , through January 31 , 2013 . We included 6182 consecutive adult patients for whom a stroke dispatch ( 44.1 % male ; mean [ SD ] age , 73.9 [ 15.0 ] years ) or regular care ( 45.0 % male ; mean [ SD ] age , 74.2 [ 14.9 ] years ) were included . INTERVENTIONS The STEMO was deployed when the dispatchers suspected an acute stroke during emergency calls . If STEMO was not available ( during control weeks , when the unit was already in operation , or during maintenance ) , patients received conventional care . The STEMO is equipped with a computed tomographic scanner plus a point-of-care laboratory and telemedicine connection . The unit is staffed with a neurologist trained in emergency medicine , a paramedic , and a technician . Thrombolysis was started in STEMO if a stroke was confirmed and no contraindication was found . MAIN OUTCOMES AND MEASURES Rates of golden hour thrombolysis , 7- and 90-day mortality , secondary intracerebral hemorrhage , and discharge home . RESULTS Thrombolysis rates in ischemic stroke were 200 of 614 patients ( 32.6 % ) when STEMO was deployed and 330 of 1497 patients ( 22.0 % ) when conventional care was administered ( P < .001 ) . Among all patients who received thrombolysis , the proportion of golden hour thrombolysis was 6-fold higher after STEMO deployment ( 62 of 200 patients [ 31.0 % ] vs 16 of 330 [ 4.9 % ] ; P < .01 ) . Compared with patients with a longer time from symptom onset to treatment , patients who received golden hour thrombolysis had no higher risks for 7- or 90-day mortality ( adjusted odds ratios , 0.38 [ 95 % CI , 0.09 - 1.70 ] ; P = .21 and 0.69 [ 95 % CI , 0.32 - 1.53 ] ; P = .36 ) and were more likely to be discharged home ( adjusted odds ratio , 1.93 [ 95 % CI , 1.09 - 3.41 ] ; P = .02 ) . CONCLUSIONS AND RELEVANCE The use of STEMO increases the percentage of patients receiving thrombolysis within the golden hour . Golden hour thrombolysis entails no risk to the patients ' safety and is associated with better short-term outcomes . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01382862 OBJECTIVE To assess the effectiveness of the PAST ( Pre-hospital Acute Stroke Triage ) protocol in reducing pre-hospital and emergency department ( ED ) delays to patients receiving organised acute stroke care , thereby increasing access to thrombolytic therapy . DESIGN Prospect i ve cohort study using historical controls . SETTING Hunter Region of New South Wales , September 2005 to March 2006 ( pre-intervention ) and September 2006 to March 2007 ( post-intervention ) . PARTICIPANTS Consecutive patients presenting with acute stroke to a regional , tertiary referral hospital . INTERVENTION PAST protocol , comprising a pre-hospital stroke assessment tool for ambulance officers , an ambulance protocol for hospital bypass for potentially thrombolysis-eligible patients , and pre-hospital notification of the acute stroke team . MAIN OUTCOME MEASURES Proportion of patients who received intravenous tissue plasminogen activator ( tPA ) , process of care time points ( symptom onset to ED arrival , ED arrival to tPA treatment , and ED transit time ) , and clinical outcomes of patients treated with tPA . RESULTS The proportion of ischaemic stroke patients treated with tPA increased from 4.7 % ( pre-intervention ) to 21.4 % ( post-intervention ) ( P < 0.001 ) . Time point outcomes also improved , with a reduction in median times from symptom onset to ED arrival from 150 to 90.5 min ( P = 0.004 ) and from ED arrival to stroke unit admission from 361 to 232.5 minutes ( P < 0.001 ) . Of those treated with tPA , 43 % had minimal or no disability at 3 months . CONCLUSIONS Organised pre-hospital and ED acute stroke care increases patient access to tPA treatment , which is proven to reduce stroke-related disability Aim : To evaluate hospital delays in thrombolytic treatment before and after organisational changes and community-based treatment rates in a previously inexperienced centre . Methods : The delays before and after organisational changes made in 2006 were compared using a prospect i ve treatment data base . In a 6-month period in 2007 , a community-based search was performed for all hospitalisations for ischaemic stroke . The number of patients admitted within the 0–3 h time window and the proportion treated with tissue plasminogen activator were analysed . Results : The number of treatments increased fourfold from 2005 to 2007 with a significant reduction in mean door-to-needle time from 60 min to 38 min ( p = 0.002 ) . In the community-based series , 14/137 patients ( 10 % ) hospitalised with ischaemic stroke and 13/32 patients ( 41 % ) admitted in the 0–3 h window were treated . Conclusions : An inexperienced stroke centre can rapidly implement the necessary logistics to deliver thrombolysis to a large proportion of patients with acute stroke with short hospital delays . Important factors are probably prenotification of a team and the initiation of thrombolytic treatment in the emergency room Background Under current guidelines , intravenous thrombolysis is used to treat acute stroke only if it can be ascertained that the time since the onset of symptoms was less than 4.5 hours . We sought to determine whether patients with stroke with an unknown time of onset and features suggesting recent cerebral infa rct ion on magnetic resonance imaging ( MRI ) would benefit from thrombolysis with the use of intravenous alteplase . Methods In a multicenter trial , we r and omly assigned patients who had an unknown time of onset of stroke to receive either intravenous alteplase or placebo . All the patients had an ischemic lesion that was visible on MRI diffusion‐weighted imaging but no parenchymal hyperintensity on fluid‐attenuated inversion recovery ( FLAIR ) , which indicated that the stroke had occurred approximately within the previous 4.5 hours . We excluded patients for whom thrombectomy was planned . The primary end point was favorable outcome , as defined by a score of 0 or 1 on the modified Rankin scale of neurologic disability ( which ranges from 0 [ no symptoms ] to 6 [ death ] ) at 90 days . A secondary outcome was the likelihood that alteplase would lead to lower ordinal scores on the modified Rankin scale than would placebo ( shift analysis ) . Results The trial was stopped early owing to cessation of funding after the enrollment of 503 of an anticipated 800 patients . Of these patients , 254 were r and omly assigned to receive alteplase and 249 to receive placebo . A favorable outcome at 90 days was reported in 131 of 246 patients ( 53.3 % ) in the alteplase group and in 102 of 244 patients ( 41.8 % ) in the placebo group ( adjusted odds ratio , 1.61 ; 95 % confidence interval [ CI ] , 1.09 to 2.36 ; P=0.02 ) . The median score on the modified Rankin scale at 90 days was 1 in the alteplase group and 2 in the placebo group ( adjusted common odds ratio , 1.62 ; 95 % CI , 1.17 to 2.23 ; P=0.003 ) . There were 10 deaths ( 4.1 % ) in the alteplase group and 3 ( 1.2 % ) in the placebo group ( odds ratio , 3.38 ; 95 % CI , 0.92 to 12.52 ; P=0.07 ) . The rate of symptomatic intracranial hemorrhage was 2.0 % in the alteplase group and 0.4 % in the placebo group ( odds ratio , 4.95 ; 95 % CI , 0.57 to 42.87 ; P=0.15 ) . Conclusions In patients with acute stroke with an unknown time of onset , intravenous alteplase guided by a mismatch between diffusion‐weighted imaging and FLAIR in the region of ischemia result ed in a significantly better functional outcome and numerically more intracranial hemorrhages than placebo at 90 days . ( Funded by the European Union Seventh Framework Program ; WAKE‐UP Clinical Trials.gov number , NCT01525290 ; and EudraCT number , 2011‐005906‐32 . IMPORTANCE Mobile stroke treatment units ( MSTUs ) with on-site treatment teams that include a vascular neurologist can provide thrombolysis in the prehospital setting faster than treatment in the hospital . These units can be made more re source efficient if the need for an on-site neurologist can be eliminated by relying solely on telemedicine for physician presence . OBJECTIVE To test whether telemedicine is reliable and remote physician presence is adequate for acute stroke treatment using an MSTU . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve observational study conducted between July 18 and November 1 , 2014 . The date s of the study analysis were November 1 , 2014 , to March 30 , 2015 . The setting was a community-based study assessing telemedicine success of the MSTU in Clevel and , Ohio . Participants were the first 100 residents of Clevel and who had an acute onset of stroke-like symptoms between 8 am and 8 pm and were evaluated by the MSTU after the implementation of the MSTU program at the Clevel and Clinic . A vascular neurologist evaluated the first 100 patients via telemedicine , and a neuroradiologist remotely assessed images obtained by mobile computed tomography ( CT ) . Data were entered into the medical record and a prospect i ve registry . MAIN OUTCOMES AND MEASURES The study compared the evaluation and treatment of patients on the MSTU with a control group of patients brought to the emergency department via ambulance during the same year . Process times were measured from the time the patient entered the door of the MSTU or emergency department , and any problems encountered during his or her evaluation were recorded . RESULTS Ninety-nine of 100 patients were evaluated successfully . The median duration of telemedicine evaluation was 20 minutes ( interquartile range [ IQR ] , 14 - 27 minutes ) . One connection failure was due to crew error , and the patient was transported to the nearest emergency department . There were 6 telemedicine disconnections , none of which lasted longer than 60 seconds or affected clinical care . Times from the door to CT completion ( 13 minutes [ IQR , 9 - 21 minutes ] ) and from the door to intravenous thrombolysis ( 32 minutes [ IQR , 24 - 47 minutes ] ) were significantly shorter in the MSTU group compared with the control group ( 18 minutes [ IQR , 12 - 26 minutes ] and 58 minutes [ IQR , 53 - 68 minutes ] , respectively ) . Times to CT interpretation did not differ significantly between the groups . CONCLUSIONS AND RELEVANCE An MSTU using telemedicine is feasible , with a low rate of technical failure , and may provide an avenue for reducing the high cost of such systems Background and Purpose — National guidelines call for door-to-imaging time ( DIT ) within 25 minutes for suspected acute stroke patients . Studies examining factors that affect DIT have focused primarily on stroke-specific care processes and patient-specific factors . We hypothesized that emergency department ( ED ) crowding is associated with longer DIT . Methods — We conducted a retrospective investigation of 1 year of consecutive patients in our prospect i ve Code Stroke registry , which included all ED stroke team activations . The registry and electronic health records were abstract ed for 27 potential predictors of DIT , including patient , stroke care process , and ED operational factors . We fit a multivariate logistic regression model and calculated odds ratios and 95 % confidence intervals . Second , we constructed a r and om forest recursive partitioning model to cross-vali date our findings and explore the proportional importance of each category of predictor . Our primary outcome was the binary variable of DIT within the 25-minute goal . Results — A total of 463 patients met inclusion criteria . In the regression model , ED occupancy rate emerged as a predictor of DIT , with odds ratio of 0.83 ( 95 % confidence interval , 0.75–0.91 ) of DIT within 25 minutes per 10 % absolute increase in ED occupancy rate . The secondary analysis estimated that ED operational factors accounted for nearly 14 % of the algorithm ’s prediction of DIT . Conclusions — ED crowding is associated with reduced odds of meeting DIT goals for acute stroke . In addition to improving stroke-specific processes of care , efforts to reduce ED overcrowding should be considered central to optimizing the timeliness of acute stroke care IMPORTANCE Given the limited time window available for treatment with tissue plasminogen activator ( tPA ) in patients with acute ischemic stroke , guidelines recommend door-to-imaging time ( DIT ) within 25 minutes of hospital arrival and door-to-needle ( DTN ) time within 60 minutes for patients with acute ischemic stroke . Despite improvements in DITs , DTN times for tPA treatment in patients with acute ischemic stroke remain suboptimal . OBJECTIVES To examine the contributions of DIT and imaging-to-needle ( ITN ) time to delays in timely delivery of tPA to patients with acute ischemic stroke and to assess between-hospital variation in DTN times . DESIGN , SETTING , AND PARTICIPANTS A cohort analysis of 1193 patients having acute ischemic stroke treated with intravenous tPA between January 2009 and December 2012 . Multilevel linear regression models included r and om effects for 25 Michigan hospitals participating in the Paul Coverdell National Acute Stroke Registry . MAIN OUTCOMES AND MEASURES The primary outcome was a continuous measure of DTN time , in minutes , from emergency department arrival to thrombolytic delivery . RESULTS The mean age was 68.1 years , the median National Institutes of Health Stroke Scale score was 11.0 ( interquartile range , 6 - 17 ) , 51.4 % were female , and 37.5 % were of nonwhite race/ethnicity . The mean ( SD ) DTN time was 82.9 ( 35.4 ) minutes , the mean ( SD ) DIT was 22.8 ( 15.9 ) minutes , and the mean ( SD ) ITN time was 60.1 ( 32.3 ) minutes . Most patients ( 68.4 % ) had DIT within 25 minutes , while 28.7 % had DTN time within 60 minutes . Hospital variation accounted for 12.7 % of variability in DTN times . Neither annual stroke volume nor primary stroke center design ation was a significant predictor of shorter DTN time . Patient factors ( age , sex , race/ethnicity , arrival mode , onset-to-arrival time , and stroke severity ) explained 15.4 % of the between-hospital variation in DTN times . After adjustment for patient-level factors , DIT explained 10.8 % of the variation in hospital risk-adjusted DTN times , while ITN time explained 64.6 % . CONCLUSIONS AND RELEVANCE Compared with DIT , ITN time is a much greater source of variability in hospital DTN times and is a more common contributor to delays in timely tPA therapy for acute ischemic stroke . More attention is needed to determine systems changes that can decrease ITN time for patients with acute ischemic stroke BACKGROUND Emergency medical services ( EMS ) prenotification to hospitals regarding the arrival of patients who have had a stroke is recommended to facilitate the workup once the patient arrives . Most hospitals have the patient enter the emergency department ( ED ) before obtaining a head computed tomography ( CT ) scan . At Capital Health , prehospital stroke-alert patients are delivered directly to CT and met by a neurological emergency team . The goal of bypassing the ED is to reduce the time to treatment . OBJECTIVE To evaluate ( 1 ) door-to-CT and door-to-needle time in patients with an acute stroke who arrive as prehospital stroke alerts and ( 2 ) the accuracy of EMS assessment . METHODS A prospect i ve data base of all prehospital stroke alert patients was kept and data retrospectively review ed for patients who were seen between July 2012 and July 2013 . RESULTS Between July 2012 and July 2013 , 141 prehospital stroke alerts were called to our emergency department , and the patients were stable enough to bypass the ED and go directly to CT . EMS assessment of stroke was accurate 66 % of the time , and the diagnosis was neurological 89 % of the time . The average time between patient arrival and acquisition of CT imaging was 11.8 minutes . Twenty-six of the 141 patients ( 18 % ) received intravenous tissue plasminogen activator . The median time from arrival to intravenous tissue plasminogen activator bolus was 44 minutes . CONCLUSION Trained EMS responders are able to correctly identify patients who are experiencing neurological/neurosurgical emergencies and deliver patients to our comprehensive stroke center in a timely fashion after prenotification . The prehospital stroke alert protocol bypasses the ED , allowing the patient to be met in CT by the neurological ED team , which has proven to decrease door-to-CT and door-to-needle times from our historical means . ABBREVIATIONS ASLS , Advanced Stroke Life SupportDTN , door-to-needleED , emergency departmentEMS , emergency medical servicesEMT , emergency medical technicianIV , intravenousMEND , Miami Emergency Neurological DeficitPHSA , prehospital stroke alerttPA , tissue plasminogen activator In patients with acute ischemic stroke , thrombolysis offers an opportunity to effectively reduce disability and dependency . The success of this treatment is time-dependent . The crucial diagnostic step before initiation of treatment is cerebral imaging . With the aim of reducing in-hospital delays , our hospital 's interdisciplinary stroke management group implemented an all-points alarm to improve in-hospital time delay ( the period between arrival to the emergency department and performance of cerebral imaging ) . The alarm simultaneously alerted all involved staff ( from the neurologist to in-hospital transport ) to the arrival of a patient potentially eligible for thrombolysis . Time delay , sociodemographic , and clinical data were assessed prospect ively at 4 months before and 8 months after alarm implementation . Data were examined by analysis of covariance for both the intention-to-treat and per- protocol groups . During the assessment , 689 patients with symptoms compatible with stroke arrived at our hospital . Among those , 111 patients ( 16 % ) were eligible for thrombolysis ( median age , 71 years ; median National Institutes of Health Stroke Scale score , 11 ; 44 % female ) . Patient characteristics ( ie , age , sex , insurance status , National Institutes of Health Stroke Scale score , cardiovascular risk factors , and prehospital delay ) did not differ significantly before ( n = 34 ) and after ( n = 77 ) alarm implementation . The median " door-to-imaging time " for patients eligible for thrombolysis was significantly reduced , from 54 minutes before implementation of the alarm to 35 minutes after implementation . Adjusted analysis of covariance demonstrated a significant influence of the intervention ( P = .001 ) on differences in time delay . The proportion of ischemic stroke patients receiving thrombolysis rose from 42 % to 66 % ( P = .04 ) . The per- protocol analysis confirmed these results . The implementation of an all-points alarm can result in significant reduction of the time needed for in-hospital pathways for acute stroke patients Background : Thrombolytic treatment has been shown to be effective in the treatment of ischemic stroke when initiated within 3 hours of symptom onset , yet few patients receive thrombolytics . Objective : To estimate expected increases in use of thrombolytics for ischemic stroke given the following interventions : educating patients to present earlier , optimizing Emergency Medical Services ( EMS ) response/transport times , optimizing hospital systems , and extending the treatment window . Methods : As part of a Centers for Disease Control – sponsored Coverdell Acute Stroke Pilot Registry , the authors prospect ively identified all patients with an initial diagnosis of ischemic stroke at 11 hospitals in California over a 3-month period . Timing of symptom onset , EMS response , hospital arrival , treatment , and reasons for nontreatment were evaluated , and hypothetical treatment rates for thrombolysis for interventions on the stroke-care continuum were derived based on observed rates of eligibility and treatment . Results : Of 374 patients with ischemic stroke , 88 ( 23.5 % ) arrived at the emergency department within 3 hours of symptom onset , of whom 16 ( 4.3 % ) received thrombolysis . If all patients with known onset times had called 911 immediately , the expected overall rate of thrombolytic treatment within 3 hours would have increased from 4.3 to 28.6 % . Expected rates of thrombolysis were lower for other interventions : instantaneous prehospital response 5.5 % , perfect hospital care 11.5 % , and extension of time window to 6 hours 8.3 % . If all patients with known onset had arrived within 1 hour and been optimally treated , 57 % could have been treated . Conclusion : Campaigns that educate patients to seek treatment sooner should be major components of system-wide interventions to increase rates of thrombolysis for acute ischemic stroke Background and Purpose — In-hospital strokes ( IHSs ) are potential c and i date s for thrombolysis . We analyzed the treatment procedures , safety , and efficacy of intravenous tissue plasminogen activator ( IV-tPA ) in IHSs compared with out-of-hospital strokes ( OHSs ) . Methods — This study was based on a multicenter prospect i ve registry of patients treated with IV-tPA divided into IHSs and OHSs . We recorded intrahospital delays and stroke outcomes . Results — Among 367 patients treated with IV-tPA , 30 were IHSs . Baseline characteristics were similar except for a greater proportion of diabetes ( 36.7 % vs 17.5 % , P=0.01 ) , cardiac failure ( 16.7 % vs 5.3 % , P=0.014 ) , and atrial fibrillation ( 33.3 % vs 17.5 % , P=0.034 ) in IHSs than OHSs . In-hospital delays were significantly longer in IHSs for door-to-computed tomography time ( 39.5±18.7 vs 22.6±19.7 minutes , P<0.0001 ) and computed tomography-to-treatment time ( 92.0±26.1 vs 65.4±25.8 minutes , P<0.0001 ) . No differences were observed in safety or efficacy . Conclusions — In-hospital procedures for thrombolysis proceed more slowly in IHSs than in OHSs . Thrombolysis is safe and efficient in IHS BACKGROUND Brain imaging is logistically the most difficult step before thrombolysis . To improve door-to-needle time ( DNT ) , it is important to underst and if ( 1 ) longer door-to-imaging time ( DIT ) results in longer DNT , ( 2 ) hospitals have different DIT performances , and ( 3 ) patient and hospital characteristics predict DIT . METHODS Prospect ively collected data in the Safe Implementation of Treatments in Stroke-EAST ( SITS-EAST ) registry from Central /Eastern European countries between 2008 and 2011 were analyzed . Hospital characteristics were obtained by question naire from each center . Patient- and hospital-level predictors of DIT of 25 minutes or less were identified by the method of generalized estimating equations . RESULTS Altogether 6 of 9 SITS-EAST countries participated with 4212 patients entered into the data base of which 3631 ( 86 % ) had all required variables . DIT of 25 minutes or less was achieved in 2464 ( 68 % ) patients ( range , 3%-93 % ; median , 65 % ; and interquartile range , 50%-80 % between centers ) . Patients with DIT of 25 minutes or less had shorter DNT ( median , 60 minutes ) than patients with DIT of more than 25 minutes ( median , 86 minutes ; P < .001 ) . Four variables independently predicted DIT of 25 minutes or less : longer time from stroke onset to admission ( 91 - 180 versus 0 - 90 minutes ; odds ratio [ OR ] , 1.6 ; 95 % confidence interval [ CI ] , 1.3 - 1.8 ) , transport time of 5 minutes or less ( OR , 2.9 ; 95 % CI , 1.7 - 4.7 ) between the place of admission and a computed tomography ( CT ) scanner , no or minimal neurologic deficit before stroke ( OR , 1.3 ; 95 % CI , 1.02 - 1.5 ) , and diabetes mellitus ( OR , .8 ; 95 % CI , .7-.97 ) . CONCLUSIONS DIT should be improved in patients arriving early and late . Place of admission should allow transport time to a CT scanner under 5 minutes Objectives : Efficacy of thrombolytic therapy for ischemic stroke decreases with time elapsed from symptom onset . We analyzed the effect of interventions aim ed to reduce treatment delays in our single-center observational series . Methods : All consecutive ischemic stroke patients treated with IV alteplase ( tissue plasminogen activator [ tPA ] ) were prospect ively registered in the Helsinki Stroke Thrombolysis Registry . A series of interventions to reduce treatment delays were implemented over the years 1998 to 2011 . In-hospital delays were analyzed as annual median door-to-needle time ( DNT ) in minutes , with interquartile range . Results : A total of 1,860 patients were treated between June 1995 and June 2011 , which included 174 patients with basilar artery occlusion ( BAO ) treated mostly beyond 4.5 hours from symptom onset . In the non-BAO patients , the DNT was reduced annually , from median 105 minutes ( 65–120 ) in 1998 , to 60 minutes ( 48–80 ) in 2003 , further on to 20 minutes ( 14–32 ) in 2011 . In 2011 , we treated with tPA 31 % of ischemic stroke patients admitted to our hospital . Of these , 94 % were treated within 60 minutes from arrival . Performing angiography or perfusion imaging doubled the in-hospital delays . Patients with in-hospital stroke or arriving very soon from symptom onset had longer delays because there was no time to prepare for their arrival . Conclusions : With multiple concurrent strategies it is possible to cut the median in-hospital delay to 20 minutes . The key is to do as little as possible after the patient has arrived at the emergency room and as much as possible before that , while the patient is being transported Objective : To investigate the factors that influence the preferences of patients and their proxies concerning thrombolytic therapy and to determine how best to convey information . Methods : A total of 613 participants were r and omly assigned to a positively or negatively framed group . Each participant completed a series of surveys . We applied latent class analysis ( LCA ) to explore participants ' patterns of choices of thrombolysis and to classify the participants into different subgroups . Then we performed regression analyses to investigate predictors of classification of the participants into each subgroup and to establish a thrombolytic decision-making model . Results : LCA indicated an optimal 3-subgroup model comprising intermediate , favorable to thrombolysis , and aversion to thrombolysis subgroups . Multiple regression analysis revealed that 10 factors predicted assignment to the intermediate subgroup and 4 factors predicted assignment to the aversion to thrombolysis subgroup compared with the favorable to thrombolysis subgroup . The χ2 tests indicated that the information presentation format and the context of thrombolysis influenced participants ' choices of thrombolysis and revealed a framing effect in different subgroups . Conclusions : The preference for thrombolysis was influenced by the positive vs negative framing scenarios , the format of item presentation , the context of thrombolysis , and individual characteristics . Inconsistent results may be due to participant heterogeneity and the evaluation of limited factors in previous studies . Based on a decision model of thrombolysis , physicians should consider the effects of positive vs negative framing and should seek a neutral tone when presenting the facts , providing an important reference point for health persuasion in other clinical domains Background The aim of this study was to investigate the factors associated with prehospital delays in patients with acute ischaemic stroke who are indicated to receive thrombolysis if arriving within 2 h. Methods Data were prospect ively collected from patients eligible for intravenous thrombolytic treatment if arriving within the therapeutic time window . Patients were divided into two groups depending on whether they arrived within 2 h to underst and factors associated prehospital delay . Results The non-delayed group included 27 patients ( 14.7 % ) and the delayed group included 157 patients ( 85.3 % ) . The factors associated with prehospital delays after symptom onset were worsening of symptoms , development of symptoms at home and arrival at the emergency department ( ED ) by self or from other institutes . Those with a risk of atrial fibrillation arrived earlier at the ED . Conclusions Early symptom recognition and arrival at the hospital are important in acute stroke . Further effort to improve these parameters should be made in terms of public health Background : Telemedicine is improving acute stroke care in remote areas . Delay in hospital-to-hospital transfer is a common reason why acute ischemic stroke patients are excluded from interventional therapy . The progressive implementation of these procedures , requiring highly specialized professionals in comprehensive stroke centers , will certainly challenge even more the geographic equity in the access to the best acute stroke treatments . We aim ed to assess the benefits of telemedicine in selecting stroke patients for endovascular treatments . Methods : In our Reference Comprehensive Stroke Center ( RCSC ) , we perform urgent intra-arterial procedures in acute stroke patients . Patients may be primarily admitted ( PA ) or referred from community hospitals with ( TMHs ; 2 centers ) or without telemedicine ( nonTMHs ; 7 centers ) . We prospect ively studied all consecutive stroke patients undergoing urgent endovascular recanalization procedures in the RCSC . We studied different outcome measures according to the patients ’ initial admission : PA patients , TMH patients or nonTMH patients . For all patients , demographic and outcome data including serial National Institute of Health Stroke Scale ( NIHSS ) and modified Rankin Scale ( mRS ) scores at 3 months were recorded . Clinical improvement was defined as a decrease ≥4 points on the NIHSS at 7 days or discharge and favorable outcome as mRS ≤2 at 3 months . Whether an endovascular procedure was indicated was decided according to clinical , radiological and transcranial Doppler ( TCD ) data , independently of the patient ’s initial admission center . Results : During a 2-year period , 119 patients received endovascular treatment : PA patients 74 ( 63.1 % ) , TMH patients 25 ( 20.5 % ) , nonTM patients 20 ( 16.4 % ) . The mean distance to the RCSC was 52 ± 15 km for TMHs and 34.5 ± 12 km for nonTMHs ( p = 0.4 ) . There were no differences in baseline characteristics including age ( 71 , 71.6 and 66.5 years ; p = 0.25 ) , baseline NIHSS ( 18.5 , 19 and 18 ; p = 0.57 ) and previous use of intravenous tissue plasminogen activator ( 56.5 , 56.5 and 57.9 % ; p = 0.95 ) . The rate of recanalization ( modified Thrombolysis in Cerebral Infa rct ion Score ≥2a ) was similar in all groups ( 75 , 66.6 and 68.4 % ; p = 0.682 ) . TMH and PA patients had similar clinical improvement ( 61 vs. 63.8 % ; p = 0.51 ) and good functional outcome ( 36.8 vs. 35.3 % ; p = 0.722 ) . Conversely , nonTMH patients presented a lesser degree of clinical improvement ( 31.3 % ) and poorer functional outcome ( 15.8 % ) than TMH ( p = 0.019 and p = 0.046 ) and PA patients ( p = 0.05 and p = 0.013 ) . TMH patients had significantly shorter door-to-groin puncture times ( 47 vs. 69 min ; p = 0.047 ) . Conclusions : Telemedicine assessment to select patients for endovascular procedures improves the efficiency in stroke management and possibly the early and long-term outcome in patients receiving intra-arterial reperfusion treatment BACKGROUND In patients with acute stroke , systemic thrombolysis needs to be administered within 3 hours of symptom onset . The aim of the present study was to reduce prehospital delays in a population -based intervention . METHODS We performed a cluster-r and omized trial with 48 zip code areas as cluster units in the catchment area of 3 inner-city hospitals in Berlin , Germany . The primary end point was time between symptom onset and hospital admission . The intervention consisted of an educational letter indicating stroke symptoms and emphasizing the importance of calling the emergency medical services . We additionally included a bookmark and sticker with the emergency medical services ' telephone number . We fitted a series of log-normal survival regression models ( time to admission ) with frailty terms shared by inhabitants of the same zip code area . RESULTS A total of 75 720 inhabitants received the intervention . Between 2004 and 2005 , 741 patients with cerebrovascular events were admitted from the control areas ( n = 24 ) and 647 from the intervention areas ( n = 24 ) . A prehospital time of 2 hours or less and 3 hours or less was achieved by 22 % and 28 % of patients , respectively , in the control group compared with 26 % and 34 % , respectively , in the intervention group . In the log-normal model , time to hospital was reduced by 27 % in the intervention group in women ( acceleration factor , 0.73 ; 95 % confidence interval , 0.58 - 0.94 ) , while no significant effect was found in men . CONCLUSIONS The population -based intervention was effective in reducing prehospital delays in women but not in men . Future research should focus on the potential transferability of the intervention , its sustainability , and sex-specific impact Background and Purpose : Early treatment ( i.e. thrombolysis ) is crucial for a successful care of ischemic stroke . In the management of stroke , two phases are crucial : the pre-hospital and the in-hospital interval . This work investigated factors influencing pre- and in-hospital delay in a large geographic area of Northern Italy . Methods : Enrolled were patients presenting with ischemic stroke in four administrative districts of Northern Italy ( Como , Lecco , Sondrio and Varese ) over a 4-month period . Pre-hospital time and in-hospital time with single management steps were recorded prospect ively . Age , gender , recruiting hospital , EMS transport and triage codes , clinical severity and thrombolytic treatment were also recorded . Univariate and multivariate analysis of factors predicting pre- and in-hospital delay were performed . Results : Median pre-hospital time and in-hospital time were , respectively , 120 min ( interquartile range , IQR 62 - 271 ) and 150 min ( IQR 80 - 214 ) . Pre-hospital time was halved in patients hospitalized via EMS ( p < 0.001 ) and clinical ly more severe ( p < 0.001 ) . At multivariate analysis , transport code was associated with delay at any time ( p < 0.05 ) . Conclusions : EMS use and transport code predicted treatment delay in patients with ischemic stroke . A more intensive use of EMS and high urgency codes could help increase the number of stroke patients treated appropriately BACKGROUND A number of emergency medical services ( EMSs ) performance measures for stroke have been proposed to promote early stroke recognition and rapid transportation to definitive care . This study examined performance measure compliance among EMS-transported stroke patients and the relationship between compliance and in-hospital stroke response . METHODS Eight quality indicators were derived from American Stroke Association guidelines . A prospect i ve cohort of consecutive , EMS-transported patients discharged from 2 large Midwestern stroke centers with a diagnosis of acute ischemic stroke was identified . Data were abstract ed from hospital and EMS records . Compliance with 8 prehospital quality indicators was calculated . Univariate and multivariable logistic regression analysis were performed to measure the association between prehospital compliance and a binary outcome of door-to-computed tomography ( CT ) time less than or equal to 25 minutes . RESULTS Over the 12 month study period , 186 EMS-transported ischemic stroke patients were identified . Compliance was highest for prehospital documentation of a glucose level ( 86.0 % ) and stroke screen ( 78.5 % ) and lowest for on-scene time less than or equal to 15 minutes ( 46.8 % ) , hospital prenotification ( 56.5 % ) , and transportation at highest priority ( 55.4 % ) . After adjustment for age , time from symptom onset , and stroke severity , transportation at highest priority ( odds ratio [ OR ] , 13.45 ) and hospital prenotification ( OR , 3.75 ) were both associated with significantly faster door-to-CT time . No prehospital quality metric was associated with tissue-plasminogen activator delivery . CONCLUSIONS EMS transportation at highest priority and hospital prenotification were associated with faster in-hospital stroke response and represent logical targets for EMS quality improvement efforts Background Basilar artery stroke causes substantial morbidity and mortality . Although its unusual clinical presentation potentially contributes to a delay in diagnosis , this problem has not been systematic ally studied . We compared intervals between symptom onset , initial presentation , and diagnosis in stroke due to basilar artery ( BA ) versus left middle cerebral artery ( LMCA ) occlusion to determine the presence of and potential reasons for diagnostic delay in BA stroke . Methods We retrospectively identified 21 consecutive adult patients diagnosed with BA stroke between 2009 and 2011 from our hospital ’s prospect i ve stroke registry . Patients were age- , sex- , and race-matched with 21 LMCA stroke patients from the same period . All subjects had confirmed clinical and radiographic diagnosis of stroke due to occlusion or stenosis of the BA , LMCA , or left internal carotid artery . Time to diagnosis was determined independently by two investigators through medical record review . The pre-specified primary outcome was latency from emergency department ( ED ) arrival to stroke diagnosis . Results Median time from ED arrival to diagnosis was 8 h 24 min ( IQR : 2:43–26:32 ) for BA and 1 h 23 min ( IQR : 0:41–1:45 ; p < 0.001 ) for LMCA . Median time from symptom onset to ED arrival was 7 h 44 min ( IQR 1:23–21:30 ) for BA and 1 h 2 min ( IQR 0:36–9:41 ; p = 0.06 ) for LMCA . Four of 21 ( 19 % ) BA patients were diagnosed within a 4-h time frame to make intravenous thrombolysis possible compared to 13 of 21 ( 62 % ) LMCA patients ( p = 0.01 ) . Conclusions Our results suggest that both pre-hospital and in-hospital processes cause substantial , clinical ly significant delays in the diagnosis of BA stroke Time after symptom onset in ischaemic stroke has to be as short as possible to increase success of treatment . We prospect ively analysed latencies from symptom onset until the start of therapy and the rate of thrombolysis in 196 patients with suspected stroke sequentially admitted to the hospital before ( 6 weeks prior , n = 83 ) and after ( n = 113 ) initiating an educational stroke programme ( EP ) . A total of 345 dispatchers , paramedics , and emergency staff were trained , each person for at least 2 h. The mean pre-hospital time interval from symptom onset until admission was significantly decreased by nearly 2 h ( p < 0.05 ) . Thrombolytic therapy frequencies increased from 2 to 10.5 % ( p < 0.01 ) because the overall mean time interval from admission to the start of therapy significantly decreased ( p < 0.01 ) by 69 min after the EP , with increasing numbers of patients suitable for acute stroke therapies within a 0- to 3-hour treatment window Background Intravenous recombinant tissue plasminogen activator ( i.v . rt-PA ) is the milestone treatment for patients with acute ischemic stroke . Stroke Fast Track ( SFT ) facilitates time reduction , guarantees safety , and promotes good clinical outcomes in i.v . rt-PA treatment . Nursing case management is a healthcare service providing clinical benefits in many specific diseases . The knowledge about the efficacy of a nurse case management for Stroke Fast Track is limited . We aim to study the effect of nurse case management on clinical outcomes in patients with acute ischemic stroke involving intravenous recombinant tissue plasminogen activator ( i.v . rt-PA ) treatment . Methods Seventy-six patients with acute ischemic stroke who received i.v . rt-PA treatment under Stroke Fast Track protocol of Thammasat University Hospital were r and omized into two groups . One group was assigned to get st and ard care ( control ) while another group was assigned to get st and ard care under a nurse case management . The National Institute of Health Stroke Scale ( NIHSS ) at 24 hours after treatment between the control and the experimental groups was evaluated . Results Time from triage to treatment in the experimental group was significantly faster than in the control group ( mean = 39.02 and 59.37 minutes , respectively ; p=.001 ) . The NIHSS at 24 hours after treatment in the nurse case management group was significantly improved as compared to the control group ( p=.001 ) . No symptomatic intracranial hemorrhage ( sICH ) was detected at 24 hours after onset in both groups . Conclusion The nurse case management should provide some benefits in the acute stroke system . Although the early benefit is demonstrated in our study , further studies are needed to ensure the long-term benefit and confirm its profit in patients with acute ischemic stroke Since stroke has become a medical emergency because intravenous tissue plasminogen activator improves outcome after ischemic stroke within 3 h of symptom onset , the focus of acute stroke management lies on the prehospital phase . Having the worst median time of emergency department arrival after stroke onset according to nationwide statistics , we examined the factors influencing a late admission of 174 consecutive patients to our stroke unit and the effects of a public campaign over 5 months . The median time from symptom onset to arrival was 5.2 h ; 36.4 % of patients presented within 3 h at hospital . A high level of education , knowledge of the time window , direct contact with an emergency facility after stroke onset , high number of known symptoms , not living alone , and a stroke in the past were connected with an earlier presentation . The public campaign had a positive effect on median time of symptom onset to arrival from 12 h in July , 7.2 in August , 4.7 in October , 5.2 in November , and 3.2 in December 2002 . This had a favorable effect on the number of thrombolysis Background The time to initiate intravenous thrombolysis for acute ischemic stroke is generally limited to within 4.5 hours after the onset of symptoms . Some trials have suggested that the treatment window may be extended in patients who are shown to have ischemic but not yet infa rct ed brain tissue on imaging . Methods We conducted a multicenter , r and omized , placebo‐controlled trial involving patients with ischemic stroke who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging . The patients were r and omly assigned to receive intravenous alteplase or placebo between 4.5 and 9.0 hours after the onset of stroke or on awakening with stroke ( if within 9 hours from the midpoint of sleep ) . The primary outcome was a score of 0 or 1 on the modified Rankin scale , on which scores range from 0 ( no symptoms ) to 6 ( death ) , at 90 days . The risk ratio for the primary outcome was adjusted for age and clinical severity at baseline . Results After 225 of the planned 310 patients had been enrolled , the trial was terminated because of a loss of equipoise after the publication of positive results from a previous trial . A total of 113 patients were r and omly assigned to the alteplase group and 112 to the placebo group . The primary outcome occurred in 40 patients ( 35.4 % ) in the alteplase group and in 33 patients ( 29.5 % ) in the placebo group ( adjusted risk ratio , 1.44 ; 95 % confidence interval [ CI ] , 1.01 to 2.06 ; P=0.04 ) . Symptomatic intracerebral hemorrhage occurred in 7 patients ( 6.2 % ) in the alteplase group and in 1 patient ( 0.9 % ) in the placebo group ( adjusted risk ratio , 7.22 ; 95 % CI , 0.97 to 53.5 ; P=0.05 ) . A secondary ordinal analysis of the distribution of scores on the modified Rankin scale did not show a significant between‐group difference in functional improvement at 90 days . Conclusions Among the patients in this trial who had ischemic stroke and salvageable brain tissue , the use of alteplase between 4.5 and 9.0 hours after stroke onset or at the time the patient awoke with stroke symptoms result ed in a higher percentage of patients with no or minor neurologic deficits than the use of placebo . There were more cases of symptomatic cerebral hemorrhage in the alteplase group than in the placebo group . ( Funded by the Australian National Health and Medical Research Council and others ; EXTEND Clinical Trials.gov numbers , NCT00887328 and NCT01580839 . Background Intravenous thrombolysis has been recently introduced in Nepal for the management of acute ischemic stroke . Pre-hospital delay is one of the main reasons that hinder thrombolytic therapy . The objective of this study was to evaluate the status of prehospital delay and thrombolysis in Nepal . Methods Data were prospect ively collected from patients of both genders , age > 18 years who arrived at the emergency department ( ED ) with symptoms and neuroimaging findings consistent with an ischemic stroke . Patient data were obtained from ED form and st and ard question naires were used to assess factors result ing in prehospital delay . Modified Rankin scale and National Institute of Health stroke scale were used to assess the degree of disability and severity of stroke respectively . Results A total of 228 patients were enrolled in the study between August 2017 and August 2018 . Only 46 ( 20.17 % ) patients arrived within the time frame for thrombolysis . Onset at daytime ( OR : 4.07 ; 95 % CI : 1.65–10.1 ; p = 0.001 ) , stroke symptoms facial deviation ( OR : 5.03 ; 95 % CI : 2.47 to 10.26 ; p = 0.000 ) and speech disturbances ( OR : 2.34 ; 95 % CI : 1.06 to 5.1 ; p = 0.021 ) , identification of stroke ( OR : 22.36 ; 95 % CI : 9.42–53.04;p = 0.000 ) , rushing to ED after onset of symptoms ( OR : 2.93 ; 95 % CI : 1.5–5.7 ; p = 0.001 ) , awareness of treatment of stroke ( OR : 10.21 ; 95 % CI : 4.8–21.6 ; p = 0.000 ) , direct presentation ( OR : 4.2 ; 95 % CI : 2.09–8.66 ; p = 0.000 ) , the distance less than 20 km ( OR : 7.9 ; 95 % CI : 3.8–16.5 ; p = 0.000 ) , and education above high school ( OR:4.85 ; 95 % CI : 2.2–10.5 ; p = 0.000 ) were associated with early arrival . Heavy traffic , income below 1000 USD per annum and diabetes mellitus were associated with delayed arrival to ED . Out of 46 early arrival patients , only 30 patients ( 13.15 % ) received tissue plasminogen activator during the study period , while others were deprived because of their inability to afford the treatment cost . Conclusion Community-based intervention to spread awareness , establishing comprehensive stroke centers , training specialists , improving emergency services , establishment of telestroke facilities and encouraging the use of low-cost tenecteplase as an alternative to alteplase can help improve care for stroke patients in Nepal ABSTRACT Background and aims : Pre-hospital delay is a crucial factor that determines the eligibility for intravenous thrombolysis in patients with acute ischemic stroke . We aim ed to evaluate the time to presentation at the emergency department ( ED ) and the factors that affect this time . Patients and methods : We prospect ively studied 682 patients who were admitted with acute ischemic stroke ( 43.3 % men , age 79.9 ± 6.6 years ) . Results : The median time to presentation at the ED was 2.1 h ( range 0.15 to 168 h ) ; 68.8 % of the patients arrived within 4.5 h and 56.5 % arrived within 3 h from the onset of symptoms . Independent predictors of presentation within 4.5 h were the use of emergency medical services ( EMS ) for transportation to the hospital ( OR 2.61 , 95 % CI 1.38–4.94 , p = .003 ) , family history of cardiovascular disease (CVD)(OR 4.0 0,95%CI 1.61–12.23 , p = .006 ) and the absence of history of smoking ( OR 2.49 , 95 % CI 1.13–5.42 , p = .021 ) . Independent predictors of presentation within 3 h were the use of EMS for transportation to the hospital ( OR 6.24 , 95 % CI 2.52–16.63 , p = .0001 ) , family history of CVD ( OR 3.07 , 95 % CI 1.14–9.43 , p = .03 ) , and a moderately severe stroke at admission ( OR vs. minor stroke 0.38 , 95 % CI 0.16–0.87 , p = .02 ) . Conclusions : A considerable proportion of patients with acute ischemic stroke arrives at the ED after the 4.5-h threshold for performing intravenous thrombolysis . Non-smokers , patients with a family history of CVD , with moderately severe stroke and those who use the EMS are more likely to arrive on time BACKGROUND AND AIMS Thrombolysis with alteplase ( recombinant tissue plasminogen activator ) is accepted hyperacute therapy for acute ischaemic stroke . Clotting must be normal before this can be administered safely . Laboratory testing of international normalised ratio ( INR ) takes 30 - 60 min , which can significantly delay administration of recombinant tissue plasminogen activator . Previous studies have suggested that point-of-care testing is useful in patients presenting with stroke and improves door-to-needle time . We performed a prospect i ve study of point-of-care testing in patients presenting with acute ischaemic stroke . METHODS Fifty patients were entered into the study to compare point-of-care testing using the CoaguChek XS system with laboratory testing of INR . RESULTS Point-of-care testing correlated well with laboratory levels ( R = 0.93 , P < 0.0001 ) . The st and ard deviation of difference between the two was 0.115 . Overall , point-of-care testing tended to underestimate INR slightly , meaning that an INR value of 1.1 or less was required to be 95 % certain that the laboratory value was 1.3 or below . Simultaneous testing using blood from a syringe was more consistent with laboratory results than testing capillary blood through finger prick . CONCLUSION Point-of-care INR testing correlates well with laboratory values . The results in this study mostly relate to values in the normal range . We suggest that it can be used to try to shorten door-to-needle time Rationale Time from symptom onset to treatment is closely associated with the effectiveness of intravenous thrombolysis in acute ischemic stroke patients . Hospitals are encouraged to take every effort to shorten delay of treatment . Despite combined efforts to streamline procedures in hospitals to provide treatment as soon as possible , most patients receive tissue plasminogen activator with considerable delay and very few of them within 90 mins . Germany has an internationally acknowledged prehospital emergency care system with specially trained doctors on ambulances . We developed an ambulance equipped with a Computed Tomography ( CT ) scanner , point-of-care laboratory , teleradiological support , and an emergency-trained neurologist on board . In the Pre-Hospital Acute Neurological Therapy and Optimization of Medical care in Stroke Patients study , we aim at a reduction of the current alarm-to-needle time by prehospital use of tissue plasminogen activator in an ambulance . Aims We hypothesized that compared with regular care , we will reduce alarm-to-needle time by a minimum of 20 mins by implementation of the stroke emergency mobile unit . Design Prospect i ve study comparing r and omly allocated periods with and without stroke emergency mobile unit availability . Study Outcomes Primary end point of the study is alarm-to-needle time . Secondary outcomes include thrombolysis treatment rates , modified Rankin scale after three-months , and alarm-to-imaging or alarm-to-laboratory time ; safety aspects to be evaluated are mortality and rates of ( symptomatic ) intracerebral hemorrhage Background Helicopters are widely used for interhospital transfers of stroke patients , but the benefit is sparsely documented . We hypothesised that helicopter transport would reduce system delay to thrombolytic treatment at the regional stroke centre . Methods In this prospect i ve controlled observational study , we included patients referred to a stroke centre if their ground transport time exceeded 30 min , or they were transported by a secondarily dispatched , physician-staffed helicopter . The primary endpoint was time from telephone contact to triaging neurologist to arrival in the stroke centre . Secondary endpoints included modified Rankin Scale at 3 months , 30-day and 1-year mortality . Results A total of 330 patients were included ; 265 with ground transport and 65 with helicopter , of which 87 ( 33 % ) and 22 ( 34 % ) , received thrombolysis , respectively ( p=0.88 ) . Time from contact to triaging neurologist to arrival in the regional stroke centre was significantly shorter in the ground group ( 55 ( 34–85 ) vs 68 ( 40–85 ) min , p<0.01 ) . The distance from scene to stroke centre was shorter in the ground group ( 67 ( 42–136 ) km ) than in the helicopter group ( 83 ( 46–143 ) km ) ( p<0.01 ) . We did not detect significant differences in modified Rankin Scale at 3 months , in 30-day ( 9.4 % vs 0 % ; p=0.20 ) nor 1-year ( 18.8 % vs 13.6 % ; p=0.76 ) mortality between ground and helicopter transport . Conclusions We found significantly shorter time from contact to triaging neurologist to arrival in the regional stroke centre if stroke patients were transported by primarily dispatched ground ambulance compared with a secondarily dispatched helicopter Background and Purpose — Time to treatment is critically important in ischemic stroke . We compared the efficacy and cost of teleneurology evaluation during patient transport with that of mobile stroke transport units . Methods — Using cellular-connected telemedicine devices , we assessed 89 presumptive stroke patients in ambulances in transit . Paramedics assisted remote teleneurologists in obtaining a simplified history and examination , then coordinating care with the receiving emergency department . We prospect ively assessed door-to-needle and last-known-well-to-needle times for all intravenous alteplase – treated stroke patients brought to our emergency departments by emergency medical services ’ transport , comparing those with and without in-transit telestroke . Results — From January 2015 through March 2016 , 111 stroke patients received intravenous alteplase at study emergency departments . Mean door to needle was 13 minutes less with in-transit telestroke ( 28 versus 41 ; P=0.02 ) . Although limitations in cellular communication de grade d transmission quality , this did not prevent the completion of satisfactory patient evaluations . Conclusions — Improvement in time to treat seems comparable with in-transit telestroke and mobile stroke transport units . The low cost/unit makes this approach scalable , potentially providing rapid management of more patients |
930 | 15,668,414 | The literature indicates that symptoms alone have relatively poor diagnostic accuracy in predicting the presence of polyneuropathy ; signs are better predictors of polyneuropathy than symptoms ; and single abnormalities on examination are less sensitive than multiple abnormalities in predicting the presence of polyneuropathy .
The combination of neuropathic symptoms , signs , and electrodiagnostic findings provides the most accurate diagnosis of distal symmetric polyneuropathy .
The highest likelihood of polyneuropathy ( useful for clinical trials ) occurs with a combination of multiple symptoms , multiple signs , and abnormal electrodiagnostic studies .
A modest likelihood of polyneuropathy ( useful for field or epidemiologic studies ) occurs with a combination of multiple symptoms and multiple signs when the results of electrodiagnostic studies are not available .
A lower likelihood of polyneuropathy occurs when electrodiagnostic studies and signs are discordant . | The objective of this report was to develop a case definition of distal symmetric polyneuropathy to st and ardize and facilitate clinical research and epidemiologic studies . | There are no data on the prevalence and other epidemiologic characteristics of chronic symmetric polyneuropathy ( CSP ) in the community . This study was design ed to assess the prevalence and risk factors of CSP in well-defined elderly ( 55 years and older ) population s from two separate areas in Italy . Thirty-five general practitioners working in the two areas were invited to interview a r and om sample of patients requesting consultation . They used a pretested question naire which focused on selected symptoms of polyneuropathy , common risk factors for CSP , and current drug treatments . Patients giving affirmative answers to the questions on screening symptoms received a further clinical evaluation by a neurologist . Details are given of the general characteristics of the study areas and population s , the methods of case ascertainment , the validation of the screening instruments , and the results of a pilot study Objective This project evaluated the utility of quantitative sensory techniques in predicting the development of neuropathy for subjects participating in a prospect i ve study . Research Design and Methods Distal symmetric polyneuropathy was evaluated in 77 insulin-dependent diabetes mellitus individuals via quantitative sensory testing , nerve conduction studies , and clinical examination . Results Although the specificity and positive predictive value were low for the quantitative sensory techniques as predictors of neuropathy diagnosed on clinical exam ∼2 yr later , the sensitivity for vibratory thresholds was high ( 100 % ) . Variability over the 2-yr interval was shown on follow-up testing for each of the objective assessment modalities and it was not explained by differences for potential risk factors measured at baseline . Conclusion Despite a cross-sectional relationship between the assessment modalities and clinical ly overt neuropathy at baseline , these follow-up data suggest that the potential for the objective modalities as predictors of clinical ly diagnosed neuropathy may be limited Article abstract -Despite prominent symptoms of neuropathic pain , patients with small-fiber sensory neuropathies have few objective abnormalities on clinical examination and routine electrodiagnostic studies . We quantified intraepidermal nerve fiber ( IENF ) density in sections of skin obtained by punch skin biopsy , and found it to be significantly reduced in patients with painful sensory neuropathies compared with age-matched control subjects . In addition , IENF density correlated with clinical estimates of neuropathy severity , as judged by the extent of clinical ly identifiable sensory abnormalities . IENF density at the calf was lower than that obtained from skin at more proximal sites , indicating the length dependency of small-fiber loss in these neuropathies . NEUROLOGY 1997;48 : 708 - We assessed the involvement of somatic unmyelinated fibers in sensory ganglionopathies by skin biopsy and quantitative sensory testing ( QST ) . Sixteen patients with ganglionopathy , 16 with axonal neuropathy , and 15 normal controls underwent skin biopsy at the proximal thigh and the distal leg . Intraepidermal nerve fibers ( IENF ) were immunostained by antiprotein gene product 9.5 , and their linear density was quantified under light microscopy . Confocal microscopy studies with double staining of nerve fibers and basement membrane were also performed . Healthy subjects and neuropathy patients showed the typical proximodistal gradient of IENF density ; in neuropathies , values were significantly lower at the distal site of the leg , confirming the length-dependent loss of cutaneous innervation . Conversely , ganglionopathy patients with hyperalgesic symptoms did not show any change of IENF density between the proximal thigh and the distal leg . The distinct pattern of epidermal denervation seen in sensory ganglionopathy reflected the degeneration of somatic unmyelinated fibers in a fashion that was not length-dependent , which was consistent with both clinical and neurophysiologic observations and supported the diagnosis |
931 | 29,910,315 | Current evidence suggests that whilst other strategies ameliorate physiological or perceptual responses throughout endurance exercise in hot conditions , ingesting cooling aids before and during exercise provides a small benefit , which is of practical significance to athletes ' time trial performance | This systematic review and meta- analysis aim ed to assess studies which have investigated cooling method ologies , their timing and effects , on endurance exercise performance in trained athletes ( Category 3 ; VO2max ≥ 55 mL·kg·min-1 ) in hot environmental conditions ( ≥28 ° C ) . | PURPOSE To investigate the effect of ice slurry ingestion on thermoregulatory responses and submaximal running time in the heat . METHODS On two separate occasions , in a counterbalanced order , 10 males ingested 7.5 g·kg(-1 ) of either ice slurry ( -1 ° C ) or cold water ( 4 ° C ) before running to exhaustion at their first ventilatory threshold in a hot environment ( 34.0 ° C ± 0.2 ° C , 54.9 % ± 5.9 % relative humidity ) . Rectal and skin temperatures , HR , sweating rate , and ratings of thermal sensation and perceived exertion were measured . RESULTS Running time was longer ( P = 0.001 ) after ice slurry ( 50.2 ± 8.5 min ) versus cold water ( 40.7 ± 7.2 min ) ingestion . Before running , rectal temperature dropped 0.66 ° C ± 0.14 ° C after ice slurry ingestion compared with 0.25 ° C ± 0.09 ° C ( P = 0.001 ) with cold water and remained lower for the first 30 min of exercise . At exhaustion , however , rectal temperature was higher ( P = 0.001 ) with ice slurry ( 39.36 ° C ± 0.41 ° C ) versus cold water ingestion ( 39.05 ° C ± 0.37 ° C ) . During exercise , mean skin temperature was similar between conditions ( P = 0.992 ) , as was HR ( P = 0.122 ) and sweat rate ( P = 0.242 ) . After ice slurry ingestion , subjects stored more heat during exercise ( 100.10 ± 25.00 vs 78.93 ± 20.52 W·m(-2 ) , P = 0.005 ) , and mean ratings of thermal sensation ( P = 0.001 ) and perceived exertion ( P = 0.022 ) were lower . CONCLUSIONS Compared with cold water , ice slurry ingestion lowered preexercise rectal temperature , increased submaximal endurance running time in the heat ( + 19 % ± 6 % ) , and allowed rectal temperature to become higher at exhaustion . As such , ice slurry ingestion may be an effective and practical precooling maneuver for athletes competing in hot environments PURPOSE To develop and investigate the efficacy of a new precooling strategy combining external and internal techniques on the performance of a cycling time trial ( TT ) in a hot and humid environment . METHODS Eleven well-trained male cyclists undertook three trials of a laboratory-based cycling TT simulating the course characteristics of the Beijing Olympic Games event in a controlled hot and humid environment ( 32 ° C-35 ° C at 50%-60 % relative humidity ) . The trials , separated by 3 - 7 d , were undertaken in a r and omized crossover design and consisted of the following : 1 ) CON-no treatment apart from the ad libitum consumption of cold water ( 4 ° C ) , 2 ) STD COOL-whole-body immersion in cold ( 10 ° C ) water for 10 min followed by wearing a cooling jacket , or 3 ) NEW COOL-combination of consumption of 14 g of ice slurry ( " slushie " ) per kilogram body mass made from a commercial sports drink while applying iced towels . RESULTS There was an observable effect on rectal temperature ( T(rec ) ) before the commencement of the TT after both precooling techniques ( STD COOL < NEW COOL < CON , P < 0.05 ) , but pacing of the TT result ed in similar T(rec ) , HR , and RPE throughout the cycling protocol in all trials . NEW COOL was associated with a 3.0 % increase in power ( approximately 8 W ) and a 1.3 % improvement in performance time ( approximately 1:06 min ) compared with the CON trial , with the true likely effects ranging from a trivial to a large benefit . The effect of the STD COOL trial compared with the CON trial was " unclear . " CONCLUSIONS This new precooling strategy represents a practical and effective technique that could be used by athletes in preparation for endurance events undertaken in hot and humid conditions PURPOSE To determine the effect of thermal state and thermal comfort on cycling performance in the heat . METHODS Seven well-trained male triathletes completed 3 performance trials consisting of 60 min cycling at a fixed rating of perceived exertion ( 14 ) followed immediately by a 20-km time trial in hot ( 30 ° C ) and humid ( 80 % relative humidity ) conditions . In a r and omized order , cyclists either drank ambient-temperature ( 30 ° C ) fluid ad libitum during exercise ( CON ) , drank ice slurry ( -1 ° C ) ad libitum during exercise ( ICE ) , or precooled with iced towels and ice slurry ingestion ( 15 g/kg ) before drinking ice slurry ad libitum during exercise ( PC+ICE ) . Power output , rectal temperature , and ratings of thermal comfort were measured . RESULTS Overall mean power output was possibly higher in ICE ( + 1.4%±1.8 % [ 90 % confidence limit ] ; 0.4 > smallest worthwhile change [ SWC ] ) and likely higher PC+ICE ( + 2.5%±1.9 % ; 1.5>SWC ) than in CON ; however , no substantial differences were shown between PC+ICE and ICE ( unclear ) . Time-trial performance was likely enhanced in ICE compared with CON ( + 2.4%±2.7 % ; 1.4>SWC ) and PC+ICE ( + 2.9%±3.2 % ; 1.9>SWC ) . Differences in mean rectal temperature during exercise were unclear between trials . Ratings of thermal comfort were likely and very likely lower during exercise in ICE and PC+ICE , respectively , than in CON . CONCLUSIONS While PC+ICE had a stronger effect on mean power output compared with CON than ICE did , the ICE strategy enhanced late-stage time-trial performance the most . Findings suggest that thermal comfort may be as important as thermal state for maximizing performance in the heat We used incorrect visual feedback of ambient and core temperature in the heat to test the hypothesis that deception would alleviate the decrement in cycling performance compared to a no deception trial . Seven males completed three 30 min cycling time trials in a r and omised order on a Kingcycle ergometer . One time trial was in temperate , control conditions ( CON : 21.8 ± 0.6 ° C ; 43.3 ± 4.3%rh ) , the others in hot , humid conditions ( HOT : 31.4 ± 0.3 ° C ; 63.9 ± 4.5%rh ) . In one of the hot , humid conditions ( 31.6 ± 0.5 ° C ; 65.4 ± 4.3%rh ) , participants were deceived ( DEC ) into thinking the ambient conditions were 26.0 ° C ; 60.0%rh and their core temperature was 0.3 ° C lower than it really was . Compared to CON ( 16.63 ± 2.43 km ) distance covered was lower in HOT ( 15.88 ± 2.75 km ; P < 0.05 ) , but DEC ameliorated this ( 16.74 ± 2.87 km ; P < 0.05 ) . Mean power output was greater in DEC ( 184.4 ± 60.4 W ) than HOT ( 168.1 ± 54.1 W ; P < 0.05 ) and no difference was observed between CON and DEC . Rectal temperature and iEMG of the vastus lateralis were not different , but RPE in the third minute was lower in DEC than HOT ( P < 0.05 ) . Deception improved performance in the heat by creating a lower RPE , evidence of a subtle mismatch between the subconscious expectation and conscious perception of the task dem and 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 ABSTRACT This investigation compared the effects of external pre-cooling and mid-exercise cooling methods on running time trial performance and associated physiological responses . Nine trained male runners completed familiarisation and three r and omised 5 km running time trials on a non-motorised treadmill in the heat ( 33 ° C ) . The trials included pre-cooling by cold-water immersion ( CWI ) , mid-exercise cooling by intermittent facial water spray ( SPRAY ) , and a control of no cooling ( CON ) . Temperature , cardiorespiratory , muscular activation , and perceptual responses were measured as well as blood concentrations of lactate and prolactin . Performance time was significantly faster with CWI ( 24.5 ± 2.8 min ; P = 0.01 ) and SPRAY ( 24.6 ± 3.3 min ; P = 0.01 ) compared to CON ( 25.2 ± 3.2 min ) . Both cooling strategies significantly ( P < 0.05 ) reduced forehead temperatures and thermal sensation , and increased muscle activation . Only pre-cooling significantly lowered rectal temperature both pre-exercise ( by 0.5 ± 0.3 ° C ; P < 0.01 ) and throughout exercise , and reduced sweat rate ( P < 0.05 ) . Both cooling strategies improved performance by a similar magnitude , and are ergogenic for athletes . The observed physiological changes suggest some involvement of central and psychophysiological mechanisms of performance improvement Abstract Although pre-cooling is known to enhance exercise performance , the optimal cooling intensity is unknown . We hypothesized that mild cooling opposed to strong cooling circumvents skin vasoconstriction and thermogenesis , and thus improves cooling efficiency reflected in improved time to exhaustion . Eight males undertook three r and omized trials , consisting of a pre-cooling and an exercise session . During the pre-cooling , performed in a room of 24.6 ± 0.4 ° C and 24 ± 6 % relative humidity , participants received either 45 min of mild cooling using an evaporative cooling shirt or strong cooling using an ice-vest . A no-cooling condition was added as a control . Subsequent cycling exercise was performed at 65%[Vdot]O2peak in a climatic chamber of 29.3 ± 0.2 ° C and 80 ± 3 % relative humidity . During the pre-cooling session , mild and strong cooling decreased the skin blood flow compared with the control . However , no differences were observed between mild and strong cooling . No thermogenesis was observed in any conditions investigated . The reduction of body heat content after pre-cooling was two times larger with strong cooling ( 39.5 ± 8.4 W · m−2 ) than mild cooling ( 21.2 ± 5.1 W · m−2 ) . This result ed in the greatest improvement in time to exhaustion with strong cooling . We conclude that the cooling intensities investigated had a similar effect on cooling efficiency ( vasoconstriction and thermogenesis ) and that the improved performance after strong cooling is attributable to the greater decrease in body heat content Abstract This study investigated the effect of ice slurry ingestion during a triathlon on intragastric temperature and 10 km running performance in the heat . Nine well-trained male triathletes performed two r and omised trials of a simulated Olympic distance triathlon in hot conditions ( 32–34 ° C ) . Exercise intensity during the swim ( 1500 m ) and cycle ( 1 hr ) legs was st and ardised , and the 10 km run leg was a self-paced time trial . During the cycle leg , either 10 g · kgBM−1 of ice slurry ( < 1 ° C ) or room temperature fluid ( 32–34 ° C ) was ingested . In the run leg of the ice slurry trial , performance time ( 43.4 ± 3.7 vs. 44.6 ± 4.0 min ; P = 0.03 ) , intragastric temperature ( at 1.5 km ; 35.5 ± 1.2 vs. 37.5 ± 0.4 ° C ; P = 0.002 ) and perceived thermal stress ( at 5 km ; 73 ± 9 vs. 80 ± 7 mm ; P = 0.04 ) were significantly lower . Oxygen consumption was significantly higher in the ice trial between 9.5–10 km ( 52.4 ± 3.4 vs. 47.8 ± 5.4 mL · kg−1 · min−1 ; P = 0.04 ) . The results suggest ice slurry ingestion was an effective ergogenic aid for triathlon running performance in the heat . The attenuation of intragastric temperature and perceived thermal stress were likely contributors to the self- selection of a higher running intensity and improved performance time The purpose of this study was to compare the effects of a cooling strategy design ed to predominately lower thermal state with a strategy design ed to lower thermal sensation on endurance running performance and physiology in the heat . Eleven moderately trained male runners completed familiarization and three r and omized , crossover 5-km running time trials on a non-motorized treadmill in hot conditions ( 33 ° C ) . The trials included ice slurry ingestion before exercise ( ICE ) , menthol mouth rinse during exercise ( MEN ) , and no intervention ( CON ) . Running performance was significantly improved with MEN ( 25.3 ± 3.5 min ; P = 0.01 ) , but not ICE ( 26.3 ± 3.2 min ; P = 0.45 ) when compared with CON ( 26.0 ± 3.4 min ) . Rectal temperature was significantly decreased with ICE ( by 0.3 ± 0.2 ° C ; P < 0.01 ) , which persisted for 2 km of the run and MEN significantly decreased perceived thermal sensation ( between 4 and 5 km ) and ventilation ( between 1 and 2 km ) during the time trial . End-exercise blood prolactin concentration was elevated with MEN compared with CON ( by 25.1 ± 24.4 ng/mL ; P = 0.02 ) . The data demonstrate that a change in the perception of thermal sensation during exercise from menthol mouth rinse was associated with improved endurance running performance in the heat . Ice slurry ingestion reduced core temperature but did not decrease thermal sensation during exercise or improve running performance Abstract The purpose of this study was to compare the effects of pre-exercise ice slurry ingestion and cold water immersion on submaximal running time in the heat . On three separate occasions , eight males ran to exhaustion at their first ventilatory threshold in the heat ( 34.0 ± 0.1 ° C , 52 ± 3 % relative humidity ) following one of three 30 min pre-exercise manoeuvres : ( 1 ) ice slurry ingestion ; ( 2 ) cold water immersion ; or ( 3 ) warm fluid ingestion ( control ) . Running time was longer following cold water immersion ( 56.8 ± 5.6 min ; P = 0.008 ) and ice slurry ingestion ( 52.7 ± 8.4 min ; P = 0.005 ) compared with control ( 46.7 ± 7.2 min ) , but not significantly different between cold water immersion and ice slurry ingestion ( P = 0.335 ) . During exercise , rectal temperature was lower with cold water immersion from 15 and 20 min into exercise compared with control and ice slurry ingestion , respectively , and remained lower until 40 min ( P = 0.001 ) . At exhaustion rectal temperature was significantly higher following ice slurry ingestion ( 39.76 ± 0.36 ° C ) compared with control ( 39.48 ± 0.36 ° C ; P = 0.042 ) and tended to be higher than cold water immersion ( 39.48 ± 0.34 ° C ; P = 0.065 ) . As run times were similar between conditions , ice slurry ingestion may be a comparable form of pre-cooling to cold water immersion |
932 | 27,699,922 | Significant reductions in ESA dosing may be achieved with optimal intravenous iron usage in the haemodialysis population , and suboptimal iron use may require higher ESA dosing to manage anaemia | AIM Higher dosages of erythropoiesis-stimulating agents ( ESAs ) have been associated with adverse effects .
Intravenous iron is used to optimize ESA response and reduces ESA doses in haemodialysis patients ; this meta- analysis evaluates the magnitude of this effect . | BACKGROUND Anemia , a common complication of chronic kidney disease , usually develops as a consequence of erythropoietin deficiency . Recombinant human erythropoietin ( epoetin alfa ) is indicated for the correction of anemia associated with this condition . However , the optimal level of hemoglobin correction is not defined . METHODS In this open-label trial , we studied 1432 patients with chronic kidney disease , 715 of whom were r and omly assigned to receive a dose of epoetin alfa targeted to achieve a hemoglobin level of 13.5 g per deciliter and 717 of whom were assigned to receive a dose targeted to achieve a level of 11.3 g per deciliter . The median study duration was 16 months . The primary end point was a composite of death , myocardial infa rct ion , hospitalization for congestive heart failure ( without renal replacement therapy ) , and stroke . RESULTS A total of 222 composite events occurred : 125 events in the high-hemoglobin group , as compared with 97 events in the low-hemoglobin group ( hazard ratio , 1.34 ; 95 % confidence interval , 1.03 to 1.74 ; P=0.03 ) . There were 65 deaths ( 29.3 % ) , 101 hospitalizations for congestive heart failure ( 45.5 % ) , 25 myocardial infa rct ions ( 11.3 % ) , and 23 strokes ( 10.4 % ) . Seven patients ( 3.2 % ) were hospitalized for congestive heart failure and myocardial infa rct ion combined , and one patient ( 0.5 % ) died after having a stroke . Improvements in the quality of life were similar in the two groups . More patients in the high-hemoglobin group had at least one serious adverse event . CONCLUSIONS The use of a target hemoglobin level of 13.5 g per deciliter ( as compared with 11.3 g per deciliter ) was associated with increased risk and no incremental improvement in the quality of life . ( Clinical Trials.gov number , NCT00211120 [ Clinical Trials.gov ] . ) BACKGROUND Diagnosis of iron deficiency in hemodialysis patients is limited by the inaccuracy of commonly used tests . Reticulocyte hemoglobin content ( CHr ) is a test that has shown promise for improved diagnosis in preliminary studies . The purpose of this study was to compare iron management guided by serum ferritin and transferrin saturation to management guided by CHr . METHODS A total of 157 hemodialysis patients from three centers were r and omized to iron management based on ( group 1 ) serum ferritin and transferrin saturation , or ( group 2 ) CHr . Patients were followed for six months . Treatment with intravenous iron dextran , 100 mg for 10 consecutive treatments was initiated if ( group 1 ) serum ferritin < 100 ng/mL or transferrin saturation < 20 % , or ( group 2 ) CHr < 29 pg . RESULTS There was no significant difference between groups in the final mean hematocrit or epoetin dose . The mean weekly dose of iron dextran was 47.7 + /- 35.5 mg in group 1 compared to 22.9 + /- 20.5 mg in group 2 ( P = 0.02 ) . The final mean serum ferritin was 399.5 + /- 247.6 ng/mL in group 1 compared to 304.7 + /- 290.6 ng/mL in group 2 ( P < 0.05 ) . There was no significant difference in final TSAT or CHr . Coefficient of variation was significantly lower for CHr than serum ferritin and transferrin saturation ( 3.4 % vs. 43.6 % and 39.5 % , respectively ) . CONCLUSIONS CHr is a markedly more stable analyte than serum ferritin or transferrin saturation , and iron management based on CHr results in similar hematocrit and epoetin dosing while significantly reducing IV iron exposure BACKGROUND Iron deficiency is a frequent cause of recombinant human erythropoietin (rhEPO)-resistant anemia in hemodialysis patients . Both reticulocyte hemoglobin content ( CHr ) and transferrin saturation ( TSAT ) have been proposed as markers of iron deficiency , but it is unclear which parameter is superior . METHODS To compare the efficacy of CHr and TSAT as an indicator for treatment of iron deficiency , we conducted a single-center , open-label , prospect i ve , r and omized , controlled trial at the Kidney Center in Shinraku-en Hospital of 197 Japanese patients on chronic hemodialysis . After 4 weeks of run-in period during which iron supplementation was suspended , 100 patients who were r and omized to the CHr group received 240 mg iron colloid intravenously over 2 weeks when CHr less than 32.5 pg , and 97 patients who were r and omized to the TSAT group received the same doses of iron colloid when TSAT less than 20 % . We measured the rhEPO dose needed to maintain pre study hematocrit levels , hematocrit , CHr , TSAT , serum ferritin , percentage of hypochromic red blood cells , and total iron administered . RESULTS Sixteen weeks later , 94 patients in the CHr group and 89 patients in the TSAT group finished the study . The doses of rhEPO required decreased by 35.8 % ( 4081 to 2629 U/week , P < 0.005 ) in the TSAT group , but not significantly in the CHr group ( 4121 to 3606 U/week ) . Although CHr increased promptly after the iron administration in both groups , TSAT increased only in the TSAT group . CONCLUSIONS Although CHr reflects the iron status more sensitively , TSAT is a better clinical marker for iron supplementation therapy Background / Aims : Renal anemia is one of the commonest complications of chronic renal failure . Iron deficiency is the most common factor which affects the efficacy of recombinant human erythropoietin ( EPO ) therapy . Intravenous ( i.v . ) iron preparations are commonly used in Western countries , but iron sucrose is seldom used in Chinese patients on maintenance hemodialysis . The aim of the present study was to explore the safety and efficacy of i.v . iron sucrose in Chinese patients on maintenance hemodialysis and to explore the optimal administration frequency . Methods : One hundred and thirty-six patients on maintenance hemodialysis were involved in this r and omized , controlled , parallel-group , single-center trial . Seventy patients received i.v . iron sucrose ( Venofer ® , delivering 100 mg iron ) twice a week for 8 weeks , then once a week for another 4 weeks . The other 66 patients received oral ( p.o . ) ferrous succinate 200 mg t.i.d . for 12 weeks . Levels of serum ferritin ( SF ) , transferrin saturation ( TSAT ) , hemoglobin ( Hb ) and hematocrit ( Hct ) were assessed at baseline and then again after 4 , 8 and 12 weeks of treatment . Results : There were no differences between i.v . and p.o . groups in terms of sex , age , duration of hemodialysis , dialysis frequency per week , EPO dosage per week , the level of intact parathyroid hormone , serum creatinine , blood urea nitrogen , or hematological parameters at baseline . After 8 and 12 weeks of treatment , mean Hb concentration and Hct were significantly increased in the i.v . group , and were also significantly higher than those in the p.o . group . Levels of SF and TSAT were also significantly increased in the i.v . group , and significantly higher than in the p.o . group . After 8 weeks , the response rate in the i.v . group was 88.6 % , which was significantly higher than that in the p.o . group . The mean EPO dose was significantly lower in the i.v . group than the p.o . group . Hb , Hct , SF and TSAT levels were maintained between 8 and 12 weeks in the i.v . group despite the decrease in dose frequency . There were no adverse events related to i.v . iron administration . Twenty-two patients in the p.o . group had adverse gastrointestinal effects . After 12 weeks , the cost of EPO + i.v . iron was significantly higher than the cost of EPO + p.o . iron . Conclusion : Intravenous iron sucrose can effectively increase serum iron parameters and Hb levels in Chinese patients on maintenance hemodialysis and is well tolerated . Infusion of i.v . iron sucrose 100 mg per week can maintain serum iron parameters and Hb levels in Chinese patients on maintenance hemodialysis and can permit reductions in the required dose of EPO . However , the total cost of i.v . iron is relatively high BACKGROUND AND OBJECTIVES Hepcidin is a key regulator of iron homeostasis , but its study in the setting of chronic kidney disease ( CKD ) has been hampered by the lack of vali date d serum assays . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS This study reports the first measurements of bioactive serum hepcidin using a novel competitive ELISA in 48 pediatric ( PCKD2 - 4 ) and 32 adult ( ACKD2 - 4 ) patients with stages 2 to 4 CKD along with 26 pediatric patients with stage 5 CKD ( PCKD5D ) on peritoneal dialysis . RESULTS When compared with their respective controls ( pediatric median = 25.3 ng/ml , adult = 72.9 ng/ml ) , hepcidin was significantly increased in PCKD2 - 4 ( 127.3 ng/ml ) , ACKD2 - 4 ( 269.9 ng/ml ) , and PCKD5D ( 652.4 ng/ml ) . Multivariate regression analysis was used to assess the relationship between hepcidin and indicators of anemia , iron status , inflammation , and renal function . In PCKD2 - 4 ( R(2 ) = 0.57 ) , only ferritin correlated with hepcidin . In ACKD2 - 4 ( R(2 ) = 0.78 ) , ferritin and soluble transferrin receptor were associated with hepcidin , whereas GFR was inversely correlated . In PCKD5D ( R(2 ) = 0.52 ) , percent iron saturation and ferritin were predictors of hepcidin . In a multivariate analysis that incorporated all three groups ( R(2 ) = 0.6 ) , hepcidin was predicted by ferritin , C-reactive protein , and whether the patient had stage 5D versus stages 2 to 4 CKD . CONCLUSIONS These findings suggest that increased hepcidin across the spectrum of CKD may contribute to abnormal iron regulation and erythropoiesis and may be a novel biomarker of iron status and erythropoietin resistance INTRODUCTION Although clinical use of recombinant human erythropoietin ( rHuEPO ) since 1989 has improved anemia in most end-stage renal disease patients , there are still many hemodialysis patients unable to maintain an adequate hematocrit ( HCT ) without large doses of rHuEPO . This suggests that anemia is not solely a consequence of rHuEPO deficiency , but may be due to other factors including functional iron deficiency . Since the optimal prescription for iron replacement is not yet known , we evaluated the effect of intravenous iron dextran ( IVFe ) infusion on serum ferritin ( SFer ) concentration and rHuEPO dose . Our objective was to raise and maintain serum ferritin concentrations to 2 different levels above the National Kidney Foundation Dialysis Outcome Quality Initiative st and ard of 100 ng/ml to determine whether , and by what degree rHuEPO dose could be lowered . METHODS HD patients on i.v . rHuEPO with a SFer concentration > or = 70 ng/ml and an HCT of < or = 33 % were enrolled . Subjects were divided as follows : Group 1 : target SFer of 200 ng/ml , Group 2 : target SFer of 400 ng/ml . Each subject below the target level received IVFe in up to 10 divided doses during consecutive dialysis sessions as needed to reach the target . HCT was maintained between 32.5 % and 36 % by adjusting rHuEPO dosage . RESULTS Mean SFer concentration at the study conclusion in Group 1 : 261 ng/ml ; Group 2 : 387 ng/ml . The mean decrease in rHuEPO dose for Group 1 was 31 U/kg body weight/week ( 250 - 219 U/kg bw/wk ) while in Group 2 it was 154 U/kg body weight/week ( 312 - 158 U/kg bw/wk ) ( p < 0.001 ) . There was no difference in HCT between groups . Our results suggest that higher target serum ferritin concentrations can be well tolerated and lower rHuEPO requirements In view of current uncertainty regarding the optimum route for iron supplementation in patients receiving recombinant human erythropoietin ( EPO ) , a prospect i ve r and omized controlled study was design ed to investigate this issue . All iron-replete renal failure patients commencing EPO who had a hemoglobin concentration < 8.5 g/dl and an initial serum ferritin level of 100 to 800 micrograms/liter were r and omized into three groups with different iron supplementation : Group 1 , i.v . iron dextran 5 ml every 2 weeks ; Group 2 , oral ferrous sulphate 200 mg tds ; Group 3 , no iron . All patients were treated with 25 U/kg of EPO thrice weekly subcutaneously . The hemoglobin concentration , reticulocyte count , serum ferritin , transferrin saturation , and EPO dose were monitored every two weeks for the first four months . Thirty-seven patients entered the study ( 12 i.v . , 13 oral , 12 no iron ) . The three groups were equivalent with regard to age , sex , and other demographic details . Even allowing for dosage adjustments , the hemoglobin response in the group receiving i.v . iron ( 7.3 + /- 0.8 to 11.9 + /- 1.2 g/dl ) was significantly greater than that for the other two groups ( 7.2 + /- 1.1 to 10.2 + /- 1.4 g/dl and 7.3 + /- 0.8 to 9.9 + /- 1.6 g/dl for Groups 2 and 3 , respectively ; P < 0.005 for both groups vs. Group 1 at 16 weeks ) . There was no difference between the groups supplemented with oral iron and no iron . Serum ferritin levels remained constant in those receiving i.v . iron ( 345 + /- 273 to 359 + /- 140 micrograms/liter ) , in contrast to the other two groups in which ferritin levels fell significantly ( 309 + /- 218 to 116 + /- 87 micrograms/liter and 458 + /- 206 to 131 + /- 121 micrograms/liter for Groups 2 and 3 , respectively ; P < 0.0005 for Group 1 vs. Group 2 , and P < 0.005 for Group 1 vs. Group 3 at 16 weeks ) . Dosage requirements of EPO were less in Group 1 ( 1202 + /- 229 U/kg/16 weeks ) than in Group 2 ( 1294 + /- 314 U/kg/16 weeks ) or Group 3 ( 1475 + /- 311 U/kg/16 weeks ; P < 0.05 vs. Group 1 ) . The results of this study suggest that , even in iron-replete patients , those supplemented with i.v . iron have an enhanced hemoglobin response to EPO with better maintenance of iron stores and lower dosage requirements of EPO , compared with those patients receiving oral iron and no iron supplementation BACKGROUND Whether correction of anemia in patients with stage 3 or 4 chronic kidney disease improves cardiovascular outcomes is not established . METHODS We r and omly assigned 603 patients with an estimated glomerular filtration rate ( GFR ) of 15.0 to 35.0 ml per minute per 1.73 m2 of body-surface area and mild-to-moderate anemia ( hemoglobin level , 11.0 to 12.5 g per deciliter ) to a target hemoglobin value in the normal range ( 13.0 to 15.0 g per deciliter , group 1 ) or the subnormal range ( 10.5 to 11.5 g per deciliter , group 2 ) . Subcutaneous erythropoietin ( epoetin beta ) was initiated at r and omization ( group 1 ) or only after the hemoglobin level fell below 10.5 g per deciliter ( group 2 ) . The primary end point was a composite of eight cardiovascular events ; secondary end points included left ventricular mass index , quality -of-life scores , and the progression of chronic kidney disease . RESULTS During the 3-year study , complete correction of anemia did not affect the likelihood of a first cardiovascular event ( 58 events in group 1 vs. 47 events in group 2 ; hazard ratio , 0.78 ; 95 % confidence interval , 0.53 to 1.14 ; P=0.20 ) . Left ventricular mass index remained stable in both groups . The mean estimated GFR was 24.9 ml per minute in group 1 and 24.2 ml per minute in group 2 at baseline and decreased by 3.6 and 3.1 ml per minute per year , respectively ( P=0.40 ) . Dialysis was required in more patients in group 1 than in group 2 ( 127 vs. 111 , P=0.03 ) . General health and physical function improved significantly ( P=0.003 and P<0.001 , respectively , in group 1 , as compared with group 2 ) . There was no significant difference in the combined incidence of adverse events between the two groups , but hypertensive episodes and headaches were more prevalent in group 1 . CONCLUSIONS In patients with chronic kidney disease , early complete correction of anemia does not reduce the risk of cardiovascular events . ( Clinical Trials.gov number , NCT00321919 [ Clinical Trials.gov ] . ) |
933 | 16,863,548 | The systematic review published in this issue suggests that particularly for omeprazole in combination with amoxicillin or amoxicillin and clarithromycin the success rate is much lower when compared to other proton pump inhibitors ( PPIs ) . | There are variations in the CYP2C19 genotypes , that are important for the metabolism of PPIs .
Patients who are heterozygotes for the mutation , but especially homozygotes , have a much slower metabolism , which will result in more profound acid suppression .
Studies have been published , that suggest that the success rate of anti-Helicobacter therapy is in part related to the CYP2C19 genotype of the patient . | BACKGROUND & AIMS The role of omeprazole in triple therapy and the impact of Helicobacter pylori resistance on treatment outcome are not established . This study investigated the role of omeprazole and influence of primary H. pylori resistance on eradication and development of secondary resistance . METHODS Patients ( n = 539 ) with a history of duodenal ulcer and a positive H. pylori screening test result were r and omized into 4 groups . OAC group received 20 mg omeprazole , 1000 mg amoxicillin , and 500 mg clarithromycin ; OMC group received 20 mg omeprazole , 400 mg metronidazole , and 250 mg clarithromycin ; and AC ( amoxicillin , 1000 mg , and clarithromycin , 500 mg ) and MC ( metronidazole , 400 mg , and clarithromycin , 250 mg ) groups received no omeprazole . All doses were administered twice daily for 1 week . H. pylori status was assessed before and after therapy by 13C-urea breath test . Susceptibility testing was performed at entry and in patients with persistent infection after therapy . RESULTS Eradication ( intention to treat [ n = 514]/per protocol [ n = 449 ] ) was 94%/95 % for OAC , 26%/25 % for AC ( P < 0.001 ) , 87%/91 % for OMC , and 69%/72 % for MC ( P < 0.001 ) . Primary resistance was 27 % for metronidazole , 3 % for clarithromycin , and 0 % for amoxicillin . Eradication in primary metronidazole-susceptible/-resistant strains was 95%/76 % for OMC and 86%/43 % for MC . Secondary metronidazole and clarithromycin resistance each developed in 12 patients : 8 treated with omeprazole and 16 without omeprazole . CONCLUSIONS Addition of omeprazole achieves high eradication rates , reduces the impact of primary resistance , and may decrease the risk of secondary resistance compared with regimens containing only two antibiotics S‐mephenytoin 4’‐hydroxylase ( CYP2C19 ) catalyses the metabolism of rabeprazole to some extent . Based on the metabolic and pharmacokinetic differences among other proton pump inhibitors such as omeprazole , lansoprazole and pantoprazole , rabeprazole appears to be the least affected proton pump inhibitor by the CYP2C19‐related genetic polymorphism Objective Helicobacter pylori treatment failure is thought to be due mainly to polymorphic cytochrome P450 2C19 ( CYP2C19 ) genetic polymorphism , associated with proton pump inhibitor metabolism , and antimicrobial susceptibility . This report has ascertained which was more important , CYP2C19 polymorphism or antimicrobial susceptibility , when using 1-week lansoprazole-based or rabeprazole-based triple therapy in Japan . Design An open , r and omized , parallel group study . Setting One hundred and forty-five subjects with H. pylori-positive gastritis or peptic ulcers were r and omly assigned to receive 30 mg lansoprazole twice daily ( LAC group ) , 10 mg rabeprazole twice daily ( RAC20 group ) , or 20 mg rabeprazole twice daily ( RAC40 group ) , with 1000 mg amoxicillin twice daily and 400 mg clarithromycin twice daily for 1 week . Antimicrobial resistance testing was performed by E-test . More than 4 weeks after completion of treatment , H. pylori status was assessed by 13C-urea breath test , histology , and culture . Results Cure rates expressed as intention-to-treat and per- protocol analyses , respectively , were 79.6 and 83.0 % with LAC , 85.4 and 89.1 % with RAC20 , and 83.3 and 88.9 % with RAC40 . In the case of clarithromycin-sensitive strains , the cure rates were more than 97 % , regardless of CYP2C19 polymorphism . However , treatment succeeded in only one out of 16 clarithromycin-resistant strains . Conclusions The key to successful eradication of H. pylori , using lansoprazole or rabeprazole with clarithromycin and amoxicillin , is clarithromycin susceptibility , not CYP2C19 polymorphism Aim : To investigate the effect of different proton pump inhibitors , S‐mephenytoin 4′‐hydroxylase ( CYP2C19 ) genotype and antibiotic susceptibility on the eradication rate of Helicobacter pylori |
934 | 23,633,347 | There is very weak unreliable evidence , based on one very small study ( n = 24 ) at high risk of bias , that coaxial superelastic NiTi may produce greater tooth movement over 12 weeks , but no information on associated pain or root resorption .
There is insufficient evidence to determine whether or not there is a difference between either thermoelastic or CuNiTi and superelastic NiTi initial arch wires .
AUTHORS ' CONCLUSIONS There is no reliable evidence from the trials included in this review that any specific initial arch wire material is better or worse than another with regard to speed of alignment or pain .
There is no evidence at all about the effect of initial arch wire material s on the important adverse effect of root resorption .
Further well- design ed and conducted , adequately-powered , RCTs are required to determine whether the performance of initial arch wire material s as demonstrated in the laboratory , makes a clinical ly important difference to the alignment of teeth in the initial stage of orthodontic treatment in patients | BACKGROUND Initial arch wires are the first arch wires to be inserted into the fixed appliance at the beginning of orthodontic treatment and are used mainly for the alignment of teeth by correcting crowding and rotations .
With a number of different types of orthodontic arch wires available for initial tooth alignment , it is important to underst and which wire is most efficient , as well as which wires cause the least amount of root resorption and pain during the initial aligning stage of treatment .
This is an up date of the review ' Initial arch wires for alignment of crooked teeth with fixed orthodontic braces ' first published in the Cochrane Data base of Systematic Review s 2010 , Issue 4 .
OBJECTIVES To assess the effects of initial arch wires for alignment of teeth with fixed orthodontic braces in relation to alignment speed , root resorption and pain intensity . | INTRODUCTION The aim of this study was to investigate the duration of m and ibular-crowding alleviation with self-ligating brackets compared with conventional appliances and the accompanying dental effects . METHODS Fifty-four subjects were selected from a pool of patients satisfying the following inclusion criteria : non extraction treatment in the m and ibular or maxillary arches ; eruption of all m and ibular teeth ; no spaces in the m and ibular arch ; irregularity index greater than 2 in the m and ibular arch ; and no therapeutic intervention planned with any extraoral or intraoral appliance . The patients were r and omly assigned to 2 groups : 1 group received treatment with a self-ligating bracket ( Damon 2 , Ormco , Glendora , Calif ) and the other with a conventional edgewise appliance ( Microarch , GAC , Central Islip , NY ) , both with 0.022-in slots . The irregularity index of the m and ibular arch was normalized between the groups , and the time to alignment was estimated in days . Treatment duration was assessed by data modeling with the Cox proportional hazard regression . Lateral cephalometric radiographs were used to assess the alteration of m and ibular incisor position before and after alignment . Measurements of intercanine and intermolar widths were also made on dental casts to determine changes associated with correction . RESULTS AND CONCLUSIONS Overall , no difference in the time required to correct m and ibular crowding with Damon 2 and conventional brackets was observed . For moderate crowding ( irregularity index < 5 ) , however , the self-ligating group had 2.7 times faster correction . This difference was marginally insignificant for subjects with irregularity index scores greater than 5 . Greater crowding prolonged treatment by an additional 20 % for each irregularity index unit . Increases in intercanine and intermolar widths associated with crowding correction regardless of bracket group were noted . The self-ligating group showed a statistically greater intermolar width increase than the conventional group . Also , an alignment-induced increase in the proclination of the m and ibular incisors was observed for both bracket groups , but no difference was found between Damon 2 and conventional brackets for this parameter In a clinical trial involving 155 dental arches with irregularity > 5 mm , the rate of alignment was used to compare the alignment efficiency of 16 mil superelastic Ni-Ti versus 17.5 mil triple-str and ed steel archwires , and to determine whether ion implantation of the Ni-Ti wire improved its performance . Subjects were r and omly assigned to archwire types ; both 18 and 22 slot edgewise appliances were employed . Pre-treatment equivalence of the experimental groups was verified . Anterior irregularity was determined monthly ( using Little 's irregularity index ) until it decreased below 2 mm , and the elastomeric ligatures were replaced at each appointment . Effective tooth movement occurred with each of the archwire types . There were no significant differences among wires , but the rate of alignment was significantly faster in the lower arch for subjects with the 22 slot appliance Two arch wires commonly used for initial tooth alignment were compared with regard to their clinical effectiveness . The two arch wires tested were 0.0155-inch diameter multiple-str and ed stainless steel wire ( Dentaflex , Dentaurium , Optident , Yorkshire , Engl and ) and 0.014-inch diameter nickel-titanium alloy wire ( NiTi , ORMCO Co. , Monrovia , Calif. ) . Consecutive patients attending an orthodontic clinic for routine placement of a fixed appliance were r and omly assigned one of these two initial arch wires . Good quality alginate impressions of the appropriate dental arch were taken before arch wire placement and also at the subsequent appointment , which was , on average , 6 weeks later . Seventy-four arches were used in this study . The degree of tooth alignment achieved for each wire type was compared with a Reflex Microscope ( Reflex Measurement Ltd. , Butleigh , Engl and ) to make detailed measurements on the result ant casts . The degree of initial alignment achieved with the two wires was similar over this 6-week period . However , some differences were found for the lower labial segment where the interbracket span is usually reduced and where the superelastic nickel-titanium wire was found to give improved alignment . No threshold of crowding was found where one arch wire performed better than the other Two nickel-titanium archwire types commonly used for initial tooth alignment were compared with regard to the pain/discomfort patients experience during the initial phase of tooth movement . The two archwires used were a superelastic nickel-titanium alloy , 0.014 inch Sentalloy , Light ( GAC International Inc. Central Islip , NY , USA ) and a 0.014 inch Nitinol ( unitek , Monrovia , CA , USA ) , a conventional nickel-titanium aligning archwire . One hundred and twenty-eight consecutive patients attending an orthodontic university clinic and 2 private practice s for routine placement of a fixed appliance were r and omly assigned one of these 2 initial archwires . Assessment s of pain/discomfort were made daily by means of a 100 mm visual analog scale ( VAS ) over the first 7-day period after bonding . On the first day , recordings were made every hour for the first 11 hours . The results showed that the level of discomfort increased continuously every hour after the insertion of either a Sentalloy or a Nitinol as first archwires , with a peak in the first night , remaining high on the second day and decreasing thereafter to baseline level after 7 days . During the first 10 hours it was apparent that the pain/discomfort experienced after placement of a Sentalloy was less than that found with the Nitinol archwire , although a significant difference could be found at 4 hours only . No significant gender-specific differences were found in either archwire group . A significant difference between the upper and lower dental arches was observed during the first 11 hours after placement of either a Sentalloy or a Nitinol archwire , with the lower arch having the higher pain experience . ZusammenfassungZwei verschiedene Bögen aus NiTi-Legierungen , die häufig für die initiale Nivellierung verwendet werden , wurden in Hinsicht auf das Auftreten von Schmerzen/Beschwerden zu Beginn der Zahnbewegung untersucht . Das eine Bogen material war eine superelastische NiTi-legierung , 0,014 inch Sentalloy , Light ( GAC International Inc. , Central Islip , N. Y. ) , das and ere ein herkömmlicher 0,014 inch Nitinol-Bogen ( Unitek , Monrovia , Kalifornien).128 fortlaufend beh and elte Patienten aus einer kieferorthopädischen Universitätsklinik und zwei privaten Praxen , bei denen routinemäßig eine Multib and apparatur eingesetzt werden sollte , wurden r and omisiert für den einen oder den and eren Bogen vorgesehen . Die Beurteilungen der Schmerzen/Beschwerden wurden täglich während der ersten sieben Tage nach dem Einsetzen der festsitzenden Apparatur auf einer visuellen Skala von 100 mm Länge ( visual analogue scale , VAS ) vorgenommen . Zusätzlich wurde am ersten Tag für die ersten elf Stunden nach dem Einsetzen stündlich die Schmerzintensität aufgezeichnet . Die Ergebnisse zeigten , daß die Beschwerden für den ersten Bogen , sowohl für den Sentalloy-als auch für den Nitinol-Bogen , kontinuierlich jede Stunde nach dem Einsetzen anstiegen . Der Höhepunkt wurde in der ersten Nacht erreicht , blieb am zweiten Tag auf derselben Höhe und verringerte sich kontinuierlich bis zum siebten Tag auf das individuelle Ausgangsniveau . Während der ersten zehn Stunden war es offensichtlich , daß nach der Eingliederung der Bögen beim Sentalloy-Bogen deutlich geringere Beschwerden auftraten als bei dem Nitinol-Bogen ; dieser Unterschied war jedoch nur für die ersten vier Stunden signifikant . Keine signifikanten Unterschiede der Beschwerden zwischen den Bogen material ien f and en sich hinsichtlich des Geschlechts der Patienten . Ein signifikanter Unterschied wurde zwischen dem Ober- und dem Unterkiefer während der ersten elf Studen nach dem Einsetzen sowohl des Sentalloy- als auch des Nitinol-Bogens beobachtet ; i m Unterkiefer traten deutlich stärkere Beschwerden auf The aim of this study was to compare three orthodontic archwire sequences . One hundred and fifty-four 10- to 17-year-old patients were treated in three centres and r and omly allocated to one of three groups : A = 0.016-inch nickel titanium ( NiTi ) , 0.018 x 0.025-inch NiTi , and 0.019 x 0.025-inch stainless steel ( SS ) ; B = 0.016-inch NiTi , 0.016-inch SS , 0.020-inch SS , and 0.019 x 0.025-inch SS ; and C = 0.016 x 0.022-inch copper ( Cu ) NiTi , 0.019 x 0.025-inch CuNiTi , and 0.019 x 0.025-inch SS . At each archwire change and for each arch , the patients completed discomfort scores on a seven-point Likert scale at 4 hours , 24 hours , 3 days , and 1 week . Time in days and the number of visits taken to reach a 0.019 x 0.025-inch SS working archwires were calculated . A periapical radiograph of the upper left central incisor was taken at the start of the treatment and after placement of the 0.019 x 0.025-inch SS wire so root resorption could be assessed . There were no statistically significant differences between archwire sequences A , B , or C for patient discomfort ( P > 0.05 ) or root resorption ( P = 0.58 ) . The number of visits required to reach the working archwire was greater for sequence B than for A ( P = 0.012 ) but this could not be explained by the increased number of archwires used in sequence The statistical methodology of health research experiments published in Lancet , the New Engl and Journal of Medicine , and Medical Care between 1975 and 1980 for the presence or absence of an error of experimental design and analysis was examined . The error is the result of inappropriately using patient-related observations as the unit of analysis to form conclusions about provider behavior or outcomes determined jointly by patients and providers . The error was present in 20 of 28 ( 71 % ) health care experiments addressing an issue of health provider professional performance . Its usual effect is to increase erroneously the power of an experiment to detect differences between experimental and control groups . It is likely that this type of error could be avoided by the explicit and prospect i ve definition of hypotheses and the population s to which they are intended to pertain Aim To compare the efficiency of orthodontic archwire sequences produced by three manufacturers . Design Prospect i ve , r and omized clinical trial with three parallel groups . Setting Private orthodontic practice in Caloundra , QLD , Australia Subjects and methods One hundred and thirty‐two consecutive patients were r and omized to one of three archwire sequence groups : ( i ) 3 M Unitek , 0·014 inch Nitinol , 0·017 inch × 0·017 inch heat activated Ni – Ti ; ( ii ) GAC international , 0·014 inch Sentalloy , 0·016 × 0·022 inch Bioforce ; and ( iii ) Ormco corporation , 0·014 inch Damon Copper Ni – Ti , 0·014 × 0·025 inch Damon Copper Ni – Ti . All patients received 0·018 × 0·025 inch slot Victory SeriesTM brackets . Outcome measures M and ibular impressions were taken before the insertion of each archwire . Patients completed discomfort surveys according to a seven‐point Likert Scale at 4 h , 24 h , 3 days and 7 days after the insertion of each archwire . Efficiency was measured by time required to reach the working archwire , m and ibular anterior alignment and level of discomfort . Results No significant differences were found in the reduction of irregularity between the archwire sequences at any time‐point ( T1 : P = 0·12 ; T2 : P = 0·06 ; T3 : P = 0·21 ) or in the time to reach the working archwire ( P = 0·28 ) . No significant differences were found in the overall discomfort scores between the archwire sequences ( 4 h : P = 0·30 ; 24 h : P = 0·18 ; 3 days : P = 0·53 ; 7 days : P = 0·47 ) . When the time‐points were analysed individually , the 3 M Unitek archwire sequence induced significantly less discomfort than GAC and Ormco archwires 24 h after the insertion of the third archwire ( P = 0·02 ) . This could possibly be attributed to the progression in archwire material and archform . Conclusions The archwire sequences were similar in alignment efficiency and overall discomfort . Progression in archwire dimension and archform may contribute to discomfort levels . This study provides clinical justification for three common archwire sequences in 0·018 × 0·025 inch slot brackets OBJECTIVES To examine whether the transition temperature of Cu-NiTi archwires has an effect on the tooth movement during the alignment phase of orthodontic treatment . DESIGN ' Split mouth ' design in r and omly selected patients . SETTING AND SAMPLE POPULATION The Department of Orthodontics , School of Dentistry , University of Aarhus . Fifteen r and omly selected patients with identical level of irregularity in the alignment phase of their treatment . Experiment Variable - Specially manufactured Cu-NiTi archwires for the upper arch were inserted . These consisted of two separate halves , each with its own transition temperature , respectively 27 degrees and 40 degrees C , and clamped together in the middle . OUTCOME MEASURE The tooth movement , expressed as two translations and a rotation , in the occlusal plane was measured from the patients ' intraoral photographs taken upon insertion of the archwires and again after 1 month . RESULTS Tooth movements tended to be larger on the 40 degrees C-side , however only in case of the total translation of the premolars was this difference significant . In general , patients had not noticed any difference between the two sides of the archwire , although one patient stated the 27 degrees C-side to be more comfortable as the 40 degrees C-side had bothered her when drinking hot beverages . CONCLUSION The transition temperature of Cu-NiTi archwires has indeed an effect on the amount of tooth movement during alignment . However , the differences are so small though that it is the question whether they can be noticed clinical ly . The study corroborates the trend towards the use of lower forces within orthodontics OBJECTIVE To clinical ly evaluate the alignment efficiency of 0.016-inch coaxial superelastic nickel-titanium ( NiTi ) and 0.016-inch superelastic NiTi in the lower anterior region over a period of 12 weeks . MATERIAL S AND METHODS A sample of 24 patients requiring lower anterior alignment were included in this single-center , single-operator , double-blind clinical trial and were r and omly allocated into two groups of 12 patients . The type of wire selected for each patient was not disclosed to the provider or to the patient . Comparison of pretreatment characteristics of the archwire groups revealed no discrimination between two sample s , thus verifying the r and om allocation of the intervention . An initial alginate impression of the lower arch was followed by impressions at 4- , 8- , and 12-week intervals . Casts were measured using the coordinate measuring machine to denote the degree of alignment . Duplicate readings of the cast series were taken to assess measurement variation . RESULTS A statistically significant difference ( P < .05 ) in the mean values of tooth movement demonstrated the superior aligning efficiency of coaxial superelastic NiTi over single-str and ed superelastic NiTi in relieving lower anterior crowding . The measurement error recorded was within acceptable limits , with range values within 95 % limits of agreement . CONCLUSION Coaxial superelastic NiTi wire proved superior to single-str and ed NiTi in its efficiency in relieving lower anterior crowding over a 12-week period OBJECTIVE To assess the distribution , prevalence and severity of malocclusion and orthodontic treatment needs in schoolchildren from the northeast of Brazil aged between 13 and 15 years . RESEARCH DESIGN Cross-sectional study . PARTICIPANTS A sample of 600 adolescents ( 264 males and 336 females ) r and omly selected and representative of schoolchildren living in Recife ( Brazil ) was obtained from 12 public schools . METHOD The need for orthodontic treatment was measured using the Dental Aesthetic Index ( DAI ) . RESULTS Most of the subjects ( 77 % ) were deemed to require orthodontic treatment . Only about 5.8 % had a h and icapping malocclusion that needed m and atory treatment . A severe malocclusion for which treatment was highly desirable was recorded in 47.5 % of the adolescents and 23.7 % had a definite malocclusion for which treatment was elective . Three main occlusal features were responsible for allocating subjects into the group of " orthodontic treatment required " : crowding ( 47.3 % ) , tooth loss ( 22.3 % ) and maxillary overjet of more than 3 mm ( 21.8 % ) . There were no significant differences ( p > 0.05 ) in mean DAI scores between males and females . CONCLUSIONS 77 % of adolescents from northeast Brazil were in need of orthodontic treatment for dental health reasons . The distribution of DAI scores among Brazilian adolescents is different from that reported in other population s. This study provides baseline data on the need and dem and for orthodontic treatment among Brazilian students To comprehend the result of a r and omized controlled trial ( RCT ) , readers must underst and its design , conduct , analysis and interpretation . That goal can be achieved only through complete transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by using a checklist and flow diagram . The revised CONSORT statement presented in this article incorporates new evidence and addresses some criticism of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Comment . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting the information is associated with biased estimates of treatment effect or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage or participants through an RCT . The revised flow diagram depicts information from 4 stages of a trial ( enrollment , intervention allocation , follow-up and analysis ) . The diagram explicitly includes the number of participants , according to each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have performed an intention-to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting or an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results INTRODUCTION There is still ambiguity about whether continuous or intermittent orthodontic forces produce more root resorption . This prospect i ve r and omized clinical trial was design ed to compare root resorption with these 2 force application patterns . METHODS The sample consisted of 16 maxillary first premolars from 8 patients who required bilateral extraction s as part of their orthodontic treatment . In each subject , a fixed experimental appliance was placed on the maxillary teeth on each side , allowing a buccally directed force . The force was generated by a segmental wire of beta-titanium-molybdenum alloy . The first premolar on 1 side received a buccally directed continuous force , and the contralateral premolar received intermittent force . The initial force magnitude for both sides was 225 cN. After 14 days of initial continuous force , the intermittent force application was obtained with subsequently repeated periods until the end of the eighth week of a 3-day rest period followed by a 4-day force application period . Force levels were set to 225 cN at each patient visit . After the experimental period of 8 weeks , the teeth were extracted under a strict protocol to prevent root surface damage and analyzed with a microcomputed-tomography scan system , and specially design ed software was used for direct volumetric measurements . RESULTS Intermittent force produced less root resorption than continuous force ( P < 0.05 ) . Analysis by position showed that the buccal-cervical region had significantly more root resorption than the other positions ( P < 0.001 ) , corresponding to a region of compression generated by tipping . CONCLUSIONS The application of intermittent orthodontic forces of 225 cN for 8 weeks ( 14 days of force application , 3 days of rest , then 4 days of force application repeated for 6 weeks ) caused less root resorption than continuous forces of 225 cN for 8 weeks . Although it might not be clinical ly practical , compared with continuous forces , intermittent forces might be a safer method to prevent significant root resorption . This regimen , however , could compromise the efficiency of tooth movement A prospect i ve r and omized clinical study was design ed to evaluate the effects of full continuous arch wires , rectangular in cross section , on the axial inclination of lower incisors . The intention of rectangular arch wires is to counteract the labial crown moment usually produced during leveling the curve of Spee with full arch mechanics . Patients were r and omly assigned to 2 groups . Group 1 ( N = 12 ) received round arch wires throughout the leveling stage . Group 2 ( N = 16 ) started with flat 0.016 x 0.022 nickel titanium arch wires progressing to 0.016 x 0.022 stainless steel . The preadjusted 0.018 x 0.025 edgewise appliance was used in all cases . Lateral cephalometric radiographs and m and ibular study models were taken before treatment and when the curve of Spee was leveled ( or in some cases when the overbite was considered clinical ly acceptable ) . In group 1 , the lower incisor proclined a mean of 6.75 degrees + /- 4.85 degrees ( P < .01 ) and in group 2 it proclined a mean of 6.10 degrees + /- 3.95 degrees ( P < .01 ) . However , no significant difference in proclination was detected between the 2 groups . Statistically significant , but low , correlations were demonstrated between change in lower incisor axial inclination and relief of crowding r = 0.45 ) and change in m and ibular arch depth r = 0.54 ) , which was in turn inversely correlated with change in intercanine width r = -0.45 ) . In both groups , the lower incisors proclined with uncontrolled tipping that can probably be attributed to the intrusive force introduced by the arch wire being labial to the center of resistance of the lower incisors . The ability of the rectangular arch wires to control labial proclination following leveling of the curve of Spee , as used in this study , was not supported OBJECTIVES To clinical ly evaluate three commonly used orthodontic tooth aligning arch wires : 016 x 022 inch active martensitic medium force nickel titanium , 016 x 022 inch grade d force active martensitic nickel titanium , and 0.0155 inch multistr and stainless steel . DESIGN A prospect i ve r and omized clinical trial . DATA SOURCE Measured serial study casts of dental arches for 112 assigned arch wires from 56 consecutive patients . Analysis based on completed records for 98 arch wires and 51 patients . METHOD A consecutive sample of 56 patients requiring both upper and lower fixed appliance therapy were r and omly allocated two different arch wires from a possible three under trial . Good quality impressions were taken of the dental arches at the design ated serial stages of alignment ( start , T0 ; 4 weeks , T4 ; 8 weeks , T8 ) . The result ant casts were measured on a Reflex Microscope to record the change in individual tooth alignment both in three and two dimensions ( horizontal plane only ) . RESULTS The measurement error was within acceptable limits ( range , 0.05 to 0.09 mm ) and showed no significant bias . ANOVA statistical models were fitted to the data to adjust for a number of variables . No significant difference in aligning capability ( p > 0.05 ) , in either two or three dimensions , was demonstrated between the three arch wires in the trial . CONCLUSION Heat activated nickel titanium arch wires failed to demonstrate a better performance than the cheaper multistr and stainless steel wires in this r and omized clinical trial . The failure to demonstrate in vivo superiority at the clinical level may be due to the confounding effects of large variations in individual metabolic response . Alternatively , it may be that in routine clinical practice NiTi-type wires are not sufficiently deformed to allow their full superelastic properties to come in to play during initial alignment INTRODUCTION The purpose of this study was to investigate the efficiency of copper-nickel-titanium ( CuNiTi ) vs nickel-titanium ( NiTi ) archwires in resolving crowding of the anterior m and ibular dentition . METHODS Sixty patients were included in this single-center , single-operator , double-blind r and omized trial . All patients were bonded with the In Ovation-R self-ligating bracket ( GAC , Central Islip , NY ) with a 0.022-in slot , and the amount of crowding of the m and ibular anterior dentition was assessed by using the irregularity index . The patients were r and omly allocated into 2 groups of 30 patients , each receiving a 0.016-in CuNiTi 35 degrees C ( Ormco , Glendora , Calif ) or a 0.016-in NiTi ( ModernArch , Wyomissing , Pa ) wire . The type of wire selected for each patient was not disclosed to the provider or the patient . The date that each patient received a wire was recorded , and all patients were followed monthly for a maximum of 6 months . Demographic and clinical characteristics between the 2 wire groups were compared with the t test or the chi-square test and the Fisher exact test . Time to resolve crowding was explored with statistical methods for survival analysis , and alignment rate ratios for wire type and crowding level were calculated with Cox proportional hazards multivariate modeling . RESULTS The type of wire ( CuNiTi vs NiTi ) had no significant effect on crowding alleviation ( 129.4 vs 121.4 days ; hazard ratio , 1.3 ; P > 0.05 ) . Severe crowding ( > 5 on the irregularity index ) showed a significantly higher probability of crowding alleviation duration relative to dental arches with a score of < 5 ( 138.5 vs 113.1 days ; hazard ratio , 2.2 ; P=0.02 ) . CONCLUSIONS The difference of the loading pattern of wires in laboratory and clinical conditions might effectively eliminate the laboratory-derived advantage of CuNiTi wires The aims of this study were to investigate the initial time at which pain occurs after insertion of two initial wires of different sizes , the duration of the pain , the areas affected within the mouth , the level of self-medication , the effect of this pain on daily life , and whether gender is important in the perception of pain . The study group consisted of 109 patients ( 52 boys , 57 girls ) with a mean chronological age of 13.6 years for boys and 14.7 years for girls . Insertion of either a 0.014 or 0.016 inch wire was by r and om selection . Following insertion of the archwires , a question naire comprising a total of 49 questions was given to the patients . They described the time of initial pain in the first question , answered the next 24 questions as ' yes ' or ' no ' , and used a visual analogue scale for the final 24 questions . No significant differences were found in terms of gender , in the perception period of initial pain as regards the areas affected within the mouth or the effect of pain on daily living when the 0.014 and 0.016 inch wire groups were compared at 6 hours , 1 , 2 , 3 , 4 , 5 , 6 and 7 days . At 24 hours , which was found to be statistically significant , more pain relief was used in the 0.014 inch archwire group . The results show that in both groups , initial pain was perceived at 2 hours , peaked at 24 hours and had decreased by day 3 The physical properties of a super-elastic archwire alloy ( Titanol ) and Nitinol were investigated by the means of a bending test . It was found that the alloy possessed super-elastic properties . A clinical trial was then carried out to compare the properties of two types of aligning archwire . Two groups of 20 patients with crowded dentitions were r and omly allocated either Titanol or Nitinol , a conventional nickel-titanium alloy aligning archwire . High quality alginate impressions were taken after archwire placement in Edgewise fixed appliances and were repeated after a mean period of 35 days . The impressions were cast in dental stone and digitized using the Reflex Metrograph . The contact points of the teeth of the labial segments , together with four stable points in the rugae were recorded . This enabled the co-ordinates for the sequential study models to be superimposed upon one another , allowing tooth movement in three dimensions to be calculated . The measurement error expressed as error variance was 0.028 mm . The coefficient of reliability was 97 per cent . When tooth movement was analysed the mean movement per contact point for Titanol was 1.7 mm and for Nitinol 1.42 mm . This difference was not statistically significant ( P less than 0.05 , t-test ) . However , a clinical impression was that the super-elastic archwire proved superior to the Nitinol , because it was more readily engaged into grossly displaced teeth OBJECTIVES Orthodontic thermoelastic archwires produce lighter and more biologic forces than superelastic archwires and could therefore offer the possibility of reducing initial orthodontic pain . Nevertheless , evidence concerning this issue is scarce . The aim of this study was to compare pain perception following first archwire placement in patients with thermal heat-activated ( HANT ) and superelastic ( SE ) nickel-titanium archwires . METHOD AND MATERIAL S Thirty subjects ( 11 males , 19 females ; range , 11 to 26 years of age ) were recruited . Metal brackets were bonded in the maxillary or m and ibular arch . Round 0.016-inch HANT or 0.016-inch SE archwires were r and omly placed and tied with elastic ligatures . Each patient was invited to score tooth pain for 7 days at different time points ( 8:00 , 12:00 , 16:00 , 20:00 , and 24:00 ) using the visual analog scale ( VAS ) . RESULTS In both groups , pain was highest at day 2 and lowest at day 7 . Patients with HANT archwires had significantly lower VAS scores ( P < .005 ) at days 2 , 3 , and 4 than subjects with SE archwires . This was also the case after adjusting for analgesic consumption , sports practicing , overlapping pain of different origin , and the concomitance of stressful events . The frequency of analgesic consumption was higher in the SE than in HANT group at day 3 ( P < .05 ) . No differences in pain perception were found between time points , nor was any correlation found between dental crowding and pain . No difference in pain perception was found between the maxillary and m and ibular dental arches . CONCLUSION Initial orthodontic pain is reduced when using HANT orthodontic archwires A r and omized controlled clinical trial was performed to compare the nature , prevalence , intensity , and duration of pain related to the use of a relatively recently developed superelastic arch wire and a more traditional multistr and ed steel arch wire . Other factors likely to influence the pain experience were also investigated . Forty-three subjects participated in the study , the pain response being assessed by each of the visual analogue scales , the question naires , and an analgesic consumption record . In 18 of the 43 subjects a st and ardized preliminary dental extraction procedure was used as a control . Subsequent to the r and om allocation of an initial arch wire in 43 patients , 22 of them underwent a second arch wire in the opposing arch , the wire again being determined by r and om allocation . It was found that the prevalence , intensity , and duration of pain after the insertion of the two types of wire was similar but much greater than in the post extraction control phase . The pain score peaked on the morning after the placement of the arch wire , lasting typically for 5 to 6 days . The pain and discomfort experienced after the insertion of the second arch wire was similar to that of the first , no conditioning response being evident . Overall a diurnal variation was found with a tendency to an increase in pain in the evenings and nights , although this did not greatly affect sleep . The pain response was found to be highly and consistently subjective , not related to the dental arch , crowding , sex , or social class ; however , a statistically significant association was found between the age and the pain experienced INTRODUCTION Our objective was to compare the effects of 2 preadjusted appliances on angular and linear changes of the m and ibular incisors , and transverse m and ibular arch dimensional changes over a minimum of 30 weeks . This was a prospect i ve , r and omized , controlled , clinical trial a the Royal London Hospital , School of Dentistry , in London and the Kent and Canterbury Hospital in Canterbury , United Kingdom . METHODS Sixty- six consecutive patients satisfying the inclusion criteria were enrolled and r and omly allocated to treatment with a self-ligating bracket system ( SmartClip , 3 M Unitek , Monrovia , Calif ) and conventional preadjusted edgewise brackets ( Victory , 3 M Unitek ) . Initial study models and cephalograms were obtained within a month of starting the trial . All subjects received treatment with the following archwire sequence : 0.016-in round , 0.017 x 0.025-in rectangular , 0.019 x 0.025-in rectangular martensitic active nickel-titanium archwires , and 0.019 x 0.025-in stainless steel archwires . Final records , including study models and a lateral cephalogram , were collected a minimum of 30 weeks after initial appliance placement . Lateral cephalograms were assessed for treatment-related changes in m and ibular incisor inclination and position . Transverse dimensional changes in intercanine , interpremolar , and intermolar dimensions , and the amount of crowding alleviated during the study period were assessed by comparison of pretreatment and posttreatment models . All measurements were made with a digital caliper ( 150 mm ISO 9001 electronic caliper , Tesa Technology , Renens , Switzerl and ) . RESULTS Sixty patients completed the study . After adjustment for pretreatment values , duration of treatment , and amount of crowding alleviated during the study period , bracket type had little effect on incisor inclination ( P = 0.437 ) and positional changes ( P = 0.35 ) , and intercanine ( P = 0.967 ) , inter-first premolar ( P = 0.495 ) , and inter-second premolar ( P = 0.905 ) dimensions . However , the self-ligating appliance produced slightly more expansion in the molar region , a difference that was statistically significant ( P = 0.009 ) . Pretreatment values for incisor inclination ( P = 0.044 ) and transverse dimensions ( P = 0.000 ) affected inclination and transverse changes , respectively , with proclination less likely when the labial segment was proclined at the outset and expansion unlikely during leveling and alignment in wider arches . Greater alleviation of crowding during the study period result ed in more incisor proclination ( P = 0.000 ) and advancement ( P = 0.000 ) . CONCLUSIONS There was little difference overall in the pattern of arch alignment and leveling related to the 2 preadjusted appliances . However , there was a statistically greater increase in intermolar width in the group treated with the self-ligating appliance , although the difference was only 0.91 mm OBJECTIVES To test the hypotheses that ( 1 ) there is no difference in the pain experience during the week following initial placement of two orthodontic appliances ( SmartClip and Victory ; 3 M Unitek , Monrovia , Calif ) ; and ( 2 ) there is no difference in the pain experience during removal and insertion of orthodontic archwires with these brackets . MATERIAL S AND METHODS Sixty-six consecutive patients were treated with a self-ligating bracket system ( SmartClip ) or a conventional appliance ( Victory ) on the basis of computer-generated r and om allocation . After appliance placement and engagement of a 0.016 ' ' nickel-titanium archwire , pain experience was recorded after 4 , 24 , and 72 hours and after 7 days with the use of a visual analog system ( VAS ) question naire . At a subsequent visit , participants documented pain experiences during removal and insertion of 0.019 x 0.025 ' ' archwires on an additional 100 mm VAS question naire . Independent t-tests and analyses of covariance were used to analyze normally distributed data ; the Mann-Whitney U-test was used for skewed distributions . RESULTS Forty-eight ( 72.2 % ) and fifty-one ( 77.3 % ) subjects completed the first and second parts of the study , respectively . Bracket type had no influence on pain experience at 4 hours ( P = .958 ) , 24 hours ( P = .289 ) , 72 hours ( P = .569 ) , and 7 days ( P = .756 ) following appliance placement . However , bracket type significantly influenced pain experience during archwire removal ( P = .001 ) and insertion ( P = .013 ) . CONCLUSIONS Hypothesis 1 can not be rejected . The bracket type had no effect on subjective pain experience during the first week after initial placement of two preadjusted orthodontic appliances . Hypothesis 2 was rejected . Significantly greater discomfort was experienced during archwire insertion and removal with the SmartClip appliance |
935 | 27,193,436 | Conclusion MRA benefits CKD patients in terms of LVMI , all-cause mortality , and MACEs with no incidence of severe hyperkalemia . | Background Mineralocorticoid receptor antagonists ( MRAs ) are used widely in treatment of heart failure , but their effects on cardiovascular complications and mortality of chronic kidney disease ( CKD ) are not well known .
Thus , we aim to assess such therapeutic effects of MRAs on CKD . | Although r and omized controlled trials have demonstrated benefits of aldosterone antagonists for patients with heart failure and reduced ejection fraction ( HFrEF ) , they excluded patients with serum creatinine > 2.5 mg/dl , and their use is contraindicated in those with advanced chronic kidney disease ( CKD ) . In the present analysis , we examined the association of spironolactone use with readmission in hospitalized Medicare beneficiaries with HFrEF and advanced CKD . Of the 1,140 patients with HFrEF ( EF < 45 % ) and advanced CKD ( estimated glomerular filtration rate [ eGFR ] < 45 ml/min/1.73 m(2 ) ) , 207 received discharge prescriptions for spironolactone . Using propensity scores ( PSs ) for the receipt of discharge prescriptions for spironolactone , we estimated PS-adjusted hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) for spironolactone-associated outcomes . Patients ( mean age 76 years , 49 % women , 25 % African-American ) had mean EF 28 % , mean eGFR 31 ml/min/1.73 m(2 ) , and mean potassium 4.5 mEq/L. Spironolactone use had significant PS-adjusted association with higher risk of 30-day ( HR 1.41 , 95 % CI 1.04 to 1.90 ) and 1-year ( HR 1.36 , 95 % CI 1.13 to 1.63 ) all-cause readmissions . The risk of 1-year all-cause readmission was higher among 106 patients with eGFR < 15 ml/min/1.73 m(2 ) ( HR 4.75 , 95 % CI 1.84 to 12.28 ) than among those with eGFR 15 to 45 ml/min/1.73 m(2 ) ( HR 1.34 , 95 % CI 1.11 to 1.61 , p for interaction 0.003 ) . Spironolactone use had no association with HF readmission and all-cause mortality . In conclusion , among hospitalized patients with HFrEF and advanced CKD , spironolactone use was associated with higher all-cause readmission but had no association with all-cause mortality or HF readmission Objectives : Hemodialysis patients have a cardiovascular mortality rate of 20–40 times that of the general population . Aldosterone inhibition by spironolactone has exerted beneficial , prognostically significant cardiovascular effects in patients with heart failure maintained on hemodialysis or peritoneal dialysis . Our aim was to investigate spironolactone 's effect in non heart failure hemodialysis patients . Methods : Fourteen stable chronic hemodialysis patients ( nine men ) , 59.5 ± 3.1 years of age were evaluated in a sequential , fixed-dose , placebo-controlled study . Heart failure was diagnosed on the basis of signs and symptoms of heart failure or left ventricular ejection fraction less than 50 % . Following an initial 4-month period of placebo administration after each dialysis , patients received spironolactone ( 25 mg thrice weekly after dialysis ) for the next 4 months . Data were recorded at baseline , at the end of placebo administration , and at the end of spironolactone treatment and included endothelial function by forearm reactive hyperemia during venous occlusion plethysmography , cardiac autonomic status by heart rate variability in the time and frequency domain , blood pressure response , and echocardiographic and laboratory data . Results : Placebo induced no changes in the aforementioned parameters . Following spironolactone , salutary effects were observed in the extent and duration of reactive hyperemia ( P < 0.05 for both ) , as well as in heart rate variability ( P < 0.05 ) and blood pressure control ( P < 0.05 ) . No changes occurred in echocardiographically derived left ventricular dimensions or mass . Conclusion : Low-dose spironolactone therapy in clinical ly stable non heart failure hemodialysis patients is associated with favorable effects on cardiovascular parameters known to adversely affect survival , such as endothelial dysfunction and heart rate variability . Spironolactone treatment might benefit long-term cardiovascular outcome of such patients We performed this study to assess whether low dose spironolactone could be administered in hemodialysis ( HD ) patients with moderate to severe heart failure to improve cardiovascular function and reduce hospitalization without inducing hyperkalemia . We enrolled 16 chronic HD patients with moderate to severe heart failure and left ventricle ejection fraction : 5 45 % . In a double blinded r and omized placebo controlled study , one group of 8 patients received 25 mg of spironolactone after each dialysis session within six months , and the rest received a placebo . Echocardiography was performed on all the patients to assess ejection fraction and left ventricular mass during 12 hours after completion of hemodialysis at the beginning and the end of study . Serum potassium was measured predialysis every 4 weeks . The mean ejection fraction increased significantly more in spironolactone group during the study period than in the placebo group ( 6.2 + /- 1.64 vs. 0.83 + /- 4.9 , P= 0.046 ) . The mean left ventricular mass decreased in the spironolactone group , but increased significantly in the placebo group during the period ( -8.4 + /- 4.72 vs. 3 + /- 7.97 . 95 % , P= 0.021 ) . The incidence of hyperkalemia was not significantly increased in the study or controlled groups . In conclusion , we found in this study that administration of spironolactone in chronic HD patients with moderate to severe heart failure substantially improved their cardiac function and decreases left ventricular mass without development of significant hyperkalemia Aims Mineralocorticoid receptor antagonists ( MRAs ) improve outcomes in patients with heart failure and reduced left ventricular ejection fraction ( HFrEF ) , but their use is limited by hyperkalaemia and /or worsening renal function ( WRF ) . BAY 94 - 8862 is a highly selective and strongly potent non-steroidal MRA . We investigated its safety and tolerability in patients with HFrEF associated with mild or moderate chronic kidney disease ( CKD ) . Methods and results This r and omized , controlled , phase II trial consisted of two parts . In part A , the safety and tolerability of oral BAY 94 - 8862 [ 2.5 , 5 , or 10 mg once daily ( q.d . ) ] was assessed in 65 patients with HFrEF and mild CKD . In part B , BAY 94 - 8862 ( 2.5 , 5 , or 10 mg q.d . , or 5 mg twice daily ) was compared with placebo and open-label spironolactone ( 25 or 50 mg/day ) in 392 patients with HFrEF and moderate CKD . BAY 94 - 8862 was associated with significantly smaller mean increases in serum potassium concentration than spironolactone ( 0.04–0.30 and 0.45 mmol/L , respectively , P < 0.0001–0.0107 ) and lower incidences of hyperkalaemia ( 5.3 and 12.7 % , respectively , P = 0.048 ) and WRF . BAY 94 - 8862 decreased the levels of B-type natriuretic peptide ( BNP ) , amino-terminal proBNP , and albuminuria at least as much as spironolactone . Adverse events related to BAY 94 - 8862 were infrequent and mostly mild . Conclusion In patients with HFrEF and moderate CKD , BAY 94 - 8862 5–10 mg/day was at least as effective as spironolactone 25 or 50 mg/day in decreasing biomarkers of haemodynamic stress , but it was associated with lower incidences of hyperkalaemia and WRF ESRD treated with dialysis is associated with increased left ventricular hypertrophy , which , in turn , is related to high mortality . Mineralocorticoid receptor antagonists improve survival in patients with chronic heart failure ; however , the effects in patients undergoing dialysis remain uncertain . We conducted a multicenter , open-label , prospect i ve , r and omized trial with 158 patients receiving angiotensin-converting enzyme inhibitor or angiotensin type 1 receptor antagonist and undergoing peritoneal dialysis with and without ( control group ) spironolactone for 2 years . As a primary endpoint , rate of change in left ventricular mass index assessed by echocardiography improved significantly at 6 ( P=0.03 ) , 18 ( P=0.004 ) , and 24 ( P=0.01 ) months in patients taking spironolactone compared with the control group . Rate of change in left ventricular ejection fraction improved significantly at 24 weeks with spironolactone compared with nontreatment ( P=0.02 ) . The benefits of spironolactone were clear in patients with reduced residual renal function . As secondary endpoints , renal Kt/V and dialysate-to-plasma creatinine ratio did not differ significantly between groups during the observation period . No serious adverse effects , such as hyperkalemia , occurred . In this trial , spironolactone prevented cardiac hypertrophy and decreases in left ventricular ejection fraction in patients undergoing peritoneal dialysis , without significant adverse effects . Further studies , including those to determine relative effectiveness in women and men and to evaluate additional secondary endpoints , should confirm these data in a larger cohort Background Patients with chronic kidney disease ( CKD ) have high cardiovascular mortality and morbidity associated with increased arterial stiffness . Plasma aldosterone levels are increased in CKD , and aldosterone has been found to increase vascular inflammation and fibrosis . It was hypothesized that aldosterone receptor inhibition with eplerenone could reduce arterial stiffness in CKD stage 3–4 . Study Design The design was r and omized , open , parallel group . Measurements of arterial stiffness markers were undertaken at weeks 1 and 24 . Intervention 24 weeks of add-on treatment with 25–50 mg eplerenone or st and ard medication . Outcomes Primary outcome parameter was carotid-femoral pulse wave velocity ( cfPWV ) . Secondary outcomes were augmentation index ( AIx ) , ambulatory arterial stiffness index ( AASI ) and urinary albumin excretion . Results Fifty-four CKD patients ( mean eGFR 36 mL/min/1.73 m2 , SD 11 ) were r and omized . Forty-six patients completed the trial . The mean difference in cfPWV changes between groups was 0.1 m/s ( 95%CI : −1.0 , 1.3 ) , P = 0.8 . The mean difference in AIx changes between groups was 4.4 % ( 0.1 , 8.6 ) , P = 0.04 . AASI was unchanged in both groups . The ratio of change in urinary albumin excretion in the eplerenone group compared to the control was 0.61 ( 0.37 , 1.01 ) , P = 0.05 . Four patients were withdrawn from the eplerenone group including three because of possible side effects ; one was withdrawn from the control group . Mild hyperkalemia was seen on three occasions and was easily managed . Limitations The full planned number of patients was not attained . The duration of the trial may have been too short to obtain full effect of eplerenone on the arteries . Conclusions Add-on treatment with eplerenone in CKD stage 3–4 did not significantly reduce cfPWV . There may be beneficial vascular effects leading to attenuated pulse wave reflection . Treatment was well-tolerated . Trial Registration Clinical Trials.gov OBJECTIVES This study investigated the influence of baseline and worsening renal function ( WRF ) on the efficacy of spironolactone in patients with severe heart failure ( HF ) . BACKGROUND Renal dysfunction or decline in renal function is a known predictor of adverse outcome in patients with HF , and treatment decisions are often on the basis of measures of renal function . METHODS We used data from the RALES ( R and omized Aldactone Evaluation Study ) in 1,658 patients with New York Heart Association functional class III or IV HF and an ejection fraction < 35 % . Participants were r and omized to spironolactone 25 mg , which could be titrated to 50 mg , or placebo daily . Renal function ( estimated glomerular filtration rate [ eGFR ] ) was estimated by the Modification of Diet in Renal Disease equation . Worsening renal function was defined as a 30 % reduction in eGFR from baseline to 12 weeks post-r and omization . RESULTS Individuals with reduced baseline eGFR exhibited similar relative risk reductions in all-cause death and the combined endpoint of death or hospital stays for HF as those with a baseline eGFR > 60 ml/min/1.73 m(2 ) and greater absolute risk reduction compared with those with a higher baseline eGFR ( 10.3 % vs. 6.4 % ) . Moreover , WRF ( 17 % vs. 7 % for spironolactone and placebo groups , p < 0.001 ) was associated with an increased adjusted risk of death in the placebo group ( hazard ratio : 1.9 , 95 % confidence interval : 1.3 to 2.6 ) but not in those r and omized to spironolactone ( hazard ratio : 1.1 , 95 % confidence interval : 0.79 to 1.5 , p interaction = 0.009 ) . The risk of hyperkalemia and renal failure was higher in those with worse baseline renal function and those with WRF , particularly in the spironolactone arm , but the substantial net benefit of spironolactone therapy remained . CONCLUSIONS The absolute benefit of spironolactone was greatest in patients with reduced eGFR . Worsening renal function was associated with a negative prognosis , yet the mortality benefit of spironolactone was maintained BACKGROUND AND OBJECTIVES Hemodialysis patients ( HD ) display high rates of cardiac diseases and mortality . In chronic kidney disease , vascular injury leads to coronary artery disease , heart failure , and stroke . Carotid intima-media thickness ( CIMT ) measurements are currently widely used in r and omized controlled trials ( RCTs ) to study the efficacy of interventions . An RCT was design ed for the assessment of the safety and effectiveness of spironolactone to inhibit the progression of CIMT in HD patients as a primary outcome . Secondary outcomes included measurements of plasma potassium . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS HD patients were r and omly assigned to receive 50 mg spironolactone or placebo thrice weekly after dialysis . In between dialysis sessions , plasma potassium concentrations were measured every month . Ultrasonographic measurements of CIMT were done at the beginning of the study and after 2 years . RESULTS Fifty-three age- and sex-adjusted patients ( 30 with drug and 23 with placebo ) successfully completed the trial . There were no significant differences between the two groups in all profiles studied at baseline . Measurements of CIMT after 2 years showed a progression in the placebo group , whereas in the spironolactone group a significant decrease or even reversed CIMT was observed . Progression rates ( mm/yr ) were : common carotid , placebo : 0.06 + /- 0.07 , spironolactone : 0.01 + /- 0.04 ; carotid bifurcation , placebo : 0.15 + /- 0.27 , spironolactone : 0.0001 + /- 0.01 ; internal carotid , placebo : 0.10 + /- 0.12 , spironolactone : -0.10 + /- 0.15 . No episodes of hyperkalemia were observed , but a slight increase in plasma potassium was found in the spironolactone group . CONCLUSIONS Fifty milligrams of spironolactone thrice weekly significantly reduced the progression of CIMT in HD patients The purpose of this 2-year multicentric , r and omized , placebo-controlled study was to evaluate the long-term effects and adverse effects of spironolactone on chronic dialysis patients . A total of 253 non-heart failure dialysis patients with end-stage renal disease were r and omly assigned to 2-year treatment with spironolactone ( 25 mg once daily , n=125 ) or a matching placebo ( n=128 ) as add-on therapy . The primary outcome was a composite of death from cardiocerebrovascular ( CCV ) events , aborted cardiac arrest , and sudden cardiac death , and the secondary outcome was death from all causes . Other CCV-related indexes such as left ventricular mass index , left ventricular ejection fraction , heart rate variability , vascular endothelial function , and blood pressure-lowering effect were analyzed for patients who completed the whole 2-year follow-up study . Sociodemographic , clinical , and relevant laboratory data were also collected . During the 2-year follow-up , the primary outcome occurred less frequently in the spironolactone group vs the control group ( 7.2 % vs 18.0 % ; adjusted hazard ratio [ HR ] , 0.42 ; 95 % confidence interval [ CI ] , 0.26 - 0.78 ) . Death from CCV events occurred in 4.0 % of patients in the spironolactone group and in 11.7 % of patients in the control group . Neither aborted cardiac arrest nor sudden cardiac death was significantly reduced by spironolactone treatment . The secondary outcome occurred less frequently in the spironolactone group vs the control group ( 9.6 % vs 19.5 % ; adjusted HR , 0.52 ; 95 % CI , 0.29 - 0.94 ) . Other CCV-related indexes except for heart rate variability were significantly improved . This study demonstrates that use of low-dose spironolactone in non-heart failure dialysis patients can effectively reduce the risks of both CCV morbidity and mortality with few side effects . Moreover , the beneficial effect was mediated through improving the endothelial function or reducing left ventricular size independent of blood pressure changes , rather than mediation through changes in salt or potassium h and ling in the kidney BACKGROUND AND OBJECTIVES Mineralocorticoid receptor antagonism reduces morbidity and mortality in patients with heart failure , but the safety of these drugs in patients receiving dialysis is unclear . This study evaluated whether hyperkalemia and /or hypotension limited the use of eplerenone , a selective mineralocorticoid receptor antagonist , in hemodialysis patients . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS This was a r and omized controlled trial of prevalent patients receiving hemodialysis at five Canadian centers . Participants were r and omly allocated to 13 weeks of eplerenone titrated to 50 mg daily ( n=77 ) or a matching placebo ( n=77 ) . The primary outcome was permanent discontinuation of the drug because of hyperkalemia or hypotension . Secondary outcomes included hyperkalemia , hypotension , and cardiovascular events . RESULTS Seventy-five eplerenone-treated patients and 71 placebo-treated patients were included in the per protocol population . The primary outcome occurred in three patients ( 4.0 % ) in the eplerenone group and two ( 2.8 % ) in the placebo group , for an absolute risk difference of 1.2 percentage points ( 95 % confidence interval , -4.7 to 7.1 percentage points ) . Eplerenone was interpreted as noninferior to placebo with respect to the primary outcome ( i.e. , a discontinuation rate for these reasons > 10 % was excluded ) . In the eplerenone group , nine patients ( 11.7 % ) developed hyperkalemia ( potassium level > 6.5 mEq/L ) , compared with two patients ( 2.6 % ) in the placebo group ( relative risk , 4.5 ; 95 % confidence interval , 1.0 to 20.2 ) . There was no significant effect on predialysis or postdialysis BP . CONCLUSION Eplerenone increased the risk of hyperkalemia but did not result in an excess need to permanently discontinue the drug . Further trials are required to determine whether mineralocorticoid receptor antagonism improves cardiovascular outcomes in patients receiving long-term dialysis BACKGROUND AND OBJECTIVES Although left ventricular hypertrophy ( LVH ) is a characteristic finding in hemodialysis ( HD ) population s , few risk factors for progressive LVH have been identified . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS As part of a multinational , blinded , r and omized , controlled trial that demonstrated no effect of hemoglobin targets on LV size , 596 incident HD patients , without symptomatic cardiac disease or cardiac dilation , had baseline echocardiograms within 18 months of starting dialysis and subsequently at 24 , 48 , and 96 weeks later . A wide array of baseline risk factors were assessed , as were BP and hemoglobin levels during the trial . RESULTS The median age and duration of dialysis were 51.5 years and 9 months , respectively . LV mass index ( LVMI ) rose substantially during follow-up ( 114.2 g/m(2 ) at baseline , 121 at week 48 , 123.4 at week 48 , and 128.3 at week 96 ) , as did fractional shortening , whereas LV volume ( 68.7 , 70.1 , 68.7 , and 68.1 ml/m(2 ) ) and E/A ratio remained unchanged . At baseline , the only multivariate associations of LVMI were gender and N terminal pro-B type natriuretic peptide . Comparing first and last echocardiograms in those without LVH at baseline , independent predictors of increase in LVMI were higher time-integrated systolic BP and cause of ESRD . An unadjusted association between baseline LVMI and subsequent cardiovascular events or death was eliminated by adjusting for age , diabetes , systolic BP , and N terminal pro-B type natriuretic peptide . CONCLUSIONS Progressive concentric LVH and hyperkinesis occur in HD patients , which is partly explained by hypertension but not by a wide array of potential risk factors , including anemia Congestive heart failure ( CHF ) is frequent in patients with chronic renal failure , and may contribute to high cardiovascular morbidity and mortality . There is little data in the literature about the safety and efficacy of use of spironolactone in patients with end-stage renal disease with heart failure . In this study , we evaluated the safety and efficacy of spironolactone in patients on continuous ambulatory peritoneal dialysis ( CAPD ) with CHF . This r and omized prospect i ve double-blind placebo-controlled clinical trial was performed at the St. Al-Zahra peritoneal dialysis center . Eighteen CAPD patients with New York Heart Association ( NYHA ) class III or IV heart failure , ejection fraction ( EF ) ≤45 % , serum potassium level ≤5.5 mEq/L and who were eligible , were r and omly assigned to taking either spironolactone ( 25 mg every other day ) or placebo for six months . The serum potassium was measured monthly and echocardiography was repeated at the end of the study period . The serum potassium levels rose in both groups , and there was no statistically significant difference intragroup and between the groups during the study period . Only in one patient in the spironolactone group did the serum potassium level reach above the critical level ( 5.70 mEq/L ) at the end of the second month of study , necessitating patient exclusion . The EF did not change significantly in the placebo group ( 33.3 ± 11.7 vs. 34.2 ± 11.6 , F = 1 , P = 0.363 ) , but in the spironolactone group the EF rose significantly ( 25.7 ± 7.3 vs. 33.3 ± 7.8 , F = 27.45 , P = 0.002 ) . Our study suggests that spironolactone could be used in CHF patients on CAPD to improve their cardiac function , but close monitoring of their serum potassium level is required OBJECTIVES Whether the spironolactone treatment remains effective for the prevention of atrial fibrillation ( AF ) in dialysis patients is unclear . METHODS We used a data base from the Registry for Catastrophic Illness from the National Health Research Institute . All dialysis patients aged 18 or older without history of AF before ESRD were incorporated . A total of 113,191 dialysis patients were enrolled in the study . The median follow-up time was 4.17 years . We collected information on prescribed drug dosage , number of days of treatment and the total number of pills dispensed from the outpatient pharmacy prescription data base . All individuals in the study cohort with the first occurrence of AF were included as cases . RESULTS In spironolactone group , the incidence of developing new AF was significantly lower than that in the control group both before ( 0.8 % vs. 3.3 % , P=0.019 ) and after PS matching ( 1.2 % vs. 3.0 % , P=0.019 ) . Before PS matching , Cox 's proportional hazard regression analyses showed that spironolactone was associated with 60 % reduction of new AF ( HR=0.372 [ 0.200 - 0.692 ] , P=0.002 ) and the protective effect is dose-responsive in accumulated dose , treatment duration and mean daily dose . After PS matching , the overall AF prevention effect remained significant ( HR=0.400 [ 0.179 - 0.895 ] , P=0.026 ) while the dose-response relationship became borderline significant . Subgroup analyses showed that the protective effect was more evident in some specific subgroup patients . CONCLUSION Our study showed that spironolactone therapy was associated with lower risk of developing AF in a dose-responsive manner in patients with dialysis . Further r and omized study is needed to confirm this observation Objectives : There is recent evidence that aldosterone play a role in the pathogenesis of cardiovascular disease in dialysis patients , which leads to the opportunity to block its actions for the benefit of these patients . In nondialytic chronic kidney disease , spironolactone was safe and effective in reducing left ventricular hypertrophy . However , routine use has been precluded in hemodialysis patients due to the risk of hyperkalemia . The aim of this study is to verify the safety and efficacy in regression of left ventricular hypertrophy with spironolactone in hemodialysis patients undergoing pharmacotherapeutic monitoring . Methods : We performed a controlled , r and omized , double blind study evaluating 17 hemodialysis patients who received spironolactone at a dose of 12.5 mg titrated , in the second week , to 25 mg of spironolactone or placebo . The patients were treated for 6 months . Results : The groups were composed of eight patients ( intervention ) and nine patients ( control ) . These groups did not differ in their baseline characteristics . The group receiving spironolactone had a left ventricular mass index reduction from 77 ± 14.6 g/m2.7 to 69 ± 10.5 g/m2.7 , p < 0.04 , whereas in placebo group there was an increase from 71 ± 14.2 g/m2.7 to 74 ± 17.4 g/m2.7 . Systolic or diastolic blood pressure did not change during the study . Potassium did not differ statistically between groups in all instances . Conclusion : Spironolactone treatment in hemodialysis patients was secure and effective in regression of left ventricular hypertrophy , a major risk factor for cardiovascular events in these patients . This effect occurred in spite of blood pressure stability . Trial registration : Clinical Trials.gov identifier BACKGROUND AND METHODS Aldosterone is important in the pathophysiology of heart failure . In a doubleblind study , we enrolled 1663 patients who had severe heart failure and a left ventricular ejection fraction of no more than 35 percent and who were being treated with an angiotensin-converting-enzyme inhibitor , a loop diuretic , and in most cases digoxin . A total of 822 patients were r and omly assigned to receive 25 mg of spironolactone daily , and 841 to receive placebo . The primary end point was death from all causes . RESULTS The trial was discontinued early , after a mean follow-up period of 24 months , because an interim analysis determined that spironolactone was efficacious . There were 386 deaths in the placebo group ( 46 percent ) and 284 in the spironolactone group ( 35 percent ; relative risk of death , 0.70 ; 95 percent confidence interval , 0.60 to 0.82 ; P<0.001 ) . This 30 percent reduction in the risk of death among patients in the spironolactone group was attributed to a lower risk of both death from progressive heart failure and sudden death from cardiac causes . The frequency of hospitalization for worsening heart failure was 35 percent lower in the spironolactone group than in the placebo group ( relative risk of hospitalization , 0.65 ; 95 percent confidence interval , 0.54 to 0.77 ; P<0.001 ) . In addition , patients who received spironolactone had a significant improvement in the symptoms of heart failure , as assessed on the basis of the New York Heart Association functional class ( P<0.001 ) . Gynecomastia or breast pain was reported in 10 percent of men who were treated with spironolactone , as compared with 1 percent of men in the placebo group ( P<0.001 ) . The incidence of serious hyperkalemia was minimal in both groups of patients . CONCLUSIONS Blockade of aldosterone receptors by spironolactone , in addition to st and ard therapy , substantially reduces the risk of both morbidity and death among patients with severe heart failure BACKGROUND Mineralocorticoid antagonists improve survival among patients with chronic , severe systolic heart failure and heart failure after myocardial infa rct ion . We evaluated the effects of eplerenone in patients with chronic systolic heart failure and mild symptoms . METHODS In this r and omized , double-blind trial , we r and omly assigned 2737 patients with New York Heart Association class II heart failure and an ejection fraction of no more than 35 % to receive eplerenone ( up to 50 mg daily ) or placebo , in addition to recommended therapy . The primary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure . RESULTS The trial was stopped prematurely , according to prespecified rules , after a median follow-up period of 21 months . The primary outcome occurred in 18.3 % of patients in the eplerenone group as compared with 25.9 % in the placebo group ( hazard ratio , 0.63 ; 95 % confidence interval [ CI ] , 0.54 to 0.74 ; P<0.001 ) . A total of 12.5 % of patients receiving eplerenone and 15.5 % of those receiving placebo died ( hazard ratio , 0.76 ; 95 % CI , 0.62 to 0.93 ; P=0.008 ) ; 10.8 % and 13.5 % , respectively , died of cardiovascular causes ( hazard ratio , 0.76 ; 95 % CI , 0.61 to 0.94 ; P=0.01 ) . Hospitalizations for heart failure and for any cause were also reduced with eplerenone . A serum potassium level exceeding 5.5 mmol per liter occurred in 11.8 % of patients in the eplerenone group and 7.2 % of those in the placebo group ( P<0.001 ) . CONCLUSIONS Eplerenone , as compared with placebo , reduced both the risk of death and the risk of hospitalization among patients with systolic heart failure and mild symptoms . ( Funded by Pfizer ; Clinical Trials.gov number , NCT00232180 . ) BACKGROUND S We investigated the relationship between spironolactone use and all-cause mortality in acute decompensated heart failure ( ADHF ) patients with severe renal dysfunction . The clinical benefit of spironolactone in the treatment of heart failure ( HF ) has been described in several large r and omized clinical trials . However , its clinical benefits have not been studied in hospitalized ADHF patients with severe renal dysfunction ( estimated glomerular filtration rate [ eGFR ] < 45 mL/min per 1.73 m(2 ) ) . METHODS AND RESULTS We retrospectively analyzed data from the Korean Heart Failure Registry . We included 1,035 ADHF patients with severe renal dysfunction . In Kaplan-Meier survival analysis , all-cause mortality in the spironolactone-treated group was significantly lower than that in the nonspironolactone group ( 18.1 % vs 24.9 % , respectively , log rank P = .028 ) . However , spironolactone use was not an independent predictor after adjusting other HF risk factors ( hazard ratio 0.974 , 95 % CI 0.681 - 1.392 , P = .884 ) and after propensity score matching ( P = .115 ) . In subgroup analysis , the clinical benefit of spironolactone use was preserved in women , prehospital spironolactone use , the chronic kidney disease stage 3b ( eGFR 30 - 44 mL/min per 1.73 m(2 ) ) , and the appropriate spironolactone use ( eGFR ≥30 mL/min per 1.73 m(2 ) and K ≤5.0 mmol/L ) . CONCLUSION The spironolactone therapy was not beneficial in ADHF patients with severe renal dysfunction after multivariable adjusting and propensity score matching . However , we reassured the current HF guidelines for spironolactone use and the clinical benefit in chronic kidney disease stage 3b should be assessed in future clinical trial OBJECTIVES We sought to determine whether the addition of spironolactone to angiotensin-converting enzyme ( ACE ) inhibitors and angiotensin receptor blockers ( ARBs ) improves left ventricular mass and arterial stiffness in early-stage chronic kidney disease ( CKD ) . BACKGROUND Chronic kidney disease is associated with a high risk of cardiovascular disease and a high prevalence of left ventricular hypertrophy and arterial stiffness that confer an adverse prognosis . It is believed that these abnormalities are in part a result of activation of the renin-angiotensin-aldosterone system . METHODS After an active run-in phase with spironolactone 25 mg once daily , 112 patients with stage 2 and 3 CKD with good blood pressure control ( mean daytime ambulatory blood pressure < 130/85 mm Hg ) on established treatment with ACE inhibitors or ARBs were r and omized to continue spironolactone or to receive a matching placebo . Left ventricular mass ( cardiac magnetic resonance ) and arterial stiffness ( pulse wave velocity/ analysis , aortic distensibility ) were measured before run in and after 40 weeks of treatment . RESULTS Compared with placebo , the use of spironolactone result ed in significant improvements in left ventricular mass ( -14 + /- 13 g vs. + 3 + /- 11 g , p < 0.01 ) , pulse wave velocity ( -0.8 + /- 1.0 m/s vs. -0.1 + /- 0.9 m/s , p < 0.01 ) , augmentation index ( -5.2 + /- 6.1 % vs. -1.4 + /- 5.9 % , p < 0.05 ) , and aortic distensibility ( 0.69 + /- 0.86 x 10(-3 ) mm Hg vs. 0.04 + /- 1.04 x 10(-3 ) mm Hg , p < 0.01 ) . CONCLUSIONS The use of spironolactone reduces left ventricular mass and improves arterial stiffness in early-stage CKD . These effects suggest that aldosterone exerts adverse cardiovascular effects in CKD and that spironolactone is worthy of further study as a treatment that could reduce adverse cardiovascular events . ( Is Spironolactone Safe and Effective in the Treatment of Cardiovascular Disease in Mild Chronic Renal Failure ; NCT00291720 ) OBJECTIVES This study sought to assess whether spironolactone treatment reduces the high incidence of cardiovascular and cerebrovascular ( CCV ) morbidity and mortality in hemodialysis ( HD ) patients . BACKGROUND Aldosterone receptor blockers reduce cardiac-related events , but the efficacy of the agents in HD patients is unclear . METHODS A 3-year r and omized trial involving 5 clinics was performed . Of the 309 oligoanuric HD patients enrolled in the study , 157 patients were r and omly assigned to receive 25 mg/day of spironolactone without any restriction on dietary potassium intake ( treatment group ) , and 152 patients were assigned to a control group . The primary outcome was a composite of death from CCV events or hospitalization for CCV events , and the secondary outcome was death from all causes . RESULTS During the 3-year follow-up , the primary outcome occurred in 5.7 % of patients in the treatment group and in 12.5 % of patients in the control group . Hazard ratios ( HRs ) for the primary outcome for treatment were 0.404 ( 95 % confidence interval [ CI ] : 0.202 to 0.809 ; p = 0.017 ) and 0.379 ( 95 % CI : 0.173 to 0.832 ; p = 0.016 ) before and after adjustment , respectively . The secondary outcome was significantly reduced in the treatment group compared with the control group ( 6.4 % vs. 19.7 % ; HRs : 0.355 [ 95 % CI : 0.191 to 0.662 ; p = 0.002 ] and 0.335 [ 95 % CI : 0.162 to 0.693 ; p = 0.003 ] before and after adjustment , respectively ) . Gynecomastia or breast pain was reported in 16 patients ( 10.2 % ) in the treatment group . Serious hyperkalemia led to treatment discontinuation in 3 patients ( 1.9 % ) . CONCLUSIONS Aldosterone receptor blockade using spironolactone may substantially reduce the risk of both CCV morbidity and death among HD patients ; however , larger-scale studies are recommended to further confirm its efficacy . ( Effects of Spironolactone on Cardio- and Cerebrovascular Morbidity and Mortality in Hemodialysis Patients ; NCT01687699 ) |
936 | 15,857,879 | Extended interval dosing of aminoglycosides in neonates is safe and effective , with a reduced risk of serum drug concentrations outside the therapeutic range | OBJECTIVES To review the evidence from controlled clinical trials of neonates given equal daily aminoglycoside doses as extended interval dosing ( dosage interval typically 24 hours in term and 36 - 48 hours in immature neonates ) compared with traditional dosing ( dosage interval typically 8 - 12 hours in term and 12 - 24 hours in immature neonates ) . | OBJECTIVE To compare the efficacy of once daily gentamicin administration to the conventional twice daily dosage schedule by estimation of serum gentamicin concentrations ( SGC ) in neonates . DESIGN R and omized controlled trial . SETTING Medical college hospital . SUBJECTS Seventy three neonates of gestational age>32 weeks at risk or with clinical features of sepsis . METHODS The subjects were divided into preterm and term groups . Babies in each of these groups were r and omized to receive a single daily dose ( 4 mg/kg ) or a twice daily dose ( 2.5 mg/kg ) of injection gentamicin intravenously . Trough and peak SGC were estimated half an hour prior and one hour after the second dose . Statistical analysis was done using the equivalence method . RESULTS In preterm as well as term babies , the mean peak and trough gentamicin levels were comparable in the two regimens . There is statistically significant evidence to show that the effect of once daily and twice daily dosage is similar . CONCLUSION Once daily gentamicin administration is as effective as twice daily therapy and would be more cost effective This article reports the results of a four-year follow-up study initiated in 1970 on the long-term effects of gentamicin and kanamycin use in newborn infants . Audiometric , vestibular , and psychometric evaluations were performed on gentamicin-treated , kanamycin-treated , and untreated , matched control infants and children . No substantial sensorineural hearing loss or vestibular dysfunction was identified in these patients that could be attributed to aminoglycoside therapy . Performances on the Illinois Test of Psycholinguistic Abilities , Beery Test of Visual Motor Integration , the Peabody Picture Vocabulary Test , and on fine and gross motor examinations were comparable for the three study groups Fifty-four neonates were included and completed the study . Twenty-seven neonates were given 2.0 - 2.5 mg/kg of gentamicin twice daily while 27 neonates were given 4.0 - 5.0 mg/kg of gentamicin once daily . The twice daily dose and the once daily dose group had mean steady state gentamicin peak concentrations of 5.94 + /- 1.57 mg/l and 8.92 + /- 1.59 mg/l , respectively ( p<0.05 ) while their trough concentrations were 1.44 + /- 0.49 mg/l and 0.90 + /- 0.35 mg/l , respectively ( p<0.05 ) . There were 3 neonates ( 11.11 % ) in the twice daily dose group whose peak and trough level were not within the desirable therapeutic range , two patients with too high trough level ( > 2 mg/l ) and one with subtherapeutic peak level ( < 4 mg/l ) . Only one patient in the once daily group had undesirable trough level that was higher than 1.5 mg/l but less than 2 mg/l . Treatment with a once daily dose did not present more nephrotoxity than a twice daily dose regimen and had the tendency to have less effect on renal function . Once daily dosage can achieve the equivalent efficacy compared to a twice-daily dosage regimen . All neonates in twice daily and once daily dosage groups showed improvement in clinical outcome . Therefore , a once daily dose of gentamicin with 4.0 - 5.0 mg/kg could be an appropriate regimen in term neonates during the first 7 days of life . This regimen produces peak concentration that may have greater clinical efficacy and trough concentration with less toxicity than conventional dosing regimen Neonates , especially preterms , are known to have low glomerular filtration rates ( GFR ) . This may result in elevated trough concentrations during multiple administration of aminoglycosides ( AGs ) , potentially leading to nephro- and ototoxic reactions . The once-daily administration ( q.d . ) of AGs has been shown to be equally or better tolerated in adults and children than the conventional schedules ( twice daily , b.i.d . ; thrice daily , t.i.d . ) , while offering potential pharmacodynamic and nursing advantages . No data , however , are available for neonates . As a consequence , this pilot study was conducted in order to assess the tolerance of the once-a-day administration of amikacin in comparison with the twice daily dose regimen , in relation to the pharmacokinetics of the drug under these two schedules . 22 Male neonates ( gestational age > or = 34 weeks ; postnatal age < or = 2 days ) were r and omized to receive amikacin ( AK ) ( 15 mg/kg/day ) q.d . ( n = 10 ) or b.i.d . ( n = 12 ) together with ampicillin ( 50 mg/kg/12 h ) . AK plasma levels were measured at days 1 , 3 , 5 and 7 of treatment just before the next dose ( trough level ) and 1 h after completion of infusion ( peak level ) and after 3 and 6 h only at day 1 . Due to the small size of the sample s , no difference in efficacy could be assessed and was not the aim per se . Glomerular dysfunction was assessed by creatinine clearance , and tubular injuries by the urinary excretion of proteins ( retinol binding protein , beta 2-microglobulin , clara cell protein ( P1 ) and microalbumin ) , enzymes ( N-acetyl-beta-D-glucosaminidase , alkaline phosphatase , alanine aminopeptidase , and gamma-glutamyltransferase ) , and total phospholipids ( TPL ) in urine . Ototoxicity was assessed by brainstem auditory evoked potentials ( BAEPs ) at days 0 , 3 and 9 of therapy . Eight healthy neonates served as controls . All patients showed a normal and similar increase of GFR during the first postnatal days . Proteinuria did not increase , but enzymuria and TPL increased significantly during the treatment in both AK groups without significant difference between groups . BAEPs at day 9 were not significantly different between treated and untreated patients . We conclude from this pilot study that , in the absence of more toxicity , the q.d . administration of AK in neonates of > or = 34 weeks of gestational age may be recommended over its bid schedule in view of its potential advantages In a prospect i ve , r and omized trial of once-daily versus twice-daily intravenous or intramuscular dosing with gentamicin , 11 neonates received 5.0 mg/kg once daily and 15 received 2.5 mg/kg twice daily for 2 ro 3 days . The once-daily intravenous dosing group and the twice-daily intravenous or intramuscular dosing group , respectively , had mean steady-state gentamicin peak concentrations of 10.7 versus 6.6 micrograms/ml ( p < 0.05 ) , 6-hour postdosing concentrations of 4.7 versus 2.8 micrograms/ml ( p < 0.05 ) , trough concentrations of 1.7 versus 1.7 micrograms/ml , elimination half-life of 8.8 versus 5.4 hours ( p < 0.05 ) , and volume of distribution at steady state of 0.67 versus 0.46 L/kg . No nephrotoxic effects were identified in any group . Once-daily gentamicin therapy with 5.0 mg/kg in neonates achieves peak serum levels that are more suitable for optimal bacterial killing than those which traditional regimens achieve . Similar trough levels suggest that even larger doses and longer dosing intervals may be ideal in term neonates OBJECTIVE : There is no uniformity in the current recommendations of dosing regimen of gentamicin for neonates . We conducted a prospect i ve , r and omized , controlled trial to compare a once-daily dosing regimen to the twice-daily dosing regimen for neonates ≥2500 g during the first 7 days after birth . STUDY DESIGN : Infants ≥2500 g admitted to the Neonatal Intensive Care Unit and prescribed gentamicin for suspected bacterial infection were r and omized to receive either 4 mg/kg every 24 hours , study group ( n=20 ) , or a st and ard regimen of 2.5 mg/kg every 12 hours , control group ( n=21 ) . Serum gentamicin concentrations ( SGCs ) were followed and gentamicin pharmacokinetics calculated on all infants . RESULTS : Peak SGC 30 minutes after the first dose was 8.2±1.7 μg/ml in the study group , compared to 6.4±1.5 μg/ml in the control group ( p=0.001 ) . Ninety-five percent of study group infants , compared to 81 % of the control group , had peak SGCs in therapeutic range after the first dose . Peak SGC at 48 hours ( steady state ) was 8.9±1.5 in the study group and 6.8±1.1 in the control group ( p=0.0001 ) . On further analysis , a significantly higher percentage of infants in the study group , compared to the control group , had peak SGCs in higher therapeutic ranges of 6 to 12 μg/ml as well as 8 to 12μg/ml . None of the study infants , compared to six control infants , had trough SGCs ≥2 μg/ml at steady state . Thus , none of the study group infants , versus six of the control group infants , needed a dosing adjustment at 48 hours ( p=0.02 , Fisher 's exact test ) . CONCLUSION : We found that 4 mg/kg gentamicin given every 24 hours achieved significantly higher peak SGCs and safe trough concentrations in all infants , compared to the twice-daily regimen of 2.5 mg/kg . We suggest that SGCs may not need to be followed in term infants prescribed a short course of this once-daily regimen for suspected early-onset sepsis if renal functions are normal Objective . We developed a simplified gentamicin dosing protocol for all neonates using a loading dose and once-daily dosing that would have an equal or lower incidence of toxicity and an equal or improved effectiveness compared with a regimen with no loading dose that included use of divided daily dosing . Methods . All neonatal intensive care unit patients with a postnatal age ≤7 days and started on gentamicin therapy at the discretion of the attending neonatologist were evaluated in this comparative cohort study . All peak and trough serum drug levels ( SDL ) , pertinent demographic data , and markers of potential nephrotoxicity , ototoxicity , and cure were tracked prospect ively during 132 consecutive , nonr and omized courses of therapy on a new gentamicin protocol . These were compared with data retrieved retrospectively throughout 103 consecutive , nonr and omized courses of therapy in a control group . Results . Initial measured peak SDL were higher ( 7.8 ± 1.1 μg/mL vs 6.1 ± 1.0 μg/mL ) and trough SDL were lower ( 0.9 ± 0.2 μg/mL vs 2.7 ± 0.6 μg/mL ) in the protocol term subset , compared with the control term subset ( gestational age , ≥37 weeks ; weight , ≥2500 g ) . One hundred percent of the initial and maintenance peak SDL in term protocol neonates were 5 to 12 μg/mL ; compared with 84 % of the initial and 61 % of maintenance peak SDL in the term control group . One hundred percent of the initial and maintenance trough SDL were in the desired range of < 2 μg/mL in term protocol neonates ; compared with 70 % of the initial and 94 % of maintenance trough SDL in the term control group . No significant differences were found in any SDL in low birth weight neonates ( gestational age < 37 weeks or weight < 2500 g and > 1500 g ) in the protocol compared with the control group . The very low birth weight ( weight < 1500 g ) protocol neonates had a significantly higher mean initial trough SDL ( 2.3 ± 0.7 μg/mL vs 1.5 ± 0.6 μg/mL ) and a lower incidence of initial trough SDL < 2.0 μg/mL ( 30 % vs 95 % ) than very low birth weight neonates in the control group . No differences were seen between groups in incidence of significant rise in serum creatinine or failure of hearing screen . Conclusion . A loading dose followed by once-daily dosing was shown to result in SDL in the safe and therapeutic range in all term neonates in this study . In low birth weight neonates , this regimen result ed in peak and trough SDL throughout therapy that were similar to those observed in the control group . Delaying the initiation of maintenance once-daily dosing until 36 to 48 hours after the loading dose would be expected to result in a higher incidence of initial trough SDL in target range for very low birth weight neonates Twenty full term neonates with suspected bacterial infection were r and omly assigned to a once daily or a twice daily dosage regimen with gentamicin ( 4 mg/kg/day ) . Concomitantly all patients were treated with ampicillin ( 200 mg/kg/day ) . The gentamicin concentration time curves were analysed by an open two compartment model under steady state conditions on day 4 of treatment . The mean theoretical maximum serum concentration in the group taking gentamicin once daily ( 10.9 micrograms/ml ) was significantly higher than in the group taking it twice daily ( 7.4 micrograms/ml ) . Potentially toxic serum concentrations were never reached . Mean trough concentrations were comparable in both groups ( once daily 0.8 micrograms/ml ; twice daily 1.0 micrograms/ml ) . Urinary alanine aminopeptidase excretion increased during and even two days after end of treatment in both groups without any significant differences . The results of the dynamic in vitro model revealed that both dosage schedules showed comparable bactericidal effects on pathogens inhibited by low concentrations of gentamicin like Escherichia coli and Staphylococcus aureus . However the once daily regimen was significantly superior in isolates with high minimal inhibitory concentrations Conventional interval dosing ( CID ) and extended interval dosing ( EID ) of gentamicin were compared in preterm infants . Gentamicin peak and trough levels , serum creatinine , urine output , and hearing screens were obtained in 40 preterm infants . Results suggest that EID is safe , provides gentamicin levels in desirable ranges ( peak , 5 to 12 microg/mL ; trough < 2 microg/mL ) , and reduces dosage adjustments OBJECTIVES To compare performance and cost analysis of two gentamicin regimens in infants > /=34 weeks ' gestation requiring antibiotics for a 72-hour rule-out sepsis evaluation . A once-daily dosing ( ODD ) regimen of 4 mg/kg was compared with a st and ard twice-daily dosing ( TDD ) regimen of 2.5 mg/kg every 12 hours . SETTING AND DESIGN Infants at two university-affiliated Level III nurseries were prospect ively temporally allocated to receive ODD ( n = 27 ) or TDD ( n = 28 ) as part of their 72-hour empirical antibiotic regimen . Performance of dosing regimens was based on target serum gentamicin concentrations ( SGC ) established prospect ively as a peak of 5 to 10 microgram/mL and a trough of < /=2 microgram/mL. SGC were determined by fluorescence polarization immunoassay on day 3 of therapy . Cost data were obtained by distributing a question naire to 15 pediatric pharmacy practice sites . Inquiries were made regarding hospital cost of drug acquisition , drug supplies , drug preparation and administration , and serum concentration analysis . Performance and cost data were then used to do a cost-effectiveness analysis . RESULTS Mean peak concentrations were higher with ODD ( 7.9 + /- 0.2 microgram/mL ) than TDD ( 6.7 + /- 0.3 microgram/mL ) . Half of the patients in the TDD group had trough concentrations > 2 microgram/mL , compared with none in the ODD group . Overall , 57 % of the SGCs in the TDD group were outside the target concentration range versus 7 % in the ODD group . Based on question naire results , a total 72-hour process cost of ODD versus TDD was compared for regimens with and without use of SGC analysis . If SGCs are obtained , more than 75 % of the cost associated with gentamicin therapy is attributable to SGC analysis . Based on a cost-effectiveness analysis , ODD was the dominant dosing strategy in all categories analyzed . CONCLUSIONS ODD of gentamicin at 4 mg/kg in neonates > /=34 weeks ' gestation is the preferable treatment strategy based on : 1 ) significantly improved SGC performance compared with TDD ; 2 ) elimination of the need for routine SGC collection in infants on short courses of therapy ; and 3 ) significant antibiotic-associated hospital cost savings when compared with conventional therapy of TDD and SGC analysis OBJECTIVE To compare the potentially toxic effects in fullterm neonates of amikacin administered once daily , versus amikacin administered twice daily . METHODOLOGY A controlled , r and omized , prospect i ve study in which one group of fullterm neonatal patients received amikacin 15 mg/kg per dose once daily ( n = 20 ) , and the other received amikacin 7.5 mg/kg per dose twice daily ( n = 20 ) . Impairment of renal glomerular function was defined as a decline of less than 50 % of the expected physiological drop in serum creatinine over time . Brainstem auditory evoked potentials were also evaluated and amikacin blood levels taken . RESULTS Fifteen patients in the once-daily group and 12 patients in the twice-daily group demonstrated at least one period of renal function impairment while in hospital . This decreased to five of 16 and four of 16 patients during follow-up . These differences were not statistically significant . Brainstem auditory evoked potentials did not find signs of ototoxicity at any time . CONCLUSION In fullterm neonatal patients , once daily dosing of amikacin is no more toxic than the twice daily regimen To determine the association of aminoglycoside levels with mortality from gram-negative bacteremia , we analyzed the case reports of patients from four prospect i ve , r and omized , and controlled clinical trials of gentamicin , tobramycin , and amikacin . Twelve ( 13.5 % ) of 89 patients died . One ( 2.4 % ) death occurred in 41 patients with early ( 1-hr postinfusion ) peak concentrations of greater than 5 micrograms/ml of gentamicin and tobramycin and of greater than 20 micrograms of amikacin/ml ; nine deaths ( 20.9 % ) occurred in 43 patients with lower concentrations . Five ( 8.3 % ) deaths occurred in 60 patients with mean peak concentrations for the entire course of therapy of greater than 5 micrograms/ml of gentamicin and tobramycin and of greater than 20 micrograms of amikacin/ml ; five ( 20.8 % ) deaths occurred in 24 patients with lower concentrations . Stepwise discriminant analysis showed that therapeutic early peak concentration was a significant factor in the presence of three other factors : severity of underlying illness , peak temperature , and initial leukocyte count . The results suggest the importance of achieving adequate early aminoglycoside levels in patients with gram-negative bacteremia OBJECTIVE To compare the peak and trough gentamicin concentrations in neonates after a once ( ODD ) vs. twice daily dosing ( TDD ) to establish the appropriate dosage for Thai neonates . MATERIAL AND METHOD Neonates of gestational age > or = 34 weeks , or body weight > or = 2000 g , suspected of having bacterial infection were r and omized to receive gentamicin intravenously , either 5 mg/kg every 24 hours or 2.5 mg/kg every 12 hours . The peak and trough serum gentamicin levels ( SGLs ) were measured . Serum creatinine cued nephrotoxicity . RESULTS Neonates were evaluated and baseline characteristics between the groups were compared . The ODD and TDD group had a mean gentamicin peak and trough concentration of 10.1 + /- 3.0 vs. 7.8 + /- 2.0 microg/ml ( p < 0.05 ) and 1.6 + /- 1.1 vs. 2.6 + /- 1.2 microg/ml ( p < 0.05 ) , respectively . The peak SGL of > or = 4 microg/ml was achieved in 100 % vs. 96 % of the ODD vs. TDD group , respectively . SGL troughs > or = 2 microg/ml were detected less often in the ODD group ( 22 % vs. 68 % , p < 0.05 ) . Abnormal change in serum creatinine was not observed in either group . CONCLUSION A once daily dose of gentamicin 5 mg/kg achieved a significantly higher peak SGL and safer trough than a twice-daily dose of 2.5 mg/kg albeit about a quarter of the ODD group had high troughs . A single daily dose of gentamicin 3.5 - 4 mg/kg/d in Thai neonates should be tested OBJECTIVE There is no uniformity in the current recommendations of dosing regimen of gentamicin for neonates . We conducted this study to compare once-daily dosing regimen to the twice-daily dosing regimen for neonates with birth weight of > /=2500 g during the first 7 days of life . METHODS Fifty full term infants with birth weight of > /=2500 gm admitted to the neonatal intensive care unit of King Abdul-Aziz University Hospital , Jeddah , Kingdom of Saudi Arabia between November 1999 to October 2000 and received gentamicin at a dose of 2.5 mg/kg every 12 hours ( control group ) were compared with 50 term infants who received gentamicin at dose of 4 mg/kg every 24 hours during the period of November 2000 until October 2002 ( protocol group ) . Trough and peak serum gentamicin levels ( SDL ) were measured on all infants . RESULTS Peak SDL was 8.4 + /- 1.8 mg/ml in the protocol group , compared to 6.7 + /- 2 mg/ml in the control group ( p=0.001 ) . Ninety-eight percent ( n=49 ) of the protocol group , compared to 86 % ( n=43 ) of the control group , had peak SDL in therapeutic range . Fifty-eight percent ( n=29 ) of infants in the protocol group , compared to 24 % ( n=12 ) of infants in the control group , had peak SDL in higher therapeutic range of 8 - 12 mg/ml . Six percent ( n=3 ) of the protocol infants , compared to 26 % ( n=13 ) of the control infants , had trough SDL > 2 mg/ml . Six infants ( 12 % ) in the protocol group , versus 20 infants ( 40 % ) of the control group , required a dosing adjustment . CONCLUSION Gentamicin dose of 4 mg/kg given at 24-hour interval achieved significantly higher peak and safe trough serum concentrations in term infants , compared to the twice-daily regimen of 2.5 mg/kg . We suggest that measurement of gentamicin concentration may be not required when once-daily regimen is prescribed for 72 hours to term infants with suspected sepsis |
937 | 28,819,018 | Compared with placebo , adjuvant alpha- , beta- and gamma-interferon were generally not significantly superior in terms of complete clearance over the short , intermediate or long term , nor with regard to intermediate- or long-term recurrence .
However , the low-dose subgroup of adjuvant alpha-interferon was significantly superior compared with placebo regarding intermediate-term complete clearance and recurrence .
No significant differences were seen in these comparisons regarding efficacy .
Overall , we found no reliable evidence favouring the systemic use of interferon after ablative treatment of AGW | Background Interferons are natural messenger proteins that are used to treat various disease entities .
Due to their immunomodulating , antiviral and antiproliferative effects , the systemic administration of interferons after ablative treatment for anogenital warts ( AGWs ) has been advocated to increase clearance and decrease recurrence rates .
However , studies investigating the efficacy of adjuvant systemic interferon have yielded inconsistent results .
The objective of this systematic review and meta- analysis was to comprehensively assess and evaluate the available evidence from r and omised controlled trials . | OBJECTIVE --To compare patient tolerance and treatment efficacy of subcutaneous interferon ( IFN ) alpha 2a plus cryotherapy versus cryotherapy alone in treatment of primary anogenital ( AG ) warts . DESIGN --R and omised placebo controlled observer blind study . Statistical analysis was by chi square and Mann Whitney U tests . PATIENTS --60 patients with newly diagnosed AG warts . INTERVENTION--29 and 31 patients were treated with subcutaneous IFN alpha 2a plus cryotherapy or placebo injections plus cryotherapy , respectively . MAIN OUTCOME MEASURES -- Clinical presence or absence of AG warts . Patients wart-free at 8 weeks were asked to re-attend at 12 weeks ; those with persistent warts at 8 weeks were withdrawn from the study . RESULTS --At 8 weeks 60.7 % ( 17/28 patients ) of the IFN group and 67.9 % ( 19/28 patients ) of the placebo group were clinical ly wart-free ( not significant ) ; corresponding figures at 12 week review were 29.6 % ( 8/27 patients ) and 40 % ( 10/25 patients ) respectively ( not significant ) . There was no difference in treatment response between males and females . Recurrence of warts at three month review , in patients cleared of warts at 8 weeks , was seen in 50 % ( 8/16 ) and 37.5 % ( 6/16 ) of patients in the IFN and placebo groups respectively ( not significant ) . Multiple warts and the presence of perianal/anal canal warts , either alone or concurrent with warts on the genitalia , at first clinic attendance , were adverse prognostic indicators ( p less than 0.001 , and p = 0.05 respectively ) . Cervical human papilloma virus ( HPV ) infection , exophytic or sub clinical , was present in 58.3 % and 77.2 % of females in the IFN and placebo groups respectively , at trial entry . Although these lesions were not directly treated , colposcopic resolution was seen in 12.5 % of affected women , in both treatment groups , by the end of the 7 week treatment period . Systemic side effects were significantly more common in the IFN than in the placebo group , 50 % versus 10.7 % of patients ( p less than 0.01 ) . Severe influenza like symptoms occurred , after the first three injections only , in one patient treated with IFN ; all other reported side effects were mild . CONCLUSIONS --Subcutaneous IFN alpha 2a combined with cryotherapy is no more effective than cryotherapy alone in the treatment of primary AG warts . The presence of multiple warts and perianal/anal canal warts are adverse prognostic indicators OBJECTIVE : To determine whether the combination of systemically administered interferon alpha-2a and ablative surgery for the treatment of genital and /or perianal warts produces a 30 % or greater improvement in lasting response rate compared with a control group receiving a combination of placebo and ablative therapy . DESIGN : R and omised , triple-blind , placebo-controlled trial using 1 or 3 MIU of interferon alpha-2a or placebo administered subcutaneously three times weekly for 10 weeks in combination with ablative surgery . SETTING : International , multicentre study in 10 genitourinary medicine clinics . PATIENTS : Two hundred and fifty patients with anogenital warts . MAIN OUTCOME MEASURES : Lasting response at week 38 . RESULTS : St and ard efficacy analysis at week 38 showed a lasting response in 51 % ( 35/68 ) of 3 MIU interferon-treated patients , 48 % ( 30/63 ) of 1 MIU interferon-treated patients and 43 % ( 29/67 ) of placebo-treated patients . CONCLUSIONS : With the doses and regime described , treatment with interferon alpha-2a in combination with ablative therapy is not significantly superior in the treatment of anogenital warts than placebo and ablative therapy In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias 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 OBJECTIVES --The primary objective was to determine if six weeks treatment with subcutaneous interferon alpha-2a ( IFN ) and podophyllin 25 % W/V administered twice per week , preceded by IFN alpha-2a three times weekly for one week showed a greater complete response rate in patients with primary condylomata acuminata when assessed at week 10 than treatment with podophyllin and placebo injections in the same schedule . The secondary objective was to compare recurrence rates in complete responders at six months in the two treatment groups . DESIGN --R and omised , double-blind parallel group study . SETTING --Multicentre study in six genitourinary clinics within the U.K. PATIENTS --One hundred and twenty-four patients with primary anogenital warts . MAIN OUTCOME MEASURES --Complete response rate at week 10 , and recurrence rate at week 26 in complete responders . RESULTS --At week 10 analysis of the efficacy population showed complete response in 36 % ( 15/42 patients ) of IFN-treated group and 26 % ( 11/43 patients ) in the placebo group ( no significant difference ) . Analysis of the safety population at week 26 showed persistence of the complete response in 57 % ( 8/14 patients ) of the IFN-treated group and 80 % ( 12/15 patients ) of the placebo group ( no significant difference ) . Adverse effects were more common in IFN-treated patients , involved particularly application site reaction and malaise but were generally mild . CONCLUSIONS --At the dose and with the regime described treatment with IFN alpha-2a in combination with podophyllin is no more effective in the treatment of primary anogenital warts than podophyllin alone and is associated with more adverse events Sexually transmitted diseases caused by human papilloma viruses , such as condylomata acuminata , are increasing in incidence and are often difficult to treat because of their tendency to recur . Many reports in the literature document the usefulness of interferons topically or systemically in these diseases . A r and omized study was conducted to evaluate interferon Alfa-2b ( Intron A ) as adjuvant therapy following CO2 laser surgery of condylomata acuminata . A low-dose regimen was administered ( two courses with 1 million I.U. s.c . daily for 6 days with a 2-week interval between the courses ) and had hardly any side-effects . The recurrence rate in the therapy group was significantly reduced ( 42 % vs 81 % ) , so routine prophylaxis of recurrence with interferons in condylomata acuminata should be discussed Systemic treatment modalities for eradication of multiple therapy resistant genital warts are so far not available . In this study laser treated patients with multiple genital warts received postoperatively either interferon alpha-2b subcutaneously ( s.c . ) 5 x 10(6 ) IU or matching placebo three times weekly for four weeks . At the conclusion of the study , 6 - 8 weeks after discontinuation of therapy , a significantly higher cure rate was found in the group of interferon-treated patients ( 14 of 27 ( 52 % ) patients cured ) than among placebo treated patients ( 5 of 22 ( 23 % ) patients cured ) ( p less than 0.05 ) . The side effects of fever , chills , myalgia , headache and leukopenia occurred more commonly in the interferon treated group than in the placebo group . However , only three of 32 patients discontinued interferon therapy because of side effects . We conclude that the addition of s.c . administered interferon alpha-2b to laser treated patients with chronic therapy resistant genital warts is fairly well tolerated and that it significantly enhances the chance of eliminating the disease Skillful laser ablation can remove any volume of human papillomavirus-associated vulvar disease but can not prevent reactivation of the surrounding latent viral reservoir during postoperative healing . Conversely , interferon and 5-fluorouracil are relatively ineffective as primary therapies in clearing bulky lesions . In this study of 71 assessable patients , topical 5-fluorouracil and systemic interferon injections were used postoperatively . Success rates within the adjuvant 5-fluorouracil and laser alone arms were essentially the same ( 9 of 18 vs 8 of 20 ) . In contrast , outcome in the interferon group was significantly better than that for the other two arms combined ( 27 of 33 [ 82 % ] vs 17 of 38 [ 45 % ] ; chi 2 10.31 ; p less than 0.002 ) . Moreover , 18 of 21 failures ( 86 % ) in the first two arms and 3 of 6 failures ( 50 % ) in the interferon arm were " rescued " from the need for a second laser surgical procedure by crossover to either the 1 or 3 MIU interferon regimen . Results from this open-label , r and omized clinical trial suggest that even a relatively low dose of recombinant interferon , used in combination with effective surgical debulking , can markedly reduce the risk of postoperative recurrence Forty-nine subjects were enrolled in a study comparing two dosages of parenterally administered interferon (IFN)-beta in combination with cryotherapy for the treatment of anogenital warts . Subjects were r and omized to receive subcutaneous injections of either 2 x 10(6 ) or 4 x 10(6 ) IU/m2 of IFN-beta ( Biogen ) three times a week for a total of 6 weeks . Cryotherapy was administered concomitantly by aerosolization of liquid nitrogen at 10-day intervals . Systemic side- effects were modest in intensity and included fever , chills , myalgia , and headaches ( flu-like symptoms ) . During the first 2 weeks of therapy , they were more common in the high dose group than in the low dose group ( P = 0.02 ) . Using survival analysis , there was no significant difference between the two groups in rates of resolution of warts present at baseline ( P = 0.62 ) . However , the rate of new lesion formation during the study was significantly lower in the high dose group ( P = 0.04 ) In the GRADE approach , r and omized trials are classified as high quality evidence and observational studies as low quality evidence but both can be rated down if a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted OBJECTIVE --To determine whether interferon alpha-2a , when utilised as adjuvant chemotherapy following ablation of condylomata acuminata ( genital warts ) by cryotherapy , is effective in the prevention of recurrences . DESIGN --R and omised , placebo-controlled , double-blind study . Statistical analysis was by 2-tailed Fisher 's Exact Test . PATIENTS --97 patients with recurrent condylomata acuminata . INTERVENTION--49 patients were treated with cryotherapy plus subcutaneously administered interferon alpha-2a , and 48 received cryotherapy plus placebo . Of these , 36 and 37 patients , respectively , completed the study and were evaluable . MAIN OUTCOME MEASURE-- Clinical eradication of condylomata for six months following adjuvant chemotherapy . RESULTS --By completion of the adjuvant chemotherapy , 10 ( 28 % ) interferon recipients and 16 ( 43 % ) placebo recipients experienced recurrences . At six months follow-up , 25 ( 69 % ) interferon and 27 ( 73 % ) placebo recipients experienced recurrences . In the six months following interferon therapy , only 31 % of interferon and 27 % of placebo recipients remained free of recurrences ( p = 0.99 ) . CONCLUSIONS --Interferon alpha-2a administered subcutaneously offers no benefit as a chemotherapeutic adjuvant to cryotherapy when used alone in the therapy of genital warts in this population of patients with recurrent condylomata |
938 | 24,797,705 | For percentage weight change , no significant differences were found among the BMI classes .
Conclusion Average weight change during lifestyle interventions only differs to a small extent among people with BMI between 25 and 40 kg m−2 .
This implies that these interventions are equally appropriate for these BMI classes | Background Lifestyle interventions are effective for weight loss and are recommended for persons with a body mass index ( BMI ) of 25–40 kg m−2 .
However , this group is very heterogeneous , which could influence outcomes from lifestyle interventions .
Purpose In this systematic review , differences in 1-year weight change and percentage weight change after lifestyle interventions were investigated for participants varying in initial BMI using meta-analyses . | BACKGROUND Recommending increased physical activity facilitates long-term weight loss , but the optimal level of physical activity to recommend is unknown . OBJECTIVE The objective of the study was to evaluate the efficacy for long-term weight loss of recommendations for much higher physical activity than those normally used in behavioral treatments . DESIGN Overweight men and women ( n = 202 ) were r and omly assigned to either a st and ard behavior therapy ( SBT ) for obesity , incorporating an energy expenditure ( EE ) goal of 1000 kcal/wk , or to a high physical activity ( HPA ) treatment , in which the goal was an EE of 2500 kcal/wk . To help HPA treatment group participants achieve this high exercise goal , their treatment included encouragement to recruit 1 - 3 exercise partners into the study , personal counseling from an exercise coach , and small monetary incentives . RESULTS The HPA treatment group reported achieving higher mean ( + /- SD ) physical activity levels than did the SBT group at 6 mo ( EE of 2399 + /- 1571 kcal/wk compared with 1837 + /- 1431 kcal/wk ) , 12 mo ( EE of 2249 + /- 1751 kcal/wk compared with 1565 + /- 1309 kcal/wk ) , and 18 mo ( EE of 2317 + /- 1854 kcal/wk compared with 1629 + /- 1483 kcal/wk ) ( all P < 0.01 ) . Mean ( + /- SEM ) cumulative weight losses at 6 , 12 , and 18 mo in the HPA treatment group were 9.0 + /- 7.1 , 8.5 + /- 7.9 , and 6.7 + /- 8.1 kg , respectively . In the SBT group , the corresponding weight losses were 8.1 + /- 7.4 , 6.1 + /- 8.8 , and 4.1 + /- 7.3 kg , respectively . Between-group differences in weight loss were significant at 12 and 18 mo . CONCLUSION These results suggest that recommendations of higher levels of physical activity ( EE of 2500 kcal/wk ) promote long-term weight loss better than do conventional recommendations OBJECTIVE : To investigate the sustained effectiveness of a novel skill-based intervention for weight loss . DESIGN : R and omized , controlled trial . SUBJECTS : A total of 80 overweight/obese women living in Connecticut . MEASUREMENTS : Absolute weight difference measured in pounds and absolute change in body mass index ( BMI ) . Secondary outcomes included changes in food frequency question naire ( FFQ ) data and waist-to-hip ratio . RESULTS : In all 61 , 35 , and 34 % of study participants completed the 6- , 12- , and 24-month assessment s , respectively . At 6 months postintervention , both counseling-based ( CBI ) and skill-based ( SBI ) intervention groups had statistically significant decreases in absolute weight ( 4.0±3.6 and 1.7±3.0 kg , respectively ) . Compared to their baseline values , both CBI and SBI groups still maintained weight losses at 24 months ( 1.1±5.8 and 0.59±3.3 kg , respectively ) ; however , the differences were not statistically significant . FFQ results showed that , within the SBI group , there was a significant decrease ( P<0.05 ) in percent fat from baseline to 12 months and a nearly significant decrease in saturated fat from baseline to 24 months ( P=0.07 ) . CONCLUSIONS : Both the novel SBI and conventional dietary counseling demonstrated some residual weight loss benefit at 2 y. Effects of the SBI on dietary intake patterns are encouraging , and warrant further study Purpose of review This review highlights recent work evaluating the relationship between exercise , physical activity and physical and mental health . Both cross-sectional and longitudinal studies , as well as r and omized clinical trials , are included . Special attention is given to physical conditions , including obesity , cancer , cardiovascular disease and sexual dysfunction . Furthermore , studies relating physical activity to depression and other mood states are review ed . The studies include diverse ethnic population s , including men and women , as well as several age groups ( e.g. adolescents , middle-aged and older adults ) . Recent findings Results of the studies continue to support a growing literature suggesting that exercise , physical activity and physical-activity interventions have beneficial effects across several physical and mental-health outcomes . Generally , participants engaging in regular physical activity display more desirable health outcomes across a variety of physical conditions . Similarly , participants in r and omized clinical trials of physical-activity interventions show better health outcomes , including better general and health-related quality of life , better functional capacity and better mood states . Summary The studies have several implication s for clinical practice and research . Most work suggests that exercise and physical activity are associated with better quality of life and health outcomes . Therefore , assessment and promotion of exercise and physical activity may be beneficial in achieving desired benefits across several population s. Several limitations were noted , particularly in research involving r and omized clinical trials . These trials tend to involve limited sample sizes with short follow-up periods , thus limiting the clinical implication s of the benefits associated with physical activity . Abbreviations CAD : coronary artery disease ; COPD : chronic obstructive pulmonary disease ; CRP : cardiac rehabilitation program ; CVD : cardiovascular disease ; GMCB : group-mediated cognitive – behavioural ; HRQOL : health-related quality of life Signal detection methods were used to identify predictors of successful weight loss in 177 mildly to moderately overweight women and men assigned to one of two weight-loss programs . Predictors included initial demographic , physiological , behavioral , and psychosocial characteristics , and program type ( e.g. diet-only and diet-plus-exercise ) . Successful weight loss was defined as a loss of at least two units of body mass index at one year . Four subgroups were identified . Participants in the diet-plus-exercise program who were initially more satisfied with their bodies and did not have a history of repeated weight loss were most likely to succeed ( 63 % succeeded ) . In contrast , participants assigned to the diet-plus-exercise program who were either extremely dissatisfied with their bodies or who had a history of repeated weight loss were at similar risk for failure as participants in the diet-only program ( only 26 % to 35 % succeeded ) . The results underscore the potential utility of exploring these subgroups further to inform the development of new treatment strategies to increase the likelihood of success BACKGROUND Although it is known that plasma leptin concentrations correlate with the amount of adipose tissue in the body , little information is available on the long-term effects on leptin concentrations of changes in diet and exercise . OBJECTIVE We wanted to examine whether changes in dietary energy sources and exercise-mediated energy expenditure , alone or in combination , affect plasma leptin concentrations . DESIGN In a r and omized , 2 x 2 factorial trial , 186 men with metabolic syndrome were divided into 4 groups : diet , exercise , a combination of diet and exercise , and control . Data on dietary intake , physical fitness , and demographics were collected and plasma leptin concentrations were measured before and after a 1-y intervention period . RESULTS Plasma leptin concentrations , body mass index , and fat mass decreased in association with long-term reductions in food intake as well as increased physical activity . By adjusting for either body mass index or fat mass , we observed a highly significant reduction in plasma leptin concentration after both the diet and the exercise interventions . There was no interaction between the interventions , suggesting a direct and additive effect of changes in diet and physical activity on plasma leptin concentrations . CONCLUSION Long-term changes in lifestyle consisting of decreased intake of dietary fat and increased physical activity reduced plasma leptin concentrations in humans beyond the reduction expected as a result of changes in fat mass CONTEXT The prevalence of overweight and obesity in the United States remains high . Commercial weight loss programs may contribute to efforts to reduce the prevalence of overweight and obesity , although few studies have examined their efficacy in controlled trials . OBJECTIVE To test whether a free prepared meal and incentivized structured weight loss program promotes greater weight loss and weight loss maintenance at 2 years compared with usual care . DESIGN , SETTING , AND PARTICIPANTS A r and omized controlled trial of weight loss and weight loss maintenance in 442 overweight or obese women ( body mass index , 25 - 40 ) aged 18 to 69 years ( mean age , 44 years ) conducted at US institutions over 2 years with follow-up between November 2007 and April 2010 . INTERVENTION The program , which involves in-person center-based or telephone-based one-to-one weight loss counseling , was available over a 2-year period . Behavioral goals were an energy-reduced , nutritionally adequate diet , facilitated by the inclusion of prepackaged food items in a planned menu during the initial weight loss phase , and increased physical activity . Participants assigned to usual care received 2 individualized weight loss counseling sessions with a dietetics professional and monthly contacts . MAIN OUTCOME MEASURES Weight loss and weight loss maintenance . RESULTS Weight data were available at 24 months for 407 women ( 92.1 % of the study sample ) . In an intent-to-treat analysis with baseline value substitution , mean weight loss was 7.4 kg ( 95 % confidence interval [ CI ] , 6.1 - 8.7 kg ) or 7.9 % ( 95 % CI , 6.5%-9.3 % ) of initial weight at 24 months for the center-based group , 6.2 kg ( 95 % CI , 4.9 - 7.6 kg ) or 6.8 % ( 95 % CI , 5.2%-8.4 % ) for the telephone-based group , and 2.0 kg ( 95 % CI , 0.6 - 3.3 kg ) or 2.1 % ( 95 % CI , 0.7%-3.5 % ) for the usual care control group after 24 months ( P < .001 for intervention effect ) . CONCLUSION Compared with usual care , this structured weight loss program result ed in greater weight loss over 2 years . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00640900 CONTEXT Although commercial weight loss programs provide treatment to millions of clients , their efficacy has not been evaluated in rigorous long-term trials . OBJECTIVE To compare weight loss and health benefits achieved and maintained through self-help weight loss vs with a structured commercial program . DESIGN AND SETTING A 2-year , multicenter r and omized clinical trial with clinic visits at 12 , 26 , 52 , 78 , and 104 weeks conducted at 6 academic research centers in the United States between January 1998 and January 2001 . PARTICIPANTS Overweight and obese men ( n = 65 ) and women ( n = 358 ) ( body mass index , 27 - 40 ) aged 18 to 65 years . INTERVENTION R and om assignment to either a self-help program ( n = 212 ) consisting of two 20-minute counseling sessions with a nutritionist and provision of self-help re sources or to a commercial weight loss program ( n = 211 ) consisting of a food plan , an activity plan , and a cognitive restructuring behavior modification plan , delivered at weekly meetings . MAIN OUTCOME MEASURES Weight change was the primary outcome measure . Secondary outcomes included waist circumference , body mass index , blood pressure , serum lipids , glucose , and insulin levels . RESULTS At 2 years , 150 participants ( 71 % ) in the commercial group and 159 ( 75 % ) in the self-help group completed the study . In the intent-to-treat analysis , mean ( SD ) weight loss of participants in the commercial group was greater than in the self-help group at 1 year ( -4.3 [ 6.1 ] kg vs -1.3 [ 6.1 ] kg , respectively ; P<.001 ) and at 2 years ( -2.9 [ 6.5 ] kg vs -0.2 [ 6.5 ] kg , respectively ; P<.001 ) . Waist circumference ( P = .003 ) and body mass index ( P<.001 ) decreased more in the commercial group . Changes in blood pressure , lipids , glucose , and insulin levels were related to changes in weight in both groups , but between-group differences in biological parameters were mainly nonsignificant by year 2 . CONCLUSION The structured commercial weight loss program provided modest weight loss but more than self-help over a 2-year period Objectives : To describe participants ’ adherence to multiple components ( attendance , energy intake , fat gram , exercise goals , and self-monitoring eating and exercise behaviors ) of a st and ard behavioral treatment program ( SBT ) for weight loss and how adherence to these components may influence weight loss and biomarkers ( triglycerides , low density lipoproteins [ LDL ] , high density lipoprotein , and insulin ) during the intensive and less-intensive intervention phases . Methods : A secondary analysis of a r and omized clinical trial consisting of a SBT with either fat-restricted st and ard or lacto-ovo vegetarian diet . The 12-month intervention was delivered in 33 group sessions . The first six months reflected the intensive phase ; the second six months , the less-intensive intervention phase . We conducted the analysis without regard to treatment assignment . Eligible participants included overweight/obese adults ( N = 176 ; mean body mass index = 34.0 kg/m2 ) . The sample was 86.9 % female , 70.5 % White , and 44.4 ± 8.6 years old . The outcome measures included weight and biomarkers . Results : There was a significant decline in adherence to each treatment component over time ( P < 0.0001 ) . In the first six months , adherence to attendance , self-monitoring and the energy goal were significantly associated with greater weight loss ( P < 0.05 ) . Adherence to attendance and exercise remained significantly associated with weight loss in the second six months ( P < 0.05 ) . Adherence to attendance , self-monitoring and exercise had indirect effects through weight loss on LDL , triglycerides , and insulin ( P < 0.05 ) . Conclusions : We observed a decline in adherence to each treatment component as the intervention intensity was reduced . Adherence to multiple treatment components was associated with greater weight loss and improvements in biomarkers . Future research needs to focus on improving and maintaining adherence to all components of the treatment protocol to promote weight loss and maintenance Despite widely publicized hypertension treatment guidelines for physicians and lifestyle recommendations for patients , blood pressure control rates remain low . In community-based primary care clinics , we performed a nested , 2 × 2 r and omized , controlled trial of physician intervention versus control and /or patient intervention versus control . Physician intervention included internet-based training , self-monitoring , and quarterly feedback reports . Patient intervention included 20 weekly group sessions followed by 12 monthly telephone counseling contacts and focused on weight loss , Dietary Approaches to Stop Hypertension dietary pattern , exercise , and reduced sodium intake . The primary outcome was change in systolic blood pressure at 6 months . Eight primary care practice s ( 32 physicians ) were r and omized to physician intervention or control groups . Within those practice s , 574 patients were r and omized to patient intervention or control groups . Patient mean age was 60 years , 61 % were women , and 37 % were black . Blood pressure data were available for 91 % of patients at 6 months . The main effect of physician intervention on systolic blood pressure at 6 months , adjusted for baseline pressure , was 0.3 mm Hg ( 95 % CI : −1.5 to 2.2 ; P=0.72 ) . The main effect of the patient intervention was −2.6 mm Hg ( 95 % CI : −4.4 to −0.7 ; P=0.01 ) . The interaction of the 2 interventions was significant ( P=0.03 ) ; the largest impact was observed with the combination of physician and patient intervention ( −9.7±12.7 mm Hg ) . Differences between treatment groups did not persist at 18 months . Combined physician and patient interventions lowers blood pressure ; future research should focus on enhancing effectiveness and sustainability of these interventions OBJECTIVES In this paper , we present the results of changes in risk factors by use of hormone therapy ( HT ) at 18 months in the Women On the Move through Activity and Nutrition ( WOMAN ) r and omized trial . METHODS The trial was design ed to test the hypothesis that aggressive dietary changes and increased physical activity to reduce weight , waist circumference ( WC ) , glucose , insulin , and lipoproteins would reduce progression of sub clinical atherosclerosis , carotid intimal media thickness and plaque , coronary artery calcification , and pulse wave velocity ( PWV ) . The study focused on postmenopausal women ( n = 508 ) , mean age of 57 , who were r and omized to the Lifestyle Change ( LC ) or Health Education ( HE ) group . RESULTS At 18 months of follow-up , there was significant , 17 lb , weight loss and 10 cm WC decrease in the LC group . There were significant differences in changes in low-density lipoprotein cholesterol ( LDL-C ) , insulin , glucose , large LDL , and LDL particles between the LC and HE groups . Risk factor changes were greater for women in the LC who lost a significant amount of weight ( > or=18.8 lb ) . Participants at 18 months were subdivided into women who had stayed on HT , 125 ( 28 % ) ; stopped HT after r and omization , 145 ( 33 % ) ; and not on HT at baseline but stopped an average of 7 months prior to r and omization , 173 ( 39 % ) . Weight loss in the LC was similar for all three groups , but LDL lipoprotein response was better for women who stopped HT after r and omization or were not on HT at baseline . CONCLUSIONS The trial has been successful in increasing exercise and diet changes and reduction in weight and WC and variables related to metabolic syndrome Objective To assess effects of multifactorial lifestyle modification on antihypertensive drug needs in treated hypertensive individuals . Design R and omized controlled trial . Setting Research studies unit . Participants Overweight hypertensive patients , receiving one or two antihypertensive drugs , were recruited by advertising , and allocated r and omly to a usual care group ( controls ; n = 118 ) or a lifestyle modification group ( programme group ; n = 123 ) . Intervention A 4-month programme of weight loss , a low-sodium ‘ Dietary Approaches to Stop Hypertension’-type diet with added fish , physical activity and moderation of alcohol intake . After 4 months , if mean 24-h ambulatory blood pressure ( ABP ) was less than 135/85 mmHg , antihypertensive drugs were withdrawn over 4 weeks and long-term home blood pressure monitoring was begun . Main outcome measures Antihypertensive drug requirements , ABP , weight , waist girth at 4 months and 1-year follow-up . Results Ninety control group and 102 programme group participants completed the study . Mean 24-h ABP changed after 4 months by −1.0/−0.3 ± 0.5/0.4 mmHg in controls and −4.1/−2.1 ± 0.7/0.5 mmHg with the lifestyle programme ( P < 0.01 ) . At follow-up , changes in the two groups were not significantly different ( 4.1/1.3 ± 1.1/1.0 mmHg in controls ; 2.5/−0.1 ± 1.1/0.8 mmHg in the programme group ; P = 0.73 ) . At 4 months , drug withdrawal differed significantly between the groups ( P = 0.038 ) in men ( control 44 % ; programme 66 % ) but not in women ( 65 and 64 % , respectively ; P = 0.964 ) . At follow-up , sex-related differences were not significant , and 41 % in the control group and 43 % in the programme group maintained drug-withdrawal status . With the programme , net weight loss was 3.3 kg ( P < 0.001 ) at 4 months and 3.0 kg ( P < 0.001 ) at follow-up ; respective net decreases in waist girth were 3.3 cm ( P < 0.001 ) and 3.5 cm ( P < 0.001 ) . Conclusions A 4-month multifactorial lifestyle modification in patients with treated hypertension reduced blood pressure in the short-term . Decreased central obesity persisted 1 year later and could reduce overall cardiovascular risk OBJECTIVE : To assess the factors that could predict a successful completion of a weight loss program . STUDY DESIGN : A single-centered , cross-sectional , prospect i ve study conducted over 4 y . SUBJECTS : Data were obtained on 1018 overweight subjects ( 788 women , 230 men ) aged 14.8–76.3 y ( mean 38.4 ) and body mass index ( BMI ) of 31.7 ( range 25.03–57.1 ) seeking help to lose weight at a specialist obesity clinic . MATERIAL S AND METHODS : A program involving a hypocaloric , Mediterranean diet was prescribed plus recommendations for free-time exercise and day-to-day activity . Follow-up was weekly until the desired weight loss was achieved ( ‘ successful completion ’ ) or the patient dropped-out of the program ( ‘ failure ’ ) . Cox 's regression analysis was used to evaluate success and the variables included were compliance with the program , age , gender , initial BMI , physical activity , alcohol consumption , smoking habit , hypertension , diabetes , hypercholesterolemia , cardiovascular disease , previous dietary programs , cause of obesity , age at which excessive weight was first noted and parental obesity . RESULTS : Factors predictive of completion were : gender ( males responded better ) , previous dietary programs ( predictive of dropout ) , initial BMI ( higher index , lower completion ) , and age ( younger age , poorer outcome ) . There was an interaction between parental obesity and offspring childhood obesity . Absence of parental obesity and adult-onset obesity had a higher probability of program completion . CONCLUSIONS : In a st and ard weight reduction program the recommendations of dietary restriction and moderate exercise seems less effective for women , persons with high BMI , younger age groups and those who have had other attempts at weight loss . Poorest outcomes applied to those subjects with childhood obesity and who had obese parents BACKGROUND To improve methods for long-term weight management , the Weight Loss Maintenance ( WLM ) trial , a four-center r and omized trial , was conducted to compare alternative strategies for maintaining weight loss over a 30-month period . This paper describes methods and results for the initial 6-month weight-loss program ( Phase I ) . METHODS Eligible adults were aged > or = 25 , overweight or obese ( BMI = 25 - 45 kg/m2 ) , and on medications for hypertension and /or dyslipidemia . Anthropomorphic , demographic , and psychosocial measures were collected at baseline and 6 months . Participants ( n=1685 ) attended 20 weekly group sessions to encourage calorie restriction , moderate-intensity physical activity , and the DASH ( dietary approaches to stop hypertension ) dietary pattern . Weight-loss predictors with missing data were replaced by multiple imputation . RESULTS Participants were 44 % African American and 67 % women ; 79 % were obese ( BMI > or = 30 ) , 87 % were taking anti-hypertensive medications , and 38 % were taking antidyslipidemia medications . Participants attended an average of 72 % of 20 group sessions . They self-reported 117 minutes of moderate-intensity physical activity per week , kept 3.7 daily food records per week , and consumed 2.9 servings of fruits and vegetables per day . The Phase-I follow-up rate was 92 % . Mean ( SD ) weight change was -5.8 kg ( 4.4 ) , and 69 % lost at least 4 kg . All race-gender subgroups lost substantial weight : African-American men ( -5.4 kg + /- 7.7 ) ; African-American women ( -4.1 kg + /- 2.9 ) ; non-African-American men ( -8.5 kg + /- 12.9 ) ; and non-African-American women ( -5.8 kg + /- 6.1 ) . Behavioral measures ( e.g. , diet records and physical activity ) accounted for most of the weight-loss variation , although the association between behavioral measures and weight loss differed by race and gender groups . CONCLUSIONS The WLM behavioral intervention successfully achieved clinical ly significant short-term weight loss in a diverse population of high-risk patients OBJECTIVE The purpose of this study was to compare weight regain in a group of perimenopausal women ( 48.0+/-4.4 years old ) , r and omized to a 12-month weight maintenance Internet intervention or to self-directed weight maintenance after a 4-month weight loss treatment . METHODS AND PROCEDURES After a 4-month behavioral weight loss program , 135 women were r and omized to either Internet or self-directed groups . The Internet group ( n=66 ) used a website to gain information and complete logs concerning their weight , diet , and exercise progress over a 12-month follow-up . The 69 self-directed women had no contact with study staff . All women were measured for weight and body composition , and diet intake , and were interviewed using the 7-day physical activity question naires at baseline , 4 months , and 16 months . RESULTS At the end of the 12-month follow-up , the Internet and self-directed groups had regained on average 0.4+/-5.0 kg and 0.6+/-4.0 kg , respectively ( P=0.5 ) . In within-group analyses , Internet diet-log entries were correlated with follow-up weight change ( r=-0.29 ; P<0.05 ) and moderately with change in exercise energy expenditure ( EEE ; r=0.44 ; P<0.01 ) . Follow-up weight change was not correlated with change in dietary intake . DISCUSSION While significant weight loss was maintained over follow-up by both groups of women , Internet use did not surpass self-direction in helping to sustain weight loss . Among Internet users , Internet use was related to weight change and EEE |
939 | 23,235,625 | Most did not find a significant reduction in pain with antibiotics .
Similarly , antibiotics were mostly not shown to be effective in reducing the need for analgesics .
The present systematic review , including meta-analyses for select outcomes , suggests that although individual studies vary in their findings , there is no evidence to support a consistent , clinical ly important impact of antibiotics in reducing the main morbid outcomes following tonsillectomy ( i.e. pain , need for analgesia and secondary haemorrhage rates ) . | BACKGROUND This is an up date of a Cochrane Review first published in The Cochrane Library in Issue 2 , 2008 and previously up date d in 2010.Tonsillectomy continues to be one of the most common surgical procedures performed in children and adults .
Despite improvements in surgical and anaesthetic techniques , postoperative morbidity , mainly in the form of pain , remains a significant clinical problem .
Postoperative bacterial infection of the tonsillar fossa has been proposed as an important factor causing pain and associated morbidity , and some studies have found a reduction in morbid outcomes following the administration of perioperative antibiotics .
OBJECTIVES To determine whether perioperative antibiotics reduce pain and other morbid outcomes following tonsillectomy . | In the r and omized , placebo-controlled , physician-blinded Canadian cooperative trial of cyclophosphamide and plasma exchange , neither active treatment regimens ( group I : IV cyclophosphamide and prednisone ; group II : weekly plasma exchange , oral cyclophosphamide , and prednisone ) were superior to placebo ( group III : sham plasma exchange and placebo medications ) using the blinded , evaluating neurologists ' assessment s of disease course ( primary analysis ) . All patients were examined by both a blinded and an unblinded neurologist at each assessment in this trial . We compared the blinded and unblinded neurologists ' judgment of treatment response and analyzed the clinical behavior of patients who correctly guessed their treatment . The unblinded ( but not the blinded ) neurologists ' scores demonstrated an apparent treatment benefit at 6 , 12 , and 24 months for the group II patients ( not group I or placebo ; p < 0.05 , two-tailed ) . There were no significant differences in the time to treatment failure or in the proportions of patients improved , stable , or worse between the group II and group III patients who correctly guessed their treatment assignments and those who did not . Physician blinding prevented an erroneous conclusion about treatment efficacy ( false positive , type 1 error ) Post-tonsillectomy bacteremia is a well-recognized aetiological factor in streptococcal endocarditis , and prophylactic penicillin has been recommended to reduce its incidence in susceptible patients undergoing tonsillectomy . Recent studies have shown a change in the microflora and an increase in the number of penicillin-resistant organisms in the tonsils of patients undergoing tonsillectomy . The aim of this study was to assess the incidence of post-tonsillectomy bacteraemia , to identify the micro-organisms associated with it and to review the suitability of penicillin in prophylactic regimens . The relationship between positive blood cultures and several clinical parameters such as fever , vomiting , pharyngeal discomfort , or dysphagia was also analysed . Of the 102 patients included in the study , 41 ( 40.1 % ) had positive post-tonsillectomy blood cultures . Haemophilus influenzae were isolated from 23 ( 56 % ) of the positive cultures and Streptococcus viridans in 15 ( 36.5 % ) . Twenty-five per cent of H. influenzae produced beta-lactamase and only 30 % of streptococci of the viridans group were penicillin-sensitive . Positivity of the blood cultures was not related to fever , discomfort , surgical technique , type of tonsil , or any of the parameters studied . Bacteraemia seems to be related to traction of the tonsil before dissection rather than direct spread of bacteria into the opened vessels . Using a beta-lactamase stable antibiotic instead of penicillin for prophylaxis would be more appropriate OBJECTIVE Systemic antibiotics given during the first week after tonsillectomy appear to be effective in reducing postoperative morbidity . We assessed the effectiveness of perioperative topical antibiotic rinses in reducing posttonsillectomy morbidity . METHODS A r and omized , double-blinded , placebo-controlled pilot study of 36 patients undergoing tonsillectomy was used to evaluate the effects of a st and ard 7-day systemic regimen of perioperative intravenous ampicillin/oral amoxicillin and 2 single-day topical antibiotic regimens : ( 1 ) clindamycin ( Cleocin ) and ( 2 ) amoxicillin/clavulanate ( Augmentin ) and ticarcillin/clavulanate ( Timentin ) . RESULTS Mean aerobic and anaerobic oral bacterial counts were decreased in both topical treatment groups compared with the placebo group on the first postoperative day , achieving statistical significance with Augmentin/Timentin ( aerobic and anaerobic bacterial counts ) and Cleocin ( aerobic counts ) . Significantly less postoperative pain and mouth odor were reported for both Cleocin ( P = 0.014 and P = 0.005 , respectively ) and Augmentin/Timentin ( P = 0.026 and P = 0.05 , respectively ) topical treatment groups when compared with the placebo group . CONCLUSIONS Preliminary results indicate a reduction in oral bacterial counts and postoperative morbidity in adult patients receiving topical antibiotics compared with patients receiving placebo ; further investigation is warranted Pain and secondary haemorrhage are the commonest complications of adult tonsillectomy , occurring mostly in the community . This is a r and omized , double-blind , placebo-controlled , prospect i ve trial of the effect of perioperative amoxycillin on these complications . The incidence and severity of post-operative haemorrhage was measured . For the first 10 post-operative days patients provided a linear pain score , a record of GP visits , and their use of additional antibiotics and analgesics . Of 95 patients considered : 23 suffered a secondary haemorrhage ; 54 consulted their general practitioner ( GP ) because of pain ; additional antibiotics were used by at least 31 and additional analgesics by at least 41 . No significant differences were demonstrated between the active and placebo groups for any of these measures . This study demonstrates that secondary haemorrhage is common after adult tonsillectomy . Post-operative pain remains a major problem requiring frequent GP consultations . There appears to be no justification for the routine use of perioperative antibiotics OBJECTIVE To investigate the effect of fusafungine spray on pain and healing process after pediatric tonsillectomy . METHODS Sixty children with ages between 4 and 14 years underwent tonsillectomy or adenotonsillectomy . The patients were r and omly divided into three groups and each group consisted of 20 patients . Group 1 was treated with antibiotic ( amoxicillin-clavulanic acid ) plus analgesic ( acetaminophen ) , group 2 was treated with fusafungine plus analgesic ( acetaminophen ) and group 3 was treated with only fusafungine . The average ages were 7.8 + 3.4 , 6.6 + 2.9 , and 8.2 + 3.7 for groups 1 , 2 , and 3 , respectively . Clinical evaluations were made after the operation on the 1st ( T1 ) , 3rd ( T3 ) , 7th ( T7 ) , 10th ( T10 ) , and 14th days ( T14 ) . RESULTS There was no significant difference in post-operative pain between study groups on the post-operative 1st , 3rd , and 7th days ( P > 0.05 ) , a statistically significant difference was present between groups 1 and 3 , and groups 1 and 2 on the post-operative 10th and 14th day ( P = 0.018 and 0.037 , respectively ) . Pain was less in groups 2 and 3 than in group 1 on the 10th and 14th day . Also there was a significant difference in healing time of the tonsillary beds between groups 1 and 2 , and groups 1 and 3 on the 10th and 14th post-operative day ( P = 0.031 and 0.001 , respectively ) . Healing was better in groups 2 and 3 than in group 1 on the 10th and 14th day . CONCLUSION Fusafungine administration after tonsillectomy was found to be beneficial on post-operative pain and wound healing of tonsillary beds in pediatric population Tonsillectomy has been performed by a number of techniques . This double blind r and omized controlled study compares the technique of tissue coblation with bipolar dissection for the removal of tonsils in 10 adult patients with a history of chronic tonsillitis . A significant reduction in post-operative pain and more rapid healing of the tonsillar fossae were found in the side removed by tissue coblation . There were no episodes of primary or secondary haemorrhage on either side . This new technique for tonsil removal warrants further study OBJECTIVE To determine the current practice s of preoperative evaluation , surgical techniques , and postoperative treatment of pediatric adenotonsillectomy . STUDY DESIGN Forty-one-item survey measuring the frequency of different evaluations , procedures , and treatments performed , including selected case scenarios , with all items scored on a five-point ordinal scale ranking frequency . METHODS The entire membership of the American Society of Pediatric Otolaryngology ( ASPO ) and active fellows and members of the American Academy of Otolaryngology-Head and Neck Surgery ( AAO-HNS ) residing in New York state were anonymously surveyed through mail-in question naires . RESULTS History alone was the most frequent modality for diagnosing both adenoid enlargement and obstructive sleep apnea . The most common preoperative laboratory test ordered before an adenotonsillectomy is a complete blood cell count ; ASPO members ordered fewer preoperative laboratory tests than AAO-HNS members . Unipolar cautery is the most frequently used tonsillectomy technique , and curettage followed by cautery is the most popular adenoidectomy technique . Steroids are the most common intraoperative medication administered during an adenotonsillectomy , and office visits remain the most frequently used methods of assessing adenotonsillectomy patients postoperatively . CONCLUSIONS Although there are statistically significant trends uncovered by the survey , the results reflect a lack of consensus regarding adenotonsillectomy management . Further r and omized controlled trials or large-scale outcomes projects are much needed to evaluate critically the current practice s of pediatric adenotonsillectomies . Additional efforts may also be required to use the information from these studies in effecting changes in actual practice patterns , moving us toward a more evidence -based paradigm of treating pediatric adenotonsillar disease A prospect i ve study of 99 adults undergoing tonsillectomy was carried out to determine the pattern of post-operative pain , intake of medication and timing of return to work and normal swallowing . The differences in the pain scores , as measured by a visual analogue scale , between every third consecutive day following post-operative day four were found to be highly significant ( p < 0.001 ) . Sixty-six patients ( 66.6 per cent ) required medication in the form of analgesics and /or antibiotics after the first post-operative day . Sixty-four out of a total of 82 patients ( 78.2 per cent ) returned to work within 14 days of surgery . Ninety-six patients ( 97 per cent ) reported normal swallowing within 14 days of surgery . These results suggest that the majority of adult patients undergoing tonsillectomy can be appropriately advised pre-operatively regarding the probable pattern and duration of post-operative pain and the timescales they can expect to return to work and normal swallowing OBJECTIVES Tonsillectomy is one of the most commonly performed otolaryngologic procedures in the United States . Many options and controversies exist regarding techniques and peri-operative management . The purpose of the study was to examine current practice patterns among otolaryngologists regarding tonsillectomy . METHODS A 13 question survey regarding tonsillectomy techniques and peri-operative management was mailed to 10 % of r and omly selected board certified otolaryngologists of the AAO-HNS in the spring of 2002 . Four hundred and eighteen anonymously completed question naires were returned , for a response rate of 58.5 % . Statistical analysis of survey data was performed by means of cross tabulation and Pearson Chi-Square Calculation . RESULTS Monopolar electrocautery was the most common technique used among those surveyed ( 53.5 % ) . There was a significant correlation between choice of monopolar electrocautery and the cited reason for choice of technique being decreased blood loss ( P < 0.001 ) . There was no relationship between pediatric fellowship training and choice of technique . 97.7 % routinely admitted sleep apnea patients for post-operative observation . There was no significant correlation between practice setting ( tertiary versus community ) and type of post-operative monitoring for sleep apnea patients , with patients most commonly admitted to an intermediate care setting . CONCLUSION In our survey , the most common surgical technique for tonsillectomy was monopolar electrocautery , chosen for the reason of decreased blood loss Tonsillectomy continues to be a commonly performed operation in the pediatric age group . The postoperative period is often protracted and characterized by throat and ear pain , intermittent fever , foul odor from the oral cavity , and poor oral intake . Consequently , antibiotics are frequently prescribed in an effort to minimize these symptoms and /or avoid complications such as dehydration or secondary infection of the operative site . However , to our knowledge , no study to date has been performed to demonstrate the efficacy of antibiotic therapy in this setting . At the Children 's Hospital of Philadelphia , a prospect i ve , r and omized , double-blind study was undertaken in which ampicillin ( or placebo ) was administered intravenously at the time of surgery and for 12 to 24 hours postoperatively . The children then continued to receive oral amoxicillin therapy ( or placebo ) for an additional seven days . The patients were then evaluated for the incidence and severity of postoperative symptoms and complications . Intraoperative cultures of the oropharynx and tonsillar tissue , as well as cultures of the tonsillar fossa , were obtained following completion of one week of therapy . Our results indicate that ampicillin sodium/amoxicillin trihydrate therapy is well tolerated and safe in the nonallergic child and is effective in minimizing fever and other troublesome postoperative symptoms , such as pain , lassitude , mouth odor , and poor oral intake after tonsillectomy One hundred and one adult patients undergoing tonsillectomy for chronic/recurrent tonsillitis completed a prospect i ve , r and omized , double-blind , placebo-controlled study in which ticarcillin disodium and clavulanate potassium ( Timentin ) or placebo was administered intravenously at the time of surgery and for 12 hours postoperatively . The patients than received oral amoxicillin and clavulanate potassium ( Augmentin ) therapy or placebo for an additional seven days . Each patient kept a daily log to assess the incidence and severity of postoperative symptoms . Tonsillar core tissue at the time of surgery , as well as tonsillar fossa cultures after 7 days of treatment , were obtained . Those patients who received antibiotics fared consistently better in the immediate postoperative period compared with the placebo group . Specifically , patients in the antibiotic group experienced significantly less mouth odor , were able to tolerate a regular diet sooner , and resumed their normal activities earlier than did patients who received placebo . Patients who received antibiotics experienced fewer days with mouth odor ( p = 0.004 ) . In addition , on postoperative days 3 to 5 , the antibiotic group was eating a regular diet ( p = 0.05 ) and had returned to their routine activities earlier ( p = 0.045 ) when compared with the placebo group . Perioperative antibiotic therapy was well tolerated and was effective in minimizing symptoms after tonsillectomy UNLABELLED Tonsillectomy with or without adenoidectomy still is one of the most commonly performed surgical procedures in the world , mostly in the pediatric population . AIM to study the impact of amoxicillin for 7 days in post-adenotonsillectomy recovery , comparing results with a control group . STUDY TYPE prospect i ve , r and omized , controlled study with 120 patients . PATIENTS AND METHODS the patients were r and omized according to surgery time to receive 7 days of amoxicillin associated with pain killers , or analgesic alone . During the first week of postoperative , we assessed the level of pain , oral intake acceptance , nausea and vomits , fever and return to daily activities . RESULTS It was only in the fourth post-operative day that the group receiving antibiotic agents showed a statistically significant difference as far as pain is concerned . There was no difference between the two groups for other data analyzed . CONCLUSION considering the results from our study and review ing the literature on the use of antibiotic agents , we agree that there is no improvement in patient recovery after adenotonsillectomy with the use of amoxicillin for 7 days in the postoperative OBJECTIVE : To compare contact diode laser ( CDL ) tonsillectomy to monopolar cautery ( MPC ) with regard to pain and other morbidity during recovery . STUDY DESIGN AND SETTING : Single-blind , r and omized trial in a tertiary-care pediatric hospital . Tonsillectomy was performed by CDL in 30 children and by MPC in 28 . Parents completed a daily question naire for 10 days after surgery . RESULTS : There was significantly less pain in the CDL group than in the MPC group . The CDL group also required much less medication , and was much less likely to experience multiple awakenings ( P < 0.001 for all comparisons ) . CONCLUSION : Recovery after CDL tonsillectomy was associated with much less pain and discomfort than after MPC surgery . SIGNIFICANCE : Postoperative pain is a major concern for surgeons , patients , and their parents . The long recovery period also has costs in school days missed for the child and work missed for the parents . CDL tonsillectomy may greatly mitigate these burdens Blinding in medical research possesses a rich history spanning a couple of centuries ( 1 ) . Most research ers and readers grasp its meaning . Unfortunately , beyond that general underst and ing lies confusion . In addition to terms such as single blind and double blind meaning different things to different people , some steadfastly refuse to use the term blinding and insist instead on the term masking . Others confuse blinding with other method ologic pre caution s , such as concealment of allocation during the process of creating comparison groups . Still others consider that r and omization is of little use unless accompanied by double-blinding , thus revealing that they have not understood that these separate aspects of methodology address separate sources of bias . A recent survey addressed whether the process historically termed blinding should be termed masking ( 2 ) . The survey revealed a lack of accord on that question and inconsistencies concerning other blinding terminology . Although many re sources address the lexicon of blinding , including clinical trial textbooks ( 3 - 5 ) , clinical trial dictionaries ( 6 , 7 ) , and a recently released epidemiology dictionary ( 8) , these sources do not entirely clear the lexicographic fog . Indeed , a recent study found that investigators , textbooks , and published articles all varied greatly in their interpretations of single- , double- , and triple-blinding ( 9 ) . In other words , terminologic tangles abound with blinding . We delve into the l and scape and lexicon of blinding in r and omized trials in the hope of untangling some of that terminology . Synopsis of the History of Blinding Scientists sometimes portray blinding as a recent method ologic achievement , but research ers have used blinding for more than 200 years . Lavoisier and Franklin introduced blinding in the late 18th century to test therapeutic cl aims made for Mesmerisma therapy founded on the notion that magnetism had healing properties ( 1 , 10 ) . Toward the middle of the 19th century , many homeopaths used blinding in their provings and in comparisons of homeopathy with mainstream medicine ( 11 ) . By the late 19th century , psychological research ers began to use blinding for traditional questions , more to minimize bias than to expose fraud ( 1 ) . The beginning of the 20th century found some physiologists and pharmacologists , particularly in Germany , using blind assessment . That use became more frequent in Germany by the 1930s . Research ers in Britain and the United States developed interest in blind assessment , but a different rationale motivated their interest . The rationale in Germany for blinding centered on the elimination of bias . In contrast , the interest in Britain and the United States initially centered on preventing attrition problems ( 1 ) . Without blinding and a placebo intervention , recruiting and retaining participants for a no-intervention control group became daunting . For Anglo-American clinical research ers , the initial adoption of a placebo sham in an experiment was an architectural device to create a viable and camouflaged concurrent no-treatment arm in a clinical trial ( 1 ) . Toward the end of the 1930s , British and U.S. research ers also began to acknowledge the benefits of blinding in avoiding bias . The evolution of the r and omized , controlled trial during the first half of the 20th century promoted greater use of blinding . Properly concealed r and om allocation to comparison groups abolished selection bias at entry to a trial , and clinical investigators began to appreciate fully the biases that could affect studies after participants had entered a trial . That realization transferred greater credibility to blinding arguments ( 1 ) . We recommend Kaptchuk ( 1 ) for a historical account . Background Blinding is intended to reduce bias in medical research . Although blinding is often associated in people 's minds with r and omized , controlled trials , it can be used in a variety of study design s to reduce observer biases ( 12 ) . For example , investigators can assess outcome measures blinded to exposure status in nonr and omized cohort studies or exposure status blinded to case or control status in casecontrol studies . Indeed , when investigators first used blinding in the 18th century , they assessed the effects of Mesmerism in nonr and omized experiments ( 1 , 10 ) . Having noted this , however , we focus on blinding in the context of r and omized comparisons of interventions . Blinding is widely recognized as reducing differential assessment of outcomes of interest ( known as ascertainment bias , information bias , or observer bias ) , prompted by knowledge of the group assignment of individuals being observed ( 3 - 5 ) . Blinding is less frequently recognized as also operationally improving compliance and retention of trial participants and reducing biased supplemental care or treatment ( sometimes called co-intervention ) ( 3 , 5 ) . We provide glimpses of the potential disadvantages of participants ' , investigators ' , and outcome assessors ' knowing the intervention group to which the participants have been assigned . In many cases , the biases that result might well be subconscious , but they are biases nonetheless . Possible Consequences of Participants ' Knowing Psychological effects could arise from participants ' knowing that they have received a promising new treatment , a thoroughly tested st and ard treatment , an untested new treatment , or a disappointing st and ard treatment . In other words , how the treatment options are perceived may influence the way in which they are evaluated . Despite evidence suggesting that new treatments are as likely to be inferior as they are to be superior to st and ard treatments ( 13 ) , we have the impression that participants generally assume that new treatments will be better than st and ard treatments . In any case , knowledge of the intervention received can affect the psychological or physical responses of the participants ( 3 - 5 ) . Furthermore , knowledge of the intervention could influence participants ' cooperation . For example , if participants believe that they were assigned to what they perceive as an inferior intervention , they may not comply well with the regimen . Moreover , they may not adhere to follow-up procedures , leading to a potentially biased loss to follow-up . Possible Consequences of Investigators ' Knowing We define investigators in an aggregate sense to include a broad trial teamfor example , trial design ers , participant enrollers , r and omization executors , health care providers , intervention counselors , and routine- data collectors . Investigators particularly pertinent to blinding include health care providers ( such as an attending physician or nurse ) and intervention counselors ( for example , someone delivering a behavioral prevention message ) who interact with the participants throughout the trial . The inclinations of investigators for or against the interventions can be directly transferred to participants by their attitudes ( 14 ) . Their inclinations may also be manifested in , for example , differential use of ancillary interventions of supplemental care or treatment ( co- interventions ) . Of note , the implementer could also encourage or discourage continuation in the trial on the basis of knowledge of the intervention group assignment . Possible Consequences of Outcome Assessors ' Knowing When they know the intervention group assignment of the participants whom they are assessing , outcome assessors with inclinations for or against any of the interventions being compared may make biased assessment s. For example , if they believe the new intervention is superior , then they could register more generous responses to that intervention . Obviously , more subjective outcomes present greater opportunities for bias . Pain scores assessed by participants are a good example of a subjective outcome . Even some outcomes considered objective can be fraught with subjectivityfor example , pelvic inflammatory disease and myocardial infa rct ion . In general , blinding becomes less important to reduce observer bias as the outcomes become less subjective . Hard outcomes leave little room for bias . For example , knowledge of the intervention would have little effect on measuring a hard outcome , such as death ( but still could influence the attributed cause of death ) . Of importance , even when participants and investigators have not been blinded , blinding of outcome assessors is often possible and advisable ( 12 ) . Placebos and Blinding Blinding frequently leads to the use of placebos . Placebos may or may not have effects mediated through psychological mechanisms , but they are administered to participants in a trial because they are otherwise inactive . An active placebo is a placebo with properties that mimic the symptoms or side effects ( for example , dry mouth , sweating ) that might otherwise reveal the identity of the ( pharmacologically ) active test treatment . The effect , in practice , of using placebos is contentious ( 15 ) , but the widespread view remains that placebos should be administered , whenever possible , to participants in control groups when assessing the effects of proposed new treatments for a condition for which no effective treatment already exists ( 3 , 4 ) . Placebos are generally used in trials of drugs , vaccines , and other medicinal interventions but can sometimes also be used in trials of procedures , such as ultrasonography , acupuncture , and , occasionally , surgery . For example , perhaps when placebo treatments are inappropriate , some closely analogous approach , such as placebo wound dressings , may suffice in a trial of laparoscopic versus open appendicectomy ( 16 ) . When an effective st and ard treatment exists , it is frequently used in the control group for comparison against a new treatment . Thus , investigators might compare two active treatment groups without a placebo group . Even then , however , investigators frequently attempt to achieve blinding by using the double-dummy method in essence , two placebos ( 12 , 17 ) . For example , in comparing two agents , one in a blue capsule OBJECTIVES : To compare postoperative tonsillectomy pain between 3 commonly used surgical devices : the Harmonic Ultrasonic Scalpel ( Ethicon Endo-Surgery , Cincinnati , OH ) , the Coblator ( ArthroCare Corp , Sunnyvale , CA ) , and electrocautery . STUDY DESIGN AND SETTING : A prospect i ve , r and omized trial . One hundred thirty-four patients were r and omly assigned to receive a tonsillectomy with 1 of 3 surgical devices . All patients were asked to fill out a postoperative diary . RESULTS : Statistically significant differences in pain scores were revealed between the Coblator and electrocautery ( P = 0.02 ) and between the Coblator and the Ultrasonic Scalpel ( P = 0.003 ) , with the Coblator having lower pain scores . Electrocautery and the Ultrasonic Scalpel did not differ significantly from each other . The Coblation method showed a strong trend toward quicker return to normal diet . CONCLUSION : Patients undergoing tonsillectomy with the Coblator device reported less pain over a 10-day period than patients undergoing tonsillectomy with electrocautery or the Ultrasonic Scalpel . Pain after tonsillectomy remains a major issue for our patients . The choice of surgical instrument appears to be one way to reduce this pain . EBM rating : A prospect i ve audit study was undertaken to assess the effect of two different management policies following tonsillectomy in children in this hospital , one of which requires a prophylactic five-day course of oral antibiotics and the other doses not . A total of 95 children were entered into the trial : 54 received post-operative antibiotics and 41 did not . The post-operative recovery was assessed by completion of a parent question naire which included the following parameters : degree of patient distress , nausea and vomiting , otalgia , halitosis , pharyngeal bleeding , analgesic requirement , day of return to a regular diet and General Practitioner consultation . There was no significant reduction in any of the morbidity measures in patients treated with antibiotics . I fact , the analgesic requirement and the incidence of otalgia and irritability on Days 6 and 7 and secondary haemorrhage were significantly higher in the antibiotic-treated patients . Although the number of patients included in this study are small , the result suggest that post-operative antibiotics do not improve the outcome of uncomplicated tonsillectomy . Our previous practice of routinely administering antibiotics to post-tonsillectomy children has been discontinued as the consequence of this audit The decision to prescribe antibiotics post-tonsillectomy still remains controversial . However , recent changing trends in the tonsillar tissue microflora have been widely reported , with Haemophilus influenzae , Staphylococcus aureus and anaerobic organisms all being implicated . All of the above are beta-lactamase producers and thus render lactamase prone antibiotics inactive . We compared two groups of children , one on Amoxycillin and clavulanic acid ( a lactamase stable antibiotic with anaerobic cover ) for 1 week post tonsillectomy -- Group A ( N = 44 ) , and another group on no treatment -- Group B ( N = 34 ) . We compared tonsillar core , surface and postoperative tonsillar fossae bacteriological profiles in the two groups . The tonsil core pathogens included H. influenzae ( 64 % ) of which 9.5 % were beta-lactamase producers , Streptococcus viridans ( 55.9 % ) , S. aureus ( 37 % ) of which 86 % were beta-lactamase producers , and anaerobes which were found in 25 % of sample s. We found that there was considerably less morbidity in those children receiving postoperative antibiotics compared to those who did not , as judged by the amount of analgesia consumed ( p = 0.379 ) , time to resumption of normal diet ( p = 0.0072 ) and pain analogue scores ( p = 0.0006 ) . We feel that treating children who have undergone tonsillectomy with amoxycillin and clavulanic acid significantly reduces postoperative morbidity OBJECTIVE To evaluate recovery after tonsillectomy and safety and efficacy of ketoprofen in pain treatment after discharge . STUDY DESIGN A prospect i ve , longitudinal study of 102 patients undergoing tonsillectomy . METHODS All patients underwent tonsillectomy ( or adenotonsillectomy ) under general anesthesia . In the hospital , 77 patients received a bolus of 0.5 mg/kg ketoprofen intravenously , followed by a 3-mg/kg continuous infusion over 24 hours , and oxycodone for rescue analgesia . Twenty-five patients received normal saline and oxycodone . At discharge , all patients were prescribed ketoprofen capsules at a dose of 3 to 5 mg/kg per day for postoperative pain control at home , with paracetamol-codeine tablets for rescue analgesia . At home , the patients recorded pain and analgesic consumption each day for the first week after surgery . At 3 weeks , patients recorded the total analgesic requirement , duration of pain , all adverse events during recovery , and return to normal daily activities . RESULTS No pre-emptive effect of ketoprofen was noticed because there was no significant difference in recovery after discharge between patients who had received ketoprofen or placebo during the first 24 hours after surgery . In the whole study group , the median of pain cessation was 11 days ( range , 3 - 24 days ) and the median of analgesic treatment was 12 days ( range , 5 - 25 days ) . More than 50 % of the patients needed 1 to 3 rescue analgesic doses daily during the first week after tonsillectomy . A return back to normal daily activities took place after 12 days ( range , 2 - 24 days ) . Nine patients needed electrocautery to stop postoperative bleeding . No other serious adverse events occurred . CONCLUSIONS The main problem after tonsillectomy is significant pain that can last 11 to 12 days after surgery . Ketoprofen combined with paracetamol-codeine provided sufficient analgesia for most patients at home , but because ketoprofen may cause an increase in the secondary hemorrhage rate , it should be prescribed with caution |
940 | 26,172,035 | Based on this systematic review and meta- analysis , there is no evidence of differences in outcomes or metabolic control in patients undergoing pancreatic transplant with portal venous drainage compared to the systemic venous drainage | Pancreas transplantation venous effluent can be drained via the portal vein or the systemic circulation ; however , no recommendation exists for the ideal technique . | It has been shown that lipid profiles do not differ between pancreas recipients with systemic and portal venous anastomosis . However , it is unclear whether venous drainage from the transplanted pancreas has an impact on recipient atherogenesis and if other factors should be considered . Increased concentration of proinsulin correlates with tachycardia and other risk factors for ischemic heart disease . The aim of this study was to compare proinsulin levels in different types of pancreatic graft venous drainage . Twenty-four simultaneous pancreas and kidney transplantation ( SPK ) recipients with systemic venous drainage ( group S , n = 12 ) and portal venous drainage ( group P , n = 12 ) under identical immunosuppressive treatment were prospect ively observed during 24 months . Following transplantation , only recipients with normoglycemia , normal HbA1c , and normal serum creatine were evaluated . Proinsulin was assessed in fasting state ; after glucagon stimulation ( Delta-proinsulin ) , and during oral 75-g glucose tolerance test twice : between 3 and 6 months and 12 to 24 months posttransplantation . All SPK patients had higher proinsulin concentration in fasting state compared with age-matched healthy controls . After stimulation , proinsulin level did not significantly differ between groups ; the type of the pancreas venous anastomosis did not change the release of proinsulin and should not have impact on cardiovascular risk factors Abstract A r and omized study of combined kidney-pancreas transplantation was performed on 30 insulin-dependent diabetic patients with end-stage renal disease to compare the consequences of pancreas transplantation with portal venous ( PV ) and systemic venous ( SV ) drainage . Fourteen patients ( SV group ) received systemically drained and sixteen ( PV group ) portally drained pancreas allografts . Enteric drainage was performed in both groups . The routine follow-up included documentation of the clinical course and detailed endocrine studies . At 1 year after transplantation , the patient survival rate was 92 % for the SV group and 96 % for the PV group ; the graft survival rate was 78 % and 82 % , respectively . Endocrine studies indicated no difference in fasting and stimulated glucose or in glycosylated hemoglobin between the two groups . In addition , no hyperinsulinemia and lipidic abnormalities were evidence d in either group Long-term studies are required to conclude whether PV and SV drainage in pancreas transplantation are equivalent in terms of patient and graft survival as well as metabolic consequences BACKGROUND Most pancreas transplants are performed with systemic venous delivery of insulin and bladder drainage of the exocrine secretions ( systemic-bladder [ S-B ] ) . To develop a more physiologic procedure , we performed pancreas transplantations with portal venous delivery of insulin and enteric drainage of the exocrine secretions ( portal-enteric [ P-E ] ) . METHODS During an 11-month period , we prospect ively alternated 32 consecutive pancreas transplant recipients to either S-B ( n = 16 ) or P-E ( n = 16 ) drainage with st and ardized immunosuppression . RESULTS Patient , kidney , and pancreas graft survival rates after simultaneous kidney-pancreas transplantation were 91 % S-B versus 92 % P-E , 91 % S-B versus 92 % P-E , and 82 % S-B versus 92 % P-E , respectively . Pancreas graft survival rates after solitary pancreas transplantation were 80 % S-B versus 75 % P-E. There were no graft losses either to immunologic or infectious complications in either group , but the incidence of acute rejection was slightly higher in the S-B group ( 44 % S-B vs 31 % P-E , P = NS ) . The cost and length of the initial hospital stay were similar between groups . The incidence of operative complications , major infections , and cytomegalovirus infections were likewise comparable . However , the S-B group was characterized by a slight increase in the number of readmissions , urinary tract infections , and urologic complications . Furthermore , metabolic acidosis and dehydration were more common in the S-B group . CONCLUSIONS Pancreas transplantation with P-E drainage can be performed with short-term results comparable to those of transplantation with S-B drainage Simultaneous pancreas‐kidney ( SPK ) transplantation is considered a valid therapeutic option for patient with type I diabetes mellitus and end‐stage diabetic nephropathy . This study was performed to determine whether the technique of pancreas venous drainage affects patient survival as well as graft survival and function . From October 1996 to April 1999 34 uremic patients with type I diabetes mellitus were r and omly assigned to two groups : the first group ( SV group=17 ) received SPK transplantation with systemic venous drainage , and the second group ( PV group=17 ) received pancreas allograft with portal drainage . A Roux‐en‐Y loop was performed in all the patients . Patient follow‐up included clinical course and metabolic studies . At 1 yr , patient survival rates were 88.2 % in the SV group and 94.1 % in the PV group while graft survival rate was 76.4 % in both groups . Several surgical complications were attributed to the enteric drainage without any graft failure in both groups . One venous thrombosis occurred in each group . No significant differences have been evidence d in kidney and pancreas function . The preliminary results of this r and omized trial did not evidence any significant differences between portal and systemic venous drainage of pancreas allograft Abstract : The impact of portal or systemic venous pancreas graft drainage on patient and graft outcome remains controversial . In the present study , the impact of venous drainage type on long‐term patient and graft survival is assessed . From July 1996 to December 2002 80 simultaneous pancreas‐kidney transplants were enrolled into a prospect i ve study : 44 received a pancreas allograft with portal ( P‐SPK group ) and 36 with systemic venous drainage ( S‐SPK group ) . Enteric exocrine drainage was performed in all recipients receiving the same immunosuppressive treatment . At one yr , the patient survival rates were 91.7 % and 95.5 % both for S‐SPK and P‐SPK groups , respectively ; no significant difference in survival was shown at any time point of the follow‐up . The one‐ , three‐ , five‐ , and eight‐yr pancreas survival rates were 75 % , 60.6 % , 56.7 % , and 44 % , respectively in the S‐SPK group compared to 88.6 % , 84.1 % , 78.4 % , and 31.3 % in the P‐SPK group . The one‐ , three‐ , five‐ , and eight‐yr kidney survival rates were 91.7 % , 78.15 % , 74.1 % , and 57.9 % , respectively in the S‐SPK group compared to 93.2 % , 88.6 % , 78.4 % , and 38.9 % in the P‐SPK group . Comparing the two groups , no significant difference was shown in the total number of surgical complications as well as in the number of each complication . No significant difference in long‐term outcomes between the two groups was shown , even if in S‐SPK group a higher incidence of pancreas graft loss has been reported and it was in part correlated to a higher number of graft thromboses Objective To test the hypothesis that pancreas transplantation using the more physiologic method of portal venous-enteric ( PE ) drainage could be performed without compromising patient and graft outcome , compared with the st and ard method of systemic venous-bladder ( SB ) drainage . Methods Between November 1995 and November 1998 , the authors prospect ively followed up 20 consecutive patients with SB drainage followed by 20 consecutive patients with PE drainage . All patients underwent simultaneous pancreas – kidney transplantation , and all were immunosuppressed with antilymphocyte serum , cyclosporin , azathioprine , and steroids . Results The actuarial patient survival rate at 1 year was 95 % in the SB group and 100 % in the PE group . Death-censored kidney graft survival was 100 % in both groups ; pancreas graft survival was 95 % in the SB group and 100 % in the PE group . The mean initial hospital stay was 15 days for both groups . However , during the first 6 months after transplantation , the SB group required more medical day-unit visits , mostly for treatment of metabolic acidosis and dehydration . The incidence of urinary tract infections was similar in both groups . The incidence of cytomegalovirus infections was significantly less in the PE group . The incidence of acute rejection was 37 % in the SB group and 15 % in the PE group . Mean serum creatinine levels 6 months after transplantation were significantly lower in the PE group than in the SB group . Glycemic control was excellent in both groups , but fasting serum insulin levels were significantly lower in the PE group . Conclusions The PE method of pancreas transplantation can be performed with excellent patient and graft outcomes Since 1995 , many centers have switched from bladder to enteric drainage of the exocrine secretions in simultaneous kidney-pancreas transplantation ( SKPT ) . Enteric exocrine drainage may be performed with either systemic ( systemic-enteric [ S-E ] ) or portal ( portal-enteric [ P-E ] ) venous delivery of insulin . Controversy exists regarding the optimal surgical technique . From March 1999 to May 2001 , a total of 297 SKPT patients were enrolled into a prospect i ve , multicenter , r and omized , open-label , comparative trial of two daclizumab dosing strategies versus no-antibody induction in combination with tacrolimus , mycophenolate mofetil , and steroids in SKPT recipients . Surgical techniques were center specific . A total of 171 patients ( 58 % ) underwent SKPT with S-E drainage , 96 ( 32 % ) with P-E drainage , and 30 ( 10 % ) with systemic-bladder ( S-B ) drainage . The two groups r and omized to daclizumab induction were similar with regard to surgical technique ( 64 % S-E , 25 % P-E , 11 % S-B drainage ) . Demographic and transplant characteristics and immunosuppression were similar among the three groups , except that more patients with P-E drainage did not receive antibody induction . At 6 months , no differences were seen in patient and graft survival rates , surgical complications including pancreas thrombosis , rates of rejection or infection , readmissions , and kidney and pancreas allograft function among the three different surgical techniques . The 6-month results of this multicenter study suggest no significant differences in outcomes in SKPT recipients according to surgical technique Objective To compare pancreas transplantation with systemic-enteric ( SE ) versus portal-enteric ( PE ) drainage in a prospect i ve fashion . Summary Background Data To improve the physiology of pancreas transplantation , the authors developed a new technique of portal venous delivery of insulin and enteric drainage of the exocrine secretions . Methods During a 26-month period , the authors prospect ively alternated 54 consecutive simultaneous kidney and pancreas transplants to either SE ( n = 27 ) or PE ( n = 27 ) drainage . The two groups were well matched for numerous characteristics . Maintenance immunosuppression in both groups consisted of tacrolimus , mycophenolate mofetil , and steroids . Results Patient survival rates were 93 % SE versus 96 % PE ; kidney graft survival rates were 93 % in both groups . Pancreas transplantation survival ( complete insulin independence ) was 74 % after SE versus 85 % after PE drainage with a mean follow-up of 17 months . The mean length of initial hospital stay was 12.4 days in the SE group and 12.8 days in the PE group . The SE group was characterized by a slight increase in the number of readmissions . The incidences of acute rejection ( 33 % ) and major infection ( 52 % ) were similar in both groups . The incidence of intraabdominal infection was slightly higher in the SE group . However , the early relaparotomy rate was similar between groups . The composite endpoint of no rejection , graft loss , or death was attained in 56 % of SE versus 59 % of PE patients . Conclusions These results suggest that simultaneous kidney and pancreas transplantation with SE or PE drainage can be performed with comparable short-term outcomes OBJECTIVE To determine the long-term effect of a functioning pancreas transplant on peripheral vasculopathy . DESIGN We compared the progression of peripheral vascular disease in 39 recipients of successful kidney-pancreas transplants ( KPT ) with 65 consecutive diabetic patients who received cadaver kidney transplants alone ( KTA ) during the same period in a nonr and omized , retrospective control study . The mean duration of follow-up was more than 4 years in both groups . SETTING Academic subspecialty referral practice . PATIENTS A consecutive sample of all KPT recipients with more than 6 months of pancreas allograft function performed between May 1 , 1988 , and April 30 , 1995 . All patients who received cadaver renal transplants for diabetic nephropathy during the same period and who maintained a functioning renal allograft for more than 6 months were included as controls . INTERVENTION Kidney-pancreas transplantation . MAIN OUTCOME MEASURE Progression of peripheral vascular complications ( PVC ) defined as any midfoot or limb amputation ( AMP ) , any ischemic ulceration requiring treatment ( ULCER ) , and lower-extremity bypass surgery or angioplasty ( LEBP ) . Ulcers leading to amputation were considered as single events ( AMP only ) . RESULTS Thirty-five ( 90 % ) of 39 KPT recipients are insulin-free . The KTA recipients had more atherosclerotic risk factors , including a higher incidence of coronary artery disease ( P = .008 ) , higher serum cholesterol levels ( P = .03 ) , and higher triglyceride levels ( P = .04 ) than KPT recipients . Peripheral vascular complications before transplantation were comparable ( P = .94 ) between groups . After transplantation , there were 35 new PVC ( 9 AMP , 11 ulcers , and 15 LEBP ) in 18 of 39 KPT recipients vs 32 PVC ( 10 AMP , 8 ulcers , and 14 LEBP ) in 20 of 65 KTA recipients ( P = .005 ) , indicating that KPT recipients had more PVC than did KTA recipients , despite a functioning pancreas . Seven bypass grafts failed after KPT , result ing in 6 limb amputations . In contrast , only 3 limb amputations were performed in 14 patients undergoing lower-extremity bypass procedures after KTA . CONCLUSIONS Despite fewer risk factors for peripheral vasculopathy and the presence of insulin independence , KPT recipients had a higher incidence of PVC than a cohort of uremic diabetic patients undergoing KTA during the same period . These data show that a functioning pancreas allograft performed with a renal transplantation not only does not alter the progression of peripheral vascular disease in patients with renal failure secondary to diabetic nephropathy but also may accelerate PVC |
941 | 30,477,408 | Results : There is a sufficient level of evidence to support the use of stretching as and effective techniques in rehabilitation .
Conclusion : The review adds stronger underst and ing with regard to stretching considerations in rehabilitation following UMNs . | ABSTRACT Background : As clinicians , muscles stretching approaches are one of the most commonly used interventions in rehabilitation .
However , there is a need for an in-depth evaluation of research on prolonged stretching in terms of the features of the stretching approaches , such as duration and frequency , as well as the compatible measures of a successful stretching approach .
Objective : This review is an effort to synthesize findings from studies on “ prolonged ” stretching approaches in patients with UMNs including stroke , spinal cord injuries , and traumatic brain injuries .
We investigated the compatible features of successful stretching regimens in terms of reducing spasticity , improving the Active Range of Motion ( AROM ) , Passive Range of Motion ( PROM ) , and gait training of spastic patient with upper motor neuron lesions . | PURPOSE To compare the effect of static holds and continuous passive motion on stiffness and force relaxation of the soft tissue structures resisting ankle joint dorsiflexion . METHODS This study used a r and omized repeated measures trial design . Twenty-four asymptomatic subjects ( 15 males and 8 females ) with a mean age of 26 yr participated . A Kin-Com dynamometer was used to measure the stiffness and force relaxation response of tissues about the ankle joint in response to a plantar flexor stretch . A comparison was made of the response for a 1 x 60-s hold , 2 x 30-s holds , 4 x 15-s holds , and continuous passive motion for 60 s. All subjects undertook all conditions . The main outcome measures were 1 ) stiffness at the ankle joint as it moved to 80 % of the maximum range of dorsiflexion , and 2 ) the decrease in force at 80 % of the maximum range of motion of the ankle joint . RESULTS Stiffness was decreased significantly ( P < 0.05 ) for the continuous passive motion condition only . The mean magnitude of the decrease in stiffness was 16 % . Across hold times , force decreased significantly ( P < 0.05 ) . Bonferonni contrasts indicated that there was a significant difference ( P < 0.05 ) between the continuous passive motion condition and all other hold conditions . There were no significant differences ( P > 0.05 ) between the 4 x 15-s , 2 x 30-s , and 1 x 60-s holds . The magnitude of the decline in force was 10.5 % , 21.5 % , 21.7 % , and 19 % for the 0- , 15- , 30- , and 60-s holds , respectively . The greatest decreases in tension were achieved in the first 20 s of a hold . CONCLUSION If decreasing stiffness is a key aim of a stretching program , the findings indicate that continuous motion is more effective than holds . In contrast , if relaxation of peak tension is the main aim , then holds are most effective Objective : To establish if isokinetic and isotonic muscle stretch ( with or without weight-bearing ) of the ankle plantar flexors improves gait in hemiplegic patients . A further aim was to compare the effectiveness of these treatment methods . Design : A r and omized , parallel group prospect i ve study . Setting : A stroke rehabilitation unit . Subjects : Ambulatory hemiparetic stroke patients with mild to moderately severe muscle hypertonia of the lower limb and a group of healthy control subjects . Intervention : Subjects were r and omized to receive a single 20-min session of isokinetic muscle stretch or isotonic muscle stretch with or without weight-bearing . Outcome measures : Selected kinematic , kinetic and spatio-temporal gait parameters were measured at baseline , immediately after the muscle stretch and 24 h later . Results : Sixty-six patients and 21 healthy control subjects were recruited and completed the study . There were statistically significant differences between the patient groups and the healthy subjects on most of the gait parameters studied . However , the differences between the patient groups or between the three measurements over time for each type of muscle stretch did not reach statistical significance . Conclusions : A single session of isokinetic or isotonic muscle stretch ( with or without weight-bearing ) of the ankle plantar flexors has no clinical ly observable effect on the gait of hemiplegic stroke patients The purpose of this study was to compare the effects of cyclic versus sustained passive stretching with a mechanical device on resting hamstring muscles ' length . Group 1 subjects ( 5 men , 17 women ) underwent cyclic stretching of their right hamstring musculature , and Group 2 subjects ( 5 men , 16 women ) underwent sustained stretching of their right hamstring musculature . The stretching procedures were performed for 15 minutes on 5 consecutive days . A follow-up examination of the subjects ' relative knee flexion range of motion was made one week posttreatment . The Group 1 subjects had a mean ROM increase of 15.4 + /- 5.0 degrees after the five stretching treatments and maintained a mean ROM increase of 10.4 + /- 5.5 degrees on the follow-up examination ( p less than .001 ) . In Group 2 , the five stretching treatments result ed in a mean ROM increase of 13.4 + /- 4.4 degrees , and a mean increase of 7.9 + /- 4.0 degrees was maintained on the follow-up examination ( p less than .001 ) . Linear regression analysis revealed that initial ROM , sex , and treatment method significantly contributed to increases in ROM from Day 1 of treatment to the follow-up examination ( F = 6.04 ; df = 4,36 ; p less than .0008 ) . The cyclic stretching method result ed in a greater gain in ROM when the other variables were considered . Predicted values of ROM increases were also examined and discussed OBJECTIVE To determine the effect of 4 weeks of 30 minutes of daily stretching on ankle mobility in patients with recent spinal cord injuries ( SCIs ) . DESIGN Assessor-blinded r and omized controlled trial . SETTING Two spinal injury units in Sydney , Australia . PATIENTS Consecutive sample of 14 recently injured patients with paraplegia and quadriplegia . INTERVENTION Treated ankles were stretched continuously into dorsiflexion with a torque of 7.5 N x m for 30 minutes each weekday for 4 weeks . Contralateral ankles received no stretches . MAIN OUTCOME MEASURES Passive torque-angle curves for both ankles were obtained at study commencement , then at weeks 2 , 4 , and 5 ( ie , during , at the end of , and 1 week after the stretching program ) . Torque-angle measurements were obtained with the knee extended and flexed . Mean values for parameters ( baseline angle , angle at 10 N x m , slope ) describing the characteristics of the torque-angle curves were derived for each knee position . Changes from pretest to each subsequent test were calculated , as well as 95 % confidence intervals ( CIs ) for differences in these changes between stretched and controlled ankles . RESULTS The stretching intervention did not significantly change any of the 3 parameters describing the torque-angle curves of the ankle in either knee position . At the beginning of the study , the mean ( + /-SD ) angles obtained with the application of a st and ardized torque with the knee extended for the control and stretch ankles were 105 degrees ( + /- 10.4 degrees ) and 106 degrees ( + /- 9.8 degrees ) , respectively . After 4 weeks , these values were 106 degrees ( + /- 10.6 degrees ) and 107 degrees ( + /- 10.6 degrees ) ( mean difference in change of angle = 0 degrees ; 95 % CI , -3.3 degrees to 3.3 degrees ) . CONCLUSION Thirty minutes of daily stretching for 4 weeks does not significantly change ankle mobility in recently injured patients with SCIs BACKGROUND AND PURPOSE Ankle plantar-flexion contractures are a common problem following traumatic head injury . Although serial casting is used to correct and prevent ankle plantar-flexion contractures , treatment efficacy has not been evaluated using an experimental design . The aim of this research was to establish the effect of a regimen of casting combined with stretching on passive ankle dorsiflexion motion . SUBJECTS Nine people who had sustained traumatic closed head injuries and had limited dorsiflexion motion participated in the study . METHODS A crossover design was used in the study . Subjects were assigned to both experimental and control groups . Torque-controlled measurements of passive ankle dorsiflexion motion were obtained for all subjects before and after 1 week of casting combined with stretching , as well as before and after a 1-week control period . The order of the experimental and control conditions was r and omized . RESULTS Passive ankle dorsiflexion increased by a mean of 13.5 degrees ( SD = 9.3 ) during the experimental condition , as compared with a mean decrease of 1.9 degrees ( SD = 10.2 ) during the control condition . The difference between the experimental and control conditions was statistically significant . CONCLUSION AND DISCUSSION These findings suggest that casting combined with stretching is an effective method of correcting ankle plantar-flexion contractures in patients with traumatic head injuries The aims of this study are to vali date the hypertonia treatment/ assessment system and to quantify the immediate effect of prolonged muscle stretch ( PMS ) on the inhibition of ankle hypertonia in stroke patients . For PMS treatment , ankle plantarflexors were stretched with a constant torque in 25 subjects with hemiplegia and ankle plantarflexors hypertonia . Using the developed hypertonia treatment/ assessment system , the effects of the PMS treatment were quantified by comparing the reactive torque measurements of the ankle joint before and after the treatment sessions in terms of elastic ( elastic-inertia ) ( K(ei ) ) and viscous ( K(v ) ) components . It was shown that an application of PMS for 30 min using a constant stretching force , approximately 80 % of the torque measured at the maximal passive ROM dorsiflexion position , significantly reduces both components of the ankle joint torque ( P < 0.05 ) . The present results suggested that the application of PMS with a constant torque could reduce not only the elasticity of the hypertonic muscles , but also their viscosity in the stroke patients Reflex behavior and tension development in upper limb muscles were analyzed and comparisons made between the unaffected and spastic sides of patients with spastic hemiparesis . During sinusoidal ( 0.3‐Hz ) isometric or isotonic elbow tracking , with a control either of joint position or of torque , r and omly timed displacements were induced ( at one of three velocities ) stretching either the activated flexor or the extensor muscles . On the spastic side , exaggerated short‐latency reflexes were apparent , but in contrast , the amplitude of long‐latency electromyography ( EMG ) responses was reduced . The latter responses were differentially modulated on the unaffected side , predominantly by the acceleration signal during control of position and more by the velocity signal during control of torque , while the mode of muscle contraction ( isometric or isotonic ) had little influence on this behavior . This difference in reflex modulation was lost on the spastic side . The functional consequence of this reduced EMG modulation could be difficulty in performing finely controlled arm movements . The ratio of torque to EMG activity during displacements was higher for both background and reflex‐induced EMG on the spastic limb than on the unaffected side . This effect was more pronounced for the flexor than for the extensor muscles . Consequently , the development of spastic muscle hypertonia can not be attributed to an increase in EMG activity . It is suggested that secondary to a supraspinal lesion , mechanical muscle properties change in such a way that the activated spastic muscle develops more tension when it is stretched OBJECTIVE To investigate the effect of repeated feedback-controlled and programmed " intelligent " stretching of the ankle plantar- and dorsiflexors to treat subjects with ankle spasticity and /or contracture in stroke . DESIGN Noncontrolled trial . SETTING Institutional research center . PARTICIPANTS Subjects with spasticity and /or contracture after stroke . INTERVENTIONS Stretching of the plantar- and dorsiflexors of the ankle 3 times a week for 45 minutes during a 4-week period by using a feedback-controlled and programmed stretching device . MAIN OUTCOME MEASURES Passive and active range of motion ( ROM ) , muscle strength , joint stiffness , joint viscous damping , reflex excitability , comfortable walking speed , and subjective experiences of the subjects . RESULTS Significant improvements were found in the passive ROM , maximum voluntary contraction , ankle stiffness , and comfortable walking speed . The visual analog scales indicated very positive subjective evaluation in terms of the comfort of stretching and the effect on their involved ankle . CONCLUSIONS Repeated feedback-controlled or intelligent stretching had a positive influence on the joint properties of the ankle with spasticity and /or contracture after stroke . The stretching device may be an effective and safe alternative to manual passive motion treatment by a therapist and has potential to be used to repeatedly and regularly stretch the ankle of subjects with spasticity and /or contracture without daily involvement of clinicians or physical therapists Application of eccentric contractions and muscle stretch are clinical ly effective in reducing spasticity and increasing ROM ( 7 ) . This may be explained by a change in the excitability of motoneurons supplying the spastic muscle . Excitability of motoneurons can be indirectly assessed using the H-reflex . Experiments were performed on 20 normal subjects and 17 subjects with spasticity result ing from neurological disorder . Subjects were seated in a secure position and the ankle joint was moved from 30 degrees plantarflexion to 20 degrees dorsiflexion at a velocity of 30 degrees/sec . Sixty eccentric contractions of the triceps surae muscle were performed using a Kin-Com dynamometer ( Chattanooga Corp , Tennessee ) . Two protocol s were used : ( 1 ) eccentric contractions only , and ( 2 ) eccentric contractions with a 5s stretch of the relaxed triceps surae after each contraction . Two sets of 10 H-reflexes were collected from the soleus muscle before ( trial 1 & 2 ) and after ( trial 3 & 4 ) eccentric and eccentric + stretch protocol s. The mean peak to peak H-reflex amplitude was calculated for each trial and compared using ANOVA . Eccentric contractions result ed in a significant and maintained increase in the H-reflex in neurological compared to normal subjects ( P < 0.05 ) . Eccentric contractions in subjects with spasticity result ed in an increase in motoneuron excitability which may assist in corticospinal activation of motoneurons during voluntary movement . The eccentric + stretch protocol , result ed in a decrease in the mean amplitude of H-reflexes in neurological subjects , however , this was not significant . The application of a stretch following eccentric contractions decreased motoneuron excitability and may thus be beneficial to decrease spasticity whilst strengthening muscle |
942 | 30,571,209 | Conclusions : PPMI is common following TAVR and is strongly associated with 30-day and 1-year mortality .
Detection of PPMI has potential to identify TAVR patients at highest risk of subsequent adverse events | Background : The aim was to assess whether periprocedural myocardial injury ( PPMI ) predicts outcomes in patients undergoing transcatheter aortic valve replacement ( TAVR ) .
PPMI is a strong predictor of outcomes following coronary intervention , but its impact in the context of TAVR remains unclear .
We performed a systematic review and meta- analysis to ascertain the association between PPMI and short- or long-term outcomes . | Objective To evaluate the relevance of the individual components of the Valve Academic Research Consortium (VARC)-2 criteria for periprocedural myocardial infa rct ion ( MI ) in transcatheter aortic valve implantation ( TAVI ) . The association between biomarkers and adverse procedural outcome has been established . However , the additive prognostic importance of signs and symptoms are more uncertain . Methods A total of 125 consecutive TAVI patients were prospect ively included in this study . Biomarkers for MI were analyzed and signs and symptoms according to VARC-2 criteria were collected from clinical records . Results The criteria of elevated biomarkers and of signs or symptoms were found in 27 ( 22 % ) and 32 ( 26 % ) of the patients , respectively . According to VARC-2 definition , 12 ( 10 % ) had MI . VARC-2 definition of MI , Troponin T ( TnT ) > 600 ng/L , and presence of signs or symptoms correlated with 6 months mortality , prolonged ICU stay , elevation of N-terminal prohormone brain natriuretic peptide , and renal impairment . No signs or symptoms were found in 7 ( 44 % ) of the patients who fulfilled the criterion of elevated TnT > 600 ng/L. In the group with positive TnT criterion , there were no significant differences between those with and without signs or symptoms in respect to levels of TnT ( 1014 [ 585–1720 ] ng/L versus 704 [ 515–905 ] ng/L , p = 0.17 ) or creatine kinase-MB ( 36 [ 25–52 ] μg/L versus 29 [ 25–39 ] μg/L , p = 0.32 ) . In the multivariate Cox regression analysis , TnT > 600 ng/L was the only significant independent variable associated with 6-months postprocedural mortality . Conclusions Myocardial injury in TAVI , measured with biomarkers , correlates well with adverse procedural outcome . In this study it is also the strongest predictor for early postprocedural mortality . The additional requirement of signs or symptoms for the diagnosis of MI results in omission of a considerable number of clinical ly significant MI AIM Risk assessment of patients undergoing transcatheter aortic valve implantation ( TAVI ) remains difficult . Biomarkers have been shown to provide potential prognostic information . Here , we aim ed to analyze whether the biomarker high-sensitivity Troponin T ( hsTNT ) could be used to improve risk stratification . METHOD We prospect ively enrolled 267 patients undergoing TAVI . Biomarkers ( hsTNT and NTproBNP ) were measured 1 day before , and 3 and 7 days postprocedure . All possible prognostic factors upon survival time were analyzed by Cox regression analysis . RESULTS A total of 259 patients ( mean age 82±6.1 years ) were available for complete follow-up . The median Logistic EuroSCORE ( Log ES ) and Log ES II were 21.16 % ( Q1=13.92 ; Q3=34.27 ) and 6.42 % ( Q1=3.89 ; Q3=11.07 ) , respectively . Median follow-up was 290 ( Q1=88 ; Q3=529 ) days . A total of 71 deaths occurred during follow-up , and the 30-day mortality was 5.8 % . Median baseline hsTNT was 27.4 pg/mL ( Q1=16.2 ; Q3=46 pg/mL ) . From all potential mortality-associated factors , only preprocedural hsTNT level ( P=.001 ) , elevated Log ES ( P=.03 ) as well as acute kidney injury ( P<.001 ) and chronic obstructive pulmonary disease ( COPD ) ( P=.039 ) emerged as independent prognostic parameters for adverse outcome . We also tested whether the Valve Academic Research Consortium-2 ( VARC-II ) cutoff for myocardial damage ( hsTNT peak value exceeding 15 × the upper reference limit + at least 50 % increase ) was of prognostic relevance . At 72-hours post-TAVI , 36.2 % of the patients matched these VARC-II criteria of myocardial damage . However , these patients did not display a difference in survival compared to patients without significant myocardial injury . CONCLUSION Elevated preprocedural hsTNT represents an independent risk predictor of all-cause death while periprocedural hsTNT elevation failed to show prognostic relevance Background —Postprocedural myocardial infa rct ion ( type 4a ) has been shown to be an adverse prognostic indicator after elective percutaneous coronary intervention ( PCI ) . The Cardiac Remote Ischemic Preconditioning in Coronary Stenting ( CRISP Stent ) study demonstrated that remote ischemic preconditioning reduced procedural symptoms , ECG ST-segment deviation , and cardiac troponin I release after elective PCI and reduced the major adverse cardiac and cerebral event ( MACCE ) rate at 6 months . We were interested to confirm if this early benefit in MACCE rate in the remote ischemic preconditioning group was sustained long-term . Methods and Results — Patients were telephoned by research ers blinded to the r and omization details . MACCE , defined as all-cause mortality , nonfatal myocardial infa rct ion , transient ischemic attack or stroke , and heart failure requiring hospital admission , were adjudicated by case note and national data base review . One hundred ninety-two ( 89.3 % ) of the 225 patients with elective PCI r and omized in the original study were available for long-term follow-up ( mean time to event or last follow-up : 1579.7±603.6 days ) . There were a total of 59 ( 30.7 % ) MACCEs . Patients with an MACCE had a higher mean cardiac troponin I after PCI ( ±SD ) : 2.07±6.99 versus 0.91±2.07 ng/mL ( P=0.05 ) . The MACCE rate at 6 years remained lower in the remote ischemic preconditioning group ( hazard ratio , 0.58 ; 95 % confidence interval , 0.35–0.97 ; P=0.039 ; absolute risk reduction=0.13 and number needed to treat=8 to prevent the MACCE at 6 years ) . Conclusions —Remote ischemic preconditioning reduces the incidence of postprocedural cardiac troponin I after elective PCI and confers an MACCE-free survival benefit at both short- and long-term follow-up . Clinical Trial Registration —URL : http://www.ukcrn.org.uk . Unique identifier : UKCRN 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 Elevated concentrations of troponin T have prognostic impact in patients with various cardiovascular diseases including those with severe aortic stenosis . Transcatheter aortic valve implantation ( TAVI ) has improved prognosis for patients without a surgical option . Whether this affects the prognostic value of preinterventional troponin T remains unclear . Methods We therefore conducted a prospect i ve study in 198 consecutive patients with subsequent , successful transfemoral TAVI and analyzed cardiac troponin T ( cTnT ) levels with a new generation , high-sensitive troponin T assay before and after TAVI , as well as their prognostic value after 12 months . Results Patients with severe aortic stenosis ( AS ) showed significant elevation of preinterventional cTnT levels . Postinterventional cTnT levels significantly rose further about sevenfold after transfemoral TAVI and peaked at day three until they steadily declined thereafter . Baseline renal function ( P = 0.011 ) , the duration of intraprocedural rapid pacing ( P = 0.0012 ) , and baseline cTnT ( P = 0.0001 ) values predicted the magnitude of postinterventional cTnT elevations . Interestingly , Kaplan – Meier curve analysis revealed , that although cTnT levels were not predictive for short-term mortality , preinterventional as well as postinterventional peak cTnT showed prognostic value for 1-year mortality , regardless of successful TAVI . Conclusions Pre- and postinterventional hscTnT levels signal adverse 1-year mortality in patients with severe AS independent of successful aortic valve replacement BACKGROUND Previous trials have shown that among high-risk patients with aortic stenosis , survival rates are similar with transcatheter aortic-valve replacement ( TAVR ) and surgical aortic-valve replacement . We evaluated the two procedures in a r and omized trial involving intermediate-risk patients . METHODS We r and omly assigned 2032 intermediate-risk patients with severe aortic stenosis , at 57 centers , to undergo either TAVR or surgical replacement . The primary end point was death from any cause or disabling stroke at 2 years . The primary hypothesis was that TAVR would not be inferior to surgical replacement . Before r and omization , patients were entered into one of two cohorts on the basis of clinical and imaging findings ; 76.3 % of the patients were included in the transfemoral-access cohort and 23.7 % in the transthoracic-access cohort . RESULTS The rate of death from any cause or disabling stroke was similar in the TAVR group and the surgery group ( P=0.001 for noninferiority ) . At 2 years , the Kaplan-Meier event rates were 19.3 % in the TAVR group and 21.1 % in the surgery group ( hazard ratio in the TAVR group , 0.89 ; 95 % confidence interval [ CI ] , 0.73 to 1.09 ; P=0.25 ) . In the transfemoral-access cohort , TAVR result ed in a lower rate of death or disabling stroke than surgery ( hazard ratio , 0.79 ; 95 % CI , 0.62 to 1.00 ; P=0.05 ) , whereas in the transthoracic-access cohort , outcomes were similar in the two groups . TAVR result ed in larger aortic-valve areas than did surgery and also result ed in lower rates of acute kidney injury , severe bleeding , and new-onset atrial fibrillation ; surgery result ed in fewer major vascular complications and less paravalvular aortic regurgitation . CONCLUSIONS In intermediate-risk patients , TAVR was similar to surgical aortic-valve replacement with respect to the primary end point of death or disabling stroke . ( Funded by Edwards Lifesciences ; PARTNER 2 Clinical Trials.gov number , NCT01314313 . ) OBJECTIVES The aim of this study was prospect i ve investigation of silent and clinical ly apparent cerebral embolic events and neurological impairment after transfemoral aortic valve implantation ( TAVI ) . BACKGROUND TAVI is a novel therapeutic approach for multimorbid patients with severe aortic stenosis . We investigated peri-interventional cerebral embolism with diffusion-weighted magnetic resonance imaging ( DW-MRI ) and its relationship to clinical and serologic parameters of brain injury . METHODS Cerebral DW-MRI was performed before , directly , and 3 months after TAVI with the current third-generation self-exp and ing CoreValve ( Medtronic , Minneapolis , Minnesota ) prosthesis . At the timepoints of the serial MRI studies , focal neurological impairment was assessed according to the National Institutes of Health Stroke Scale ( NIHSS ) , and serum concentration of neuron-specific enolase ( NSE ) , a marker of the volume of brain tissue involved in an ischemic event , were determined . RESULTS Thirty patients were enrolled ; 22 completed the imaging protocol . Three patients ( 10 % ) had new neurological findings after TAVI , of whom only 1 ( 3.6 % ) had a permanent neurological impairment . Of the 22 TAVI patients with complete imaging data , 16 ( 72.7 % ) had 75 new cerebral lesions after TAVI presumed to be embolic . The NIHSS and NSE were not correlated with DW-MRI lesions . CONCLUSIONS The incidence of clinical ly silent peri-interventional cerebral embolic lesions after TAVI is high . However , in this cohort of 30 patients , the incidence of persistent neurological impairment was low . ( Incidence and Severity of Silent and Apparent Cerebral Embolism After Conventional and Minimal-invasive Transfemoral Aortic Valve Replacement ; NCT00883285 ) |
943 | 31,665,040 | Conclusions School-based interventions are generally effective in reducing excessive weight gain of children . | Background Childhood obesity is a serious public health concern .
School-based interventions hold great promise to combat the rising trend of childhood obesity .
This systematic review aim ed to assess the overall effects of school-based obesity prevention interventions , and to investigate characteristics of intervention components that are potentially effective for preventing childhood obesity . | Background Obesity has become a global public health problem , which also affects children . It has been proposed that the educational interventions during childhood could be a key strategy in the prevention of obesity . Objective To evaluate the efficacy of an intervention on food habits and physical activity in school children . Methods A 2-year cluster-r and omised prospect i ve study with two parallel arms was used to evaluate an intervention programme in children in their first year of primary schooling ( 5–6 years of age ) in schools in the city of Granollers . The intervention consisted of the promotion of healthy eating habits and physical activity by means of the educational methodology Investigation , Vision , Action and Change ( IVAC ) . At the beginning and at the end of the study ( 2006 and 2008 ) the weight and height of each child was measured in situ , while the families were given a self-report physical activity question naire and the Krece Plus quick test . Results Two years after the beginning of the study , the body mass index of the children in the control group was 0.89 kg/m2 higher than that of the intervention schools . The intervention reduced by 62 % the prevalence of overweight children . Similarly , the proportion of children that ate a second piece of fruit and took part in an after-school physical activity increased in the intervention group . In the control group , the weekly consumption of fish was reduced . Conclusions The educational intervention in healthy eating habits and physical activity in the school could contribute to lessen the current increase in child obesity Summary Background Although childhood overweight and obesity prevalence has increased substantially worldwide in the past three decades , scarce evidence exists for effective preventive strategies . We aim ed to establish whether a school-based intervention for children aged 9–10 years would prevent excessive weight gain after 24 months . Methods This pragmatic cluster r and omised controlled trial of the Healthy Lifestyles Programme ( HeLP ) , a school-based obesity prevention intervention , was done in 32 schools in southwest Engl and . All state-run primary and junior schools in Devon and Plymouth ( UK ) with enough pupils for at least one year-5 class were eligible . Schools were assigned ( 1:1 ) using a computer-generated sequence to either intervention or control , stratified by the number of year-5 classes ( one vs more than one ) and the proportion of children eligible for free school meals ( < 19 % [ the national average ] vs ≥19 % ) . HeLP was delivered to year-5 children ( ages 9–10 years ) over 1 year , and included dynamic and interactive activities such as physical activity workshops , education sessions delivered by teachers with short homework tasks , drama sessions , and setting goals to modify behaviour ( with parental support and one-to-one discussion s with HeLP coordinators ) . The primary outcome was change in body-mass index ( BMI ) st and ard deviation score ( SDS ) between baseline and 24 months , analysed in children with BMI data available for both timepoints . This study is registered with the International St and ard R and omised Controlled Trial register , number IS RCT N15811706 , and the trial status is complete . Findings Between March 21 , 2012 , and Sept 30 , 2013 , 32 eligible schools with 1324 children were recruited , of which 16 schools ( 676 children ) were r and omly assigned to the HeLP intervention and 16 schools ( 648 children ) to control . All schools that began the trial completed the intervention , and 1244 children ( 628 in intervention group and 616 in control group ) had BMI data at both baseline and 24 months for the primary outcome analysis . Mean BMI SDS was 0·32 ( SD 1·16 ) at baseline and 0·35 ( 1·25 ) at 24 months in the intervention group , and 0·18 ( 1·14 ) at baseline and 0·22 ( 1·22 ) at 24 months in the control group . With adjustment for school-level clustering , baseline BMI scores , sex , cohort , and number of year-5 classes and socioeconomic status of each school , the mean difference in BMI SDS score ( intervention – control ) at 24 months was −0·02 ( 95 % CI −0·09 to 0·05 ) , p=0·57 . One parent reported an adverse event related to their child 's eating and activity behaviours , but agreed for the child to continue trial participation after discussion with the chief investigator . Interpretation Despite a theoretically informed and extensively piloted intervention that achieved high levels of engagement , follow-up , and fidelity of delivery , we found no effect of the intervention on preventing overweight or obesity . Although schools are an ideal setting in which to deliver population -based interventions , school-based interventions might not be sufficiently intense to affect both the school and the family environment , and hence the weight status of children . Future research should focus on more upstream determinants of obesity and use whole-systems approaches . Funding UK National Institute for Health Research , Public Health Research Programme Few studies have investigated the impact of school-based physical activity interventions on anthropometric characteristics concomitantly with aerobic and anaerobic capacities in young children . The present study aim ed to assess the effect of a 6-month physical activity program on body composition and physical fitness among primary schoolchildren . Four hundred fifty-seven children aged 6 to 10 years were r and omly assigned to the intervention group ( 229 children ) or observational group ( 228 children ) . Participants ’ height and weight were assessed , and obesity was determined using French reference curves for BMI . The sum of the four skinfolds and fat-free mass were determined . Ground tests were used to assess aerobic ( 20-m shuttle run test ) and anaerobic ( cycling peak power ) fitness before and after a 6-month physical activity intervention . The anthropometric modifications obtained over the 6 months can not be attributed to the intervention as the ANOVA revealed no group effect ( intervention vs. group ) . However , anaerobic and aerobic fitness were significantly improved , thanks to the program in both lean and obese children . A 6-month school-based physical activity intervention in 6- to 10-year-old children did not yield positive anthropometric improvements , but appears effective in terms of aerobic and anaerobic physical fitness . Two physical activity sessions per week in addition to st and ard physical education classes in primary schoolchildren bring effective results for the prevention of childhood obesity Objective : To evaluate the effectiveness of the Shaping Healthy Choices Program ( SHCP ) . Design : A clustered , r and omized , controlled intervention lasting 1 school year . Setting : Schools in northern and central California . Participants : Fourth‐ grade rs ( aged 9–10 years ) at 2 control schools ( n = 179 ) and 2 intervention schools ( n = 230 ) . Intervention : Garden‐enhanced education , family , and community partnerships ; increased regionally procured produce in the lunchroom ; and school‐site wellness committees . Main Outcome Measures : Changes in body mass index ( BMI ) percentiles/Z‐scores ; nutrition knowledge , science process skills , and vegetable identification and preferences ; and reported fruit and vegetable intake . Analysis : Student t test , chi‐square , ANOVA of change , and multilevel regression mixed model to evaluate change in outcomes with school as a r and om effect to account for cluster design effects . Statistical significance was set at P < .05 . Results : There was a greater improvement in BMI percentile ( −6.08 ; P < 0.01 ) , BMI Z‐score ( −0.28 ; P < .001 ) , and waist‐to‐height ratio ( −0.02 ; P < .001 ) in the intervention compared with the control schools . Conclusions and Implication s : The SHCP result ed in improvements in nutrition knowledge , vegetable identification , and a significant decrease in BMI percentiles . This supports the concept that the SHCP can be used to improve the health of upper elementary school students The global rate of obesity in childhood is becoming an epidemic and many authors have established a significant association between childhood obesity and overweight in adulthood . It is therefore necessary to seek effective strategies to reduce these levels of obesity . The aim of this study was to evaluate the impact of the Healthy Habits Program ( HHP ) . The participants comprised 158 children from the fifth and sixth grade s ( intervention group , n = 82 ; control group , n = 76 ) . The HHP is a school-based physical activity program focusing on promoting a healthy lifestyle . It lasted for 8 months , and measurements were taken at the beginning and end of the program . Physiological variables ( total cholesterol , triglycerides , blood glucose , blood pressure , and maximal oxygen consumption ) , anthropometric variables ( body mass index ( BMI ) ) and behavioral variables ( breakfast , quality of diet , meal frequency , physical activity , sedentary behavior , sleep , and perceived health ) were evaluated . Repeated- measures ANOVA showed significant improvements ( p < 0.05 ) after the intervention for the intervention group in triglycerides , blood glucose and maximal oxygen consumption . Significant improvements were also observed in breakfast habits and quality of diet . Finally , a significant improvement in prevalence of normal levels was observed for total cholesterol , blood pressure , and BMI . It can therefore be stated that the HHP is an innovative and useful school-based program that can help to improve diet and health in childhood Background : To investigate whether changing the play environment in primary schools to one that includes greater risk and challenge increases physical activity and reduces body mass index ( BMI ) .Subjects/ Methods : A 2-year cluster r and omised controlled trial was undertaken in 16 New Zeal and schools ( years 1–8 ) . Intervention schools ( n=8 ) re design ed their play environments to encourage imaginative and independent free play by increasing opportunities for risk and challenge ( for example , rough- and -tumble play ) , reducing rules and adding new playground components ( for example , loose parts ) . Control schools ( n=8 ) were asked to not change their play environment . A qualified playworker rated all school play environments at baseline and 1 year . Primary outcomes were moderate-to-vigorous physical activity ( 7-day accelerometry ) and BMI z-score , collected in 840 children at baseline , 1 and 2 years . Data were analysed using generalised estimating equations . Results : Multiple changes were made to the school play environments result ing in a significant difference in overall play evaluation score between intervention and control schools of 4.50 ( 95 % confidence interval : 1.82 to 7.18 , P=0.005 ) , which represents a substantial improvement from baseline values of 19.0 ( s.d . 3.2 ) . Overall , schools liked the intervention and reported many benefits , including increased physical activity . However , these beliefs did not translate into significant differences in objective ly measured physical activity , either as counts per minute ( for example , 35 ( −51 to 120 ) during lunch break ) or as minutes of moderate-to-vigorous physical activity ( 0.4 , −1.1 to 2.0 ) . Similarly , no significant differences were observed for BMI , BMI z-score or waist circumference at 1 or 2 years ( all P>0.321 ) . Conclusions : Altering the school play environment to one that promoted greater risk and challenge for children did not increase physical activity , nor subsequently alter body weight . Although schools embraced the concept of adding risk and challenge in the playground , our findings suggest that children may have been involved in different , rather than additional activities BACKGROUND Childhood obesity is a major public health problem in the United States , particularly among American Indian communities . OBJECTIVE The objective was to evaluate the effectiveness of a school-based , multicomponent intervention for reducing percentage body fat in American Indian schoolchildren . DESIGN This study was a r and omized , controlled , school-based trial involving 1704 children in 41 schools and was conducted over 3 consecutive years , from 3rd to 5th grade s , in schools serving American Indian communities in Arizona , New Mexico , and South Dakota . The intervention had 4 components : 1 ) change in dietary intake , 2 ) increase in physical activity , 3 ) a classroom curriculum focused on healthy eating and lifestyle , and 4 ) a family-involvement program . The main outcome was percentage body fat ; other outcomes included dietary intake , physical activity , and knowledge , attitudes , and behaviors . RESULTS The intervention result ed in no significant reduction in percentage body fat . However , a significant reduction in the percentage of energy from fat was observed in the intervention schools . Total energy intake ( by 24-h dietary recall ) was significantly reduced in the intervention schools but energy intake ( by direct observation ) was not . Motion sensor data showed similar activity levels in both the intervention and control schools . Several components of knowledge , attitudes , and behaviors were also positively and significantly changed by the intervention . CONCLUSIONS These results document the feasibility of implementing a multicomponent program for obesity prevention in elementary schools serving American Indian communities . The program produced significant positive changes in fat intake and in food- and health-related knowledge and behaviors . More intense or longer interventions may be needed to significantly reduce adiposity in this population Background Adolescence is an established period of physical activity decline . Multi-component school-based interventions have the potential to slow the decline in adolescents ’ physical activity ; however , few interventions have been conducted in schools located in low-income or disadvantaged communities . This study aims to assess the effectiveness of a multi-component school-based intervention in reducing the decline in physical activity among students attending secondary schools located in disadvantaged communities . Methods / Design The cluster r and omised trial will be conducted with 10 secondary schools located in selected regions of New South Wales , Australia . The schools will be selected from areas that have a level of socio-economic status that is below the state average . Five schools will be allocated to receive an intervention based on the Health Promoting Schools framework , and will be supported by a part-time physical activity consultant placed in intervention schools who will implement a range of intervention adoption strategies . Study measures will be taken at baseline when students are in Year 7 ( 12–13 years ) and again after 12- and 24-months . The primary outcome , minutes of moderate- to-vigorous- intensity physical activity per day and percentage of time in moderate- to vigorous-intensity physical activity ( MVPA ) , will be objective ly assessed using accelerometers ( Actigraph GT3x+ ) . Group allocation and intervention delivery will commence after baseline data collection . The intervention will continue during school terms through to 24-month follow-up . Discussion The study will provide evidence regarding the effectiveness of a multi-component school-based intervention that includes an in-school physical activity consultant targeting the physical activity levels of adolescents in disadvantaged Australian secondary schools . Trial registration Australian New Zeal and Clinical Trials Registry ACTRN12612000382875 Background Childhood obesity has been increasing rapidly worldwide . There is limited evidence for effective lifestyle interventions to prevent childhood obesity worldwide , especially in developing countries like China . The objective of this study was to assess the effectiveness of a school-based multi-component lifestyle childhood obesity prevention program ( the CLICK-Obesity study ) in Mainl and China . Methods A cluster r and omized controlled trial was developed among grade 4 students from 8 urban primary schools ( 638 students in intervention , 544 as control ) in Nanjing City , China . Students were r and omly allocated to the control or intervention group at school-level . A one-year multi-component intervention program ( classroom curriculum , school environment support , family involvement and fun programs/events ) together with routine health education was provided to the intervention group , while the control group received routine health education only . The main outcome variables assessed were changes in body mass index , obesity occurrence , obesity-related lifestyle behaviors and knowledge . Results Overall , 1108 ( 93.7 % ) of the 1182 enrolled students completed the intervention study . The intervention group had a larger marginal reduction than did the control group in overall mean BMI value ( -0.32±1.36 vs. -0.29±1.40 , p = 0.09 ) , although this was not significant . Compared with the control group , the intervention group was more likely to decrease their BMI ( OR = 1.44 , 95%CI = 1.10 , 1.87 ) by 0.5 kg/m2 or above , increase the frequency of jogging/running ( OR = 1.55 , 95%CI = 1.18 , 2.02 ) , decrease the frequency of TV/computer use ( OR = 1.41 , 95%CI = 1.09 , 1.84 ) and of red meat consumption ( OR = 1.50 , 95%CI = 1.15 , 1.95 ) , change commuting mode to/from school from sedentary to active mode ( OR = 2.24 , 95%CI = 1.47 , 3.40 ) , and be aware of the harm of selected obesity risk factors . Conclusions The school-based lifestyle intervention program was practical and effective in improving health behaviors and obesity-related knowledge for children in China . This study provides important policy implication s on school-based intervention programs for modifications of obesity-related lifestyles . Trial Registration Chinese Clinical Trial Registry Background School-based interventions that target prevention of overweight and obesity in children have been tested with mixed results . Thus , successful interventions are still called for . The aim of the present study was to investigate effects of a multicomponent school-based intervention programme targeting physical activity , sedentary and dietary behaviours on anthropometric outcomes . Methods A 20-month intervention was evaluated in a cluster r and omised , controlled study of 1324 11-year-olds . Outcome variables were body mass index ( BMI ) , BMI -for-age z-score ( BMI z ) , waist circumference ( WC ) , waist-to-height ratio ( WTHR ) and weight status ( International Obesity Task Force 's cut-offs ) . Weight , height and WC were measured objective ly ; pubertal status was self-reported and parental education was self-reported by the parents . Intervention effects were determined by one-way analysis of covariance and logistic regression , after checking for clustering effects of school , and moderating effects of gender , pubertal status and parental education . Results Beneficial effects were found for BMI ( p=0.02 ) and BMI z ( p=0.003 ) in girls , but not in boys . While a beneficial effect was found for BMI ( p=0.03 ) in participants of parents reporting a high level of education , a negative effect was found for WTHR in participants with parents reporting a low level of education ( p=0.003 ) . There were no intervention effects for WC and weight status . Conclusions A multicomponent 20-month school-based intervention had a beneficial effect on BMI and BMI z in adolescent girls , but not in boys . Furthermore , children of higher educated parents seemed to benefit more from the intervention , and this needs attention in future interventions to avoid further increase in social inequalities in overweight and obesity Objective : To assess the efficacy of a school-based intervention programme to reduce the prevalence of overweight in 6 to 10-year-old children . Design : Cluster-r and omized , controlled study .Subjects : A total of 3135 boys and girls in grade s 1–4 were included in the study . Methods : Ten schools were selected in Stockholm county area and r and omized to intervention ( n=5 ) and control ( n=5 ) schools . Low-fat dairy products and whole-grain bread were promoted and all sweets and sweetened drinks were eliminated in intervention schools . Physical activity ( PA ) was aim ed to increase by 30 min day−1 during school time and sedentary behaviour restricted during after school care time . PA was measured by accelerometry . Eating habits at home were assessed by parental report . Eating disorders were evaluated by self-report . Results : The prevalence of overweight and obesity decreased by 3.2 % ( from 20.3 to 17.1 ) in intervention schools compared with an increase of 2.8 % ( from 16.1 to 18.9 ) in control schools ( P<0.05 ) . The results showed no difference between intervention and controls , after cluster adjustment , in the longitudinal analysis of BMI sds changes . However , a larger proportion of the children who were initially overweight reached normal weight in the intervention group ( 14 % ) compared with the control group ( 7.5 % ) , P=0.017 . PA did not differ between intervention and control schools after cluster adjustment . Eating habits at home were found to be healthier among families with children in intervention schools at the end of the intervention . There was no difference between children in intervention and control schools in self-reported eating disorders . Conclusions : A school-based intervention can reduce the prevalence of overweight and obesity in 6 to 10-year-old children and may affect eating habits at home . The effect of the intervention was possibly due to its effect on healthy eating habits at school and at home rather than on increased levels of PA Objective To investigate the effectiveness of a school based intervention to increase physical activity , reduce sedentary behaviour , and increase fruit and vegetable consumption in children . Design Cluster r and omised controlled trial . Setting 60 primary schools in the south west of Engl and . Participants Primary school children who were in school year 4 ( age 8 - 9 years ) at recruitment and baseline assessment , in year 5 during the intervention , and at the end of year 5 ( age 9 - 10 ) at follow-up assessment . Intervention The Active for Life Year 5 ( AFLY5 ) intervention consisted of teacher training , provision of lesson and child-parent interactive homework plans , all material s required for lessons and homework , and written material s for school newsletters and parents . The intervention was delivered when children were in school year 5 ( age 9 - 10 years ) . Schools allocated to control received st and ard teaching . Main outcome measures The pre-specified primary outcomes were accelerometer assessed minutes of moderate to vigorous physical activity per day , accelerometer assessed minutes of sedentary behaviour per day , and reported daily consumption of servings of fruit and vegetables . Results 60 schools with more than 2221 children were recruited ; valid data were available for fruit and vegetable consumption for 2121 children , for accelerometer assessed physical activity and sedentary behaviour for 1252 children , and for secondary outcomes for between 1825 and 2212 children for the main analyses . None of the three primary outcomes differed between children in schools allocated to the AFLY5 intervention and those allocated to the control group . The difference in means comparing the intervention group with the control group was –1.35 ( 95 % confidence interval –5.29 to 2.59 ) minutes per day for moderate to vigorous physical activity , –0.11 ( –9.71 to 9.49 ) minutes per day for sedentary behaviour , and 0.08 ( –0.12 to 0.28 ) servings per day for fruit and vegetable consumption . The intervention was effective for three out of nine of the secondary outcomes after multiple testing was taken into account : self reported time spent in screen viewing at the weekend ( –21 ( –37 to –4 ) minutes per day ) , self reported servings of snacks per day ( –0.22 ( –0.38 to –0.05 ) ) , and servings of high energy drinks per day ( –0.26 ( –0.43 to –0.10 ) ) were all reduced . Results from a series of sensitivity analyses testing different assumptions about missing data and from per protocol analyses produced similar results . Conclusion The findings suggest that the AFLY5 school based intervention is not effective at increasing levels of physical activity , decreasing sedentary behaviour , and increasing fruit and vegetable consumption in primary school children . Change in these activities may require more intensive behavioural interventions with children or upstream interventions at the family and societal level , as well as at the school environment level . These findings have relevance for research ers , policy makers , public health practitioners , and doctors who are involved in health promotion , policy making , and commissioning services . Trial registration Current Controlled Trials IS RCT N50133740 Background Although school-based interventions to promote physical activity in adolescents have been suggested in several recent review s , questions have been raised regarding the effects of the strategies and the methodology applied and for whom the interventions are effective . The aim of the present study was to investigate effects of a school-based intervention program : the HEalth in Adolescents ( HEIA ) study , on change in physical activity , and furthermore , to explore whether potential effects varied by gender , weight status , initial physical activity level and parental education level . Methods This was a cluster r and omized controlled 20 month intervention study which included 700 11-year-olds . Main outcome -variable was mean count per minute ( cpm ) derived from ActiGraph accelerometers ( Model 7164/GT1 M ) . Weight and height were measured objective ly . Adolescents reported their pubertal status in a question naire and parents reported their education level on the consent form . Linear mixed models were used to test intervention effects and to account for the clustering effect of sampling by school . Results The present study showed an intervention effect on overall physical activity at the level of p = 0.05 with a net effect of 50 cpm increase from baseline to post intervention in favour of the intervention group ( 95 % CI −0.4 , 100 ) . Subgroup analyses showed that the effect appeared to be more profound among girls ( Est 65 cpm , CI 5 , 124 , p = 0.03 ) and among participants in the low-activity group ( Est 92 cpm , CI 41 , 142 , p < 0.001 ) , as compared to boys and participants in the high-activity group , respectively . Furthermore , the intervention affected physical activity among the normal weight group more positively than among the overweight , and participants with parents having 13–16 years of education more positively than participants with parents having either a lower or higher number of years of education . The intervention seemed to succeed in reducing time spent sedentary among girls but not among boys . Conclusions A comprehensive but feasible , multi-component school-based intervention can affect physical activity patterns in adolescents by increasing overall physical activity . This intervention effect seemed to be more profound in girls than boys , low-active adolescents compared to high-active adolescents , participants with normal weight compared to the overweight , and for participants with parents of middle education level as opposed to those with high and low education levels , respectively . An implementation of the HEIA intervention components in the school system may have a beneficial effect on public health by increasing overall physical activity among adolescents and possibly among girls and low-active adolescents in particular CONTEXT Some observational studies have found an association between television viewing and child and adolescent adiposity . OBJECTIVE To assess the effects of reducing television , videotape , and video game use on changes in adiposity , physical activity , and dietary intake . DESIGN R and omized controlled school-based trial conducted from September 1996 to April 1997 . SETTING Two sociodemographically and scholastically matched public elementary schools in San Jose , Calif. PARTICIPANTS Of 198 third- and fourth- grade students , who were given parental consent to participate , 192 students ( mean age , 8.9 years ) completed the study . INTERVENTION Children in 1 elementary school received an 18-lesson , 6-month classroom curriculum to reduce television , videotape , and video game use . MAIN OUTCOME MEASURES Changes in measures of height , weight , triceps skinfold thickness , waist and hip circumferences , and cardiorespiratory fitness ; self-reported media use , physical activity , and dietary behaviors ; and parental report of child and family behaviors . The primary outcome measure was body mass index , calculated as weight in kilograms divided by the square of height in meters . RESULTS Compared with controls , children in the intervention group had statistically significant relative decreases in body mass index ( intervention vs control change : 18.38 to 18.67 kg/m2 vs 18.10 to 18.81 kg/m2 , respectively ; adjusted difference -0.45 kg/m2 [ 95 % confidence interval [ CI ] , -0.73 to -0.17 ] ; P = .002 ) , triceps skinfold thickness ( intervention vs control change : 14.55 to 15.47 mm vs 13.97 to 16.46 mm , respectively ; adjusted difference , -1.47 mm [ 95 % CI , -2.41 to -0.54 ] ; P=.002 ) , waist circumference ( intervention vs control change : 60.48 to 63.57 cm vs 59.51 to 64.73 cm , respectively ; adjusted difference , -2.30 cm [ 95 % CI , -3.27 to -1.33 ] ; P<.001 ) , and waist-to-hip ratio ( intervention vs control change : 0.83 to 0.83 vs 0.82 to 0.84 , respectively ; adjusted difference , -0.02 [ 95 % CI , -0.03 to -0.01 ] ; P<.001 ) . Relative to controls , intervention group changes were accompanied by statistically significant decreases in children 's reported television viewing and meals eaten in front of the television . There were no statistically significant differences between groups for changes in high-fat food intake , moderate-to-vigorous physical activity , and cardiorespiratory fitness . CONCLUSIONS Reducing television , videotape , and video game use may be a promising , population -based approach to prevent childhood obesity Background Low levels of physical activity , high levels of sedentary behaviour and low levels of fruit and vegetable consumption are common in children and are associated with adverse health outcomes . The aim of this paper is to describe the protocol for a cluster r and omised controlled trial ( RCT ) design ed to evaluate a school-based intervention that aims to increase levels of physical activity , decrease sedentary behaviour and increase consumption of fruit and vegetables in school children . Methods / design The Active for Life Year 5 ( AFLY5 ) study is a school-based , cluster RCT that targets school children in Year 5 ( age 9 - 10 years ) . All state junior/ primary schools in the area covered by Bristol City and North Somerset Council are invited to participate ; special schools are excluded . Eligible schools are r and omised to one of two arms : intervention arm ( receive the intervention 2011 - 2012 ) and control arm ( receive the intervention after the final follow-up assessment , 2013 - 2014 ) . The primary outcomes of the trial are levels of accelerometer assessed physical activity and sedentary behaviour and question naire assessed fruit and vegetable consumption . A number of secondary outcomes will also be measured , including body mass index , waist circumference and overweight/obesity . Outcomes will be assessed at baseline ( prior to intervention when the children are in Year 4 ) , at the end of intervention ' immediate follow-up ' and ' 12 months long-term ' follow-up . We will use r and om effects linear and logistic regression models to compare outcomes by r and omised arm . The economic evaluation from a societal perspective will take the form of a cost consequence analysis . Data from focus groups and interviews with pupils , parents and teachers will be used to increase underst and ing of how the intervention has any effect and is integrated into normal school activity . Discussion The results of the trial will provide information about the public health effectiveness of a school-based intervention aim ed at improving levels of physical activity , sedentary behaviour and diet in children . Trial registration IS RCT OBJECTIVE To evaluate the impact of an 18-month school obesity prevention intervention on the health behaviors of 4th and 5th grade students based on ecological principles and formative research conducted in Mexico . MATERIAL S AND METHODS A R and omized Control Trial ( RCT ) , design was used to assign 27 schools to one of three conditions : basic or plus interventions and control . School environment measures , children 's eating and physical activity behaviors , and body mass index were assessed four times over a 2-year period in a sample of 830 students . RESULTS In the intervention schools , the availability of healthy foods increased with a concomitant decrease in unhealthy food availability . Food intake showed the same trend . In the intervention schools , children did not engage in more moderate to vigorous physical activity ( MVPA ) in physical education ( PE ) class or recess but increased steps taken . Obesity prevalence did not change . CONCLUSION The intervention improved the school food environment and child healthy behaviors Physical activity ( PA ) could be protective against hypertension , atherosclerosis , coronary heart disease and cardiovascular disease . This quantitative study assessed the association between a PA intervention and three anthropometric parameters ( weight , body mass index , body fat ) and four physiological parameters ( cholesterol level , systolic blood pressure , diastolic blood pressure , heart rate ) among secondary school pupils ( N = 160 ) in Egypt through the school term . The pupils were r and omised to an intervention group ( 80 pupils ) and controls ( 80 pupils ) . Measurements were obtained for all pupils twice : at baseline ; and then again after three months . The PA intervention programme comprised an ‘ afterschool ’ one hour of moderate exercise three times a week for three months . Both the controls and the intervention pupils attended the ‘ normal ’ exercise schedule provided by the school ; in addition , the intervention group attended afterschool PA programme from about 2–3 o’clock in the afternoon . At baseline , employing pupil ’s BMI , 27.5 % and 28.8 % of the intervention and control pupils respectively were classified as overweight . After three months , the percentage of overweight decreased to 12.5 % in the intervention pupils , while it increased to 37.3 % in the controls . At the end of the three months period , there were significant improvements across most anthropometric and physiological parameters of the intervention pupils when compared with the control children . The correlation coefficient of the improvements for the boys and the girls was 0.97 , indicating clearly that the intervention was having nearly the same beneficial effect for boys and girls . A moderate PA programme for a modest period of 3 months could be effective in maintaining or enhancing pupil ’s anthropometric and physiological parameters in comparison to the controls where there was deterioration in both parameters . Policy makers and secondary schools in Egypt might need to pay more attention to PA programmes conducted on school days , in order to motivate pupils to attend such programmes . There is also an urgent need to look at current PA systems within schools in Egypt in order to assess PA outside school times Background Childhood obesity is the result of a long lasting imbalance between energy intake and energy expenditure . A major contributing factor is physical inactivity which is closely linked to bone health , cardiovascular disease risk , fitness and psychological factors . The school seems to provide an excellent setting to enhance levels of physical activity ( PA ) . However , there is insufficient data from previous school-based intervention trials on how to enhance overall PA . It is also unknown whether an intervention aim ed at increasing PA is effective in improving the children 's health . The purpose of this paper is to outline the design of a school-based r and omized , controlled trial ( RCT ) aim ing to increase overall PA and to improve fitness and health in 6- to 13-year-old children . Methods / Design 15 schools were r and omized to the intervention ( n = 9 ) or the control ( n = 6 ) group , stratified by geographic region ( urban vs. rural ) and by age ( 1st and 5th grade ) . Participation was given for all children in the intervention group since in this group the intervention was part of the normal school curriculum . The intervention during one academic year consisted of : 1 . two additional physical education classes per week given by trained physical education teachers adding up to a total of five PA classes per week , 2 . short PA breaks ( 2–5 min each ) during academic lessons , 3 . PA home work , and 4 . adaptation of recreational areas around the school . All children underwent anthropometric measurements , blood pressure assessment , fitness testing , measurement of PA and they filled out question naires . At least 70 % of all children agreed to blood sampling and measurements of body composition and bone mineral measurements by dual energy x-ray absorptiometry . The primary endpoints of the study after one year were an increase in total PA by accelerometry , an increase in aerobic fitness measured by the 20 m shuttle run , a decrease in percent body fat derived from skinfold measurements and an increase in quality of life as assessed by the child health question naire in the intervention group compared to the control group . Secondary outcomes were overall fitness , differences in body composition including body fat distribution , cardiovascular risk factors , psychosocial health , bone mineral content and density of femur , lumbar spine and total body and food intake . Discussion Our preliminary data suggest that the children were representative of Swiss children with respect to sex , socio-demographic status , and body mass index . Short-term results can be expected by the beginning of 2007 . We hypothesized that our intervention will lead to an increase in PA , fitness and overall health . Based on our data , we aim to provide important information regarding the influence of such an intervention on these outcome measures in school-aged children and to provide nationwide guidelines to improve PA in children This study tested the efficacy of two school-based programs for prevention of body weight/fat gain in comparison to a control group , in all participants and in overweight children . The Louisiana ( LA ) Health study utilized a longitudinal , cluster r and omized 3-arm controlled design , with 28 months of follow-up . Children ( N=2060 ; M age = 10.5 years , SD = 1.2 ) from rural communities in Grade s 4 to 6 participated in the study . 17 school clusters ( M = 123 children/cluster ) were r and omly assigned to one of three prevention arms : 1 ) Primary Prevention ( PP ) , an environmental modification program , 2 ) Primary + Secondary Prevention ( PP+SP ) , the environmental program with an added classroom and internet education component , or 3 ) Control ( C ) . Primary outcomes were changes in percent body fat and body mass index z scores . Secondary outcomes were changes in behaviors related to energy balance . Comparisons of PP , PP+SP , and C on changes in body fat and BMI z scores found no differences . PP and PP+SP study arms were combined to create an environmental modification arm ( EM ) . Relative to C , EM decreased body fat for boys ( −1.7 % ± 0.38 % versus −0.14 % ± 0.69 % ) and attenuated fat gain for girls ( 2.9 % ± 0.22 % versus 3.93 % ± 0.37 % ) , but st and ardized effect sizes were relatively small ( < 0.30 ) . In conclusion , this school-based environmental modification programs had modest beneficial effects on changes in percent body fat . Addition of a classroom/internet program to the environmental program did not enhance weight/fat gain prevention , but did impact physical activity and social support in overweight children 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 determine whether a multicomponent health promotion intervention for Dutch adolescents would be successful in influencing body composition and aerobic fitness . DESIGN R and omized controlled trial . SETTING Ten intervention and 8 control prevocational secondary schools . PARTICIPANTS A total of 978 adolescents ( mean age , 12.7 years ) . INTERVENTION An interdisciplinary multicomponent intervention program with an adapted curriculum for 11 biology and physical education lessons and environmental change options , including additional lessons on physical education and advice on the school canteen selection . MAIN OUTCOME MEASURES Body height and weight , hip and waist circumference , 4 skinfold thickness measurements , and aerobic fitness . RESULTS Multilevel analyses showed significant differences in changes after the 8-month intervention period in favor of the intervention group with regard to hip circumference ( mean difference , 0.53 cm ; 95 % confidence interval , 0.07 to 0.98 ) and sum of skinfolds among girls ( mean difference , -2.31 mm ; 95 % confidence interval , -4.34 to -0.28 ) . In boys , the intervention result ed in a significant difference in waist circumference ( mean difference , -0.57 cm ; 95 % confidence interval , -1.10 to -0.05 ) . No significant intervention effects were found related to aerobic fitness . CONCLUSIONS The multicomponent Dutch Obesity Intervention in Teenagers program positively influenced several measures of body composition among both girls and boys . Our results indicate that secondary prevocational school curriculum changes may contribute to excessive weight gain prevention among adolescents Background In Lebanon , childhood obesity doubled during the past decade . Preventive measures should start early in life and Schools are considered an important environment to promote energy balance health behaviours . School-based programmes promoting healthy lifestyles are lacking . The purpose of this study was to evaluate the feasibility and effectiveness of a multicomponent school-based intervention to promote healthy eating and physical activity ( and prevent obesity ) with school children aged 9–11 years in Lebanon . Methods The intervention was developed based on the constructs of the Social Cognitive Theory and adapted to the culture of Lebanese and Arab population s. It consisted of three components : class curriculum , family involvement and food service . Eight schools were purposively selected from two communities of different socioeconomic status ( SES ) in Beirut and , within each school type , were matched on SES , religious sect profile , and then r and omly assigned to either the intervention or control group . Anthropometric measurements and question naires on determinants of behavioural change , eating and physical activity habits were completed by the students in both groups at baseline and post intervention . Focus group interviews were conducted in intervention schools at the end of the study . Challenges encountered during the programme implementation were also identified , since Lebanon is considered a country with political unrest and no similar research projects were conducted in the area . Results Students in the intervention group reported purchasing and consuming less chips and sweetened drinks post-intervention compared with controls ( 86 % & 88 % less respectively p < 0.001 ) . Knowledge and self-efficacy scores increased for the intervention ( + 2.8 & + 1.7 points respectively p < 0.001 ) but not for the control group . There was no difference in physical activity and screen time habits and no changes in BMI between groups at post intervention . Interview data from focus groups showed that the programme was generally well accepted . Limitations for better outcomes include the length of the programme and the school environment . Conclusion “ Health-E-PALS ” intervention is a promising innovative , theory-based , culturally sensitive intervention to promote healthy eating habits and physical activity in Lebanese school children with a potential to be scaled up , replicated and sustained OBJECTIVES To determine whether a large-scale physical activity intervention could affect body composition in primary school students in Beijing , China . METHODS The study design was one-year cluster r and omized controlled trial of physical activity intervention ( 20 min of daily exercise in the classroom ) with an additional year of follow-up among 4 700 students aged 8 - 11 years at baseline . RESULTS After the one-year intervention , BMI increased by 0.56 kg/m(2 ) ( SD 1.15 ) in the intervention group and by 0.72 kg/m(2 ) ( SD 1.20 ) in the control group , with a mean difference of -0.15 kg/m(2 ) ( 95 % CI : -0.28 to -0.02 ) . BMI z score decreased by -0.05 ( SD 0.44 ) in the intervention group , but increased by 0.01 ( SD 0.46 ) in the control group , with a mean difference of -0.07 ( -0.13 to -0.01 ) . After another year of follow up , compared to the control group , children in the intervention group had significantly lower BMI ( -0.13 , -0.25 to -0.01 ) , BMI z score ( -0.05 , -0.10 to -0.01 ) , fat mass ( -0.27 kg , -0.53 to -0.02 ) and percent body fat ( -0.53 , -1.00 to -0.05 ) . The intervention had a more pronounced effect on weight , height , BMI , BMI z score , and body composition among obese children than among normal weight or overweight children . Compared to the control group , the intervention group had a significantly higher percentage of children who maintained or reduced their BMI z score at year 1 ( P=0.008 ) and year 2 ( P=0.04 ) . CONCLUSIONS These findings suggest that 20 min of daily moderate to vigorous physical activity during the school year is a feasible and effective way to prevent excessive gain of body weight , BMI , and body fatness in primary school students BACKGROUND / OBJECTIVES : Obesity prevention during adolescence is a health priority . The ‘ Physical Activity 4 Everyone ’ ( PA4E1 ) study tested a multi-component physical activity intervention in 10 secondary schools from socio-economically disadvantaged communities . This paper aim ed to report the secondary outcomes of the study ; to determine whether the intervention impacted on adiposity outcomes ( weight , body mass index ( BMI ) , BMI z-score ) , and whether any effect was moderated by sex , baseline BMI and baseline physical activity level , at 12 and 24 months . SUBJECTS/ METHODS : A cluster r and omised controlled trial was conducted in New South Wales , Australia . The school-based intervention included seven physical activity strategies targeting the following : curriculum ( strategies to maximise physical activity in physical education , student physical activity plans , an enhanced school sport programme ) ; school environment ( physical activity during school breaks , modification of school policy ) ; and parents and the community ( parent engagement , links with community physical activity providers ) . Students ’ weight ( kg ) , BMI and BMI z-score , were collected at baseline ( Grade 7 ) , 12 and 24 months . Linear Mixed Models were used to assess between-group mean difference from baseline to 12 and 24 months . Exploratory sub-analyses were undertaken according to three moderators of energy balance . RESULTS : A total of 1150 students ( mean age=12 years ) provided outcome data at baseline , 1051 ( 91 % ) at 12 months and 985 ( 86 % ) at 24 months . At 12 months , there were group-by-time effects for weight ( mean difference=–0.90 kg ( 95 % confidence interval (CI)=–1.50 , −0.30 ) , P<0.01 ) and BMI ( −0.28 kg m−2 ( −0.50 , −0.06 ) , P=0.01 ) in favour of the intervention group , but not for BMI z-score ( −0.05 ( −0.11 ; 0.01 ) , P=0.13 ) . These findings were consistent for weight ( −0.62 kg ( −1.21 , 0.03 ) , P=0.01 ) and BMI ( −0.28 kg m−2 ( −0.49 , −0.06 ) , P=0.01 ) at 24 months , with group-by-time effects also found for BMI z-score ( −0.08 ( −0.14 ; −0.02 ) , P=0.02 ) favouring the intervention group . CONCLUSION : The PA4E1 school-based intervention achieved moderate reductions in adiposity among adolescents from socio-economically disadvantaged communities . Multi-component interventions that increase adolescents ’ engagement in moderate-to-vigorous physical activity ( MVPA ) may assist in preventing unhealthy weight gain Background The prevalence of childhood obesity among adolescents has been rapidly rising in Mainl and China in recent decades , especially in urban and rich areas . There is an urgent need to develop effective interventions to prevent childhood obesity . Limited data regarding adolescent overweight prevention in China are available . Thus , we developed a school-based intervention with the aim of reducing excess body weight in children . This report described the study design . Methods / design We design ed a cluster r and omized controlled trial in 8 r and omly selected urban primary schools between May 2010 and December 2013 . Each school was r and omly assigned to either the intervention or control group ( four schools in each group ) . Participants were the 4th grade rs in each participating school . The multi-component program was implemented within the intervention group , while students in the control group followed their usual health and physical education curriculum with no additional intervention program . The intervention consisted of four components : a ) classroom curriculum , ( including physical education and healthy diet education ) , b ) school environment support , c ) family involvement , and d ) fun programs/events . The primary study outcome was body composition , and secondary outcomes were behaviour and behavioural determinants . Discussion The intervention was design ed with due consideration of Chinese cultural and familial tradition , social convention , and current primary education and exam system in Mainl and China . We did our best to gain good support from educational authorities , school administrators , teachers and parents , and to integrate intervention components into schools ’ regular academic programs . The results of and lesson learned from this study will help guide future school-based childhood obesity prevention programs in Mainl and China . Trial registration Registration number : The purpose of this study was to assess the effects of a six-months ’ nutrition program , delivered and taught by classroom teachers with in-service nutrition training , on the prevention of overweight and obesity among children in grade s 1 to 4 . In this r and omized trial , four hundred and sixty four children from seven elementary schools were allocated to a nutrition educational program delivered by their own teachers . Intervened teachers had 12 sessions of three hours each with the research ers throughout six months , according to the topics nutrition and healthy eating , the importance of drinking water and healthy cooking activities . After each session , teachers were encouraged to develop activities in class focused on the learned topics . Sociodemographic , anthropometric , dietary , and physical activity assessment s were performed at baseline and at the end of the intervention . In the intervention group the increase in Body Mass Index ( BMI ) z-score was significantly lower than in the control group ( p = 0.009 ) ; fewer proportion of children became overweight in the intervened group compared with the control ( 5.6 % vs. 18.4 % ; p = 0.037 ) . Our study provides further support to decrease the overweight epidemic , involving classroom teachers in a training program and making them dedicated interventionists Background School-based intervention studies promoting a healthy lifestyle have shown favorable immediate health effects . However , there is a striking paucity on long-term follow-ups . The aim of this study was therefore to assess the 3 yr-follow-up of a cluster-r and omized controlled school-based physical activity program over nine month with beneficial immediate effects on body fat , aerobic fitness and physical activity . Methods and Findings Initially , 28 classes from 15 elementary schools in Switzerl and were grouped into an intervention ( 16 classes from 9 schools , n = 297 children ) and a control arm ( 12 classes from 6 schools , n = 205 children ) after stratification for grade ( 1st and 5th grade rs ) . Three years after the end of the multi-component physical activity program of nine months including daily physical education ( i.e. two additional lessons per week on top of three regular lessons ) , short physical activity breaks during academic lessons , and daily physical activity homework , 289 ( 58 % ) participated in the follow-up . Primary outcome measures included body fat ( sum of four skinfolds ) , aerobic fitness ( shuttle run test ) , physical activity ( accelerometry ) , and quality of life ( question naires ) . After adjustment for grade , gender , baseline value and clustering within classes , children in the intervention arm compared with controls had a significantly higher average level of aerobic fitness at follow-up ( 0.373 z-score units [ 95%-CI : 0.157 to 0.59 , p = 0.001 ] corresponding to a shift from the 50th to the 65th percentile between baseline and follow-up ) , while the immediate beneficial effects on the other primary outcomes were not sustained . Conclusions Apart from aerobic fitness , beneficial effects seen after one year were not maintained when the intervention was stopped . A continuous intervention seems necessary to maintain overall beneficial health effects as reached at the end of the intervention . Trial Registration ControlledTrials.com IS RCT Objectives To assess the behavioural and weight status outcomes in English children in a feasibility study of a novel primary school-based obesity prevention programme . Design Exploratory cluster r and omised controlled trial of the Healthy Lifestyles Programme . Setting Four city primary schools ( two control and two intervention ) in the South West of Engl and . Participants 202 children aged 9–10 years , of whom 193 and 188 were followed up at 18 and 24 months , respectively . No child was excluded from the study ; however , to be eligible , schools were required to have at least one single Year 5 class . Intervention Four-phase multicomponent programme using a range of school-based activities including lessons , assemblies , parents ' evenings , interactive drama workshops and goal setting to engage and support schools , children and their families in healthy lifestyle behaviours . It runs over the spring and summer term of Year 5 and the autumn term of Year 6 . Primary and secondary outcomes Weight status outcomes were body mass index , waist circumference and body fat st and ard deviation scores ( SDS ) at 18 and 24 months , and behavioural outcomes were physical activity , television ( TV ) viewing/screen time and food intake at 18 months . Results At 18 months of follow-up , intervention children consumed less energy-dense snacks and more healthy snacks ; had less ‘ negative food markers ’ , more ‘ positive food markers ’ , lower mean TV/screen time and spent more time doing moderate-vigorous physical activity each day than those in the control schools . Intervention children had lower anthropometric measures at 18 and 24 months than control children , with larger differences at 24 months than at 18 months for nearly all measures . Conclusions Results from this exploratory trial show consistent positive changes in favour of the intervention across all targeted behaviours , which , in turn , appear to affect weight status and body shape . A definitive trial is now justified Objective . To evaluate the effectiveness of a 12-month multicomponent obesity prevention intervention . Setting . 9 elementary schools in Santiago , Chile . Subjects . 6–8 y old low-income children ( N = 1474 ) . Design . R and omized controlled study ; 5 intervention/4 control schools . We trained teachers to deliver nutrition contents and improve the quality of PE classes . We determined % healthy snacks brought from home , children 's nutrition knowledge , nutritional status , duration of PE classes , and % time in moderate/vigorous activity ( MVA ) . Effectiveness was determined by comparing Δ BMI Z between intervention and control children using PROCMIXED . Results . % obesity increased in boys from both types of schools and in girls from control schools , while decreasing in girls from intervention schools ( all nonsignificant ) . % class time in MVA declined ( 24.5–16.2 ) while remaining unchanged ( 24.8–23.7 % ) in classes conducted by untrained and trained teachers , respectively . In boys , BMI Z declined ( 1.33–1.24 ) and increased ( 1.22–1.35 ) in intervention and control schools , respectively . In girls , BMI Z remained unchanged in intervention schools , while increasing significantly in control schools ( 0.91–1.06 , P = 0.024 ) . Interaction group ∗ time was significant for boys ( P < 0.0001 ) and girls ( P = 0.004 ) . Conclusions . This intervention was effective in controlling obesity , but not preventing it . Even though impact was small , results showed that when no intervention is implemented , obesity increases Objectives To assess the reproducibility of an educational intervention EdAl-2 ( Educació en Alimentació ) programme in ‘ Terres de l'Ebre ’ ( Spain ) , over 22 months , to improve lifestyles , including diet and physical activity ( PA ) . Design Reproduction of a cluster r and omised controlled trial . Setting Two semi-rural town-group primary -school clusters were r and omly assigned to the intervention or control group . Participants Pupils ( n=690 ) of whom 320 constituted the intervention group ( 1 cluster ) and 370 constituted the control group ( 1 cluster ) . Ethnicity was 78 % Western European . The mean age ( ±SD ) was 8.04±0.6 years ( 47.7 % females ) at baseline . Inclusion criteria for clusters were towns from the southern part of Catalonia having a minimum of 500 children aged 7–8 year ; complete data for participants , including name , gender , date and place of birth , and written informed consent from parents or guardians . Intervention The intervention focused on eight lifestyle topics covered in 12 activities ( 1 h/activity/session ) implemented by health promoting agents in the primary school over three academic years . Primary and secondary outcomes The primary outcome was obesity ( OB ) prevalence and the secondary outcomes were body mass index ( BMI ) collected every year and dietary habits and lifestyles collected by question naires filled in by parents at baseline and end-of- study . Results At 22 months , the OB prevalence and BMI values were similar in intervention and control groups . Relative to children in control schools , the percentage of boys in the intervention group who performed ≥4 after-school PA h/week was 15 % higher ( p=0.027 ) , whereas the percentage of girls in both groups remained similar . Also , 16.6 % more boys in the intervention group watched ≤2 television ( TV ) h/day ( p=0.009 ) , compared to controls ; and no changes were observed in girls in both groups . Conclusions Our school-based intervention is feasible and reproducible by increasing after-school PA ( to ≥4 h/week ) in boys . Despite this improvement , there was no change in BMI and prevalence of OB . Trial registration number : Clinical Trials NCT01362023 The effectiveness of a health and nutrition education programme , in changing certain chronic disease risk factors , was assessed after the 6 years intervention period was completed . The school-based intervention programme was applied to all children registered in the first grade ( age 5.5 - 6.5 years ) in 1992 in two counties of Crete , while the children from a third county served as a control group . In order to assess the effectiveness of the intervention , a variety of biological and behavioural parameters were measured before and following completion of the intervention in a r and omly selected school-based sample of 602 intervention group ( IG ) and 444 control group ( CG ) pupils . At the end of the 6-year period , it was found that biochemical indices generally improved significantly more in the IG compared with the CG ( mean change for IG v. CG was -0.27 v. -0.12 mmol/l for total cholesterol ( TC ) ; -0.07 v. + 0.24 for TC : HDL and -0.13 v. + 0.14 for LDL : HDL ) . Similarly , the changes observed in the anthropometric variables in the two groups were in favour of the IG ( + 3.68 v. + 4.28 kg/m2 for BMI ; + 2.97 v. + 4.47 mm for biceps skinfold ) . Total energy intake and consumption of total fat and saturated fat increased significantly less in the IG compared with the CG ( + 747.7 v. 1534.7 kJ ( + 178.7 v. + 366.8 kcal ) ; + 5.9 v. + 18.8 g and + 0.8 v. + 5.1 g respectively ) , while time devoted to leisure time physical activity and cardiovascular run test performance increased significantly more in the IG ( + 281 v. + 174 min/week and + 2.5 v. + 1.2 stages respectively ) . The findings of the present study underline the importance of such programmes in health promotion and disease prevention . Although the long-term effects of these programmes can only be assessed by tracking this population through to adolescence and adulthood , these programmes seem to have the potential to lead to a healthier lifestyle and thus a reduction in risk factor levels Background The EdAL ( Educació enAlimentació ) study is a long-term , nutrition educational , primary -school-based program design ed to prevent obesity by promoting a healthy lifestyle that includes dietary recommendations and physical activity . The aims are : 1 ) to evaluate the effects of a 3-year school-based life-style improvement program on the prevalence of obesity in an area of north-west Mediterranean 2 ) To design a health-promotion program to be implemented by health-promoter agents ( university students ) in primary schools . Methods / Design 1 ) The intervention study is a r and omised , controlled , school-based program performed by university-student health-promoter agents . Initial pupil enrolment was in 2006 and continued for 3 years . We considered two clusters ( design ated as cluster A and cluster B ) as the units for r and omisation . The first cluster involved 24 schools from Reus and the second involved 14 schools from surrounding towns Cambrils , Salou and Vilaseca combined in order to obtain comparable groups . There are very good communications between schools in each town , and to avoid cross influence of the programs result ing from inter-school dialogue , the towns themselves were the unit for r and omisation . Data collected included name , gender , date and place of birth at the start of the program and , subsequently , weight , height , body mass index ( BMI ) and waist circumference every year for 3 years . Question naires on eating and physical activity habits are filled-in by the parents at the start and end of the study and , providing that informed consent is given , the data are analysed on the intention-to-treat basis . The interventions are based on 8 nutritional and physical activity objectives . They are implemented by university students as part of the university curriculum in training health-promoter agents . These 8 objectives are developed in 4 educational activities/year for 3 years ( a total of 12 activities ; 1 h/activity ) performed by the health-promoter agents in primary schools . Control pupils follow their usual activities.2 ) Courses on education and promotion of health , within in the curriculum of medicine and health sciences for university students , are design ed to train health-promoter agents to administer these activities in primary schools . Discussion This controlled school-based intervention will test the possibility of preventing childhood obesity . Trial registration numberIS RCT N : IS RCT BACKGROUND Identification of the behavioural , normative and control beliefs influencing children 's behaviour is an important prerequisite in design ing effective interventions . The current study aims to evaluate the effectiveness of an intervention program , based on the Theory of Planned Behaviour ( TPB ) , on obesity indices and blood pressure ( BP ) in Ioannina , Greece . METHODS Participants were 646 fifth grade pupils ( 360 girls and 286 boys ) . The intervention group ( IG ) consisted of 321 children in 13 r and omly selected schools while the rest ( n = 325 children ) served as the control group ( CG ) . Based on the outcome of the TPB question naire , the intervention focused on overcoming the barriers in accessing physical activity areas , increasing the availability of fruits and vegetables and increasing parental support . General linear mixed model and mediating variable analysis were used to evaluate the differences between the two groups and to test whether changes in certain dietary , physical activity and anthropometrical indices mediated the effect of the intervention on BP . RESULTS IG had higher consumption of fruits and lower consumption of fats/oils and sweets/beverages compared with the CG . Intervention 's effect on BMI could be explained by the changes in fruit and fats/oils intake whereas the reduction of systolic and diastolic BP could be explained by the reduction of BMI . CONCLUSIONS The findings indicate favourable changes in BP and obesity indices after the implementation of a 1-year school-based intervention program based on the TPB . These results highlight the importance of developing a social and physical environment that promotes balanced eating behaviours and extra-curricular access to physical activity venues OBJECTIVE To determine whether an educational programme aim ed at discouraging students from drinking sugar-sweetened beverages could prevent excessive weight gain . DESIGN Forty-seven classes in twenty-two schools were r and omised as intervention or control . SUBJECTS Participants were 1140 , 9 - 12-year-old fourth grade rs ( 435 in the intervention group and 608 in the control group ) . Sugar-sweetened beverages and juice intake were measured through one 24 h recall at baseline and another at the end of the trial . The main outcome was the change in BMI ( BMI = weight (kg)/height ( m2 ) ) , measured at the beginning and at the end of the school year . Intention-to-treat analysis was performed taking into account the cluster ( classes ) effect . RESULTS A statistically significant decrease in the daily consumption of carbonated drinks in the intervention compared to control ( mean difference = -56 ml ; 95 % CI -119 , -7 ml ) was followed by a non-significant overall reduction in BMI , P = 0.33 . However , among those students overweight at baseline , the intervention group showed greater BMI reduction ( -0.4 kg/m2 compared with -0.2 kg/m2 in the control group ( P = 0.11 ) ) , and this difference was statistically significant among girls ( P = 0.009 ) . Fruit juice consumption was slightly increased in the intervention group ( P = 0.08 ) , but not among girls . CONCLUSION Decreasing sugar-sweetened beverages intake significantly reduced BMI among overweight children , and mainly among girls . Efforts to reduce energy intake through liquids need to emphasise overall sweetened beverages and addition of sugar on juices Objective To assess the effectiveness of a school based physical activity programme during one school year on physical and psychological health in young schoolchildren . Design Cluster r and omised controlled trial . Setting 28 classes from 15 elementary schools in Switzerl and r and omly selected and assigned in a 4:3 ratio to an intervention ( n=16 ) or control arm ( n=12 ) after stratification for grade ( first and fifth grade ) , from August 2005 to June 2006 . Participants 540 children , of whom 502 consented and presented at baseline . Intervention Children in the intervention arm ( n=297 ) received a multi-component physical activity programme that included structuring the three existing physical education lessons each week and adding two additional lessons a week , daily short activity breaks , and physical activity homework . Children ( n=205 ) and parents in the control group were not informed of an intervention group . For most outcome measures , the assessors were blinded . Main outcome measures Primary outcome measures included body fat ( sum of four skinfolds ) , aerobic fitness ( shuttle run test ) , physical activity ( accelerometry ) , and quality of life ( question naires ) . Secondary outcome measures included body mass index and cardiovascular risk score ( average z score of waist circumference , mean blood pressure , blood glucose , inverted high density lipoprotein cholesterol , and triglycerides ) . Results 498 children completed the baseline and follow-up assessment s ( mean age 6.9 ( SD 0.3 ) years for first grade , 11.1 ( 0.5 ) years for fifth grade ) . After adjustment for grade , sex , baseline values , and clustering within classes , children in the intervention arm compared with controls showed more negative changes in the z score of the sum of four skinfolds ( −0.12 , 95 % confidence interval −0.21 to −0.03 ; P=0.009 ) . Likewise , their z scores for aerobic fitness increased more favourably ( 0.17 , 0.01 to 0.32 ; P=0.04 ) , as did those for moderate-vigorous physical activity in school ( 1.19 , 0.78 to 1.60 ; P<0.001 ) , all day moderate-vigorous physical activity ( 0.44 , 0.05 to 0.82 ; P=0.03 ) , and total physical activity in school ( 0.92 , 0.35 to 1.50 ; P=0.003 ) . Z scores for overall daily physical activity ( 0.21 , −0.21 to 0.63 ) and physical quality of life ( 0.42 , −1.23 to 2.06 ) as well as psychological quality of life ( 0.59 , −0.85 to 2.03 ) did not change significantly . Conclusions A school based multi-component physical activity intervention including compulsory elements improved physical activity and fitness and reduced adiposity in children . Trial registration Current Controlled Trials IS RCT N15360785 BACKGROUND . The prevalence and seriousness of childhood obesity has prompted calls for broad public health solutions that reach beyond clinic setting s. Schools are ideal setting s for population -based interventions to address obesity . OBJECTIVE . The purpose of this work was to examine the effects of a multicomponent , School Nutrition Policy Initiative on the prevention of overweight ( 85.0th to 94.9th percentile ) and obesity ( > 95.0th percentile ) among children in grade s 4 through 6 over a 2-year period . METHODS . Participants were 1349 students in grade s 4 through 6 from 10 schools in a US city in the Mid-Atlantic region with ≥50 % of students eligible for free or reduced-price meals . Schools were matched on school size and type of food service and r and omly assigned to intervention or control . Students were assessed at baseline and again after 2 years . The School Nutrition Policy Initiative included the following components : school self- assessment , nutrition education , nutrition policy , social marketing , and parent outreach . RESULTS . The incidences of overweight and obesity after 2 years were primary outcomes . The prevalence and remission of overweight and obesity , BMI z score , total energy and fat intake , fruit and vegetable consumption , body dissatisfaction , and hours of activity and inactivity were secondary outcomes . The intervention result ed in a 50 % reduction in the incidence of overweight . Significantly fewer children in the intervention schools ( 7.5 % ) than in the control schools ( 14.9 % ) became overweight after 2 years . The prevalence of overweight was lower in the intervention schools . No differences were observed in the incidence or prevalence of obesity or in the remission of overweight or obesity at 2 years . CONCLUSION . A multicomponent school-based intervention can be effective in preventing the development of overweight among children in grade s 4 through 6 in urban public schools with a high proportion of children eligible for free and reduced-priced school meals Background This pragmatic evaluation investigated the effectiveness of the Children ’s Health , Activity and Nutrition : Get Educated ! ( CHANGE ! ) Project , a cluster r and omised intervention to promote healthy weight using an educational focus on physical activity and healthy eating . Methods Participants ( n = 318 , aged 10–11 years ) from 6 Intervention and 6 Comparison schools took part in the 20 weeks intervention between November 2010 and March/April 2011 . This consisted of a teacher-led curriculum , learning re sources , and homework tasks . Primary outcome measures were waist circumference , body mass index ( BMI ) , and BMI z-scores . Secondary outcomes were objective ly-assessed physical activity and sedentary time , and food intake . Outcomes were assessed at baseline , at post-intervention ( 20 weeks ) , and at follow-up ( 30 weeks ) . Data were analysed using 2-level multi-level modelling ( levels : school , student ) and adjusted for baseline values of the outcomes and potential confounders . Differences in intervention effect by subgroup ( sex , weight status , socio-economic status ) were explored using statistical interaction . Results Significant between-group effects were observed for waist circumference at post-intervention ( β for intervention effect = −1.63 ( 95 % CI = −2.20 , -1.07 ) cm , p<0.001 ) and for BMI z-score at follow-up ( β=−0.24 ( 95 % CI = −0.48 , -0.003 ) , p=0.04 ) . At follow-up there was also a significant intervention effect for light intensity physical activity ( β=25.97 ( 95 % CI = 8.04 , 43.89 ) min , p=0.01 ) . Interaction analyses revealed that the intervention was most effective for overweight/obese participants ( waist circumference : β=−2.82 ( 95 % CI = −4.06 , -1.58 ) cm , p<0.001 ) , girls ( BMI : β=−0.39 ( 95 % CI = −0.81 , 0.03 ) kg/m2 , p=0.07 ) , and participants with higher family socioeconomic status ( breakfast consumption : β=8.82 ( 95 % CI = 6.47 , 11.16 ) , p=0.07 ) . Conclusions The CHANGE ! intervention positively influenced body size outcomes and light physical activity , and most effectively influenced body size outcomes among overweight and obese children and girls . The findings add support for the effectiveness of combined school-based physical activity and nutrition interventions . Additional work is required to test intervention fidelity and the sustained effectiveness of this intervention in the medium and long term . Trial registration Current Controlled Trials IS RCT N03863885 Background The Healthy Lifestyles Programme ( HeLP ) trial is being conducted to determine whether a novel school-based intervention is effective and cost-effective in preventing obesity in 9–10 year-old children . This article describes the detailed statistical analysis plan for the HeLP trial , including an amendment ( and rationale for amendment ) made to originally planned sensitivity analyses . Methods and design The HeLP trial is a definitive , pragmatic , superiority , cluster r and omised controlled trial with two parallel groups and blinded outcome assessment . This up date article describes in detail ( 1 ) the primary and secondary outcomes , ( 2 ) the statistical analysis principles ( including which children will be included in each analysis , how the clustered nature of the study design will be accounted for , which covariates will be included in each analysis , how the results will be presented ) , ( 3 ) planned sensitivity analyses , planned subgroup analyses and planned adherence-adjusted analyses for the primary outcome , ( 4 ) planned analyses for the secondary outcomes and ( e ) planned longitudinal analyses . Trial registration International St and ard R and omised Controlled Trial Number ( IS RCT N ) register : IS RCT N15811706 . Registered on 1 May 2012 Objective To assess the long term effects of an obesity prevention programme in schools . Design Longitudinal results after a cluster r and omised controlled trial . Setting Schools in southwest Engl and . Participants Of the original sample of 644 children aged 7 - 11 , 511 children were tracked and measurements were obtained from 434 children three years after baseline . Intervention The intervention was conducted over one school year , with four sessions of focused education promoting a healthy diet and discouraging the consumption of carbonated drinks . Main outcome measures Anthropometric measures of height , weight , and waist circumference . Body mass index ( BMI ) converted to z scores ( SD scores ) and to centile values with growth reference curves . Waist circumference was also converted to z scores ( SD scores ) . Results At three years after baseline the age and sex specific BMI z scores ( SD scores ) had increased in the control group by 0.10 ( SD 0.53 ) but decreased in the intervention group by −0.01 ( SD 0.58 ) , with a mean difference of 0.10 ( 95 % confidence interval −0.00 to 0.21 , P=0.06 ) . The prevalence of overweight increased in both the intervention and control group at three years and the significant difference between the groups seen at 12 months was no longer evident . The BMI increased in the control group by 2.14 ( SD 1.64 ) and the intervention group by 1.88 ( SD 1.71 ) , with mean difference of 0.26 ( −0.07 to 0.58 , P= 0.12 ) . The waist circumference increased in both groups after three years with a mean difference of 0.09 ( −0.06 to 0.26 , P=0.25 ) . Conclusions These longitudinal results show that after a simple year long intervention the difference in prevalence of overweight in children seen at 12 months was not sustained at three years OBJECTIVE To assess the effectiveness of a school and family based healthy lifestyle programme ( WAVES intervention ) compared with usual practice , in preventing childhood obesity . DESIGN Cluster r and omised controlled trial . SETTING UK primary schools from the West Midl and s. PARTICIPANTS 200 schools were r and omly selected from all state run primary schools within 35 miles of the study centre ( n=980 ) , oversampling those with high minority ethnic population s. These schools were r and omly ordered and sequentially invited to participate . 144 eligible schools were approached to achieve the target recruitment of 54 schools . After baseline measurements 1467 year 1 pupils aged 5 and 6 years ( control : 28 schools , 778 pupils ) were r and omised , using a blocked balancing algorithm . 53 schools remained in the trial and data on 1287 ( 87.7 % ) and 1169 ( 79.7 % ) pupils were available at first followup ( 15 month ) and second follow-up ( 30 month ) , respectively . INTERVENTIONS The 12 month intervention encouraged healthy eating and physical activity , including a daily additional 30 minute school time physical activity opportunity , a six week interactive skill based programme in conjunction with Aston Villa football club , signposting of local family physical activity opportunities through mailouts every six months , and termly school led family workshops on healthy cooking skills . OUTCOME MEASURES The protocol defined primary outcomes , assessed blind to allocation , were between arm difference in body mass index ( BMI ) z score at 15 and 30 months . Secondary outcomes were further anthropometric , dietary , physical activity , and psychological measurements , and difference in BMI z score at 39 months in a subset . RESULTS Data for primary outcome analyses were : baseline , 54 schools : 1392 pupils ( 732 controls ) ; first follow-up ( 15 months post-baseline ) , 53 schools : 1249 pupils ( 675 controls ) ; second follow-up ( 30 months postbaseline ) , 53 schools : 1145 pupils ( 621 controls ) . The mean BMI z score was non-significantly lower in the intervention arm compared with the control arm at 15 months ( mean difference −0.075 ( 95 % confidence interval −0.183 to 0.033 , P=0.18 ) in the baseline adjusted models . At 30 months the mean difference was −0.027 ( −0.137 to 0.083 , P=0.63 ) . There was no statistically significant difference between groups for other anthropometric , dietary , physical activity , or psychological measurements ( including assessment of harm ) . CONCLUSIONS The primary analyses suggest that this experiential focused intervention had no statistically significant effect on BMI z score or on preventing childhood obesity . Schools are unlikely to impact on the childhood obesity epidemic by incorporating such interventions without wider support across multiple sectors and environments . TRIAL REGISTRATION Current Controlled Trials IS RCT N97000586 . Introduction Excess weight in childhood is a global problem , affecting around 41 million children under the age of 5 years . In addition to physical and psychosocial health consequences in these early years , childhood For numbered affiliations see end of article . Correspondence to : P Adab [email protected] Cite this as : BMJ 2018;360:k211 http://dx.doi.org/10.1136/bmj.k211 Accepted : 19 December 2017 WhAT IS AlReAdy knoWn on ThIS TopIC Comprehensive systematic review s have suggested that school based interventions could be effective in preventing childhood obesity in high income countries Heterogeneity in intervention components and outcomes limit practical recommendations Furthermore , inconsistent findings in relation to differential effects on subgroups , and impact on inequalities , limited data on potential harms , process measures , and long term effects , as well as lack of data on cost effectiveness , restrict interpretation and wider applicability WhAT ThIS STudy AddS The WAVES study evaluated a theoretically informed , skills based intervention targeting children ’s diet and physical activity behaviours through schools and families It did not result in any meaningful effect on adiposity , dietary intake , or physical activity after 15 or 30 months Although such interventions can fulfil the responsibility of schools for wider education , without upstream support they are unlikely to halt the childhood obesity BACKGROUND Physical Activity Across the Curriculum ( PAAC ) was a three-year cluster r and omized controlled trial to promote physical activity and diminish increases in overweight and obesity in elementary school children . METHODS Twenty-four elementary schools were cluster r and omized to the Physical Activity Across the Curriculum intervention or served as control . All children in grade s two and three were followed to grade s four and five . Physical Activity Across the Curriculum promoted 90 min/wk of moderate to vigorous intensity physically active academic lessons delivered by classroom teachers . Body Mass Index was the primary outcome , daily Physical activity and academic achievement were secondary outcomes . RESULTS The three-year change in Body Mass Index for Physical Activity Across the Curriculum was 2.0+/-1.9 and control 1.9+/-1.9 , respectively ( NS ) . However , change in Body Mass Index from baseline to 3 years was significantly influenced by exposure to Physical Activity Across the Curriculum . Schools with > or = 75 min of Physical Activity Across the Curriculum/wk showed significantly less increase in Body Mass Index at 3 years compared to schools that had < 75 min of Physical Activity Across the Curriculum ( 1.8+/-1.8 vs. 2.4+/-2.0 , p=0.02 ) . Physical Activity Across the Curriculum schools had significantly greater changes in daily Physical activity and academic achievement scores . CONCLUSIONS The Physical Activity Across the Curriculum approach may promote daily Physical activity and academic achievement in elementary school children . Additionally , 75 min of Physical Activity Across the Curriculum activities may attenuate increases in Body Mass Index OBJECTIVE To assess the impact of a 2-year recreational physical activity program in 1044 fourth- and fifth- grade primary schoolchildren from the Province of Cuenca , Spain . STUDY DESIGN Cluster-r and omized controlled trial with 10 intervention and 10 control schools . The program consisted of 3 90-minute sessions of physical activity per week , during 28 weeks every year . Changes in endpoints between baseline ( September 2004 ) and the end of follow-up ( June 2006 ) were compared between the control and intervention group by using mixed regression models , with adjustment for the baseline endpoint value , age , and the school . RESULTS Compared with control subjects , intervention girls reduced the frequency of overweight ( odds ratio , 0.55 ; 95 % CI , 0.39 - 0.78 ; P<.001 ) . However , intervention was associated with an increase in the percentage of body fat in boys ( 0.97 % ; 95 % CI , 0.14 - 1.81 ; P=.02 ) . Girls in the intervention group had lower total cholesterol level ( -6.86 mg/dL ; 95 % CI , -9.70 - -4.01 ; P<.001 ) and apolipoprotein B level ( -3.61 mg/dL ; 95 % CI , -6.27 - -0.95 ; P=.008 ) than control subjects . Results were similar in boys . CONCLUSION In 2 years , the physical activity program lowered the frequency of overweight in girls and reduced total cholesterol and apolipoprotein B in both girls and boys BACKGROUND Over the years schools have reduced physical education and recess time in favor of more academic instruction . Due to the drastic rise in obesity levels among children , some states have begun to m and ate minimum amounts of physical activity ( PA ) that school children receive , causing schools to find alternative methods for increasing PA levels . Physical Activity Across the Curriculum ( PAAC ) is a 3-year r and omized clinical trial incorporating moderate-intensity PA in elementary schools to reduce childhood obesity . This paper describes the rational , design , and methods of the PAAC intervention study . METHODS Twenty-two elementary schools were r and omized to either a control or intervention condition . In schools r and omized to the intervention condition ( PAAC ) , regular classroom teachers were taught how to incorporate PA into st and ard academic lessons . Teachers were asked to accumulate 90 - 100 min/week of PAAC each week through out the 3-year study period . Schools r and omized to the control group did not alter their teaching methods . Direct observation of PA levels in the classroom was collected weekly . Height and weight was measured twice a year to calculate BMI . RESULTS Two years of the intervention have been completed and only one school has left the study . The remaining 21 schools are participating in the final intervention year . CONCLUSIONS The results from the PAAC intervention may provide schools with an alternative method to increase PA levels in children and reduce childhood obesity Through-school nutrition and physical activity interventions are design ed to help reduce excess weight gain and risk of chronic disease . From 2004 to 2006 , Project Energize was delivered in the Waikato Region of New Zeal and as a longitudinal r and omised controlled study of 124 schools ( year 1 - 6 ) , stratified by rurality and social deprivation , and r and omly assigned to intervention or control . Children ( 686 boys and 662 girls ) aged 5 ( 1926 ) and 10 ( 1426 ) years ( 692 interventions and 660 controls ) had height , weight , body fat ( by bioimpedance ) and resting blood pressure ( BP ) measured at baseline and 2 years later . Each intervention school was assigned an ' Energizer ' ; a trained physical activity and nutrition change agent , who worked with the school to achieve goals based on healthier eating and quality physical activity . After adjustment for baseline measures , rurality and social deprivation , the intervention was associated with a reduced accumulation of body fat in younger children and a reduced rate of rise in systolic BP in older children . There was some evidence that the pattern of change within an age group varied with rurality , ethnicity and sex . We conclude that the introduction of an ' Energizer led ' through-school programme may be associated with health benefits over 2 years , but the trajectory of this change needs to be measured over a longer period . Attention should also be paid to the differing response by ethnicity , sex , age group and the effect of rurality and social deprivation OBJECTIVE To assess the feasibility , acceptability , and potential efficacy of a school-based obesity prevention program among adolescent boys with sub-optimal cardiorespiratory fitness . METHODS In 2007 , a 6-month , 2-arm parallel group , r and omized controlled pilot trial was conducted in a single school setting ( Sydney , Australia ) . Thirty-three 7th Grade boys ( mean age=12.5+/-0.4 years ) were r and omly assigned to intervention ( n=16 ) or active comparison group ( n=17 ) . The intervention consisted of one 60-minute curriculum session and two 20-minute lunchtime physical activity sessions per week . The active comparison group continued with their usual physical activity curriculum sessions ( Friday afternoons 2 - 3 pm ) . The pilot trial 's curriculum sessions were additional to Physical Education ( PE ) lessons . The primary outcome was BMI , and secondary outcomes included waist circumference , percentage body fat , cardiorespiratory fitness , objective ly measured physical activity and small screen recreation time . RESULTS Screening , recruitment and retention goals were exceeded . The majority of data were collected as planned . Implementation and attendance rates were acceptable . At follow-up , compared with boys in the active comparison group , boys in the intervention group displayed a smaller increase in BMI ( adjust diff.=-0.2 , 95 % confidence interval [ CI ] -0.78 , 0.39 ; Cohen 's d=0.05 ) ; greater reductions in waist circumference ( -1.65 cm [ -4.67 , 1.36 ] ; d=0.15 ) ; percentage body fat ( -1.69 % [ -4.98 , 1.60 ] ; d=0.22 ) and time spent in small screen recreation on weekends ( -1.13 h [ -5.06 , 2.80 ] ; d=0.19 ) ; and a greater increase in cardiorespiratory fitness ( 2.13 laps [ 6.22 , 10.48 ] ; d=0.16 ) ; and participation in total weekday physical activity ( 140.74 counts/min [ -159.44 , 440.92 ] ; d=0.36 ) . CONCLUSIONS This study verified the feasibility , acceptability and potential efficacy of a multifaceted school-based intervention to prevent unhealthy weight gain among adolescent boys Objectives : To determine whether a school obesity prevention project developed in the United States can be adapted for use in Engl and . Methods : A pilot cluster r and omised controlled trial and interviews with teachers were carried out in 19 primary schools in South West Engl and . Participants included 679 children in year 5 ( age 9–10 ) . Baseline and follow-up assessment s were completed for 323 children ( screen viewing ) and 472 children ( body mass index ) . Sixteen lessons on healthy eating , physical activity and reducing TV viewing were taught over 5 months by teachers . Main outcome measures were hours of screen activities , body mass index , mode of transport to school and teachers ’ views of the intervention . Results : Children from intervention schools spent less time on screen-viewing activities after the intervention but these differences were imprecisely estimated : mean difference in minutes spent on screen viewing at the end of the intervention ( intervention schools minus control schools ) adjusted for baseline levels and clustering within schools was −11.6 ( 95 % CI −42.7 to 19.4 ) for a week day and was −15.4 ( 95 % CI −57.5 to 26.8 ) for a Saturday . There was no difference in mean body mass index or the odds of obesity . Conclusions : It is feasible to transfer this US school-based intervention to UK schools , and it may be effective in reducing the time children spend on screen-based activities . The study has provided information for a full-scale trial , which would require 50 schools ( ∼1250 pupils ) to detect effects on screen viewing and body mass index over 2 years of follow-up AIM Despite recognition that regular physical activity is essential for good health , many children do not accumulate sufficient daily physical activity . The aim of this study was to examine the effect of a classroom-based activity break on accelerometer-determined moderate-to-vigorous intensity physical activity ( MVPA ) and adiposity in primary school children . METHODS One hundred twenty children from seven primary schools in Northern Irel and participated in the study . In each school , one class of children was r and omly assigned to an intervention group and another class to a control group . Teachers of the intervention classes led a 5-min activity break three times per day for 12 weeks . Accelerometer-determined MVPA , height , weight and four skinfolds were measured at baseline and post-intervention . RESULTS Compared with the control group , the intervention group significantly increased weekday MVPA ( + 9.5 min ) from baseline to post-intervention . There were no significant changes in BMI ; however , an increase in sum-of-skinfolds of the intervention group was observed . CONCLUSIONS Classroom-based activity breaks led by the teacher are successful in increasing children 's physical activity levels . The programme shows a positive step in improving overall physical activity levels and contributing to the goal of 60 min daily MVPA BACKGROUND Childhood obesity has become a health problem in urban areas in China . Intervention to reduce childhood obesity should be of high priority . School-based intervention programmes are needed to deal with the growing prevalence of childhood obesity in China . METHODS Five primary schools were selected r and omly for this study in the Beijing urban area in China ; two were allocated to the intervention group and three to the control group . A total of 2425 children ( 1029 children in intervention schools and 1396 children in control schools ) took part in the study for 3 years . In the intervention group , children and their parents were involved in a programme of nutrition education and physical activity . Control school students followed their usual health and physical education curriculum with no extra intervention . RESULTS After the 3-year intervention , the prevalence of overweight and obesity were significantly lower in the intervention schools than in the control schools ( overweight : 9.8 % vs. 14.4 % , P < 0.01 ; obesity : 7.9 % vs. 13.3 % , P < 0.01 ) . The prevalence of overweight and obesity decreased by 26.3 % and 32.5 % in intervention schools respectively after intervention . The prevalence of overweight and obesity increased in control schools . There was also significant difference in body mass index between intervention and control schools ( 18.2 + /- 2.6 vs. 20.3 + /- 3.4 , P < 0.01 ) after intervention . More non-obese children became obese in the control schools ( 7.0 % ) than in the intervention schools ( 2.4 % ) at end line ( P < 0.01 ) . Among the children who were obese at baseline , 49.2 % remained obese at end line in intervention schools while 61.9 % remained obese in control schools ( P < 0.01 ) . CONCLUSIONS Our study showed that an intervention programme could be feasible in schools in Beijing , China . The prevalence of overweight and obesity was reduced in schoolchildren in Beijing through an intervention focused on nutrition education and physical activity . Overweight and obesity children as well as normal weight children and their parents should be involved in such an intervention programme BACKGROUND This study aim ed to assess whether a school-based physical education intervention was effective in improving physical abilities and influencing daily physical activity habits in primary school children . The possible effect on body mass index ( BMI ) was also considered . METHODS Twenty-six 3rd- grade classes were r and omly selected stratifying by geographic location ( city , plain , hills ) and were assigned either to an intervention ( 127 boys ; 120 girls ) or to a traditional ( 129 boys ; 121 girls ) physical education program . At baseline ( age : 8 - 9 years ) and after a 2-year follow-up ( age : 10 - 11 years ) , information was collected about sport participation and daily activity habits using a self-administered question naire . Height , weight , and BMI were measured and physical performance was assessed by means of st and ardized tests . RESULTS The enhanced program of physical education was effective in improving physical abilities of children and determining a decrease ( boys : 10 % ; girls : 12 % ) in daily sedentary activities ( preintervention versus postintervention , p < .05 ; intervention versus control group , p < .01 ) . The percentages of overweight and obese children did not vary significantly , but the experimental group showed a significantly lower rise in BMI compared to the control group ( p < .001 ) . CONCLUSION The school proved to be an ideal setting for promoting physical activity and achieving the required daily activity levels Background Obesity is one of the main determinants of avoidable disease burden . To implement a program by university students acting as “ health promoting agents ” ( HPAs ) and to evaluate the effects on obesity prevalence of the primary -school-based program that promotes healthy lifestyle , including dietary and physical activity recommendations over 28 months . Methods Two school clusters were r and omly assigned to intervention ( 24 schools , 1,222 pupils ) or control ( 14 schools , 717 pupils ) ; 78 % of pupils were Western European . Mean age ( ±SD ) was 8.4 ± 0.6 years ( 49.9 % females ) at baseline . Generalized linear mixed models were used to analyze differences in primary outcome between both groups . Data collected included body mass index ( BMI ) every year . Dietary habits and lifestyle question naires were filled in by the parents at baseline and at the end of the study . The interventions focused on eight lifestyle topics covered in 12 activities ( 1 hour/activity/session ) implemented by HPAs over 3 school academic years . Results At 28 months , obesity prevalence in boys was decreased −2.36 % in the intervention group ( from 9.59 % to 7.23 % ) and increased 2.03 % ( from 7.40 % to 9.43 % ) in the control group ; the difference was 4.39 % ( 95 % CI 3.48 to 5.30 ; P = 0.01 ) . The boys in the intervention group had an effective reduction of −0.24 units in the change of BMI z-score ( from 0.01 to −0.04 ) , compared to control ( from −0.10 to 0.09 ) ; 5.1 % more intervention pupils undertook physical activity > 5 hours/week than control pupils ( P = 0.02).Fish consumption was a protector ( odds ratio 0.39 ; 95 % CI 0.23 to 0.67 ) while “ fast-food ” consumption was a risk factor for childhood obesity ( odds ratio : 2.27 ; 95 % CI 1.08 to 4.77 ) . Conclusions Our school-based program , conducted by HPA students , successfully reduced childhood obesity prevalence in boys . Trial registration International St and ard R and omized Controlled Trial Number : IS RCT N29247645 OBJECTIVES The purpose of this study was to evaluate the effect of a school-based intervention program to reduce overweight and improve fitness in primary school children . METHODS A cluster r and omized controlled design was used over one school year with schools as unit of r and omization . In total 20 schools and 2,622 children aged 6 - 12 years ( grade s 3 - 8 ) from multi-ethnic , low income inner-city neighbourhoods in Rotterdam , Netherl and s , participated . The intervention , named Lekker Fit ! ( Enjoy being fit ! ) was a multi-component intervention based on behavioural and ecological models . Main components of the intervention are the implementation of three physical education ( PE ) sessions a week by a professional PE teacher , additional sport and play activities outside school hours and an educational program . Main primary outcome measures were weight status , body mass index ( BMI ) , waist circumference and fitness ( 20 m shuttle run ) . RESULTS Significant positive intervention effects were found for percentage overweight children ( OR 0.53 ; 95 % CI 0.36 - 0.78 ) , waist circumference ( -1.29 cm ; 95 % CI -2.16 to -0.42 cm ) and 20 m shuttle run ( 0.57 laps ; 95 % CI 0.13 - 1.01 laps ) among pupils of grade s 3 - 5 ( 6 - 9-year olds ) . The prevalence of overweight in grade s 3 - 5 increased by 4.3 % in the control group and by 1.3 % in the intervention group . No significant effects were found for BMI or for grade s 6 - 8 ( 9 - 12-year olds ) . CONCLUSIONS Our results provide evidence for the effectiveness of the multi-component intervention Lekker Fit ! among pupils of grade s 3 - 5 and adds to the growing body of evidence that school-based programs with a focus on PA are most effective in reducing childhood obesity . [ IS RCT N84383524 ] BACKGROUND Programs to improve cardiovascular health in schoolchildren need careful scientific evaluation . METHOD In a r and omized controlled trial of nutrition and fitness programs over a period of about 9 months , 1,147 10- to 12-year-olds from 30 schools were allocated to one of five health programs : fitness , fitness + school nutrition , school-based nutrition , school + home nutrition , home-based nutrition , or a control group . Nutrient intake , fitness , anthropometry , blood pressure , and blood cholesterol were measured before and after intervention . RESULTS Fitness increased and diastolic blood pressure and triceps skinfolds decreased significantly for girls in the fitness groups . Baseline consumption of sugar , fat , and fiber was outside national guidelines ; blood cholesterol exceeded recommendations in one-third of children . In girls , fat intake decreased significantly in the two home nutrition groups and fiber intake increased in the school + home nutrition and fitness groups . Boys in the fitness , fitness + school nutrition , and school + home nutrition group reduced sugar intake . Change in sugar intake correlated negatively with change in fat intake in both boys and girls . CONCLUSIONS Teacher-implemented health packages are feasible with minimal training but programs should differ between boys and girls . Fitness programs were more successful than nutrition education particularly in girls . Clearer nutrition messages should prevent reciprocal changes in sugar and fat . For girls , the 3 mm Hg reduction of diastolic blood pressure , less obesity , and increased fitness could translate into a substantial reduction in cardiovascular risk in adult life OBJECTIVE To provide a framework for implementation of multicomponent , school-based nutrition interventions . This article describes the research methods for the Shaping Healthy Choices Program , a model to improve nutrition and health-related knowledge and behaviors among school-aged children . DESIGN Longitudinal , pretest/posttest , r and omized , controlled intervention . SETTING Four elementary schools in California . PARTICIPANTS Fourth- grade students at intervention ( n = 252 ) and control ( n = 238 ) schools and their parents and teachers . Power analyses demonstrate that a minimum of 159 students per group will be needed to achieve sufficient power . The sample size was determined using the variables of nutrition knowledge , vegetable preference score , and body mass index percentile . INTERVENTION A multicomponent school-based nutrition education intervention over 1 academic year , followed by activities to support sustainability of the program . MAIN OUTCOME MEASURES Dietary and nutrition knowledge and behavior , critical thinking skills , healthy food preferences and consumption , and physical activity will be measured using a nutrition knowledge question naire , a food frequency question naire , a vegetable preferences assessment tool , the Test of Basic Science Process Skills , digital photography of plate waste , PolarActive accelerometers , anthropometrics , a parent question naire , and the School and Community Actions for Nutrition survey . ANALYSIS Evaluation will include quantitative and qualitative measures . Quantitative data will use paired t , chi-square , and Mann-Whitney U tests and regression modeling using P = .05 to determine statistical significance OBJECTIVE To assess whether the benefits seen in nutrition , physical activity . and body mass index were maintained at 2 years of completion of the educational intervention . MATERIAL AND METHODS An experimental , longitudinal , 4-year , two-arm , parallel study with cluster r and omization to assess an intervention program aim ed at children in their first year of primary schooling attending schools in the city of Granollers . Intervention consisted of promoting healthy dietary habits and increasing physical activity through the educational pedagogy Investigation , Vision , Action and Change ( IVAC ) , applied over 2 school years ( 2006 - 2008 ) . Weight and height of each child wee measured in situ , and families self-completed a physical activity survey and the Krece Plus quick test in 2006 , 2008 , and 2010 . RESULTS A greater increase in body mass index was seen in 2010 in children from the control group ( 2.84 ± 0.22 vs 1.96 ± 0.163 kg/m(2 ) , < .001 ) . Prevalence of overweight and obesity increased by 8 % and 0.5 % respectively in schoolchildren in the control group , while the intervention group showed a 5.3 % increase in prevalence of overweight and a 3.6%decrease in prevalence of obesity . Prevalence of excess weight therefore increased by 8.5 % in the control group and by 1.8 % in the intervention group . Reduction in body mass indexincrease was maintained 2 years after completion of educational intervention regardless of sex , origin , maternal obesity , and educational level of parents . CONCLUSIONS These results confirm that school-based interventions may help contain the current increase in childhood obesity There is a worldwide epidemic of obesity with far-reaching consequences for the health of our nation . Prevention of obesity , especially in children , has been deemed by public health policy makers to be one of the most important objectives for our country . This prevention project , called Louisiana ( LA ) Health , will test whether modification of environmental and behavioral factors can prevent inappropriate weight gain in children from rural parishes of Louisiana who are enrolled in the fourth to sixth grade s during Year 1 . The primary aim of the LA Health project is to test the efficacy of two school-based approaches for obesity prevention : primary prevention alone and a combination of primary and secondary prevention which will be compared to a no-intervention control group using a cluster r and omization research design , with 17 school clusters r and omly assigned to the three treatment arms . The study will span 3 years and will provide critical tests of strategies that : 1 ) modify the child 's environment as a primary prevention strategy and 2 ) provide health behavior modification via classroom instruction and internet counseling as a secondary prevention strategy . The study will also recruit a similar sample of students to measure changes in body weight relative to height , gender , and age over the same three-year period BACKGROUND A comprehensive approach involving both environmental and individual strategies offers opportunities to strengthen school-based interventions for childhood obesity . OBJECTIVES To evaluate a theory-based comprehensive intervention implemented within primary schools for childhood obesity in China . METHODS A 1-year , cluster r and omized controlled trial was conducted in twelve primary schools ( 7 - 11 years old ) in Beijing , China . Environmental and individual factors were improved in the intervention group ( 6 schools , 930 children ) to promote knowledge and behaviors related to energy balance . The control group ( 6 schools , 959 children ) did not receive any intervention . The primary outcome was body mass index ( BMI ) and its Z-score at 12 months . Generalized linear mixed models were used controlling for the cluster effect of school . RESULTS No significant differences were found between groups on BMI ( 0.07 kg/m2 [ 95 % confidence interval ( CI ) -0.16 to 0.31 , p = 0.54 ] ) and its Z-score ( 0.02 [ 95 % CI : -0.08 to 0.11 , p = 0.73 ] ) at 12 months . Self-reported knowledge , daily consumption of sugar-sweetened beverage , and frequency of moderate to vigorous physical activity improved at 12 months . CONCLUSIONS The intervention did not mitigate excess weight gain , but did improve children 's knowledge and several behaviors related to energy balance Background : Childhood obesity has been becoming a worldwide public health problem . We conducted a community-based physical activity ( PA ) intervention program aim ing at childhood obesity prevention in general student population in Nanjing of China , the host city of the 2nd World Summer Youth Olympic Games ( YOG-Obesity study ) . Methods : This was a cluster r and omized controlled intervention study . Participants were the 4th ( mean age±s.e . : 9.0±0.01 ) and 7th ( mean age±s.e . : 12.0±0.01 ) grade students ( mean age±s.e . : 10.5±0.02 ) from 48 schools and r and omly allocated ( 1:1 ) to intervention or control groups at school level . Routine health education was provided to all schools , whereas the intervention schools additionally received an 1-year tailored multi-component PA intervention program , including classroom curricula , school environment support , family involvement and fun programs/events . The primary outcome measures were changes in body mass index , obesity occurrence and PA . Results : Overall , 9858 ( 97.7 % ) of the 10091 enrolled students completed the follow-up survey . Compared with the baseline , PA level increased by 33.13 min per week ( s.e . 10.86 ) in the intervention group but decreased by 1.76 min per week ( s.e . 11.53 ) in the control group ( P=0.028 ) . After adjustment for potential confounders , compared with the control group , the intervention group were more likely to have increased time of PA ( adj . Odds ratio=1.15 , 95 % confidence interval=1.06–1.25 ) , but had a smaller increase in mean body mass index ( BMI ) ( 0.22 ( s.e . 0.02 ) vs 0.46 ( 0.02 ) , P=0.01 ) and BMI z-score ( 0.07 ( 0.01 ) vs 0.16 ( 0.01 ) , P=0.01 ) , and were less likely to be obese ( adj . Odds ratio=0.7 , 95 % confidence interval=0.6 , 0.9 ) at study end . The intervention group had fewer new events of obesity/overweight but a larger proportion of formerly overweight/obese students having normal weight by study end . Conclusions : This large community-based PA intervention was feasible and effective in promoting PA and preventing obesity among the general student population in a large city in China . Experiences from this study are the lessons for China to control the childhood obesity epidemic |
944 | 27,328,740 | Our findings indicate that FeNO levels significantly decreased with corticosteroid treatment in ex-smokers with COPD . | INTRODUCTION To our knowledge , no meta- analysis has investigated the response of FeNO levels to corticosteroid treatment in ex-smokers with chronic obstructive pulmonary disease ( COPD ) .
OBJECTIVES This meta- analysis assessed the potential role of fraction of exhaled nitric oxide ( FeNO ) as a biomarker for corticosteroid response in ex-smokers with stable COPD . | Background : A subset of patients with chronic obstructive pulmonary disease ( COPD ) may respond more favorably to inhaled corticosteroids ( ICS ) , but no simple method is currently utilized to predict the presence or absence of ICS responses in patients with COPD . We evaluated the ability of exhaled nitric oxide ( FENO ) and serum inflammatory markers ( C-reactive protein [ CRP ] , interleukin-6 [ IL-6 ] , and interleukin-8 [ IL-8 ] ) to independently predict spirometric responses to ICS in patients with COPD . Methods : Among 60 ex-smokers with severe COPD ( mean FEV1 1.07 L , 36 % of predicted ) , we conducted a single-arm , open-label study . Participants spent four weeks free of any ICS , followed by four weeks of ICS use ( fluticasone propionate 500 mcg twice daily ) . FENO , CRP , IL-6 , IL-8 , and pre-bronchodilator spirometry were measured immediately before and after the four weeks of ICS use . Results : Baseline FENO , CRP , IL-6 , and IL-8 showed no correlations to FEV1 responses to ICS . ICS responders ( increase in FEV1 ≥ 200 mL after four weeks of ICS ) did have significantly higher baseline FENO levels compared with non-responders ( 46.5 parts per billion [ ppb ] vs. 25 ppb , p = 0.028 ) . The receiver operating characteristic curve for FENO to discriminate responders from non-responders had an area under curve of 0.72 . Baseline serum inflammatory markers did not differ between responders and non-responders . Conclusion : In ex-smokers with severe COPD , a measure of local pulmonary inflammation , FENO , may be more closely associated with FEV1 responses to four weeks of ICS than are st and ard markers of systemic inflammation , serum CRP , IL-6 , and BACKGROUND The use of inhaled corticosteroids in mild to moderate COPD is controversial . The aim of this study was to determine whether airway hyperresponsiveness to mannitol might identify patients who are likely to respond to add-on inhaled corticosteroids . METHODS Ninety subjects with mild to moderate COPD were recruited and 68 subsequently r and omized in a double-blind manner to receive inhaled budesonide ( 1,600 μg/d , n = 31 ) or placebo ( n = 37 ) for 3 months . Thirty-eight subjects had airway hyperresponsiveness to mannitol ( 17 received budesonide , 21 placebo ) . All subjects received tiotropium throughout the study , including 4 weeks before r and omization . Spirometry , quality of life ( St. George Respiratory Question naire ) , degree of dyspnea , airway responsiveness to mannitol , and exhaled nitric oxide were assessed at week 0 ( recruitment ) , week 4 ( baseline prior to r and omization ) , and week 16 ( posttreatment ) . RESULTS Compared with placebo , budesonide was associated with improved quality of life in subjects showing airway hyperresponsiveness to mannitol ( difference of changes in quality of life score between r and omization and study completion , −9.1 ; 95 % CI , −15.8 to −2.3 ; P < .01 ) . Treatment with inhaled budesonide also led to a reduction in airway responsiveness to mannitol compared with placebo ( difference in log10 response-dose ratio , −0.3 ; 95 % CI , −0.6 to −0.04 ; P < .01 ) . However , postr and omization changes in FEV1 % predicted , quality of life , and exhaled nitric oxide showed no difference between budesonide and placebo . CONCLUSIONS In subjects with mild to moderate COPD and airway hyperresponsiveness to mannitol , quality of life and airway responsiveness improved after treatment with inhaled corticosteroids added to long-acting bronchodilator therapy BACKGROUND The exhaled nitric oxide ( FeNO ) is a non-invasive marker of airway inflammation in asthma . A very recent statement has suggested FeNO as potential outcome in chronic obstructive pulmonary disease ( COPD ) . Recently , a new h and -held FeNO analyzer ( NIOX MINO ) has been developed . PATIENTS AND METHODS We have evaluated the NIOX MINO in COPD patients and monitored FeNO levels during 1-year assessment in the outpatient setting . Short-term variability in FeNO was compared using a NIOX MINO and a stationary chemiluminescence analyzer ( NOA , Sensormedics ) in healthy volunteers and COPD patients on two consecutive months . Long-term FeNO variability was assessed on a cohort of 70 COPD out patients measuring FeNO for 1 year . The intra-individual FeNO coefficient of variation ( eNOCoV ) was taken as index FeNO long-term variability . RESULTS In COPD there were no significant differences between NIOX MINO and NOA FeNO values recorded at baseline and 1 month later . Ninety five percent limits of agreement between NIOX MINO and NOA were-2.7 and 1.9ppb with significant reliability ( r=0.96 , p<0.0001 ) . Mean FeNO at baseline was 15.0+/-9.5ppb . Over the 1-year period the overall mean FeNO was 15.5+/-10.1ppb . The long-term eNOCoV was 33.9+/-16.4 % ( range 8.1 - 83.1 % ) , and it was significantly associated with exacerbation rate ( r=0.57 , p<0.0001 ) . CONCLUSION FeNO electrochemical h and -held analyzer is feasible in COPD showing good agreement with stationary chemiluminescence analyzer . COPD patients exhibit a wide range of FeNO levels and a high variability of FeNO over time , which was positively associated with the number of exacerbations BACKGROUND Inhaled corticosteroids ( ICS ) treatment for asthma control is generally focused on lung function and symptoms , but inadequately correlated with airway inflammation . OBJECTIVE To compare asthma control in a group of patients whose treatment was based on fraction of exhaled nitric oxide ( FENO ) and sputum eosinophils ( intervention group ) with a group in whom treatment was based on clinical score ( control group ) . Study design and primary outcome : R and omized parallel-group longitudinal 24-month study including 5 visits every 6 months . A combination of asthma exacerbation rate and symptom score at 24 months was the primary outcome . PARTICIPANTS Fourteen patients with eosinophilic asthma per group were included . RESULTS In the intervention group , exacerbation rate/patient/year was reduced at 12 months ( 0.82 ) ( -73 % ) and , to a greater extent at 24 months ( 0.5 ) ( -84 % ) compared with baseline ( 3.21 , p<0.01 ) . In the control group , a significant reduction in exacerbation rate/patient/year was only observed between month 12 ( 3.0 ) and 24 ( 2.0 , -33 % , p<0.01 ) . At 24 months , exacerbation rate was lower ( -75 % ) in the intervention ( 0.5 ) than in the control group ( 2.0 , p<0.05 ) . Compared with baseline , mean symptom scores at 24 months were reduced in both groups ( intervention group : -72 % ; control group : - 60 % ) , but were lower in the intervention ( 8.1±1.0 , p<0.05 ; -27 % ) than in the control group ( 11±2.6 ) . ICS dose gradually increased in both groups throughout the study , with no between-group differences . CONCLUSION Compared with conventional strategy , longitudinal monitoring of FENO and sputum eosinophils improves eosinophilic asthma control in terms of reduced symptoms and exacerbations without additional increase e in ICS treatment RATIONALE Predicting corticosteroid response in COPD is important but difficult . Response is more likely to occur in association with eosinophilic airway inflammation , for which the fraction of exhaled nitric oxide ( Fe(NO ) ) is a good surrogate marker . OBJECTIVES We aim ed to establish whether Fe(NO ) levels would predict the clinical response to oral corticosteroid in COPD . METHODS We performed a double-blind , crossover trial of steroid in patients with COPD . After a 4-week washout of inhaled steroids , patients received prednisone 30 mg/d or matching placebo , in r and om order , with an intervening 4-week washout . The predictive values of Fe(NO ) for clinical ly significant changes in 6-minute-walk distance ( 6MWD ) , spirometry ( FEV(1 ) ) , and St. George 's Respiratory Question naire ( SGRQ ) were calculated . MEASUREMENTS AND MAIN RESULTS A total of 65 patients ( mean FEV(1 ) = 57 % predicted ) were r and omized . With prednisone , there was a net increase of 13 m in 6MWD ( P = 0.02 ) and 0.06 L in postbronchodilator FEV(1 ) ( P = 0.02 ) compared with placebo . The change in SGRQ was not significant . Using receiver operator characteristic analysis , the area under the curve for an increase of 0.2 L in FEV(1 ) was 0.69 ( P = 0.04 ) with an optimum Fe(NO ) cut-point of 50 ppb . The positive and negative predictive values were 67 and 82 % , respectively . FE(NO ) was not a significant predictor for changes in 6MWD or SGRQ . CONCLUSIONS Fe(NO ) is a weak predictor of short-term response to oral corticosteroid in COPD , its usefulness being limited to predicting increase in FEV(1 ) . Clinical trial registered with www.anzctr.org.au ( ACTRN12605000683639 ) The aim of the study was to evaluate the exhaled nitric oxide ( F(ENO ) ) in clinical ly stable chronic obstructive pulmonary disease ( COPD ) , its relationship to the severity of the disease , pulmonary function , smoking status , reversibility of airflow limitation , and ICS therapy . The study was conducted in 47 patients with COPD and 40 healthy controls . Flow/volume spirometry and F(ENO ) measurement were performed before and after 2 months of ICS therapy . F(ENO ) were significantly elevated in current smokers and ex-smoking COPD patients . In both groups of COPD patients inhaled corticosteroids ( ICS ) therapy caused a significant decrease in F(ENO ) without significant changes in FEV1 . A positive correlation between initial F(ENO ) and postbronchodilator FEV1 ( % predicted ) was observed in the group of ex-smoking COPD patients , but not in the currently smoking COPD group . In both groups of COPD patients , the initial level of F(ENO ) correlated with the reversibility of airway obstruction , the increase in postbronchodilator FEV1 and the decrease in F(ENO ) following ICS treatment . F(ENO ) increases in patients with stable COPD . ICS therapy decreased elevated F(ENO ) levels in these patients without statistically significant changes in lung function . The selection of COPD patients with increased F(ENO ) level and partial reversibility of airway obstruction should be helpful in terms of proposed ICS treatment There is controversy about the role of inhaled corticosteroids in chronic obstructive pulmonary disease ( COPD ) . Although they appear to have little impact on airways obstruction or its progression , their use may reduce the frequency and /or severity of exacerbations in a subset of patients . We undertook the following study to determine the impact of inhaled corticosteroid on two noninvasive markers of airways inflammation . We assigned 20 stable nonsmoking patients with COPD in r and om , double-blind crossover fashion to two 2-wk treatment periods with inhaled beclomethasone 500 microg twice daily or matching placebo , followed by a 2-wk washout period . We measured exhaled nitric oxide ( ENO ) , breath condensate H(2)O(2 ) , and flow volume spirometry at weekly intervals . Median baseline ENO was 26.2 ( 19.3 to 54.8 ) ppb and fell significantly following 1 and 2 wk of beclomethasone ( -10.6 ppb , p = 0.002 , and -6.3 ppb , p = 0.013 , respectively ) but was unchanged by placebo inhalation . Breath condensate H(2)O(2 ) levels did not change significantly with inhaled beclomethasone or placebo . Although there were no significant changes in FEV(1 ) with BDP therapy , there was a moderate inverse correlation between changes in ENO and changes in FEV(1 ) ( r -0.50 ) . We conclude that inhaled beclomethasone reduces ENO levels in stable nonsmoking patients with COPD , a finding compatible with an antiinflammatory mechanism of action The use of noninvasive methods of monitoring airway inflammation , such as exhaled nitric oxide ( eNO ) and induced sputum , has been shown to improve asthma monitoring and optimize treatment in adult patients with asthma . There is a lack of comparable data in children . Forty children with stable asthma eligible for inhaled steroid reduction were review ed every 8 weeks , and their inhaled steroid dose halved if clinical ly indicated . eNO , sputum induction combined with bronchial hyperreactivity testing , and exhaled breath condensate collection were performed at each visit to predict success or failure of reduction of inhaled steroids . Thirty of 40 ( 75 % ) children tolerated at least one dose reduction , 12 of 40 ( 30 % ) were successfully weaned off , and in total , 15 of 40 ( 38 % ) children experienced loss of asthma control . Treatment reduction was successful in all children who had no eosinophils in induced sputum before the attempted reduction . Using multiple logistic regression , increased eNO ( odds ratio , 6.3 ; confidence interval , 3.75 - 10.58 ) and percentage of sputum eosinophils ( odds ratio , 1.38 ; confidence interval , 1.06 - 1.81 ) were significant predictors of failed reduction . These findings suggest that monitoring airway inflammation may be useful in optimizing treatment in children with asthma Fractional exhaled nitric oxide ( FENO ) may be a pulmonary biomarker in chronic obstructive pulmonary disease ( COPD ) . In this prospect i ve study , the relationship between FENO and airway inflammation was assessed in COPD exacerbations . FENO and lung function were measured , and sputum was collected from 49 ex-smoking COPD patients , first at the time of hospital admission and again at discharge following treatment . There was a significant positive correlation between the percentage of sputum eosinophils and FENO concentrations , both at exacerbation ( r = 0.593 , p < 0.001 ) and discharge ( r = 0.337 , p = 0.044 ) . The increase in forced expiratory volume in one second ( FEV1 ) after treatment was greater in patients with sputum eosinophilia ( ΔFEV1 0.35 ± 0.12 vs. 0.13 ± 0.04 L , p = 0.046 ) , and FENO was a strong predictor of sputum eosinophilia ( area under the receiver operating characteristic curve , 0.89 ) . The optimum cut point was 19 parts per billion ( sensitivity : 90 % ; specificity : 74 % ) . Our data suggest that FENO is a good surrogate marker of eosinophilic inflammation in COPD patients with exacerbations |
945 | 22,431,677 | Low- quality evidence has found that in persons with acute coronary syndromes , glycoprotein IIb/IIIa inhibitors or clopidogrel plus st and ard care compared with st and ard care alone had little or no effect on all-cause or cardiovascular mortality or on myocardial infa rct ion but increased serious bleeding .
Benefits for antiplatelet therapy among persons with CKD are uncertain and are potentially outweighed by bleeding hazards . | BACKGROUND Antiplatelet agents are used to prevent cardiovascular events ; however , treatment effects may differ in persons with chronic kidney disease ( CKD ) because atherosclerotic disease is less prevalent , whereas bleeding hazards may be increased in this population .
PURPOSE To summarize the effects of antiplatelet treatment on cardiovascular events , mortality , and bleeding in persons with CKD . | OBJECTIVE Type 2 diabetes accompanied by renal damage is a strong risk factor for atherosclerotic events . The purpose of this study was to investigate the efficacy of low-dose aspirin therapy on primary prevention of atherosclerotic events in patients with type 2 diabetes and coexisting renal dysfunction . RESEARCH DESIGN AND METHODS The Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes ( JPAD ) trial was a prospect i ve , r and omized , open-label trial conducted throughout Japan that enrolled 2,539 type 2 diabetic patients without a history of atherosclerotic diseases . Patients were assigned to the aspirin group ( 81 mg/day or 100 mg/day ) or the nonaspirin group and followed for a median of 4.37 years . The primary end points were atherosclerotic events of fatal and nonfatal ischemic heart disease , stroke , and peripheral arterial disease . RESULTS The analysis included 2,523 patients who had serum creatinine measured . In 1,373 patients with baseline estimated glomerular filtration rate ( eGFR ) 60–89 mL/min/1.73 m2 , the incidence of primary end points was significantly lower in the aspirin group than in the nonaspirin group ( aspirin , 30/661 ; nonaspirin , 55/712 ; hazard ratio 0.57 [ 95 % CI 0.36–0.88 ] ; P = 0.011 ) . Low-dose aspirin therapy did not reduce primary end points in patients with eGFR ≥90 mL/min/1.73 m2 ( aspirin , 9/248 ; nonaspirin , 11/270 ; 0.94 [ 0.38–2.3 ] ) or those with eGFR < 60 mL/min/1.73 m2 ( aspirin , 29/342 ; nonaspirin , 19/290 ; 1.3 [ 0.76–2.4 ] ) . The Cox proportional hazard model demonstrated a significant interaction between mild renal dysfunction ( eGFR 60–89 mL/min/1.73 m2 ) and aspirin ( P = 0.02 ) . CONCLUSIONS These results suggest a differential effect of low-dose aspirin therapy in diabetic patients with eGFR 60–89 mL/min/1.73 m2 Background —The role of glycoprotein IIb/IIIa receptor antagonists for the treatment of patients with acute coronary syndrome and renal insufficiency remains undefined . Methods and Results — Patients from the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms ( PRISM-PLUS ) trial were stratified by creatinine clearance ( CrCl ) and assessed with respect to treatment assignment to tirofiban/heparin versus heparin alone for the risk of adverse outcomes and bleeding . Patients with severe renal insufficiency ( defined as a serum creatinine ≥2.5 mg/dL ) were excluded from PRISM-PLUS as a whole . Patients with the lowest CrCl ( < 30 mL/min ) were more likely to present with high-risk clinical features . Decreasing renal function was strongly associated with adverse outcome , increasing the risk for ischemic complications at all time points examined ( all P < 0.002 ) . Irrespective of CrCl , therapy with tirofiban reduced the odds of the composite end point of death , myocardial infa rct ion , or refractory ischemia at 48 hours ( odds ratio [ OR ] , 0.68 ; 95 % confidence interval [ CI ] , 0.46 to 1.0;P = 0.05 ) , 7 days ( OR , 0.68 ; 95 % CI , 0.52 to 0.88;P = 0.003 ) , 30 days ( OR , 0.78 ; 95 % CI , 0.63 to 0.98;P = 0.03 ) , and 6 months ( OR , 0.81 ; 95 % CI , 0.68 to 0.98;P = 0.03 ) . The risk of myocardial infa rct ion/death was also significantly decreased to a similar magnitude at all time points examined . There was no evidence of treatment-by-CrCl interaction . The presence of declining renal function independently increased the risk for bleeding ( OR , 1.57;P < 0.001 for trend across categories ) , as did therapy with tirofiban , but no unexpected incremental risk of bleeding due to tirofiban was observed among lowest CrCl categories . Conclusions —Among patients with mild-to-moderate renal insufficiency in PRISM-PLUS , tirofiban was well tolerated and effective in reducing ischemic acute coronary syndrome complications Idiopathic membranoproliferative glomerulonephritis ( MPGN ) has a poor prognosis , with 90 % of patients requiring dialysis treatment after 20 years regardless of therapy . Up to 34 % of patients may die due to thrombotic complications or sepsis . This study investigates the influence of aspirin plus dipyridamole on proteinuria and renal function in nephrotic MPGN patients with moderately reduced glomerular filtration rate . Eighteen patients with biopsy-proven MPGN ( 15 type I , 3 type II ) and nephrotic syndrome were r and omly assigned to receive protein restriction , antihypertensive therapy ( control group ) or in addition aspirin and dipyridamole ( treatment group ) . Patients were prospect ively followed for a mean of 36 months . Serum creatinine remained unchanged after 36 months compared to baseline in both groups . In the treatment group proteinuria was reduced from 8.3 + /- 1.4 to 1.6 + /- 0.7 g/day ( P < 0.05 ) . In control patients proteinuria decreased from 7.1 + /- 1.6 to 4.3 + /- 1.1 g/day . After 36 months proteinuria was significantly lower in the treatment group compared to control ( P < 0.02 Mann-Whitney rank sum test ) . In conclusion , aspirin plus dipyridamole may be of value in reversing nephrotic syndrome and associated risks in patients with MPGN and moderately reduced renal function Since platelet cyclo-oxygenase is much more sensitive to inactivation by aspirin than is the enzyme in the arterial wall and low doses of aspirin may prevent thrombosis by blocking thromboxane synthesis , we conducted a r and omized , double-blind trial of aspirin ( 160 mg per day ) vs. placebo in 44 patients on chronic hemodialysis . The study was continued until there were 24 patients with thrombi and both groups had been under observation for a mean of nearly five months . Thrombi occurred in 18 of 25 ( 72 per cent ) of patients given placebo and 16 of 19 ( 32 per cent ) of those given aspirin ( P less than 0.01 ) . The incidence of thrombosis was reduced from 0.46 thrombi per patient month in the placebo group to 0.16 thrombi per patient month in the aspirin group ( p less than 0.005 ) . A dose of 160 mg of aspirin per day is an effective , nontoxic antithrombotic regimen in patients on hemodialysis Background — Reduced renal function is associated with a poorer prognosis and increased bleeding risk in patients with acute coronary syndromes and may therefore alter the risk-benefit ratio with antiplatelet therapies . In the Platelet Inhibition and Patient Outcomes ( PLATO ) trial , ticagrelor compared with clopidogrel reduced the primary composite end point of cardiovascular death , myocardial infa rct ion , and stroke at 12 months but with similar major bleeding rates . Methods and Results — Central laboratory serum creatinine levels were available in 15 202 ( 81.9 % ) acute coronary syndrome patients at baseline , and creatinine clearance , estimated by the Cockcroft Gault equation , was calculated . In patients with chronic kidney disease ( creatinine clearance < 60 mL/min ; n=3237 ) , ticagrelor versus clopidogrel significantly reduced the primary end point to 17.3 % from 22.0 % ( hazard ratio [ HR ] , 0.77 ; 95 % confidence interval [ CI ] , 0.65 to 0.90 ) with an absolute risk reduction greater than that of patients with normal renal function ( n=11 965 ) : 7.9 % versus 8.9 % ( HR , 0.90 ; 95 % CI , 0.79 to 1.02 ) . In patients with chronic kidney disease , ticagrelor reduced total mortality ( 10.0 % versus 14.0 % ; HR , 0.72 ; 95 % CI , 0.58 to 0.89 ) . Major bleeding rates , fatal bleedings , and non – coronary bypass – related major bleedings were not significantly different between the 2 r and omized groups ( 15.1 % versus 14.3 % ; HR , 1.07 ; 95 % CI , 0.88 to 1.30 ; 0.34 % versus 0.77 % ; HR , 0.48 ; 95 % CI , 0.15 to 1.54 ; and 8.5 % versus 7.3 % ; HR , 1.28 ; 95 % CI , 0.97 to 1.68 ) . The interactions between creatinine clearance and r and omized treatment on any of the outcome variables were nonsignificant . Conclusions — In acute coronary syndrome patients with chronic kidney disease , ticagrelor compared with clopidogrel significantly reduces ischemic end points and mortality without a significant increase in major bleeding but with numerically more non – procedure-related bleeding . Clinical Trial Registration — URL : http://www.clinicatrials.gov . Unique identifier : NCT00391872 When constructing arteriovenous fistulas for haemodialysis in chronic renal failure patients , one of the main problems is still their clotting tendency . Ticlopidine is an effective inhibitor of platelet aggregation . In this r and omized double-blind study placebo or ticlopidine 250 mg twice daily was given to chronic uremic patients up to 4 weeks after construction of an arteriovenous fistula . 42 patients were recruited and 36 completed the trial . The fistula clotted in 8 patients on placebo and in 2 patients on ticlopidine . The difference is significant . This effect was achieved without an increased frequency of side effects compared with placebo . It is concluded that ticlopidine has a function as a thromboprophylactic drug in chronic uremic patients The optimal vascular access for chronic maintenance hemodialysis is the arteriovenous fistula ( AVF ) . Several studies suggest a role for antiplatelet agents in the prevention of primary AVF failure . A double-blind , r and omized trial was conducted to assess the efficacy and safety of clopidogrel in hemodialysis patients . Ninety three patients were r and omized to receive 75 mg/daily of clopidogrel or placebo . The treatment was initiated 7–10 days prior to scheduled access surgery and continued up to six weeks postoperatively , and then patients were monitored for six months . The primary outcome was AVF failure eight weeks after fistula creation . With a permuted block r and omization schedule , 46 patients received clopidogrel and 47 patients received control placebo . The primary AVF failures at two months were 21.6 % in placebo group and 5.2 % in clopidogrel group ( P = 0.03 ) . The hazard ratio for the incidence of primary AVF failure was 0.72 ( CI 95 % , 0.41–1.01 ) . Analysis of covariables indicated that this effect occurred principally as a result of clopidogrel administration . First hemodialysis from newly created AVF in clopidogrel group was significantly more successful than placebo group ( P = 0.008 ) . No life-threatening adverse event or severe bleeding was recorded in both groups . Clopidogrel seems to be effective and safe for prevention of primary AVF failure in hemodialysis patients In a prospect i ve r and omized trial the anti-thrombotic effect of dipyridamole was studied in 64 patients after cadaveric kidney allotransplantation . The frequency of early graft function was significantly higher in the control group , whereas the incidence of arterial and venous thromboses were not different . One-year graft survival could not be improved by dipyridamole . Therefore , dipyridamole should not be recommended in cadaveric kidney allotransplantation BACKGROUND Mild and moderate chronic kidney disease ( CKD ) is associated with decreased survival and increased adverse events after a percutaneous coronary intervention ( PCI ) . Therapy with clopidogrel decreases adverse events in large patient population s. Therefore , we sought to determine the efficacy and safety of long-term clopidogrel therapy in patients with CKD . METHODS Two thous and two patients from the CREDO trial in whom an elective PCI of a single or multiple vessels was planned were analyzed . Patients were r and omly assigned to a 300-mg loading dose of clopidogrel before PCI followed by clopidogrel 75 mg/d for a year versus a placebo loading dose at the time of the PCI procedure and clopidogrel 75 mg/d for 28 days and placebo for the remainder of a year . Patients were categorized by their estimated creatinine clearance ( > 90 [ normal , n = 999 ] , 60 - 89 [ mild CKD , n = 672 ] , < 60 mL/min [ moderate CKD , n = 331 ] ) . RESULTS Diminished renal function was associated with worse outcomes . Patients with normal renal function who received 1 year of clopidogrel had a marked reduction in death , myocardial infa rct ion , or stroke compared with those who received placebo ( 10.4 % vs 4.4 % , P < .001 ) , whereas patients with mild and moderate CKD did not have a significant difference in outcomes with clopidogrel therapy versus placebo ( mild : 12.8 % vs 10.3 % , P = .30 ; moderate : 13.1 % vs 17.8 % , P = .24 ) . Clopidogrel use was associated with an increased relative risk of major or minor bleeding , but this increased risk was not different based on renal function ( relative risk 1.2 , 1.3 , 1.1 ) . CONCLUSIONS Clopidogrel in mild or moderate CKD patients may not have the same beneficial effect as it does in patients with normal renal function , but was not associated with a greater relative risk of bleeding based on renal function . Further studies are needed to define the role of clopidogrel therapy in patients with CKD BACKGROUND The presence of coexisting conditions has a substantial effect on the outcome of acute myocardial infa rct ion . Renal failure is associated with one of the highest risks , but the influence of milder degrees of renal impairment is less well defined . METHODS As part of the Valsartan in Acute Myocardial Infa rct ion Trial ( VALIANT ) , we identified 14,527 patients with acute myocardial infa rct ion complicated by clinical or radiologic signs of heart failure , left ventricular dysfunction , or both , and a documented serum creatinine measurement . Patients were r and omly assigned to receive captopril , valsartan , or both . The glomerular filtration rate ( GFR ) was estimated by means of the four-component Modification of Diet in Renal Disease equation , and the patients were grouped according to their estimated GFR . We used a 70-c and i date variable model to adjust and compare overall mortality and composite cardiovascular events among four GFR groups . RESULTS The distribution of estimated GFR was wide and normally shaped , with a mean ( + /-SD ) value of 70+/-21 ml per minute per 1.73 m2 of body-surface area . The prevalence of coexisting risk factors , prior cardiovascular disease , and a Killip class of more than I was greatest among patients with a reduced estimated GFR ( less than 45.0 ml per minute per 1.73 m2 ) , and the use of aspirin , beta-blockers , statins , or coronary-revascularization procedures was lowest in this group . The risk of death or the composite end point of death from cardiovascular causes , reinfa rct ion , congestive heart failure , stroke , or resuscitation after cardiac arrest increased with declining estimated GFRs . Although the rate of renal events increased with declining estimated GFRs , the adverse outcomes were predominantly cardiovascular . Below 81.0 ml per minute per 1.73 m2 , each reduction of the estimated GFR by 10 units was associated with a hazard ratio for death and nonfatal cardiovascular outcomes of 1.10 ( 95 percent confidence interval , 1.08 to 1.12 ) , which was independent of the treatment assignment . CONCLUSIONS Even mild renal disease , as assessed by the estimated GFR , should be considered a major risk factor for cardiovascular complications after a myocardial infa rct ion Thrombosis of hemodialysis vascular access grafts represents a major medical and economic burden . Experimental and clinical models suggest a role for antiplatelet agents in the prevention of thrombosis . The study was design ed to determine the efficacy of the combination of aspirin and clopidogrel in the prevention of graft thrombosis . The study was a r and omized , double-blind trial conducted at 30 hemodialysis units at Veterans Affairs medical centers . Participants undergoing hemodialysis with a polytetrafluoroethylene graft in the arm were r and omized to receive either double placebos or aspirin ( 325 mg ) and clopidogrel ( 75 mg ) daily . Participants were to be monitored while receiving study medications for a minimum of 2 yr . The study was stopped after r and omization of 200 participants , as recommended by the Data Safety and Monitoring Board because of a significantly increased risk of bleeding among the participants receiving aspirin and clopidogrel therapy . The cumulative incidence of bleeding events was significantly greater for those participants , compared with participants receiving placebos [ hazard ratio , 1.98 ; 95 % confidence interval ( CI ) , 1.19 to 3.28 ; P = 0.007 ] . Twenty-three participants in the placebo group and 44 participants in the active treatment group experienced a bleeding event ( P = 0.006 ) . There was no significant benefit of active treatment in the prevention of thrombosis ( hazard ratio , 0.81 ; 95 % CI , 0.47 to 1.40 ; P = 0.45 ) , although there was a trend toward a benefit among participants who had not experienced previous graft thrombosis ( hazard ratio , 0.52 ; 95 % CI , 0.22 to 1.26 ; P = 0.14 ) . In the hemodialysis population , therapy with aspirin and clopidogrel was associated with a significantly increased risk of bleeding and probably would not result in a reduced frequency of graft thrombosis OBJECTIVES The purpose of this study was to determine the benefit and risk associated with antiplatelet therapy in the chronic kidney disease ( CKD ) population . BACKGROUND Cardiovascular and possibly bleeding risks are elevated in patients with CKD . The balance of benefit and harm associated with antiplatelet therapy remains uncertain . METHODS The HOT ( Hypertension Optimal Treatment ) study r and omly assigned participants with diastolic hypertension to aspirin ( 75 mg ) or placebo . Study treatment effects were calculated using univariate proportional hazards regression models stratified by baseline estimated glomerular filtration rate ( eGFR ) with trends tested by adding interaction terms . End points included major cardiovascular events , total mortality , and major bleeding . RESULTS The study included 18,597 participants treated for 3.8 years . Baseline eGFR was < 60 ml/min/1.73 m(2 ) in 3,619 participants . Major cardiovascular events were reduced by 9 % ( 95 % confidence interval [ CI ] : -9 % to 24 % ) , 15 % ( 95 % CI : -17 % to 39 % ) , and 66 % ( 95 % CI : 33 % to 83 % ) for patients with baseline eGFR of ≥ 60 , 45 to 59 , and < 45 ml/min/1.73 m(2 ) , respectively ( p trend = 0.03 ) . Total mortality was reduced by 0 % ( 95 % CI : -20 % to 17 % ) , 11 % ( 95 % CI : -31 % to 40 % ) , and 49 % ( 95 % CI : 6 % to 73 % ) , respectively ( p trend = 0.04 ) . Major bleeding events were nonsignificantly greater with lower eGFR ( hazard ratio [ HR ] : 1.52 [ 95 % CI : 1.11 to 2.08 ] , HR : 1.70 [ 95 % CI : 0.74 to 3.88 ] , and HR : 2.81 [ 95 % CI : 0.92 to 8.84 ] , respectively ; p trend = 0.30 ) . Among every 1,000 persons with eGFR < 45 ml/min/1.73 m(2 ) treated for 3.8 years , 76 major cardiovascular events and 54 all-cause deaths will be prevented while 27 excess major bleeds will occur . CONCLUSIONS Aspirin therapy produces greater absolute reduction in major cardiovascular events and mortality in hypertensive patients with CKD than with normal kidney function . An increased risk of major bleeding appears to be outweighed by the substantial benefits Objective : Our aim was to determine the effect of short-term therapy with anti-platelet drugs on type-2 diabetic nephropathy for which a generally accepted therapy is missing . Material and Methods : Seventy-six patients with type-2 diabetic nephropathy , who had normal renal function tests were r and omized into the 4 groups ; each group ( n = 19 ) received one of the following treatments : aspirin ( 1000 mg ) , dipyridamole ( 750 mg ) , their combination or placebo daily for 2 months . Blood pressure , fasting blood sugar , serum electrolytes , creatinine clearance and 24 hours urine protein excretion rate was measured just before and at the end of the trial . Results : Proteinuria and urinary protein : creatinine ratio decreased significantly in all 3 groups receiving aspirin and /or dipyridamole compared with the placebo group , also in each of those 3 groups comparing pre- and post-treatment values , while creatinine clearance rate , blood pressure , and blood sugar remained unchanged . At the end of the trial , the percentage proteinuria change was-15.9%,-14.8%,-37.3 % and 1.9 % in aspirin , dipyridamole , their combination and placebo groups respectively . The percentage proteinuria change had no positive correlation with demographic , clinical and laboratory findings but showed a strong positive correlation with mode of the therapy ( r = 0.38 , p = 0.0007 ) . The percentage decline in proteinuria was significantly higher in the combination group than in the aspirin and dipyridamole groups . No side effects related to aspirin or dipyridamole was seen during the trial . Conclusions : Short-term trial of aspirin and /or dipyridamole significantly reduces proteinuria of type-2 diabetic nephropathy , with the most prominent effect seen with combination of the 2 drugs Picotamide both inhibits thromboxane synthetase and acts as a thromboxane antagonist at the receptor level . We investigated the long-term effect of picotamide on urinary albumin excretion ( UAE ) at rest and induced by exercise in 30 type 2 diabetic patients who were normotensive and had microalbuminuria while at rest . The subjects of our study had a mean age of 52.5 + /- 1.6 years , BMI of 28.5 + /- 0.7 kg/m2 , diabetes duration of 9.1 + /- 1.8 years , and HbA1c of 7.0 + /- 0.8 % . The study was a r and omized double-blind placebo-controlled trial . The patients were r and omly allocated to receive for 1 year either picotamide , 300 mg , 3 tablets/day , or placebo , 3 tablets/day . The patients were asked to visit our outpatient clinic after 1 , 3 , 6 , 9 , and 12 months of treatment . At all times , blood pressure , microalbuminuria at rest , blood glucose , serum creatinine , serum picotamide , and creatinine clearance were measured ; at baseline and after 6 and 12 months , all patients underwent submaximal physical exercise . After 6 months of picotamide , baseline and exercise-induced microalbuminuria were significantly decreased ( up to one-third ) as compared with the baseline and placebo level , with no further drops at month 12 of picotamide treatment . On placebo treatment , UAE at rest and after exercise was slightly increased compared with baseline values . The effects of picotamide occurred without significant side effects or changes in either blood pressure levels or glycometabolic control . Our study is the first long-term intervention trial in type 2 diabetes showing that an antithromboxane agent is able to decrease microalbuminuria , which in this disease is a dual marker of macro- and microangiopathy . Our findings suggest an important role for thromboxane in the pathophysiology of microalbuminuria in diabetes ; moreover , we hypothesize that antithromboxane agents may have a place in the treatment/prevention of both macro- and microvascular complications in type 2 diabetic patients Summary In a prospect i ve double blind study prophylactic administration of Acetylsalicylic acid ( ASA ) in low doses decreased significantly the rate of fistula clotting in the immediately p.o . period in uremic patients . The risk of fistula clotting was related to poor arterial blood flow , female sex and number of unsuccessful previous fistula operations . The incidence of side effects ( g.i . and non g.i . bleeding ) was acceptable with low doses of ASA and prophylactic administration of antacids . ZusammenfassungIn einer prospektiven Doppelblindstudie wurde der Einfluß von Acetylsalicylsäure auf die Häufigkeit von Cimino-Fistelthrombosen in der ersten p.o . Phase untersucht . Durch prophylaktische Gabe von Acetylsalicylsäure ließ sich der thrombotische Fistelverschluß auf 4 % senken ( Placebogruppe : 23 % ) . Ein erhöhtes Thromboserisiko best and bei schlechtem arteriellen Blutfluß , weiblichem Geschlecht und vorausgegangenen erfolglosen Fisteloperationen . Die Nebenwirkungen von Acetylsalicylsäure waren vertretbar , sofern Aspirin in niedriger Dosierung und in Verbindung mit Antacida verabreicht wurde No prospect i ve r and omized trial has specifically examined the long-term outcomes of clopidogrel use in patients with chronic kidney disease . This study aim ed to determine the risks and benefits of long-term clopidogrel administration in patients with diabetic nephropathy , the most common form of chronic kidney disease . We performed a post hoc analysis of the CHARISMA trial , which r and omly assigned patients without active acute coronary syndrome , but with established atherosclerotic disease ( symptomatic ) or multiple risk factors for atherosclerotic disease ( asymptomatic ) , to clopidogrel plus aspirin versus placebo plus aspirin . All CHARISMA patients ( n = 15,603 ) were separated into the 3 groups : nondiabetic patients , diabetic patients without nephropathy , and diabetic patients with nephropathy . Within each group , outcomes of patients r and omly assigned to clopidogrel were compared with those of patients r and omly assigned to placebo . Outcomes in the prespecified CHARISMA subgroups of asymptomatic and symptomatic patients were also compared with respect to study drug assignment and nephropathy status . Patients with nephropathy who received clopidogrel had no difference in bleeding , but experienced significantly increased cardiovascular ( CV ) and overall mortality compared with those r and omly assigned to placebo . There were no differences in bleeding , overall mortality , or CV mortality for nondiabetic or diabetic patients without nephropathy who received clopidogrel versus placebo . In the asymptomatic cohort , patients with nephropathy r and omly assigned to clopidogrel had significantly increased overall and CV mortality compared with placebo , whereas asymptomatic patients without nephropathy r and omly assigned to clopidogrel had no significant mortality difference compared with placebo . In conclusion , this post hoc analysis suggested that clopidogrel may be harmful in patients with diabetic nephropathy . Additional studies are needed to investigate this possible interaction Two hundred and fifty-eight patients with uremia who were offered surgery for placement of an arteriovenous fistula for hemodialysis were recruited in nine regional dialysis centers . The patients were r and omized to receive the platelet aggregation inhibitory compound ticlopidine , 250 mg b.d . , or matching placebo . Study medication was targeted at 7 , minimum 3 , days before scheduled surgery and continued for 28 days after surgery . The overall rate of occlusion was 41/260 evaluable operations ( 16 % ) , 25/131 ( 19 % ) in the placebo group and 16/129 ( 12 % ) in the ticlopidine group . The risk of early occlusion was a non-significant 35 % lower in the ticlopidine group . Limited risk factor analysis did not clearly identify any subgroup other than females at greater risk of early thrombosis nor any subgroup deriving particular benefit from ticlopidine treatment Treatment of the anaemia of renal disease with recombinant human erythropoietin results in an improvement of haemostasis and an increased risk of thrombovascular accidents . In this prospect i ve , placebo-controlled , double-blind , and cross-over study , the effects of low-dose acetylsalicylic acid ( 30 mg daily ) on thrombotic and bleeding events during the initial period of treatment with erythropoietin in anaemic haemodialysis patients without previous thrombovascular accidents or known increased risk for thrombosis were investigated . During correction of the haematocrit and the first 3 months thereafter , group A ( n = 68 ) received placebo and group B ( n = 69 ) 30 mg acetylsalicylic acid daily . Cross-over took place after the 3rd month of a stable haematocrit . The study ended 3 months later . Target haematocrit ( 30 - 35 % ) was reached in 12.4 + /- 8 weeks ( M + /- SD ) . In group A the bleeding time was 382 + /- 285 s , decreasing to 282 + /- 208 before cross-over ( P < 0.01 ) , and increasing to 395 + /- 271 ( P < 0.05 ) thereafter . In group B the bleeding time was 390 + /- 381 s , 406 + /- 267 ( NS ) , and 285 + /- 238 ( P < 0.05 ) respectively . Twenty-two thrombovascular accidents were seen ( 16 % , 13 during acetylsalicylic acid and 9 during placebo , NS ) , including 17 fistula thromboses . The incidence of bleeding events was not significantly different between regimens . In conclusion , erythropoietin treatment result ed in a reduction of the bleeding time . When 30 mg acetylsalicylic acid was taken during the treatment , the bleeding time did not decrease . ( ABSTRACT TRUNCATED AT 250 WORDS Hemodialysis ( HD ) vascular access thrombosis remains a major cause of morbidity , accounting for 17.4 % of all HD patient hospital admissions in 1986 . We initiated this prospect i ve , r and omized , double-blind , placebo-controlled , parallel group study to examine if dipyridamole and /or aspirin decreased the rate of thrombosis of exp and ed polytetrafluoroethylene ( ePTFE ) grafts in HD patients . Two patient groups were studied : Type I -- with a new ePTFE graft ; and Type II -- with thrombectomy and /or revision of a previously placed ePTFE graft . One hundred and seven patients were followed for 18 months or until the first thrombotic episode . Actuarial analysis of Type I patients showed cumulative thrombosis rates ( mean + /- SEM ) of 21 + /- 9 % on dipyridamole alone , compared with 25 + /- 11 % on dipyridamole and aspirin combination , 42 + /- 13 % on placebo , and 80 + /- 12 % on aspirin alone . The relative risk of thrombosis with dipyridamole was 0.35 ( P = 0.02 ) and that for aspirin was 1.99 ( P = 0.18 ) . In Type II patients , the rate of thrombosis was high in all study drug and placebo groups ( overall 78 % thrombosis ) and actuarial analysis was not carried out because of the small number of patients enrolled . We conclude that dipyridamole is beneficial in patients with new ePTFE grafts and that aspirin does not improve the risk of thrombosis in ePTFE grafts . Neither dipyridamole nor aspirin has any beneficial effect in patients with prior thrombosis of ePTFE grafts Forty patients with Type I membranoproliferative glomerulonephritis were treated for one year with dipyridamole , 225 mg per day , and aspirin , 975 mg per day , in a prospect i ve , r and omized , double-blind , placebo-controlled study . At the base line , the half-life of 51Cr-labeled platelets was reduced in 12 of 17 patients . The platelet half-life became longer and renal function stabilized in the treated group , as compared with the placebo group , suggesting a relation between platelet consumption and the glomerulopathy . The glomerular filtration rate , determined by iothalamate clearance , was better maintained in the treated group ( average decrease , 1.3 ml per minute per 1.73 m2 of body-surface area per 12 months ) than in the placebo group ( average decrease , 19.6 ) . Fewer patients in the treated group than in the placebo group had progression to end-stage renal disease ( 3 of 21 after 62 months as compared with 9 of 19 after 33 months ) . The data suggest that dipyridamole and aspirin slowed the deterioration of renal function and the development of end-stage renal disease CONTEXT The arteriovenous fistula is the preferred type of vascular access for hemodialysis because of lower thrombosis and infection rates and lower health care expenditures compared with synthetic grafts or central venous catheters . Early failure of fistulas due to thrombosis or inadequate maturation is a barrier to increasing the prevalence of fistulas among patients treated with hemodialysis . Small , inconclusive trials have suggested that antiplatelet agents may reduce thrombosis of new fistulas . OBJECTIVE To determine whether clopidogrel reduces early failure of hemodialysis fistulas . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial conducted at 9 US centers composed of academic and community nephrology practice s in 2003 - 2007 . Eight hundred seventy-seven participants with end-stage renal disease or advanced chronic kidney disease were followed up until 150 to 180 days after fistula creation or 30 days after initiation of dialysis , whichever occurred later . INTERVENTION Participants were r and omly assigned to receive clopidogrel ( 300-mg loading dose followed by daily dose of 75 mg ; n = 441 ) or placebo ( n = 436 ) for 6 weeks starting within 1 day after fistula creation . MAIN OUTCOME MEASURES The primary outcome was fistula thrombosis , determined by physical examination at 6 weeks . The secondary outcome was failure of the fistula to become suitable for dialysis . Suitability was defined as use of the fistula at a dialysis machine blood pump rate of 300 mL/min or more during 8 of 12 dialysis sessions . RESULTS Enrollment was stopped after 877 participants were r and omized based on a stopping rule for intervention efficacy . Fistula thrombosis occurred in 53 ( 12.2 % ) participants assigned to clopidogrel compared with 84 ( 19.5 % ) participants assigned to placebo ( relative risk , 0.63 ; 95 % confidence interval , 0.46 - 0.97 ; P = .018 ) . Failure to attain suitability for dialysis did not differ between the clopidogrel and placebo groups ( 61.8 % vs 59.5 % , respectively ; relative risk , 1.05 ; 95 % confidence interval , 0.94 - 1.17 ; P = .40 ) . CONCLUSION Clopidogrel reduces the frequency of early thrombosis of new arteriovenous fistulas but does not increase the proportion of fistulas that become suitable for dialysis . Trial Registration clinical trials.gov Identifier : NCT00067119 Abstract The effects of sulfinpyrazone and a placebo on the incidence of thrombosis of arteriovenous shunts was investigated in a double-blind study in 52 patients on chronic hemodialysis over a six-month period . Thrombi occurred in 86 per cent of patients on placebo and 50 per cent of those on sulfinpyrazone ( p<0.01 ) . The incidence of thrombosis was reduced from 0.76 thrombi per patient month in the placebo group to 0.18 thrombi per patient month in the sulfinpyrazone group ( p<0.001 ) . Venous-shunt revisions were required in 48 per cent of patients given placebo and in only 16 per cent of those receiving sulfinpyrazone ( p<0.05 ) . Side effects were minimal and necessitated withdrawal from the study in only one patient . This study supports the results of animal experiments showing that sulfinpyrazone decreases thrombus formation the high-flow systems . ( N Engl J Med 290:304–306 , 1974 The antiplatelet drug ticlopidine was assessed as an agent for improving the patency of Brescia-Cimino arteriovenous fistulas as access for hemodialysis . In a double-blind r and omized study over 1 month , two of six fistulas in the ticlopidine group and five of nine in the placebo group failed . A further one placebo and two ticlopidine patients still had functioning fistulas at the time of withdrawal for technical reasons from the trial . Ticlopidine appears , therefore , to enhance the efficacy of Brescia-Cimino fistulas , at least in the short term BACKGROUND Arteriovenous graft stenosis leading to thrombosis is a major cause of complications in patients undergoing hemodialysis . Procedural interventions may restore patency but are costly . Although there is no proven pharmacologic therapy , dipyridamole may be promising because of its known vascular antiproliferative activity . METHODS We conducted a r and omized , double-blind , placebo-controlled trial of extended-release dipyridamole , at a dose of 200 mg , and aspirin , at a dose of 25 mg , given twice daily after the placement of a new arteriovenous graft until the primary outcome , loss of primary unassisted patency ( i.e. , patency without thrombosis or requirement for intervention ) , was reached . Secondary outcomes were cumulative graft failure and death . Primary and secondary outcomes were analyzed with the use of a Cox proportional-hazards regression with adjustment for prespecified covariates . RESULTS At 13 centers in the United States , 649 patients were r and omly assigned to receive dipyridamole plus aspirin ( 321 patients ) or placebo ( 328 patients ) over a period of 4.5 years , with 6 additional months of follow-up . The incidence of primary unassisted patency at 1 year was 23 % ( 95 % confidence interval [ CI ] , 18 to 28 ) in the placebo group and 28 % ( 95 % CI , 23 to 34 ) in the dipyridamole-aspirin group , an absolute difference of 5 percentage points . Treatment with dipyridamole plus aspirin significantly prolonged the duration of primary unassisted patency ( hazard ratio , 0.82 ; 95 % CI , 0.68 to 0.98 ; P=0.03 ) and inhibited stenosis . The incidences of cumulative graft failure , death , the composite of graft failure or death , and serious adverse events ( including bleeding ) did not differ significantly between study groups . CONCLUSIONS Treatment with dipyridamole plus aspirin had a significant but modest effect in reducing the risk of stenosis and improving the duration of primary unassisted patency of newly created grafts . ( Clinical Trials.gov number , NCT00067119 . |
946 | 24,263,707 | Overall , there was no statistically significant intervention effect on measures of injury .
There is a paucity of high- quality research in the area of bicycle skills training programmes .
Educational and skills training bicycling programmes may increase knowledge of cycling safety , but this does not seem to translate into a decrease in injury rate , or improved bicycle h and ling ability and attitudes | BACKGROUND Bicycling is a popular means of recreation and transportation for children ; however , it is a leading cause of recreational injury .
Bicycle skill development and safety education are important methods of bicycle injury prevention .
OBJECTIVE To determine the effectiveness of bicycle skills training programmes in reducing bicycle-related injuries in children and youth . | OBJECTIVE The purpose of this study was to evaluate the " Bike Smart " program , an eHealth software program that teaches bicycle safety behaviors to young children . METHODS Participants were 206 elementary students in grade s kindergarten to 3 . A r and om control design was employed to evaluate the program , with students assigned to either the treatment condition ( Bike Smart ) or the control condition ( a video on childhood safety ) . Outcome measures included computer-based knowledge items ( safety rules , helmet placement , hazard discrimination ) and a behavioral measure of helmet placement . RESULTS Results demonstrated that regardless of gender , cohort , and grade the participants in the treatment group showed greater gains than control participants in both the computer-presented knowledge items ( p > .01 ) and the observational helmet measure ( p > .05 ) . CONCLUSIONS Findings suggest that the Bike Smart program can be a low cost , effective component of safety training packages that include both skills-based and experiential training OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity Objective —To evaluate the effectiveness of a skills training program in improving safe cycling behavior , knowledge , and attitudes in young children . Methods — Grade 4 children from six elementary schools in East York ( a borough of Metropolitan Toronto ) participated . The intervention — playground based instruction on bicycle h and ling skills by certified instructors — was r and omly allocated to three schools . Altogether 141 children participated : 73 in the intervention group and 68 in the control group , with follow up evaluations available on 117 ( 83 % ) . The primary outcome was safe cycling behavior ( straight line riding , coming to a complete stop , and shoulder checking before a left turn ) . A self report question naire collected data on knowledge and attitudes . Baseline assessment s were made in June , with follow up evaluations in September , 1995 . Results —The prevalence of safe cycling behaviors at follow up in the intervention and control groups respectively , were : straight line riding ( 90 % v 88 % ; p=0.782 ) , coming to a complete stop ( 90 % v 76 % ; p=0.225 ) , and shoulder checking ( 0 % v 2 % ; p=1.000 ) . Over time ( from baseline to follow up ) children in both groups were more likely to maintain straight line riding , less likely to ride on the sidewalk , and less likely to consider that a car had more right to the road . Conclusions —This brief skills training program was not effective in improving safe cycling behavior , knowledge , or attitudes among grade 4 children Two training methods were developed to teach young cyclists ( 8/9 years ) how to behave in priority situations . One method was developed along the lines of the modelling principle . In earlier studies it was shown that this method is effective in teaching crossing strategies to young pedestrians . The other training method was based upon And erson 's Adaptive Control of Thought ( ACT ) theory , which describes the development of cognitive skills by proceduralisation and composition of behaviour and knowledge elements into automatic behaviour sequences . Two groups of children were trained with one of these methods . A control group did not receive traffic-related training in that period . The effect of the training was assessed by a knowledge test and a behaviour test . The results showed that the partly theoretical ACT approach initially result ed in an increased level of knowledge , which was found to have disappeared after a month . The modelling approach did not affect the level of knowledge . Both approaches had an equally positive effect on simple behavioural strategies , such as signalling and visual search behaviour . Correct application of priority rules appeared to be very difficult to teach . There was no effect of the two training methods . It seemed that children apply informal rules rather than formal rules when dealing with other traffic . It is hypothesized that these informal rules should form the starting point for training activities , because formal rules do not fit into children 's cognitive framework of schemes , and therefore can not be stored and retrieved effectively Objectives —To evaluate possible benefits of a school based bicycle safety education program ( “ Bike Ed ” ) on the risk of bicycle injury in children . Methods —A population based case-control study was undertaken in a region of Melbourne , Australia . Cases were children presenting at hospital emergency departments with injuries received while riding bicycles . Controls were recruited by calling r and omly selected telephone numbers . Data were collected by personal interview . Results — Analysis , based on 148 cases and 130 controls aged 9 to 14 years , showed no evidence of a protective effect and suggested a possible harmful effect of exposure to the bicycle safety course ( odds ratio ( OR ) 1.64 , 95 % confidence interval ( CI ) 0.98 to 2.75 ) . This association was not substantially altered by adjustment for sex , age , socioeconomic status , and exposure , measured as time or distance travelled . Subgroup analysis indicated that the association was strongest in boys ( OR 2.0 , 95 % CI 1.1 to 3.8 ) , younger children , children from families with lower parental education levels , and children lacking other family members who bicycle . Conclusions —It is concluded that this educational intervention does not reduce the risk of bicycle injury in children and may possibly produce harmful effects in some children , perhaps due to inadvertent encouragement of risk taking or of bicycling with inadequate supervision |
947 | 19,120,508 | Clinical impressions have generally been favourable and support the findings of laboratory and animal-based investigations . | OBJECTIVE The aim of this study was to present a review of the reported literature on : ( i ) the physical and chemical properties ; and ( ii ) clinical applications of mineral trioxide aggregate ( MTA ) in the practice of paediatric dentistry .
CONCLUSION Paediatric dentists have successfully employed MTA in a variety of endodontic/restorative applications since the late 1990s . | PURPOSE The purpose of this study was to compare mineral trioxide aggregate ( MTA ) with calcium hydroxide ( Ca(OH)2 ) clinical ly and radiographically as a pulpotomy agent in immature permanent teeth ( apexogenesis ) . METHODS Fifteen children , each with at least 2 immature permanent teeth requiring pulpotomy ( apexogenesis ) , were selected for this study . All selected teeth were evenly divided into 2 test groups . In group 1 , the conventional Ca(OH)2pulpotomy ( control ) was performed , whereas in group 2 , the MTA pulpotomy ( experimental ) was done . The children were recalled for clinical and radiographic evaluations after 3 , 6 , and 12 months . RESULTS The follow-up evaluations revealed failure due to pain and swelling detected at 6 and 12 months postoperative evaluations in only 2 teeth treated with Ca(OH)2 . The remaining 28 teeth appeared to be clinical ly and radiographically successful 12 months postoperatively . Calcific metamorphosis was a radiographic finding in 2 teeth treated with Ca(OH)2 and 4 teeth treated with MTA . CONCLUSIONS Mineral trioxide aggregate showed clinical and radiographic success as a pulpotomy agent in immature permanent teeth ( apexogenesis ) and seems to be a suitable alternative to calcium hydroxide PURPOSE To evaluate the results of using mineral trioxide aggregate ( MTA ) in pulpotomy procedures in primary teeth . METHODS Seven patients were selected and a total of 20 molars and two canines were treated with pulpotomy procedures using MTA instead of formocresol . RESULTS After 6 months , 55 % of the molars and 100 % of the canines treated showed radiographic signs of dentin bridge formation . Also , 6 months after treatment , 60 % of the molars showed root canal calcification ( obliteration ) . Color change of the crown of the canines treated was noticeable . No clinical or radiographic signs of pathology was observed Purpose The aim of this study was to compare the effect of white mineral trioxide aggregate ( MTA ) to that of formocresol ( FC ) as pulp dressing agents in pulpotomised primary molars . Methods In this clinical trial study , 60 lower second primary molars of 46 children were treated by a conventional pulpotomy technique . The teeth were r and omly assigned to the MTA ( experimental ) and FC ( control ) groups by r and om numbered table . Following removal of the coronal pulp and haemostasis , the pulp stumps were covered with an MTA paste in the experimental group . In the control group , FC was placed with a cotton pellet over the pulp stumps . The teeth of both groups were restored with stainless steel crowns . Children arrived for clinical and radiographic follow-up evaluation after 6 , 12 and 24 months . Results The treated teeth in FC group ( n = 18 ) were clinical ly and radiographically successful after 24 months . The radiographic follow-up evaluation revealed one failure ( furcation involvement ) in 18 molars treated with MTA after 24 months . The treated teeth in MTA group were clinical ly successful 24 months postoperatively . Pulp canal obliteration was observed in one of the teeth treated with MTA and four of the teeth treated with FC . Conclusion MTA could be used as a safe medicament for pulpotomy in cariously exposed primary molars and could be a substitute for FC The objective of the present study was to test the hypothesis that the fracture strength of calcium hydroxide and mineral trioxide aggregate (MTA)-filled immature teeth decreased over time . Immature m and ibular incisors from sheep were extracted and the pulps were extirpated using an apical approach with a barbed broach , and the teeth were divided into three experimental groups . Group 1 : untreated teeth . Group 2 : the root canals were filled with calcium hydroxide paste . Group 3 : the root canals were filled with MTA . All specimens were kept in saline with 1 % antibiotics at 4 degrees C for certain periods of time : 2 weeks , 2 months , and 1 year . Then they were tested for fracture strength in an Instron testing machine . The results were subjected to statistical analysis by the Tukey-Kramer tests . A P-value ( < 0.05 ) was considered statistically significant . One tooth from each group was selected r and omly for a histological study , examining matrix metalloproteinases ( MMP2 and MMP14 ) and tissue inhibitor of metalloproteinase ( TIMP ) . The results showed the mean fracture strengths decreased over time for all the three groups . Although the untreated teeth showed the highest value ( 45.5 MPa ) at 2 weeks , the fracture strengths decreased significantly after 2 months ( P < 0.05 ) . On the other h and , the teeth treated with calcium hydroxide or MTA decreased , but not significantly over time ( P > 0.05 ) . For the MTA-treated teeth , the fracture strengths were not found significantly different from the untreated or calcium hydroxide-treated teeth at 2 weeks or 2 months ( P > 0.05 ) . However , the strength was significantly higher in the MTA group compared with the other two groups after 1 year ( P < 0.05 ) . Immunofluorescence images revealed expression of collagen type 1 , MMP-2 and MMP-14 in both untreated and endodontically treated teeth . However , TIMP-2 was only observed in the MTA-treated teeth . In conclusion , the teeth with root treatment with MTA showed the highest fracture resistance at 1 year ( P < 0.05 ) . An explanation could be that MTA induced the expression of TIMP-2 in the dentin matrix and thereby possibly prevented destruction of the collagen matrix The purpose of this study was to compare the ability of different thicknesses of mineral trioxide aggregate ( MTA ) to prevent apical leakage through the use of a protein-dye complex with Coomassie Brilliant Blue G. Sixty-four teeth were divided into 4 groups , then filled with MTA to depths of 1 , 2 , 3 , or 4 mm . Two teeth served as the positive controls . Another 2 teeth served as the negative controls . Root-filled teeth were mounted in an apparatus and then challenged with protein solution . The evaluation was conduced at 24-hour intervals for 60 days . The 1-mm-thick MTA was the least effective in preventing apical leakage ( P < .05 ) . No significance difference was found between 2- and 3-mm-thick MTA ( P > .05 ) . Four-millimeter-thick MTA was significantly more effective than the other thicknesses tested ( P < .05 ) . The results of this study suggest that the thickness of 4 mm is most adequate for the use of MTA as a root-end filling material PURPOSE The objective of this study was to assess the effect of mineral trioxide aggregate ( MTA ) as pulp dressing material following pulpotomy in primary molars with carious pulp exposure and compare them to those of formocresol ( FC ) . METHODS Of 33 children , primary molars treated via a conventional pulpotomy technique were r and omly assigned to the MTA group ( 33 teeth ) or FC group ( 29 teeth ) . Clinical and radiographic follow-up ranged between 4 and 74 months . The mean follow-up time was 38 months , with no difference between the groups . Twenty-nine teeth were followed until uneventful shedding ( mean=33 months ) . Failures were detected after a mean period of 16 months ( range=4 to 30 ) . RESULTS The success rate of pulpotomy was 97 % for MTA ( 1 failure ) and 83 % for FC ( 5 failures ) . Eight teeth presented internal resorption . In 4 of them ( 2 of each group ) , progress of the resorption process stopped and the pulp tissue was replaced by a radioopaque calcified tissue . Pulp canal obliteration was observed in 58 % of the MTA group and in 52 % of the FC group ( total=55 % ) . CONCLUSIONS MTA showed a higher ( though not statistically significant ) long-term clinical and radiographic success rate than formocresol , and can be recommended as its replacement as , unlike FC , MTA does not induce undesirable responses The purpose of the study was to compare several methods that have been used to assess marginal leakage of root canal fillings . Sixty-three extracted , single-rooted teeth were instrumented and filled in a st and ardized manner . Teeth were r and omly divided into groups of twenty and exposed to solutions containing methylene blue dye , calcium-45 , carbon-14-labeled urea , and iodine-125-labeled albumin for 48 hours to compare the degree of leakage indicated by each technique . Methylene blue dye was found to penetrate farther up the canal than any of the isotope tracers . Carbon-14-labeled urea penetrated farther than the calcium-45- or iodine-125-labeled albumin . The mean volume of solution penetrating the teeth was exceedingly small ( 0.0011 ml ) and probably unimportant physiologically PURPOSE To evaluate the clinical , radiographical and histological findings in human third molars in which mechanical pulp exposures were capped with white ProRoot mineral trioxide aggregate ( WMTA ) . METHODS Forty-eight human third molars , caries-free or with incipient caries , scheduled to be extracted , were used and r and omly divided into two groups : Group A : ( n= 24 ) received WMTA and control Group B : ( n= 24 ) received chemical set calcium hydroxide ( Dycal ) . The teeth were isolated with rubber dam and Class I cavities prepared . Pulp exposure was performed using a sterile diamond bur and confirmed by frank bleeding . A sterile cotton pellet dipped in saline solution was placed over the exposure for 60 seconds . The preparation was then lightly rinsed with water and gently air-dried . WMTA or CH was placed over the exposure site followed by a small amount of a light-cured compomer . After etching with 35 % phosphoric acid gel for 15 seconds , rinsing and blot drying , Prime and Bond NT adhesive was applied and light-cured . The cavity was then restored with a resin composite and light-cured . Evaluations were performed by phone after 7 days and clinical ly at 30 + /- 5 and 136 + /- 24 days , using st and ardized tests and radiographs . The teeth were extracted after 136 + /- 24 days ; the roots were cut + /- 4 - 5 mm from the apex to allow for rapid fixation in 10 % neutral buffered formalin . They were then processed for routine histological evaluation , embedded in paraffin , sectioned and stained with hematoxylin and eosin and Brown and Brenn for recognition of bacteria . Statistical analyses were performed using a Mann-Whitney U-test , a Chi-square test , a Fisher 's exact test and an ANOVA . RESULTS No significant differences in post-operative sensitivity were reported after 7 days between the two material s ( P > 0.05 ) . Clinical examination demonstrated no significant differences at 30 + /- 5 days ( P > 0.05 ) and at 136 + /- 24 days ( P > 0.05 ) . Histological findings : 45 of 48 teeth were suitable for microscopic evaluation ( 22 with WMTA and 23 with CH ) . Twenty from the WMTA and 18 from the CH group had developed a bridge . No statistically significant differences were found for superficial and deep inflammatory cell response ( P > 0.05 ) , presence of a dentin bridge ( P > 0.01 ) , and pulp vitality ( P > 0.01 ) , between WMTA and calcium hydroxide . A statistically significant difference was found for the diameter of exposure ( P < or = 0.05 ) between WMTA ( x= 0.35 + /- 0.19 mm ) and CH ( x= 0.25 + /- 0.09 mm ) . Only a minimal association between clinical and histological findings could be established for either material After 2 yrs ' follow-up , mineral trioxide aggregate ( MTA ) appeared suitable for this purpose AIM To compare the outcome after 6 months of the application of formocresol ( FC ) or mineral trioxide aggregate ( MTA ) during pulpotomy in primary molar teeth . METHODOLOGY A maximum of 126 children ( aged 5 - 9 years ) with carious primary teeth that required pulpotomy were selected . Following r and omization , a st and ard pulpotomy preparation was undertaken , and the coronal pulp removed and bleeding arrested . In the FC group , cotton balls , soaked in FC , were placed for 5 min , and then the pulp chamber was filled with Zonalin , a pulpotomy agent . In the MTA group , a 1-mm-thick paste of MTA was used as a pulpotomy agent . The crowns in both groups were restored with amalgam or glass ionomer . The teeth of 100 patients were evaluated and compared clinical ly and radiographically after 3 and 6 months . RESULTS No signs of clinical failure were observed at the 3- and 6-month follow-up appointments in either group . There were no significant differences in the radiographic findings of the teeth and surrounding tissue at the 3-month follow-up . However , at the 6-month follow-up , significantly more cases ( P = 0.036 ) with root resorption were seen in the FC group ; no cases of resorption occurred amongst the MTA cases . The surrounding tissue showed radiographic signs of post-treatment disease in four FC cases ; none was seen in the MTA cases . CONCLUSION After 6 months , pulpotomy with MTA was associated with fewer cases of root resorption and post-treatment disease . MTA appears to be a reliable alternative material for pulpotomy in primary molar teeth PURPOSE The aim of this study was to compare the effect of mineral trioxide aggregate ( MTA ) to that of formocresol ( FC ) as pulp dressing agents in pulpotomized primary molars with carious pulp exposure . METHODS Forty-five primary molars of 26 children were treated by a conventional pulpotomy technique . The teeth were r and omly assigned to the MTA ( experimental ) or FC ( control ) group by a toss of a coin . Following removal of the coronal pulp and hemostasis the pulp stumps were covered with an MTA paste in the experimental group . In the control group , FC was placed with a cotton pellet over the pulp stumps for 5 minutes and removed ; the pulp stumps were then covered by zinc oxide-eugenol ( ZOE ) paste . The teeth of both groups were restored with stainless steel crowns . Eighteen children with 32 teeth arrived for clinical and radiographic follow-up evaluation ranging from 6 to 30 months . RESULTS The follow-up evaluations revealed only one failure ( internal resorption detected at a 17 months postoperative evaluation ) in a molar treated with formocresol . None of the MTA-treated teeth showed any clinical or radiographic pathology . Pulp canal obliteration was observed in 9 of 32 ( 28 % ) evaluated molars . This finding was detected in 2 out of the 15 teeth treated with FC ( 13 % ) and in 7 out of the 17 treated with MTA ( 41 % ) . CONCLUSION MTA showed clinical and radiographic success as a dressing material following pulpotomy in primary teeth and seems to be a suitable replacement for formocresol in primary teeth OBJECTIVE To evaluate the effect of matrix on mineral trioxide aggregate ( MTA ) when used to repair furcal perforations . STUDY DESIGN Forty-five human molars with furcal perforations were r and omly divided into 3 groups and repaired with MTA either alone or over a barrier ( calcium sulfate or Collaplug ) . Eight teeth without perforations provided negative control sample s. After assessing repair quality , 1 mol/L glucose solution was used as the tracer to detect the leakage . The concentration of leaked glucose was measured after 1 , 2 , 4 , 7 , 15 , and 20 days using a glucose oxidase method . RESULTS No significant difference in either leakage or overfilling was found between the groups with Collaplug and MTA alone ( P > .05 ) . Although no overfilling was detected in the group with calcium sulfate , that group had the most leakage ( P < .05 ) . CONCLUSIONS Neither of the 2 internal matrices improved the sealing ability and reduced the incidence of overfilling simultaneously PURPOSE The aim of this study was to use clinical , radiographic , and histologic examinations to compare the relative success of gray mineral trioxide aggregate ( MTA ) , white MTA , and formocresol as pulp dressings in pulpotomized primary teeth . METHODS Twenty-four children , each with at least 3 primary molars requiring pulpotomy , were selected for this study 's clinical and radiographic portion . An additional 15 carious primary teeth planned for serial extraction were selected for this study 's histologic portion . All selected teeth were evenly divided into 3 test groups and treated with pulpotomies . Gray MTA was used as the pulp dressing for one third of the teeth , white MTA was the dressing for one third , and the remaining one third were treated with formocresol . The treated teeth selected for the clinical and radiographic evaluations were monitored periodically for 12 months . The treated teeth selected for histologic study were monitored periodically and extracted 6 months postoperatively . RESULTS Four children with 12 pulpotomized teeth failed to return for any follow-up evaluations in the clinical and radiographic study . Of the remaining 60 teeth in 20 patients , 1 tooth ( gray MTA ) exfoliated normally and 6 teeth ( 4 white MTA and 2 formocresol ) failed due to abscesses . The remaining 53 teeth appeared to be clinical ly and radiographically successful 12 months postoperatively . Pulp canal obliteration was a radiographic finding in 11 teeth treated with gray MTA and 1 tooth treated with white MTA . In the histologic study , both types of MTA successfully induced thick dentin bridge formation at the amputation sites , while formocresol induced thin , poorly calcified dentin . Teeth treated with gray MTA demonstrated pulp architecture nearest to normal pulp by preserving the odontoblastic layer and delicate fibrocellular matrix , yet few inflammatory cells or isolated calcified bodies were seen . Teeth treated with white MTA showed a denser fibrotic pattern , with more isolated calcifications in the pulp tissue along with secondary dentin formation . CONCLUSIONS Gray MTA appears to be superior to white MTA and formocresol as a pulp dressing for pulpotomized primary teeth This study utilized clinical and radiographic examinations to compare the effectiveness of calcium hydroxide paste and mineral trioxide aggregate ( MTA ) for pulpotomies of primary molars in children . Ninety primary molars that showed clinical and radiographic indications for pulpotomy treatment were selected . The pulpotomies were performed in two sessions , using a corticosteroid/antibiotic solution as therapeutic dressing . The sample was divided into two groups of 45 teeth , in which the pulpal remains were protected with either calcium hydroxide paste ( Group 1 ) or MTA ( Group 2 ) . Radiographs were taken immediately and at 3- , 6- , and 12-month follow-up appointments . Three teeth in Group 1 failed after three months , while two cases failed after six months and one more failed at one year . Two failures were found in Group 2 at the 12-month follow-up . These results indicate that both material s may be utilized for pulpotomies in primary teeth In the present study , multivariate analyses were performed on clinical and treatment variables that may influence the outcome of endodontic treatment . Data collected in a previous clinical -radiographic follow-up study were used . Of 810 treated , 675 roots in 498 teeth were followed for 6 months to 4 yr . Of these , 192 ( the CAP group ) had pre-existing , chronic apical periodontitis and 483 ( the NAP group ) had not . Root canal treatment followed a st and ard procedure with one of three sealers chosen at r and om . Demographic , clinical and radiographic variables were recorded at the start of , and during treatment . The periapical index ( PAI ) score was used to record the outcome of treatment , and applied in two different endpoint modes ( END1 and END2 ) as the dependent variable for multivariate statistical analyses using logistic regression and the general model . The modes reflected increasing PAI scores ( END1 ) and conventional success/failure assessment ( END2 ) . Dropouts were largely similar to the cases followed up . A total of 10 preoperative and peroperative variables were found to be significantly associated with treatment outcome by the multivariate analyses of either the total material or the NAP or CAP subgroups . Several of these were not significant in univariate analyses ( e.g. the effect of sealer ) . Conventional success/failure analyses ( END2 ) identified fewer of the influential variables and had low explanatory power , whereas PAI scores on an ordinal scale ( END1 ) were most sensitive in identifying variables of influence on the treatment outcome AIM To compare the effectiveness of mineral trioxide aggregate ( MTA ) , calcium hydroxide ( CH ) and formocresol ( FC ) as pulp dressing agents in carious primary teeth . METHODOLOGY Forty-five primary m and ibular molars with dental caries in 23 children [ AUTHOR QUERY : How many children ? ] between 5 and 9 years old were treated by a conventional pulpotomy technique . The teeth were r and omly assigned to the experimental ( CH or MTA ) or control ( FC ) groups . After coronal pulp removal and haemostasis , remaining pulp tissue was covered with MTA paste or CH powder in the experimental groups . In the control group , diluted FC was placed with a cotton pellet over the pulp tissue for 5 min and removed ; the pulp tissue was then covered with zinc oxide-eugenol ( ZOE ) paste . All teeth were restored with reinforced ZOE base and resin modified glass-ionomer cement . Clinical and radiographic successes and failures were recorded at 3 , 6 , 12 , 18 and 24 month follow-up . RESULTS Forty-three teeth were available for follow-up . In the FC and MTA groups , 100 % of the available teeth were clinical ly and radiographically successful at all follow-up appointments ; dentine bridge formation could be detected in 29 % of the teeth treated with MTA . In the CH group , 64 % of the teeth presented clinical and radiographic failures detected throughout the follow-up period , and internal resorption was a frequent radiographic finding . CONCLUSIONS Mineral trioxide aggregate was superior to CH and equally as effective as FC as a pulpotomy dressing in primary m and ibular molars . Internal resorption was the most common radiographic finding up to 24 month after pulpotomies performed with CH |
948 | 21,224,258 | Women reported significant improvement in self-efficacy and incontinence-related quality of life . | BACKGROUND many older women with urinary incontinence remain under-treated .
OBJECTIVE to develop and evaluate an evidence -based self-management urinary incontinence risk factor modification tool for older women . | OBJECTIVES To examine the relationship of urinary incontinence ( UI ) and depressive symptoms ( DS ) in older adults . DESIGN A r and omized , controlled trial to determine the effects of clinical practice guideline implementation on provider attitudes and behavior , and patients ' UI , health status , quality of life , and satisfaction with care . Baseline and endpoint data were collected from patients via computer-assisted telephone interviewing . SETTING Forty-one nonacademic primary care practice s ( PCP ) in North Carolina . PARTICIPANTS A total of 668 community-dwelling adults ( age > 60 ) who had visited the one of the selected PCPs . INTERVENTION PCPs in the intervention group were given instruction in the detection and management of UI , educational material s for providers and patients , office system supports , and academic detailing . MEASUREMENTS The dependent measure was assessed using an eight-item screener for DS . UI ( status , frequency , amount ) , health ( physical , mental ) , and demographic ( age , gender , marital status ) and self-report information about bladder control served as predictors . RESULTS Wilcoxon rank sum tests showed that UI status was associated with moderate to severe DS ( 43 % vs 30 % , P = .05 ) . Multivariate analyses showed that UI status , physical and mental health , and gender were significant predictors of DS . Among UI adults ( n = 230 ) , physical and mental health , life satisfaction , and the perception that UI interfered with daily life were significant predictors of DS . CONCLUSIONS This study provides clear evidence that UI is related to DS in older adults PURPOSE Initial weight loss improves urinary incontinence in overweight and obese women . In this study we examined the longer term effects of a weight loss intervention on urinary incontinence . MATERIAL S AND METHODS Overweight and obese women ( mean + /- SD age 53 + /- 10 years ) with 10 or more urinary incontinence episodes weekly were r and omized to an 18-month behavioral weight loss intervention ( 226 ) or control group ( 112 ) . Outcome measures were collected at 12 and 18 months . RESULTS At baseline women had a mean body mass index of 36 + /- 6 kg/m(2 ) and reported a mean of 24 + /- 18 incontinence episodes weekly . Of the patients 86 % completed 18-month measurements . The percent weight loss in the intervention group averaged 8.0 % , 7.5 % and 5.5 % at 6 , 12 and 18 months , respectively , vs approximately 1.5 % in the control group ( all values p < 0.001 ) . Compared with controls at 12 months the intervention group reported a greater percent reduction in weekly stress urinary incontinence episodes ( 65 % vs 47 % , p < 0.001 ) , and a greater proportion achieved at least a 70 % decrease in weekly total and stress urinary incontinence episodes . At 18 months a greater proportion of women in the weight loss intervention group had more than 70 % improvement in urge incontinence episodes but there were no significant differences between the groups for stress or total urinary incontinence . The intervention group also reported greater satisfaction with changes in urinary incontinence than the control group at 6 , 12 and 18 months . CONCLUSIONS Weight loss intervention reduced the frequency of stress incontinence episodes through 12 months and improved patient satisfaction with changes in incontinence through 18 months . Improving weight loss maintenance may provide longer term benefits for urinary incontinence OBJECTIVES To determine whether a multifaceted intervention based on the Agency for Health Care Policy and Research ( AHCPR ) Clinical Practice Guidelines for Urinary Incontinence would increase primary care physician screening for and management of urinary incontinence ( UI ) . DESIGN Group r and omized trial , conducted from 1996 to 1997 . SETTING Internal medicine and family medicine community practice s. PARTICIPANTS Forty-one primary care practice s , including 57 physicians and their staff and 1,145 patients aged 60 and older . INTERVENTION Twenty of the 41 primary care practice s in North Carolina were r and omized to a composite intervention that included a 3-hour continuing medical education accredited course , training in management of UI , patient educational material s , and on-site physician and office support . The remaining 21 practice s served as " usual care " controls . Telephone surveys of UI status and quality of life were obtained from 1,145 patients before the intervention . At 1 year , patients and physicians were contacted by telephone and mail to determine the effect of the educational intervention . MEASUREMENTS Patients completed telephone surveys to assess screening for UI , UI status , treatment interventions , and quality of life . Physicians completed surveys related to UI treatment and practice patterns . RESULTS Baseline and endpoint telephone surveys were completed by 668 of 1,145 ( 58 % ) of patients , who were cared for by 45 physicians ( 10 internists , 35 family medicine ) . Physician screening rates for UI were 22 % for those patients who did not report UI . UI was reported by 39.5 % of patients at baseline , of whom 30 % reported being asked about UI by their primary care physician during the study . Rates of assessment and management of existing UI were low in both the control and intervention groups . Additional historical question ing indicated that 54.2 % reported that they had ever undergone assessment , including history , urinalysis , or testing , or had had management of their UI by any physician . CONCLUSION Attempts at increasing screening and management of UI by primary care physicians using the AHCPR st and ardized guidelines using a multifaceted system of educational and logistical support were not successful . These guidelines may not be the best approach to treating UI in the primary care setting OBJECTIVES To report on the responsiveness testing and clinical utility of the 12-item Geriatric Self-Efficacy Index for Urinary Incontinence ( GSE-UI ) . DESIGN Prospect i ve cohort study . SETTING Six urinary incontinence ( UI ) outpatient clinics in Quebec , Canada . PARTICIPANTS Community-dwelling incontinent adults aged 65 and older . MEASUREMENTS The abridged 12-item GSE-UI , measuring older adults ' level of confidence for preventing urine loss , was administered to all new consecutive incontinent patients 1 week before their initial clinic visit , at baseline , and 3 months posttreatment . At follow-up , a positive rating of improvement in UI was ascertained from patients and their physicians using the Patient 's and Clinician 's Global Impression of Improvement scales , respectively . Responsiveness of the GSE-UI was calculated using Guyatt 's change index . Its clinical utility was determined using receiver operating curves . RESULTS Eighty-nine of 228 eligible patients ( 39.0 % ) participated ( mean age 72.6 + 5.8 , range 65 - 90 ) . At 3-month follow-up , 22.5 % of patients were very much better , and 41.6 % were a little or much better . Guyatt 's change index was 2.6 for patients who changed by a clinical ly meaningful amount and 1.5 for patients having experienced any level of improvement . An improvement of 14 points on the 12-item GSE-UI had a sensitivity of 75.1 % and a specificity of 78.2 % for detecting clinical ly meaningful changes in UI status . Mean GSE-UI scores varied according to improvement status ( P<.001 ) and correlated with changes in quality -of-life scores ( r=0.7 , P<.001 ) and reductions in UI episodes ( r=0.4 , P=.004 ) . CONCLUSION The GSE-UI is responsive and clinical ly useful OBJECTIVES To assess whether urinary incontinence ( UI ) and its severity are associated with poor self-rated health in a national sample of community-living older adults and whether this relationship persists after controlling for confounding attributable to functional status , comorbidity , and demographic factors . DESIGN A cross-sectional analysis using multivariate logistic regression . SETTING Subjects were from the 1990 - 1991 National Survey of Self-Care and Aging ( N = 3485 ) , a r and om sampling in geographic clusters of community-dwelling Medicare beneficiaries 65 years of age or older in the contiguous United States . MEASURES The responses to an interviewer-administered question naire regarding urinary incontinence , Basic Activities of Daily Living ( BADL ) , Instrumental Activities of Daily Living ( IADL ) , Mobility Activities of Daily Living ( MADL ) , age , gender , place of residence , race , education , need for proxy response to the survey , and number of medical conditions . RESULTS Unadjusted analysis showed the presence of urinary incontinence to be associated with poor self-rated health ( OR 2.7 , 2.1 - 3.3 ) . With gender , number of comorbid conditions , race , IADL impairment , and interaction terms of incontinence/race and incontinence/IADL in the final model , UI was associated with poor self-rated health in certain subgroups . White subjects with no IADL impairment and mild-moderate incontinence had an OR of 2.0 ( 95 % CI 1.5 - 2.9 ) and those with severe incontinence had an OR of 4.5 ( 95 % CI 2.4 - 8.4 ) of rating their health as poor , whereas those with no IADL impairment and no incontinence were the referent group . For those with a lot of difficulty performing one or more IADL activity , the association of UI and poor self-rated health was weak . For non-white subjects , there was no association , or a very weak association , of UI and poor self-rated health . CONCLUSION In this national sample , urinary incontinence was independently and positively associated with poor self-rated health after adjustment for age , comorbidity , and frailty for most community-dwelling older adults . This association between UI and poor self-rated health was weaker and statistically insignificant when IADL impairment was present or in non-white subjects . Further research is indicated to better underst and the impact of urinary incontinence in specific cultural setting BACKGROUND AND PURPOSE The effects of a home exercise program for persons with chronic peripheral neuropathies ( CPN ) have not been documented . We compared changes in impairment and health-related quality of life ( HRQL ) between exercise and control groups , investigated the relationship between HRQL and measures of impairment , and contrasted the HRQL of individuals with CPN to that previously described for the general population . SUBJECTS Twenty-eight subjects with CPN , aged 23 to 84 years ( mean = 56.2 , SD = 14.9 ) , completed the study . METHODS Impairment measures included average muscle score ( AMS ) , h and grip force , walking time , and forced vital capacity . The HRQL instrument measured the eight scales of the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) and the component scales . The exercise group ( n = 14 ) completed a 6-week home exercise program . The control group ( n = 14 ) did not participate in a home exercise program . RESULTS There was an increase in the AMS in the exercise group compared with the control group . No other between-group differences were found . The exercise group improved in scores on the role limitation scales of the SF-36 . The AMS and walking time were moderately correlated with the physical function scale of the SF-36 ( r = .55 and -.62 , respectively ) . The SF-36 scores of individuals with CPN were lower than scores previously described for the general population . CONCLUSION AND DISCUSSION The home exercise program appears to be an important component of the treatment of persons with CPN . Compared with the general population , patients with CPN appear to have a lower HRQL , but some areas appear to improve following a home exercise program OBJECTIVE Diabetes is associated with increased urinary incontinence risk . Weight loss improves incontinence , but exercise may worsen this condition . We examined whether an intensive lifestyle intervention or metformin therapy among overweight pre-diabetic women was associated with a lower prevalence of incontinence . RESEARCH DESIGN AND METHODS We analyzed data from the Diabetes Prevention Program , a r and omized controlled trial in 27 U.S. centers . Of the 1,957 women included in this analysis , 660 ( 34 % ) were r and omized to intensive lifestyle therapy , 636 ( 32 % ) to metformin , and 661 ( 34 % ) to placebo with st and ard lifestyle advice . The main outcome measure was incontinence symptoms by frequency and type by a vali date d question naire completed at the end-of-trial visit ( mean 2.9 years ) . RESULTS The prevalence of total ( stress or urge ) weekly incontinence was lower among women in the intensive lifestyle group ( 38.3 % ) than those r and omized to metformin ( 48.1 % ) or placebo ( 45.7 % ) . This difference was most apparent among women with stress incontinence ( 31.3 % for intensive lifestyle group vs. 39.7 % for metformin vs. 36.7 % for placebo , P = 0.006 ) . Changes in weight accounted for most of the protective effect of the intensive lifestyle intervention on stress incontinence . CONCLUSIONS Less-frequent urinary incontinence may be a powerful motivator for women to choose lifestyle modification to prevent diabetes AIMS Few studies have documented the effectiveness of continence promotion programs targeting older incontinent women . We sought to evaluate the impact of an interactive continence workshop on changing participants ' attitudes , knowledge and skills in relation to self-managing or seeking care for incontinence . METHODS A quasi-experimental prospect i ve cohort study with repeated measures was carried out on a population of 90 incontinent women aged 55 - 87 participating in a continence promotion workshop . Inclusion criteria were a weekly average of one or more episodes of involuntary urine loss during the preceding 3 months and having never sought help for this problem . Incontinence-related knowledge , attitudes , skills and intentions for seeking care were assessed immediately prior and subsequent to the workshop . Three- and 6-month telephone follow-ups were conducted to determine rates of healthcare seeking and reasons for not seeking care . RESULTS Improvements in incontinence-related knowledge and attitudes occurred in up to 94 % participants . Forty-three percent of the study participants initiated and were satisfied with self-treatment , and an additional 42 % consulted a health care professional . CONCLUSION Interactive continence workshops promote self-management and consultation seeking among older women with incontinence . Further testing of different strategies for promoting continence awareness needs to occur in larger studies with more sensitive instruments , a control group , and better specification of the goals , process and outcomes of the health promotion activity being tested PURPOSE We evaluated the effect of weight loss on urinary incontinence ( UI ) in overweight and obese women . MATERIAL S AND METHODS A r and omized , controlled clinical trial was conducted among overweight and obese women experiencing at least 4 UI episodes per week . Women were r and omly assigned to a 3-month liquid diet weight reduction program ( 24 in the immediate intervention group ) or a wait-list delayed intervention group ( 24 in the wait-list control group ) . Participants in the wait-list control group began the weight reduction program in month 3 of the study . All women were followed for 6 months after completing the weight reduction program . Wilcoxon tests were used to compare intergroup differences in change in weekly UI episodes and quality of life scores . RESULTS A total of 48 women were r and omized and 40 were assessed 3 months after r and omization . Median ( with 25 % to 75 % interquartile range [ IQR ] ) baseline age was 52 years ( IQR 47 to 59 ) , weight was 97 kg ( IQR 87 to 106 ) and UI episodes were 21 weekly ( IQR 11 to 33 ) . Women in the immediate intervention group had a 16 kg ( IQR 9 to 20 ) weight reduction compared with 0 kg ( IQR -2 to 2 ) in the wait-list control group ( p < 0.0001 ) . The immediate intervention group experienced a 60 % reduction ( IQR 30 % to 89 % ) in weekly UI episodes compared with 15 % ( IQR -9 % to 25 % ) in the wait-list control group ( p < 0.0005 ) and had greater improvement in quality of life scores . Stress ( p = 0.003 ) and urge ( p = 0.03 ) incontinent episodes decreased in the immediate intervention vs wait-list control group . Following the weight reduction program the wait-list control group experienced a similar median reduction in weekly UI episodes ( 71 % ) . Among all 40 women mean weekly UI episodes decreased 54 % ( 95 % CI 40 % to 69 % ) after weight reduction and the improvement was maintained for 6 months . CONCLUSIONS Weight reduction is an effective treatment for overweight and obese women with UI . Weight loss of 5 % to 10 % has an efficacy similar to that of other nonsurgical treatments and should be considered a first line therapy for incontinence BACKGROUND A reliable method of documenting the frequency of incontinent episodes is essential for assessment of treatment outcome in both clinical practice and research studies . Bladder diaries , completed prospect ively by the patient , have been widely used for this purpose . This study investigated the number of consecutive days of bladder diary reports of incontinence frequency necessary to obtain adequate internal consistency ( reliability ) . METHODS Participants were 214 community-dwelling women , aged 40 to 90 years , with a history of stress , urge , or mixed urinary incontinence , persisting at least 3 months with a frequency of two or more episodes of urine leakage per week . Each participant kept a 14-day bladder diary documenting the time and circumstances of each incontinence episode . RESULTS The mean age of participants was 63.5 years ; 16.9 % were African American . Women with predominantly urge incontinence ( n = 138 ) reported a daily frequency of 2.1 incontinent episodes . Although there was a statistically significant difference between Week 1 ( 2.4 episodes per day ) and Week 2 ( 2.0 episodes per day ; p < .0001 ) , five days were necessary to obtain an internal consistency of .90 for Cronbach 's alpha . Women with predominantly stress incontinence ( n = 76 ) had no statistical difference between Week 1 and Week 2 in frequency of incontinence , reporting an average 2.2 accidents per week in Week 1 and 2.1 in Week 2 . However , 7 days of bladder diary were required before adequate internal consistency was reached . CONCLUSION Seven consecutive days of bladder diary provides a stable and reliable measurement of the frequency of incontinence episodes in community-dwelling women OBJECTIVES To determine whether urinary incontinence ( UI ) is an independent predictor of death , nursing home admission , decline in activities of daily living ( ADLs ) , or decline in instrumental activities of daily living ( IADLs ) . DESIGN A population -based prospect i ve cohort study from 1993 to 1995 . SETTING Community-dwelling within the United States . PARTICIPANTS Six thous and five hundred six of the 7,447 subjects aged 70 and older in the Asset and Health Dynamics Among the Oldest Old study who had complete information on continence status and did not require a proxy interview at baseline . MEASUREMENTS The predictor was UI , and the outcomes were death , nursing home admission , ADL decline , and IADL decline . Potential confounders considered were comorbid conditions , baseline function , sensory impairment , cognition , depressive symptoms , body mass index , smoking and alcohol , demographics , and socioeconomic status . RESULTS The prevalence of UI was 14.8 % ( 18.5 % in women ; 8.5 % in men ) . At 2-year follow-up , subjects incontinent at baseline were more likely to have died ( 10.9 % vs 8.7 % ; unadjusted odds ratio (OR)=1.29 , 95 % confidence interval (CI)=1.02 - 1.64 ) , be admitted to a nursing home ( 4.4 % vs 2.6 % , OR=1.77 ; 95 % CI=1.18 - 2.63 ) , and to have declined in ADL function ( 13.6 % vs 8.1 % ; OR=1.78 , 95 % CI=1.36 - 2.33 ) and IADL function ( 21.2 % vs 13.8 % ; OR 1.69 , 95 % CI 1.39 - 2.05 ) . However , after adjusting for confounders , UI was not an independent predictor of death ( adjusted OR (AOR)= 0.90 , 95 % CI=0.67 - 1.21 ) , nursing home admission ( AOR=1.33 , 95 % CI=0.86 - 2.04 ) , or ADL decline ( AOR=1.24 , 95 % CI=0.92 - 1.68 ) . Incontinence remained a predictor of IADL decline ( AOR=1.31 ; 95 % CI=1.05 - 1.63 ) , although adjustment markedly reduced the strength of this association . CONCLUSION Higher levels of baseline illness severity and functional impairment appear to mediate the relationship between UI and adverse outcomes . The results suggest that , although UI appears to be a marker of frailty in community-dwelling elderly , it is not a strong independent risk factor for death , nursing home admission , or functional decline BACKGROUND Although millions of individuals have symptoms suggestive of overactive bladder ( OAB ) , few ever seek or receive medical treatment for their condition . OBJECTIVE The purpose of this study was to describe coping strategies and health care-seeking behavior in a community-based sample of adults with symptoms suggestive of OAB . METHODS A cross-sectional household telephone survey of an age- and sex-stratified sample of adults was conducted . The survey consisted of general health-related questions as well as questions related to OAB symptoms . A total of 4896 adults completed the interview Respondents were considered to have OAB if they reported > or = 1 symptom of urinary urgency , frequency , or urge incontinence . A follow-up question naire was then mailed to a sub sample of the telephone interview respondents . The mailed question naire contained questions related to type and severity of OAB symptoms , coping strategies , medical care/treatment , feelings/beliefs about OAB , and quality of life . Half of the phone respondents with urinary incontinence ( n = 638 ) and a r and om sample of all other phone respondents received the mailed question naire ( n = 873 ) ; 1,034 question naires were returned . RESULTS Of the respondents with OAB , 69.6 % tried > or = 1 nonmedical coping strategy . Respondents with incontinent OAB were significantly more likely than those with continent OAB or those with no OAB ( controls ) to use nonmedical coping strategies ( incontinent OAB , 76.1 % ; continent OAB , 59.0 % ; controls , 31.9 % ; P < 0.001 ) . Fewer than half of the respondents with OAB ( 43.5 % ) had spoken with a provider about OAB in the previous 12 months . Medical consultation was associated with sex , type and severity of OAB , number of nonmedical coping strategies tried , number of OAB information sources consulted , inclination to try new OAB medications , and feelings/beliefs about OAB . In 90 % of patient-provider discussion s about OAB , the patient initiated the topic . CONCLUSIONS Individuals manage symptoms suggestive of OAB primarily by using nonmedical coping strategies rather than consulting health care providers . Results of this study support the need for improved clinical recognition of OAB and increased patient-provider communication about this condition Caffeine reduction is an internationally accepted treatment strategy for patients with urinary symptoms . However , there is little trial evidence in support of a caffeine/urinary symptom effect . A prospect i ve r and omized trial was conducted among 95 consecutive adult patients with urinary symptoms presenting to two nurse continence advisers . Frequency , urgency and leakage outcomes were tested 1 month postenrolment . Trial findings indicate that caffeine intake was reduced ( P<0.0001 ) in the experimental group and that urgency ( P=0.002 ) and frequency ( P=0.037 ) outcomes were significantly improved . Caffeine practice s and habits were surveyed and self-reports of caffeine effects indicate that urinary symptoms figured prominently as a reported effects but less so as a driver of caffeine reduction OBJECTIVE To determine current knowledge , attitudes , and management of urinary incontinence among family physicians in Canada . DESIGN Cross-sectional mailed survey . SETTING Family physicians in Canada . PARTICIPANTS A r and om sample of 1500 members of the College of Family Physicians of Canada . MAIN OUTCOME MEASURES Self-assessed knowledge , self-reported attitudes , and rating of various tests and treatments in the investigation and management of incontinence . RESULTS The overall unadjusted response rate was 43.3 % ( 650/1500 ) . Although most respondents reported that urinary incontinence was common in their practice s , less than half ( 46.0 % , 284/617 ) indicated that they clearly understood incontinence and just 37.9 % ( 232/612 ) had an organized plan for incontinence problems . Only 35.0 % ( 214/612 ) of respondents felt very comfortable dealing with incontinence . Physical examination , urodynamic studies , urinalysis , and testing blood sugar levels were all considered important investigations by more than 90 % of respondents . CONCLUSION There are wide variations in knowledge , attitudes , practice s , and comfort level among family physicians dealing with urinary incontinence |
949 | 21,491,378 | Ten interventions were found to have some benefit with regard to preventing or reducing the severity of mucositis associated with cancer treatment . | BACKGROUND Treatment of cancer is increasingly more effective but is associated with short and long term side effects .
Oral side effects remain a major source of illness despite the use of a variety of agents to prevent them .
One of these side effects is oral mucositis ( mouth ulcers ) .
OBJECTIVES To evaluate the effectiveness of prophylactic agents for oral mucositis in patients with cancer receiving treatment , compared with other potentially active interventions , placebo or no treatment . | Painful oral mucositis is a common complication after bone marrow transplantation ( BMT ) . Glutamine is a nutrient for rapidly dividing cells and the major energy source for intestinal epithelium . This study tested whether an oral glutamine preparation could decrease the severity of oral mucositis in patients undergoing BMT . Glutamine or a placebo ( glycine ) were administered from admission until day + 28 in 193 BMT patients in a r and omized , double-blind , placebo-controlled study at a dose of 1.0 g amino acid/m2/dose swish and swallow four times a day . In autologous BMT patients ( n = 87 ) glutamine was associated with significantly less mouth pain by self report and by opiate use ( 5.0 ± 6.2 days of morphine for glutamine vs 10.3 ± 9.8 days for placebo ; P = 0.005 ) . Matched sibling BMT patients had no effect by self report and an increased duration of opiate use ( 23.2 ± 5.7 days for glutamine vs 16.3 ± 8.3 days for placebo ) ( P = 0.002 ) . However , day 28 survival of allogeneic patients was improved by glutamine . No significant differences in TPN use , rate of relapse or progression of malignancy , parenteral antibiotic use , acute or chronic GVHD , or days of hospitalization were observed in either autologous or allogeneic recipients . No toxicity of glutamine was observed . We conclude that oral glutamine can decrease the severity and duration of oropharyngeal mucositis in autologous BMT patients but not in allogeneic BMT patients , possibly due to interaction with methotrexate Based on the assumption that an accelerated proliferation process prevails in tumour cell residues after surgery , the possibility that treatment acceleration would offer a therapeutic advantage in postoperative radiotherapy of locally advanced head and neck cancer was investigated . The value of Tpot in predicting the treatment outcome and in selecting patients for accelerated fractionation was tested . Seventy patients with ( T2/N1–N2 ) or ( T3 - 4/any N ) squamous cell carcinoma of the oral cavity , larynx and hypopharynx who underwent radical surgery , were r and omized to either ( a ) accelerated hyperfractionation : 46.2 Gy per 12 days , 1.4 Gy per fraction , three fractions per day with 6 h interfraction interval , treating 6 days per week or ( b ) Conventional fractionation : 60 Gy per 6 weeks , 2 Gy per fraction , treating 5 days per week . The 3-year locoregional control rate was significantly better in the accelerated hyperfractionation ( 88±4 % ) than in the CF ( 57±9 % ) group , P=0.01 ( and this was confirmed by multivariate analysis ) , but the difference in survival ( 60±10 % vs 46±9 % ) was not significant ( P=0.29 ) . The favourable influence of a short treatment time was further substantiated by demonstrating the importance of the gap between surgery and radiotherapy and the overall treatment time between surgery and end of radiotherapy . Early mucositis progressed more rapidly and was more severe in the accelerated hyperfractionation group ; reflecting a faster rate of dose accumulation . Xerostomia was experienced by all patients with a tendency to be more severe after accelerated hyperfractionation . Fibrosis and oedema also tended to be more frequent after accelerated hyperfractionation and probably represent consequential reactions . Tpot showed a correlation with disease-free survival in a univariate analysis but did not prove to be an independent factor . Moreover , the use of the minimum and corrected P-values did not identify a significant cut-off . Compared to conventional fractionation , accelerated hyperfractionation did not seem to offer a survival advantage in fast tumours though a better local control rate was noted . This limits the use of Tpot as a guide for selecting patients for accelerated hyperfractionation . For slowly growing tumours , tumour control and survival probabilities were not significantly different in the conventional fractionation and accelerated hyperfractionation groups . A rapid tumour growth was associated with a higher risk of distant metastases ( P=0.01 ) . In conclusion , tumour cell re population seems to be an important determinant of postoperative radiotherapy of locally advanced head and neck cancer despite lack of a definite association between Tpot and treatment outcome . In fast growing tumours accelerated hyperfractionation provided an improved local control but without a survival advantage . To gain a full benefit from treatment acceleration , the surgery-radiotherapy gap and the overall treatment time should not exceed 6 and 10 weeks respectively The aim of this study was to see if antibiotic pastilles could reduce radiation mucositis , pain , dysphagia and weight loss in patients undergoing radical radiotherapy for head and neck cancer . A total of 275 patients with T1-T4 tumours entered the study ; 136 were allocated to suck four times daily a pastille containing amphotericin , polymyxin and tobramycin . The remaining 139 patients received an identical placebo . In all , 54 patients were unevaluable ( 24 active , 30 placebo ) . Bacteriological monitoring was carried out before and twice weekly during treatment . Both arms of the study were well balanced for T and N stage , age , sex and radiation dose ( 60 Gy ) . There was a slight imbalance in the site of disease which had no substantive effect on the results . The primary study end point was the percentage of patients who developed intermediate or thick pseudomembranes . No statistically significant difference was found in this end point , with 36 % of patients in the active arm developing this type of membrane compared with 48 % in the placebo arm ( P = 0.118 ) . The estimated odds ratio ( placebo/active ) of developing an intermediate or thick pseudomembrane was 1.59 ( 95 % CI 0.89 - 2.82 ) . However a more sensitive test comparing the worst recorded mucositis grade between the two arms was statistically significant ( P = 0.009 ) . This indicated that the active pastilles had a beneficial effect , but the magnitude was probably smaller than the trial was design ed to detect . There was a reduction in mucositis distribution ( P = 0.002 ) , mucositis area ( P = 0.028 ) , dysphagia ( P = 0.006 ) and weight loss ( P = 0.009 ) in the active arm . There was a clear tendency for patients with positive cultures for aerobic Gram-negative bacteria ( AGNB ) ( P = 0.003 ) and yeasts ( P = 0.026 ) during treatment to have more severe mucositis . The active pastilles reduced the percentage of patients with yeast cultures ( P = 0.003 ) but had less effect on AGNB . The benefit derived from the pastilles should material ly increase patient tolerance to radical radiotherapy for head and neck cancer Background . Oral mucositis is a common complication of bone marrow transplantation ( BMT ) conditioning therapy . Sequelae consist of increased risk for infection , moderate to severe pain , compromised oral function , and bleeding . This study investigated helium‐neon laser treatment for prevention of conditioning‐induced oral mucositis in BMT patients . Patterns and severity of mucositis for specific conditioning drug regimens also were analyzed PURPOSE In a single-institution , double-blind , prospect i ve , r and omized trial , we determined whether oral aloe vera gel can reduce radiation-induced mucositis in head- and -neck cancer patients . METHODS AND MATERIAL S We r and omized 58 head- and -neck cancer patients between oral aloe vera and placebo . To be included in this Phase II protocol , patients had to be treated with radiotherapy with curative intent at Stanford University between February 1999 and March 2002 . We examined patients biweekly for mucositis at 15 head- and -neck subsites and administered quality -of-life question naires . RESULTS Patients in the aloe and placebo groups were statistically identical in baseline characteristics . By the end of treatment , the two groups were also statistically identical in maximal grade of toxicity , duration of Grade 2 or worse mucositis , quality -of-life scores , percentage of weight loss , use of pain medications , hydration requirement , oral infections , and prolonged radiation breaks . CONCLUSION In our r and omized study , oral aloe vera was not a beneficial adjunct to head- and -neck radiotherapy . The mean quality -of-life scores were greater in the aloe vera group , but the differences were not statistically significant . Oral aloe vera did not improve tolerance to head- and -neck radiotherapy , decrease mucositis , reduce soreness , or otherwise improve patient well-being BACKGROUND Oral mucositis is a complication of intensive chemotherapy and radiotherapy with no effective treatment . We tested the ability of palifermin ( recombinant human keratinocyte growth factor ) to decrease oral mucosal injury induced by cytotoxic therapy . METHODS This double-blind study compared the effect of palifermin with that of a placebo on the development of oral mucositis in 212 patients with hematologic cancers ; 106 patients received palifermin ( 60 microg per kilogram of body weight per day ) and 106 received a placebo intravenously for three consecutive days immediately before the initiation of conditioning therapy ( fractionated total-body irradiation plus high-dose chemotherapy ) and after autologous hematopoietic stem-cell transplantation . Oral mucositis was evaluated daily for 28 days after transplantation . RESULTS The incidence of oral mucositis of World Health Organization ( WHO ) grade 3 or 4 was 63 percent in the palifermin group and 98 percent in the placebo group ( P<0.001 ) . Among patients with this degree of mucositis , the median duration of mucositis was 6 days ( range , 1 to 22 ) in the palifermin group and 9 days ( range , 1 to 27 ) in the placebo group . Among all patients , regardless of the occurrence of mucositis , the median duration of oral mucositis of WHO grade 3 or 4 was 3 days ( range , 0 to 22 ) in the palifermin group and 9 days ( range , 0 to 27 ) in the placebo group ( P<0.001 ) . As compared with placebo , palifermin was associated with significant reductions in the incidence of grade 4 oral mucositis ( 20 percent vs. 62 percent , P<0.001 ) , patient-reported soreness of the mouth and throat ( area-under-the-curve score , 29.0 [ range , 0 to 98 ] vs. 46.8 [ range , 0 to 110 ] ; P<0.001 ) , the use of opioid analgesics ( median , 212 mg of morphine equivalents [ range , 0 to 9418 ] vs. 535 mg of morphine equivalents [ range , 0 to 9418 ] , P<0.001 ) , and the incidence of use of total parenteral nutrition ( 31 percent vs. 55 percent , P<0.001 ) . Adverse events , mainly rash , pruritus , erythema , mouth and tongue disorders , and taste alteration , were mild to moderate in severity and were transient . CONCLUSIONS Palifermin reduced the duration and severity of oral mucositis after intensive chemotherapy and radiotherapy for hematologic cancers PURPOSE Experimental and clinical data suggest a reduction of radiation-induced acute toxicity by amifostine . We investigated this issue in a r and omized trial comparing radiochemotherapy ( RCT ) versus radiochemotherapy and amifostine ( RCT + A ) in patients with head and neck cancer . PATIENTS AND METHODS Forty-seven patients with pharyngeal or laryngeal cancer ( T1 - 2 N1 - 2 G3 , T3 - 4 N0 - 2 G1 - 3 ) were r and omized to receive RCT alone ( 21 patients ) or RCT + A ( 21 patients ) . Patients were irradiated up to 60 Gy ( R0 ) or 70 Gy ( R1/2 ) . Chemotherapy consisted of 70 mg/m2 carboplatin and was administered over 5 days in the 1st and 5th week of the radiotherapy course . 250 mg amifostine were applied daily just before each radiotherapy session . Acute toxicity was evaluated according to the Common Toxicity Criteria ( CTC ) . As for xerostomia no patients with laryngeal cancer were assessed because in these cases only small volumes of the salivary gl and s were within the treatment volume . To evaluate the overall toxicity a summarized CTC score of all observed side effects was calculated . RESULTS Forty-two patients were evaluable . Clinical characteristics ( age , sex , Karnofsky index , tumor-staging ) were well balanced in both treatment groups ( Tables 2 and 3 ) . Amifostine provided reduction in xerostomia and mucositis ( Figures 5 and 6 ) but had no obvious influence on Karnofsky index , body weight , cutaneous side effects and alopecia ( Figures 1 to 4 ) . CONCLUSIONS According to our preliminary results amifostine has a radioprotective effect on salivary gl and s. Mucositis can be reduced during radiochemotherapy . At this point of patient accrual the difference between both groups are statistically not significant . To improve the radioprotective effects of amifostine in clinical practice the application of a higher dose ( > 250 mg ) seems to be necessary Oral mucositis is frequent but serious adverse event associated with radiotherapy or radiochemotherapy in head and neck cancer severely impairs health‐related quality of life , leading to poor prognosis due to discontinuation of the therapy . Although a number of compounds have been tested for prophylaxis of oral mucositis , few of them are satisfactory . We investigated the effect of polaprezinc ( zinc L‐carnosine ) , a gastric mucosal protective drug , on radiochemotherapy‐induced oral mucositis , pain , xerostomia and taste disturbance in patients with head and neck cancer . Patients were r and omly assigned to receive polaprezinc ( n = 16 ) or azulene oral rinse as the control ( n = 15 ) . The incidence rates of mucositis , pain , xerostomia and taste disturbance were all markedly lower in polaprezinc group than in control . Moreover , the use of analgesics was significantly ( p = 0.003 ) less frequent and the amount of food intake was significantly ( p = 0.002 ) higher in polaprezinc group than in control . On the other h and , tumor response rate in patients with neoadjuvant radiochemotherapy was not significantly affected by polaprezinc , in which the response rate ( complete plus partial response ) was 88 % for polaprezinc and 92 % for control ( p = 1.000 ) . Therefore , it is highly assumable that polaprezinc is potentially useful for prevention of oral mucositis and improvement of quality of life without reducing the tumor response This study aim ed to investigate the effect of oral pilocarpine ( OP ) in reducing the incidence of chemotherapy-induced oral mucositis . 32 adult cancer patients completed a total of 82 courses of chemotherapy in which either OP or placebo was given prophylactically in a double-blind cross-over design to prevent mucositis . Mucositis was documented in 20 out of 41 courses in which patients were given placebo , whereas mucositis was documented in only six out of 41 courses when patients were given OP ( P<0.005 ) . OP treatment was found to significantly reduce the mucositis score when assessed by the method of Donnelly and colleagues ( Donnelly JP , Muus P , Schattenberg A , De Witte T , Horrevorts A , De Pauw BE . Bone Marrow Transplant 1992 , 9 , 409 - 413 ) . Using this score , all patients scored a total of 52 when they were given the placebo versus eleven when they were treated with OP ( P<0.001 ) . A similar reduction in mucositis score was noticed using the World Health Organization ( WHO ) mucositis score ; the total patient score was 25 for the placebo-treated group versus 6 for the OP group ( P<0.001 ) . We therefore conclude that oral pilocarpine is highly effective in the prevention of oral mucositis when given prophylactically to adult patients receiving a variety of cancer chemotherapy regimens Temozolomide ( Temodal ) is an oral imidazotetrazine . Increased temozolomide exposure and subsequent depletion of O6-alkylguanine alkyltransferase may improve the activity of temozolomide . The rationale for investigating temozolomide plus Caelyx is based on their antitumor activity , their formulation and no significant overlapping toxicities . We conducted a study of a prolonged schedule of temozolomide ( orally on days 1–7 and 15–21 ) plus Caelyx ( day 1 ) every 28 days . Twenty-one patients ( melanoma n=10 , sarcoma n=7 and other n=4 ) were assigned to four dose levels ( DL ; temozolomide+Caelyx , mg/m2 ) : DL1 : 100 + 30 ( n=3 patients ) , DL2 : 100 + 40 ( n=6 patients ) , DL3 : 125 + 40 ( n=6 patients ) and DL4 : 150 + 40 ( n=6 patients ) . Dose-limiting toxicities were noted after 2 or more cycles in one patient at DL3 ( stomatitis ) and one patient at DL4 ( grade 4 ANC ≥7 days ) . Treatment delays and /or dose reductions ( due to hematological toxicity ) were necessary in five of six patients receiving DL4 compared with one of six patients at DL3 , and one patient at DL1 and 2 . Thus , the recommended dose was temozolomide 125 mg/m2 ( daily for 7 days every other week ) plus Caelyx 40 mg/m2 ( day 1 every 4 weeks ) . Other toxicities were mild . Antitumor activity was observed in eight patients , including one complete response ( melanoma ) , three partial responses ( one melanoma , two sarcomas ) and four patients with stable disease ( three melanomas , one Ewing ) , with a duration lasting from 14 to 135+weeks . Two melanoma patients showed tumor stabilization in non-irradiated cerebral lesions . This schedule of temozolomide allowed higher dose intensity ( 1750 mg/m2 in 4 weeks ) compared to the st and ard 5-day regimen ( 1000 mg/m2 in the same amount of time ) PURPOSE To assess the impact on survival of increasing dose-intensity ( DI ) of cyclophosphamide , doxorubicin , and etoposide ( CDE ) in small-cell lung cancer ( SCLC ) . PATIENTS AND METHODS Previously untreated SCLC patients were r and omized to st and ard CDE ( cyclophosphamide 1,000 mg/m(2 ) and doxorubicin 45 mg/m(2 ) on day 1 , and etoposide 100 mg/m(2 ) on days 1 to 3 every 3 weeks , for five cycles ) or intensified CDE ( cyclophosphamide 1,250 mg/m(2 ) and doxorubicin 55 mg/m(2 ) on day 1 , and etoposide 125 mg/m(2 ) on days 1 to 3 with granulocyte colony-stimulating factor [ G-CSF ] 5 micro g/kg/d on days 4 to 13 every 2 weeks , for four cycles ) . Projected cumulative dose was almost identical on the two arms , whereas projected DI was nearly 90 % higher on the intensified arm . Two hundred forty-four patients were enrolled . The first 163 patients were also r and omized ( 2 x 2 factorial design ) to prophylactic antibiotics or placebo to assess their impact on preventing febrile leukopenia ( FL ) . This report focuses on chemotherapy DI results . RESULTS With a median follow-up of 54 months , 216 deaths have occurred . Actually delivered DI on the intensified arm was 70 % higher than on the st and ard arm . Intensified CDE was associated with more grade 4 leukopenia ( 79 % v 50 % ) , grade 4 thrombocytopenia ( 44 % v 11 % ) , anorexia , nausea , and mucositis . FL and number of toxic deaths were similar on the two arms . The objective response rate was 79 % for the st and ard arm and 84 % for the intensified arm ( P = .315 ) . Median survival was 54 weeks and 52 weeks , and the 2-year survival rates were 15 % and 18 % , respectively ( P = .885 ) . CONCLUSION A 70 % increase of CDE actual DI does not translate into an improved outcome in SCLC patients The aim of the study was to test whether the addition of three cycles of chemotherapy during st and ard radiation therapy would improve disease-free survival in patients with stages III and IV oropharynx carcinoma . A total of 226 patients have been entered in a phase III multicentric r and omized trial comparing radiotherapy alone ( arm A ) to radiotherapy with concomitant chemotherapy ( arm B ) . Radiotherapy was identical in the two arms , delivering , with conventional fractionation , 70 Gy in 35 fractions . In arm B patients received simultaneously 3 cycles of a four-day regimen containing carboplatin ( 70 mg/m2/d ) and 5 fluorouracil ( 600 mg/m2/d ) continuous infusion . The two arms were equally balanced regarding to age , gender , stage , performance status , histology , and primary tumor site . Radiotherapy compliance was similar in the two arms regarding to total dose , treatment duration and treatment interruption . Grade 3 and 4 mucositis rate was significantly higher in arm B ( 67 % versus 36 % ) . Skin toxicity was not different . Haematologic toxicity was higher in arm B on neutrophil count and hemoglobin level . Three-year overall actuarial survival and disease-free survival rates were respectively 51 % versus 31 % and 42 % versus 20 % for patients treated with combined modality versus radiation alone ( p = 0.022 and 0.043 ) . Local and regional control rate has been improved in arm B ( 66 % versus 42 % ) . The statistically significant improvement in overall survival obtained support the use of concomitant chemotherapy as an adjunct to radiotherapy in the management of carcinoma of the oropharynx PURPOSE Experimental and clinical data suggest a reduction of radiation-induced acute toxicity by amifostine ( A ) . We investigated this issue in a r and omized trial comparing radiochemotherapy ( RT + CT ) versus radiochemotherapy plus amifostine ( RC + CT + A ) in patients with head and neck cancer . PATIENTS AND METHODS 56 patients with oro-/hypopharynx or larynx cancer ( T1 - 2 N1 - 2 G3 , T3 - 4 N0 - 2 G1 - 3 ) were r and omized to receive RC + CT alone or RC + CT + A. Patients were irradiated up to 60 Gy ( R0 ) or 70 Gy ( R1/2 ) and received chemotherapy ( 70 mg/m(2 ) carboplatin , day 1 - 5 in week 1 and 5 of radiotherapy ) . 250 mg amifostine were applied daily before each radiotherapy session . Acute toxicity was evaluated according to the Common Toxicity Criteria ( CTC ) . As for acute xerostomia , patients with laryngeal cancer were excluded from evaluation . RESULTS 50 patients were evaluable ( 25 patients in the RC + CT , 25 patients in the RC + CT + A group ) . Clinical characteristics were well balanced in both treatment groups . Amifostine provided reduction in acute xerostomia and mucositis but had no obvious influence on Karnofsky performance status , body weight , cutaneous side effects , and alopecia . The differences between both groups were statistically significant for acute xerostomia and nonsignificant , but with a trend for mucositis . CONCLUSIONS According to our results , there is a radioprotective effect on salivary gl and s and a potential effect on oral mucosa by amifostine in postoperative radiotherapy combined with carboplatin . To improve the radio- and chemoprotective effects of amifostine in clinical practice , the application of a higher dose ( > 250 mg ) seems to be necessary We evaluated the efficacy of topically applied human recombinant epidermal growth factor ( rhEGF ) for the treatment of oral mucositis induced by radiotherapy ( RT ) , with or without chemotherapy , in patients with head and neck cancer BACKGROUND A considerable amount of experimental and clinical data prove the cytoprotective effect of amifostine on normal tissue exposed to different types of antineoplastic treatments . The present study examines its influence on the short-term toxicity of either radiotherapy alone or combined radio-chemotherapy in patients with advanced head and neck cancer . PATIENTS AND METHODS Twenty-three patients with advanced head and neck cancer , mainly Stage III and IV , were treated with preoperative radiation ( n = 1 ) , pre- as well as postoperative radiotherapy ( n = 5 ) , postoperative radiation ( n = 9 ) or combined postoperative radio-chemotherapy ( n = 6 ) . Before each radiation application a total dose of 500 mg amifostine was administered intravenously over 15 minutes . The documentation of this unselected patient group was compared retrospectively to a historical control group comprising 17 patients . RESULTS In 15 patients ( 65 % ) of the amifostine group , therapy induced side effects such as mucositis and dermatitis of WHO Grade < or = 2 were detected , requiring interruptions of the radiotherapy ( mean : 6.5 , maximum 17 days ) . No mucosa or dermatologic toxicity of WHO Grade 3 or 4 was observed in this group . Significantly more acute toxicity was detected in the historical control group . Stomatitis or epitheliolysis of WHO Grade 3 occurred in 7 patients ( 41 % ) . The side effects induced by the antineoplastic therapy caused an interruption of treatment in 15 patients ( 88 % ) ( mean : 16 , maximum 40 days ; p = 0.0016 ) . CONCLUSION The application of amifostine before each radiation treatment seems to result in a distinct reduction of short-term toxicity of radiotherapy or combined radio-chemotherapy in patients with head and neck cancer , allowing for a better adherence to the planned radiation time schedule BACKGROUND Unresectable carcinomas of the oropharynx and hypopharynx still have a poor long-term prognosis . Following a previous phase II study , this phase III multicenter trial was conducted between November 1997 and March 2002 . METHODS Nontreated , strictly unresectable cases were eligible . Twice-daily radiation : two fractions of 1.2 Gy/day , 5 days per week , with no split ( D1 - ->D46 ) . Total tumor doses : 80.4 Gy/46 day ( oropharynx ) , 75.6 Gy/44 day ( hypopharynx ) . Chemotherapy ( arm B ) : Cisplatin 100 mg/m2 ( D1 , D22 , D43 ) ; 5FU , continuous infusion ( D1 - ->D5 ) , 750 mg/m2/day cycle 1 ; 430 mg/m2/day cycles 2 and 3 . RESULTS A total of 163 evaluable patients . Grade 3 - 4 acute mucositis 82.6 % arm B/69.5 % arm A ( NS ) ; Grade 3 - 4 neutropenia 33.3 % arm B/2.4 % arm A ( p < 0.05 ) . Enteral nutrition through gastrostomy tube was more frequent in arm B before treatment and at 6 months ( p < 0.01 ) . At 24 months , overall survival ( OS ) , disease-free survival ( DFS ) , and specific survival ( SS ) were significantly better in arm B. OS : 37.8 % arm B vs. 20.1 % arm A ( p = 0.038 ) ; DFS : 48.2 % vs. 25.2 % ( p = 0.002 ) ; SS : 44.5 % vs. 30.2 % ( p = 0.021 ) . No significant difference between the two arms in the amount of side effects at 1 and 2 years . CONCLUSION For these unresectable cases , chemoradiation provides better outcome than radiation alone , even with an " aggressive " dose-intensity radiotherapy schedule Summary : Severe mucositis is a common cause of morbidity in hematopoietic stem cell transplant ( HSCT ) recipients . Glutamine has been shown to reduce mucositis in children receiving chemotherapy . Patients were r and omized in a double-blind manner to receive glutamine or glycine at a dose of 2 g/m2/dose ( maximum dose 4 g ) twice daily until 28 days post transplant or discharge if sooner . Mucositis was grade d by use of a modified Walsh scale . A total of 120 children were evaluable : 57 children received glutamine and 63 received glycine . The mean mucositis score was 3.0±0.3 vs 3.9±0.4 ( P=0.07 ) in the glutamine and glycine groups , respectively . The glutamine group demonstrated a reduction in mean number of days of intravenous narcotics use ( 12.1±1.5 vs 19.3±2.8 in the glycine group , P=0.03 ) and total parenteral nutrition ( 17.3±1.7 vs 27.3±3.6 in glycine group , P=0.01 ) . There was no statistically significant difference in toxicity between the two groups . Glutamine appears to be safe and beneficial in reducing the severity of mucositis . Strong consideration should be given to include oral glutamine supplementation as a routine part of supportive care of SCT patients Interleukin-11 ( IL-11 ) decreases cytokine release and increases survival in murine BMT models . In these systems , it reduces gut permeability , partially polarizes T cells to a Th2 phenotype , down-regulates IL-12 , prevents mucositis , and accelerates recovery of oral and bowel mucosa . We conducted a r and omized double-blind pilot study of rhIL-11 administered with cyclosporine/MTX prophylaxis after cytoxan/TBI conditioning and allogeneic stem cell transplantation for hematologic malignancies . Patients received rhIL-11 , 50 μg/kg subcutaneously daily or placebo in a 3:1 ratio . Treatment was administered prior to the start of conditioning and continued up to 21 days . The study was design ed to assess safety with stopping rules for cardiac arrhythmias and mortality . Although projected to accrue 20 patients , only 13 patients ( 10 IL-11 , three placebo ) were enrolled because the early stopping rule for mortality was triggered . Of 10 evaluable patients who received IL-11 , four died by day 40 and one died on day 85 . Deaths were attributable to transplant-related toxicity . One of three placebo recipients died of suicide , the other two are alive . Patients receiving IL-11 had severe fluid retention and early mortality , making it impossible to determine whether IL-11 given in this schedule can reduce the rate of GVHD . Grade B – D acute GVHD occurred in two of eight evaluable patients on IL-11 and one of three patients on placebo . The primary adverse events of the study were severe fluid retention resistant to diuresis ( average weight gain 9 ± 4 % ) and multiorgan failure in five of 10 evaluable patients . The use of IL-11 as GVHD prophylaxis in allogeneic transplantation can not be recommended as administered in this trial . Bone Marrow Transplantation ( 2002 ) 29 , 373–377 . PURPOSE With the aim to increase the dose intensity of radiation therapy ( RT ) , and subsequently the locoregional control rate , a very accelerated RT regimen was compared with conventional RT in a series of patients with head and neck squamous cell carcinoma ( HNSCC ) . PATIENTS AND METHODS Between 1994 and 1998 , 268 patients with T3 or T4 , N0 to N3 HNSCC ( staged by 1997 International Union Against Cancer criteria ) that was not eligible for surgery were r and omly assigned to receive either conventional RT , delivering 70 Gy in 7 weeks to the primary tumor and 35 fractions of 2 Gy over 49 days , or to receive very accelerated RT , delivering 62 to 64 Gy in 31 to 32 fractions of 2 Gy over 22 to 23 days ( 2 Gy/fraction bid ) . RESULTS The most common tumor site was the oropharynx and most of the patients ( 70 % ) had T4 and N1 to N3 tumors in 72 % of patients . The main patient and tumor characteristics were well-balanced between the two arms . The median total doses were 63 Gy ( accelerated ) and 70 Gy ( conventional ) , with a median overall time of 22 days and 48 days , respectively . Acute mucositis was markedly increased in the accelerated-RT arm ( P < .001 ) . The locoregional control rate was improved by 24 % at 6 years with accelerated RT . In contrast , disease-free survival and overall survival were not significantly different between the two arms . There was no difference in late effects between the two arms . CONCLUSION The very accelerated RT regimen was feasible and provided a major benefit in locoregional control but had a modest effect on survival Introduction Mucositis is a major complication in myeloablative therapy , which often necessitates advanced pharmacological pain treatment , including i.v . opioids . Attempts to prevent oral mucositis have included oral cryotherapy , which has been shown to reduce mucositis , but there is a lack of knowledge concerning the effect of oral cryotherapy on opioid use by reducing the mucositis for patients treated with myeloablative therapy before bone marrow transplantation ( BMT ) . Aim The aim of the present study was to evaluate if oral cryotherapy could delay or alleviate the development of mucositis and thereby reduce the number of days with i.v . opioids among patients who receive myeloablative therapy before BMT . Material s and methods Eighty patients 18 years and older , scheduled for BMT , were included consecutively and r and omised to oral cryotherapy or st and ard oral care . A stratified r and omisation was used with regard to type of transplantation . Intensity of pain , severity of mucositis and use of opioids were recorded using pain visual analogue scale ( VAS ) scores , mucositis index scores and medical and nursing charts . Results This study showed that patients receiving oral cryotherapy had less pronounced mucositis and significantly fewer days with i.v . opioids than the control group . In the autologous setting , cryotherapy patients also needed significantly lower total dose of opioids . Conclusion Oral cryotherapy is an effective and well-tolerated therapy to alleviate mucositis and consequently reduce the number of days with i.v . opioids among patients treated with myeloablative therapy before BMT BACKGROUND AND PURPOSE Early reactions after radiotherapy for head and neck cancer may become the limiting factor in current attempts to intensify loco-regional therapy through altered fractionation or combination of radiotherapy with chemotherapy . The aim of the present study was to quantify the dependence of early reactions on the dose-fractionation used in radiotherapy and on patients ' age and radiation field size . PATIENTS AND METHODS The data analyzed are from the r and omized controlled trial of CHART ( continuous hyperfractionated accelerated radiotherapy ) vs. conventional radiotherapy in head and neck cancer . The trial accrued 918 patients from March 1990 to April 1995 . Several early morbidity items were evaluated weekly for the first 8 weeks after the start of treatment . Weekly evaluation was continued in patients with early reactions extending beyond 8 weeks . Linear regression was used to analyze the time with reactions in individual patients . Polychotomous ordinal response regression was used to analyze the peak grade of early reactions in individual patients . RESULTS The main findings of this analysis were as follows . ( 1 ) The incidence and peak prevalence of confluent mucositis was higher after CHART than after conventional radiotherapy . Therefore , the average time spent with confluent mucositis per patient treated was significantly longer after CHART than after conventional fractionation . ( 2 ) In patients who actually developed confluent mucositis , the average duration of this grade of reaction was not significantly different after CHART compared with conventional radiotherapy . ( 3 ) Confluent mucositis developed earlier after the start of treatment ( 2.9 vs. 4.9 weeks ) but also started to improve sooner ( 5.4 vs. 7.5 weeks after the start of treatment ) after CHART than after conventional radiotherapy . ( 4 ) The dose recovered per 1-day protraction of overall treatment time , D(prolif ) , was estimated at 0.80 Gy with 95 % confidence limits 0.7 and 1.1 Gy/day for human mucosa . ( 5 ) For human skin erythema , the estimate of D(prolif ) was 0.12 Gy/day with 95 % confidence limits -0.12 and 0.22 Gy/day . ( 6 ) Highly significant relationships were found between the grade of morphological mucositis on one h and and dysphagia , pain on swallowing and prescribed analgesics on the other . Patients with confluent mucositis had fewer functional problems if this was confined to the larynx as compared with other subsites in the head and neck . ( 7 ) Although the incidence of confluent mucositis was higher in the oral cavity and oropharynx than in the hypopharynx and larynx , the radiobiological properties of mucosal reactions did not show significant variation among the various subsites within the head and neck region . ( 8) For a given dose and overall treatment time , a highly significant increase in incidence and severity of both mucositis and erythema was seen with increasing field size . Thus , a significant dose-volume or dose-area effect exists for both of these tissues . ( 9 ) Patients ' age had no significant influence on the incidence and severity of mucositis or erythema . CONCLUSIONS This study provides quantitative estimates of the dose-time and dose-volume relationships for human skin and normal mucosa in the head and neck region based on an analysis of data from 918 patients entered into a r and omized-controlled trial of altered dose fractionation in radiotherapy PURPOSE Oral mucositis ( OM ) causes significant morbidity during the course of radiotherapy ( RT ) treatment of head- and -neck cancer . It is hypothesized that infection plays a role in the development of OM . We tested the efficacy of iseganan HCl ( iseganan ) , a synthetic peptide with broad-spectrum antimicrobial activity , for preventing RT-associated OM . METHODS A multinational , r and omized , double-blind , controlled trial was performed on patients receiving primary RT , primary chemoradiotherapy or postoperative RT . Patients were r and omized to receive iseganan oral solution plus st and ard-of-care oral hygiene ( SOC ) , placebo plus SOC , or SOC alone throughout the RT administration period . The severity of OM was assessed by NCI-CTC scoring and clinical symptoms by patient question naire . RESULTS A total of 545 patients were r and omized to the study . Nine percent of the patients in both the iseganan and placebo groups did not develop ulcerative OM ( Grade s 2 , 3 , 4 ) ( p = 0.998 ) whereas only 2 % of the patients receiving SOC alone remained free of oral ulceration ( p = 0.049 ) . The maximum severity of mouth pain and difficulty swallowing did not differ in patients treated with iseganan or placebo . However , patients in both intervention groups reported less mouth pain and difficulty swallowing than did patients receiving SOC alone . Nausea was the only adverse event that occurred with > /=5 % increased frequency in the iseganan group than in either the placebo or SOC groups ( 51 % vs. 42 % vs. 46 % ) . Adverse events leading to study drug discontinuation and death did not differ significantly between groups . CONCLUSION Iseganan oral solution was safe but did not reduce the risk for developing ulcerative OM relative to placebo . Intensified oral hygiene or the administration of the vehicle used to deliver study drug in this trial appears to have reduced the risk and severity of OM . Our results suggest that antimicrobial intervention may not meaningfully affect the pathogenesis of radiation-induced OM Multiple center r and omized controlled double blind clinical trait was conducted to evaluate the anti-radiotherapy effect by SOD ( produced by Hunan Biochemical Work ) in 159 patients . Injection of 4000U SOD immediately after receiving radiotherapy significantly reduced the occurrence rate of skin , oral mucosal , pelvic visceral and systematic adverse reaction , only the reduction of leukopenia did not reach the statistical significant level . No adverse effect of SOD injection was observed . The results suggest that SOD is a safe and effective agent to attenuate the radiotherapy reactions Oral flora is thought to contribute to irradiation mucositis in patients with head and neck cancer . Neglect of oral hygienic care may also contribute to mucositis . The purpose of this prospect i ve , r and omized , placebo-controlled , double-blind study was to evaluate the effect of chlorhexidine 0.1 % mouthrinses on oral flora and irradiation mucositis . This study included 30 patients with head and neck cancer who had comparable irradiation portals . One group ( N = 15 ) rinsed four times daily with chlorhexidine 0.1 % , the other group ( N = 15 ) with a placebo . The oral flora was cultured ( oral washing technique ) twice before and three times per week during the period of radiotherapy . On the same days , the severity of mucositis was determined . The colonization index of viridans streptococci was significantly reduced only after 5 weeks of chlorhexidine 0.1 % treatment . The colonization patterns of C and ida species , Streptococcus faecalis , staphylococci , and Enterobacteriaceae , Pseudomonadaceae , and Acinetobacter species were not influenced by 5 weeks of use of chlorhexidine rinses when compared with the placebo . No differences were seen between the two study groups in the development and severity of mucositis . In conclusion , suppression of oral flora and a lowering of the severity of mucositis by means of disinfecting mouthrinses were not successful The toxicities of oral Ftorafur ( 1 g/m2/day 1 - 21 ) and intravenous 5-fluorouracil ( 5-FU ) ( 500 mg/m2/day 1 - 5 ) were compared in a prospect i ve r and omized study in patients with colorectal cancer . The treatment courses were repeated every 6th week . Leucopenia was more common after 5-FU . Leucocyte nadir in connection with first treatment cycle was on average seen on day 15 in patients receiving 5-FU and on day 28 in patients receiving Ftorafur . Significantly more patients on 5-FU developed stomatitis . There was no difference in the number of patients with diarrhea or nausea/vomiting . Median survival and response rates were not significantly different after the two treatment schedules PURPOSE The aim of the study was to test the hypothesis that aerobic Gram-negative bacteria ( AGNB ) play a crucial role in the pathogenesis of radiation-induced mucositis ; consequently , selective elimination of these bacteria from the oral flora should result in a reduction of the mucositis . METHODS AND MATERIAL S Head- and -neck cancer patients , when scheduled for treatment by external beam radiation therapy ( EBRT ) , were r and omized for prophylactic treatment with an oral paste containing either a placebo or a combination of the antibiotics polymyxin E , tobramycin , and amphotericin B ( PTA group ) . Weekly , the objective and subjective mucositis scores and microbiologic counts of the oral flora were noted . The primary study endpoint was the mucositis grade after 3 weeks of EBRT . RESULTS Seventy-seven patients were evaluable . No statistically significant difference for the objective and subjective mucositis scores was observed between the two study arms ( p = 0.33 ) . The percentage of patients with positive cultures of AGNB was significantly reduced in the PTA group ( p = 0.01 ) . However , complete eradication of AGNB was not achieved . CONCLUSIONS Selective elimination of AGNB of the oral flora did not result in a reduction of radiation-induced mucositis and therefore does not support the hypothesis that these bacteria play a crucial role in the pathogenesis of mucositis |
950 | 23,023,028 | Many of the reported SNPs had diverse association with specific human cancers .
For example , there was a positive association between the OGG1 Ser326Cys variant and gastric and lung cancer , while the XRCC1 Arg399Gln variant was associated with reduced cancer risk . | Genetic variation in DNA repair genes can modulate DNA repair capacity and may be related to cancer risk .
However , study findings have been inconsistent .
Inheritance of variant DNA repair genes is believed to influence individual susceptibility to the development of environmental cancer .
Reliable knowledge on which the base excision repair ( BER ) sequence variants are associated with cancer risk would help eluci date the mechanism of cancer .
Given that most of the previous studies had inadequate statistical power , we have conducted a systematic review on sequence variants in three important BER proteins . | Several polymorphisms in DNA repair genes have been reported to be associated with lung cancer risk including XPA ( -4G/A ) , XPD ( Lys751Gln and Asp312Asn ) , XRCC1 ( Arg399Gln ) , APE1 ( Asp148Glu ) and XRCC3 ( Thr241Met ) . As there is little information on the combined effects of these variants , polymorphisms were analyzed in a case-control study including 463 lung cancer cases [ among them 204 adenocarcinoma and 212 squamous cell carcinoma ( SCC ) ] and 460 tumor-free hospital controls . Odds ratios ( OR ) adjusted for age , gender , smoking and occupational exposure were calculated for the variants alone and combinations thereof . For homozygous individuals carrying the Glu variant of APE1 , a protective effect was found ( OR = 0.77 , CI = 0.51 - 1.16 ) . Individuals homozygous for the variants XPA ( -4A ) ( OR = 1.53 , CI = 0.94 - 2.5 ) , XPD 751Gln ( OR = 1.39 , CI = 0.90 - 2.14 ) or XRCC3 241Met ( OR = 1.29 , CI = 0.85 - 1.98 ) showed a slightly higher risk for lung cancer overall . In the subgroup of adenocarcinoma cases , adjusted ORs were increased for individuals homozygous for XPA ( -4A ) ( OR = 1.62 , CI = 0.91 - 2.88 ) and XRCC3 241Met ( OR = 1.65 ; CI = 0.99 - 2.75 ) . When analyzing the combined effects of variant alleles , 54 patients and controls were identified that were homozygous for two or three of the potential risk alleles [ i.e. the variants in nucleotide excision repair , XPA ( -4A ) and XPD 751Gln , and in homologous recombination , XRCC3 - 241Met ] . ORs were significantly increased when all patients ( OR = 2.37 ; CI = 1.26 - 4.48 ) , patients with SCC ( OR = 2.83 ; CI = 1.17 - 6.85 ) and with adenocarcinoma ( OR = 3.05 ; CI = 1.49 - 6.23 ) were analyzed . Combinations of polymorphisms in genes involved in the same repair pathway ( XPA + XPD or XRCC1 + APE1 ) affected lung cancer risk only in patients with SCC . These results indicate that lung cancer risk is only moderately increased by single DNA repair gene variants investigated but it is considerably enhanced by specific combinations of variant alleles . Analyses of additional DNA repair gene interactions in larger population -based studies are warranted for identification of high-risk subjects Several single nucleotide polymorphisms ( SNPs ) affecting DNA repair capacity and modifying cancer susceptibility have been described . We evaluated the association of SNPs Arg194Trp , Arg280His , and Arg399Gln in the X-ray cross-complementing group 1 ( XRCC1 ) and Thr241Met in the X-ray cross-complementing group 3 ( XRCC3 ) DNA repair genes with the risk of brain tumors . The Caucasian study population consisted of 701 glioma ( including 320 glioblastoma ) cases , 524 meningioma cases , and 1,560 controls in a prospect i ve population -based case – control study conducted in Denmark , Finl and , Sweden , and the UK . The studied SNPs were not significantly associated with the risk of brain tumors . The highest odds ratios ( ORs ) for the associations were observed between the homozygous variant genotype XRCC1 Gln399Gln and the risk of glioma ( OR = 1.32 ; 95 % confidence interval , CI , 0.97–1.81 ) , glioblastoma ( OR = 1.48 ; 95 % CI , 0.98–2.24 ) , and meningioma ( OR = 1.34 ; 95 % CI , 0.96–1.86 ) . However , in pair-wise comparisons a few SNP combinations were associated with the risk of brain tumors : Among others , carriers of both homozygous variant genotypes , i.e. , XRCC1 Gln399Gln and XRCC3 Met241Met , were associated with a three-fold increased risk of glioma ( OR = 3.18 ; 95 % CI , 1.26–8.04 ) and meningioma ( OR = 2.99 ; 95 % CI , 1.16–7.72 ) . In conclusion , no significant association with brain tumors was found for any of the polymorphisms , when examined one by one . Our results indicated possible associations between combinations of XRCC1 and XRCC3 SNPs and the risk of brain tumors Environmental carcinogens contained in air pollution , such as polycyclic aromatic hydrocarbons , aromatic amines or N-nitroso compounds , predominantly form DNA adducts but can also generate interstr and cross-links and reactive oxygen species . If unrepaired , such lesions increase the risk of somatic mutations and cancer . Our study investigated the relationships between 22 polymorphisms ( and their haplotypes ) in 16 DNA repair genes belonging to different repair pathways in 1094 controls and 567 cancer cases ( bladder cancer , 131 ; lung cancer , 134 ; oral-pharyngeal cancer , 41 ; laryngeal cancer , 47 ; leukaemia , 179 ; death from emphysema and chronic obstructive pulmonary disease , 84 ) . The design was a case-control study nested within a prospect i ve investigation . Among the many comparisons , few polymorphisms were associated with the diseases at the univariate analysis : XRCC1 - 399 Gln/Gln variant homozygotes [ odds ratios ( OR ) = 2.20 , 95 % confidence intervals ( CI ) = 1.16 - 4.17 ] and XRCC3 - 241 Met/Met homozygotes ( OR = 0.51 , 95 % CI = 0.27 - 0.96 ) and leukaemia . The recessive model in the stepwise multivariate analysis revealed a possible protective effect of XRCC1 - 399Gln/Gln in lung cancer ( OR = 0.22 , 95 % CI = 0.05 - 0.98 ) , and confirmed an opposite effect ( OR = 2.47 , 95 % CI = 1.02 - 6.02 ) in the leukaemia group . Our results also suggest that the XPD/ERCC1-GAT haplotype may modulate leukaemia ( OR = 1.28 , 95 % CI = 1.02 - 1.61 ) , bladder cancer ( OR = 1.38 , 95 % CI = 1.06 - 1.79 ) and possibly other cancer risks . Further investigations of the combined effects of polymorphisms within these DNA repair genes , smoking and other risk factors may help to clarify the influence of genetic variation in the carcinogenic process |
951 | 29,745,422 | In most of the nine mindfulness and six yoga studies , significant between-group effects were found indicating moderate to large effect size advantages for these treatments . | OBJECTIVE To systematic ally review outcomes from r and omized controlled trials ( RCTs ) of mind-body treatments for PTSD . | Objective : Multiple Sclerosis ( MS ) is a demyelinating autoimmune disease that imposes a significant emotional burden with heavy psychosocial consequences . Several studies have investigated the association between MS and mental disorders such as depression and anxiety , and recently research ers have focused also on Post-traumatic Stress Disorder ( PTSD ) . This is the first study that investigates the usefulness of proposing a treatment for PTSD to patients with MS . Methods : A r and omized controlled trial with patients with MS diagnosed with PTSD comparing Eye Movement Desensitization and Reprocessing ( EMDR ; n = 20 ) and Relaxation Therapy ( RT ; n = 22 ) . The primary outcome measure was the proportion of participants that no longer meet PTSD diagnosis as measured with Clinician Administered PTSD Scale 6-months after the treatment . Results : The majority of patients were able to overcome their PTSD diagnosis after only 10 therapy sessions . EMDR treatment appears to be more effective than RT in reducing the proportion of patients with MS suffering from PTSD . Both treatments are effective in reducing PTSD severity , anxiety and depression symptoms , and to improve Quality of Life . Conclusion : Although our results can only be considered preliminary , this study suggests that it is essential that PTSD symptoms are detected and that brief and cost-effective interventions to reduce PTSD and associated psychological symptoms are offered to patients , in order to help them to reduce the psychological burden associated with their neurological condition . Trial registration : NCT01743664 , https:// clinical BACKGROUND More than a third of the approximately 10 million women with histories of interpersonal violence in the United States develop posttraumatic stress disorder ( PTSD ) . Currently available treatments for this population have a high rate of incomplete response , in part because problems in affect and impulse regulation are major obstacles to resolving PTSD . This study explored the efficacy of yoga to increase affect tolerance and to decrease PTSD symptomatology . METHOD Sixty-four women with chronic , treatment-resistant PTSD were r and omly assigned to either trauma-informed yoga or supportive women 's health education , each as a weekly 1-hour class for 10 weeks . Assessment s were conducted at pretreatment , midtreatment , and posttreatment and included measures of DSM-IV PTSD , affect regulation , and depression . The study ran from 2008 through 2011 . RESULTS The primary outcome measure was the Clinician-Administered PTSD Scale ( CAPS ) . At the end of the study , 16 of 31 participants ( 52 % ) in the yoga group no longer met criteria for PTSD compared to 6 of 29 ( 21 % ) in the control group ( n = 60 , χ²₁ = 6.17 , P = .013 ) . Both groups exhibited significant decreases on the CAPS , with the decrease falling in the large effect size range for the yoga group ( d = 1.07 ) and the medium to large effect size decrease for the control group ( d = 0.66 ) . Both the yoga ( b = -9.21 , t = -2.34 , P = .02 , d = -0.37 ) and control ( b = -22.12 , t = -3.39 , P = .001 , d = -0.54 ) groups exhibited significant decreases from pretreatment to the midtreatment assessment . However , a significant group × quadratic trend interaction ( d = -0.34 ) showed that the pattern of change in Davidson Trauma Scale significantly differed across groups . The yoga group exhibited a significant medium effect size linear ( d = -0.52 ) trend . In contrast , the control group exhibited only a significant medium effect size quadratic trend ( d = 0.46 ) but did not exhibit a significant linear trend ( d = -0.29 ) . Thus , both groups exhibited significant decreases in PTSD symptoms during the first half of treatment , but these improvements were maintained in the yoga group , while the control group relapsed after its initial improvement . DISCUSSION Yoga significantly reduced PTSD symptomatology , with effect sizes comparable to well- research ed psychotherapeutic and psychopharmacologic approaches . Yoga may improve the functioning of traumatized individuals by helping them to tolerate physical and sensory experiences associated with fear and helplessness and to increase emotional awareness and affect tolerance . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00839813 Background A large proportion of mindfulness-based therapy trials report statistically significant results , even in the context of very low statistical power . The objective of the present study was to characterize the reporting of “ positive ” results in r and omized controlled trials of mindfulness-based therapy . We also assessed mindfulness-based therapy trial registration s for indications of possible reporting bias and review ed recent systematic review s and meta-analyses to determine whether reporting biases were identified . Methods CINAHL , Cochrane CENTRAL , EMBASE , ISI , MEDLINE , PsycInfo , and SCOPUS data bases were search ed for r and omized controlled trials of mindfulness-based therapy . The number of positive trials was described and compared to the number that might be expected if mindfulness-based therapy were similarly effective compared to individual therapy for depression . Trial registries were search ed for mindfulness-based therapy registration s. CINAHL , Cochrane CENTRAL , EMBASE , ISI , MEDLINE , PsycInfo , and SCOPUS were also search ed for mindfulness-based therapy systematic review s and meta-analyses . Results 108 ( 87 % ) of 124 published trials reported ≥1 positive outcome in the abstract , and 109 ( 88 % ) concluded that mindfulness-based therapy was effective , 1.6 times greater than the expected number of positive trials based on effect size d = 0.55 ( expected number positive trials = 65.7 ) . Of 21 trial registration s , 13 ( 62 % ) remained unpublished 30 months post-trial completion . No trial registration s adequately specified a single primary outcome measure with time of assessment . None of 36 systematic review s and meta-analyses concluded that effect estimates were overestimated due to reporting biases . Conclusions The proportion of mindfulness-based therapy trials with statistically significant results may overstate what would occur in practice Posttraumatic stress disorder ( PTSD ) is a debilitating condition that affects approximately 10 % of women in the United States . Although effective psychotherapeutic treatments for PTSD exist , clients with PTSD report additional benefits of complementary and alternative approaches such as yoga . In particular , yoga may downregulate the stress response and positively impact PTSD and comorbid depression and anxiety symptoms . We conducted a pilot study of a r and omized controlled trial comparing a 12-session Kripalu-based yoga intervention with an assessment control group . Participants included 38 women with current full or subthreshold PTSD symptoms . During the intervention , yoga participants showed decreases in reexperiencing and hyperarousal symptoms . The assessment control group , however , showed decreases in reexperiencing and anxiety symptoms as well , which may be a result of the positive effect of self-monitoring on PTSD and associated symptoms . Between-groups effect sizes were small to moderate ( 0.08 - 0.31 ) . Although more research is needed , yoga may be an effective adjunctive treatment for PTSD . Participants responded positively to the intervention , suggesting that it was tolerable for this sample . Findings underscore the need for future research investigating mechanisms by which yoga may impact mental health symptoms , gender comparisons , and the long-term effects of yoga practice Yoga may be effective in the reduction of PTSD symptomology . The purpose of this study was to evaluate the impact of a Kundalini Yoga ( KY ) treatment on PTSD symptoms and overall wellbeing . To supplement the current field of inquiry , a pilot r and omized control trial ( RCT ) was conducted comparing an 8-session KY intervention with a waitlist control group . 80 individuals with current PTSD symptoms participated . Both groups demonstrated changes in PTSD symptomology but yoga participants showed greater changes in measures of sleep , positive affect , perceived stress , anxiety , stress , and resilience . Between-groups effect sizes were small to moderate ( 0.09–0.25 ) . KY may be an adjunctive or alternative intervention for PTSD . Findings indicate the need for further yoga research to better underst and the mechanism of yoga in relation to mental and physical health , gender and ethnic comparisons , and short- and long-term yoga practice for psychiatric conditions BACKGROUND Posttraumatic stress disorder ( PTSD ) is prevalent among military veterans and is associated with significant negative health outcomes . However , stigma and other barriers to care prevent many veterans from pursuing traditional mental health treatment . We developed a group-based Integrative Exercise ( IE ) program combining aerobic and resistance exercise , which is familiar to veterans , with mindfulness-based practice s suited to veterans with PTSD . This study aim ed to evaluate the effects of IE on PTSD symptom severity and quality of life , as well as assess the feasibility and acceptability of IE . METHODS Veterans ( N = 47 ) were r and omized to either IE or waitlist control ( WL ) . Veterans in IE were asked to attend three 1-h group exercise sessions for 12 weeks . RESULTS Compared with WL , veterans r and omized to IE demonstrated a greater reduction in PTSD symptom severity ( d = -.90 ) , a greater improvement in psychological quality of life ( d = .53 ) and a smaller relative improvement in physical quality of life ( d = .30 ) Veterans ' ratings of IE indicated high feasibility and acceptability . LIMITATIONS The sample was relatively small and recruited from one site . The comparison condition was an inactive control . CONCLUSIONS This initial study suggests that IE is an innovative approach to treating veterans with symptoms of PTSD that reduces symptoms of posttraumatic stress and improves psychological quality of life . This approach to recovery may exp and the reach of PTSD treatment into non-traditional setting s and to veterans who may prefer a familiar activity , such as exercise , over medication or psychotherapy OBJECTIVE This study 's objective was to evaluate the effect of two common components of meditation ( mindfulness and slow breathing ) on potential mechanistic pathways . METHODS A total of 102 combat veterans with posttraumatic stress disorder ( PTSD ) were r and omized to ( a ) the body scan mindfulness meditation ( MM ) , ( b ) slow breathing ( SB ) with a biofeedback device , ( c ) mindful awareness of the breath with an intention to slow the breath ( MM+SB ) , or ( d ) sitting quietly ( SQ ) . Participants had 6 weekly one-on-one sessions with 20 minutes of daily home practice . The mechanistic pathways and measures were as follows : ( a ) autonomic nervous system ( hyperarousal symptoms , heart rate [ HR ] , and heart rate variability [ HRV ] ) ; ( b ) frontal cortex activity ( attentional network task [ ANT ] conflict effect and event-related negativity and intrusive thoughts ) ; and ( c ) hypothalamic-pituitary-adrenal axis ( awakening cortisol ) . PTSD measures were also evaluated . RESULTS Meditation participants had significant but modest within-group improvement in PTSD and related symptoms , although there were no effects between groups . Perceived impression of PTSD symptom improvement was greater in the meditation arms compared with controls . Resting respiration decreased in the meditation arms compared with SQ . For the mechanistic pathways , ( a ) subjective hyperarousal symptoms improved within-group ( but not between groups ) for MM , MM+SB , and SQ , while HR and HRV did not ; ( b ) intrusive thoughts decreased in MM compared with MM+SB and SB , while the ANT measures did not change ; and ( c ) MM had lower awakening cortisol within-group ( but not between groups ) . CONCLUSION Treatment effects were mostly specific to self-report rather than physiological measures . Continued research is needed to further evaluate mindfulness meditation 's mechanism in people with PTSD This preliminary study examined whether the practice of mind – body techniques decreases symptoms of posttraumatic stress in adolescents . Posttraumatic Stress Reaction Index question naires were collected from 139 high school students in Kosovo who participated in a 6-week program that included meditation , biofeedback , drawings , autogenic training , guided imagery , genograms , movement , and breathing techniques . Three separate programs were held approximately 2 months apart . There was no control group . Posttraumatic stress scores significantly decreased after participation in the programs . These scores remained decreased in the 2 groups that participated in the follow-up study when compared to pretest measures . These data indicate that mind – body skills groups were effective in reducing posttraumatic stress symptoms in war-traumatized high school students OBJECTIVES This r and omized controlled trial of yoga for military veterans and active duty personnel with posttraumatic stress disorder ( PTSD ) evaluated the efficacy of a 10-week yoga intervention on PTSD . METHOD Fifty-one participants were r and omized into yoga or no-treatment assessment -only control groups . Primary outcome measures included question naires and the Clinician Administered PTSD Scale . RESULTS Both yoga ( n = 9 ) and control ( n = 6 ) participants showed significant decreases in reexperiencing symptoms , with no significant between-group differences . Secondary within-group analyses of a self-selected wait-list yoga group ( n = 7 ) showed significant reductions in PTSD symptoms after yoga participation , in contrast to their control group participation . Consistent with current literature regarding high rates of PTSD treatment dropout for veterans , this study faced challenges retaining participants across conditions . CONCLUSION These results are consistent with recent literature indicating that yoga may have potential as a PTSD therapy in a veteran or military population . However , additional larger sample size trials are necessary to confirm this conclusion OBJECTIVE Exposure to trauma reminders has been considered imperative in psychotherapy for posttraumatic stress disorder ( PTSD ) . The authors tested interpersonal psychotherapy ( IPT ) , which has demonstrated antidepressant efficacy and shown promise in pilot PTSD research as a non-exposure-based non-cognitive-behavioral PTSD treatment . METHOD The authors conducted a r and omized 14-week trial comparing IPT , prolonged exposure ( an exposure-based exemplar ) , and relaxation therapy ( an active control psychotherapy ) in 110 unmedicated patients who had chronic PTSD and a score > 50 on the Clinician-Administered PTSD Scale ( CAPS ) . R and omization stratified for comorbid major depression . The authors hypothesized that IPT would be no more than minimally inferior ( a difference < 12.5 points in CAPS score ) to prolonged exposure . RESULTS All therapies had large within-group effect sizes ( d values , 1.32 - 1.88 ) . Rates of response , defined as an improvement of > 30 % in CAPS score , were 63 % for IPT , 47 % for prolonged exposure , and 38 % for relaxation therapy ( not significantly different between groups ) . CAPS outcomes for IPT and prolonged exposure differed by 5.5 points ( not significant ) , and the null hypothesis of more than minimal IPT inferiority was rejected ( p=0.035 ) . Patients with comorbid major depression were nine times more likely than nondepressed patients to drop out of prolonged exposure therapy . IPT and prolonged exposure improved quality of life and social functioning more than relaxation therapy . CONCLUSIONS This study demonstrated noninferiority of individual IPT for PTSD compared with the gold-st and ard treatment . IPT had ( nonsignificantly ) lower attrition and higher response rates than prolonged exposure . Contrary to widespread clinical belief , PTSD treatment may not require cognitive-behavioral exposure to trauma reminders . Moreover , patients with comorbid major depression may fare better with IPT than with prolonged exposure We examined the therapeutic efficacy of a culturally adapted form of CBT ( CA-CBT ) for PTSD as compared to applied muscle relaxation ( AMR ) for female Latino patients with treatment-resistant PTSD . Participants were r and omized to receive either CA-CBT ( n = 12 ) or AMR ( n = 12 ) , and were assessed before treatment , after treatment , and at a 12-week follow-up . The treatments were manualized and delivered in the form of group therapy across 14 weekly sessions . Assessment s included a measure of PTSD , anxiety , culturally relevant idioms of distress ( nervios and ataque de nervios ) , and emotion regulation ability . Patients receiving CA-CBT improved significantly more than in the AMR condition . Effect size estimates showed very large reductions in PTSD symptoms from pretreatment to posttreatment in the CA-CBT group ( Cohen 's d = 2.6 ) but only modest improvements in the AMR group ( 0.8 ) . These results suggest that CA-CBT can be beneficial for previously treatment-resistant PTSD in Latino women Purpose : To assess the feasibility , effect sizes , and satisfaction of mantram repetition — the spiritual practice of repeating a sacred word/phrase throughout the day — for managing symptoms of posttraumatic stress disorder ( PTSD ) in veterans . Design : A two group ( intervention vs. control ) by two time ( pre- and postintervention ) experimental design was used . Methods : Veterans were r and omly assigned to intervention ( n = 14 ) or delayed-treatment control ( n = 15 ) . Measures were PTSD symptoms , psychological distress , quality of life , and patient satisfaction . Effect sizes were calculated using Cohen 's d. Findings : Thirty-three male veterans were enrolled , and 29 ( 88 % ) completed the study . Large effect sizes were found for reducing PTSD symptom severity ( d = –.72 ) , psychological distress ( d = –.73 ) and increasing quality of life ( d = –.70 ) . Conclusions : A spiritual program was found to be feasible for veterans with PTSD . They reported moderate to high satisfaction . Effect sizes show promise for symptom improvement but more research is needed The purpose of this experiment was to conduct a dismantling study of cognitive processing therapy in which the full protocol was compared with its constituent components -- cognitive therapy only ( CPT-C ) and written accounts (WA)--for the treatment of posttraumatic stress disorder ( PTSD ) and comorbid symptoms . The intent-to-treat ( ITT ) sample included 150 adult women with PTSD who were r and omized into 1 of the 3 conditions . Each condition consisted of 2 hr of therapy per week for 6 weeks ; blind assessment s were conducted before treatment , 2 weeks following the last session , and 6 months following treatment . Measures of PTSD and depression were collected weekly to examine the course of recovery during treatment as well as before and after treatment . Secondary measures assessed anxiety , anger , shame , guilt , and dysfunctional cognitions . Independent ratings of adherence and competence were also conducted . Analyses with the ITT sample and with study completers indicate that patients in all 3 treatments improved substantially on PTSD and depression , the primary measures , and improved on other indices of adjustment . However , there were significant group differences in symptom reduction during the course of treatment whereby the CPT-C condition reported greater improvement in PTSD than the WA condition Objective Brain imaging studies in patients with post-traumatic stress disorder ( PTSD ) have implicated a circuitry of brain regions including the medial prefrontal cortex , amygdala , hippocampus , parietal cortex , and insula . Pharmacological treatment studies have shown a reversal of medial prefrontal deficits in response to traumatic reminders . Mindfulness-based stress reduction ( MBSR ) is a promising non-pharmacologic approach to the treatment of anxiety and pain disorders . The purpose of this study was to assess the effects of MBSR on PTSD symptoms and brain response to traumatic reminders measured with positron-emission tomography ( PET ) in Operation Enduring Freedom/Operation Iraqi Freedom ( OEF/OIF ) combat veterans with PTSD . We hypothesized that MBSR would show increased prefrontal response to stress and improved PTSD symptoms in veterans with PTSD . Method Twenty-six OEF/OIF combat veterans with PTSD who had recently returned from a combat zone were block r and omized to receive eight sessions of MBSR or present-centered group therapy ( PCGT ) . PTSD patients underwent assessment of PTSD symptoms with the Clinician-Administered PTSD Scale ( CAPS ) , mindfulness with the Five Factor Mindfulness Question naire ( FFMQ ) and brain imaging using PET in conjunction with exposure to neutral and Iraq combat-related slides and sound before and after treatment . Nine patients in the MBSR group and 8 in the PCGT group completed all study procedures . Results Post-traumatic stress disorder patients treated with MBSR ( but not PCGT ) had an improvement in PTSD symptoms measured with the CAPS that persisted for 6 months after treatment . MBSR also result ed in an increase in mindfulness measured with the FFMQ . MBSR-treated patients had increased anterior cingulate and inferior parietal lobule and decreased insula and precuneus function in response to traumatic reminders compared to the PCGT group . Conclusion This study shows that MBSR is a safe and effective treatment for PTSD . Furthermore , MBSR treatment is associated with changes in brain regions that have been implicated in PTSD and are involved in extinction of fear responses to traumatic memories as well as regulation of the stress response BACKGROUND Unanswered questions from controlled studies of posttraumatic stress disorder concern the value of cognitive restructuring alone without prolonged exposure therapy and whether its combination with prolonged exposure is enhancing . METHODS In a controlled study , 87 patients with posttraumatic stress disorder of at least 6 months ' duration were r and omly assigned to have 10 sessions of 1 of 4 treatments : prolonged exposure ( imaginal and live ) alone ; cognitive restructuring alone ; combined prolonged exposure and cognitive restructuring ; or relaxation without prolonged exposure or cognitive restructuring . RESULTS Integrity of audiotaped treatment sessions was satisfactory when rated by an assessor unaware of the treatment assignment . Seventy-seven patients completed treatment . The pattern of results was similar regardless of rater , statistical method , measure , occasion , and therapist . Exposure and cognitive restructuring , singly or combined , improved posttraumatic stress disorder markedly on a broad front . Gains continued to 6-month follow-up and were significantly greater than the moderate improvement from relaxation . CONCLUSION Both prolonged exposure and cognitive restructuring were each therapeutic on their own , were not mutually enhancing when combined , and were each superior to relaxation OBJECTIVE This pilot r and omized controlled trial evaluated a novel trauma-informed model of mindfulness-based stress reduction ( TI-MBSR ) as a phase I trauma intervention for female survivors of interpersonal violence ( IPV ) . METHOD A community-based sample of women ( mean age = 41.5 , st and ard deviation = 14.6 ) with a history of IPV was r and omly assigned to an 8-week TI-MBSR intervention ( n = 23 ) or a waitlist control group ( n = 22 ) . Symptoms of posttraumatic stress disorder ( PTSD ) and depression as well as anxious and avoidant attachment were assessed pre- and postintervention . RESULTS Relative to the control group , participation in TI-MBSR was associated with statistically and clinical ly significant decreases in PTSD and depressive symptoms and significant reductions in anxious attachment . Retention in the intervention was high , with most participants completing at least 5 of the 8 sessions for the intervention . Minutes of mindfulness practice per week significantly predicted reductions in PTSD symptoms . CONCLUSION TI-MBSR appears to be a promising and feasible phase I intervention for female survivors of interpersonal trauma OBJECTIVES To assess outcomes of veterans who participated in mindfulness-based stress reduction ( MBSR ) . DESIGN Posttraumatic stress disorder ( PTSD ) symptoms , depression , functional status , behavioral activation , experiential avoidance , and mindfulness were assessed at baseline , and 2 and 6 months after enrollment . RESULTS At 6 months , there were significant improvements in PTSD symptoms ( st and ardized effect size , d = -0.64 , p < 0.001 ) ; depression ( d = -0.70 , p<0.001 ) ; behavioral activation ( d = 0.62 , p<0.001 ) ; mental component summary score of the Short Form-8 ( d = 0.72 , p<0.001 ) ; acceptance ( d = 0.67 , p<0.001 ) ; and mindfulness ( d = 0.78 , p<0.001 ) , and 47.7 % of veterans had clinical ly significant improvements in PTSD symptoms . CONCLUSIONS MBSR shows promise as an intervention for PTSD and warrants further study in r and omized controlled trials OBJECTIVES Primary care ( PC ) patients typically do not receive adequate posttraumatic stress disorder ( PTSD ) treatment . This study tested if a brief mindfulness training ( BMT ) offered in PC can decrease PTSD severity . METHOD VA PC patients with PTSD ( N = 62 ) were recruited for a r and omized clinical trial comparing PCBMT with PC treatment as usual . PCBMT is a 4-session program adapted from mindfulness-based stress reduction . RESULTS PTSD severity decreased in both conditions , although PCBMT completers reported significantly larger decreases in PTSD and depression from pre- to posttreatment and maintained gains at the 8-week follow-up compared with the control group . Exploratory analyses revealed that the describing , nonjudging , and acting with awareness facets of mindfulness may account for decreases in PTSD . CONCLUSION Our data support preliminary efficacy of BMT for Veterans with PTSD . Whether PCBMT facilitates engagement into , or improves outcomes of , full-length empirically supported treatment for PTSD remains to be evaluated The field of traumatic stress has experienced significant growth in the number of psychotherapy treatment studies conducted , especially in the past 10 years . In this article , the author aims to help both the readers of this work and psychotherapy research ers by review ing key concepts in trial design and discussing issues unique to psychotherapy ( and other nonpharmacological interventions ) . The discussion is broad and nontechnical , particularly with respect to statistical issues . The focus is on between-group r and omized design s , and on outcome rather than process . Examples are drawn from posttraumatic stress disorder treatment studies to enhance relevance to the field of traumatic stress Changes in psychological and physiological functioning following participation in Tai Chi were assessed for 33 beginners and 33 practitioners . The variables in the three-way factorial design were experience ( beginners vs practitioners ) , time ( morning vs afternoon vs evening ) , and phase ( before Tai Chi vs during Tai Chi vs after Tai Chi ) . Phase was a repeated measures variable . Relative to measures taken beforeh and , practice of Tai Chi raised heart rate , increased noradrenaline excretion in urine , and decreased salivary cortisol concentration . Relative to baseline levels , subjects reported less tension , depression , anger , fatigue , confusion and state-anxiety , they felt more vigorous , and in general they had less total mood disturbance . The data suggest that Tai Chi results in gains that are comparable to those found with moderate exercise . There is need for research concerned with whether participation in Tai Chi has effects over and above those associated with physical exercise Thirty-six patients with PTSD were r and omly allocated to individual treatment with imaginal exposure ( image habituation training -- IHT ) , or applied muscle relaxation ( AMR ) or eye movement desensitization ( EMD ) . Assessment by a blind independent rater and self-report instruments applied pre and posttreatment and at 3-month follow-up indicated that all groups improved significantly compared with a waiting list and that treatment benefits were maintained at follow-up . Despite a failure to demonstrate differences among groups , there was some suggestion that immediately after treatment EMD was superior for intrusive memories IMPORTANCE Mindfulness-based interventions may be acceptable to veterans who have poor adherence to existing evidence -based treatments for posttraumatic stress disorder ( PTSD ) . OBJECTIVE To compare mindfulness-based stress reduction with present-centered group therapy for treatment of PTSD . DESIGN , SETTING , AND PARTICIPANTS R and omized clinical trial of 116 veterans with PTSD recruited at the Minneapolis Veterans Affairs Medical Center from March 2012 to December 2013 . Outcomes were assessed before , during , and after treatment and at 2-month follow-up . Data collection was completed on April 22 , 2014 . INTERVENTIONS Participants were r and omly assigned to receive mindfulness-based stress reduction therapy ( n = 58 ) , consisting of 9 sessions ( 8 weekly 2.5-hour group sessions and a daylong retreat ) focused on teaching patients to attend to the present moment in a nonjudgmental , accepting manner ; or present-centered group therapy ( n = 58 ) , an active-control condition consisting of 9 weekly 1.5-hour group sessions focused on current life problems . MAIN OUTCOMES AND MEASURES The primary outcome , change in PTSD symptom severity over time , was assessed using the PTSD Checklist ( range , 17 - 85 ; higher scores indicate greater severity ; reduction of 10 or more considered a minimal clinical ly important difference ) at baseline and weeks 3 , 6 , 9 , and 17 . Secondary outcomes included PTSD diagnosis and symptom severity assessed by independent evaluators using the Clinician-Administered PTSD Scale along with improvements in depressive symptoms , quality of life , and mindfulness . RESULTS Participants in the mindfulness-based stress reduction group demonstrated greater improvement in self-reported PTSD symptom severity during treatment ( change in mean PTSD Checklist scores from 63.6 to 55.7 vs 58.8 to 55.8 with present-centered group therapy ; between-group difference , 4.95 ; 95 % CI , 1.92 - 7.99 ; P=.002 ) and at 2-month follow-up ( change in mean scores from 63.6 to 54.4 vs 58.8 to 56.0 , respectively ; difference , 6.44 ; 95 % CI , 3.34 - 9.53 , P < .001 ) . Although participants in the mindfulness-based stress reduction group were more likely to show clinical ly significant improvement in self-reported PTSD symptom severity ( 48.9 % vs 28.1 % with present-centered group therapy ; difference , 20.9 % ; 95 % CI , 2.2%-39.5 % ; P = .03 ) at 2-month follow-up , they were no more likely to have loss of PTSD diagnosis ( 53.3 % vs 47.3 % , respectively ; difference , 6.0 % ; 95 % CI , -14.1 % to 26.2 % ; P = .55 ) . CONCLUSIONS AND RELEVANCE Among veterans with PTSD , mindfulness-based stress reduction therapy , compared with present-centered group therapy , result ed in a greater decrease in PTSD symptom severity . However , the magnitude of the average improvement suggests a modest effect . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01548742 BACKGROUND " Mindfulness-based " interventions show promise for stress reduction in general medical conditions , and initial evidence suggests that they are accepted in trauma-exposed individuals . Mindfulness-based cognitive therapy ( MBCT ) shows substantial efficacy for prevention of depression relapse , but it has been less studied in anxiety disorders . This study investigated the feasibility , acceptability , and clinical outcomes of an MBCT group intervention adapted for combat posttraumatic stress disorder ( PTSD ) . METHODS Consecutive patients seeking treatment for chronic PTSD at a VA outpatient clinic were enrolled in 8-week MBCT groups , modified for PTSD ( four groups , n = 20 ) or brief treatment-as-usual ( TAU ) comparison group interventions ( three groups , n = 17 ) . Pre and posttherapy psychological assessment s with clinician administered PTSD scale ( CAPS ) were performed with all patients , and self-report measures ( PTSD diagnostic scale , PDS , and posttraumatic cognitions inventory , PTCI ) were administered in the MBCT group . RESULTS Intent to treat analyses showed significant improvement in PTSD ( CAPS ( t(19 ) = 4.8 , P < .001 ) ) in the MBCT condition but not the TAU conditions , and a significant Condition × Time interaction ( F[1,35 ] = 16.4 , P < .005 ) . MBCT completers ( n = 15 , 75 % ) showed good compliance with assigned homework exercises , and significant and clinical ly meaningful improvement in PTSD symptom severity on posttreatment assessment in CAPS and PDS ( particularly in avoidance/numbing symptoms ) , and reduced PTSD-relevant cognitions in PTCI ( self blame ) . CONCLUSIONS These data suggest group MBCT as an acceptable brief intervention/adjunctive therapy for combat PTSD , with potential for reducing avoidance symptom cluster and PTSD cognitions . Further studies are needed to examine efficacy in a r and omized controlled design and to identify factors influencing acceptability and efficacy CONTEXT Abnormal cortisol levels are a key pathophysiological indicator of post-traumatic stress disorder ( PTSD ) . Endogenous normalization of cortisol concentration through exercise may be associated with PTSD symptom reduction . OBJECTIVE The aim of the study was to determine whether mindfulness-based stretching and deep breathing exercise ( MBX ) normalizes cortisol levels and reduces PTSD symptom severity among individuals with sub clinical features of PTSD . DESIGN AND SETTING A r and omized controlled trial was conducted at the University of New Mexico Health Sciences Center . PARTICIPANTS Twenty-nine nurses ( 28 female ) aged 45 - 66 years participated in the study . INTERVENTION Sixty-minute MBX sessions were conducted semiweekly for 8 weeks . MAIN OUTCOME MEASURES Serum cortisol was measured , and the PTSD Checklist-Civilian version ( PCL-C ) was performed at baseline and weeks 4 , 8 , and 16 . RESULTS Twenty-nine participants completed the study procedures , 22 ( 79 % ) with PTSD symptoms ( MBX , n = 11 ; control , n = 11 ) , and 7 ( 21 % ) without PTSD ( BASE group ) . Eight-week outcomes for the MBX group were superior to those for the control group ( mean difference for PCL-C scores , -13.6 ; 95 % confidence interval [ CI ] , -25.6 , -1.6 ; P = .01 ; mean difference for serum cortisol , 5.8 ; 95 % CI , 0.83 , 10.8 ; P = .01 ) . No significant differences were identified between groups in any other items . The changes in the MBX group were maintained at the 16-week follow-up ( P = .85 for PCL-C ; P = .21 for cortisol ) . Our data show that improved PTSD scores were associated with normalization of cortisol levels ( P < .05 ) . CONCLUSIONS The results suggest that MBX appears to reduce the prevalence of PTSD-like symptoms in individuals exhibiting sub clinical features of PTSD |
952 | 24,416,238 | The findings from present study indicated that higher MET gene amplification and expression in gastric cancer was an indicator of poor prognosis | BACKGROUND AND AIMS MET , the hepatocyte growth factor receptor , is a receptor tyrosine kinase overexpressed and activated in a subset of gastric cancer .
Several studies investigated the relationship between MET amplification and expression with the clinical outcome in patients with gastric cancer , but yielded conflicting results .
We performed a systematic review and meta- analysis to determine the influence of MET amplification and expression on prognosis in gastric cancer . | BACKGROUND Trastuzumab , a monoclonal antibody against human epidermal growth factor receptor 2 ( HER2 ; also known as ERBB2 ) , was investigated in combination with chemotherapy for first-line treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer . METHODS ToGA ( Trastuzumab for Gastric Cancer ) was an open-label , international , phase 3 , r and omised controlled trial undertaken in 122 centres in 24 countries . Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumours showed overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation . Participants were r and omly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine plus cisplatin or fluorouracil plus cisplatin given every 3 weeks for six cycles or chemotherapy in combination with intravenous trastuzumab . Allocation was by block r and omisation stratified by Eastern Cooperative Oncology Group performance status , chemotherapy regimen , extent of disease , primary cancer site , and measurability of disease , implemented with a central interactive voice recognition system . The primary endpoint was overall survival in all r and omised patients who received study medication at least once . This trial is registered with Clinical Trials.gov , number NCT01041404 . FINDINGS 594 patients were r and omly assigned to study treatment ( trastuzumab plus chemotherapy , n=298 ; chemotherapy alone , n=296 ) , of whom 584 were included in the primary analysis ( n=294 ; n=290 ) . Median follow-up was 18.6 months ( IQR 11 - 25 ) in the trastuzumab plus chemotherapy group and 17.1 months ( 9 - 25 ) in the chemotherapy alone group . Median overall survival was 13.8 months ( 95 % CI 12 - 16 ) in those assigned to trastuzumab plus chemotherapy compared with 11.1 months ( 10 - 13 ) in those assigned to chemotherapy alone ( hazard ratio 0.74 ; 95 % CI 0.60 - 0.91 ; p=0.0046 ) . The most common adverse events in both groups were nausea ( trastuzumab plus chemotherapy , 197 [ 67 % ] vs chemotherapy alone , 184 [ 63 % ] ) , vomiting ( 147 [ 50 % ] vs 134 [ 46 % ] ) , and neutropenia ( 157 [ 53 % ] vs 165 [ 57 % ] ) . Rates of overall grade 3 or 4 adverse events ( 201 [ 68 % ] vs 198 [ 68 % ] ) and cardiac adverse events ( 17 [ 6 % ] vs 18 [ 6 % ] ) did not differ between groups . INTERPRETATION Trastuzumab in combination with chemotherapy can be considered as a new st and ard option for patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer . FUNDING F Hoffmann-La Roche The optimal adjuvant treatment for gastric cancer remains controversial . We compared the efficacy of a docetaxel and platinum adjuvant chemotherapy regimen , in patients with high-risk gastric cancer , with that of the same chemotherapy plus radiation therapy ( RT ) . In addition , we evaluated the prognostic and /or predictive value of a panel of molecular markers . Patients with histologically proven , radically resected gastric cancer , stage ≥T3 and /or N+ were r and omized to 6 cycles of docetaxel with cisplatin , both at 75 mg/m2 every 3 weeks ( arm A ) or the same treatment with RT ( arm B ; 45 Gy ) . Due to excessive nausea and vomiting , cisplatin was substituted by carboplatin at AUC ( area under the curve ) of 5 after the first 45 patients ( 22 group A , 23 group B ) . The prognostic value of EGFR , ERCC1 , HER2 , MET/HGFR , MAP-Tau , and PTEN expression was also studied in a subset of 67 patients using immunohistochemistry on tissue microarrays ( TMAs ) . A total of 147 patients were r and omized . After a median follow-up of 53.7 months , no differences in overall ( OS ) and disease-free survival ( DFS ) were found between the two arms . The most common grade 3/4 toxicities for arms A and B ( excluding alopecia ) were non-febrile neutropenia ( 11 and 17 % , respectively ) , febrile neutropenia ( 9 and 7 % ) and diarrhea ( 7 and 4 % , respectively ) . Patients with ERCC1 positive tumors had significantly longer median DFS ( 33.1 vs. 11.8 months , Wald P = 0.016 ) and OS ( 63.2 vs. 18.8 months , Wald P = 0.046 ) . Our results indicate that the addition of RT to platinum/docetaxel adjuvant chemotherapy does not appear to improve survival in high-risk , radically resected gastric cancer . However , the possibility that a benefit by the addition of RT was not detected due to decreased power of the study should not be excluded PURPOSE Amplification of the MET proto-oncogene in gastroesophageal cancer ( GEC ) may constitute a molecular marker for targeted therapy . We examined a GEC cohort with follow-up and reported the clinical response of four additional patients with MET-amplified tumors to the small molecule inhibitor crizotinib as part of an exp and ed phase I cohort study . PATIENTS AND METHODS From 2007 to 2009 , patients with GEC were genetically screened as a consecutive series of 489 tumors ( stages 0 , I , and II , 39 % ; III , 25 % ; IV , 36 % ; n = 222 esophageal , including n = 21 squamous carcinomas ) . MET , EGFR , and HER2 amplification status was assessed by using fluorescence in situ hybridization . RESULTS Ten ( 2 % ) of 489 patients screened harbored MET amplification ; 23 ( 4.7 % ) harbored EGFR amplification ; 45 ( 8.9 % ) harbored HER2 amplification ; and 411 ( 84 % ) were wild type for all three genes ( ie , negative ) . MET-amplified tumors were typically high- grade adenocarcinomas that presented at advanced stages ( 5 % ; n = 4 of 80 ) . EGFR-amplified tumors showed the highest fraction of squamous cell carcinoma ( 17 % ; n = 4 of 23 ) . HER2 , MET , and EGFR amplification were , with one exception ( MET and EGFR positive ) , mutually exclusive events . Survival analysis in patients with stages III and IV disease showed substantially shorter median survival in MET/EGFR-amplified groups , with a rank order for all groups by median survival ( from most to least aggressive ) : MET ( 7.1 months ; P < .001 ) less than EGFR ( 11.2 months ; P = .16 ) less than HER2 ( 16.9 months ; P = .89 ) when compared with the negative group ( 16.2 months ) . Two of four patients with MET-amplified tumors treated with crizotinib experienced tumor shrinkage ( -30 % and -16 % ) and experienced progression after 3.7 and 3.5 months . CONCLUSION MET amplification defines a small and aggressive subset of GEC with indications of transient sensitivity to the targeted MET inhibitor crizotinib ( PF-02341066 ) PURPOSE To investigate whether prognosis of patients with high-risk gastric cancer may depend on MET copy number gain ( CNG ) or an activating truncation within a deoxyadenosine tract element ( DATE ) in the promoter region of the MET lig and HGF . PATIENTS AND METHODS A single-institution cohort of 230 patients with stage II/III gastric cancer was studied . Formalin-fixed paraffin-embedded tumor specimens were used for DNA extraction . Quantitative polymerase chain reaction ( qPCR ) for MET CNG and sequencing for HGF DATE truncation ( < 25 deoxyadenosines instead of 30 ) were used . Results were analyzed for association with disease-free survival ( DFS ) and overall survival ( OS ) . To assess the reliability of the qPCR measurement , a r and om sample of cases was reanalyzed using an alternative assay ( fluorescent in situ hybridization [ FISH ] ) with calculation of the intracorrelation coefficient ( ICC ) . RESULTS In 216 assessable patients , MET CNG five or more copies and homozygous HGF-truncated DATE occurred in 21 patients ( 10 % ) and 30 patients ( 13 % ) , respectively . Patients with MET CNG five or more copies ( MET-positive ) showed significantly worse prognosis with multivariate hazard ratio ( HR ) of 3.02 ( 95 % CI , 1.71 to 5.33 ; P < .001 ) for DFS and multivariate HR of 2.91 ( 95 % CI , 1.65 to 5.11 ; P < .001 ) for OS . The agreement between qPCR and FISH was high , with ICC = 0.9 % ( 95 % CI , 0.81 % to 0.95 % ; the closer the ICC is to 1 , the greater is the agreement ) . HGF-truncated DATE did not show relevant prognostic effect . CONCLUSION In this study , qPCR revealed approximately 10 % of white patients with gastric cancer harboring MET CNG of five or more copies . This marker was significantly associated with unfavorable prognosis . This information is relevant to the current clinical development of anti-MET compounds |
953 | 22,962,216 | However , it is important to note that NGAL , in the absence of diagnostic increases in serum creatinine , is able to detect some patients affected by sub clinical AKI who have an increased risk of adverse outcomes . | Abstract Acute kidney injury ( AKI ) is a common and serious condition , currently diagnosed by functional biomarkers , such as serum creatinine measurements .
Unfortunately , creatinine increase is a delayed and unreliable indicator of AKI .
The lack of early biomarkers of structural kidney injury has hampered our ability to translate promising experimental therapies to human AKI .
The recent discovery , translation and validation of neutrophil gelatinase-associated lipocalin ( NGAL ) , possibly the most promising novel AKI biomarker , is review ed here .
NGAL may be measured by several methods both in plasma and urine for the early diagnosis of AKI and for the prediction of clinical outcomes , such as dialysis requirement and mortality , in several common clinical scenarios , including in the intensive care unit , cardiac surgery and renal damage due the exposition to toxic agent and drugs , and renal transplantation .
Furthermore , the predictive properties of NGAL , may play a critical role in expediting the drug development process . | Background : Acute renal dysfunction ( ARD ) and subsequent acute renal failure after cardiac surgery are associated with high mortality and morbidity . Early therapeutic or preventive intervention is hampered by the lack of an early biomarker for acute renal injury . Recent studies showed that urinary neutrophil gelatinase – associated lipocalin ( NGAL or lipocalin 2 ) is up-regulated early ( within 1–3 h ) after murine renal injury and in pediatric ARD after cardiac surgery . The authors hypothesized that postoperative urinary NGAL concentrations are increased in adult patients developing ARD after cardiac surgery compared with patients without ARD . Methods : After institutional review board approval , 81 cardiac surgical patients were prospect ively studied . Urine sample s were collected immediately before incision and at various time intervals after surgery for NGAL analysis by quantitative immunoblotting . ARD was defined as peak postoperative serum creatinine increase by 50 % or greater compared with preoperative serum creatinine . Results : Sixteen of 81 patients ( 20 % ) developed postoperative ARD , and the mean urinary NGAL concentrations in patients who developed ARD were significantly higher early after surgery ( after 1 h : 4,195 ± 6,520 [ mean ± SD ] vs. 1,068 ± 2,129 ng/ml ; P < 0.01 ) compared with patients who did not develop ARD . Mean urinary NGAL concentrations continued to increase and remained significantly higher at 3 and 18 h after cardiac surgery in patients with ARD . In contrast , urinary NGAL in patients without ARD decreased rapidly after cardiac surgery . Conclusions : Patients developing postoperative ARD had significantly higher urinary NGAL concentrations early after cardiac surgery . Urinary NGAL may therefore be a useful early biomarker of ARD after cardiac surgery . These findings may facilitate the early detection of acute renal injury and potentially prevent progression to acute renal failure BACKGROUND AND OBJECTIVES The authors have previously shown that urine neutrophil gelatinase-associated lipocalin ( NGAL ) , measured by a research ELISA , is an early predictive biomarker of acute kidney injury ( AKI ) after cardiopulmonary bypass ( CPB ) . In this study , whether an NGAL immunoassay developed for a st and ardized clinical platform ( ARCHITECT analyzer , Abbott Diagnostics Division , Abbott Laboratories , Abbott Park , IL ) can predict AKI after CPB was tested . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS In a pilot study with 136 urine sample s ( NGAL range , 0.3 to 815 ng/ml ) and 6 calibration st and ards ( NGAL range , 0 to 1000 ng/ml ) , NGAL measurements by research ELISA and by the ARCHITECT assay were highly correlated ( r = 0.99 ) . In a subsequent study , 196 children undergoing CPB were prospect ively enrolled and serial urine NGAL measurements obtained by ARCHITECT assay . The primary outcome was AKI , defined as a > or = 50 % increase in serum creatinine . RESULTS AKI developed in 99 patients ( 51 % ) , but the diagnosis using serum creatinine was delayed by 2 to 3 d after CPB . In contrast , mean urine NGAL levels increased 15-fold within 2 h and by 25-fold at 4 and 6 h after CPB . For the 2-h urine NGAL measurement , the area under the curve was 0.95 , sensitivity was 0.82 , and the specificity was 0.90 for prediction of AKI using a cutoff value of 100 ng/ml . The 2-h urine NGAL levels correlated with severity and duration of AKI , length of stay , dialysis requirement , and death . CONCLUSIONS Accurate measurements of urine NGAL are obtained using the ARCHITECT platform . Urine NGAL is an early predictive biomarker of AKI severity after CPB Objective : To compare the value of novel with conventional serum biomarkers in the prediction of acute kidney injury ( AKI ) in adult cardiac surgical patients according to preoperative renal function . Design : Single-center , prospect i ve observational study . Setting : Tertiary hospital . Patients : One hundred adult cardiac surgical patients . Measurements and Main Results : We measured concentrations of plasma neutrophil gelatinase-associated lipocalin ( NGAL ) , and serum cystatin C , and creatinine and urea at baseline , on arrival in the intensive care unit ( ICU ) and at 24 hours postoperatively . We assessed such biomarkers in relation to the development of AKI ( > 50 % increase in creatinine from baseline ) and to a composite end point ( need for renal replacement therapy and in-hospital mortality ) . We defined an area under the receiver operating characteristic curve of 0.60–0.69 as poor , 0.70–0.79 as fair , 0.80–0.89 as good , and 0.90–1.00 as excellent in terms of predictive value . On arrival in ICU , plasma NGAL and serum cystatin C were of good predictive value , but creatinine and urea were of poor predictive value . After exclusion of patients with preoperative renal impairment ( estimated glomerular filtration rate < 60 mL/min ) , the predictive performance for AKI of all renal biomarkers on arrival in ICU remained unchanged except for cystatin C , which was of fair value in such patients . At 24 hours postoperatively , all renal biomarkers were of good predictive value . On arrival in ICU , novel biomarkers were superior to conventional biomarkers ( p < 0.05 ) . Plasma NGAL ( p = 0.015 ) and serum cystatin C ( p = 0.007 ) were independent predictors of AKI and of excellent value in the prediction of the composite end point . Conclusions : Early postoperative measurement of plasma NGAL was of good value in identifying patients who developed AKI after adult cardiac surgery . Plasma NGAL and serum cystatin C were superior to conventional biomarkers in the prediction of AKI and were also of prognostic value in this setting Neutrophil gelatinase‐associated lipocalin ( NGAL ) is a measure of acute kidney injury . Renal dysfunction portends significant risk after discharge from acute heart failure ( AHF ) . Thus , a sensitive marker of renal injury might also help to risk stratify HF patients OBJECTIVES The aim of this study was to test the hypothesis that , without diagnostic changes in serum creatinine , increased neutrophil gelatinase-associated lipocalin ( NGAL ) levels identify patients with sub clinical acute kidney injury ( AKI ) and therefore worse prognosis . BACKGROUND Neutrophil gelatinase-associated lipocalin detects sub clinical AKI hours to days before increases in serum creatinine indicate manifest loss of renal function . METHODS We analyzed pooled data from 2,322 critically ill patients with predominantly cardiorenal syndrome from 10 prospect i ve observational studies of NGAL . We used the terms NGAL(- ) or NGAL(+ ) according to study -specific NGAL cutoff for optimal AKI prediction and the terms sCREA(- ) or sCREA(+ ) according to consensus diagnostic increases in serum creatinine defining AKI . A priori-defined outcomes included need for renal replacement therapy ( primary endpoint ) , hospital mortality , their combination , and duration of stay in intensive care and in-hospital . RESULTS Of study patients , 1,296 ( 55.8 % ) were NGAL(-)/sCREA(- ) , 445 ( 19.2 % ) were NGAL(+)/sCREA(- ) , 107 ( 4.6 % ) were NGAL(-)/sCREA(+ ) , and 474 ( 20.4 % ) were NGAL(+)/sCREA(+ ) . According to the 4 study groups , there was a stepwise increase in subsequent renal replacement therapy initiation-NGAL(-)/sCREA(- ) : 0.0015 % versus NGAL(+)/sCREA(- ) : 2.5 % ( odds ratio : 16.4 , 95 % confidence interval : 3.6 to 76.9 , p < 0.001 ) , NGAL(-)/sCREA(+ ) : 7.5 % , and NGAL(+)/sCREA(+ ) : 8.0 % , respectively , hospital mortality ( 4.8 % , 12.4 % , 8.4 % , 14.7 % , respectively ) and their combination ( 4-group comparisons : all p < 0.001 ) . There was a similar and consistent progressive increase in median number of intensive care and in-hospital days with increasing biomarker positivity : NGAL(-)/sCREA(- ) : 4.2 and 8.8 days ; NGAL(+)/sCREA(- ) : 7.1 and 17.0 days ; NGAL(-)/sCREA(+ ) : 6.5 and 17.8 days ; NGAL(+)/sCREA(+ ) : 9.0 and 21.9 days ; 4-group comparisons : p = 0.003 and p = 0.040 , respectively . Urine and plasma NGAL indicated a similar outcome pattern . CONCLUSIONS In the absence of diagnostic increases in serum creatinine , NGAL detects patients with likely sub clinical AKI who have an increased risk of adverse outcomes . The concept and definition of AKI might need re- assessment We hypothesized that use of Schwartz formula underestimates the prevalence of CKD in PHT recipients . This study determined the prevalence and risk factors for CKD in PHT using novel methods -serum cystatin C , CKiD formula , Revised Schwartz formula , s- and u-NGAL . Serum BUN , creatinine , cystatin C and s- and u-NGAL were measured after prospect i ve enrollment . Schwartz formula GFR was compared with novel methods . CKD was defined as CKiD GFR < 90 mL/min/1.73 m(2 ) . The s- and u-NGAL were compared between those with and without CKD . Potential risk factors for CKD were analyzed . Seventy-nine patients ( 46 male children or boys ) , mean age 9.9 ± 5.8 yr formed the study cohort . The prevalence of mild and moderate CKD was 2- to 3-fold higher using novel methods compared to Schwartz formula . u-NGAL and u-NGAL/Cr were significantly higher in patients with CKD . u- and s-NGAL had negative correlation with estimates of GFR . Women were at a higher risk for CKD ( odds ratio 8.7 ) as was longer duration since transplant ( p = 0.009 ) . In conclusion , use of novel methods of GFR estimation unmasked 2- to 3-fold increased prevalence of CKD in PHT . Women and those with longer duration since transplant are at higher risk for CKD In very low birth weight ( VLBW ) infants , acute renal impairment ( ARI ) is common , but there is no consensus about criteria for its diagnosis . Neutrophil gelatinase-associated lipocalin ( NGAL ) is an early and sensitive indicator of renal impairment in experimental animals , children , and adults . Urinary NGAL ( UNGAL ) is detectable in VLBW infants ; however , there is no reference range in this population . The objective of this study is to define the reference range for UNGAL in VLBW infants with no risk factors for acute renal impairment . UNGAL concentration was determined in urine sample s collected from day of life ( DOL ) 4 through DOL 30 in 50 newborns with uncomplicated clinical courses , selected from a total of 145 prospect ively enrolled appropriate for gestational age inborn VLBW premature infants . The birth weight and gestational age ranges were 790 - 1490 g and 26–33 wk , respectively . The median , 95th and 99th percentiles , and range of pooled UNGAL values were 5 ng/mL , 50 ng/mL , 120 ng/mL , and 2–150 ng/mL , respectively . Greater variability and higher quantile levels of UNGAL were observed in females versus males . In conclusion , a reference range for UNGAL in VLBW infants , similar to that in children and adults , has been established Background / Aims : Contrast-induced nephropathy ( CIN ) is at present the third leading cause of hospital-acquired acute kidney injury ( AKI ) . Traditionally , it is diagnosed by measuring the increase of the serum creatinine concentration . However , in patients with acute changes in their glomerular filtration rate , serum creatinine is an insensitive marker . This clinical study was design ed to investigate whether human urinary interleukin-18 ( IL-18 ) and neutrophil gelatinase-associated lipocalin ( NGAL ) are early predictive markers for AKI after coronary angiography and their correlation with later cardiac events . Methods : Patients undergoing coronary angiography using low-osmolar contrast medium were enrolled and then followed up for at least 17 months . Urine sample s were collected before and 24 h after coronary angiography and IL-18 and NGAL levels measured by using an ELISA kit . Results : CIN was diagnosed in 13 of 150 ( 8.7 % ) patients ( CIN group ) ; 27 patients without CIN served as control group . At 24 h after the procedure , the urinary IL-18 and NGAL levels were significantly increased in the CIN group , but not in the control group ( p < 0.05 ) . The predictable time of AKI onset determined by IL-18 was 24 h earlier than determined by serum creatinine ( p < 0.01 ) . Receiver operating characteristic curve analysis showed that both IL-18 and NGAL showed a good performance in early diagnosis of CIN as compared with serum creatinine ( p < 0.05 ) . We also found that IL-18 is an independent predictive marker for later major cardiac events : relative risk = 2.09 ( p < 0.01 ) . Conclusions : We conclude that urinary IL-18 or NGAL could be early biomarkers of CIN and that urinary IL-18 is well associated with the later cardiac outcomes in patients after coronary angiography We hypothesized that neutrophil gelatinase-associated lipocalin ( NGAL ) is an early predictive biomarker of contrast-induced nephropathy ( CIN ) . We prospect ively enrolled 91 children ( age 0–18 years ) with congenital heart disease undergoing elective cardiac catheterization and angiography with contrast administration ( CC ; Ioversol ) . Serial urine and plasma sample s were analyzed in a double-blind fashion by NGAL enzyme-linked immunosorbent assay ( ELISA ) . CIN , defined as a 50 % increase in serum creatinine from baseline , was found in 11 subjects ( 12 % ) , but detection using increase in serum creatinine was only possible 6–24 h after CC . In contrast , significant elevation of NGAL concentrations in urine ( 135 ± 32 vs. 11.6 ± 2 ng/ml without CIN , p < 0.001 ) and plasma ( 151 ± 34 vs. 36 ± 4 without CIN , p < 0.001 ) were noted within 2 h after CC in those subjects . Using a cutoff value of 100 ng/ml , sensitivity , specificity , and area under the receiver-operating characteristic ( ROC ) curve for prediction of CIN were excellent for the 2-h urine NGAL ( 73 % , 100 % , and 0.92 , respectively ) and 2-h plasma NGAL ( 73 % , 100 % , and 0.91 , respectively ) . By multivariate analysis , the 2-h NGAL concentrations in the urine ( R2 = 0.52 , p < 0.0001 ) and plasma ( R2 = 0.72 , p < 0.0001 ) were found to be powerful independent predictors of CIN . Patient demographics and contrast volume were not predictive of CIN Introduction Acute kidney injury ( AKI ) is a frequent complication of cardiopulmonary bypass ( CPB ) . The lack of early biomarkers has impaired our ability to intervene in a timely manner . We previously showed in a small cohort of patients that plasma neutrophil gelatinase-associated lipocalin ( NGAL ) , measured using a research enzyme-linked immunosorbent assay , is an early predictive biomarker of AKI after CPB . In this study we tested whether a point-of-care NGAL device can predict AKI after CPB in a larger cohort . Methods First , in a cross-sectional pilot study including 40 plasma sample s ( NGAL range 60 to 730 ng/ml ) and 12 calibration st and ards ( NGAL range 0 to 1,925 ng/ml ) , NGAL measurements by enzyme-linked immunosorbent assay and by Triage ® NGAL Device ( Biosite Inc. , San Diego , CA , USA ) were highly correlated ( r = 0.94 ) . Second , in a subsequent prospect i ve uncontrolled cohort study , 120 children undergoing CPB were enrolled . Plasma was collected at baseline and at frequent intervals for 24 hours after CPB , and analyzed for NGAL using the Triage ® NGAL device . The primary outcome was AKI , which was defined as a 50 % or greater increase in serum creatinine . Results AKI developed in 45 patients ( 37 % ) , but the diagnosis using serum creatinine was delayed by 2 to 3 days after CPB . In contrast , mean plasma NGAL levels increased threefold within 2 hours of CPB and remained significantly elevated for the duration of the study . By multivariate analysis , plasma NGAL at 2 hours after CPB was the most powerful independent predictor of AKI ( β = 0.004 , P < 0.0001 ) . For the 2-hour plasma NGAL measurement , the area under the curve was 0.96 , sensitivity was 0.84 , and specificity was 0.94 for prediction of AKI using a cut-off value of 150 ng/ml . The 2 hour postoperative plasma NGAL levels strongly correlated with change in creatinine ( r = 0.46 , P < 0.001 ) , duration of AKI ( r = 0.57 , P < 0.001 ) , and length of hospital stay ( r = 0.44 , P < 0.001 ) . The 12-hour plasma NGAL strongly correlated with mortality ( r = 0.48 , P = 0.004 ) and all measures of morbidity mentioned above . Conclusion Accurate measurements of plasma NGAL are obtained using the point-of-care Triage ® NGAL device . Plasma NGAL is an early predictive biomarker of AKI , morbidity , and mortality after pediatric CPB Acute kidney injury ( AKI ) has significant prognostic implication s for long-term outcomes in patients undergoing liver transplantation . In several retrospective studies , perioperative variables have been associated with AKI . These variables have been mainly associated with changes in creatinine concentrations over several days or months post-transplantation . To better define AKI , new markers have become available that help to identify patients at risk for renal injury within hours of a triggering insult . We prospect ively enrolled liver transplant patients at our institutions to evaluate neutrophil gelatinase-associated lipocalin ( NGAL ) , a marker of early renal injury , as a surrogate for AKI in patients undergoing liver transplantation . Blood was prospect ively collected at predetermined time points from 59 patients at 2 institutions . The electronic anesthesia records and the hospital computer data system were review ed for perioperative variables . Data collection included patient demographics , intraoperative variables such as fluid management , transfusion requirements , hemodynamics , and urine output . Subsequently , patients were grouped according to the presence of risk for developing AKI as defined by the RIFLE ( risk , injury , failure , loss , and end-stage kidney disease ) criteria . The difference between the NGAL concentration 2 hours after reperfusion and the baseline NGAL concentration was predictive of AKI in all patients , including patients with preexisting renal dysfunction . In patients with creatinine concentrations less than 1.5 mg/dL , a single NGAL determination 2 hours after reperfusion of the liver was associated with the development of AKI . Total occlusion of the inferior vena cava was associated with AKI . In conclusion , NGAL concentrations obtained during surgery were highly associated with postoperative AKI in patients undergoing liver transplantation . These findings will allow the design of larger interventional studies . Our findings regarding the impact of surgical techniques and glucose require validation in larger studies Urine neutrophil gelatinase-associated lipocalin ( uNGAL ) has shown promise as a biomarker for the early detection of acute kidney injury ( AKI ) in fixed models of injury , but its ability to predict AKI and provide prognostic information in critically ill adults is unknown . We prospect ively studied a heterogeneous population of 451 critically ill adults , 64 ( 14 % ) and 86 ( 19 % ) of whom developed AKI within 24 and 48 h of enrollment , respectively . Median uNGAL at enrollment was higher among patients who developed AKI within 48 h compared with those who did not ( 190 versus 57 ng/mg creatinine , P < 0.001 ) . The areas under the receiver operating characteristic curves describing the relationship between uNGAL level and the occurrence of AKI within 24 and 48 h were 0.71 ( 95 % Confidence Intervals [ CI ] : 0.63 to 0.78 ) and 0.64 ( 95 % CI : 0.57 to 0.71 ) , respectively . Urine neutrophil gelatinase-associated lipocalin remained independently associated with the development of AKI after adjustment for age , serum creatinine closest to enrollment , illness severity , sepsis , and intensive care unit ( ICU ) location , although it only marginally improved the predictive performance of the clinical model alone . A Cox proportional hazards model using time to first dialysis , adjusted for APACHE II score , suggested that uNGAL independently predicts severe AKI during hospitalization [ HR 2.60 , 95 % CI:1.55 to 4.35 ] . In summary , although a single measurement of uNGAL exhibited moderate predictive utility for the development and severity of AKI in a heterogeneous ICU population , its additional contribution to conventional clinical risk predictors appears limited Acute kidney injury ( AKI ) occurs commonly after pediatric cardiac surgery and associates with poor outcomes . Biomarkers may help the prediction or early identification of AKI , potentially increasing opportunities for therapeutic interventions . Here , we conducted a prospect i ve , multicenter cohort study involving 311 children undergoing surgery for congenital cardiac lesions to evaluate whether early postoperative measures of urine IL-18 , urine neutrophil gelatinase-associated lipocalin ( NGAL ) , or plasma NGAL could identify which patients would develop AKI and other adverse outcomes . Urine IL-18 and urine and plasma NGAL levels peaked within 6 hours after surgery . Severe AKI , defined by dialysis or doubling in serum creatinine during hospital stay , occurred in 53 participants at a median of 2 days after surgery . The first postoperative urine IL-18 and urine NGAL levels strongly associated with severe AKI . After multivariable adjustment , the highest quintiles of urine IL-18 and urine NGAL associated with 6.9- and 4.1-fold higher odds of AKI , respectively , compared with the lowest quintiles . Elevated urine IL-18 and urine NGAL levels associated with longer hospital stay , longer intensive care unit stay , and duration of mechanical ventilation . The accuracy of urine IL-18 and urine NGAL for diagnosis of severe AKI was moderate , with areas under the curve of 0.72 and 0.71 , respectively . The addition of these urine biomarkers improved risk prediction over clinical models alone as measured by net reclassification improvement and integrated discrimination improvement . In conclusion , urine IL-18 and urine NGAL , but not plasma NGAL , associate with subsequent AKI and poor outcomes among children undergoing cardiac surgery Background : Cardiopulmonary bypass ( CPB ) is associated with a significant risk of postoperative renal dysfunction . We studied the utility of a novel biomarker in predicting acute kidney injury ( AKI ) in adult patients undergoing cardiac surgery . Methods and Results : Blood and urine were obtained from 50 patients undergoing CPB-requiring surgery . Patients were divided into group A ( n = 41 ) with normal creatinine pre-bypass and post-bypass and group B ( n = 9 ) who developed an increase in serum creatinine of > 0.5 mg/dL within the first 48 hours post CPB . Plasma and urinary neutrophil gelatinase-associated lipocalin ( NGAL ) was determined at baseline and 2 hours after CPB . Plasma levels of NGAL were higher in patients who developed AKI [ 214 ± 16.7 ng/mL ( 95 % CI 176.9 - 252.9 ) ] compared with those who did not [ 149.5 ± 13.5 ng/mL ( 95 % CI 122.1 - 175.7 ) ; P = 0.035 ] . Two hours after CPB , there was a significant increase ( P = 0.0003 ) in NGAL levels , greater in those patients who developed AKI [ 476.1 ± 41.1 ng/mL ( 95 % CI 380.6 - 571.6 ) ; P = 0.0003 ] compared with those who did not [ 278.4 ± 22 ng/mL ( 95 % CI 233.9 - 323.0 ) ] . In the AKI group , urinary NGAL increased from 7.13 ± 2.30 ng/mL ( 95 % CI 2.5 - 11.8 ) to 2924 ± 786 ng/mL ( 95 % CI 1110 - 4739 ) . In the non-AKI group , there was an increase from 1.6 ± 0.6 ( 95 % CI 0.3 - 3.0 ) to 749 ± 179 ng/mL ( 95 % CI 386 - 1113 ) . The post-CPB levels of urinary NGAL were significantly different in the AKI group ( P < 0.0001 ) such that a suitable threshold for use as a diagnostic test could be determined . Receiver operating characteristics were determined for plasma and urinary NGAL with area under the curve ( AUC ) of 0.80 and 0.96 , respectively . For a threshold of 433 ng/mmol creatinine , the test had 90 % sensitivity and 78 % specificity for the detection of post-CPB renal dysfunction . Conclusions : Measurement of this novel biomarker in the urine or plasma of patients in the first hours after CPB is predictive of subsequent renal injury . Although the AUC for plasma NGAL seemed inferior to urine , even an AUC of 0.8 as reported compares very favorably to that for other “ outst and ing ” biomarkers ( eg , AUCs in the 0.7 range for troponin ) Current methods for predicting graft recovery after kidney transplantation are not reliable . We performed a prospect i ve , multicenter , observational cohort study of deceased-donor kidney transplant patients to evaluate urinary neutrophil gelatinase-associated lipocalin ( NGAL ) , IL-18 , and kidney injury molecule-1 ( KIM-1 ) as biomarkers for predicting dialysis within 1 wk of transplant and subsequent graft recovery . We collected serial urine sample s for 3 d after transplant and analyzed levels of these putative biomarkers . We classified graft recovery as delayed graft function ( DGF ) , slow graft function ( SGF ) , or immediate graft function ( IGF ) . Of the 91 patients in the cohort , 34 had DGF , 33 had SGF , and 24 had IGF . Median NGAL and IL-18 levels , but not KIM-1 levels , were statistically different among these three groups at all time points . ROC curve analysis suggested that the abilities of NGAL or IL-18 to predict dialysis within 1 wk were moderately accurate when measured on the first postoperative day , whereas the fall in serum creatinine ( Scr ) was not predictive . In multivariate analysis , elevated levels of NGAL or IL-18 predicted the need for dialysis after adjusting for recipient and donor age , cold ischemia time , urine output , and Scr . NGAL and IL-18 quantiles also predicted graft recovery up to 3 mo later . In summary , urinary NGAL and IL-18 are early , noninvasive , accurate predictors of both the need for dialysis within the first week of kidney transplantation and 3-mo recovery of graft function Acute kidney injury ( AKI ) is a frequent complication of cardiac surgery and increases morbidity and mortality . The identification of reliable biomarkers that allow earlier diagnosis of AKI in the postoperative period may increase the success of therapeutic interventions . Here , we conducted a prospect i ve , multicenter cohort study involving 1219 adults undergoing cardiac surgery to evaluate whether early postoperative measures of urine IL-18 , urine neutrophil gelatinase-associated lipocalin ( NGAL ) , or plasma NGAL could identify which patients would develop AKI and other adverse patient outcomes . Urine IL-18 and urine and plasma NGAL levels peaked within 6 hours after surgery . After multivariable adjustment , the highest quintiles of urine IL-18 and plasma NGAL associated with 6.8-fold and 5-fold higher odds of AKI , respectively , compared with the lowest quintiles . Elevated urine IL-18 and urine and plasma NGAL levels associated with longer length of hospital stay , longer intensive care unit stay , and higher risk for dialysis or death . The clinical prediction model for AKI had an area under the receiver-operating characteristic curve ( AUC ) of 0.69 . Urine IL-18 and plasma NGAL significantly improved the AUC to 0.76 and 0.75 , respectively . Urine IL-18 and plasma NGAL significantly improved risk prediction over the clinical models alone as measured by net reclassification improvement ( NRI ) and integrated discrimination improvement ( IDI ) . In conclusion , urine IL-18 , urine NGAL , and plasma NGAL associate with subsequent AKI and poor outcomes among adults undergoing cardiac surgery Background . This prospect i ve observational study aim ed to assess the relevance of serial postoperative plasma neutrophil gelatinase-associated lipocalin ( NGAL ) measurements on prediction of early renal transplant function . Methods . Plasma NGAL ( pNGAL ) was measured ( Triage NGAL Test ; Biosite Inc. , Inverness Medical ) in 41 patients scheduled for kidney transplantation from deceased or living donors , immediately before and after surgery , and at 12 hr , day 1 , day 3 , and day 7 . A delayed graft function ( DGF ) was defined as the need for dialysis during the first week . The results were expressed as median ( Q1 , Q3 ) . Results . Of the 41 consecutive patients enrolled , all had a high preoperative pNGAL level : 453 ng/mL ( 382 , 595 ) . Fifteen ( 36.6 % ) presented a DGF . In patients with DGF , pNGAL was significantly higher at 12 hr ( 571 [ 467 , 634 ] vs. 242 [ 158 , 299 ] ng/mL , P<0.0001 ) and at day 1 ( 466 [ 356 , 627 ] vs. 165 [ 91 , 248 ] ng/mL , P<0.0001 ) . A pNGAL higher than 400 ng/mL 12 hr after transplantation predicted DGF with a sensitivity of 93.3 % , a specificity of 88.5 % , and an odds ratio of 63.2 ( P=0.0004 ) . This predictive performance was higher than for plasma creatinine . Conclusions . pNGAL level early and accurately predicted DGF after renal transplantation . pNGAL measurements allowed monitoring of the renal function in this striking situation of ischemia-reperfusion aggression . Early identification of patients at risk of DGF , before graft lesions are consoli date d , opens the field of a precise monitoring of renal injury and the impact of future protective therapeutics Background / Aims : The value of neutrophil-gelatinase-associated lipocalin ( NGAL ) , a novel biomarker in the detection of acute renal failure in children after cardiac surgery , has been highlighted in previous studies . The incidence of percutaneous coronary intervention ( PCI ) increases , which may possibly result in increased incidences of contrast nephropathy , its potentially serious complication . Therefore , the aim of our study was to assess prospect ively NGAL in patients undergoing elective PCI in relation to serum creatinine . Methods : NGAL was assessed in the serum and urine using commercially available kits . Results : We measured urinary and serum NGAL before , and 2 , 4 , 12 , 24 and 48 h after PCI . We found a significant rise in serum NGAL 2 and 4 h after PCI , and a rise in urinary NGAL 4 and 12 h after PCI . Before PCI , serum NGAL was significantly associated with serum creatinine , urea , urinary NGAL , hemoglobin , hematocrit , albumin , age and presence of diabetes . In multivariate analysis , serum creatinine was the only predictor of serum NGAL . Serum NGAL 2 h after PCI correlated with serum creatinine , duration of PCI , HbA1c , hematocrit , hemoglobin and urinary NGAL . In multivariate analysis , the only predictors of serum NGAL 2 h after PCI were serum creatinine , time of PCI and HbA1c . Serum NGAL before PCI was significantly higher in diabetics than in non-diabetics . Conclusions : NGAL may represent a sensitive early biomarker of renal impairment after PCI . Serum creatinine , duration of PCI , but not type and amount of contrast agent , and appropriate treatment of diabetes , reflected by HbA1c , predict a rise in serum NGAL and kidney function following PCI BACKGROUND Proteinuria is an established marker of decreased kidney function after kidney transplant . It recently has been suggested that albuminuria might be a more reliable marker . Although albuminuria often is regarded as a marker of glomerular damage , because chronic renal allograft damage is believed to be predominantly an interstitial process , albuminuria in this case might reflect tubular damage . Accordingly , we investigated the value of albuminuria , proteinuria , and tubular damage markers ( KIM-1 [ kidney injury molecule 1 ] , NAG [ N-acetyl-β-d-glucosaminidase ] , NGAL [ neutrophil gelatinase-associated lipocalin ] , and H-FABP [ heart fatty acid binding protein ] ) in predicting graft outcome in kidney transplant recipients . STUDY DESIGN Prospect i ve observational cohort study . SETTING & PARTICIPANTS 606 patients visiting our outpatient kidney transplant clinic in 2001 - 2003 were included and used in the analysis for death-censored graft failure . Median follow-up was 4.7 ( 25th-75th percentile , 3.8 - 5.2 ) years . 577 patients had follow-up longer than 1 year and were included in the analysis for estimated glomerular filtration rate ( eGFR ) decrease . Median follow-up was 3.2 ( 25th-75th percentile , 2.7 - 3.7 ) years . PREDICTORS Urine protein , albumin , and tubular damage markers in 24-hour urine sample s. OUTCOMES Death-censored graft failure and decrease in eGFR . RESULTS There were 42 patients with graft failure ; mean eGFR change was -0.46 ± 3.7 ( st and ard deviation ) mL/min/1.73 m(2)/y . The area under the receiver operating characteristic curve for death-censored graft failure showed that albuminuria ( 0.78 ; 95 % CI , 0.59 - 0.76 ) was significantly higher than proteinuria ( 0.67 ; 95 % CI , 0.59 - 0.76 ; P = 0.001 ) , NGAL ( 0.63 ; 95 % CI , 0.52 - 0.74 ; P = 0.02 ) , and H-FABP ( 0.62 ; 95 % CI , 0.53 - 0.73 ; P = 0.005 ) and not significantly different from KIM-1 ( 0.74 ; 95 % CI , 0.66 - 0.82 ) and NAG ( 0.75 ; 95 % CI , 0.67 - 0.83 ) . Results were similar for the eGFR decrease outcome . LIMITATIONS Single-center observational study . CONCLUSIONS Measuring albuminuria may provide superior predictions for long-term renal outcomes after kidney transplant than total proteinuria . Additional assessment of urinary excretion of tubular damage markers may have limited value Background . About 30–50 % patients develop acute kidney injury ( AKI ) after cardiac surgery , which is still diagnosed by serum creatinine on clinic . However , the increase of serum creatinine is insensitive and delayed . The aim of this study is to test the hypothesis that neutrophil gelatinase-associated lipocalin ( NGAL ) and interleukin-18 ( IL-18 ) are early biomarkers for AKI in patients after cardiac surgery . Methods . Thirty-three cases undergoing cardiac surgery were classified into an AKI group and non-AKI group , according to the AKI definition ( > 26.5 μmol/L increase of serum creatinine , more than or equal to 50 % increase of serum creatinine within 48 h , or a reduction in urine output < 0.5 mL/Kg per hour for more than six hours ) . The concentrations of serum NGAL , urine NGAL , and urine IL-18 at different time-points were measured . Results . Nine cases ( 27.27 % ) developed postoperative AKI , but diagnosis with serum creatinine was 12–48 h postoperation . The concentrations of serum NGAL were not significantly increased postoperation . The concentrations of urine NGAL and IL-18 were significantly increased in the AKI group , which reached the peak at 2–4 h postoperation , and a more significant difference could be seen after correction for urine creatinine . The concentrations of urine NGAL and IL-18 2 h postoperation , either corrected for urine creatinine or not , showed good sensitivity and specificity . Increased levels of urine NGAL and IL-18 2 h postoperation were significantly correlated with increased level of serum creatinine 12 h postoperation . Logistic regression analysis showed that urine NGAL corrected for urine creatinine 2 h postoperation and urine IL-18 2 h postoperation emerged as powerful independent predictors of AKI after cardiac surgery . Conclusions . The concentrations of urine NGAL and IL-18 could be useful biomarkers for AKI in patients after cardiac surgery , especially after correction for urine creatinine BACKGROUND AND OBJECTIVES Several novel urinary biomarkers have shown promise in the early detection and diagnostic evaluation of acute kidney injury ( AKI ) . Clinicians have limited tools to determine which patients will progress to more severe forms of AKI at the time of serum creatinine increase . The diagnostic and prognostic utility of novel and traditional AKI biomarkers was evaluated during a prospect i ve study of 123 adults undergoing cardiac surgery . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Urinary neutrophil gelatinase-associated lipocalin ( NGAL ) , cystatin C ( CyC ) , kidney injury molecule-1 ( KIM-1 ) , hepatocyte growth factor ( HGF ) , π-glutathione-S-transferase ( π-GST ) , α-GST , and fractional excretions of sodium and urea were all measured at preoperative baseline , postoperatively , and at the time of the initial clinical diagnosis of AKI . Receiver operator characteristic curves were generated and the areas under the curve ( AUCs ) were compared . RESULTS Forty-six ( 37.4 % ) subjects developed AKI Network stage 1 AKI ; 9 ( 7.3 % ) of whom progressed to stage 3 . Preoperative KIM-1 and α-GST were able to predict the future development of stage 1 and stage 3 AKI . Urine CyC at intensive care unit ( ICU ) arrival best detected early stage 1 AKI ( AUC = 0.70 , P < 0.001 ) ; the 6-hour ICU NGAL ( AUC = 0.88 ; P < 0.001 ) best detected early stage 3 AKI . π-GST best predicted the progression to stage 3 AKI at the time of creatinine increase ( AUC = 0.86 ; P = 0.002 ) . CONCLUSION Urinary biomarkers may improve the ability to detect early AKI and determine the clinical prognosis of AKI at the time of diagnosis There is a need to develop early biomarkers of acute kidney injury following cardiac surgery , where morbidity and mortality are increased by its presence . Plasma cystatin C ( CyC ) and plasma and urine Neutrophil Gelatinase Associated Lipocalin ( NGAL ) have been shown to detect kidney injury earlier than changes in plasma creatinine in critically ill patients . In order to determine the utility of urinary CyC levels as a measure of kidney injury , we prospect ively collected plasma and urine from 72 adults undergoing elective cardiac surgery for analysis . Acute kidney injury was defined as a 25 % or greater increase in plasma creatinine or renal replacement therapy within the first 72 hours following surgery . Plasma CyC and NGAL were not useful predictors of acute kidney injury within the first 6 hours following surgery . In contrast , both urinary CyC and NGAL were elevated in the 34 patients who later developed acute kidney injury , compared to those with no injury . The urinary NGAL at the time of ICU arrival and the urinary CyC level 6 hours after ICU admission were most useful for predicting acute kidney injury . A composite time point consisting of the maximum urinary CyC achieved in the first 6 hours following surgery outperformed all individual time points . Our study suggests that urinary CyC and NGAL are superior to conventional and novel plasma markers in the early diagnosis of acute kidney injury following adult cardiac surgery |
954 | 20,802,345 | DISCUSSION S The current evidence suggests that selected patients with malignant pleural mesothelioma may benefit from EPP , especially when combined with neoadjuvant or adjuvant chemotherapy and adjuvant radiotherapy | INTRODUCTION The primary objective of the present systematic review was to evaluate the safety and efficacy of extrapleural pneumonectomy ( EPP ) for patients with malignant pleural mesothelioma . | BACKGROUND Malignant pleural mesothelioma is a mainly asbestos-related neoplasm that occurs with increasing frequency and is associated with a poor prognosis . Extrapleural pneumonectomy which was initially performed as a st and -alone treatment in patients with resectable disease is now currently almost uniformly applied as part of a multi-modal approach . Its value and advantage over other therapeutic strategies remain points of discussion . We therefore analysed our experience with extrapleural pneumonectomy in the treatment of malignant pleural mesothelioma . METHODS We retrospectively review ed our institutional experience with all consecutive patients undergoing extrapleural pneumonectomy for malignant pleural mesothelioma from 1994 to 2005 . Patients were analysed with regard to hospital mortality and morbidity and long-term outcome . RESULTS Forty-nine patients ( 10 female/39 male , mean age 58 + 12 years ) underwent extrapleural pneumonectomy during the observation period . Median ICU stay was 1 day , median postoperative length of hospital stay was 13 days . After a mean follow-up of 2573 days , median survival was 376 days ( mean 672 + 121 days , range 9 - 3384 ) . One-year survival was 53 % , 3-year survival 27 % and 5-year survival 19 % . CONCLUSION Extrapleural pneumonectomy as part of a multi-modality treatment regimen is a good treatment option for selected patients with malignant pleural mesothelioma . The long-term results of this limited series compare favourably to non-surgical treatment regimens . Larger r and omised prospect i ve multi-centre trials are warranted to establish clear guidelines BACKGROUND Trimodality therapy seems to be the best treatment for malignant pleural mesothelioma ( MPM ) . A large experience served to evaluate the efficacy of surgery followed by adjuvant chemo-radiotherapy . Trimodality therapy results have led us to test induction chemotherapy followed by EPP and adjuvant radiotherapy in stages I-III of MPM . The aim of our study was to evaluate the feasibility of this protocol and to estimate survival . METHODS From 2000 to 2003 , 21 patients with MPM ( 14 males and 7 females , median age 59 years ) were enrolled in the prospect i ve study . Induction chemotherapy consisted of Carboplatin ( AUC 5mg/mL/min on Day 1 ) and Gemcitabine ( 1000mg/m(2 ) on Days 1 , 8 , 15 ) for three to four cycles . EPP was performed 3 - 5 weeks after induction therapy , while post-operative RT was given 4 - 6 weeks after operation . RESULTS Ten patients received three cycles of chemotherapy , 10 patients received four cycles and 1 patient had two cycles . Grade s 3 - 4 haematological toxicity occurred in eight ( 38.1 % ) patients . Chemotherapy response rate was : complete 0 % , partial 33.3 % and stable disease 66.7 % . Seventeen ( 80.9 % ) out of 21 patients underwent EPP with no intra or post-operative mortality with an overall major and minor morbidity rate at 52.4 % . Median survival was 25.5 months , with an overall 1 , 3 and 5-year survival rate of 71 , 33 and 19 % , respectively . CONCLUSIONS In MPM , the combined modality approach using the Carboplatin/Gemcitabine combination as induction chemotherapy is feasible , with good results in terms of survival and morbidity . Our results are similar to those of other studies using a heavier modality treatment Aprotinin has been used to decrease blood loss with complicated cardiac surgery but has not been investigated in extrapleural pneumonectomy , an operation that does not use cardiopulmonary bypass . In this prospect i ve , r and omized , placebo‐controlled , double‐blind trial , the authors investigated whether aprotinin decreased blood loss in patients who underwent this operation Abstract Background : We analyzed morbidity and mortality , sites of recurrence , and possible prognostic factors in 95 ( 78 male , 17 female ) patients with MPM on phase I – III trials since 1990 . A debulking resection to a requisite , residual tumor thickness of ≤ 5 mm was required for inclusion . Methods : Preoperative tumor volumes were determined by three-dimensional reconstruction of chest computerized tomograms . Pleurectomy ( n=39 ) or extrapleural pneumonectomy ( EPP ; n=39 ) was performed . Seventeen patients could not be debulked . Preoperative EPP platelet counts ( 404,000 ) and mean tumor volume ( 491 cm3 ) were greater than that seen for pleurectomy ( 344,000 , 114 cm3 ) . Results : Median survival for all patients was 11.2 months , with that for pleurectomy 14.5 months , that for EPP 9.4 months , and that for unresectable patients 5.0 months . Arrhythmia ( n=14 ; 15 % ) was the most common complication , and there were two deaths related to surgery ( 2.0 % ) . Tumor volume of > 100 ml , biphasic histology , male sex , and elevated platelet count were associated with decreased survival ( p<0.05 ) . Both EPP and pleurectomy had equivalent recurrence rates ( 27 of 39 [ 69 % ] and 31 of 39 [ 79 % ] , respectively ) ; however , 17 of 27 EPP recurrences as opposed to 28 of 31 pleurectomy recurrences were locoregional ( p2=0.013 ) . Conclusions : Debulking resections for MPM can be performed with low operative mortality . Size and platelet count are important preoperative prognostic parameters for MPM . Patients with poor prognostic indicators should probably enter nonsurgical , innovative trials where toxicity or response to therapy can be evaluated BACKGROUND The factors influencing outcome after resection of malignant pleural mesothelioma ( MPM ) are controversial . This analysis of a prospect i ve surgical data base identifies important prognostic factors . METHODS Tumors were staged by the International Mesothelioma Interest Group staging system , and patients were followed until death . Prognostic factors were analyzed by log rank and Cox regression , and were considered significant if p was less than 0.05 . RESULTS From Oct 1983 to May 1998 , 231 patients underwent thoracotomy , 115 had extrapleural pneumonectomy ( EPP ) , and 59 pleurectomy/decortication ( P/D ) . Among patients having EPP or P/D , 142 received adjuvant therapy . The median survival for stage I tumors was 29.9 months , for stage II 19 months , for stage III 10.4 months , and for stage IV 8 months . By multivariate analysis , stage , histology , gender , adjuvant therapy , but not the type of surgical resection , were significant . CONCLUSIONS The better survival previously reported for P/D compared with EPP is not seen in a large data base with long follow-up . Stages I and II have better survival rates than generally assumed for MPM . Locally advanced T and N status , and nonepithelial histology , identify poor prognosis patients who should be considered for novel treatment regimens OBJECTIVE The authors examine the feasibility and efficacy of trimodality therapy in the treatment of malignant pleural mesothelioma and identify prognostic factors . BACKGROUND Mesothelioma is a rare , uniformly fatal disease that has increased in incidence in recent decades . Single and bimodality therapies do not improve survival . METHODS From 1980 to 1995 , 120 patients underwent treatment for pathologically confirmed malignant mesothelioma at Brigham and Women 's Hospital and Dana-Farber Cancer Institute ( Boston , MA ) . Initial patient evaluation was performed by a multimodality team . Patients meeting selection criteria and with resectable disease identified by computed tomography scan or magnetic resonance imaging underwent extrapleural pneumonectomy followed by combination chemotherapy and radiotherapy . RESULTS The cohort included 27 women and 93 men with a mean age of 56 years . Operative mortality rate was 5.0 % , with a major morbidity rate of 22 % . Overall survival rates were 45 % at 2 years and 22 % at 5 years . Two and 5-year survival rates were 65 % and 27 % , respectively , for patients with epithelial cell type , and 20 % and 0 % , respectively , for patients with sarcomatous or mixed histology tumors . Nodal involvement was a significant negative prognostic factor . Patients who were node negative with epithelial histology had 2- and 5-year survival rates of 74 % and 39 % , respectively . Involvement of margins at time of resection did not affect survival , except in the case of full-thickness , transdiaphragmatic invasion . Classification on the basis of a revised staging system stratified median survivals , which were 22 , 17 , and 11 months for stages I , II , and III , respectively ( p = 0.04 ) . CONCLUSIONS Extrapleural pneumonectomy with adjuvant therapy is appropriate treatment for selected patients with malignant mesothelioma selected using a revised staging system PURPOSE Patients with malignant pleural mesothelioma , a rapidly progressing malignancy with a median survival time of 6 to 9 months , have previously responded poorly to chemotherapy . We conducted a phase III trial to determine whether treatment with pemetrexed and cisplatin results in survival time superior to that achieved with cisplatin alone . PATIENTS AND METHODS Chemotherapy-naive patients who were not eligible for curative surgery were r and omly assigned to receive pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1 , or cisplatin 75 mg/m2 on day 1 . Both regimens were given intravenously every 21 days . RESULTS A total of 456 patients were assigned : 226 received pemetrexed and cisplatin , 222 received cisplatin alone , and eight never received therapy . Median survival time in the pemetrexed/cisplatin arm was 12.1 months versus 9.3 months in the control arm ( P = .020 , two-sided log-rank test ) . The hazard ratio for death of patients in the pemetrexed/cisplatin arm versus those in the control arm was 0.77 . Median time to progression was significantly longer in the pemetrexed/cisplatin arm : 5.7 months versus 3.9 months ( P = .001 ) . Response rates were 41.3 % in the pemetrexed/cisplatin arm versus 16.7 % in the control arm ( P < .0001 ) . After 117 patients had enrolled , folic acid and vitamin B12 were added to reduce toxicity , result ing in a significant reduction in toxicities in the pemetrexed/cisplatin arm . CONCLUSION Treatment with pemetrexed plus cisplatin and vitamin supplementation result ed in superior survival time , time to progression , and response rates compared with treatment with cisplatin alone in patients with malignant pleural mesothelioma . Addition of folic acid and vitamin B12 significantly reduced toxicity without adversely affecting survival time BACKGROUND The aim of this multicenter trial was to prospect ively evaluate neo-adjuvant chemotherapy followed by extrapleural pneumonectomy ( EPP ) and radiotherapy , including quality of life as outcome . PATIENTS AND METHODS Eligible patients had malignant pleural mesothelioma of all histological types , World Health Organization performance status of zero to two and clinical stage T1-T3 , N0 - 2 , M0 disease considered completely resectable . Neo-adjuvant chemotherapy consisted of three cycles of cisplatin and gemcitabine followed by EPP . Postoperative radiotherapy was considered for all patients . RESULTS In all , 58 of 61 patients completed three cycles of neo-adjuvant chemotherapy . Forty-five patients ( 74 % ) underwent EPP and in 37 patients ( 61 % ) the resection was complete . Postoperative radiotherapy was initiated in 36 patients . The median survival of all patients was 19.8 months [ 95 % confidence interval ( CI ) 14.6 - 24.5 ] . For the 45 patients undergoing EPP , the median survival was 23 months ( 95 % CI 16.6 - 32.9 ) . Psychological distress showed minor variations over time with distress above the cut-off score indicating no morbidity with 82 % ( N = 36 ) at baseline and 76 % ( N = 26 ) at 3 months after surgery ( P = 0.5 ) . CONCLUSIONS The observed rate of operability is promising . A median survival of 23 months for patients undergoing EPP compares favourably with the survival reported from single center studies of upfront surgery . This approach was not associated with an increase in psychological distress OBJECTIVE To report on the experience with radical surgery , with emphasis on the long-term outcome , for malignant pleural mesothelioma ( MPM ) at a single institution . METHODS From our prospect i ve data base over a 17-year period , we review ed 83 consecutive patients undergoing radical surgery for MPM in a multimodality programme . The long-term overall survival was analysed using the Kaplan-Meier method . RESULTS A total of 83 patients ( 65 males , median age : 60 years ) underwent an extra-pleural pneumonectomy ( EPP ) with a curative intent . Epitheliod MPM was the most frequent ( 82 % ) cause . A right-sided disease was present in half of the cases ( n=42 ) . The International Mesothelioma Interest Group ( IMIG ) stage of the disease was 2 in 36 % , 3 in 45 % and 4 in 9 % of the cases . Preoperative chemotherapy consisting of a doublet cisplatin-pemetrexed ( mean of three cycles ) was offered to 10 patients ( 12 % ) . Postoperative therapies , either chemotherapy or radiotherapy , were given in 25 patients ( 30 % ) . The 30-day and 90-day mortality rates were 4.8 % and 10.8 % , respectively . Postoperative complications occurred in 39.8 % and were major in 23 patients ( 27.7 % ) . Re-operation was necessary in 12 cases ( 14.5 % ) for one of the following reasons : broncho-pleural fistula ( n=4 ) , bleeding ( n=3 ) , diaphragmatic patch rupture ( n=3 ) , oesophago-pleural fistula ( n=1 ) and empyaema ( n=1 ) . The mean hospital stay was 43 days . The median survival was 14.5 months , while the overall 1- , 2- and 5-year survival rates were 62.4 % , 32.2 % and 14.3 % , respectively . CONCLUSIONS These results concur with the published data of the most experienced centre with regards to the mortality and morbidity after EPP for MPM . In line with the biggest series reported in the past , the observed 5-year survival rate of almost 15 % is disappointing PURPOSE To investigate neoadjuvant chemotherapy with cisplatin and gemcitabine followed by extrapleural pneumonectomy with or without radiation therapy in patients with potentially resectable malignant pleural mesothelioma ( MPM ) . PATIENTS AND METHODS Eligible patients had MPM with clinical stage T1 - 3 , N0 - 2 , M0 disease considered to be completely resectable and a WHO performance status of 0 to 2 . Neoadjuvant chemotherapy consisted of three cycles of cisplatin 80 mg/m2 on day 1 and gemcitabine 1,000 mg/m2 on days 1 , 8 , and 15 , given every 28 days . Surgery had to consist of a complete extrapleural pneumonectomy , including resection of pericardium and diaphragm . Postoperative radiotherapy was to be considered for all patients . RESULTS Nineteen patients with MPM were included in this pilot study . According to the European Organization for Research and Treatment of Cancer prognostic score , two patients were in the good prognosis group , and 17 patients were in the poor prognosis group . The response rate to neoadjuvant chemotherapy was 32 % . The major toxicity was thrombocytopenia . Extrapleural pneumonectomy was performed in 16 patients with no perioperative mortality . Major surgical complications occurred in six patients , and all were treated successfully . Thirteen patients received postoperative radiotherapy . The median survival time was 23 months . Two patients remain alive and free of disease 41 and 38 months after initiation of therapy . CONCLUSION For patients with potentially operable MPM , the availability of active and well-tolerated chemotherapy regimens , the fact that extrapleural pneumonectomy can be safely performed after neoadjuvant chemotherapy in an experienced center , and the promising results regarding survival in our pilot study warrant further investigation of the role of neoadjuvant chemotherapy in a multimodality strategy BACKGROUND The primary aim of this study was to evaluate prognostic features of long-term survivors with pleural mesothelioma . METHODS Overall survival outcome was analyzed in 456 patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy ( EPP ) , pleurectomy/decortications , or pleurodesis/biopsy with at least 18 months of follow-up . Prospect ively collected clinicopathologic and treatment data were assessed for their correlations with actual 18-month survivors in both univariate and multivariate analyses . RESULTS The actual 18-month survival was 28 % . Epithelial subtype was present in 185 patients ( 41 % ) and nonepithelial subtype in 183 ( 40 % ) . Procedures were EPP in 59 patients ( 13 % ) , pleurectomy/decortication in 250 ( 55 % ) , and pleurodesis/biopsy in 147 ( 32 % ) . Forty-two patients ( 9 % ) underwent positron emission tomography ( PET ) scanning . Forty patients ( 9 % ) received adjuvant radiotherapy and 45 ( 10 % ) received postoperative pemetrexed combination chemotherapy . In univariate analysis , age 65 years or younger ( p < 0.001 ) , malignant pleural effusion ( p = 0.041 ) , epithelial subtype ( p < 0.001 ) , EPP ( p < 0.001 ) , PET scan ( p = 0.012 ) , adjuvant radiotherapy ( p = 0.042 ) , and postoperative pemetrexed combination chemotherapy ( p = 0.035 ) were strongly associated with 18-month survivors . In multivariate analysis , epithelial histopathologic subtype ( p < 0.001 ) and EPP ( p < 0.001 ) were independently associated with 18-month survivors . CONCLUSIONS The actual 18-month survival was 28 % in 456 pleural mesothelioma patients who underwent operation . Epithelial histologic subtype and EPP were identified as independent predictors for 18-month survivors AIM Even though followed by a prolonged survival in highly selected patients , the promising results of Sugarbaker 's trimodality treatment for malignant pleural mesothelioma ( MPM ) are debated and not yet uniformly replicated . The purpose of this study is to evaluate prospect ively the reproducibility of the trimodality treatment results in a patient population with mesothelioma staged by the IMIG classification . METHODS Fifty-four patients with MPM have been judged c and idable to extended pleuropneumonectomy ( EPP ) , to be followed by chemotherapy ( paclitaxel+carboplatin ) and radiotherapy ( 50 Gy ) . RESULTS At thoracotomy , 44 of the 54 surgical c and i date s ( 81 % ) underwent EPP ; 73 % of the operated patients completed the entire adjuvant chemo-radiotherapy with no major toxicity . The 30-day or in-hospital operative mortality rate was 4.5 % ( 2 deaths ) , the major morbidity 36 % , and the overall complication rate 50 % . At 5 years the projected survival of the 42 surgical survivors su bmi tted to EPP is 19 % ; median survival is 20 months . The restricted group of patients with epithelial , N0 - 1 , completely resected MPM ( microscopic negative margins ) exhibits a projected 50 % 5-year survival . Clinical understaging has shown up to be noticeable both at the thoracotomy exploration and pathology examination . Most of the disease recurrences are loco-regional and the current insufficiency of intraoperative or postsurgical radicality needs improvement , along with earlier diagnosis , more accurate staging , and preoperative induction for the multimodality treatment of pleural mesothelioma to become an established curative option . CONCLUSIONS This series confirms the reproducibility of the trimodality treatment for MPM , which is associated with prolonged survival for early-stage tumors at the cost of a not prohibitive treatment-related mortality rate OBJECTIVE With the increasing incidence of malignant pleural mesothelioma and renewed interest in radical surgery as a therapeutic option , we have examined our experience of extra-pleural pneumonectomy , to document the incidence and management of its peri-operative complications . METHODS This analysis was conducted using prospect ively entered data contained within the departmental data base , with additional information from retrospective case note review . Details of patient selection criteria and operative modifications are included . RESULTS Over a 59-month period , extra-pleural pneumonectomy was carried out on 74 patients ( 66 men ; 8 women ; median age 57 years ) . Fifteen patients ( 20 % ) received cisplatin-doublet induction chemotherapy . The majority ( 80 % ) of patients had epithelial tumours and 85 % of patients had disease in International Mesothelioma Interest Group stages III and IV . The 30-day post-operative mortality was 6.75 % ( five patients ) and significant morbidity was recorded in 47 patients ( 63 % ) . Major complications included those of technical origin ( diaphragmatic patch dehiscence 8.1 % ; chylothorax 6.7 % ; intra-thoracic haemorrhage 6.7 % ; bronchopleural fistula 6.7 % ) , cardiovascular morbidity ( atrial fibrillation 17.5 % ; mediastinal shift with subacute tamponade 10.8 % ; right ventricular failure 4 % ; pulmonary embolus 2.7 % ) and respiratory morbidity ( pneumonia 10.8 % ; acute lung injury 8.1 % ) . Admission to intensive care was required in 19 patients ( 26 % ) . Univariate analysis identified the incidence of acute lung injury and mediastinal shift to be significantly associated with induction chemotherapy ( P=0.005 and 0.014 , respectively ) . In addition to this , laterality of operation influenced respiratory morbidity ( P=0.018 ) and admission to intensive care ( P=0.025 ) . Finally , prolonged operations ( greater than the median ) were associated with an increased risk of technical ( P=0.018 ) and gastro-intestinal ( P=0.023 ) complications . CONCLUSIONS Extra-pleural pneumonectomy is associated with a high rate of morbidity , but an acceptable mortality rate can be achieved with increasing peri-operative experience . Surgery following induction chemotherapy requires extra vigilance for the development of post-operative respiratory complications OBJECTIVES Our objective was to analyze the impact of preoperative and postresection solid tumor volumes on outcomes in 47 of 48 consecutive patients undergoing resection for malignant pleural mesothelioma who were treated prospect ively and r and omized to photodynamic therapy or no photodynamic therapy . METHODS From July 1993 to June 1996 , 48 patients with malignant pleural mesothelioma had cytoreductive debulking to 5 mm or less residual tumor by extrapleural pneumonectomy ( n = 25 ) or pleurectomy/decortication ( n = 23 ) . Three-dimensional computed tomographic reconstructions of preresection and postresection solid tumor were prospect ively performed and the disease was staged postoperatively according to the new International Mesothelioma Interest Group staging . RESULTS Median survival for all patients is 14.4 months ( extrapleural pneumonectomy , 11 months ; pleurectomy/decortication , 22 months ; p2 = 0.07 ) . Median survival for preoperative volume less than 100 was 22 months versus 11 months if more than 100 cc , p2 = 0.03 . Median survival for postoperative volume less than 9 cc was 25 months versus 9 months if more than 9 cc , p2 = 0.0002 . Thirty-two of forty-seven ( 68 % ) had positive N1 or N2 nodes . Tumor volumes associated with negative nodes were significantly smaller ( median 51 cc ) than those with positive nodes ( median 166 cc , p2 = 0.01 ) . Progressively higher stage was associated with higher median preoperative volume : stage I , 4 cc ; stage II , 94 cc ; stage III , 143 cc ; stage IV , 505 cc ; p2 = 0.007 for stage I versus II versus III versus IV . Patients with preoperative tumor volumes greater than 52 cc had shorter progression-free intervals ( 8 months ) than those 51 cc or less ( 11 months ; p2 = 0.02 ) . CONCLUSIONS Preresection tumor volume is representative of T status in malignant pleural mesothelioma and can predict overall and progression-free survival , as well as postoperative stage . Large volumes are associated with nodal spread , and postresection residual tumor burden may predict outcome Malignant pleural mesothelioma is usually a fatal cancer for which operation has been the mainstay of treatment because chemotherapy and radiation are relatively ineffective . The choice of operation for malignant pleural mesothelioma remains controversial . Extrapleural pneumonectomy has been advocated because it allows complete removal of gross tumor and can be associated with long-term survival . To evaluate extrapleural pneumonectomy , we conducted a prospect i ve multiinstitutional trial in patients with biopsy-proved previously untreated malignant pleural mesothelioma . Criteria for extrapleural pneumonectomy were ( 1 ) potentially completely resectable unilateral disease by computed tomography scan , ( 2 ) predicted postresection forced expiratory volume in 1 second greater than 1 L/sec , and ( 3 ) no other major medical problems . Patients who were not c and i date s for extrapleural pneumonectomy had a more limited operation with or without adjuvant therapy or had nonsurgical treatment . From September 1985 to June 1988 83 eligible patients ( 64 male , 19 female ) were entered . The mean age for all patients was 59.7 years . Only 20 of the 83 patients ( 24 % ) underwent extrapleural pneumonectomy . Three of these 20 patients ( 15 % ) died postoperatively . The recurrence-free survival was significantly longer for the patients undergoing extrapleural pneumonectomy than for the other two groups ( p = 0.03 ) , but there was no difference in overall survival among the three groups . In univariate analyses , epithelial versus sarcomatoid and mixed histologic findings and platelet count less than 400,000 were associated with a better overall survival ( p = 0.02 ) , and performance status ( Karnofsky less than 80 ) was predictive of recurrence ( p = 0.02 ) . In a multivariate analysis , histologic findings , sex , age , extrapleural pneumonectomy , weight loss , and performance status all had no significant impact on survival . Extrapleural pneumonectomy was associated with a greater likelihood of relapse in distant sites than were limited operation and nonsurgical treatment . We conclude that ( 1 ) only a small proportion of all patients with malignant pleural mesothelioma are c and i date s for extrapleural pneumonectomy , ( 2 ) extrapleural pneumonectomy carries a significant operative mortality and does not seem to improve overall survival compared with more conservative forms of treatment , ( 3 ) extrapleural pneumonectomy alters the patterns of relapse , and ( 4 ) factors previously thought to have an impact on survival in other series did not affect outcome in this trial Introduction : Trimodality therapy ( TMT ) , consisting of extrapleural pneumonectomy ( EPP ) , preoperative or postoperative combination chemotherapy , and high-dose hemithoracic radiotherapy , is the only therapy reported to achieve long-term survival in selected patients with malignant pleural mesothelioma ( MPM ) . Thus , TMT was introduced as an option for such patients in Western Australia in 2004 . However , TMT has never been compared with non-TMT therapy in the same patient population , thereby introducing a potential for selection bias . Method : We performed a retrospective review of all patients referred for TMT consisting of EPP , adjuvant chemotherapy , and hemithoracic radiotherapy at a quaternary referral institution . Patient eligibility for referral for TMT was based on patients ’ tolerability for pneumonectomy , epithelioid subtype , and computed tomography and positron emission tomography scanning indicating operable disease , with the exclusion of extrapleural lymphadenopathy and metastatic disease ( clinical stage T1 - 3N0 - 1M0 ) . Eligible patients consenting to TMT also underwent a surgical staging procedure ( bilateral thoracoscopy , mediastinoscopy , and laparoscopy ) to confirm eligibility before EPP . Results : Thirty-six patients have been referred for TMT since 2004 , and there has been a median of 27 months follow-up ; of 31 patients having surgical staging , eight were ineligible for EPP and one declined EPP . Of the 22 planned for EPP , 18 underwent EPP and four had unresectable disease at surgery . There was one death in hospital six days post-EPP and another death postdischarge and 28 days post-EPP ( 30-day mortality 11 % ) ; 15 of 16 EPP survivors received adjuvant chemotherapy and 14 completed adjuvant radiotherapy . Pathologic analysis of the 18 resected EPP specimens revealed N2 disease in seven patients ( 39 % ) and nonepithelioid subtype in six patients ( 33 % ) . Local recurrence did not occur among EPP survivors ; however , 56 % ( 9 of 16 patients ) developed distant recurrence . Median and 1-year survival did not differ between the 18 EPP patients and 18 non-EPP patients ( 20.4 versus 20.7 months and 76 versus 78 % , respectively ; p = NS ) . Discussion : In this case series , we could not demonstrate a survival benefit for patients in the EPP group compared with that in the non-EPP group . After surgical staging , 26 % of patients were ineligible for TMT . Thus , surgical staging is essential before proceeding with EPP . Despite aggressive imaging and surgical staging , 39 % of patients will have N2 disease and 18 % will have unresectable disease at operation . Although complete locoregional control was achieved with TMT , distant recurrence affected most EPP survivors despite careful patient selection and a high rate of completion of adjuvant therapy . We conclude that TMT for operable epithelioid MPM requires further assessment in r and omized controlled trials Introduction : Most studies describing the natural history and prognostic factors for malignant pleural mesothelioma ante date accurate pathologic diagnosis , staging by computed tomography , and a universal staging system . We conducted a large single-institution analysis to identify prognostic factors and assess the association of resection with outcome in a contemporary patient population . Methods : Patients with biopsy-proven malignant pleural mesothelioma at our institution were identified and clinical data were obtained from an institutional data base . Survival and prognostic factors were analyzed by the Kaplan-Meier method , log-rank test , and Cox proportional hazards analysis . A p value < 0.05 was considered statistically significant . Results : From 1990 to 2005 , 945 patients were identified : 755 men , 190 women ; median age , 66 years ( range , 26–93 ) . Extrapleural pneumonectomy was performed in 208 ( 22 % ) , pleurectomy/decortication in 176 ( 19 % ) . Operative mortality was 4 % ( 16/384 ) . Multimodality therapy including surgery was associated with a median survival of 20.1 months . Significant predictors of overall survival included histology , gender , smoking , asbestos exposure , laterality , surgical resection by extrapleural pneumonectomy or pleurectomy/decortication , American Joint Committee on Cancer stage , and symptoms . A Cox model demonstrated a hazard ratio of 1.4 without surgical resection when controlling for histology , stage , gender , asbestos exposure , smoking history , symptoms , and laterality ( p = 0.003 ) . Conclusions : In addition to tumor histology and pathologic stage , predictors of survival include gender , asbestos exposure , smoking , symptoms , laterality , and clinical stage . Surgical resection in a multimodality setting was associated with improved survival The Eastern Cooperative Oncology Group has conducted a retrospective review of their experience of 96 patients with a tissue diagnosis of malignant mesothelioma treated between 1972 and 1980 on four separate sarcoma chemotherapy protocol s. Thirty‐two of the 96 patients were diagnosed and treated in South Africa . There were 75 males and 21 females with an age range of 27 to 78 with a median of 58.1 years . All , except for 28 patients , had some form of prior therapy . The median time from the onset of symptoms to diagnosis was 12 weeks ; from the diagnosis to r and omization was 15.1 weeks . Only 12 of the 96 patients demonstrated an objective regression . The responses were 7/51 on Adriamycin with 2 complete responses ( complete responses—38 weeks and 52 weeks ) , 2/24 on Adriamycin combinations , 2/7 on cycloleucine , 1/3 on bleomycin , and 0/10 on non‐Adriamycin combinations . Only 1/28 responded to a cross‐over therapy ( Adriamycin ) . The median survival from the start of protocol chemotherapy was 7.4 months and 7.5 months for Adriamycin treated patients . The median survival for responders was 29.9 months , compared to 6.3 months for nonresponders . The median survival for this entire series from the time of first symptoms was 15.2 months . The median survival for the 7 patients with abdominal mesothelioma was 12 weeks . There was a slight improvement in survival for the South Africans as compared to the Americans . Malignant mesothelioma in this series , was a rapidly lethal , nonresponsive disease whose treatment will require new therapies . Cancer 52:1981‐1985 , 1983 Three-hundred thirty-two cases of pleural diffuse malignant mesothelioma ( DMM ) seen at large centers in Ontario and Quebec from 1965 to 1984 were review ed retrospectively . Previous asbestos exposure was found in 44 % of patients . Diagnosis was most often made by exploratory thoracotomy ; pleural biopsy or cytology were rarely contributory . The delay in diagnosis was often long ( median time , 3.5 months ) and thrombocytosis ( platelets greater than or equal to 400,000/microL ) was common ( 41 % of cases ) . The median survival ( MS ) was only 9 months . Eleven clinical variables were analyzed for prognostic significance . The three most important prognostic factors using a univariate analysis were stage , weight loss , and histologic type . For 118 patients with complete data , multivariate analysis showed that the stage of disease , high platelet count , and asbestos exposure were the most important prognostic factors . There was no cure of DMM , and we did not find any drastic differences in survival among groups of patients subjected to the different therapeutic measures . Radical surgery and radiotherapy were ineffective and we confirmed the low response rate to chemotherapeutic agents . This large retrospective trial can serve as a baseline for future studies in this field . In particular , it provides the basis for appropriate stratification variables to be used in future therapeutic trials BACKGROUND In patients with malignant pleural mesothelioma undergoing a multimodality therapy , treatment toxicity may outweigh the benefit of progression-free survival . The subjective experience across different treatment phases is an important clinical outcome . This study compares a st and ard with an individual quality of life ( QoL ) measure used in a multi-center phase II trial . PATIENTS AND METHODS Sixty-one patients with stage I-III technically operable pleural mesothelioma were treated with preoperative chemotherapy , followed by pleuropneumonectomy and subsequent radiotherapy . QoL was assessed at baseline , at day 1 of cycle 3 , and 1 , 3 and 6 months post-surgery by using the Rotterdam Symptom Checklist ( RSCL ) and the Schedule for the Evaluation of Quality of Life-Direct Weighting ( SEIQoL-DW ) , a measure that is based on five individually nominated and weighted QoL-domains . RESULTS Completion rates were 98 % ( RSCL ) and 92 % ( SEIQoL ) at baseline and 98%/89 % at cycle 3 , respectively . Of the operated patients ( N=45 ) RSCL and SEIQoL were available from 86%/72 % , 93%/74 % , and 94%/76 % at months 1 , 3 , and 6 post-surgery . Average assessment time for the SEIQoL was 24min compared to 8min needed for the RSCL . Median changes from baseline indicate that both RSCL QoL overall score and SEIQoL index remained stable during chemotherapy with a clinical ly significant deterioration ( change > or=8 points ) 1 month after surgery ( median change of -66 and -14 for RSCL and SEIQoL , respectively ) . RSCL QoL overall scores improved thereafter , but remained beneath baseline level until 6 months after surgery . SEIQoL scores improved to baseline-level at month 3 after surgery , but worsened again at month 6 . RSCL QoL overall score and SEIQoL index were moderately correlated at baseline ( r=.30 ; p < or=.05 ) and at 6-month follow-up ( r=.42 ; p < or=.05 ) but not at the other time points . CONCLUSION The SEIQoL assessment seems to be feasible within a phase II clinical trial , but may require more effort from staff . More distinctive QoL changes in accordance with clinical changes were measured with the RSCL . Our findings suggest that the two measures are not interchangeable : the RSCL is to favor when mainly information related to the course of disease- and treatment is of interest BACKGROUND Surgical resection of malignant pleural mesothelioma is reported to have up to an 80 % rate of local recurrence . We performed a phase II trial of high-dose hemithoracic radiation after complete resection to determine feasibility and to estimate rates of local recurrence and survival . METHODS Patients were eligible if they had a resectable tumor , as determined by computed tomographic scanning , and adequate cardiopulmonary function for extrapleural pneumonectomy or pleurectomy/decortication . After complete resection , patients received hemithoracic radiation ( 54 Gy ) and then were followed up with serial computed tomographic scanning . RESULTS From 1995 to 1998 , 88 patients ( 73 men and 15 women ; median age , 62.5 years ) were entered into the study . The operations performed included 62 extrapleural pneumonectomies ( 70 % ) and 5 pleurectomies/decortications ; procedures for exploration only were performed in 21 patients . Seven ( 7.9 % ) patients died postoperatively . Adjuvant radiation administered to 57 patients ( 54 undergoing extrapleural pneumonectomy and 3 undergoing pleurectomy/decortication ) at a median dose of 54 Gy was well tolerated ( grade 0 - 2 fatigue , esophagitis ) , except for one late esophageal fistula . The median survival was 33.8 months for stage I and II tumors but only 10 months for stage III and IV tumors ( P = .04 ) . For the patients undergoing extrapleural pneumonectomy , the sites of recurrence were locoregional in 2 , locoregional and distant in 5 , and distant only in 30 . CONCLUSION Hemithoracic radiation after complete surgical resection at a dose not previously reported is feasible . This approach dramatically reduces local recurrence and is associated with prolonged survival for early-stage tumors . Stage III disease has a high risk of early distant relapse and should be considered for trials of systemic therapy added to this regimen of resection and radiation OBJECTIVE We sought to prospect ively determine the feasibility and safety of hyperthermic intraoperative intracavitary cisplatin perfusion immediately after extrapleural pneumonectomy in the treatment of malignant pleural mesothelioma . METHODS Patients with malignant pleural mesothelioma who were surgical c and i date s underwent extrapleural pneumonectomy followed by hyperthermic intraoperative intracavitary cisplatin perfusion , consisting of a 1-hour lavage of the chest and abdomen with cisplatin ( 42 degrees C ) at 225 mg/m(2 ) . Pharmacologic cytoprotection consisted of intravenous sodium thiosulfate with or without amifostine . Morbidity and mortality were recorded prospect ively . RESULTS Ninety-six ( 79 % ) of 121 enrolled patients underwent extrapleural pneumonectomy , of whom 92 ( 76 % ) received hyperthermic intraoperative intracavitary cisplatin perfusion after extrapleural pneumonectomy . Fifty-three ( 58 % ) patients had epithelial tumors , and 39 ( 42 % ) had nonepithelial histology . Hospital mortality was 4.3 % . Morbidity ( grade 3 or 4 , 49 % ) included atrial fibrillation in 22 ( 23.9 % ) patients , venous thrombosis in 12 ( 13 % ) patients , and laryngeal nerve dysfunction in 10 ( 11 % ) patients . Nine patients had renal toxicity , which was attributable to cisplatin in 8 of them . Among the 27 patients who also received amifostine ( 910 mg/m(2 ) ) , 1 patient had grade 3 renal toxicity attributable to cisplatin . Recurrence of malignant pleural mesothelioma was documented in 47 ( 51 % ) patients , with ipsilateral recurrence in 17.4 % of patients . The median survival of the 121 enrolled patients was 12.8 months . CONCLUSIONS Hyperthermic intraoperative intracavitary cisplatin perfusion following extrapleural pneumonectomy can be performed with acceptable morbidity and mortality . The use of amifostine in addition to sodium thiosulfate might reduce cisplatin-associated renal toxicity . Hyperthermic intraoperative intracavitary cisplatin perfusion following extrapleural pneumonectomy might enhance local control in the chest Hypothesis : The effectiveness of extrapleural pneumonectomy ( EPP ) to extend quality -adjusted survival in malignant pleural mesothelioma within multimodality treatment should be proven in a r and omized controlled trial if this radical surgery is to be regarded as the st and ard of care . The question was whether r and omization to surgery versus no surgery would be possible . Methods : The Mesothelioma and Radical Surgery trial was planned to r and omize 50 patients to test feasibility . There was a two-stage consent process . At first consent , the patients who were possible c and i date s for radical surgery were registered into the trial for completion of assessment and staging . All received platinum-based chemotherapy . If still eligible , they completed a second consent to be r and omized to have either EPP followed by radical hemithorax radiotherapy or to have continued best care . Results : Patients were recruited through 11 collaborating centers in the United Kingdom . One hundred twelve potentially eligible patients gave informed consent to enter the registration phase and undergo chemotherapy . One died , 27 progressed , five were inoperable , four were treated off trial , and 18 withdrew either during or after chemotherapy but before final review . Additionally six were deemed inoperable at review after completing chemotherapy and one more patient withdrew . The remaining 50 were r and omized ; 24 to EPP and 26 to continued best care . Conclusions : In this study , 50/112 ( 45 % ) of patients entering the evaluation and induction phase of the trial went on to be r and omized . We have shown that this r and omization between surgery and no surgery is feasible . This was the primary aim of the Mesothelioma and Radical Surgery trial Malignant pleural mesothelioma has been considered a uniformly fatal disease associated with a median survival of 4 to 18 months . Extrapleural pneumonectomy alone has proved disappointing in the treatment of this disease , as have chemotherapy and radiotherapy . From 1980 to 1990 , 31 patients with pleural mesothelioma underwent multimodality therapy that included extrapleural pneumonectomy with resection of the pericardium and diaphragm . The age of the patients was 53.4 + /- 8.6 years ; 26 were male . All patients had the pathologic diagnosis review ed before treatment . At thoracotomy six patients had residual ( unresectable ) gross disease , and in 23 there was histologic evidence of disease at the resection margin . The perioperative morbidity and mortality rates were 19 % and 6 % , respectively . The mean length of hospital stay for the 29 patients who survived the operation was 10.9 + /- 3.5 days . Postoperatively 26 patients received cyclophosphamide , doxorubicin , and cis-platinum chemotherapy with or without radiotherapy . The survival rates were 70 % at 1 year and 48 % at 2 years . Trends toward improved survival in the patients with complete resections approached but did not reach statistical significance . These data suggest that this multimodality protocol can be administered with acceptable morbidity and mortality . Prospect i ve trials are justified to further clarify the role of this approach OBJECTIVE This study was undertaken to determine maximum tolerated dose and toxicity of intraoperative intracavitary hyperthermic cisplatin perfusion with amifostine after extrapleural pneumonectomy for malignant pleural mesothelioma . METHODS Patients with mesothelioma were prospect ively enrolled . Those with resectable disease received amifostine and 1-hour hyperthermic cisplatin perfusion of ipsilateral hemithorax and abdomen . Morbidity , recurrence , and survival were recorded . RESULTS Forty-two patients were enrolled ; 29 underwent resection ( operative mortality 7 % , 2/29 ) . Median age was 57 years . Eighteen were in pathologic stage I or II ; 11 were in stage III . Median hospitalization was 15 days . Common complications were atrial fibrillation ( 66 % , 19 patients ) , deep venous thrombosis ( 31 % , 9 patients ) , and grade 3 + renal toxicity ( 31 % , 9 patients ) . Feasibility was determined . Renal toxicity was unrelated to cisplatin dose , with no maximum tolerated dose determined . Overall median survival was 17 months ( resected 20 months , unresected 10 months ) . Median survivals were 26 months for patients receiving higher cisplatin doses and 16 months for those receiving lower doses ( P = .35 ) . Survival was significantly longer with negative extrapleural nodes ( 31 vs 14 months , P = .0115 ) and early stage ( all resected 35 months for stage I-II vs 14 months for stage III , P = .0022 , epithelial 39 months for stage I-II vs 15 months for stage III , P = .0072 ) . CONCLUSION Early stage and negative extrapleural lymph nodes were associated with prolonged survival . Single-dose amifostine did not protect adequately against cisplatin-induced renal toxicity . Additional cytoprotective strategies are needed to allow determination of cisplatin maximum tolerated dose PURPOSE Malignant pleural mesothelioma ( MPM ) remains associated with poor outcome . We examined the results of trimodality therapy with cisplatin-based chemotherapy followed by extrapleural pneumonectomy ( EPP ) and adjuvant high-dose ( 50 to 60 Gy ) hemithoracic radiation therapy for MPM . PATIENTS AND METHODS We conducted a retrospective review of all patients prospect ively evaluated for trimodality therapy protocol between January 2001 and December 2007 in our institution . RESULTS A total of 60 patients were suitable c and i date s. Histology was epithelioid ( n = 44 ) or biphasic ( n = 16 ) . Chemotherapy regimens included cisplatin/vinorelbine ( n = 26 ) , cisplatin/pemetrexed ( n = 24 ) , cisplatin/raltitrexed ( n = 6 ) , or cisplatin/gemcitabine ( n = 4 ) . EPP was performed in 45 patients , and hemithoracic radiation therapy to at least 50 Gy was administered postoperatively to 30 patients . Completion of the trimodality therapy in the absence of mediastinal node involvement was associated with the best survival ( median survival of 59 months v < or= 14 months in the remaining patients , P = .0003 ) . The type of induction chemotherapy had no significant impact on survival . Pathologic nodal status remained a significant predictor of poor survival despite completion of the trimodality therapy . After completion of the protocol , the 5-year disease-free survival was 53 % for patients with N0 disease , reaching 75 % in patients with ypT1 - 2N0 and 45 % in patients with ypT3 - 4N0 . CONCLUSION This large , single-center experience with induction chemotherapy followed by EPP and adjuvant high-dose hemithoracic radiation for MPM shows that half of the patients are able to complete this protocol . The results are encouraging for patients with N0 disease . However , N2 disease remains a major factor impacting on survival , despite completion of the entire trimodality regimen PURPOSE Neoadjuvant pemetrexed plus cisplatin was administered , followed by extrapleural pneumonectomy ( EPP ) and hemithoracic radiation ( RT ) , to assess the feasibility and efficacy of trimodality therapy in stage I to III malignant pleural mesothelioma . PATIENTS AND METHODS Requirements included stage T1 - 3 N0 - 2 disease , no prior surgical resection , adequate organ function ( including predicted postoperative forced expiratory volume in 1 second > or = 35 % ) , and performance status 0 to 1 . Patients received pemetrexed 500 mg/m(2 ) plus cisplatin 75 mg/m(2 ) for four cycles . Patients without disease progression underwent EPP followed by RT ( 54 Gy ) . The primary end point was pathologic complete response ( pCR ) rate . RESULTS Seventy-seven patients received chemotherapy . All four cycles were administered to 83 % of patients . The radiologic response rate was 32.5 % ( 95 % CI , 22.2 to 44.1 ) . Fifty-seven patients proceeded to EPP , which was completed in 54 patients . Three pCRs were observed ( 5 % of EPP ) . Forty of 44 patients completed irradiation . Median survival in the overall population was 16.8 months ( 95 % CI , 13.6 to 23.2 months ; censorship , 33.8 % ) . Patients completing all therapy had a median survival of 29.1 months and a 2-year survival rate of 61.2 % . Radiologic response of complete or partial response was associated with a median survival of 26.0 months compared with 13.9 months for patients with stable disease or progressive disease ( P = .05 ) . CONCLUSION This multicenter trial showed that trimodality therapy with neoadjuvant pemetrexed plus cisplatin is feasible with a reasonable long-term survival rate , particularly for patients who completed all therapy . Radiologic response to chemotherapy , but not sex , histology , disease stage , or nodal status , was associated with improved survival |
955 | 27,623,210 | There is moderate quality evidence that detection and treatment of chlamydia infection can reduce the risk of PID in women at individual level .
There is an absence of RCT evidence about the effects of chlamydia screening in pregnancy . | BACKGROUND Genital infections caused by Chlamydia trachomatis are the most prevalent bacterial sexually transmitted infection worldwide .
Screening of sexually active young adults to detect and treat asymptomatic infections might reduce chlamydia transmission and prevent reproductive tract morbidity , particularly pelvic inflammatory disease ( PID ) in women , which can cause tubal infertility and ectopic pregnancy .
OBJECTIVES To assess the effects and safety of chlamydia screening versus st and ard care on chlamydia transmission and infection complications in pregnant and non-pregnant women and in men . | Background High prevalence rates of Chlamydia trachomatis ( CT ) and Neisseria gonorrhoeae ( NG ) have been reported in Aboriginal people in remote and regional areas of Australia for well over two decades , and repeat positivity rates are high . To interrupt disease transmission and reduce the risk of complications , early diagnosis and treatment is important . However in many remote and regional areas there are long delays between testing for these curable sexually transmissible infections and providing treatment , due to both physical distance from laboratories and difficulties when recalling patients for subsequent management once results are available . Point-of-care ( POC ) tests have the potential to provide more timely diagnosis , to increase treatment and contact tracing , and in turn reduce CT and NG infection rates . Methods / design TTANGO ( Test , Treat , ANd GO ) is a cross-over cluster r and omised controlled trial in 12 regional or remote Australian health services , which predominantly provide clinical services to Aboriginal people . The overall aim of TTANGO is to measure the clinical effectiveness , cost-effectiveness and cultural and operational acceptability of molecular POC testing for CT and NG infection . The primary outcome is repeat positivity at three months after treatment of an initial CT or NG infection . Participating health services will undertake the clinical management of CT and NG under two different modalities for one year each . In the first year , six health services will be r and omly assigned to manage these infections under current diagnostic guidelines . The other six will supplement current diagnostic guidelines with POC testing , whereby diagnosis is made and subsequent treatment for those with positive POC tests is offered at the initial consultation . In the second year , the health services will cross over to the opposite management modality . TTANGO will be conducted over four years ; 1.5 years of trial initiation and community consultation , 2 years of trial conditions and evaluation , and 6 months of data analysis and feedback . Discussion TTANGO is the first cluster r and omised trial of POC testing for CT and NG internationally . The results of this trial will provide crucial information to guide sexual health clinical practice in remote Aboriginal communities and other high prevalence setting s . Trial registration Australian and New Zeal and Clinical Trials Registry Objective To evaluate the effectiveness of register based , yearly chlamydia screening . Design Controlled trial with r and omised stepped wedge implementation in three blocks . Setting Three regions of the Netherl and s : Amsterdam , Rotterdam , and South Limburg . Participants 317 304 women and men aged 16 - 29 years listed on municipal registers at start of trial . Intervention From March 2008 to February 2011 , the Chlamydia Screening Implementation programme offered yearly chlamydia screening tests . Postal invitations asked people to use an internet site to request a kit for self collection of sample s , which would then be sent to regional laboratories for testing . Treatment and partner notification were done by the general practitioner or at a sexually transmitted infection clinic . Main outcome measures Primary outcomes were the percentage of chlamydia tests positive ( positivity ) , percentage of invitees returning a specimen ( uptake ) , and estimated chlamydia prevalence . Secondary outcomes were positivity according to sex , age , region , and sociodemographic factors ; adherence to screening invitations ; and incidence of self reported pelvic inflammatory disease . Results The participation rate was 16.1 % ( 43 358/269 273 ) after the first invitation , 10.8 % after the second , and 9.5 % after the third , compared with 13.0 % ( 6223/48 031 ) in the control block invited at the end of round two of the intervention . Chlamydia positivity in the intervention blocks at the first invitation was the same as in the control block ( 4.3 % ) and 0.2 % lower at the third invitation ( odds ratio 0.96 ( 95 % confidence interval 0.83 to 1.10 ) ) . No substantial decreases in positivity were seen after three screening rounds in any region or sociodemographic group . Among the people who participated three times ( 2.8 % of all invitees ) , positivity fell from 5.9 % to 2.9 % ( odds ratio 0.49 ( 0.47 to 0.50 ) ) . Conclusions There was no statistical evidence of an impact on chlamydia positivity rates or estimated population prevalence from the Chlamydia Screening Implementation programme after three years at the participation levels obtained . The current evidence does not support a national roll out of this register based chlamydia screening programme . Trial registration NTR 3071 ( Netherl and s Trial Register , www.trialregister.nl ) Abstract Background High blood pressure in patients with stroke increases the risk of recurrence but management in the community is often inadequate . Home blood pressure monitoring may increase patients ' involvement in their care , increase compliance , and reduce the need for patients to attend their General Practitioner if blood pressure is adequately controlled . However the value of home monitoring to improve blood pressure control is unclear . In particular its use has not been evaluated in stroke patients in whom neurological and cognitive ability may present unique challenges . Design Community based r and omised trial with follow up after 12 months . Participants : 360 patients admitted to three South London Stroke units with stroke or transient ischaemic attack within the past 9 months will be recruited from the wards or out patients and r and omly allocated into two groups . All patients will be visited by the specialist nurse at home at baseline when she will measure their blood pressure and administer a question naire . These procedures will be repeated at 12 months follow up by another research er blind as to whether the patient is in intervention or control group . Intervention : Intervention patients will be given a vali date d home blood pressure monitor and support from the specialist nurse . Control patients will continue with usual care ( blood pressure monitoring by their practice ) . Main outcome measures in both groups after 12 months : 1 . Change in systolic blood pressure.2 . Cost effectiveness : Incremental cost of the intervention to the National Health Service and incremental cost per quality adjusted life year gained . Trial registration Clinical Trials.gov registration OBJECTIVE The objective of the study was to estimate whether midpregnancy genitourinary tract infection with Chlamydia trachomatis is associated with an increased risk of subsequent preterm delivery . STUDY DESIGN Infection with C. trachomatis was determined using a ligase chain reaction assay ( performed in batch after delivery ) of voided urine sample s collected at the r and omization visit ( 16(0/7 ) to 23(6/7 ) weeks ' gestation ) and the follow-up visit ( 24(0/7 ) to 29(6/7 ) weeks ) among 2470 gravide women with bacterial vaginosis or Trichomonas vaginalis infection enrolled in 2 multicenter r and omized antibiotic treatment trials ( metronidazole versus . placebo ) . RESULTS The overall prevalence of genitourinary tract C. trachomatis infection at both visits was 10 % . Preterm delivery less than 37 weeks ' or less than 35 weeks ' gestational age was not associated with the presence or absence of C. trachomatis infection at either the r and omization ( less than 37 weeks : 14 % versus 13 % , P=.58 ; less than 35 weeks : 6.4 % versus 5.5 % , P=.55 ) or the follow-up visit ( less than 37 weeks : 13 % versus 11 % , P=.33 ; less than 35 weeks : 4.4 % versus 3.7 , P=.62 ) . Treatment with an antibiotic effective against chlamydia infection was not associated with a statistically significant difference in preterm delivery . CONCLUSION In this secondary analysis , midtrimester chlamydia infection was not associated with an increased risk of preterm birth . Treatment of chlamydia was not associated with a decreased frequency of preterm birth The objective of this research was to identify determinants of the magnitude of intracluster correlation coefficients ( ICCs ) in cluster r and omized trials from the field of implementation research . A survey of experts was conducted to generate a priori hypotheses of factors that might affect ICC size . Hypotheses were tested on empirical estimates of ICCs calculated from 21 implementation research data sets , mainly from the UK . Effects of setting ( primary or secondary care ) , type of variable ( process or outcome ) , type of measurement ( objective or subjective ) , prevalence of outcome and size of cluster were tested . In total , 220 ICCs were available ( range 0 to 0.415 ) . Significant differences in ICC magnitude were found . The ICCs were significantly higher for process than for outcome variables , and for secondary care outcomes compared with primary care outcomes . The effects of prevalence and size were less clear cut . There was no evidence to suggest that type of measurement affected ICC size . In conclusion , accurate estimates of ICCs are essential for sample size calculations for cluster r and omized trials of professional behaviour change interventions . This study demonstrates that ICCs are sensitive to a number of trial factors , particularly setting and outcome type . These factors must be considered when planning such cluster r and omized trials OBJECTIVE To determine whether asking general practitioners to offer chlamydia screening at the same time as Pap screening increases chlamydia screening rates . DESIGN A pragmatic cluster r and omised controlled trial . PARTICIPANTS AND SETTING Doctors from 31 general practice s in the Australian Capital Territory performing more than 15 Pap smear screens per year , and all women aged 16 - 39 years attending those practitioners between 1 November 2004 and 31 October 2005 . INTERVENTION Doctors in the intervention practice s were asked to routinely offer combined chlamydia and Pap screening to eligible women ; doctors in the control practice s were asked to implement screening guidelines based on a risk assessment of the individual patient ( ie , usual practice ) . MAIN OUTCOME MEASURE Chlamydia screening rate per visit . RESULTS There were 26 876 visits by eligible women during the study period : 16 082 to intervention practice s and 10 794 to control practice s. Chlamydia screening occurred during 6.9 % ( 95 % CI , 6.5%-7.3 % ) of visits to intervention practice s and 4.5 % ( 95 % CI , 4.1%-4.9 % ) of visits to control practice s. After controlling for clustering and potential confounders , there were twofold greater odds of chlamydia screening occurring during a visit by an eligible woman to an intervention practice than to a control practice ( adjusted odds ratio , 2.1 [ 95 % CI , 1.3 - 3.4 ] ) . CONCLUSION Combining chlamydia and Pap screening increases the rate of chlamydia screening in general practice . Implementing this approach would require little additional infrastructure support in setting s where a cervical screening program already exists Background Sexual health problems such as unwanted pregnancy and sexually transmitted infection are important public health concerns and there is huge potential for health promotion using digital interventions . Evaluations of digital interventions are increasingly conducted online . Trial administration and data collection online offers many advantages , but concerns remain over fraudulent registration to obtain compensation , the quality of self-reported data , and high attrition . Objective This study addresses the feasibility of several dimensions of online trial design —recruitment , online consent , participant identity verification , r and omization and concealment of allocation , online data collection , data quality , and retention at 3-month follow-up . Methods Young people aged 16 to 20 years and resident in the United Kingdom were recruited to the “ Sexunzipped ” online trial between November 2010 and March 2011 ( n=2036 ) . Participants filled in baseline demographic and sexual health question naires online and were r and omized to the Sexunzipped interactive intervention website or to an information-only control website . Participants were also r and omly allocated to a postal request ( or no request ) for a urine sample for genital chlamydia testing and receipt of a lower ( £ 10/US$16 ) or higher ( £ 20/US$32 ) value shopping voucher compensation for 3-month outcome data . Results The majority of the 2006 valid participants ( 90.98 % , 1825/2006 ) were aged between 18 and 20 years at enrolment , from all four countries in the United Kingdom . Most were white ( 89.98 % , 1805/2006 ) , most were in school or training ( 77.48 % , 1545/1994 ) , and 62.81 % ( 1260/2006 ) of the sample were female . In total , 3.88 % ( 79/2036 ) of registration s appeared to be invalid and another 4.00 % ( 81/2006 ) of participants gave inconsistent responses within the question naire . The higher value compensation ( £ 20/US$32 ) increased response rates by 6 - 10 % , boosting retention at 3 months to 77.2 % ( 166/215 ) for su bmi ssion of online self-reported sexual health outcomes and 47.4 % ( 118/249 ) for return of chlamydia urine sample s by post . Conclusions It was quick and efficient to recruit young people to this online trial . Our procedures for obtaining online consent , verifying participant identity , automated r and omization , and concealment of allocation worked well . The optimal response rate for the online sexual health outcome measurement was comparable to face-to-face trials . Multiple methods of participant contact , requesting online data only , and higher value compensation increased trial retention at 3-month follow-up . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 55651027 ; http://www.controlled-trials.com/IS RCT N55651027 ( Archived by WebCite at http://www.webcitation.org/6LbkxdPKf ) Abstract Objective To evaluate whether a screening strategy in pregnancy lowers the rate of preterm delivery in a general population of pregnant women . Design Multicentre , prospect i ve , r and omised controlled trial . Setting Non-hospital based antenatal clinics . Participants 4429 pregnant women presenting for their routine prenatal visits early in the second trimester were screened by Gram stain for asymptomatic vaginal infection . In the intervention group , the women 's obstetricians received the test results and women received st and ard treatment and follow up for any detected infection . In the control group , the results of the vaginal smears were not revealed to the caregivers . Main outcome measures The primary outcome variable was preterm delivery at less than 37 weeks . Secondary outcome variables were preterm delivery at less than 37 weeks combined with different birth weight categories equal to or below 2500 g and the rate of late miscarriage . Results Outcome data were available for 2058 women in the intervention group and 2097 women in the control group . In the intervention group , the number of preterm births was significantly lower than in the control group ( 3.0 % v 5.3 % , 95 % confidence interval 1.2 to 3.6 ; P = 0.0001 ) . Preterm births were also significantly reduced in lower weight categories at less than 37 weeks and ≤ 2500 g. Eight late miscarriages occurred in the intervention group and 15 in the control group . Conclusion Integrating a simple infection screening programme into routine antenatal care leads to a significant reduction in preterm births and reduces the rate of late miscarriage in a general population of pregnant women Objective To determine whether screening and treating women for chlamydial infection reduces the incidence of pelvic inflammatory disease over the subsequent 12 months . Design R and omised controlled trial . Setting Common rooms , lecture theatres , and student bars at universities and further education colleges in London . Participants 2529 sexually active female students , mean age 21 years ( range 16 - 27 ) . Intervention Participants completed a question naire and provided self taken vaginal swabs , with follow-up after one year . Sample s were r and omly allocated to immediate testing and treatment for chlamydial infection , or storage and analysis after a year ( deferred screening controls ) . Main outcome measure Incidence of clinical pelvic inflammatory disease over 12 months . Results Baseline prevalence of chlamydia was 5.4 % ( 68/1254 ) in screened women and 5.9 % ( 75/1265 ) in controls . 94 % ( 2377/2529 ) of women were followed up after 12 months . The incidence of pelvic inflammatory disease was 1.3 % ( 15/1191 ) in screened women compared with 1.9 % ( 23/1186 ) in controls ( relative risk 0.65 , 95 % confidence interval 0.34 to 1.22 ) . Seven of 74 control women ( 9.5 % , 95 % confidence interval 4.7 % to 18.3 % ) who tested positive for chlamydial infection at baseline developed pelvic inflammatory disease over 12 months compared with one of 63 ( 1.6 % ) screened women ( relative risk 0.17 , 0.03 to 1.01 ) . However , most episodes of pelvic inflammatory disease occurred in women who tested negative for chlamydia at baseline ( 79 % , 30/38 ) . 22 % ( 527/2377 ) of women reported being tested independently for chlamydia during the trial . Conclusion Although some evidence suggests that screening for chlamydia reduces rates of pelvic inflammatory disease , especially in women with chlamydial infection at baseline , the effectiveness of a single chlamydia test in preventing pelvic inflammatory disease over 12 months may have been overestimated . Trial registration Clinical Trials.gov NCT00115388 OBJECTIVES ( 1 ) To compare the effectiveness of two clinical protocol s for the management of vaginal discharge in the situations where no laboratory facilities are available but speculum examination is possible and where basic laboratory facilities are available . ( 2 ) To determine clinical and simple laboratory indicators for diagnosis of patients with vaginal discharge in the local setting . DESIGN Alternate allocation of subjects to one of two management protocol s. SUBJECTS Women presenting to university gynaecology out patients department with a complaint of vaginal discharge . METHODS Subjects were alternately allocated management according to one of two protocol s : one without ( group A ) and one with ( group B ) immediate access to results of basic laboratory tests . Full clinical assessment including speculum examination and microbiological assessment for infection with gonorrhoea , chlamydia , c and ida , trichomonas , and bacterial vaginosis was performed on all women . Follow up assessment of clinical and microbiological response was performed 1 - 2 weeks later . RESULTS At initial assessment , both groups were similar in all respects except that more group B women had inflammation of the vulva . The prevalences of various conditions were : c and idiasis 22 % , bacterial vaginosis 38 % , trichomoniasis 4 % , chlamydia 4 % , gonorrhoea 0.4 % . There was no association between any demographic characteristic and diagnosis of cause of the discharge . Both protocol s result ed in clinical ly and statistically significant improvements for women with c and idiasis , bacterial vaginosis , and trichomoniasis . There were no clinical ly important differences in outcomes between the two protocol s. The sensitivities and specificities of various indicators were : curd-like vaginal discharge for c and idiasis , 72 % and 100 % ; homogeneous vaginal discharge for bacterial vaginosis or trichomoniasis , 94 % and 88 % ; absent or scanty lactobacilli for bacterial vaginosis , 99 % and 68 % ; > 20 % clue cells for bacterial vaginosis , 81 % and 99 % ; visible endocervical mucopus for chlamydia or gonorrhoea , 36 % and 86 % ; microscopic endocervical mucopus for chlamydia or gonorrhoea , 64 % and 69 % . CONCLUSIONS Both protocol s were equally effective in managing women with abnormal vaginal discharge . Simple clinical indicators for c and idiasis , bacterial vaginosis , or trichomonas as in protocol A are sufficiently sensitive and specific for use in situations with no laboratory support . A modification to protocol A could increase detection of bacterial vaginosis at basic health service level . Further work is needed to identify appropriate indicators for infection with chlamydia or gonorrhoea Study objective : To assess whether opportunistic and postal screening strategies for Chlamydia trachomatis can be compared with usual care in a r and omised trial in general practice . Design : Feasibility study for a r and omised controlled trial . Setting : Three West of Scotl and general medical practice s : one rural , one urban/deprived , and one urban/affluent . Participants : 600 women aged 16–30 years , 200 from each of three participating practice s selected at r and om from a sample of West of Scotl and practice s that had expressed interest in the study . The women could opt out of the study . Those who did not were r and omly assigned to one of three groups : postal screening , opportunistic screening , or usual care . Results : 38 % ( 85 of 221 ) of the approached practice s expressed interest in the study . Data were collected successfully from the three participating practice s. There were considerable workload implication s for staff . Altogether 124 of the 600 women opted out of the study . During the four month study period , 55 % ( 81 of 146 ) of the control group attended their practice but none was offered screening . Some 59 % ( 80 of 136 ) women in the opportunistic group attended their practice of whom 55 % ( 44 of 80 ) were offered screening . Of those , 64 % ( 28 of 44 ) accepted , representing 21 % of the opportunistic group . Forty eight per cent ( 59 of 124 ) of the postal group returned sample s. Conclusion : A r and omised controlled trial comparing postal and opportunistic screening for chlamydial infection in general practice is feasible , although re source intensive . There may be problems with generalising from screening trials in which patients may opt out from the offer of screening Background A selective , systematic , Internet-based , Chlamydia Screening Implementation for 16 to 29-year-old residents started in three regions in the Netherl and s in April 2008 : in the cities of Amsterdam and Rotterdam and a more rural region , South Limburg . This paper describes the evaluation design and discusses the implication s of the findings from the first screening round for the analysis . The evaluation aims to determine the effects of screening on the population prevalence of Chlamydia trachomatis after multiple screening rounds . Methods A phased implementation or ' stepped wedge design ' was applied by grouping neighbourhoods ( hereafter : clusters ) into three r and om , risk-stratified blocks ( A , B and C ) to allow for impact analyses over time and comparison of prevalences before and after one or two screening rounds . Repeated simulation of pre- and postscreening Chlamydia prevalences was used to predict the minimum detectable decline in prevalence . Real participation and positivity rates per region , block , and risk stratum ( high , medium , and low community risk ) from the 1st year of screening were used to substantiate predictions . Results The results of the 1st year show an overall participation rate of 16 % of 261,025 invitees and a positivity rate of 4.2 % , with significant differences between regions and blocks . Prediction by simulation methods adjusted with the first-round results indicate that the effect of screening ( minimal detectable difference in prevalence ) may reach significance levels only if at least a 15 % decrease in the Chlamydia positivity rate in the cities and a 25 % decrease in the rural region after screening can be reached , and pre- and postscreening differences between blocks need to be larger . Conclusions With the current participation rates , the minimal detectable decline of Chlamydia prevalence may reach our defined significance levels at the regional level after the second screening round , but will probably not be significant between blocks of the stepped wedge design . Evaluation will also include other aspects and prediction models to obtain rational advice about future Chlamydia screening in the Netherl and Background The advent of urine testing for Chlamydia trachomatis has raised the possibility of large-scale screening for this sexually transmitted infection , which is now the most common in the United Kingdom . The purpose of this study was to investigate the effect of an invitation to be screened for chlamydia and of receiving a negative result on levels of anxiety , depression and self-esteem . Methods 19,773 men and women aged 16 to 39 years , selected at r and om from 27 general practice s in two large city areas ( Bristol and Birmingham ) were invited by post to send home-collected urine sample s or vulvo-vaginal swabs for chlamydia testing . Question naires enquiring about anxiety , depression and self-esteem were sent to r and om sample s of those offered screening : one month before the dispatch of invitations ; when participants returned sample s ; and after receiving a negative result . Results Home screening was associated with an overall reduction in anxiety scores . An invitation to participate did not increase anxiety levels . Anxiety scores in men were lower after receiving the invitation than at baseline . Amongst women anxiety was reduced after receipt of negative test results . Neither depression nor self-esteem scores were affected by screening . Conclusion Postal screening for chlamydia does not appear to have a negative impact on overall psychological well-being and can lead to a decrease in anxiety levels among respondents . There is , however , a clear difference between men and women in when this reduction occurs INTRODUCTION Genitourinary Chlamydia trachomatis infection is common and associated with considerable personal and public health cost . Effective detection strategies are needed . AIM To assess feasibility of an opportunistic incentivised chlamydia screening programme in general practice over six months . METHODS This study was design ed as a pilot for a r and omised controlled trial in primary care . Three general practice s were r and omly allocated to intervention ( two practice s ) and control groups . The intervention involved practice education , self- sample collection and practice incentives ( funding and feedback ) for a three-month ' active ' intervention period . Feedback and education was discontinued during the second three-month period . Practice -specific nurse- or doctor-led strategies were developed for identifying , testing , treating and recalling male and female patients aged 16 - 24 years . The main outcome measure was the difference between the practice s ' chlamydia screening rates over the six months following introduction of the intervention , controlling for baseline rates from the previous year . RESULTS Chlamydia testing rates during the year prior to the intervention ranged from 2.9 % to 7.0 % of practice attendances by 16 - 24-year-olds . The intervention practice s had higher rates of screening compared with the control practice ( p<0.001 ) at three months , but both practice s reverted to pre-intervention rates by six months . The nurse-led screening strategy was more effective ( 35 % declining to 5.5 % over six months ) than the doctor-led strategy ( 15 % declining to 1.6 % over six months ) ( p=0.04 ) . DISCUSSION Incentivised opportunistic chlamydia screening of 16 - 24-year-old patients attending their general practitioner with a programme involving practice education , feedback and self- sample collection can increase screening rates CONTEXT Chlamydia trachomatis infection is a serious public health concern that disproportionately affects adolescent girls . Although annual C trachomatis screening of sexually active adolescent girls is recommended by health professional organizations and is a Health Employer Data and Information Set ( HEDIS ) performance measure , this goal is not being met . OBJECTIVE To test the effectiveness of a system-level , clinical practice improvement intervention design ed to increase C trachomatis screening by using urine-based tests for sexually active adolescent girls identified during their routine checkups at a pediatric clinic . DESIGN , SETTING , AND PARTICIPANTS A r and omized cluster of 10 pediatric clinics in the Kaiser Permanente of Northern California health maintenance organization , where adolescent girls aged 14 to 18 years had a total of 7920 routine checkup visits from April 2000 through March 2002 . INTERVENTION Five clinics were r and omly assigned to provide usual care and 5 to provide the intervention , which required that leadership be engaged by showing the gap between best practice and current practice ; a team be assembled to champion the project ; barriers be identified and solutions developed through monthly meetings ; and progress be monitored with site-specific screening proportions . MAIN OUTCOME MEASURE Chlamydia trachomatis screening rate for sexually active 14- to 18-year-old girls during routine checkups at each participating clinic . RESULTS The population of adolescents was ethnically diverse with an average age of 15.4 years . Twenty-four percent of girls in the experimental clinics and 23 % in the control clinics were sexually active . Of the 1017 patients eligible for screening in the intervention clinic , 478 ( 47 % ) were screened ; of 1194 eligible for screening in the control clinic , 203 ( 17 % ) were screened . At baseline , the proportion screened was 0.05 ( 95 % confidence interval [ CI ] , 0.00 - 0.17 ) in the intervention and 0.14 ( 95 % CI , 0.01 - 0.26 ) in the control clinics . By months 16 to 18 , screening rates were 0.65 ( 95 % CI , 0.53 - 0.77 ) in the intervention and 0.21 ( 95 % CI , 0.09 - 0.33 ) in the control clinics ( time period by study group interaction , F(6,60 ) = 5.33 ; P<.001 ) . The average infection rate for the experimental clinics was 5.8 % ( 23 positive test results out of 393 total urine tests and a total of 3986 clinic visits ) vs 7.6 % in controls ( 12 positive test results out of 157 tests and 3934 clinic visits ) . CONCLUSIONS Implementation of this clinical practice intervention in a large health maintenance organization system is feasible , and it significantly increased the C trachomatis screening rates for sexually active adolescent girls during routine checkups BACKGROUND Azithromycin or doxycycline is recommended for nongonococcal urethritis ( NGU ) ; recent evidence suggests their efficacy has declined . We compared azithromycin and doxycycline in men with NGU , hypothesizing that azithromycin was more effective than doxycycline . METHODS From January 2007 to July 2011 , English-speaking males ≥16 years , attending a sexually transmitted diseases clinic in Seattle , Washington , with NGU ( visible urethral discharge or ≥5 polymorphonuclear leukocytes per high-power field [ PMNs/HPF ] ) were eligible for this double-blind , parallel-group superiority trial . Participants received active azithromycin ( 1 g ) + placebo doxycycline or active doxycycline ( 100 mg twice daily for 7 days ) + placebo azithromycin . Urine was tested for Chlamydia trachomatis ( CT ) , Mycoplasma genitalium ( MG ) , Ureaplasma urealyticum biovar 2 ( UU-2 ) , and Trichomonas vaginalis ( TV ) using nucleic acid amplification tests . Clinical cure ( < 5 PMNs/HPF with or without urethral symptoms and absence of discharge ) and microbiologic cure ( negative tests for CT , MG , and /or UU-2 ) were determined after 3 weeks . RESULTS Of 606 men , 304 were r and omized to azithromycin and 302 to doxycycline ; CT , MG , TV , and UU-2 were detected in 24 % , 13 % , 2 % , and 23 % , respectively . In modified intent-to-treat analyses , 172 of 216 ( 80 % ; 95 % confidence interval [ CI ] , 74%-85 % ) receiving azithromycin and 157 of 206 ( 76 % ; 95 % CI , 70%-82 % ) receiving doxycycline experienced clinical cure ( P = .40 ) . In pathogen-specific analyses , clinical cure did not differ by arm , nor did microbiologic cure differ for CT ( 86 % vs 90 % , P = .56 ) , MG ( 40 % vs 30 % , P = .41 ) , or UU-2 ( 75 % vs 70 % , P = .50 ) . No unexpected adverse events occurred . CONCLUSIONS Clinical and microbiologic cure rates for NGU were somewhat low and there was no significant difference between azithromycin and doxycycline . Mycoplasma genitalium treatment failure was extremely common . Clinical Trials Registration .NCT00358462 OBJECTIVE Our purpose was to analyze ( 1 ) the effects of prevalent lower reproductive tract infections and ( 2 ) the effect of systematic diagnosis and treatment to reduce risks of early pregnancy loss ( < 22 weeks ) , preterm premature rupture of membrances , and overall preterm birth . STUDY DESIGN A prospect i ve , controlled treatment trial was conducted on 1260 women . During the first 7 months of the program ( observation , phase I ) , women were examined at initiation of prenatal care for a panel of lower genital tract microorganisms and bacterial vaginosis . Women were followed up with reexaminations at 22 to 29 weeks and after 32 weeks ' gestation . The recommended treatments of the Centers for Disease Control ( i.e. , 300 mg of clindamycin orally twice daily for 7 days for bacterial vaginosis ) were used for infected women during the second 8 months of the study ( treatment , phase II ) . Data were analyzed according to intent to treat by means of univariate and multivariate methods . RESULTS Overall , presence of bacterial vaginosis ( 32.5 % ) at enrollment was associated with pregnancy loss at < 22 weeks ' gestation ( relative risk 3.1 , 95 % confidence interval 1.4 to 6.9 ) . Among women in the observation phase bacterial vaginosis was associated with increased risk of both preterm birth ( relative risk 1.9 , 95 % confidence interval 1.2 to 3.0 ) and preterm premature rupture of membranes ( relative risk 3.5 , 95 % confidence interval 1.4 to 8.9 ) . Within this population ( phase I ) 21.9 % of preterm birth overall ( 43.8 % premature rupture of membranes ) is estimated as attributable to bacterial vaginosis . Among women with bacterial vaginosis phase II ( treatment ) was associated with reduced preterm birth ( relative risk 0.5 , 95 % confidence interval 0.3 to 0.9 ) ; there was a similar reduction for women with preterm premature rupture of membranes ( relative risk 0.5 , 95 % confidence interval 0.2 to 1.4 ) . Women with both bacterial vaginosis and trichomoniasis were at highest risk of preterm birth ( 28 % ) ; treatment of both conditions ( phase II ) reduced preterm birth ( 17 % ) but did not eliminate this risk . Earlier patient enrollment and oral antibiotic treatment were associated with reduced preterm birth . CONCLUSIONS This prospect i ve , controlled trial confirms that the presence of bacterial vaginosis is associated with increased risks of pregnancy loss at < 22 weeks , preterm premature rupture of membranes , and preterm birth . Orally administered clindamycin treatment is associated with a 50 % reduction of bacterial vaginosis-linked preterm birth and preterm premature rupture of membranes . Women at risk for preterm birth or preterm premature rupture of membranes because of bacterial vaginosis or common genital tract infections should be screened , treated , reevaluated for cure , and re-treated if necessary Objective : The purpose of this study was to determine if treatment of pregnant women with Chlamydia trachomatis infection would lower the incidence of preterm delivery and /or low birth weight . Methods : Pregnant women between the 23rd and 29th weeks of gestation were r and omized in double-blind fashion to receive either erythromycin 333 mg three times daily or an identical placebo . The trial continued until the end of the 35th week of gestation . Results : When the results were examined without regard to study site , erythromycin had little impact on reducing low birth weight ( 8 % vs. 11 % , P = 0.4 ) or preterm delivery ( 13 % vs. 15 % , P = 0.7 ) . At the sites with high persistence of C. trachomatis in the placebo-treated women , low birth weight infants occurred in 9 ( 8 % ) of 114 erythromycin-treated and 18 ( 17 % ) of 105 placebo-treated women ( P = 0.04 ) and delivery < 37 weeks occurred in 15 ( 13 % ) of 115 erythromycin-treated and 18 ( 17 % ) of 105 placebo-treated women ( P = 0.4 ) . Conclusions : The results of this trial suggest that the risk of low birth weight can be decreased by giving erythromycin to some women with C. trachomatis . Due to the high clearance rate of C. trachomatis in the placebo group , these data do not provide unequivocal evidence that erythromycin use in all C. trachomatis-infected women prevents low birth weight Background DNA amplification assays are increasingly being used to facilitate the testing of asymptomatic individuals for urogenital Chlamydia trachomatis . The long-term clinical benefit in terms of avoided infertility and ectopic pregnancy is unknown . Methods In 1997 , 15 459 women and 14 980 men aged 21–23 years were living in Aarhus County , Denmark . A r and om sample of 4000 women and 5000 men was contacted by mail and offered the opportunity to be tested for C trachomatis by means of a sample obtained at home and mailed directly to the laboratory . The remaining 11 459 women and 9980 men received usual care and constituted the control population . All men and women were subsequently followed for 9 years by the use of Danish health registers . Data were collected on pelvic inflammatory disease ( PID ) , ectopic pregnancy ( EP ) , infertility diagnoses , in-vitro fertilisation ( IVF ) treatment and births in women , and on epididymitis in men . The intervention and control groups were compared using Cox regression analyses and the intention-to-screen principle . Results Among women , no differences were found between the intervention group and the control group : HR ( 95 % CI ) for PID 1.12 ( 0.70 to 1.79 ) ; EP 0.97 ( 0.63 to 1.51 ) ; infertility 0.87 ( 0.71 to 1.07 ) ; IVF treatment 0.88 ( 0.62 to 1.26 ) and births 1.02 ( 0.95 to 1.10 ) . In men , the HR for epididymitis was 1.25 ( 0.70 to 2.24 ) . Conclusions A population -based offer to be tested for urogenital C trachomatis infection by the use of non-invasive sample s and DNA amplification did not reduce the long-term risk of reproductive complications in women or of epididymitis in men . Trial registration number in www . clinical trials.gov NCT 00827970 OBJECTIVES We sought to determine the effectiveness of a systems-based intervention design ed to increase Chlamydia trachomatis ( CT ) screening among adolescent boys . METHODS An intervention aim ed at increasing CT screening among adolescent girls was extended to adolescent boys ( 14 - 18 years ) . Ten pediatric clinics in a health maintenance organization with an ethnically diverse population were r and omized . Experimental clinics participated in a clinical practice improvement intervention ; control clinics received traditional information on screening . RESULTS The intervention significantly increased CT screening at the experimental sites from 0 % ( baseline ) to 60 % ( 18-month posttest ) ; control sites evidence d a change only from 0 % to 5 % . The overall prevalence of CT was 4 % . CONCLUSIONS Although routine CT screening is currently recommended only for young sexually active women , the present results show that screening interventions can be successful in the case of adolescent boys , among whom CT is a moderate problem Introduction . Group-r and omized trials ( GRTs ) are one of the most rigorous methods for evaluating the effectiveness of group-based health risk prevention programs . Efficiently design ing GRTs with a sample size that is sufficient for meeting the trial ’s power and precision goals while not wasting re sources exceeding them requires estimates of the intraclass correlation coefficient (ICC)—the degree to which outcomes of individuals clustered within groups ( e.g. , schools ) are correlated . ICC estimates vary widely depending on outcome , population , and setting , and small changes in ICCs can have large effects on the sample size needed to estimate intervention effects . This study addresses a gap in the literature by providing estimates of ICCs for adolescent sexual risk-taking outcomes under a range of study conditions . Method . Multilevel regression analyses were applied to existing data from four federally funded GRTs of school-based HIV/STI/pregnancy prevention programs to obtain a variety of ICC estimates . Results . ICCs ranged from 0 to 0.15 , with adjustment for covariates and repeated measurements reducing the ICC in the majority of cases . Minimum detectable effect sizes with 80 % power and 0.05 significance levels ranged from small to medium Cohen ’s d ( 0.13 to 0.53 ) assuming 20 schools of 100 students each . Conclusions . This study provides the first known set of ICC estimates for investigators to use when planning studies of school-based programs to prevent sexual risk behaviors in youth . The results provide further evidence of the importance of using the appropriate adjusted ICC estimate at the design stage to maximize re sources in costly GRTs In this cluster r and omised trial ( N=1060 ) , we tested the impact of financial incentives ( £ 5 voucher vs. £ 200 lottery ) framed as a gain or loss to promote Chlamydia screening in students aged 18 - 24 years , mimicking the st and ard outreach approach to student in halls of residence . Compared to the control group ( 1.5 % ) , the lottery increased screening to 2.8 % and the voucher increased screening to 22.8 % . Incentives framed as gains were marginally more effective ( 10.5 % ) that loss-framed incentives ( 7.1 % ) . This work fundamentally contributes to the literature by testing the predictive validity of Prospect Theory to change health behaviour in the field STUDY OBJECTIVE --The aim was to evaluate the effectiveness of a programme for the prevention of sexually transmitted diseases which affect fertility . DESIGN OF THE PREVENTION PROGRAMME -- The programme took place in six French geographical departments . Three of these , r and omly selected , served as experimental departments while the other three were matched with the first three and served as controls . DESIGN OF THE EVALUATION -- Genital discharge was used as the indicator of a sexually transmitted disease . In each department , about 40 voluntarily participating general practitioners ( 263 in total ) gathered information on the frequency of infected patients and on their characteristics , both before and after the campaign . PATIENTS --Before and after the programme respectively , 412 and 288 women and 117 and 94 men with a genital discharge were described . MEASUREMENTS AND MAIN RESULTS --After the programme , tests for chlamydia trachomatis were prescribed more often to both women and men with a discharge in the experimental departments . The characteristics of women having consulted a general practitioner with a discharge differed according to the department group studied . In the experimental departments , the women were younger than those in the control departments and had fewer sexual partners . In contrast to the results obtained for women , no behavioural changes were observed among men with a discharge . CONCLUSIONS --The results may indicate a decreased risk in spread of infection . Method ological problems associated with such a design are discussed . There is a need to develop specific messages aim ed at changing male sexual behaviour . The study design has implication s for the best strategy in delivering prevention messages to the general population which are relevant to the present AIDS epidemic Summary Background Previous community-r and omised trials of interventions to control sexually transmitted infections ( STIs ) have involved rural setting s , were rarely multicomponent , and had varying results . We aim ed to assess the effect of a multicomponent intervention on curable STIs in urban young adults and female sex workers ( FSWs ) . Methods In this community-r and omised trial , baseline STI screening was done between August , and November , 2002 , in r and om household sample s of young adults ( aged 18–29 years ) and in FSWs in Peruvian cities with more than 50 000 inhabitants . Geographically separate cities were selected , matched into pairs , and r and omly allocated to intervention or control groups with an S-PLUS program . Follow-up surveys of r and om sample s were done after 2 years and 3 years . The intervention comprised four modalities : strengthened STI syndromic management by pharmacy workers and clinicians ; mobile-team outreach to FSWs for STI screening and pathogen-specific treatment ; periodic presumptive treatment of FSWs for trichomoniasis ; and condom promotion for FSWs and the general population . Individuals in control cities received st and ard care . The composite primary endpoint was infection of young adults with Chlamydia trachomatis , Trichomonas vaginalis , or Neisseria gonorrhoeae , or syphilis seroreactivity . Laboratory workers and the data analyst were masked , but fieldworkers , the Peruvian study team , and participants in the outcome surveys were not . All analyses were done by intention to treat . This trial is registered , IS RCT N43722548 . Findings We did baseline surveys of 15 261 young adults in 24 Peruvian cities . Of those , 20 geographically separate cities were matched into pairs , in each of which one city was assigned to intervention and the other to st and ard of care . In the 2006 follow-up survey , data for the composite primary outcome were available for 12 930 young adults . We report a non-significant reduction in prevalence of STIs in young adults , adjusted for baseline prevalence , in intervention cities compared with control cities ( relative risk 0·84 , 95 % CI 0·69–1·02 ; p=0·096 ) . In subgroup analyses , significant reductions were noted in intervention cities in young adult women and FSWs . Interpretation Syndromic management of STIs , mobile-team outreach to FSWs , presumptive treatment for trichomoniasis in FSWs , and condom promotion might reduce the composite prevalence of any of the four curable STIs investigated in this trial . Funding Wellcome Trust and Burroughs Wellcome Fund , National Institutes of Health , Center for AIDS Research , CIPRA , and USAID-Peru 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 As part of a community-r and omized trial of a multicomponent intervention to prevent sexually transmitted infections , we created Mobile Teams ( MTs ) in ten intervention cities across Peru to improve outreach to female sex workers ( FSW ) for strengthened STI prevention services . Methods Throughout 20 two-month cycles , MTs provided counseling ; condoms ; screening and specific treatment for Neisseria gonorrhoeae ( NG ) , Chlamydia trachomatis ( CT ) , and vaginal Trichomonas vaginalis ( TV ) infections ; and periodic presumptive metronidazole treatment for vaginal infections . Results MTs had 48,207 separate encounters with 24,814 FSW ; numbers of sex work venues and of FSW reached increased steadily over several cycles . Approximately 50 % of FSW reached per cycle were new . Reported condom use with last client increased from 73 % to 93 % . Presumptive metronidazole treatment was accepted 83 % of times offered . Over 38 months , CT prevalence declined from 15·4 % to 8·2 % , and TV prevalence from 7·3 % to 2·6 % . Among participants in ≥9 cycles , CT prevalence decreased from 12·9 % to 6·0 % ( p < 0·001 ) ; TV from 4·6 % to 1·5 % ( p < 0·001 ) ; and NG from 0·8 % to 0·4 % ( p = 0·07 ) . Conclusions Mobile outreach to FSW reached many FSW not utilizing government clinics . Self-reported condom use substantially increased ; CT and TV prevalences declined significantly . The community-r and omized trial , reported separately , demonstrated significantly greater reductions in composite prevalence of CT , NG , TV , or high-titer syphilis serology in FSW in these ten intervention cities than in ten matched control cities Background As most genital Chlamydia trachomatis infections are asymptomatic , many patients do not seek health care for testing . Infections remain undiagnosed and untreated . We studied whether screening with information and home sampling result ed in more young people getting tested , diagnosed and treated for chlamydia in the three months following the intervention compared to the current strategy of testing in the health care system . Method We conducted a population based r and omized controlled trial among all persons aged 18–25 years in one Norwegian county ( 41 519 persons ) . 10 000 persons ( intervention ) received an invitation by mail with chlamydia information and a mail-back urine sampling kit . 31 519 persons received no intervention and continued with usual care ( control ) . All sample s from both groups were analysed in the same laboratory . Information on treatment was obtained from the Norwegian Prescription Data base ( NorPD ) . We estimated risk ratios and risk differences of being tested , diagnosed and treated in the intervention group compared to the control group . Results In the intervention group 16.5 % got tested and in the control group 3.4 % , risk ratio 4.9 ( 95 % CI 4.5 - 5.2 ) . The intervention led to 2.6 ( 95 % CI 2.0 - 3.4 ) times as many individuals being diagnosed and 2.5 ( 95 % CI 1.9 - 3.4 ) times as many individuals receiving treatment for chlamydia compared to no intervention in the three months following the intervention . Conclusion In Norway , systematic screening with information and home sampling results in more young people being tested , diagnosed and treated for chlamydia in the three months following the intervention than the current strategy of testing in the health care system . However , the study has not established that the intervention will reduce the chlamydia prevalence or the risk of complications from chlamydia . Trial registration Clinical Trials.gov Urogenital infections caused by Chlamydia trachomatis are common and may cause female infertility and ectopic pregnancy . Such infections are treatable but as C trachomatis often causes no symptoms they may remain undetected . As screening for C trachomatis reduces the number of complications,1 and self reportable screening criteria seem to have a low predictive value for infection,2 testing people not seeking medical care seems relevant . C trachomatis can be detected by amplification of DNA from urine and vaginal secretions— sample s that can be obtained at home and mailed directly to the laboratory . 3 4 Usually a swab sample is taken by a doctor but if a patient can collect a sample at home this may result in improved screening rates and thus more infections being detected . We r and omised all 17 high schools in Aarhus County into two screening groups . In the home sampling group the females were asked to collect two urine sample s and one vaginal flush sample 3 and the males were asked to collect one first OBJECTIVE To develop and evaluate an intervention to increase Chlamydia trachomatis ( CT ) screening among sexually active adolescent girls during pediatric urgent care . DESIGN Ten pediatric clinics were r and omly assigned to an intervention ( 5 clinics ) or control group ( 5 clinics ) . The proportion of sexually active girls screened for CT was estimated over 18 months ( April 2005-September 2006 ) . SETTING Large health maintenance organization in northern California . PARTICIPANTS Pediatric clinics providing urgent care services for adolescent girls aged 14 to 18 years . INTERVENTION In the intervention clinics , a team of providers and clinic staff met monthly to re design their clinic system to improve CT screening during urgent care . Controls received an informational lecture on CT screening . MAIN OUTCOME MEASURES Clinic-specific proportions of sexually active adolescent girls screened for CT . RESULTS The change over time in clinic-specific CT screening rates in urgent care was significantly greater in the intervention group than in the control group ( likelihood ratio , chi(2)(1 ) = 18.7 ; P < .001 ) . Between baseline and the fifth intervention period , the proportions of girls screened for CT increased by 15.93 % in the intervention group and decreased by 2.13 % in the comparison clinics . CONCLUSIONS The intervention significantly improved the proportion of adolescent girls screened for CT during urgent care . Despite this success , substantial barriers to screen for CT in urgent care remain . Innovative strategies to provide basic information about CT , other sexually transmitted infections , and pregnancy are greatly needed since many teens are never seen for preventive care in a given year Background Repeat infection with Chlamydia trachomatis is common and increases the risk of sequelae in women and HIV seroconversion in men who have sex with men ( MSM ) . Despite guidelines recommending chlamydia retesting three months after treatment , retesting rates are low . We are conducting the first r and omised controlled trial to assess the effectiveness of home collection combined with short message service ( SMS ) reminders on chlamydia retesting and reinfection rates in three risk groups . Methods / Design The REACT ( retest after Chlamydia trachomatis ) trial involves 600 patients diagnosed with chlamydia : 200 MSM , 200 women and 200 heterosexual men recruited from two Australian sexual health clinics where SMS reminders for retesting are routine practice . Participants will be r and omised to the home group ( 3-month SMS reminder and home- collection ) or the clinic group ( 3-month SMS reminder to return to the clinic ) . Participants in the home group will be given the choice of attending the clinic if they prefer . The mailed home- collection kit includes a self-collected vaginal swab ( women ) , UriSWAB ( Copan ) for urine collection ( heterosexual men ) , and UriSWAB plus rectal swab ( MSM ) . The primary outcome is the retest rate at 1 - 4 months after a chlamydia diagnosis , and the secondary outcomes are : the repeat positive test rate ; the reinfection rate ; the acceptability of home testing with SMS reminders ; and the cost effectiveness of home testing . Sexual behaviour data collected via an online survey at 4 - 5 months , and genotyping of repeat infections , will be used to discriminate reinfections from treatment failures . The trial will be conducted over two years . An intention to treat analysis will be conducted . Discussion This study will provide evidence about the effectiveness of home- collection combined with SMS reminders on chlamydia retesting , repeat infection and reinfection rates in three risk groups . The trial will determine client acceptability and cost effectiveness of this strategy .Trial registration Australian and New Zeal and Clinical Trials Registry ACTRN12611000968976 Background : Few data exist on potential harms of chlamydia screening . We assessed the psychosocial impact of receiving a positive Chlamydia trachomatis test result . Methods : We prospect ively studied women ≥16 years of age undergoing chlamydia testing in 2 Midwestern family planning clinics . We surveyed women at baseline and about 1 month after receiving test results , using 9 vali date d psychosocial scales/subscales and chlamydia-specific questions . Changes in scale scores were calculated for each woman . Mean percent changes in scores for chlamydia-positive and -negative women were compared using a t test . Results : We enrolled 1807 women ( response rate , 84 % ) . Of the 1688 women with test results , 149 ( 8.8 % ) tested positive . At follow-up , chlamydia-positive women ( n = 71 ) had a 75 % increase in anxiety about sexual aspects of their life on the Multidimensional Sexual Self-Concept Question naire ( P < 0.001 ) , significantly greater than the 26 % increase among 280 r and omly selected chlamydia-negative women ( P = 0.02 ) . There were no differences for the other 8 scales/subscales , including general measures of anxiety , depression , and self-esteem . Chlamydia-positive women were more likely than chlamydia-negative women to be “ concerned about chlamydia ” ( 80 % vs. 40 % , P < 0.001 ) and to report breaking up with a main partner ( 33 % vs. 11 % , P < 0.001 ) at follow-up . Women testing positive reported a range of chlamydia-specific concerns . Conclusions : Chlamydia-positive women had significant increases in anxiety about sex and concern about chlamydia , but did not have marked changes in more general measures of psychosocial well-being about 1 month after diagnosis . Chlamydia diagnoses were associated with some disruption of relationships with main partners . Chlamydia-specific concerns may guide counseling messages to minimize psychosocial impact 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 evaluate the feasibility and efficacy of population -based outreach strategies to improve genital Chlamydia trachomatis ( CT ) screening in men . Study Design : In a r and omized trial , male enrollees ages 21–25 ( n = 8820 ) were selected from the automated files of Group Health Cooperative and r and omized to : a letter + test-request card for a CT urine home sampling kit ( arm 1 , n = 2940 ) ; a letter + mail-back sampling kit ( arm 2 , n = 2940 ) ; or a usual care control ( arm 3 , n = 2940 ) . One reminder was sent to arms 1 and 2 . The outcome was CT testing rates in the 4 months postr and omization . Results : 105 of 2940 ( 3.6 % ) men in arm 1 and 230 of 2940 ( 7.8 % ) in arm 2 returned mailed specimens . All 335 respondents were sexually experienced , 43 % had > 2 sex partners in the past year , and 80 % reported no genitourinary symptoms . Compared to arm 3 , the relative risk of being tested was 5.6 ( 95 % confidence interval ( CI ) 3.6–8.7 ) for arm 1 and 11.1 ( 95 % CI 7.3–16.9 ) for arm 2 . Arm 2 was significantly more likely to be tested than arm 1 . CT prevalence for mailed-back specimens was 1.0 % ( 1 of 105 ) for arm 1 and 2.6 % ( 6 of 230 ) for arm 2 ; 70 % of all positive intervention tests were from mailed sample s. Conclusions : Both strategies result ed in significantly higher CT testing than usual care , but the intervention response rate was low ( 5.7 % overall ) . Direct kit mailing performed best . In US population s , the value of mailed outreach strategies to men must be considered in the context of other CT screening priorities 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 Few studies have estimated Chlamydia trachomatis ( CT ) prevalence in the general population , most prevalence studies being based on people already attending healthcare setting s. Objectives To estimate the prevalence of CT in France , assess the feasibility of home sampling without any face-to-face intervention and identify risk factors associated with CT infection using data from the Context e de la Sexualité ( CSF ) survey on sexual behaviour ; a national population -based survey , carried out by telephone in 2006 . Methods A r and om sub sample of sexually experienced people aged 18–44 ( N=4957 ) were invited to participate in a CT home-sampling study ( NatChla study ) . Participants ' sample s were tested for CT by PCR . Percentages were weighted for unequal selection probabilities and post-stratified based on French population census data . Independent risk factors were identified by logistic regression . Results CT prevalence in people aged 18–44 was estimated at 1.4 % ( 95 % CI 0.8 % to 2.6 % ) for men , and 1.6 % ( 95 % CI 1.0 % to 2.5 % ) for women . Increased rates were found in subjects aged 18–29 : 2.5 % ( 95 % CI 1.2 % to 5.0 % ) for men and 3.2 % ( 95 % CI 2.0 % to 5.3 % ) for women . CT infection was associated , for both genders , with having their last sexual intercourse with a casual partner . Other risk factors were for men , having last intercourse with a new partner , living in the Paris area , and for women , multiple partners during the previous year , same sex partners and a low level of education . Conclusions CT prevalence in France is similar to that in other developed countries . Home sampling proved feasible and useful to reach members of the population with limited access to traditional care CONTEXT Chlamydial and gonococcal infections are important causes of pelvic inflammatory disease , ectopic pregnancy , and infertility . Although screening for Chlamydia trachomatis is widely recommended among young adult women , little information is available regarding the prevalence of chlamydial and gonococcal infections in the general young adult population . OBJECTIVE To determine the prevalence of chlamydial and gonococcal infections in a nationally representative sample of young adults living in the United States . DESIGN , SETTING , AND PARTICIPANTS Cross-sectional analyses of a prospect i ve cohort study of a nationally representative sample of 14,322 young adults aged 18 to 26 years . In-home interviews were conducted across the United States for Wave III of The National Longitudinal Study of Adolescent Health ( Add Health ) from April 2 , 2001 , to May 9 , 2002 . This study sample represented 66.3 % of the original 18,924 participants in Wave I of Add Health . First-void urine specimens using ligase chain reaction assay were available for 12,548 ( 87.6 % ) of the Wave III participants . MAIN OUTCOME MEASURES Prevalences of chlamydial and gonococcal infections in the general young adult population , and by age , self-reported race/ethnicity , and geographic region of current residence . RESULTS Overall prevalence of chlamydial infection was 4.19 % ( 95 % confidence interval [ CI ] , 3.48%-4.90 % ) . Women ( 4.74 % ; 95 % CI , 3.93%-5.71 % ) were more likely to be infected than men ( 3.67 % ; 95 % CI , 2.93%-4.58 % ; prevalence ratio , 1.29 ; 95 % CI , 1.03 - 1.63 ) . The prevalence of chlamydial infection was highest among black women ( 13.95 % ; 95 % CI , 11.25%-17.18 % ) and black men ( 11.12 % ; 95 % CI , 8.51%-14.42 % ) ; lowest prevalences were among Asian men ( 1.14 % ; 95 % CI , 0.40%-3.21 % ) , white men ( 1.38 % ; 95 % CI , 0.93%-2.03 % ) , and white women ( 2.52 % ; 95 % CI , 1.90%-3.34 % ) . Prevalence of chlamydial infection was highest in the south ( 5.39 % ; 95 % CI , 4.24%-6.83 % ) and lowest in the northeast ( 2.39 % ; 95 % CI , 1.56%-3.65 % ) . Overall prevalence of gonorrhea was 0.43 % ( 95 % CI , 0.29%-0.63 % ) . Among black men and women , the prevalence was 2.13 % ( 95 % CI , 1.46%-3.10 % ) and among white young adults , 0.10 % ( 95 % CI , 0.03%-0.27 % ) . Prevalence of coinfection with both chlamydial and gonococcal infections was 0.030 % ( 95 % CI , 0.18%-0.49 % ) . CONCLUSIONS The prevalence of chlamydial infection is high among young adults in the United States . Substantial racial/ethnic disparities are present in the prevalence of both chlamydial and gonococcal infections Background : Chlamydia notifications are increasing in Australia , and the use of a computer alert prompting general practitioners to test young women is a potential way to increase opportunistic chlamydia testing . The aim of this trial was to determine the effectiveness of a computer alert in general practice on chlamydia testing in young women . Methods : In 2006 , clinics ( n = 68 ) in Melbourne , Australia were cluster r and omized into 2 groups : the intervention group received a computerized alert advising the general practitioner to discuss chlamydia testing with their patient which popped up when the medical record of a 16- to 24-year-old woman was opened ; the control group received no alert . The outcome was whether or not that patient received a chlamydia test at the level of a single consultation with an eligible patient . A mixed effects logistic regression model adjusting for clustering was used to assess the impact of the alert on the proportion of women tested for chlamydia during the trial period . Results : Testing increased from 8.3 % ( 95 % confidence interval ( CI ) : 6.8 , 9.8 ) to 12.2 % ( 95 % CI : 9.1 , 15.3 ) ( P < 0.01 ) in the intervention group , and from 8.8 % ( 95 % CI : 6.8 , 10.7 ) to 10.6 % ( 95 % CI : 8.5 , 12.7 ) ( P < 0.01 ) in the control group . Overall , the intervention group had a 27 % ( OR = 1.3 ; 95 % CI : 1.1 , 1.4 ) greater increase in testing . Conclusion : The results of this study suggest that alerts alone may not be sufficient to get chlamydia testing levels up sufficiently high enough to have an impact on the burden of chlamydia in the population but that they could be included as part of a more complex intervention 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 Objective : To test the utility of screening the urine sample s used to diagnose pregnancies at urban teen clinics for Chlamydia trachomatis and Neisseria gonorrhoeae by polymerase chain reaction ( PCR ) . We hypothesized that urine screening would increase the proportion of teenagers treated for these two sexually transmitted diseases ( STDs ) before they initiated pregnancy-related care . Design : A r and omly selected subset of the urine sample s used to diagnose 212 teen pregnancies were tested for C. trachomatis and N. gonorrhoeae by PCR . Endocervical testing was at the providers ' discretion . Bivariate analyses were used to compare the teenagers r and omized to the urine screening group ( n = 102 ) and the non-screening group ( n = 110 ) . Results : Of the 102 urine PCR tests , 14 ( 13.7 % ) were positive . Endocervical swabs were obtained in 31 ( 14.6 % ) of the 212 teenagers and five ( 16.1 % ) were positive . Since pelvic examinations were performed so infrequently , the net endocervical swab detection rate was significantly lower than the urine-based detection rate ( 1.8 % compared to 13.7 % ; p = 0.001 ) . Only one infected teenager was untreated when she initiated pregnancy-related care . Thus , the treatment rate was more than six times higher when urine sample s were screened ( 12.7 % compared to 1.8 % ; p = 0.003 ) . Conclusions : Screening the urine sample s used to diagnose teen pregnancies for two common STDs is a simple , non-invasive procedure that is acceptable to providers and patients , and significantly increases the number of teenagers who are treated for genital infection before they initiate pregnancy-related care 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 Objectives : To test whether more women are screened for sexually transmitted infections when offered home-based versus clinic-based testing and to evaluate the feasibility and acceptability of self-sampling and self-testing in home and clinic setting s in a re source -poor community . Methods : Women aged 14–25 were r and omised to receive a home kit with a pre-paid addressed envelope for mailing specimens or a clinic appointment , in Gugulethu , South Africa . Self-collected vaginal swabs were tested for gonorrhoea , chlamydia and trichomoniasis using PCR and self-tested for trichomoniasis using a rapid dipstick test . All women were interviewed at enrolment on sociodemographic and sexual history , and at the 6-week follow-up on feasibility and acceptability . Results : 626 women were enrolled in the study , with 313 in each group ; 569 ( 91 % ) completed their 6-week follow-up visit . Forty-seven per cent of the women in the home group successfully mailed their packages , and 13 % reported performing the rapid test and /or mailing the kit ( partial responders ) , versus 42 % of women in the clinic group who kept their appointment . Excluding partial responders , women in the home group were 1.3 ( 95 % CI 1.1 to 1.5 ) times as likely to respond to the initiative as women in the clinic group . Among the 44 % who were tested , 22 % tested positive for chlamydia , 10 % for trichomoniasis , and 8 % for gonorrhoea . Conclusions : Self-sampling and self-testing are feasible and acceptable options in low-income communities such as Gugulethu . As rapid diagnostic tests become available and laboratory infrastructure improves , these method ologies should be integrated into services , especially services aim ed at young women Objective : Home screening tests could eliminate several barriers to testing sexually transmitted diseases ( STDs ) . Aim : To determine whether offering repeated home screening tests would increase the rate of testing for chlamydia and gonorrhoea in a high-risk sample of young women . Methods : In this r and omised controlled trial , 403 young women ( mean age 18.9 years , 70 % black ) with a recent STD or with STD-related risk factors were enrolled . Participants were recruited from clinics and high-prevalence neighbourhoods and then r and omly assigned to receive either a home testing kit or an invitation to attend a medical clinic for testing at 6 , 12 and 18 months after enrollment . Over 80 % of women were followed for 2 years . The trial is registered with Clinical Trials.gov , number NCT 00177437 . Results : Of 197 women in the intervention group , 140 ( 71 % ) returned at least one home test and 25 of 249 ( 10 % ) home tests were positive . Women who received home screening tests completed significantly more STD tests overall ( 1.94 vs 1.41 tests per woman-year , p<0.001 ) and more STD tests in the absence of symptoms ( 1.18 vs 0.75 tests per woman-year , p<0.001 ) . More women in the intervention group completed at least one test when asymptomatic ( 162 ( 82.2 % ) vs 117 ( 61.3 % ) , p<0.001 ) . The intervention was most effective among women recruited outside medical clinics . There was no significant difference in the overall rate of STDs detected . Conclusions : Home screening significantly increased the utilisation of chlamydia and gonorrhoea testing in this sample of high-risk young women , and thus represents a feasible strategy to facilitate STD testing in young women Objective To determine whether treatment of bacterial vaginosis ( BV ) in early pregnancy decreases the risk of preterm delivery and peripartum infectious morbidity . Methods In this multicenter , r and omized , double-masked , placebo-controlled intervention trial , screening for BV was performed by vaginal Gram stain obtained from 5432 healthy women with singleton pregnancies during the first antenatal clinic visit at 10–17 weeks ' gestation . Bacterial vaginosis-positive women with no past history of preterm delivery were r and omized to a single course of treatment with either 2 % vaginal clindamycin cream or identical placebo cream for 7 days . Repeat Gram stains were taken 1 week after treatment and at 30–36 weeks ' gestation . Preterm delivery was defined as spontaneous delivery before 37 gestational weeks . Peripartum infectious morbidity was defined as postpartum endometritis , postpartum sepsis , postcesarean wound infection , or episiotomy wound infection , necessitating antimicrobial therapy . According to the power analysis , 180 patients were needed for both treatment arms to show a three-fold difference in the rates of preterm births . Results The overall prevalence of BV was 10.4 % . Of all BV-positive women , 375 ( 66 % ) were r and omized to the treatment arms . The primary cure rate was 66 % in the clindamycin group ; in the placebo group , 34 % spontaneously cleared BV ( odds ratio [ OR ] 1.9 , 95 % confidence interval [ CI ] 1.3 , 2.8 ) . The rate of preterm deliveries was 5 % in the clindamycin group and 4 % in the placebo group ( OR 1.3 , 95 % CI 0.5 , 3.5 ) . The rate of peripartum infectious morbidity was 11 % in the clindamycin group and 18 % in the placebo group ( OR 1.6 , 95 % CI 0.9 , 2.8 ) . Bacterial vaginosis recurred in 7 % of women . The rate of preterm deliveries was 15 % in this subgroup compared with 2 % among women who remained BV negative ( OR 9.3 , 95 % CI 1.6 , 53.5 ) . Conclusion Vaginal clindamycin did not decrease the rate of preterm deliveries or peripartum infections , but recurrent or persistent BV increased the risk for these complications OBJECTIVE : To determine whether home-based screening for sexually transmitted infections results in a higher sexually transmitted infection screening rate compared with clinic-based screening in participants using long-acting reversible contraception . METHODS : We performed a r and omized clinical trial of women using long-acting reversible contraception methods in the Contraceptive CHOICE Project ( n=558 ) . Participants were r and omly assigned to home-based testing ( swabs mailed to the participant 's home ) or clinic-based testing . Self-collected vaginal swabs were tested for Chlamydia trachomatis and Neisseria gonorrhoeae using str and displacement analysis . We estimated the relative risk ( RR ) of screening by group using Poisson regression with robust error variance . RESULTS : The r and omization groups were similar at baseline , except for marital status ; the clinic group had more never-married women ( 62.0 % compared with 51.6 % ) , and the home group had more divorced women ( 12.1 % compared with 5.6 % , P=.007 ) . Women in the home group were more likely to self-report screening compared with women in the clinic group in the multivariable analysis ( 56.3 % compared with 32.9 % ; RR 1.7 ; 95 % confidence interval [ CI ] 1.4–2.0 ) . When analyzed by tests received or documented in medical records , similar results were obtained ( 56.3 % compared with 25.0 % ; RR 2.2 ; 95 % CI 1.7–2.7 ) . Women who completed screening had higher levels of education and were more likely to receive public assistance compared with those who did not complete screening . CONCLUSION : Long-acting reversible contraception users r and omized to sexually transmitted infection screening at home were more likely to complete screening than those r and omized to traditional clinic-based screening . Home-based screening may be useful in women using long-acting reversible contraceptive methods who may not present for regular screening . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT01184157 . LEVEL OF EVIDENCE : High-risk human papillomaviruses ( hrHPV ) cause anogenital and oropharyngeal cancers . HPV-16/18 virus-like particle vaccine formulated with an AS04 adjuvant is very efficacious against hrHPV associated precancers but the herd effects of different vaccination scenarios are not known . Our cluster r and omized trial ( NCT00534638 ) assesses the overall and herd effects of vaccinating girls vs. girls and boys . In two school-years ( 2007 - 2008 and 2008 - 2009 ) we invited 80,272 1992 - 1995 born early adolescents to a CRT in 33 communities a priori stratified by low , intermediate and high HPV-16/18 seroprevalence . In 11 Arm A communities 90 % of participating girls and boys were assigned to receive HPV-16/18 vaccine , in 11 Arm B communities 90 % of girls were assigned to receive HPV-16/18 vaccine - boys were assigned to receive hepatitis B-virus ( HBV ) vaccine , and in 11 Arm C communities all were assigned to receive HBV-vaccine . Prevalence of HPV in vaccinated and unvaccinated girls is studied at age 18.5 years . Recruitment result ed in equal enrolment of four birth cohorts ( born 1992 - 1995 ) comprising altogether 32,175 ( 40 % response ) early adolescents : 20,514 girls ( 50.5 - 53.0 % response by arm ) and 11,661 boys ( 21.9 - 31.6%% response by arm ) . At the age of 15 years , 79.3 % of the vaccinees completed a question naire . Among them > 98 % were living at , and during the week-ends 1.3 - 1.6 % stayed outside , the study site communities . Smoking habit and alcohol consumption were similar in the different trial arms , also mean-age of menarche ( 12.4 years ) and 1st ejaculation ( 12.6 years ) , and sexual behaviour ( among those < 25 % , who had had sexual debut ) did not differ by arm : mean-age at the sexual debut 14.3 and 14.4 in girls and boys , and proportions of those with multiple ( ≥5 ) life-time sexual partners ( 6.5 - 7.5 % ) at the age of 15 years . Uniform residential , life-style and sexual behaviour characteristics indicate successful r and omization/enrolment of the CRT . Our CRT will verify modelled predictions on up to 31 % herd effect of vaccinating both girls and boys with moderate vaccine coverage - quantifying overall effectiveness of different strategies which will soon guide how to implement HPV vaccination OBJECTIVE This study sought to quantify the risks of preterm birth that are ascribable to potentially treatable reproductive tract infections among black women in Denver , Colorado . STUDY DESIGN A secondary analysis was conducted of 4 prospect i ve studies in Denver , Colorado , that included 1038 women who were enrolled at < 29 weeks of gestation and whose cases were followed through delivery . Rates of preterm birth , preterm labor , and preterm premature rupture of membranes were the primary outcomes that were examined . RESULTS Bacterial vaginosis , infection with Chlamydia trachomatis , Trichomonas vaginalis , Mycoplasma hominis , Neisseria gonorrhoeae , and group B streptococcal colonization were more common among black women ( P < .01 ) than among comparators . Preterm birth occurred more often among black women with infections that were being studied ( 20.4 % ) , compared with uninfected black women ( 9.5 % ; relative risk , 2.2 ; 95 % CI , 1.1 - 4.1 ) . Up to 42 % of preterm births among black women were attributable to the presence of bacterial vaginosis , T vaginalis , or C trachomatis alone or in combinations . The risk for preterm birth among infected black women who received Centers for Disease Control and Prevention recommended treatment was reduced significantly ( relative risk , 0.16 ; 95 % CI , 0.04 - 0.66 ) . CONCLUSION Black women have increased risks of prematurity that are associated with prevalent reproductive tract infections during pregnancy . Preterm birth among similar urban black women could be reduced by > 40 % by the screening and treatment of common genitourinary tract infections in pregnancy Objectives A r and omised controlled trial was conducted to assess and quantify the efficacy and acceptability of non-invasive testing ( NIT ) for sexually transmitted infections ( STI ) in asymptomatic patients within a genitourinary medicine clinic . Methods Patients were r and omly assigned to either st and ard of care ( SOC — STI testing with genital examination ) or NIT . The length of time patients spent in the clinic was recorded and patients were asked to complete a satisfaction survey . Results 391 participants were r and omly assigned . The length of time male and female patients spent in the clinic was significantly shorter with NIT ( men 26 min ; women 23 min ) compared with SOC ( men 41 min ; women 45 min , p<0.0001 ) , but most of this decrease was due to reduced patient waiting time within the clinic , rather than less time spent with medical or nursing staff . Those r and omly assigned to NIT were significantly more likely to state they were in clinic for less time than expected ( p<0.01 ) and report that the tests were less uncomfortable than expected ( p≤0.04 ) . For both men and women , more patients in the SOC group declined testing for syphilis ( 14 % ) and HIV ( 20 % ) compared with NIT ( 7 % and 13 % , respectively ) , but this was only significantly different between treatments for female patients ( p≤0.02 ) . Conclusions NIT for STI in asymptomatic patients can reduce the time patients spend in the clinic when combined with appropriate patient care pathways , and is an acceptable alternative to physician-taken genital swabs Background Clients diagnosed and treated for Chlamydia trachomatis are a recognised high-risk group for subsequent infection . An estimated 8 % of clients treated for chlamydia at Cairns Sexual Health Service return for re-testing within the recommended 3–4-month period . There is no recall or reminder system in place . This study assesses the effectiveness of using short messaging service ( SMS ) reminders with and without incentive payments to increase re-testing rates . Methods Eligible consenting clients were r and omly allocated to one of three groups . Group 1 ( controls ) received the st and ard advice from the clinician to return for re-testing in 3–4 months . Group 2 received the st and ard advice and an SMS reminder at 10–12 weeks post-treatment . Group 3 received the st and ard advice and the SMS reminder , which also offered an incentive payment on clinic attendance . Results 32 participants were recruited to groups 1 and 2 and 30 participants to group 3 . 62 SMS reminders were sent with 13 ( 21.0 % ) reported as undelivered . Re-testing rates were 6.3 % , 28.1 % and 26.7 % for groups 1 , 2 and 3 , respectively . Conclusion SMS reminders with or without an incentive payment increased re-testing rates in our clients who were diagnosed and treated for chlamydia . However , re-testing remained less than ideal , and the high rate of undelivered SMS reminders suggest that this intervention alone will not achieve desired re-testing rates and that a range of strategies will be required to increase re-testing in this population OBJECTIVE Despite the recommendations of numerous clinical practice guidelines , testing of at-risk women for Chlamydia trachomatis infection remains low . We evaluated an intervention to increase guideline -recommended chlamydia screening . METHOD In a two-by-two factorial design r and omized trial conducted in 2001 - 2002 , 23 primary care clinics at Group Health Cooperative in Washington State were r and omized to either control ( st and ard ) or intervention ( enhanced ) guideline implementation arms . Clinic-level intervention strategies included use of clinic-based opinion leaders , individual measurement and feedback , and exam room reminders . A second patient-level intervention , a chart prompt to screen for chlamydia , was delivered in a r and om sample of 3509 women . The outcome measure was post-intervention chlamydia testing rates among sexually active women ages 14 - 25 . RESULTS The clinic-level intervention did not significantly affect overall chlamydia testing ( odds ratio ( OR ) = 1.08 , 95 % confidence interval ( CI ) 0.92 - 1.26 , P = 0.31 ) . However , testing rates increased significantly among women making preventive care visits ( OR , Pap test visit = 1.23 , 95 % CI , 1.01 - 1.51 , P = 0.04 ; OR , physical exam visit = 1.22 , 95 % CI 1.06 - 1.42 , P = 0.009 , intervention vs. control clinics ) . The chart prompt intervention had no significant effect ( OR = 1.08 , 95 % CI 0.94 - 1.23 , P = 0.27 ) . CONCLUSIONS Interventions to improve guideline -recommended chlamydia testing increased testing among women making preventive care visits . Additional organizational change and /or patient activation strategies may improve plan-wide testing , particularly among asymptomatic women |
956 | 23,827,204 | RESULTS Meta-analyses found statistically significant effects for SCIT and SLIT compared with placebo across a number of outcome measures and for the vast majority of subgroup analyses ( type and amount of allergen , duration of treatment ) .
There was less evidence for children , but some results in favour of SLIT were statistically significant .
Indirect comparisons did not provide conclusive results in favour of either SCIT or SLIT .
A benefit from both SCIT and SLIT compared with placebo has been consistently demonstrated , but the extent of this effectiveness in terms of clinical benefit is unclear . | BACKGROUND Severe allergic rhinitis uncontrolled by conventional medication can substantially affect quality of life .
Immunotherapy involves administering increasing doses of a specific allergen , with the aim of reducing sensitivity and symptomatic reactions .
Recent meta-analyses have concluded that both subcutaneous immunotherapy ( SCIT ) and sublingual immunotherapy ( SLIT ) are more effective than placebo in reducing symptoms .
It is uncertain which route of administration is more effective and whether or not treatment is cost-effective .
OBJECTIVE To determine the comparative clinical effectiveness and cost-effectiveness of SCIT and SLIT for seasonal allergic rhinitis in adults and children . | Twenty-six patients were recruited for a study of the safety and efficacy of immunotherapy with IPG . They were r and omly assigned to two groups based on skin test titrations to grass allergens . One group was treated in a double-blind fashion before the 1982 grass season with 12 weekly injections totaling approximately 48,000 PNU , and the other group was treated with 12 weekly injections of caramelized glucose histamine placebo . Daily symptom and medication score sheets were completed by all patients each day of the grass season . Blocking antibody rose ninefold in the IPG group ( p less than 0.007 ) but was unchanged in the placebo group . There was no significant change in IgE against rye grass group I in either the IPG or the placebo group . Symptom-score mean in the IPG group was 217 + /- 71 ( S.E.M. ) , statistically lower ( p less than 0.02 ) than the mean in the placebo group 496 + /- 117 ( S.E.M. ) . There were no systemic reactions and only minor local reactions . There was no change in routine laboratory tests in either group . Although two prior studies with grass allergen immunotherapy reported efficacy , these studies did not use symptom-score analysis . This is the first double-blind , histamine placebo-controlled study of grass immunotherapy that demonstrates efficacy by symptom-score index evaluation . IPG is a safe , clinical ly effective , and potentially cost-effective therapy for grass pollinosis BACKGROUND The natural history of allergic sensitization is complex and poorly understood . A prospect i ve nonr and omized study was carried out in a population of asthmatic children younger than 6 years of age whose only allergic sensitivity was to house dust mites ( HDMs ) . OBJECTIVES The study was design ed to determine whether specific immunotherapy ( SIT ) with st and ardized allergen extracts could prevent the development of new sensitizations over a 3-year follow-up survey . METHODS We studied 22 children monosensitized to HDM who were receiving SIT with st and ardized allergen extracts and 22 other age-matched control subjects who were monosensitized to HDM . The initial investigation included a full clinical history , skin tests with a panel of st and ardized allergens , and the measurement of allergen-specific IgE , depending on the results of skin tests . Children were followed up on an annual basis for 3 years , and the development of new sensitizations in each group was recorded . RESULTS Ten of 22 children monosensitized to HDM who were receiving SIT did not have new sensitivities compared with zero of 22 children in the control group ( p = 0.001 , chi square test ) . CONCLUSIONS This study suggests that SIT in children monosensitized to HDM alters the natural course of allergy in preventing the development of new sensitizations Background : The clinical efficacy and safety of a six‐grass pollen allergoid has been studied . The advent of more exacting clinical guidelines and a better appreciation of the possible mechanisms of treatment prompted this re appraisal BACKGROUND The efficacy and safety of the 300-index of reactivity ( IR ) dose of 5-grass-pollen sublingual immunotherapy ( SLIT ) tablets ( Stallergènes , Antony , France ) have been demonstrated for the treatment of hay fever in adults . OBJECTIVE We sought to assess the efficacy and safety of this tablet in children and adolescents with grass pollen-related allergic rhinitis . METHODS In this multinational , r and omized , double-blind , placebo-controlled study , 278 children ( 5 - 17 years of age ) with grass pollen-related rhinoconjunctivitis ( confirmed by means of a positive grass pollen skin prick test response and serum-specific IgE measurement ) received once-daily SLIT tablets or placebo . Treatment was initiated 4 months before the estimated pollen season and continued throughout the season . The primary outcome was the rhinoconjunctivitis total symptom score ( RTSS ) , a sum of 6 individual symptom scores : sneezing , runny nose , itchy nose , nasal congestion , watery eyes , and itchy eyes . Secondary end points included rescue medication intake , individual scores , and safety . RESULTS The intent-to-treat population included 266 children ( mean age , 10.9 + /- 3.22 years ) . The RTSS for the 300-IR group was highly significantly different from that of the placebo group ( P = .001 ) . The 300-IR group showed a mean improvement for the RTSS of 28.0 % over that seen with placebo and a median improvement of 39.3 % . Significant differences between the 300-IR and placebo groups were also observed regarding rescue medication score and proportion of days using rescue medication during the pollen season ( P = .0064 and P = .0146 , respectively ) . Adverse events were generally mild or moderate in intensity and expected . No serious side effects were reported . CONCLUSION Five-grass-pollen SLIT tablets ( 300 IR ) reduce both symptom scores and rescue medication use in children and adolescents with grass pollen-related rhinoconjunctivitis Background : Data supporting a carry‐over effect with sublingual immunotherapy ( SLIT ) are scarce . This r and omized , double‐blind , placebo‐controlled study evaluated the efficacy , carry‐over effect and safety of grass pollen SLIT using co‐seasonal treatment BACKGROUND This is an interim analysis of a r and omized , double-blind , placebo-controlled phase III trial with 3 years of daily treatment with grass tablet immunotherapy ( GRAZAX ; ALK-Abelló A/S , Hørsholm , Denmark ) or placebo , followed by 2 years of follow-up to assess the persistent efficacy . OBJECTIVE We sought to evaluate the efficacy and safety of specific immunotherapy with grass allergen tablets compared with placebo after treatment covering 2 consecutive grass pollen seasons . METHODS The interim analyses included 351 adult participants with moderate-to-severe allergic rhinoconjunctivitis caused by grass pollen . Participants were treated with active ( n = 189 ) or placebo ( n = 162 ) tablets for an average of 22 months . All participants were allowed to use symptomatic rescue medication . RESULTS The primary efficacy analysis showed highly significant mean reductions of 36 % in rhinoconjunctivitis symptom score ( P < .0001 ; median reduction , 44 % ) and 46 % in rhinoconjunctivitis medication score ( P < .0001 ; median reduction , 73 % ) in the active group relative to the placebo group . Mean rhinoconjunctivitis quality of life was 33 % better ( P < .0001 ; median , 40 % ) . Clinical improvements were paralleled by significant changes in allergen-specific immunoglobulins . The treatment was well tolerated , and adverse events led to withdrawal in less than 1 % of participants . There were no serious adverse events related to treatment . CONCLUSION Grass allergen tablet immunotherapy showed progressive immunologic changes and highly significant efficacy over 2 years of continued treatment Sublingual immunotherapy ( SLIT ) with monomeric carbamylated allergoid administered in accordance with the st and ard regimen has proven to be effective and safe . Achieving clinical benefit , however , requires a lengthy period of time so it is not very suitable for short-lasting allergies . We thus performed this study to compare an administration protocol starting in the coseasonal period ( with a 4-day build-up phase ) with a precoseasonal scheme to verify if the former regimen provides the same benefit in a shorter period of time . The prospect i ve , r and omized , drug therapy-controlled study was conducted in 33 rhinitic patients monosensitized to Olea with or without asthma . Ten patients were assigned to the coseasonal therapy with 5000 allergic units (AU)/week for 6 weeks , 11 to the precoseasonal therapy with 3000 AU/week for 10 weeks , and 12 to drug therapy . They were treated from April or May to June 2008 . A visual analog scale ( VAS ) was performed at baseline and after treatment to assess the well being of the patients . Drug consumption was evaluated by means of a monthly diary . There was greater VAS improvement in both the SLIT groups versus the controls , but it was statistically significant only in the coseasonal group ( p < 0.01 ) . Furthermore , there was a reduction in the rescue medication only in the coseasonal SLIT ( p < 0.05 versus drug therapy ) . One mild adverse event was observed . The allergoid SLIT was shown to be effective and safe in Olea allergy in particular when a coseasonal regimen was used BACKGROUND The safety and efficacy of specific immunotherapy for mold allergy are not known in children and adolescents . OBJECTIVE We evaluated the efficacy and safety of specific immunotherapy with a st and ardized allergen extract in a r and omized , double-blind , placebo-controlled , 3-year prospect i ve study of patients who were allergic to only Alternaria alternata . METHODS Fifty children and adolescents ( 25 girls ; 5 - 18 years of age ) with A alternata-induced seasonal allergic rhinoconjunctivitis and /or bronchial asthma were r and omly assigned to groups given treatment ( Novo-Helisen Depot , A alternata 100 % ) or placebo . The primary end point was the combined symptom medication score . Secondary end points included safety , quality of life , and sensitivity to allergen-specific nasal challenge . RESULTS Forty-five children completed the 3-year study . Although there was no significant change in year 1 , the combined symptom medication score decreased in years 2 and 3 of the study ( by 38.7 % and 63.5 % , respectively ; P < .001 for each ) . The reduction in symptoms was associated with a significant improvement in quality of life ( P < .05 ) and decrease in sensitivity after allergen-specific nasal challenge . Side effects were observed in 7 patients ; the most common ( edema at the site of injection ) occurred after 11 injections . CONCLUSIONS Allergen-specific immunotherapy with st and ardized A alternata extract reduces symptoms of asthma and rhinoconjunctivitis in children and adolescents without serious side effects Background : Local application of allergen extracts in specific immunotherapy is accompanied by increased compliance and significantly reduced side effects . However , efficacy of local immunotherapy in children has yet not been sufficiently demonstrated . This study was performed to determine clinical efficacy of high dose sublingual swallow immunotherapy ( SLIT ) by a double‐blind placebo‐controlled study in children with grass pollen allergy using high dose allergen extracts UNLABELLED SAFETY and efficacy of sublingual ( sublingual-swallow ) immunotherapy ( IT ) with house dust mite extract were evaluated in 30 children ( 6 - 15 2/3 years of age ) over the first 12 months of an ongoing study . The cumulative dose was 570 micrograms Der p I ( five times that administered with subcutaneous therapy ) . SAFETY One patient on active treatment dropped out after 8 weeks because of a subjective feeling of severe weakness , question ably induced by the therapy . Five patients on active therapy and one patient on placebo reported minor local side effects . EFFICACY Pulmonary symptoms were reduced after 12 months in actively treated asthmatics , but this was not consistent with the lack of improvement in bronchial reactivity , skin sensitivity and specific IgG and IgG4 against D.pt . in this group . In patients with rhinitis nasal sensitivity was reduced in the placebo group without concomitant improvement in the nasal symptom score . Specific IgE ( D.pt . and D.f . ) increased significantly more in the active treatment group after 3 and 12 months . We conclude that sublingual IT over 12 months with the fivefold Der p 1 dose of subcutaneous IT was well tolerated , but there was no consistent clinical or immunological benefit compared to placebo A double-blind , placebo-controlled study of immunotherapy was conducted in 31 patients with allergic rhinitis due to Parietaria pollen to evaluate the efficacy and safety of high doses of allergen via the sublingual route . The patients were assessed before and after a 10-month period of treatment by clinical ( symptom-medication scores and specific nasal reactivity ) and immunological ( total IgE , specific IgE , IgG and IgG4 antibodies ) parameters . High doses of Parietaria extract corresponding to a cumulative dose of 105 BU for each patient were administered with negligible side effects . The actively treated patients had significantly lower medication scores than those on placebo ( p < 0.05 ) when the maximum pollen count was recorded , and at the end of the trial they showed a significant decrease in nasal reactivity ( p < 0.02 ) and a significant increase in serum specific IgG4 ( p = 0.02 ) . No differences were detected in any of these parameters in the placebo group . Possible explanations for the mechanisms of sublingual immunotherapy are proposed OBJECTIVE To evaluate the safety and efficacy of sublingual immunotherapy with ' Dermatophagoides Farinae Drops ' in D. farinae allergic asthma and /or rhinitis patients . METHODS A 25-week double-blind , placebo-controlled , multi-centered trail was conducted in 278 children ( aged 4 - 18 yr ) with mite-induced asthma and /or rhinitis . Patients were r and omly assigned to receive sublingual immunotherapy ( SLIT ) with ' Dermatophagoides Farinae Drops ' ( n = 139 ) or placebo ( n = 139 ) for 25 weeks and the dosage and administration strictly followed the manufacturer 's instructions . At the beginning of the 2nd , 3rd , 4th , 6th , 10th , 14th , 18th , 22nd week of the treatment , the patients were asked to accept follow-up visit , during the clinical trial all patients and parents were asked to keep a daily record of their asthma symptom scores , rescue medicine use , rhinitis symptom scores , morning and evening peak expiratory flow . Asthma symptom scores , reduction in use of rescue medicine , rhinitis symptom scores , lung function tests , skin sensitivity to mite , mite-specific immunoglobulin ( Ig ) E and IgG4 , and quality of life and adverse effect were assessed during the study . RESULT ( 1 ) Of the 278 children , 27 dropped out before the study completion . ( 2 ) After 25 weeks of treatment , the median variability of PEFR was -1.38 for SLIT group and -0.90 for the placebo ( P < 0.05 ) . ( 3 ) Besides , the mean variability of medicine score of asthma was -0.08 for SLIT group and 0.52 for the plcebo ( P < 0.05 ) . ( 4 ) The median variability of rhinitis symptom score was -1.96 for SLIT group and -1.03 for the placebo ( P < 0.01 ) . ( 5 ) The rescue medicine usage of SLIT reduced but did not show significant differences between SLIT and placebo . ( 6 ) After 25 weeks treatment , the increase of D. farinae specific IgE antibody of two groups were similar , while specific IgG4 increased significantly in SLIT compared to the patients in control one ( P < 0.01 ) ; ( 7 ) No severe adverse events happened in the trial and the most-likely adverse events were mild asthma and local rash . CONCLUSION Dermatophagoides Farinae Drops is safe and effective in treating allergic asthma and atopic rhinitis BACKGROUND Allergen immunotherapy ( desensitization ) by injection is effective for seasonal allergic rhinitis and has been shown to induce long-term disease remission . The sublingual route also has potential , although definitive evidence from large r and omized controlled trials has been lacking . OBJECTIVE The aim was to confirm the efficacy of a rapidly dissolving grass allergen tablet ( GRAZAX , ALK-Abelló , Hørsholm , Denmark ) compared with placebo in patients with seasonal rhinoconjunctivitis . METHODS A longitudinal , double-blind , placebo-controlled , parallel-group study that included 51 centers from 8 countries . Subjects were r and omized ( 1:1 ) to receive a grass allergen tablet or placebo once daily . A total of 634 subjects with a history of grass pollen-induced rhinoconjunctivitis for at least 2 years and confirmation of IgE sensitivity ( positive skin prick test and serum-specific IgE ) were included in the study . Subjects commenced treatment at least 16 weeks before the grass pollen season , and treatment was continued throughout the entire season . RESULTS The primary efficacy analysis showed a reduction of 30 % in rhinoconjunctivitis symptom score ( P < .0001 ) and a reduction of 38 % in rhinoconjunctivitis medication score ( P < .0001 ) compared with placebo . Side effects mainly comprised mild itching and swelling in the mouth that was in general well tolerated and led to treatment withdrawal in less than 4 % of participants . There were no serious local side effects and no severe systemic adverse events . CONCLUSION Sublingual immunotherapy with grass allergen tablets was effective in grass pollen-induced rhinoconjunctivitis . The tablet was well tolerated with minor local side effects . CLINICAL IMPLICATION S The grass allergen tablet represents a safe alternative to injection immunotherapy suitable for home use BACKGROUND Sublingual immunotherapy ( SLIT ) is accepted as a safe and effective route for the treatment of grass pollen allergy , but clarification of its clinical and biological efficacy requires more study . OBJECTIVE To evaluate the efficacy , safety , and compliance of SLIT with a st and ardized 3-grass pollen extract in patients with grass pollen seasonal allergic rhinoconjunctivitis , with or without mild asthma . METHODS This multicenter , r and omized , double-blind study included 127 patients ( aged 12 - 41 years ; mean age , 24.9 years ) with grass pollen seasonal allergic rhinoconjunctivitis , with or without mild asthma . They received either SLIT with a high-dose , st and ardized , 3-grass pollen extract or placebo for 10 months before and during the grass pollen season . The efficacy evaluation compared weekly clinical scores ( defined as the sum of the symptom score and rescue medication score ) to measure rhinoconjunctivitis and asthma for the first 8 weeks of the pollen season . We also evaluated safety and compliance and measured changes in anti-Dactylis specific IgG4 antibody levels . RESULTS There was a trend in favor of the study group in the mean adjusted clinical score . The groups were not comparable on inclusion ( P = .02 ) : the SLIT group included more subjects with asthma and had a higher mean IgG4 serum level . Additional exploration according to subgroups with and without asthma found that among the patients without asthma , the SLIT group had a significantly better clinical score ( P = .045 ) . Anti-Dactylis specific IgG4 levels increased significantly in the SLIT group . CONCLUSION SLIT with a st and ardized , high-dose , 3-grass pollen extract is safe and significantly improves the clinical score in patients with hay fever and without asthma during the pollen season Thirty-four patients suffering from rhinoconjunctivitis with or without asthma due to grass pollen , were su bmi tted to sublingual immunotherapy according to a double blind placebo controlled experimental plan ; eighteen patients received the active therapy , sixteen the placebo . A rush preseasonal treatment schedule was followed in order to reach the maintenance dose in 15 days with two administrations per day ; the top dose reached was then administered three times a week until the end of the pollen season . The symptoms and drugs related to rhinoconjunctivitis and asthma were recorded by means of diary cards and grass pollen counts were performed during the season . The actively treated group showed a reduction of symptoms of rhinoconjunctivitis and asthma and a lower intake of drugs for the same symptoms ; all these differences result ed to be statistically significant . No patient showed local or systemic side effects of any relevance . According to these results of our study , sublingual rush immunotherapy is clinical ly effective and because of the ease of h and ling , the shortness of the treatment , the absence of relevant side effects and the high compliance of the patient can be considered as an alternative to classic injective immunotherapy in grass pollen allergic patients 58 patients under 12 years of age , positive to mites ( Dermatophagoides pteronyssinus and D. farinae ) according to prick , in vitro specific IgE and challenge tests , suffering from asthma and rhinitis , have been r and omly assigned on a double blind basis to receive per os either a biologically st and ardized extract of mites ( active therapy TA = 30 patients ) or a saline buffered solution ( placebo TP = 28 patients ) . The serologic results are interesting . The specific IgE level differences of significance are , in comparison with the placebo group . In particular , we did observe the increase of the specific IgE level in the placebo group during the autumn , whereas after 12 months and after 24 months of active treatment there was a clear ( p < 0.01 ) decline in serum specific IgE antibody . In the active group , there was a significant increase in IgG antibodies level after 12 and 24 months and a significant increase in IgG4 level after 24 months . In the placebo group , the level of IgG antibodies was unchanged . In the actively treated patients , a significant increase of CD8 + values and a significant reduction of the ratio CD4+/CD8 + was observed BACKGROUND Sublingual swallow immunotherapy has been increasingly recognized as a safe and efficacious alternative to parenteral specific immunotherapy . OBJECTIVE To determine the safety and efficacy of sublingual swallow immunotherapy ragweed allergen extract for rhinoconjunctivitis treatment starting just before and continuing through the ragweed pollen season . METHODS This r and omized , double-blind , placebo-controlled study was performed in children and adults with a documented history of allergic rhinoconjunctivitis during ragweed season at 9 Canadian allergy centers . Active treatment was st and ardized extract of ragweed allergen administered as sublingual swallow drops at increasing doses starting shortly before the pollen season and maintenance doses continued daily during the season . Primary efficacy variables were symptom and medication scores , and secondary variables included global evaluation of efficacy and immunologic measurements . RESULTS Eighty-three patients were included in the safety analysis ; 76 patients were included in the intent-to-treat analysis . Nine placebo recipients and 1 treatment recipient withdrew for lack of efficacy ( P = .004 ) . Nine patients in the treatment group withdrew because of adverse events , none serious ( P = .003 ) . Investigator evaluation of efficacy showed that significantly more patients improved and fewer deteriorated in the treatment group vs the placebo group ( P = .047 ) . Ragweed IgE and IgG4 levels increased significantly in treatment recipients vs placebo users ( P < .001 ) . Sneezing and nasal pruritus approached significant improvement in the treatment group vs the placebo group ( P = .09 and .06 , respectively ) . Quebec City experienced low pollen counts . Excluding Quebec City , significant improvement was seen for these 2 symptoms ( P = .04 ) . CONCLUSION Sublingual swallow immunotherapy seems to be safe and efficacious for ragweed rhinoconjunctivitis even when started immediately before the ragweed pollen season Summary A new type of desensitising vaccine , enzyme potentiated was subjected to a double-blind r and omised study during the hay fever season . The vaccine is a convenient single injection given in March and the results show good protection throughout the grass pollen season Background : Especially in childhood , sublingual immunotherapy ( SLIT ) could offer advantages over subcutaneous therapy . However , limited data on its efficacy is available The aim of the study was to confirm the safety of an orodispersible grass allergen tablet 75,000 SQ-T ( Grazax , ALK-Abelló A/S , Hørsholm , Denmark ) in children aged 5 - 12 yr . The study was r and omized , double-blinded and placebo-controlled . Sixty children aged 5 - 12 yr suffering from grass pollen-induced rhinoconjunctivitis ( with or without asthma ) from five centres in two countries ( three in Germany and two in Spain ) participated in the study . They were r and omized at the ratio of 3:1 as receiving either Grazax or placebo tablet given sublingually once daily for 28 days outside the grass pollen season . A total of 810 treatment-related adverse events were reported in the Grazax group . The majority of these were local reactions in the mouth or throat and were mostly mild ( 71 % ) to moderate ( 27 % ) in severity and resolved within days . Thirty-five ( 78 % ) subjects treated with Grazax and five ( 33 % ) treated with placebo reported at least one treatment-related adverse event . Oral pruritus , throat irritation , mouth oedema and ear pruritus appeared as the most frequently reported treatment-related adverse events . 62 % ( 28 of 45 ) of the actively treated subjects reported oral pruritus , 36 % ( 16 of 45 ) throat irritation , 31 % ( 14 of 45 ) mouth oedema and 22 % ( 10 of 45 ) ear pruritus . Two actively treated subjects withdrew from the study : one subject due to four adverse events ( moderate eye pruritus , moderate pharyngolaryngeal pain , moderate non-cardiac chest pain and moderate dysphagia ) and one subject due to a serious adverse event ( asthmatic attack ) . The subjects recovered completely from the events . In conclusion , in the present study , Grazax was in general tolerated in a paediatric population and considered suitable for further clinical investigations in children Sublingual immunotherapy has been suggested for the treatment of respiratory allergies . Many controversial studies have been reported on the efficacy of sublingual immunotherapy . The aim of this prospect i ve study was to evaluate whether sublingual immunotherapy was effective according to clinical and laboratory results in pediatric allergies . Thirty-nine allergic , grass pollen sensitive children were admitted into the study . Sublingual immunotherapy was given over a 12-month period to 21 children ( mean age 10.5 + /- 3.3 years ) , 10 of whom had seasonal allergic rhinitis and 11 seasonal allergic asthma . During the same period , 18 children ( mean age 11.1 + /- 2.5 years ) , 10 with seasonal allergic rhinitis and eight with seasonal allergic asthma , received placebo . Symptom scores and drug requirements were recorded and urine sample s were collected to detect urinary levels of leukotrienes ( Uc-LTB4 and Uc-LTE4 ) . In patients who received sublingual immunotherapy , the symptom scores of seasonal allergic rhinitis significantly decreased , but no statistically significant changes were observed in terms of symptoms of seasonal allergic asthma . Uc-LTE4 and Uc-LTB4 levels of seasonal allergic rhinitis , with a geometric mean and 95 % confidence interval ( CI ) , were significantly decreased from 216 ( 103 - 464 ) and 61 ( 22 - 198 ) pmol/mmol creatinine to 78 ( 29 - 159 ) and 35 ( 12 - 118 ) pmol/mmol creatinine , respectively ( p < 0.05 and p < 0.05 ) . On the other h and , Uc-LTE4 and Uc-LTB4 levels for seasonal allergic asthma were 180 ( 92 - 355 ) and 78 ( 44 - 258 ) pmol/mmol creatinine and decreased to 156 ( 72 - 402 ) and 69 ( 32 - 254 ) pmol/mmol creatinine , respectively . These changes were not statistically significant ( p > 0.05 ) . According to our clinical results and urinary levels of leukotrienes , which are mediators showing the severity of allergic inflammation , it can be suggested that sublingual immunotherapy may be useful in the treatment of seasonal allergic rhinitis but not of seasonal allergic asthma BACKGROUND sublingual immunotherapy has been recognised as safe and effective but it is still poorly documented in tree pollen allergy . Allergy to alder , birch and hazel is important in Northern European countries but its clinical relevance is increasing in Southern Europe . METHODS thirty patients , selected and observed for one pollen season , were r and omised to receive placebo ( 15 patients ) or active treatment ( 15 patients ) . Twenty-seven patients completed the first year and 24 of them were treated with active therapy during the second year of the study in comparison to a parallel group of ten patients treated only with drugs . Symptom and drug scores during each pollen season , birch-specific IgE , changes in skin test reactivity , changes in specific Nasal Provocation Test and the daily average pollen count for the relevant trees were considered for the assessment of the efficacy of the treatment . RESULTS both active and placebo group showed a statistically significant improvement in scores in comparison to the previous year , under a lower allergenic pressure . The improvement was higher in the active group ( 76.04 % reduction of drugs ) but not significantly different from that registered in the placebo group ( 37.05 % reduction ) . In the open phase of the study , treated patients showed significantly better scores in comparison to the control group . No significant changes in skin reactivity , specific IgE and Nasal Provocation Test were registered . SLIT tolerance was very good . CONCLUSIONS our data show a better but not statistically significant clinical outcome for patients actively treated with SLIT , but the placebo effect and the year-by-year variability of the environmental allergenic load in our small-size pilot study do not allow for a conclusive statement about the efficacy of this form of therapy Specific immunotherapy is effective in grass pollen allergy with st and ardized extracts and formalinized allergoids ; but systemic reactions are not uncommon . A high-molecular-weight ( greater than 85,000 daltons ) , formalinized allergoid was investigated in a double-blind , placebo-controlled study to assess its safety and efficacy . Twenty patients received a placebo and 39 the allergoid using a rather aggressive protocol . Five patients developed a mild and transient systemic reaction with high doses of allergoid and one had a more severe reaction requiring treatment . Nasal challenges performed with orchard grass pollen grains showed that the threshold number of grains eliciting nasal symptoms was significantly ( p less than 0.01 ) greater in the treated group . This group had significantly ( p less than 0.01 ) less nasal symptoms during the season and specific IgG levels were significantly ( p less than 0.01 ) elevated . There was a significant ( p less than 0.01 ) correlation between nasal challenges and nasal symptoms during the season but no correlation between IgG and symptoms . There was no dose-dependent effect of allergoids BACKGROUND Sublingual immunotherapy with grass allergen tablets may be the future treatment for grass pollen allergy because it reduces symptoms and medication use , improves quality of life and is easy to use . Rhinoconjunctivitis and asthma co-exist and we aim ed to find a safe dose range of a self-administered grass allergen tablet ( ALK Abello A/S ) in patients suffering from rhinoconjunctivitis and asthma . METHODS Four doses were investigated in a r and omised , double-blind , placebo-controlled , dose escalation trial . Outside the pollen season 4 groups of 12 patients commenced treatment in a staggered manner , at intervals of 1 week . For 28 days doses of 75000 ( approximately 15microg Phleum pratense protein 5 ) , 150,000 , 300,000 , 500,000 st and ardised quality tablet ( SQ-T ) units or placebo were given once daily as sublingual tablets . RESULTS Fourty three patients were r and omised to receive either active treatment or placebo ( 3:1 ) . Each dose group consisted of 12 patients except the 500000 SQ-T group ( 5 active , 2 placebo ) . No asthma exacerbations were seen and no serious or severe adverse events were reported . The majority of adverse events were local reactions . The number of adverse events was dose related . No patients withdrew from the study . CONCLUSIONS Treatment with grass allergen tablets in doses up to 500000 SQ-T in patients with asthma and rhinoconjunctivitis was safe and well tolerated Background : The efficacy of st and ardized Juniperus ashei extract was assessed in patients with allergic rhinoconjunctivitis due to European cypress pollens . Methods : Forty adults with European cypress-allergic rhinoconjunctivitis were r and omized to receive immunotherapy or a matched placebo . Specific immunotherapy was performed with a st and ardized , aluminum hydroxide-adsorbed J. ashei extract with a potency of 100 IR ( arbitrary index of reactivity ) containing 54 µg of Jun a 1/ml ( Alustal , Stallergenes , France ) . Subcutaneous injections started in October 2000 . The maintenance dose was 0.30 ml of the 100-IR concentration per month . Rhinitis and conjunctivitis symptoms were rated according to a 4-point score . Results : Seventeen patients from the treated group and 15 patients from the placebo group completed year 2001 ; 14 in each group completed year 2002 . A statistically significant improvement ( 41 % , p < 0.02 ) in the conjunctivitis symptom score was observed in actively treated patients compared to the placebo group at the peak of the 2001 pollen season . Improvement in rhinitis ( 17 % ) was not significant . This significant improvement was greater at the peak of the 2002 pollen season ( 63 % , p < 0.01 ) . Conclusions : This study therefore indirectly vali date s the concept of treatment by major allergen because J. ashei is absent from the region in which this study was conducted Background : There is only very limited documentation of the efficacy and safety of high‐dose subcutaneous birch pollen immunotherapy ( IT ) in double‐blind , placebo‐controlled ( DBPC ) studies . Birch pollen is a major cause of allergic morbidity in northern Europe and in eastern parts of North America BACKGROUND Specific allergen immunotherapy is most often delivered subcutaneously , but sublingual immunotherapy may confer greater benefit in terms of tolerability and safety , accessibility , and improved antigen delivery . OBJECTIVE This r and omized , double-blind , placebo-controlled trial was conducted to identify a safe and effective maintenance dose range of sublingual st and ardized glycerinated short ragweed pollen extract in adults with ragweed-induced rhinoconjunctivitis . METHODS In May 2006 , a total of 115 patients with ragweed-induced rhinoconjunctivitis were r and omly allocated to placebo ( n = 40 ) , medium-dose extract ( 4.8 microg Amb a 1/d ; n = 39 ) , or high-dose extract ( 48 microg Amb a 1/d ; n = 36 ) . In a 1-day ( rush ) dose-escalation regimen , ragweed pollen extract was administered sublingually in incremental doses until maximum tolerable or scheduled dose was reached and then maintained during the ragweed pollen season . Patient diaries were used to monitor nasal and ocular symptoms and medication . The primary endpoint was symptom score . RESULTS Both active treatment groups achieved a 15 % reduction in total rhinoconjunctivitis symptom scores compared with placebo during the entire ragweed pollen season , but the difference was not statistically significant ( P > .10 ) However , in an analysis of covariance correcting for preseasonal symptoms , both mean daily symptom scores ( 0.19 + /- 1.16 vs 1.00 + /- 2.30 ) and medication scores ( 0.0003 + /- 1.64 vs 0.63 + /- 1.06 ) for the entire pollen season were significantly reduced in the high-dose versus placebo groups , respectively ( P < or= .05 ) . Ragweed-specific IgG , IgG(4 ) , and IgA antibodies were increased after treatment in the medium- and high-dose groups and not the placebo group . Frequency of adverse events was similar between the placebo and treatment groups , but oral-mucosal adverse events occurred more often with treatment . CONCLUSION St and ardized glycerinated short ragweed pollen extract administered sublingually at maintenance doses of 4.8 to 48 microg Amb a 1/d was safe and can induce favorable clinical and immunologic changes in ragweed-sensitive subjects . However , additional trials are needed to establish efficacy OBJECTIVE --To evaluate the efficacy and safety of immunotherapy ( hyposensitisation ) in patients with severe summer hay fever . DESIGN --A r and omised , double blind , placebo controlled study of a biologically st and ardised depot grass pollen extract . SETTING --Allergy clinic , Royal Brompton and National Heart Hospital , London . PATIENTS --40 adults ( mean age 35 years ) with a history of severe grass pollen allergy uncontrolled by st and ard antiallergic drugs . Patients with perennial asthma were specifically excluded . INTERVENTION-- Patients were r and omised to receive either an active preparation ( Alutard SQ , a grass pollen ( Phleum pratense ) extract ) or placebo at a rate of two subcutaneous injections a week in increasing doses until a maintenance dose was reached . This maintenance dose was given once a month . MAIN OUTCOME MEASURES -- Clinical efficacy was evaluated by symptom and drug diary cards , visual analogue scores during the grass pollen season , and a postseasonal assessment by the patients and a doctor . Conjunctival and skin sensitivity to local allergen provocation was measured before and after eight months of treatment . RESULTS --There was a highly significant decrease ( median Alutard SQ v median placebo ( 95 % confidence interval for difference between medians ] in total symptom scores ( p=0.001 ) in the Alutard SQ treated group ( 360 v 928 ( 238 to 825 ] . Significant differences were also found in total drug use ( p=0.002 , 129 v 627 ( 178 to 574 ] . Visual analogue symptom scores were also reduced in the active group ( p=0.02 , 2.2 v 5.5 ( -4.8 to -0.5 ] . The postseasonal assessment , by either the doctor or the patients , showed a large improvement ( p less than 0.001 ) in favour of Alutard SQ . Provocation tests showed a greater than 10-fold reduction for the active group in immediate conjunctival allergen sensitivity ( p=0.001 ) , a 40 % decrease in early phase response ( p=0.02 ) , and a 57 % decrease in the late phase ( p=0.001 ) cutaneous response after intradermal allergen . A total of 523 active injections were given . There was one systemic reaction at 10 minutes after injection , which was rapidly reversed with intramuscular adrenaline . There was one mild delayed urticarial reaction at 2 1/2 hours . CONCLUSION --Immunotherapy is effective in patients with severe summer hay fever , but immediate anaphylactic reactions limit its use to specialised centres . Patient selection is extremely important , and chronic perennial asthma should be specifically excluded . As serious reactions occur within minutes a two hour wait for all patients after each injection seems unnecessary In a double-blind , placebo-controlled , pilot clinical trial we evaluated the clinical efficacy and safety of immunotherapy ( IT ) with an extract of the pollen of the tree Olea europaea administered sublingually . The parameters tested were symptom score , dose-response bioassay of skin prick test and specific IgE and IgG , and the absolute value at a single serum dilution of each IgG subclass . Fifteen patients allergic to this pollen with symptomatology of rhinitis and /or rhinoconjunctivitis were r and omly allocated to the placebo group ( 6 patients ) or to the extract group ( 9 patients ) . Immunotherapy was administered in a short preseasonal period of time , practically no side effects being recorded . The group of patients treated with extract presented a slightly lower incidence ( 0.05 < p < 0.1 ) of nasal symptoms of sneezing and obstruction , and , more importantly , developed less dyspnea ( p < 0.05 ) than the group treated with placebo , suggesting that IT can act as prophylaxis for the development of bronchial symptoms . No differences were observed in the immunological determinations . Differences in skin tests between the two groups displayed a slight significance ( 0.05 < p < 0.1 ) at the end of the trial ; hence , a higher concentration of the allergen was needed in the group treated with extract to induce the same wheal as in the placebo group . In both groups the size of the wheal showed a time-dependent variation , which was dependent on the time of the year and independent of the type of treatment received , indicating a significant modification in the in vivo skin response to allergen challenge , demonstrated by a shift in the kinetics of allergen-lig and binding ( slope ) and in the magnitude of the measured response ( intercept ) BACKGROUND Seasonal allergic rhinoconjunctivitis affects millions of persons . The efficacy of allergen sublingual immunotherapy ( SLIT ) was demonstrated in previous short-term studies . OBJECTIVES We sought to evaluate the sustained efficacy of 2 dosing regimens of a pre- and coseasonal treatment with 300 IR ( index of reactivity ) 5-grass-pollen SLIT tablets ( Oralair ) compared with placebo assessed by using the average adjusted symptom score ( AAdSS ) at season 3 in adults with grass pollen-induced rhinoconjunctivitis . METHODS Six hundred thirty-three patients were treated for either 2 or 4 months before and then during the grass pollen season with active or placebo treatment for 3 consecutive seasons . The primary outcome was the AAdSS , a symptom score adjusted for rescue medication use , after 3 consecutive treatment seasons . Secondary outcomes were symptoms and rescue medication score , quality -of-life , and safety assessment s. RESULTS The mean AAdSS was reduced by 36.0 % and 34.5 % at season 3 in the 2- and 4-month pre- and coseasonal active treatment groups , respectively , compared with that in the placebo group ( P < .0001 for both ) . Reductions were observed in total symptom scores and ISSs and the medication score , with a marked improvement in quality of life for both active groups compared with the placebo group at season 3 . Most treatment-emergent adverse events were local reactions expected with SLIT , decreasing in number and intensity in each treatment season . CONCLUSIONS Sustained efficacy of 2- and 4-month pre- and coseasonal treatment with the 300 IR tablet over 3 pollen seasons was demonstrated , with reduction in symptoms and rescue medication use . The treatment was well tolerated . Adverse events decreased in number and intensity over the 3 seasons Allergic rhinitis and asthma are examples of allergic airways disease . Despite their differing symptomatology , both disorders affect the mucosal lining of the respiratory tract and are linked by common underlying cellular processes , thus , using the ‘ united airways ’ approach , they can be considered part of the same allergic disease . The conditions are often comorbid , and there is evidence to suggest that allergic rhinitis in children is a significant risk factor for subsequent development of asthma . Management strategies that target the underlying cause of allergic rhinitis in children have the potential to offer additional symptom control above that of symptomatic medications , and prevent disease progression . Specific immunotherapy ( SIT ) is the only currently available treatment that is proven to target the disease in this way . SIT affects the underlying cause of allergic rhinitis , producing changes in antibody responses to allergens . It has been shown to be effective in the reduction of allergic rhinitis symptoms in both children and adults , with effects being sustained for several years after treatment completion . Furthermore , a number of trials provide evidence that SIT may prevent the development of new sensitisations and asthma in children and adults with allergic rhinitis . One such open-label , r and omised controlled study in children/adolescents ( the Preventive Allergy Treatment Study ) showed that significantly fewer patients who received 3 years of SIT for grass/birch pollen-induced allergic rhinitis had developed asthma 10 years after treatment initiation versus controls . Some clinical guidelines acknowledge this potential asthma preventive effect in children and the need for additional data from double-blind , placebo-controlled trials to support these findings BACKGROUND Specific immunotherapy is the only treatment modality that has the potential to alter the natural course of allergic diseases . Sublingual immunotherapy has been developed to facilitate access to this form of treatment and to minimize serious adverse events . OBJECTIVE To investigate the efficacy and safety of sublingual grass allergen tablets in seasonal allergic rhinoconjunctivitis . METHODS A multinational , multicenter , r and omized , placebo-controlled trial conducted during 2002 and 2003 . Fifty-five centers in 8 countries included 855 participants age 18 to 65 years who gave a history of grass pollen-induced allergic rhinoconjunctivitis and had a positive skin prick test and elevated serum allergen-specific IgE to Phleum pratense . Participants were r and omized to 2500 , 25,000 , or 75,000 SQ-T grass allergen tablets ( GRAZAX ; ALK-Abelló , Hørsholm , Denmark ) or placebo for sublingual administration once daily . Mean duration of treatment was 18 weeks . RESULTS Average rhinoconjunctivitis scores during the season showed moderate reductions of symptoms ( 16 % ) and medication use ( 28 % ) for the grass allergen tablet 75,000 SQ-T ( P = .0710 ; P = .0470 ) compared with placebo . Significantly better rhinoconjunctivitis quality of life scores ( P = .006 ) and an increased number of well days ( P = .041 ) were also observed . Efficacy was increased in the subgroup of patients who completed the recommended preseasonal treatment of at least 8 weeks before the grass pollen season ( symptoms , 21 % , P = .0020 ; and medication use , 29 % , P = .0120 ) . No safety concerns were observed . CONCLUSION This study confirms dose-dependent efficacy of the grass allergen tablet . Although further studies are required , the greater tolerability of the tablet may permit immunotherapy to be available to a much broader group of patients with impaired quality of life caused by grass pollen allergy . CLINICAL IMPLICATION S For patients with grass pollen allergy , sublingual immunotherapy is well tolerated and can reduce symptoms and improve quality of life BACKGROUND We wondered whether short-term coseasonal sublingual immunotherapy ( SLIT ) can reduce the development of asthma in children with hay fever in an open r and omized study . OBJECTIVE We sought to determine whether SLIT is as effective as subcutaneous immunotherapy in reducing hay fever symptoms and the development of asthma in children with hay fever . METHODS One hundred thirteen children aged 5 to 14 years ( mean age , 7.7 years ) with hay fever limited to grass pollen and no other clinical ly important allergies were r and omized in an open study involving 6 Italian pediatric allergy centers to receive specific SLIT for 3 years or st and ard symptomatic therapy . All of the subjects had hay fever symptoms , but at the time of study entry , none reported seasonal asthma with more than 3 episodes per season . Symptomatic treatment was limited to cetirizine , loratadine , nasal budesonide , and salbutamol on dem and . The hay fever and asthma symptoms were quantified clinical ly . RESULTS The actively treated children used less medication in the second and third years of therapy , and their symptom scores tended to be lower . From the second year of immunotherapy , subjective evaluation of overall allergy symptoms was favorable in the actively treated children . Development of asthma after 3 years was 3.8 times more frequent ( 95 % confidence limits , 1.5 - 10.0 ) in the control subjects . CONCLUSIONS Three years of coseasonal SLIT improves seasonal allergic rhinitis symptoms and reduces the development of seasonal asthma in children with hay fever BACKGROUND Pollen immunotherapy is effective in selected patients with IgE-mediated seasonal allergic rhinitis , although it is question able whether there is long-term benefit after the discontinuation of treatment . METHODS We conducted a r and omized , double-blind , placebo-controlled trial of the discontinuation of immunotherapy for grass-pollen allergy in patients in whom three to four years of this treatment had previously been shown to be effective . During the three years of this trial , primary outcome measures were scores for seasonal symptoms and the use of rescue medication . Objective measures included the immediate conjunctival response and the immediate and late skin responses to allergen challenge . Cutaneous-biopsy specimens obtained 24 hours after intradermal allergen challenge were examined for T-cell infiltration and the presence of cytokine-producing T helper cells ( TH2 cells ) ( as evidence d by the presence of interleukin-4 messenger RNA ) . A matched group of patients with hay fever who had not received immunotherapy was followed as a control for the natural course of the disease . RESULTS Scores for seasonal symptoms and the use of rescue antiallergic medication , which included short courses of prednisolone , remained low after the discontinuation of immunotherapy , and there was no significant difference between patients who continued immunotherapy and those who discontinued it . Symptom scores in both treatment groups ( median areas under the curve in 1995 , 921 for continuation of immunotherapy and 504 for discontinuation of immunotherapy ; P=0.60 ) were markedly lower than those in the group that had not received immunotherapy ( median value in 1995 , 2863 ) . Although there was a tendency for immediate sensitivity to allergen to return late after discontinuation , there was a sustained reduction in the late skin response and associated CD3 + T-cell infiltration and interleukin-4 messenger RNA expression . CONCLUSIONS Immunotherapy for grass-pollen allergy for three to four years induces prolonged clinical remission accompanied by a persistent alteration in immunologic reactivity BACKGROUND To assess the efficacy and safety of sublingual immunotherapy in patients with allergic rhinitis/conjunctivitis , a double blind placebo controlled study was performed . METHODS AND RESULTS Fifty-seven ( 57 ) patients with a well-documented history of seasonal grass pollen allergy were evaluated in a DBPC trial over a period of 10 months ( January to November 1995 ) with a view to investigating the efficacy and safety of sublingual immunotherapy with a grass pollen extract , 9,500 BU/ml . The course of treatment consisted of an incremental phase of approximately 3 weeks followed by a twice weekly maintenance dosage of 9,500 BU . Compared with the placebo group ( 30 patients ) , the group treated with grass pollen extract ( 27 patients ) showed a significant ( p < 0.03 ) lower mean severity of allergic complaints , i.e. sneezing , and itchy nose , a watery runny nose and itching of the eyes during the maximum pollen counts of the season . The use of anti-allergic medication was similar in the two groups . Both groups showed a significant increase in grass-pollen-specific IgG serum levels . However , the increase shown in the patients treated with grass pollen extract occurred earlier in the season and was significantly ( p < 0.002 ) higher than the increase detected in the placebo group . Side effects were limited to a small number of generally mild local reactions . CONCLUSIONS The treatment with sublingually applied grass pollen extract in patients suffering from allergic rhinoconjunctivitis caused by grass pollen was well tolerated and served to reduce the severity of allergic complaints , without reducing the consumption of anti-allergic medication BACKGROUND Immunotherapy with the SQ-st and ardized grass tablet Grazax is efficacious and well-tolerated in adult patients with rhinoconjunctivitis . Allergic asthma and rhinoconjunctivitis are closely linked , and a strategy combining treatment of the upper and lower airways is recommended . OBJECTIVE To investigate the efficacy of treatment with the grass tablet on grass pollen-induced rhinoconjunctivitis and asthma as well as the immunologic response and the safety profile in children . METHODS A total of 253 children age 5 to 16 years , with grass pollen-induced rhinoconjunctivitis with/without asthma , were r and omized 1:1 to active treatment or placebo . Treatment was initiated 8 to 23 weeks before the start of the grass pollen season 2007 and continued throughout the entire season . Symptomatic medication was provided as relief medication to both groups in a stepwise fashion . Primary endpoints were rhinoconjunctivitis symptom and medication scores . RESULTS The rhinoconjunctivitis symptom and medication scores and the asthma symptom score were all statistically significantly different between the 2 treatment groups . The differences in medians relative to placebo were 24 % , 34 % , and 64 % in favor of active treatment . The immunologic response was similar to that observed in adults . The most common adverse reaction was oral pruritus , reported by 40 subjects ( 32 % ) in the active and 3 ( 2 % ) in the placebo group . Six subjects withdrew because of adverse events . No serious adverse events were assessed as treatment-related . CONCLUSION Immunotherapy with the grass tablet reduced grass pollen-induced rhinoconjunctivitis and asthma symptoms in a pediatric population and introduced an immunomodulatory response , consistent with treatment of the underlying allergic disease . The treatment was well tolerated In a double-blind study , we compared the effects of the Rinkel method of immunotherapy with ragweed pollen extract and placebo on symptoms of ragweed hay fever and immunologic parameters in 24 ragweed-sensitive patients . Each had a skin-test end point by Rinkel serial dilution titration to ragweed pollen extract at 1:312,500 w/v or greater dilution , a 2 + skin test to ragweed AgE at 0.1 microgram /ml or greater dilution , and in vitro leukocyte histamine release by ragweed pollen extract . None had had immunotherapy for at least 7 yr . Patients matched on the basis of leukocyte histamine release by ragweed were assigned to two treatment groups ( 12 patients in each group ) . One group received ragweed pollen extract , and the other , placebo , both administered by the Rinkel method between June and October , 1978 . Treatment doses were derived from skin-test end points . The median maintenance ( " optimal dose " ) for patients receiving ragweed pollen extract was 0.53 ml of 1:312,500 w/v and the mean cumulative dose of ragweed pollen extract given during the study contained 0.094 micrograms of ragweed AgE. Symptom-medication scores of all patients rose and fell with ragweed pollen counts . No significant differences were observed in mean daily symptom-medication scores , antiragweed IgG or IgE levels , leukocyte histamine release by ragweed , total IgE levels , or skin-test end-point dilutions with ragweed pollen extract between the group receiving ragweed pollen extract and the group receiving placebo . Despite the absence of specific effect on symptom-medication scores and measured immunologic variates , 10 3f the 12 ragweed-treated patients and 10 of the 12 placebo-treated patients were of the opinion that their hay fever symptoms during the ragweed pollen season were less severe in 1978 than in 1977 and that they had been helped by Rinkel method immunotherapy . Under the conditions of the study , Rinkel method immunotherapy with ragweed pollen extract was no more effective than placebo given in an imitation of the Rinkel method BACKGROUND Allergic rhinoconjunctivitis is a global health problem . Around 14 million people in Spain , France , Italy , and Austria suffer from grass pollen induced allergic rhinitis . St and ard care only provides symptoms relief , while allergen specific immunotherapy ( SIT ) treats the underlying cause of the disease . Grazax from ALK-Abelló is a new , tablet-based , effective route of SIT for home treatment . The objective was to assess the cost-effectiveness of Grazax in four Southern European countries . METHODS A prospect i ve pharmacoeconomic analyses was carried out alongside a multinational , clinical trial measuring the efficacy of Grazax . Pooled data on re source use and health outcomes were collected . A societal perspective was adopted , and the analysis had a nine-year time horizon . The primary outcome measure was quality adjusted life years ( QALYs ) . RESULTS Grazax was superior to st and ard care for all efficacy endpoints , including QALYs gained , and result ed in significantly less use of rescue medication and fewer hours missed from work . Grazax was cost-effective for all countries for an annual price in the range of 1500 euros - 1900 euros . The result was improved by inclusion of future costs of asthma and exclusion of Spanish trial centers which experienced an exceptionally low pollen season . CONCLUSION The analysis illustrates that allergen SIT with Grazax for grass pollen induced rhinoconjunctivitis is a cost-effective intervention in Southern Europe In a prospect i ve , double-blind , placebo-controlled study , we examined the effect of mountain cedar ( MC ) immunotherapy on the MC-induced late cutaneous response ( LCR ) . Fourteen MC-sensitive patients were intradermally skin tested before and after immunotherapy with MC extract . We measured the size of the wheal at 15 minutes and the area of tissue swelling at 6 hours . Patients were matched by the size of the LCR and started receiving either MC immunotherapy or placebo immunotherapy . MC-specific immunoglobulins ( MC sIgG , MC sIgG1 , MC sIgG4 , and MC sIgE ) were measured by ELISA . Symptom-medication scores ( SMSs ) were recorded on a daily basis during the MC season and tabulated at the end of the study . Comparison of the 14 paired patients revealed no significant differences between MC-treated and placebo-treated groups in preimmunotherapy MC sIgG1 and SIgG4 . However , when MC immunotherapy was compared to placebo immunotherapy , patients receiving MC immunotherapy developed significantly higher MC sIgG1 ( p less than 0.04 ) and MC sIgG4 ( p less than 0.01 ) after immunotherapy . Patients receiving MC immunotherapy also demonstrated significantly greater suppression of the LCR after immunotherapy ( p less than 0.005 ) with the postimmunotherapy LCR correlating significantly with both MC sIgG4 ( rs = 0.715 ; p = 0.008 ) and cumulative dose of MC received ( rs = 0.808 ; p = 0.004 ) . MC sIgE was similar in both groups after immunotherapy . The reduction in SMSs in the MC-treated group did not reach significance , nor was there a correlation of SMSs with MC sIgE , sIgG , sIgG1 , or sIgG4 . ( ABSTRACT TRUNCATED AT 250 WORDS 4 patients suffering from severe pollinosis and /or allergic rhinitis , with or without asthma , were treated as follows : 30 minutes before breakfast the vaccine was dropped sublingually and retained for 2 - 3 minutes before being swallowed . It was a commercial preparation of allergen , diluted 50 % w/v in glycerin . This stock solution was then diluted in physiological saline containing 0.05 % human albumin and kept refrigerated in a dark glass bottle for up to 4 weeks . Of the first dilution which contained 10 Au/ml , 1 drop was given on day 1 and 1 drop more each day until days 5 to 17 , when 5 drops were given daily . Then 1000 and then 2500 Au/ml were given sequentially in the same manner , and finally 5000 was given for up to 2 years . A maintenance dose of 3 drops of 5000 Au/ml twice weekly was then prescribed . 41 patients showed striking clinical improvement after about 6 months of treatment . A definite reduction in the use of other medications was achieved in all . Sublingual immunotherapy is practically free of unwanted side effects and easy to self-administer at home . To establish the specificity of sublingual immunotherapy , patients who had severe allergic symptoms to one pollen allergen causing symptoms in the spring and to a second in the autumn , were first immunized sublingually against a single allergen . A year later , after symptoms due to this allergen had subsided , and if symptoms caused by the second allergen had not improved , immunization against the second allergen was started . Sublingual immunotherapy acts by increasing mucosal antibodies at the site of entry of the allergen into the respiratory tract . It is a safe and practical procedure with results comparable to subcutaneous allergy injections Forty-one patients suffering from grass pollen allergy underwent specific immunotherapy with st and ardized allergen extract consisting of six grass pollens ( H-Al per os ) administered either sublingually or supralingually for one year . In order to investigate clinical and immunological changes induced by the administration of allergens via the oral mucosa , the double-blind , placebo-controlled , r and omized design of the trial with 30 other patients enrolled in placebo groups was applied . Specific immunotherapy with oral drops administered sublingually or supralingually was performed in the same way , keeping the drops under or on the tongue , respectively , for 1 - 2 min before swallowing them ; at the end of the trial the cumulative dose of the allergen was almost 20 times higher than that of the subcutaneous therapy with corresponding allergen preparation . Data about symptoms scores and drugs intake during grass pollen season , as well as skin reactivity , levels of specific IgG and IgE antibodies , before the study and after the study 's completion , were obtained . It was found that both routes of administration are effective according to subjective clinical parameters and drug consumption , with a highly significant reduction of symptoms and drug intake favoring sublingual administration where a reduction of more than 60 % was achieved . Only sublingual active group showed a significant increase in Dactylis glomerata-specific IgG serum levels . Adverse effects were limited to a small number of generally mild local and /or systemic reactions . The results suggest that the administration of allergens via the oral mucosa is safe and clinical ly effective , favoring the sublingual rather than supralingual route OBJECTIVE To investigate the health and monetary consequences of treating allergy with specific immunotherapy ( SIT ) compared with symptomatic treatment/st and ard care among patients with grass pollen or mite allergy . METHODS We performed an economic analysis based on 253 grass- and /or mite allergic patients who started SIT from 1.1.1996 to 1.1.2002 at the Allergy Unit , Aarhus University Hospital and at a specialist practice in Aarhus . Relevant data were collected before , during and after SIT treatment from the national health service based on each patient 's personal identification number and medical records and from a specifically design ed question naire . A cost-benefit analysis including direct and indirect costs before , during and after SIT was performed . In addition direct costs were related to the clinical effect ( improvement in well-being ) in the form of a cost-effectiveness analysis . RESULTS The direct cost per patient/year before SIT ( equivalent to st and ard care ) was DKK 2,580 . The investment in SIT was DKK 27,545 ( in present values ) per patient over a 4-year period . After SIT the cost was reduced to DKK 1,072 per patient/year . In the long term , prospect i ve introduction of SIT incurred additional present-value direct costs of DKK 13,676 per patient treated and DKK 2,784 per patient/year of improved well-being . However , when indirect costs were included in the economic evaluation SIT was shown to be net beneficial . CONCLUSION This study reveals that SIT is associated with initial re source investments and subsequent re source savings in the long term compared with st and ard care . When all consequences are measured in monetary terms , and assuming that sick days are associated with a loss of productivity , this analysis suggests that SIT increases societal welfare . This conclusion also holds if there is no loss of productivity Two groups of 15 patients with respiratory allergy due to the pollen of Parietaria judaica were studied ; one received a treatment of oral specific hyposensitization , the other one a placebo . All of them were monosensitized and clinical ly matched according to age , gender , score symptoms , drug consumption , skin test and RAST , and nasal or bronchial provocation test . The pollen counts were the same during this period . The study was double-blind and lasted 2 years . The clinical tests including score symptoms , drug consumption , and nasal or bronchial provocation test , revealed a statistically significant improvement in the treated group as compared to the placebo group . No side effects were observed The objective of this study was to develop and test a health‐related quality of life question naire for clinical trials in rhinoconjunctivitis . The Rhinoconjunctivitis Quality of Life Question naire ( RQLQ ) was developed by asking patients to identify areas of their lives affected by rhinoconjunctivitis . The result ant RQLQ was tested for reproducibility , responsiveness and validity in a r and omized , double‐blind trial of regular versus ‘ as required ’ aqueous beclomethasone dipropionate ( BDP ) nasal spray in ragweed pollen‐induced rhinoconjunctivitis . Eighty‐five patients from previous rhinoconjunctivitis studies participated in the developmental survey . Sixty ragweed‐sensitive patients , from previous trials and media notices , were enrolled in the clinical trial . Aqueous BDP ( 800 μg ) nasal spray was administered regularly or ‘ as required ’ throughout the ragweed pollen season . The survey revealed that , in addition to local symptoms of rhinoconjunctivitis , patients experienced impairment of quality of life through systemic symptoms , sleep disturbance , practical problems , activity limitations and emotional problems . The RQLQ includes 28 questions related to these dimensions . Repeated administration of the RQLQ demonstrated good reproducibility . During the clinical trial , the RQLQ proved responsive in its ability to distinguish between regular and ‘ as required ’ medication use . Validity was shown by moderate to strong relations between changes in symptom diary scores and changes in RQLQ scores . In conclusion the RQLQ is likely to prove useful as a measure of health‐related quality of life in clinical trials in both rhinoconjunctivitis and rhinitis Background The allergological relevance of Ambrosia in Europe is growing but the efficacy of the injective immunotherapy for this allergen has been documented only in Northern America BACKGROUND Although the efficacy of allergen immunotherapy has been demonstrated in seasonal pollen allergy , there is no report of a double-blind placebo-controlled trial with st and ardized pollen extract in seasonal respiratory allergy from India . In the agricultural area of eastern India , Phoenix sylvestris Roxb or date sugar palm is grown or cultivated and seasonal allergic rhinitis is common during the pollen season . OBJECTIVE The objective of the present study was to observe the clinical and immunological changes during a 2-year double-blind placebo-controlled trial of immunotherapy with st and ardized P sylvestris pollen extract in respiratory patients sensitive to pollen from this wild date palm . Thirty-five subjects with typical seasonal allergic rhinitis with or without bronchial asthma were selected . A symptom-medication score ( based on a question naire and diary ) was correlated with pollen counts as recorded in a Burkard sample r. Eighteen subjects were r and omized to a specific immunotherapy ( SIT ) group receiving regular injections containing st and ardized allergen extract and 17 to a placebo control group . Changes in the level of specific immunoglobulin ( Ig ) E , IgG1 , and IgG4 were recorded at 3-month intervals . Measurement of wheal diameter , total IgE level and forced expiratory volume in 1 second ( FEV1 ) were performed before starting and a month after finishing therapy . RESULTS The SIT group showed decreases of 33.5 % and 57 % from the baseline symptom-medication scores during the first and second treatment season , respectively . This group showed significant decreases in skin-reactivity to P sylvestris pollen extract and in specific IgE levels , and significant increases in FEV , , specific IgGI ( 1.95 - 3.2 times higher ) and IgG4 ( 21.24 - 30.83 times higher ) . There were no significant changes in total IgE levels . The control group showed no significant changes for any parameter except the development of new sensitization in 2 cases ( to Saccharum officinarum pollen grain and Alternaria species spores ) . The rate of local adverse reactions was 0.024 % . CONCLUSION After a 2-year study , allergen immunotherapy with st and ardized P sylvestris pollen extract was found to be effective in seasonal respiratory allergic subjects susceptible to P sylvestris pollen with a narrow range of sensitization Forty-five grass pollen-allergic patients were r and omly assigned to three groups according to their skin test and RAST sensitivities and the severity of seasonal rhinitis . Eleven patients were treated with placebo ( group 1 ) , 19 patients ( group 2 ) were treated with a six-mixed grass-pollen allergoid prepared by mild formalinization with a two-step procedure , and 15 other patients were treated with a st and ardized orchard grass-pollen extract ( group 3 ) . Because of a different immunotherapy schedule , only patients placed in groups 1 and 2 received the extracts in a double-blind fashion . Rush immunotherapy was performed in 3 to 6 days , and the maintenance dose was subsequently administered weekly for 4 weeks and every 2 weeks until the end of the grass-pollen season . During the season , a coseasonal treatment was administered . Systemic reactions occurred during the rush protocol in 36.8 % of patients treated with allergoid and 20 % of patients who received the st and ardized extract . Only patients treated with allergoid had systemic reactions during maintenance dose . The reactions observed with the st and ardized extract were more severe . Total doses of allergoid ranged from 2350 to 13,500 protein nitrogen units . Symptoms and medication scores during the peak of the season were analyzed . Patients treated with the st and ardized allergen had a significant reduction of the number of days of symptoms during the month of June ( 9.5 + /- 6.7 days ; p less than 0.005 ) and of medication scores ( 1.3 + /- 1.4 ; p less than 0.01 ) compared to patients receiving placebo ( 19.4 + /- 8.1 days ; medication score , 2.8 + /- 2.1 ) . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Children with allergic rhinitis are likely to develop asthma . OBJECTIVE The purpose of this investigation was to determine whether specific immunotherapy can prevent the development of asthma and reduce bronchial hyperresponsiveness in children with seasonal allergic rhinoconjunctivitis . METHODS From 6 pediatric allergy centers , 205 children aged 6 to 14 years ( mean age , 10.7 years ) with grass and /or birch pollen allergy but without any other clinical ly important allergy were r and omized either to receive specific immunotherapy for 3 years or to an open control group . All subjects had moderate to severe hay fever symptoms , but at inclusion none reported asthma with need of daily treatment . Symptomatic treatment was limited to loratadine , levocabastine , sodium cromoglycate , and nasal budesonide . Asthma was evaluated clinical ly and by peak flow . Methacholine bronchial provocation tests were carried out during the season(s ) and during the winter . RESULTS Before the start of immunotherapy , 20 % of the children had mild asthma symptoms during the pollen season(s ) . Among those without asthma , the actively treated children had significantly fewer asthma symptoms after 3 years as evaluated by clinical diagnosis ( odds ratio , 2.52 ; P < .05 ) . Methacholine bronchial provocation test results improved significant in the active group ( P < .05 ) . CONCLUSION Immunotherapy can reduce the development of asthma in children with seasonal rhinoconjunctivitis UNLABELLED Sublingual immunotherapy ( SLIT ) has been recognized as a viable alternative to subcutaneous immunotherapy for respiratory allergies both in adults and children , but clinical documentation about safety and efficacy in children is still poor . The purpose of this study was to assess the efficacy and tolerance of SLIT in children who are sensitized to grass pollen . METHODS Children with a clinical history of intermittent rhinoconjunctivitis , with or without mild asthma and positive skin prick tests to grass pollen , were selected to participate in a 2-year double-blind , placebo-controlled study with SLIT , using a grass extract ( ALK-Abellò ) . RESULTS 22 children were analyzed at the end of the study . No relevant side effects occurred in the active group . A statistically significant difference ( p = 0.05 ; Mann-Whitney test ) in favor of the active group ( n = 10 ) could be shown for drug consumption during the second year , as well as a significant improvement as compared to the first year of SLIT ( p = 0.05 ; Wilcoxon test ) . CONCLUSIONS Despite the small number of patients , our data suggest that SLIT with a grass pollen extract is well tolerated in children and is able to significantly reduce drug consumption during the second year of treatment . Studies in larger groups of children sensitized to both grass and tree pollens are needed to definitively assess the role of SLIT in intermittent , seasonal rhinitis and pollen asthma Background Immunotherapy is a recognized treatment for allergic respiratory diseases BACKGROUND Short-term immunotherapy ( STI ) can be beneficial for patients who are noncompliant with long-term specific immunotherapy . OBJECTIVE The efficacy and tolerance of STI with seven preseasonal injections of molecular st and ardized allergens from grass and rye pollen has been investigated in a double-blind , placebo-controlled multicenter study with 87 patients at 12 German University hospitals . METHODS Symptoms of the eyes , nose , and bronchi and use of symptomatic drugs were documented daily in diaries by patients with allergic rhinitis to grass and /or rye pollen and without bronchial asthma . Patients were monitored by skin prick test titration and measurement of levels of specific IgE and IgG4 . RESULTS The median nasal score for the 10 weeks with the strongest symptoms during the grass pollen season was significantly lower ( p = 0.014 ) with 35.0 for STI ( n = 41 ) versus 69.0 for placebo ( n = 40 ) ; the overall symptom score was 54.0 for STI versus 97.5 for placebo ( p = 0.020 ) . Only STI-treated patients exposed to less than 40 pollen grains per cubic meter per week showed a significantly lower nasal symptom score of 39.0 versus 75.0 for placebo ( p = 0.006 ) ; these patients also had fewer nasal symptoms and less use of topical nasal drugs ( p < 0.001 ) . The threshold dose in skin prick tests was significantly higher , being 9.06 histamine equivalent for skin prick test ( HEP ) for STI-treated patients who received the maximum dose ( n = 22 ) versus 4.33 HEP for placebo ( p = 0.005 ) . Specific IgE levels were significantly higher , being 55.9 SU/ml for STI versus 39.2 SU/ml for placebo after seven injections ( p = 0.006 ) and level of specific IgG4 was 5.36 % for STI versus 1.28 % for placebo ( p < 0.001 ) . No severe systemic reactions were observed . CONCLUSION STI with seven preseasonal injections with molecular st and ardized allergens is effective and well tolerated Parallel follow-up of clinical and inflammatory markers during sub-lingual immunotherapy ( SLIT ) is highly beneficial . Twenty-four children ( age 4 - 16 ) monosensitized to house dust mite were r and omized to receive either active or placebo SLIT for 1 yr in a double-blind placebo controlled design ( Marcucci et al. , Allergy 2003 : 58 : 657 - 62 ) . Thereafter , for 2 yr they all received active treatment . Symptom scores for rhinitis , asthma , and drug usage were daily recorded . Eosinophil cationic protein ( ECP ) and tryptase in sputum and nasal secretions , serum and nasal mite-specific immunoglobulin E ( IgE ) were recorded before treatment and at 10 - 12 months intervals . Nasal ECP and nasal tryptase after specific nasal provocation tests were significantly reduced as compared to baseline values ( p = 0.0043 and 0.0195 , respectively ) in the third year of active treatment . None of the other inflammatory parameters was increased . In placebo treated patients all these parameters tended to decrease only after switching to active treatment . Clinical scores did not improve in treated vs. placebo patients in the double-blind placebo-controlled phase of the study . In both cohorts a clinical benefit was observed as intra-group score reduction as compared to baseline . A significant difference was reached in patients treated for 2 yr for rhinitis and asthma ( p = 0.0009 and 0.0019 , respectively ) but not for drug usage and in patients treated for 3 yr for rhinitis , asthma , and drug usage ( p = 0.0105 , 0.0048 , and 0.02 , respectively ) . SLIT in children monosensitized to mites reverted the spontaneous increase in nasal IgE and in local parameters of allergic inflammation . These outcomes were followed by a consoli date d clinical improvement in the second and third year of treatment To cite this article : Häfner D , Reich K , Matricardi PM , Meyer H , Kettner J , Narkus A. Prospect i ve validation of ‘ Allergy‐Control‐SCORETM ’ : a novel symptom – medication score for clinical trials . Allergy 2011 ; 66 : BACKGROUND Sublingual immunotherapy ( SLIT ) is considered safer and more convenient than subcutaneous therapy and therefore has been proposed as especially suitable for children and in primary care . Most efficacy studies in children lack power to be conclusive , and all have been performed in referral centers . OBJECTIVE To investigate the efficacy of SLIT with grass pollen allergen in children and adolescents with rhinoconjunctivitis in a primary care setting . METHODS Youngsters aged 6 - 18 years with hay fever were enrolled from general practice s and r and omly assigned to receive placebo or grass pollen mix for 2 years . The primary outcome was the mean daily total symptom score ( scale 0 - 15 ) comprising sneezing , itching nose , watery running nose , nasal blockage , and itching eyes during the months May-August of the second treatment year . RESULTS Out of 204 youngsters r and omized , 168 entered the intention-to-treat analysis ( 91 verum , 77 placebo ) . The mean daily total symptom score did not differ between participants allocated to verum and those allocated to placebo ( difference for verum minus placebo : -0.08 , 95%CI , -0.66 - 0.50 ; P = .78 ) . No differences were found for rescue medication-free days , disease-specific quality of life , and overall evaluation of the treatment effect . Local side effects were more frequent in the verum group ( 39 % vs 17 % of participants ; P = .001 ) . CONCLUSION Sublingual immunotherapy with grass pollen in a primary care setting is not effective in children and adolescents . CLINICAL IMPLICATION S Currently , SLIT can not be recommended for general practitioners as a therapeutic modality in youngsters with grass pollen allergy Specific immunotherapy is a well-established treatment for allergic rhinoconjunctivitis ; conventional regimens are lengthy , however , reducing convenience and cost-effectiveness . This study evaluated the efficacy and safety of an ultrashort course ( four doses ) of the immunotherapy Grass Modified Allergen Tyrosine Adsorbate ( Allergy Therapeutics , Worthing , U.K. ) monophosphoryl lipid A ( MATA MPL ) . Subjects were r and omized to receive four injections of either Grass MATA MPL ( n = 514 ; 300 - 2000 st and ardized units/injection ) or placebo ( n = 514 ) before the grass pollen season . They used electronic diaries to record allergy symptoms and medication use during the pollen season . The primary end point was the difference between the mean combined symptom and medication scores in the Grass MATA MPL and placebo groups during the 4 local peak pollen weeks . The injection course was completed by 95.3 and 97.7 % of the Grass MATA MPL and placebo groups , respectively , and was well tolerated . Grass MATA MPL treatment afforded a 13.4 % benefit over placebo in the 4 peak pollen weeks ( p = 0.0038 ) . The benefit in subjects with 28 complete diary entries during the 4 peak pollen weeks was 26.9 % ( p = 0.0031 ) . Significant benefits over placebo were observed in subjects with severe symptoms ( 17.1 % ; p = 0.0023 ) , in those who had a history of allergic rhinoconjunctivitis for up to 35 years ( up to 37.2 % ; p = 0.0059 ) and at sites with a higher burden of disease ( 38.3 % ; p < 0.0001 ) . The ultrashort course of Grass MATA MPL was well tolerated and provided a significant benefit over placebo in relieving allergy symptoms BACKGROUND Sublingual immunotherapy is well tolerated and data suggest its effectiveness for the treatment of allergic rhinitis in adults , but it lacks optimum dose definition . OBJECTIVE To assess the efficacy , safety , and optimal dose of grass pollen tablets for immunotherapy of patients with allergic rhinoconjunctivitis . METHODS In this multinational , r and omized , double-blind , placebo-controlled study , 628 adults with grass pollen rhinoconjunctivitis ( confirmed by positive skin prick test and serum-specific IgE ) received 1 of 3 doses of a st and ardized 5-grass pollen extract , or placebo , administered sublingually using a once-daily tablet formulation . The treatment was initiated 4 months before the estimated pollen season and continued throughout the season . The primary outcome was Rhinoconjunctivitis Total Symptom Score ; secondary outcomes included 6 individual symptom scores , rescue medication use , quality of life , and safety assessment s. RESULTS Both the 300-index of reactivity ( IR ) and 500-IR doses significantly reduced mean Rhinoconjunctivitis Total Symptom Score ( 3.58 + /- 3.0 , P = .0001 ; and 3.74 + /- 3.1 , P = .0006 , respectively ) compared with placebo ( 4.93 + /- 3.2 ) in the intent-to-treat and per- protocol analyses . The 100-IR group ( 4.70 + /- 3.1 ) score was not significantly different from placebo . Analysis of all secondary efficacy variables ( sneezing , runny nose , itchy nose , nasal congestion , watery eyes , itchy eyes , rescue medication usage , and quality of life ) confirmed the efficacy of the 300-IR and 500-IR doses . No serious side effects were reported . CONCLUSION In the first pollen season , the efficacy and safety of sublingual immunotherapy with grass tablets was confirmed . The 300-IR and 500-IR doses both demonstrated significant efficacy compared with placebo . CLINICAL IMPLICATION S The risk-benefit ratio favors the use of 300-IR tablets for clinical practice Background Previous studies suggest that sublingual immunotherapy ( SLIT ) represents a safer alternative to injection immunotherapy but equivalent efficacy is yet to be confirmed BACKGROUND Conjugating immunostimulatory sequences of DNA to specific allergens offers a new approach to allergen immunotherapy that reduces acute allergic responses . METHODS We conducted a r and omized , double-blind , placebo-controlled phase 2 trial of a vaccine consisting of Amb a 1 , a ragweed-pollen antigen , conjugated to a phosphorothioate oligodeoxyribonucleotide immunostimulatory sequence of DNA ( AIC ) in 25 adults who were allergic to ragweed . Patients received six weekly injections of the AIC or placebo vaccine before the first ragweed season and were monitored during the next two ragweed seasons . RESULTS There was no pattern of vaccine-associated systemic reactions or clinical ly significant laboratory abnormalities . AIC did not alter the primary end point , the vascular permeability response ( measured by the albumin level in nasal-lavage fluid ) to nasal provocation . During the first ragweed season , the AIC group had better peak-season rhinitis scores on the visual-analogue scale ( P=0.006 ) , peak-season daily nasal symptom diary scores ( P=0.02 ) , and midseason overall quality -of-life scores ( P=0.05 ) than the placebo group . AIC induced a transient increase in Amb a 1-specific IgG antibody but suppressed the seasonal increase in Amb a 1-specific IgE antibody . A reduction in the number of interleukin-4-positive basophils in AIC-treated patients correlated with lower rhinitis visual-analogue scores ( r=0.49 , P=0.03 ) . Clinical benefits of AIC were again observed in the subsequent ragweed season , with improvements over placebo in peak-season rhinitis visual-analogue scores ( P=0.02 ) and peak-season daily nasal symptom diary scores ( P=0.02 ) . The seasonal specific IgE antibody response was again suppressed , with no significant change in IgE antibody titer during the ragweed season ( P=0.19 ) . CONCLUSIONS In this pilot study , a 6-week regimen of the AIC vaccine appeared to offer long-term clinical efficacy in the treatment of ragweed allergic rhinitis . ( Clinical Trials.gov number , NCT00346086 [ Clinical Trials.gov ] . ) Background : Sublingual immunotherapy ( SLIT ) allergy vaccines have an excellent safety profile , but opinions vary on their efficacy , and treatment regimens are often lengthy . This study assessed the effects of the Toll-like receptor 4 agonist monophosphoryl lipid A ( MPL ® ) on safety/tolerability and clinical and immunological efficacy when combined with grass pollen SLIT formulations in treating patients with seasonal allergic rhinitis . This is the first reported study of adjuvanted SLIT . Methods : In this double-blind placebo-controlled phase I/IIa study , 80 grass pollen-sensitive subjects were r and omized into 4 groups of 20 subjects to receive daily treatment for 8 weeks . Sixteen patients per group received SLIT and 4 received placebo . The formulation given to each group varied with respect to grass pollen extract and MPL content . Grass allergen nasal challenge tests ( NCTs ) were performed prior to dosing and in weeks 4 and 10 . Grass pollen-specific immunoglobulin G ( IgG ) and IgE antibodies were measured at baseline and prior to dosing in weeks 2 , 3 , 4 , 5 and 10 . Results : Local and systemic adverse events were generally comparable for patients who received active treatment and placebo . Patients in the 2 groups given SLIT containing the highest amount of MPL experienced the highest proportion of negative NCTs after 10 weeks ( 47 and 44 % , vs. 20 % with placebo ) . These patients also showed earlier median increases in specific IgG and smaller increases in IgE levels than those receiving other formulations . Conclusions : These results suggest that SLIT preparations containing MPL are well tolerated and alter the immunological response to grass antigens after 3 weeks of exposure , with an associated suppression of nasal challenge responses BACKGROUND Allergen-specific immunotherapy uses aqueous extracts of natural source material s as a basis for preparations to down regulate the allergic response . Recombinant DNA technology has enabled the cloning of many allergens , thus facilitating investigations aim ed at improving efficacy and safety of immunotherapy . OBJECTIVE To determine the effectiveness of a mixture of 5 recombinant grass pollen allergens in reducing symptoms and need for symptomatic medication in patients allergic to grass pollen . METHODS A r and omized , double-blind , placebo-controlled study of subcutaneous injection immunotherapy was performed in subjects with allergic rhinoconjunctivitis , with or without asthma . Primary endpoint was a symptom medication score compiled from separate symptom and medication scores . Secondary endpoints included a rhinitis quality of life question naire , conjunctival provocation , and specific antibody responses . RESULTS The symptom medication score showed significant improvements in subjects receiving recombinant allergens as opposed to placebo , with reductions in both symptoms and medication usage . The rhinitis quality of life question naire revealed clinical ly relevant significant improvements in overall assessment and in 5 of 7 separate domains , and conjunctival provocation showed a clear trend in favor of active treatment . All treated subjects developed strong allergen-specific IgG(1 ) and IgG(4 ) antibody responses . Some patients were not sensitized to Ph l p 5 but nevertheless developed strong IgG antibody responses to that allergen . CONCLUSION A recombinant allergen vaccine can be a effective and safe treatment to ameliorate symptoms of allergic rhinitis . The clinical benefit is associated with modification of the specific immune response with promotion of IgG(4 ) and reduction of IgE antibodies consistent with the induction of IL-10-producing regulatory T cells The Preventive Allergy Treatment Study , the PAT Study , is a European multi-center study . The end-point is to show in what capacity allergen specific subcutaneous immunotherapy can reduce the outcome of asthma in children with allergic rhinoconjunctivitis sensitized to birch and /or timothy pollen . Two hundred and ten children aged from 5 to 13 years were included in the study . Children were r and omized to the active treatment group receiving allergen specific immunotherapy with birch and /or timothy pollen allergen extract or to the control group receiving the optimal pharmacotherapy . Immunotherapy was given for the course of three years . Preliminary data show that immunotherapy has been effective , it has been safe and statistically significantly less children in the actively treated group had asthmatic symptoms than children in the control group . Data have not been evaluated from all centers at the moment . The study is a prospect i ve follow-up study , the patients ' data will be evaluated next time in the year 2002 To evaluate the efficacy of specific sublingual immunotherapy ( SLIT ) , we enrolled 15 children with asthma and rhinitis ( 7 girls , 8 boys , mean + /- SD age of 11.7 + /- 3.3 ) allergic to house dust mite ( HDM ) into a double-blind , placebo-controlled study . After a run-in period , patients were r and omized to receive either placebo ( n = 7 ) or SLIT ( n = 8) with a st and ardized Dermatophagoides pteronyssinus ( D. pteronyssinus ) + Dermatophagoides farinea ( D. farinea ) 50/50 extract . They received increasing doses up to 100 index units of reactivity ( IR ) every day for 4 weeks , then 100 IR/day for another 4 weeks , followed by maintenance therapy consisting of 20 drops 2 times a week for 4 months . Efficacy was assessed at the end of 6 months of therapy according to symptom and medication scores , serum total IgE levels , results of lung function tests , methacholine provocation tests , and skin prick tests . Daily means for the asthma score and use of inhaled beta-2-mimetics decreased significantly in the SLIT group ( P = 0.05 , P = 0.028 , respectively ) , whereas no such difference was observed in the placebo group . At the end of follow-up , mean daily doses of intranasal steroids needed for control of rhinitis symptoms decreased significantly in the SLIT group ( P = 0.04 ) . Baseline skin sensitivity to D. pteronyssinus and D. farinea was not significantly different between in the two groups , whereas end-point wheal diameter obtained with D. pteronyssinus extract was significantly less in the SLIT vs. the placebo group ( P = 0.026 ) . At the end of 6 months , peak expiratory flow ( PEF ) values in the placebo group was significantly lower than in the SLIT group ( P = 0.049 ) . Throughout the treatment period , the SLIT group was found to have less asthma exacerbations than the placebo group ( P = 0.007 ) . The provocation concentration causing a 20 % drop in forced expired volume in 1 sec did not change throughout the treatment period in either groups . None of the patients reported local or systemic side effects from SLIT . Results of this study suggests that SLIT may be a useful alternative or additional therapy in the treatment of children with asthma/rhinitis due to HDM BACKGROUND Sublingual-swallow immunotherapy was recently recognized in the World Health Organization Position Paper ( Allergen immunotherapy : therapeutic vaccines for allergic diseases ) " as a viable alternative to parenteral injection therapy to treat allergic diseases " in adults . More controlled studies were required to assess the efficacy and safety of this treatment in children . OBJECTIVE This study was carried out to assess the clinical efficacy and safety profile of sublingual-swallow immunotherapy with high-dose allergen in children with allergies . METHODS We used a double-blind placebo-controlled design . Forty-one children with Parietaria -induced rhinoconjunctivitis were r and omized to receive sublingual st and ardized Parietaria judaica extract ( n = 20 ) or placebo ( n = 21 ) for 2 years . The cumulative dose of allergen was 375 times higher than that used in parenteral immunotherapy and the cumulative dose of Par j 1 major allergen was 52.5 mg over 2 years . The main efficacy assessment criteria were symptoms and rescue medication scores recorded on the patients ' diary cards . Secondary criteria were changes in skin and conjunctival specific reactivity as well as blood parameters , analyzed after 1 and 2 years of immunotherapy . The safety of the treatment was assessed by evaluating the frequency and severity of adverse effects . RESULTS A significant reduction in rhinitis symptoms was observed in the active treatment group during the second season ( P = .02 ) , with no difference in medication scores . A significant decrease in skin reactivity ( P = .002 after 2 years of treatment ) and an increase in the threshold dose for conjunctival allergen provocation test ( P = .02 ) were observed in the active treatment group compared with the group receiving placebo . A significant increase in specific IgG(4 ) levels ( P = .02 ) was also observed in the active group . Immunotherapy was well tolerated . CONCLUSION Sublingual-swallow immunotherapy in Parietaria -allergic children provided a clinical benefit and a decreased specific reactivity to the allergen . The safety profile of this treatment , which constitutes an important issue , indicated good tolerance and compliance A double‐blind histamine placebo controlled immunotherapy trial was performed to investigate the clinical effect of a purified and st and ardized Cladosporium herbarum allergen preparation . Thirty children with a clinical history suggesting mould‐induced asthma and /or rhinoconjuctivitis were included . The diagnosis was confirmed by positive skin prick test and Phadebas RAST ® as well as positive bronchial and /or conjunctival provocation test to Cladosporium herbarum . Immunotherapy was given for 10 months in a double‐blind manner to r and omized groups with either Pharmalgen ® /Cladosporium herbarum preparation or histamine placebo . Allergic side effects to injections were common , especially during the peak of the mould season ( July‐September in Sc and inavia ) . In the active group , 13/16 patients experienced general reactions during the first 10 months of treatment . After 6 months of treatment , eye , nose and bronchial symptom scores and peak expiratory flow rates were similar for the groups , maybe because most of the children were also sensitive to many other allergens , including Alternaria alternala . However , medication scores were significantly lower in the treated group ( P < 0.01 ) . Bronchial ( P < 0.01 ) and conjunctival sensitivity ( P= 0.01 ) were significantly reduced in the Cladosporium‐treated group but not in the placebo group after 10 mouths of treatment . This is the first double‐blind clinical trial showing the clinical efficacy of immunotherapy in children with mould‐induced asthma The efficacy and tolerance of short‐term immunotherapy ( STI ) by seven preseasonal injections of tree‐pollen allergens ( ALK7 FrUhbltihermischung ® ) was investigated in a double‐blind , placebo‐controlled , multicenter study with 111 rhinoconjunctivitis patients . Nasal and bronchial symptoms simultaneously analyzed , and nasal symptoms as a single end point , but not the overall score of nasal , bronchial , and conjunctival symptoms , showed a significantly lower increase with STI during birch‐pollen exposure ( both P= 0.033 , n= 105 , Mann‐Whitney U‐test ) . However , a selective analysis with patients from centers with high recruitment figures ( nS10 patients , n=29 STI , n=32 placebo ) showed a significantly lower increase of nasal , bronchial , and overall symptom score ( STI 11.0 vs placebo 18.0 , P=0.001 , U‐test ) . STI had equidirected effects on conjunctival , nasal , and bronchial symptoms analyzed as multiple end points , although conjunctival symptoms were not significantly different as a single end point . The seasonal increase in drug use was reduced by 62 % in the STI group compared with placebo ( P=0.032 , Mest ) , Specific IgG4 increased only after STI ( P<0,001 ) ; IgE was not significantly different . Eosinophil cationic protein remained unchanged with STI , but significantly increased with placebo in the pollen season ( P = Qm3 ) . STI was well tolerated . In conclusion , STI was shown to be efficacious and safe for the treatment of patients with tree‐pollen rhinoconjunctivitis BACKGROUND Sublingual immunotherapy ( SLIT ) is increasingly being used for the treatment of allergic rhinitis , but there are conflicting study results demonstrating clinical ly relevant efficacy . OBJECTIVE To show clinical efficacy and safety of a new high-dose grass pollen preparation for SLIT . METHODS In a 2-year , double-blind , placebo-controlled trial , 185 subjects with rhinitis or rhinoconjunctivitis , with or without asthma , were treated with a recently developed , high-dose , 6-grass pollen mixture for SLIT once daily . RESULTS The primary end point , a combined symptom-medication score , showed almost no change in the placebo group during a 42-day evaluation period in the grass pollen season from 2003 to 2005 , whereas active treatment was associated with a significant and clinical ly relevant improvement ( full analysis set , P = .01 ; main data set , P = .002 ) . The effect was irrespective of asthma diagnosis . Allergen-specific IgE showed no difference in both groups , and specific IgG4 and IgG1 increased with active treatment in the first and second study years compared with placebo , clearly indicating the immunogenic effect of the active treatment . The SLIT was well tolerated . No serious adverse drug reactions occurred . CONCLUSIONS High-dose , sublingual , specific immunotherapy with an extract of a 6-grass pollen mixture showed a significant and clinical ly relevant improvement in subjects with grass pollen-associated rhinitis or rhinoconjunctivitis , with or without asthma . The treatment with the sublingual solution was well tolerated BACKGROUND Double-blind , placebo-controlled studies have established that injection allergen immunotherapy is clinical ly effective . However , it is not known to what extent the doses of allergen extract commonly used in clinical practice match those that have been used in these controlled studies . OBJECTIVE The aim of this study was to determine by question naire the doses of st and ardized allergen extracts commonly used by board-certified allergists in the United States and to compare these with doses that have proven effective in double-blind , placebo-controlled studies . METHODS A question naire containing a hypothetical case and asking for a recommended allergen prescription for maintenance immunotherapy was mailed to 500 r and omly selected board-certified members of the American Academy of Allergy , Asthma and Immunology living in the United States . The recommended doses were compared with those doses of the extracts that had been proven effective by using major allergen content figures for representative st and ardized US allergen extracts provided by an allergy extract laboratory . RESULTS Responses were received from 118 ( 23 % ) of the addressees . Eighty ( 16 % ) contained interpretable data on maintenance dosing for extracts . The median doses of pollen recommended were comparable with those that have been demonstrated to be clinical ly effective . Median doses of house dust mites were only slightly lower than those that have proven effective . Median doses of animal d and er , on the other h and , were well below those used effectively in controlled studies . Although the median doses used were often in the range of proven doses , the range of doses recommended by allergists included some that were one tenth to one five hundredth those of the median doses . CONCLUSION In the absence of useful guidance from the federal regulatory authorities , American allergists , for the most part , use doses of pollens and house dust mites that are within the proven range . Their dosing of animal d and er is generally below proven effective doses . There is , however , a wide range of dosing of all extracts used , and there is use of mixes that have no botanical basis . Therefore there is need for studies defining what are effective and ineffective allergen extract doses A double‐blind , placebo‐controlled study was conducted to evaluate the efficacy and safety of immunotherapy ( IT ) with a partially purified alginate‐conjugated extract of Parietaria judaica ( Conjuvac ® Parietaria , Dome/Hollister‐Stier ) in patients suffering from rhinoconjunctivitis caused by Parietaria pollen . Eighteen patients ( 10 women , 8 men , mean age 35 years ) received active treatment and 17 ( 10 women , 7 men , mean age 42.5 years ) received placebo . Actively treated patients had significantly lower nasal symptom/medication scores ( running nose P= 0.0087 and sneezing P= 0.048 ) during the Parietaria pollen season . Significant decreases in specific skin ( P > 0.01 ) , nasal ( P > 0.05 ) , and conjunctival ( P > 0.01 ) reactivity to the Parietaria extract and significant increases of specific IgG ( P > 0.001 ) , IgGI ( P > 0.001 ) , and IgG4 ( P > 0.001 ) in actively treated patients , but not in placebo , were found . IT was well tolerated , the active extract inducing five mild systemic reactions ( four rhinitis and one urticaria ) and placebo two ( rhinitis ) . A significant correlation was found between low skin reactivity and high specific IgG ( P= 0.0002 ) and IgG4 ( P= 0.036 ) . These findings indicate that IT with a partially purified P. judaica extract is an effective and safe treatment for Parietaria pollen allergy . The correlation between low immediate skin reactivity and high specific IgG and IgG4 suggests that , at least in the studied cutaneous model , these antibodies may exert a blocking effect Allergy to Parietaria judaica pollen causes significant morbidity in many areas of the world . In addition to rhinitis , patients who are allergic to this pollen have a high incidence of asthma . The pollinating season is long , making this particular allergy challenging for clinicians to treat . This study was design ed to determine if immunotherapy with an alum adsorbed partially purified Parietaria extract ( Alpare Parietaria ) containing a targeted maintenance dose of 12 500 BUs was effective in decreasing rhinitis symptoms in patients allergic to Parieiaria . Using a double‐blind placebo‐controlled technique 36 patients received placebo or active extract for 2 years . Twenty ( 11 placebo and nine active ) completed the 2 year study . Efficacy of treatment was evaluated by determining changes in skin reactivity , visual analog scores , diary symptom scores and end of study assessment s. Reactions were monitored as well . Skin‐test suppression was marginally significant in the actively treated group after 1 year and showed even more significant suppression after the second year . Nasal block , rhinorrhoea and sneezing all were significantly decreased in the active group . The nasal provocation test did not show a significant change after 1 year , in either group , but after 2 years of treatment the active group did show significant improvement . Although almost all patients in the actively treated group experienced local reactions , the incidence of systemic reactions was not different between the two groups . In conclusion , immunotherapy with this extract at this dose was effective in ameliorated rhinitis symptoms in patients allergic to Parietaria judaica Background : We present data showing that a Th1‐inducing adjuvant can reduce the number of injections required for allergy vaccination . Allergy vaccination is the only treatment for type 1 hypersensitivity that can alter the underlying disease process . A switch of specific T‐cell activity from Th2>Th1 to Th1>Th2 is believed to be an important change seen after long‐term vaccination therapy . An immunologic adjuvant that enhances such a switch could be used to reduce the number of injections required . This would improve compliance with the treatment and provide pharmacoeconomic advantages . Such an adjuvant is 3‐deacylated monophosphoryl lipid A ( MPL ® adjuvant , Corixa ) Specific immunotherapy ( SIT ) using a st and ardized mite extract is effective and safe when administered under optimal conditions . However , the duration of its effectiveness after cessation of treatment remains unknown . Forty asthmatic subjects who had received SIT with a st and ardized Dermatophagoides pteronyssinus ( Der p ) extract under the same protocol were studied . All had received SIT for a period of 12 - 96 months and were not receiving pharmacologic treatment . The FEV1 was within normal range in all patients . After cessation of treatment , patients were followed for up to 3 years at 6-month intervals . The patient was considered to have relapsed when symptoms of asthma and /or rhinitis occurred and /or when pulmonary function tests were impaired . Skin tests with increasing concentrations of Der p were carried out before and at the end of SIT . Forty-five percent of the patients did not relapse . The duration of efficacy of SIT was related to the duration of SIT itself ( P < 0.04 ) . Most patients who did not relapse had a decrease in skin test reactivity at the end of SIT , whereas most patients who relapsed did not show any change ( P < 0.003 ) . The duration of efficacy of SIT after its cessation depends upon the duration of SIT and may be predicted by the effect of SIT on skin tests BACKGROUND Data for trends in prevalence of asthma , allergic rhinoconjunctivitis , and eczema over time are scarce . We repeated the International Study of Asthma and Allergies in Childhood ( ISAAC ) at least 5 years after Phase One , to examine changes in the prevalence of symptoms of these disorders . METHODS For the ISAAC Phase Three study , between 2002 and 2003 , we did a cross-sectional question naire survey of 193,404 children aged 6 - 7 years from 66 centres in 37 countries , and 304,679 children aged 13 - 14 years from 106 centres in 56 countries , chosen from a r and om sample of schools in a defined geographical area . FINDINGS Phase Three was completed a mean of 7 years after Phase One . Most centres showed a change in prevalence of 1 or more SE for at least one disorder , with increases being twice as common as decreases , and increases being more common in the 6 - 7 year age-group than in the 13 - 14 year age-group , and at most levels of mean prevalence . An exception was asthma symptoms in the older age-group , in which decreases were more common at high prevalence . For both age-groups , more centres showed increases in all three disorders more often than showing decreases , but most centres had mixed changes . INTERPRETATION The rise in prevalence of symptoms in many centres is concerning , but the absence of increases in prevalence of asthma symptoms for centres with existing high prevalence in the older age-group is reassuring . The divergent trends in prevalence of symptoms of allergic diseases form the basis for further research into the causes of such disorders BACKGROUND The main aim of specific immunotherapy is sustained effect due to changes in the immune system that can be demonstrated only in long-term trials . OBJECTIVE To investigate sustained efficacy and disease modification in a 5-year double-blind , placebo-controlled trial , including 2 years of blinded follow-up after completion of a 3-year period of treatment , with the SQ-st and ardized grass allergy immunotherapy tablet , Grazax ( Phleum pratense 75,000 SQ-T/2,800 BAU,(∗ ) ALK , Denmark ) or placebo . METHODS A r and omized , double-blind , placebo-controlled , multinational , phase III trial included adults with a history of moderate-to-severe grass pollen-induced allergic rhinoconjunctivitis , with or without asthma , inadequately controlled by symptomatic medications . Two hundred thirty-eight participants completed the trial . End points included rhinoconjunctivitis symptom and medication scores , combined scores , asthma symptom and medication scores , quality of life , days with severe symptoms , immunologic end points , and safety parameters . RESULTS The mean rhinoconjunctivitis daily symptom score was reduced by 25 % to 36 % ( P ≤ .004 ) in the grass allergy immunotherapy tablet group compared with the placebo group over the 5 grass pollen seasons covered by the trial . The rhinoconjunctivitis DMS was reduced by 20 % to 45 % ( P ≤ .022 for seasons 1 - 4 ; P = .114 for season 5 ) , and the weighted rhinoconjunctivitis combined score was reduced by 27 % to 41 % ( P ≤ .003 ) in favor of active treatment . The percentage of days with severe symptoms during the peak grass pollen exposure was in all seasons lower in the active group than in the placebo group , with relative differences of 49 % to 63 % ( P ≤ .0001 ) . Efficacy was supported by long-lasting significant effects on the allergen-specific antibody response . No safety issues were identified . CONCLUSION The results confirm disease modification by SQ-st and ardized grass allergy immunotherapy tablet in addition to effective symptomatic treatment of allergic rhinoconjunctivitis BACKGROUND The fast-dissolving grass allergy immunotherapy tablet ( grass AIT ) , Grazax , has proven effective in grass pollen-induced rhinoconjunctivitis . OBJECTIVE To investigate the immunological and cutaneous changes induced after a short course with grass AIT . METHODS We performed a r and omized , double-blind placebo-controlled trial with 78 patients r and omly assigned to receive either grass AIT or placebo in a 2:1 ratio . Treatment lasted at least 8 weeks before the grass pollen season ( GPS ) , and continued until the season finished . Specific immunoglobulin ( Ig ) G4 , IgE , and IgE-blocking factor to Phleum pratense were measured at the beginning of the trial and at different intervals during treatment . Immediate and delayed skin tests with P pratense were also performed . Safety endpoints were defined in terms of adverse events reported . RESULTS A total of 75 patients completed the trial ( 50 active and 25 placebo ) . P pratense IgG4 , IgE , and IgE-blocking factor in actively treated patients increased significantly from baseline to the start of the GPS compared to placebo ( P > .001 , P = .017 , and P = .005 , respectively ) . The immediate cutaneous response was reduced during therapy in actively treated subjects , whereas placebo-treated subjects showed a decrease only after the start of the GPS . The delayed response to the intradermal test in grass AIT-treated subjects diminished , although not in a significantly different way from the placebo-treated subjects . CONCLUSION Treatment with grass AIT for grass pollen allergic rhinoconjunctivitis induces immunological changes after only 1 month of treatment BACKGROUND Specific immunotherapy is widely used to treat allergic rhinitis , but few large-scale clinical trials have been performed . OBJECTIVE We sought to assess the efficacy and safety of specific immunotherapy with 2 doses of Alutard grass pollen in patients with moderately severe seasonal allergic rhinitis inadequately controlled with st and ard drug therapy . METHODS We performed a double-blind , r and omized , placebo-controlled study of 410 subjects ( 203 r and omized to 100,000 st and ardized quality units [ SQ-U ] maintenance , 104 to 10,000 SQ-U , and 103 to placebo ) . Three hundred forty-seven ( 85 % ) completed treatment . Groups were well matched for demographics and symptoms . RESULTS Across the whole pollen season , mean symptom and medication scores were 29 % and 32 % lower , respectively , in the 100,000-SQ-U group compared with those in the placebo group ( both P < .001 ) . Over the peak pollen season , mean symptom and medication scores were 32 % and 41 % lower , respectively , than those in the placebo group . The 10,000-SQ-U group had 22 % less symptoms than the placebo group over the whole season ( P < .01 ) , but medication scores reduced by only 16 % ( P = .16 ) . Quality -of-life measures confirmed the superiority of both doses to placebo . Local and delayed side effects were common but generally mild . Clinical ly significant early and delayed systemic side effects were confined to the 100,000-SQ-U group , but no life-threatening reactions occurred . CONCLUSIONS One season of immunotherapy with Alutard grass pollen reduced symptoms and medication use and improved the quality of life of subjects with moderately severe hay fever . The 100,000-SQ-U regimen was more effective , but the 10,000-SQ-U regimen caused fewer side effects Background Injective immunotherapy is a well‐known and recognized treatment for allergic diseases , but its safety has been question ed during recent years . Alternative administration routes have been proposed and there is a growing interest and experience in sublingual therapy . The safety of alternative routes is nonetheless a real advantage , so long as it is not counterbalanced by a loss of clinical benefit Sixty-two ragweed-sensitive adult subjects volunteered to take part in a 2-year , placebo-controlled efficacy study of polyethylene glycol (PEG)-modified ragweed extract , in ragweed pollen-induced rhinoconjunctivitis . At the beginning of the study , subjects were stratified according to skin sensitivity to ragweed extract and PEG-modified ragweed and the severity of hay fever in the previous year . There was r and om allocation of half to active treatment and half to placebo treatment . Before the first ragweed pollen season the 36 most sensitive subjects received 10 weekly injections ( group 1 ) , and the remaining 26 received six injections ( group 2 ) . Before the second season all subjects received 10 injections . Doses increased by half a log concentration each week unless there were adverse reactions . The mean total dose received by group 1 in year 1 was 385 micrograms of protein ( 28.9 micrograms AgE ) and received by group 2 was 218 micrograms of protein ( 16.4 micrograms AgE ) . In year 2 the mean total dose was 1829 micrograms ( 137.2 micrograms AgE ) . Sixty-six percent of injections elicited no reaction or a mild local reaction ; the remaining injections produced local redness and swelling more than 2 inches in diameter . Four percent of injections produced systemic symptoms . PEG-modified ragweed stimulated increases in ragweed specific IgG antibody both years , but increases in ragweed specific IgE antibody were significant only in group 1 in year 1 . The magnitude of the IgG antibody changes was directly related to the total dose injected . At the beginning of the second year , PEG-modified ragweed-treated subjects still had elevated IgG antibody levels . ( ABSTRACT TRUNCATED AT 250 WORDS Fifteen grass pollen -- sensitive asthmatic patients were selected from 200 patients with grass pollenosis on the basis of positive SPTs and RASTs that were restricted to grass pollens ( except Bermuda grass ) , no previous IT , and residence and occupation in an area monitored by serial pollen counts . They underwent a double-blind trial of specific IT with a mixture of three grass pollen -- aqueous extracts ( velvet , sweet vernal , and timothy ) or placebo . After 10 mo , the mean maintenance dose of pollen extract ( assayed by RAST inhibition ) in eight actively treated patients was 6000 RAST units ( range 3000 to 8000 ) and the mean total dose was 18,700 RAST units ( range 10,200 to 30,000 ) . Results were assessment done by the following clinical and immunological data : ( 1 ) during the pollen season , daily symptom scores ; ( 2 ) PD 20 % FEV1 , IgE antibody to timothy by RAST in serum and in nasal secretions , serum IgG antibody to purified timothy allergen D by solid-phase radioimmunoassay , and the four IgG subclass antibodies by enzyme immunoassay were all measured before treatment and before and after the pollen season . Symptom scores of both treated patients and controls correlated with pollen counts ( R = 0.88 , p less than 0.05 and R = 0.71 , p less than 0.05 , respectively ) . There was a significant difference between the mean symptom score values of treated patients versus controls ( Kruskal-Wallis test , p less than 0.001 ) . No significant differences or changes either in the PD 20 % FEV1 or IgE antibody to timothy in serum and nasal secretions were found in the two groups before or after IT . ( ABSTRACT TRUNCATED AT 250 WORDS Background : New routes of administering immunotherapy in respiratory allergy are being studied as an alternative to conventional injective immunotherapy . We carried out a study to evaluate the clinical efficacy and effects of sublingual immunotherapy in patients with Parietaria judaica‐induced respiratory allergy BACKGROUND Grass pollen immunotherapy is an effective treatment for seasonal allergic rhinitis that provides the opportunity to study the induction and maintenance of allergen-specific immune tolerance . OBJECTIVES We investigated the relationship between clinical responsiveness , regulatory cytokine production , and antibody responses to allergen during 1 year of immunotherapy . METHODS Eighteen subjects with severe seasonal allergic rhinitis were r and omized double-blind to receive active or placebo injections of an alum-adsorbed grass pollen vaccine ( Alutard SQ ) . Subjects underwent repeated testing of early- and late-phase skin responses to intradermal allergen , and cellular responses to grass pollen allergen were tested . Sera were tested for allergen-specific IgG4 , IgA , and inhibitory activity in biologic assays of IgE responses . RESULTS Grass pollen immunotherapy was effective in reducing overall symptom scores ( P < .05 ) and conjunctival reactivity ( P < .05 ) . In the active group significant IL-10 production occurred early at low allergen doses and at a similar time as inhibition of late skin responses at 2 to 4 weeks . Serum allergen-specific IgG4 , IgA , and inhibitory antibody activity for basophil histamine release and IgE-facilitated allergen binding to B cells occurred later , at 6 to 12 weeks , at higher allergen doses and preceded inhibition of early skin responses . CONCLUSION IL-10 responses occur early but at immunotherapy doses that are not clinical ly effective . Later induction of inhibitory antibodies , including IgG4 and IgA , might be required for efficacy through modulation of IgE-mediated events AIM Assessment of clinical and immunological effects of use of bacterial therapeutic polycomponent vaccine Immunovac-VP4 for allergen-specific immunotherapy ( ASIT ) of hay fever . MATERIAL S AND METHODS Five doses of Immunovac-VP4 vaccine consisted of antigens of opportunistic bacteria was used and administered by nasal-oral route . ASIT was performed with st and ard water-saline solution of allergens according to defined schedule . Sixty-nine patients with season rhinoconjunctivitis , asthma and their combinations were included in the study and divided to two groups . Skin scarification test was performed , total level of serum IgE , IgG4 and IgE to pollen allergens were measured by ELISA . Also , question naire was sent to patients yearly . RESULTS Administration of bacterial therapeutic vaccine Immunovac-VP4 before start of ASIT result ed in marked clinical and immunological effect . In group of patients receiving combination therapy compared to control group , 8.5 times lower incidence of acute respiratory infections was registered . According to results of analysis of patients ' question naires after 7 years , effectiveness of therapy was 90 % that points to achievement of prolonged remission after completion of ASIT course . CONCLUSION Utilization of natural lig and s of Toll-like receptors is a perspective direction for development of new immunotherapeutic strategies for treatment of allergic diseases A double-blind study comparing formaldahyde modified ragweed allergen ( allergoid ) and placebo in the treatment of allergic rhinitis was carried out . Twenty ragweed-sensitive patients were studied , ten receiving 10,710 PNU of allergoid pre-seasonally and ten receiving placebo injections . Daily symptom score sheets were kept by each patient during August and September of 1983 . A significant difference in average daily symptom scores ( P = 0.01 ) between the two groups was noted . Significant differences were also observed in symptom scores for individual weeks during the ragweed season . Post-treatment allergen-specific IgG blocking antibody was significantly higher ( P = 0.001 ) in the treatment group compared to pre-treatment levels and when compared to the control group ( P = 0.01 ) . No significant local or systemic reactions occurred . The results suggest that the dosage protocol used in this study is appropriate as an initial treatment schedule in clinical practice For evaluation of the efficacy and the safety of specific sublingual immunotherapy with high allergen dose , 66 children with seasonal asthma , rhinitis , and conjunctivitis due to sensitization to olive pollen were enrolled in a double‐blind , r and omized , placebo‐controlled study between October 1994 and October 1996 in Greece . Thirty‐four patients were r and omly allocated to the active group , and 32 received placebo . Immunotherapy consisted of olive‐allergen extracts ( Stallergenes SA ) administered sublingually pre‐ and coseasonally from January to July for 2 consecutive years . Serial concentrations from 1 to 300 IR were used up to the maintenance dose of 20 drops of 300 IR daily . The cumulative dose for each patient was 300 times higher than in parenteral immunotherapy , and the cumulative dose of the major allergen Ole e 1 was 8.1 mg/2 years . The patients were assessed by clinical parameters ( symptom and medication scores from patients ' daily diaries ) and immunologic measurements ( specific IgE. lgG4 . eosinophil cationic protein [ ECP ] ) were performed . The actively treated patients had a significantly lower score for dyspnea ( P<0.04 during the first season ; P<0.03 during the second season ) . At the poUinic peak during the second year , a lower score of conjunctivitis was recorded ( P<0.05 ) in the actively treated patients . The analysis of intragroup evolution showed that the total score of rhinitis increased significantly during the pollinic peak in the group under placebo , whereas there was no symptomatic peak for the same period in the group under active treatment . However , the difference between the groups was not significant . The medication score did not differ significantly between the groups . Oral steroids were the only variables with a P value near the significance level ( P=0.06 ) in favor of the actively treated group . A significant decrease in skin reactivity was recorded in the active group after 2 years of treatment . No significant variation in specific IgE and IgG4 was detected . A significantly lower level of serum ECP was observed at the pollinic peak in the actively treated patients during the first pollen season ( P=0.01 ) , but this was not confirmed the second year when the ECP levels doubled in both groups without correlation to the clinical findings . Tolerance was excellent with only a few minor side‐effects reported . In conclusion , high‐dose specific sublingual immunotherapy appears to be safe and effective in improving mild seasonal asthma and conjunctivitis linked to olive‐pollen sensitization We investigated the effects of immunotherapy ( IT ) on the early ( ER ) , late ( LPR ) , and rechallenge reactions ( RCRs ) to nasal challenge with antigen as well as on the cutaneous ER and LPR to intradermal skin challenge . Our expectation was that IT would have a preferential effect on the LPR , and our aim was to underst and the mechanism . Twenty-one ragweed hay fever-sensitive subjects were treated with a moderate dose of antigen extract ( maintenance dose of 1.94 micrograms of antigen E ( Amb a I ) ) during a period of 8 months ( total dose equivalent to 24 micrograms of antigen E ) , and 20 matched subjects received placebo injections in a double-blind manner . Both groups underwent identical nasal challenges and intradermal skin tests with ragweed-antigen extract both before ( 1985 ) and during ( 1986 ) IT . Symptom and medication diaries , recorded during seasonal exposure , and changes in specific serum IgE and IgG antibodies confirmed the efficacy of the administered IT dose . Between-group analysis revealed that IT significantly reduced the levels of histamine , TAME-esterase activity , and kinins , as well as symptoms of rhinorrhea and congestion generated during the ER to nasal challenge . Within-group paired analysis demonstrated ER , LPR , and RCR mediators and symptoms also to be reduced by IT . Surprisingly , the placebo-treated group demonstrated an increase in the ER . There was no decrease of the LPR without an antecedent decrease of the ER . IT did not clearly change the late cellular inflammatory response . In the case of skin challenge , IT significantly reduced the cutaneous ER . The reduction of the cutaneous LPR was more pronounced . We speculate that moderate-dose IT ameliorates seasonal symptoms of allergic rhinitis by reducing the ER , LPR , and RCR to antigen challenge but does not preferentially reduce the nasal LPR Bet v 1 , the major allergen in birch pollen , is recognized by more than 90 % of patients allergic to birch in northern and central Europe . Immunotherapy is commonly performed with birch pollen extracts . Recently , hypoallergenic derivatives of Bet v 1 ( rBet v 1 fragments , rBet v 1 dimer and trimer ) were constructed and purified BACKGROUND Sustained and disease-modifying effects of sublingual immunotherapy have never before been confirmed in a large-scale r and omized , double-blind , placebo-controlled trial . OBJECTIVE We sought to investigate sustained efficacy 1 year after a 3-year period of daily treatment with the SQ-st and ardized grass allergy immunotherapy tablet Grazax ( Phleum pratense 75,000 SQ-T/2,800 BAU ; ALK-Abelló , Hørsholm , Denmark ) . METHODS A r and omized , double-blind , placebo-controlled , phase III trial including adults with a history of moderate-to-severe grass pollen induced rhinoconjunctivitis inadequately controlled by symptomatic medications . The analysis set comprised 257 subjects at the follow-up . Efficacy end points were rhinoconjunctivitis symptom and medication scores , quality of life , and percentages of symptom and medication free days . Immunologic end points included grass pollen-specific serum IgG4 and IgE-blocking factor . Safety was assessed based on adverse events . RESULTS Significant improvements in efficacy were consistently shown during 3 years ' treatment . One year after treatment , the active group showed sustained reductions in mean rhinoconjunctivitis symptom scores ( 26 % , P < .001 ) and medication scores ( 29 % , P = .022 ) when compared with placebo . This level was similar to the efficacy observed during the 3-year treatment period . The differences in percentages of symptom- and medication-free days were significant during and 1 year after treatment . The active group also reported sustained and significant improvements in quality of life . Sustained clinical benefit was accompanied by immunologic changes . No safety issues were identified . CONCLUSION Three years of treatment with the SQ-st and ardized grass allergy immunotherapy tablet result ed in consistent clinical improvement and accompanying immunologic changes that were sustained 1 year after treatment , which is indicative of disease modification and associated long-term benefits BACKGROUND Grass pollen immunotherapy significantly reduces hay fever symptoms and medication requirements . Effects on seasonal asthma are less clear , and concerns over safety persist . OBJECTIVE The goal of this study was to assess the effects of grass pollen immunotherapy on symptoms , bronchial hyperresponsiveness , and quality of life in seasonal rhinitis and asthma . METHODS Forty-four patients with severe summer hay fever ( of whom 36 reported seasonal chest symptoms and 28 had seasonal bronchial hyperresponsiveness ) participated in a r and omized , double-blind , placebo-controlled , parallel group study . After symptom monitoring for one summer , participants received injections of a depot grass pollen vaccine ( n = 22 ) or matched placebo injections ( n = 22 ) in a rapid updosing cluster regimen for 4 weeks , followed by monthly injections for 2 years . Outcome measures included hay fever symptoms and medication use , health-related quality of life , and measurements of nonspecific bronchial responsiveness . RESULTS Significant reductions were observed in the immunotherapy group compared with the placebo group in hay fever symptoms ( 49 % , 15 % ; P = .01 ) , medication scores ( 80 % , 18 % ; P = .007 ) , and seasonal chest symptoms ( 90 % , 11 % ; P < .05 ) . Impairment of overall quality of life ( mean score of 7 domains ) during the pollen season was less in the immunotherapy group than in the placebo group ( median difference [ 95 % CI ] , 0.8 [ 0.18 - 1.5 ] ; P = .02 ) . During the pollen season there was no change in airway methacholine PC(20 ) ( provocation concentration producing a 20 % fall in FEV(1 ) ) in the immunotherapy-treated group ( P = .5 ) , compared with an almost 3 doubling-dose decrease in the placebo-treated group ( P = .01 , between-group difference ) . There were no significant local or systemic side effects during the study . CONCLUSION Grass pollen immunotherapy improves quality of life in seasonal allergic rhinitis and reduces seasonal asthma symptoms and bronchial hyperresponsiveness Background : Bronchial hyperresponsiveness ( BHR ) and airway inflammation are frequently associated with allergic rhinitis , and may be important risk factors for the development of asthma . Specific immunotherapy ( SIT ) reduces symptom in subjects with allergic rhinitis , but the mechanisms are not clear BACKGROUND Sublingual immunotherapy ( SLIT ) is currently considered a valid option to subcutaneous immunotherapy ( SCIT ) , but only a few studies made a direct comparison of their effectiveness . The aim of this study was to compare the clinical and immunological effects of SCIT and SLIT in pollinosis induced by Betulaceae . METHODS Forty-seven adult patients were r and omized to receive SCIT or SLIT , performed by Betulaceae ( alder , birch , and hazel ) extracts from Stallergenes ( Antony , France ) st and ardized in index of reactivity ( IR ) with the treatment schedules proposed by the producer . The clinical effects were established by symptom-medication scores recorded during the month of March . Side effects were reported directly by the physicians for SCIT and were registered in diary cards by the patients for SLIT . Immunologic evaluation was done by measuring specific IgE and IgG4 to Bet v 1 . RESULTS Thirty-four patients ( 19 for SCIT and 15 for SLIT ) completed the registration of symptoms and drug consumption during pollen period of Betulaceae . Mean cumulative doses of respectively 50.65 IR by SCIT and 4653.1 IR by SLIT were administered , with a SLIT/SCIT ratio of 92 . There was no significant difference in mean symptom-medication score between SCIT and SLIT . Systemic reactions occurred in 16 % of SCIT treated but in none of SLIT treated . As to immunologic evaluation , Bet v 1 specific IgE did not rise after the pollen season in SCIT treated , while increased non significantly in SLIT treated . Bet v 1 specific IgG4 increased in both treatment , buy only the increase with SCIT was significant ( p = 0.001 ) . CONCLUSION SLIT and SCIT with a ratio of about 100 are equally effective in controlling rhinoconjunctivitis caused by tree pollen allergy . SLIT is safer than SCIT , but does not show the same immunologic effects on serum specific IgE and lgG4 antibodies BACKGROUND To date , there have been no r and omized , double-blind studies showing the effectiveness of sublingual immunotherapy with multiple allergens . OBJECTIVE The purpose of this study was to examine whether the efficacy of sublingual immunotherapy ( SLIT ) with st and ardized timothy extract was reduced by combination with other allergen extracts . METHODS A single-center , r and omized , double-blind , placebo-controlled trial with SLIT was conducted . After an observational grass season , SLIT was administered for 10 months to 54 patients r and omized to 1 of 3 treatment arms : placebo , timothy extract ( 19 microg Phl p 5 daily ) as monotherapy , or the same dose of timothy extract plus 9 additional pollen extracts . Symptom and medication scores were collected and titrated nasal challenges , titrated skin prick tests , specific IgE , IgG4 and cytokines release by timothy-stimulated lymphocyte proliferation were performed . RESULTS Perhaps because of a very low grass pollen season in 2008 , there were no significant differences in medication or symptom scores in either treatment group compared with placebo . Compared with placebo , in the timothy monotherapy group , thresholds for titrated nasal challenge and skin prick tests ( P = .03 and P = .001 , respectively ) , and serum-specific IgG4 levels ( P = .005 ) significantly increased , and IFN- gamma levels decreased ( P = .02 ) , whereas in the multiallergen group , there was significant improvement only in the titrated skin prick tests ( P = .04 ) which was less than in the monotherapy group . There were no significant differences between the 2 active groups in any outcome measure , and both active groups experienced more adverse events than placebo . There were no systemic reactions . CONCLUSION Improvement in multiple relevant outcomes strongly suggests that SLIT with timothy extract alone was effective ; however , the results for symptom and medication scores were not significant . The differences between multiple allergen SLIT and placebo only in skin sensitivity to timothy suggest a reduction in SLIT efficacy in this group . However , further studies are required to confirm these observations BACKGROUND The inhalation of Salsola kali pollen is a common cause of respiratory diseases in Europe and North America . OBJECTIVE To evaluate the efficacy and safety of a depigmented and glutaraldehyde-polymerized therapeutic vaccine of S kali . METHODS The trial was r and omized , double-blind , and placebo-controlled using a rush protocol in the build-up phase . Sixty patients with rhinoconjunctivitis ( 19 also had mild asthma ) were r and omly allocated to receive either active treatment ( polymerized extract ) or placebo . The final distribution was 41 patients in the active and 19 in the placebo group . Side effects were registered . Symptom and medication scores and the number of days free of symptoms during the pollen season were assessed to evaluate the clinical efficacy . A Rhinoconjunctivitis Quality of Life Question naire was completed in the previous pollen season ( before treatment ) and during the pollen season 1 year later ( in the trial ) . Dose-response skin tests were performed at baseline and at the end of the trial . RESULTS There was a significant difference ( P < .05 ) in symptom and medication scores between both groups during the pollen season , with the active group the one that had fewer symptoms and lower intake of medication . The number of days without symptoms was higher in the active group ( P < .05 ) . This group also had a significant improvement in the Rhinoconjunctivitis Quality of Life Question naire and a reduction in skin sensitivity . No moderate or severe systemic reactions were registered . CONCLUSION Immunotherapy with this modified vaccine of S kali pollen is safe and efficacious to treat patients clinical ly sensitive to this pollen . CLINICAL IMPLICATION S Patients allergic to S kali ( Russian thistle ) can be successfully treated with immunotherapy to improve symptoms of allergic rhinitis and asthma , reduce medication use , and improve quality of life parameters BACKGROUND Respiratory allergy due to Alternaria is a relevant clinical problem , and specific immunotherapy may represent a viable treatment option . Sublingual immunotherapy ( SLIT ) is safe and effective , but data for Alternaria are lacking . OBJECTIVE To assess the efficacy of st and ardized SLIT in patients sensitized to Alternaria in a r and omized , prospect i ve , double-blind , placebo-controlled trial . METHODS Patients with rhinitis with or without intermittent asthma and ascertained allergy to Alternaria were enrolled . After a baseline season , SLIT or matched placebo was given for 10 months . Symptoms and rescue medication intake were recorded on diary cards between June and October . Skin prick testing was performed and specific IgE , IgG4 , and precipitin levels were measured at baseline and at the end of the study . RESULTS Twenty-seven patients ( age range , 14 - 42 years ) were r and omized , and 26 completed the study . The baseline characteristics were homogeneous in the 2 groups . After treatment , patients receiving SLIT had a significant improvement in symptoms and a reduction in medication intake vs placebo and vs the run-in season , whereas no change was seen in the placebo group . Skin prick test reactivity significantly decreased only in the SLIT group . No change was seen in specific IgG4 levels in the 2 groups , whereas Alt a 1 specific IgE levels significantly increased in the active group . One patient in the active group reported oral itching and conjunctivitis at the beginning of treatment . CONCLUSION SLIT seems effective and safe and may represent a valuable therapeutic option in respiratory allergy due to Alternaria A double-blind study was carried out to determine the effect of dosage in the treatment of ragweed hay fever with injections of aqueous ragweed pollen extract . Two concentrations of extract were used , one 20-fold smaller than the other . The volumes administered were such that the dose at the higher concentration was close to the maximum that it is practical to administer . During the ragweed season , the group of patients receiving the higher concentration fared significantly better than the group receiving the lower concentration . It is concluded that large dosages of pollen extract are more effective than small dosages in the treatment of hay fever . The findings indicate that the very low dosages recommended by some would have little influence on the course of pollenosis BACKGROUND The safety and efficacy of high-dose sublingual-swallow immunotherapy ( SLIT ) has been established in pollen rhinoconjunctivitis . This treatment has now been evaluated using an ultra-rush incremental dose regimen with a Juniperus ashei allergen extract in patients allergic to Cupressus sempervirens and Cupressus arizonica . METHODS Patients received either placebo or SLIT . Evaluation of safety was based on the frequency of adverse events during the incremental dose period ( half a day ) and during maintenance therapy ( 4 months ) . Evaluation of efficacy was based on symptom and medication scores at the pollen peak . RESULTS Seventy of the 76 patients included completed the study . There were no drop-outs during the rush procedure . One patient in the active group dropped out during the maintenance therapy due to adverse events : gastric pain and vomiting . There was also 1 drop-out in the placebo group due to pregnancy . Adverse events were infrequent , local and mild . Symptom scores for rhinitis and conjunctivitis were not statistically different between groups , but there was a marked and significant ( p < 0.03 ) decrease of the medication score ( about 50 % ) and nasal steroid consumption ( about 75 % ) in the active treatment group . An increase from baseline of serum IgE and IgG4 J. ashei-specific antibodies was only observed in actively treated patients ( p < 0.04 and p < 0.01 , respectively ) . CONCLUSIONS The tolerability and safety of high-dose ultra-rush SLIT were comparable to those reported in previous SLIT studies . SLIT with J. ashei extract , due to its high Jun a 1 content , significantly reduced nasal steroid consumption in patients allergic to European cypress A five-year study has been done on children sensitive to ragweed in which a comparison was made between specific hyposensitization injections and placebo injections . Even though the allergen injections may have had some beneficial effect on some children , the amount of benefit was indistinguishable from differences likely to occur in pure r and omization experiments . No justification was found for promising any greater benefit to children treated with allergens than they would obtain from placebo injections A double‐blind , placeo‐controlled study was performed in order to confirm the safety , suitability , and efficacy of an alum‐adsorbed Parietaria judaica‐pollen allergoid , Allergovit ® , for allergen‐specific immunotherapy . Parietaria pollen is an important cause of pollinosis , particularly in the Mediterranean zone , where it may be encountered for up to 8–9 months of the year . It is an aggressive allergen , and the doses tolerated during immunotherapy are less than those achieved with grass pollen . This factor increases the desirability of using therapeutic preparations with minimal IgE‐binding activity , such as allergoids , in order to reduce the risk of side‐effects and enable patients to tolerate a higher dose of allergen , thereby increasing the chances of successful specific immunotherapy . Forty patients with rhinitis and /or asthma were allocated at r and om to active‐ or placebo‐treatment groups at the beginning of the study . All patients received the active preparation during the second year of the study . Immunotherapy was well tolerated by all patients and the incidence of side‐effects was low . Treatment result ed in significant reductions in specific cutaneous reactivity and increases in nasal tolerance . A progressive improvement in nasal inspiratory peak flow in association with the immunotherapy indicated a reduction in nasal inflammation . These objective assessment s of efficacy endorsed the results from the patients ’ diary cards , which indicated significant improvements in symptoms and reductions in the use of medication . The immunologic activity of the therapeutic preparation was demonstrated by the induction of a significant specific‐IgG antibody response , with increases in IgG4 during the second year of treatment . We conclude that the safety and efficacy of immunotherapy with the Parietaria allergoid make it suitable for consideration in the treatment of patients with Parietaria‐pollen‐induced rhinitis or asthma BACKGROUND Allergy immunotherapy tablet ( AIT ) treatment might be a safe and convenient form of specific immunotherapy but it has not been investigated in North American children and adolescents . OBJECTIVE We sought to investigate the efficacy and safety of timothy grass AIT treatment in North American children/adolescents with grass pollen-induced allergic rhinoconjunctivitis ( ARC ) with or without asthma . METHODS Three hundred forty-five subjects ( 5 - 17 years old ) were r and omized to once-daily grass AIT treatment ( 2,800 bioequivalent allergen units , 75,000 st and ardized quality tablet , approximately 15 μg of Phl p 5 ) or placebo approximately 16 weeks before the 2009 grass pollen season ( GPS ) . Treatment continued through the GPS . Daily symptoms and allergy rescue medication use were recorded . The primary end point was the total combined score ( TCS ) of the daily symptom score ( DSS ) and daily medication score ( DMS ) for the entire GPS . DSS , DMS , Rhinoconjunctivitis Quality of Life Question naire score , and Phl p 5-specific IgG4 and IgE-blocking factor levels were secondary end points . Safety was assessed through adverse events . RESULTS Eighty-nine percent of subjects were multisensitized . TCS , DSS , DMS , and Rhinoconjunctivitis Quality of Life Question naire score versus placebo improved 26 % ( P = .001 ) , 25 % ( P = .005 ) , 81 % ( P = .006 ) , and 18 % ( P = .04 ) . Phl p 5-specific IgG4 and IgE-blocking factor levels were significantly higher at the peak and end of the GPS ( P < .001 ) . Treatment was well tolerated . Adverse events were generally mild and transient . Although no investigator-assessed systemic allergic reactions were reported , 1 grass AIT-treated subject experienced an event indicating a systemic reaction ( lip angioedema , dysphagia , and cough ) . CONCLUSIONS Use of once-daily timothy grass AIT treatment effectively treats timothy grass ( cross-reactive with Festucoideae grasses ) pollen-induced ARC in North American children 5 years and older . Given its convenient administration , lack of dose build-up requirement , safety profile , and efficacy , AIT treatment might become an important addition to the North American ARC treatment armamentarium Specific immunotherapy is still widely used in grass-pollen allergy , but its side effects may limit its use . We tested the safety and efficacy of a formalinized high-molecular-weight allergoid prepared from a mixed grass-pollen extract with two injection schedules in a double-blind , placebo-controlled study . Eighteen patients received placebo , 19 received the low-dose schedule ( maximal dose : 2000 PNU ) and 20 received the high-dose schedule ( maximal dose : 10,000 PNU ) . Only one patient presented a systemic reaction of moderate severity for a dose of 1200 PNU . Before the onset of the pollen season , patients had a nasal challenge with orchard grass-pollen grains , a skin test titration , and the titration of serum-specific IgG. Both groups of patients presented a significant reduction in nasal and skin sensitivities and a significant increase in IgG compared to placebo . Symptoms and medications for rhinitis and asthma were studied during the season , and both groups receiving allergoids had a significant reduction of symptom-medication scores for nasal and bronchial symptoms . There was a highly significant correlation between nasal symptom-medication scores during the season and the results of nasal challenges . High-molecular-weight allergoids are safe and effective The aims of this study were to examine the therapeutic effects of sublingual immunotherapy ( SLIT ) and to identify potential biomarkers that would predict the therapeutic response in a r and omized , double-blind , placebo-controlled clinical trial . The trial was carried out over two pollinosis seasons in 2007 and 2008 . Carry-over therapeutic effects were analyzed in 2009 . SLIT significantly ameliorated the symptoms of pollinosis during the 2008 and 2009 pollen seasons . Cry j 1-specific cytokine production in a subgroup of patients with mild disease in the SLIT group was significantly attenuated . The ratio of specific IgE to total IgE before treatment correlated with the symptom-medication score in the SLIT group in 2008 . Patients with increased Cry j 1-iTreg in the SLIT group had significantly improved QOL and QOL-symptom scores . In summary , the specific IgE to total IgE ratio and upregulation of Cry j 1-iTreg are c and i date s for biomarker of the clinical response to SLIT Background : Both sublingual allergen‐specific immunotherapy ( SLIT ) and subcutaneous immunotherapy ( SCIT ) have a documented clinical efficacy , but only few comparative studies have been performed Thirty patients with asthma and /or monosensitized allergic rhinitis caused by grass pollen whose ages ranged from 15 to 35 years were selected . Two groups were established at r and om : an active group and a placebo group , and a double‐blind study was done on treatment with immunotherapy for a period of 3 continuous years , with initiation doses administered according to the rush immunotherapy technique . Grass‐pollen allergen extract Alutard SQ and histamine as a placebo were used . The objective parameters of efficacy evaluated were end‐point cutaneous tests , conjunctival provocation , bronchial provocation , and symptom/medication scores , as well as specific immunoglobulin determinations . The statistical evaluation of the results was significant for the differences existing between the initial and final time of the active group , and there were significant differences between the two groups for all of the parameters considered . We found no relationship between clinical improvement and the range of specific immunoglobulin E values . Regarding the safety of the treatment , systemic adverse effects were manifested only in the initial phase ( rush immunotherapy ) . and were easily controlled by treatment . We conclude that the efficacy and safety of immunotherapy with grass pollen make it possible to consider this treatment fundamental in these patients BACKGROUND The summary of product characteristics of the grass allergy immunotherapy tablet ( AIT ) ( Phleum pratense grass pollen allergen extract ) states that clinical effect may be observed in the first pollen season of treatment , if treatment is initiated ≥2 months ( 8 weeks ) before the start of the grass pollen season . However , because patients with grass allergy may first present to physicians during the season , immediate treatment initiation ( ie , in-season initiation ) may increase treatment compliance and reduce the risk for disease progression compared with asking patients to return before the next pollen season to initiate treatment . This " in-season approach " may offer more patients the potentially beneficial treatment option of specific immunotherapy . However , to date , the immunomodulatory effects and tolerability of in-season treatment initiation is unknown . OBJECTIVE The aim of this study was to assess the immunologic effects and tolerability of in-season initiation of treatment with the grass AIT . METHODS This multicenter , r and omized , double-blind , placebo-controlled trial was carried out in Germany and Austria . Adults with grass pollen allergy ( positive skin-prick test and specific grass-pollen immunoglobulin [ Ig ] E ) and grass pollen-induced moderate to severe persistent rhinoconjunctivitis were enrolled . Patients were r and omly assigned to receive once-daily grass AIT or placebo , starting during the 2008 grass pollen season and continuing for 8 to 10 weeks . The primary end point was change from baseline in IgE-blocking factor ( serum components competing with IgE for allergen binding ) . Secondary end points included changes from baseline in specific IgE and IgG(4 ) and measures of tolerability ( assessed mainly by adverse events [ AEs ] ) . Blood sample s for immunologic assessment were obtained by the investigators at baseline and after treatment . All AEs observed by the investigator and /or reported by the patient were recorded throughout the trial and follow-up . RESULTS A total of 276 patients were enrolled and formed the full analysis set ( mean age , 35 years ; 55 % men , 45 % women ; 99 % white ; mean weight , 76 kg ; history of asthma , 41 % ; mean duration of grass allergy , 15.1 years ) . No major differences in medical history were found between the grass AIT group ( n = 219 ) and the placebo group ( n = 57 ) . The change from baseline in mean concentration of IgE-blocking factor was significantly greater with grass AIT compared with placebo ( + 0.14 vs + 0.05 ; P < 0.0001 ) . The changes from baseline in specific IgE and specific IgG(4 ) concentrations were significantly greater with AIT compared with placebo ( IgE , + 0.59 vs + 0.21 log kU/L ; IgG(4 ) , + 0.18 vs + 0.04 log relative units ; both , P < 0.0001 ) . At least 1 AE was reported in 58 % of patients in the AIT group and in 40 % of patients in the placebo group . Most AEs considered related to AIT were mild or moderate events in the mouth , throat , and /or ears ( eg , oral pruritus ) . Four serious AEs were reported in the AIT group ( sinusitis , road traffic accident , salmonellosis , meniscus lesion ) , but all were considered unlikely to be related to treatment . Three percent of the grass AIT group and 2 % of the placebo group were withdrawn from the trial due to an AE . CONCLUSIONS In-season initiation of grass AIT was associated with an immunomodulatory response in terms of induction of IgE-blocking factor , specific IgE , and specific IgG(4 ) . In-season initiation of grass AIT was generally well tolerated in this group of adults with moderate to severe grass pollen-induced rhinoconjunctivitis . These findings are consistent with those related to the preseasonal initiation of AIT therapy BACKGROUND Sublingual allergen immunotherapy ( SLIT ) is a commonly used alternative route of administration to st and ard subcutaneous immunotherapy ( SCIT ) in Europe . Despite its wide use , the cost-effectiveness of SLIT vs SCIT has not been well established . OBJECTIVE To evaluate the cost and effectiveness of SLIT compared with SCIT in patients with allergic rhinoconjunctivitis during a 3-year specific allergen immunotherapy ( SIT ) from a third-party payer 's , a patient 's , and society 's perspectives . METHODS We performed an open-label r and omized clinical trial of patients receiving SLIT ( n = 19 ) , patients receiving SCIT ( n = 23 ) , and a control group ( n = 22 ) . The outcome measures were Rhinoconjunctivitis Quality of Life Question naire score , visual analog scale score , symptomatic medication reduction , and direct and indirect costs . RESULTS SLIT offered clinical benefits to patients comparable to those provided by SCIT . From the perspective of a third-party payer , the total average direct medical cost per patient of 3-year SIT was estimated at Euro 416 vs Euro 482 in the SLIT and SCIT groups , respectively . A patient who received SLIT paid less than a patient who received SCIT for all out-of-pocket costs ( Euro176 for SLIT vs Euro 255 for SCIT ) but more for sole allergen extracts ( Euro 72 for SLIT vs Euro 55 for SCIT ) . When both direct and indirect costs were considered , the 3-year SIT expenditures per patient reached Euro 684 vs Euro 1,004 in the SLIT and SCIT groups , respectively . CONCLUSIONS SLIT represents a less expensive alternative relative to subcutaneous administration from all perspectives . However , from a patient 's perspective , SCIT offers a less expensive alternative for patients who do not experience loss of income and travel costs associated with treatment Background : Recent studies have demonstrated the efficacy of sublingual‐swallow immunotherapy ( SLIT ) in seasonal and perennial rhinitis . Sublingual administration of solutions is not convenient for all patients . The aim of the study was to evaluate the efficacy and safety of immunotherapy administered sublingually , initially as drops , and then as tablets during maintenance therapy Background : We assessed the efficacy of preseasonal local allergoid immunotherapy in a group of children with asthma and /or rhinitis and /or rhinoconjunctivitis due to grass pollen Control of seasonal symptoms by means of a preventive and easy to use ( only one intradermal injection eight weeks before the pollen peak ) immunotherapy , is recommended nowadays . We verified the clinical efficacy of E.P.D. ( Enzyme Potentiated Desensibilization ) in a double-blind , placebo-controlled study . This particular immunotherapy consists of an intradermal injection mix , made up of allergenic extracts at extremely low doses and an enzyme called beta-glucuronidase . The vaccine is administered once a year , eight weeks before pollen peaks . We studied a group of 40 patients allergic to grass pollen . The results , analysed statistically on the basis of a symptoms score , showed good clinical efficacy and a significant reduction of drug consumption during the high pollen period . Due to the clinical effectiveness , easy administration ( only on injection ) and excellent tolerance of the immunotherapy , E.P.D. is particularly suited for the prevention of seasonal symptoms in patients allergic to grass pollen BACKGROUND The local ( noninjection ) routes of immunotherapy are presently regarded as viable therapeutic options for respiratory allergy , and their mechanisms of action are currently undergoing investigation . OBJECTIVE We evaluated the clinical efficacy of a preseasonal rush sublingual-swallow immunotherapy and its effects on allergic inflammation in patients with seasonal rhinoconjunctivitis caused by Parietaria species . METHODS Thirty patients with Parietaria species-induced rhinoconjunctivitis ( 13 with mild intermittent asthma ) were r and omly assigned sublingual-swallow immunotherapy or placebo in a rush preseasonal course . We assessed the seasonal symptom-drug intake score by diary card and the inflammatory infiltration and the intercellular adhesion molecule 1 expression on nasal epithelium after specific allergenic challenge before and after treatment . RESULTS The investigated immunotherapy was well tolerated , and no side effects were recorded . A significant reduction of the symptom score ( P = .016 ) and drug intake score ( P = . 008 ) after immunotherapy was observed only in the active group . A decrease of the cumulative score was observed also in the placebo group ( P = .046 ) , but the significance was clearly higher ( P = .006 ) in the active group . In the active group a reduction of neutrophils ( P = .001 ) , eosinophils ( P = .01 ) , and intercellular adhesion molecule 1 expression ( P = .04 ) after specific nasal challenge was also detected . CONCLUSION The present results suggest that this sublingual-swallow immunotherapy administered through a rush schedule is clinical ly effective and safe and that it decreases the immune-mediated inflammatory responses to the allergen Abstract In a double-blind study , we compared the effects of the Rinkel and the current st and ard methods of immunotherapy with ragweed pollen extract and those of placebo on symptoms of ragweed hay fever and immunologic parameters in 43 patients highly sensitive to ragweed . Each had a skin-test end point by Rinkel serial titration at 1:312,500 w/v or greater dilution , a 2 + skin test to ragweed AgE 0.01 μg/ml , and in vitro histamine release by ragweed pollen extract . None had had immunotherapy for at least 7 yr . Patients were matched on the basis of leukocyte histamine release to ragweed pollen extract and assigned to treatment groups . Fourteen received ragweed pollen extract by the Rinkel method , 14 received placebo , and 15 received ragweed pollen extract by the current st and ard method weekly between February and October , 1979 . Rinkel method doses were derived from skin-test end points and were advanced to 0.5 ml of the end-point dilution ; current st and ard method doses were advanced to the highest tolerated dose . The median maintenance dose for Rinkel method patients was 0.5 ml of 1:1,562,500 w/v ( 0.001 μg AgE ) , and for current st and ard method patients was 0.3 ml of 1:100 w/v ( 11 μg AgE ) . An additional unmatched group of nine similar patients received Rinkel method immunotherapy in both 1978 and 1979 . Under the conditions of this study , the current st and ard method of immunotherapy produced a significant decrease in ragweed hay fever symptom-medication scores , increase in antiragweed IgG levels , and decrease in seasonal rise in antiragweed IgE levels in comparison with the effects of either Rinkel method or placebo . The effect of the Rinkel method on these variates was not significantly different from the effects of placebo Abstract 1.1 . Ragweed-sensitive patients who had never received previous hyposensitization therapy were divided r and omly into 3 groups . Either repository , placebo , or aqueous therapy was administered to each group . Following aqueous therapy , 16 of 21 patients responded satisfactorily . In both the repository and placebo groups , 11 of 19 patients had a satisfactory clinical response . The study was conducted in a double-blind manner . 2.2 . There was no correlation between the clinical response and the change in hemagglutination titer . 3.3 . There was a slight suggestion that patients with an elevated reagin titer or a rising reagin titer have a poorer therapeutic response to specific therapy The effectiveness of Cocos nucifera pollen extract immunotherapy ( CPE-IT ) was studied in 96 patients allergic to C. nucifera pollen . A placebo-controlled study was performed at r and om for a period of 6 - 12 months . The clinical status of the patients measured by the symptom-medication scores demonstrated that C. nucifera pollen-allergic patients had significant ( p < 0.005 ) clinical improvement after CPE-IT in comparison to placebo treatment . Serological study result ed a significant reduction ( p < 0.001 ) of specific IgE and significant elevation ( p < 0.01 ) of specific IgG in post-therapeutic patients ' sera which were correlated significantly ( r = 0.45 , p < 0.001 ) ; the changes of the above immunoglobulin levels in the placebo-treated patients were nonsignificant . However , there was no correlation between symptom-medication scores and changes in specific serum IgE or IgG levels Background Rhinoconjunctivitis due to birch pollen sensitization is common in Northern Europe . A depigmented polymerized birch pollen extract – Depigoid ® has been developed for immunotherapy BACKGROUND Recombinant DNA technology has the potential to produce allergen-specific immunotherapy vaccines with defined composition . OBJECTIVE To evaluate the effectiveness of a new recombinant birch pollen allergen vaccine in patients with birch pollen allergy . METHODS A multicenter , r and omized , double-blind , placebo-controlled trial was undertaken to compare the following 3 vaccines in 134 adults with birch pollen allergy : recombinant birch pollen allergen vaccine ( rBet v 1a ) , licensed birch pollen extract , natural purified birch pollen allergen ( nBet v 1 ) , and placebo . Patients received 12 weekly injections followed by monthly injections of the maintenance dose containing 15 microg Bet v 1 for 2 years . RESULTS Significant reductions ( about 50 % ) in rhinoconjunctivitis symptoms ( rBet v 1 , P = .0002 ; nBet v 1 , P = .0006 ; birch extract , P = .0024 ) , rescue medication ( rBet v 1 , P = .0011 ; nBet v 1 , P = .0025 ; birch extract , P = .0063 ) , and skin sensitivities ( P < .0001 ) were observed in the 3 actively treated groups compared with placebo during 2 consecutive pollen seasons . Clinical improvement was accompanied by marked increases in Bet v 1-specific IgG levels , which were higher in the rBet v 1-treated group than in the birch and nBet v 1-treated groups . New IgE specificities were induced in 3 of 29 patients treated with birch pollen extract , but in none of the 32 rBet v 1-treated or 29 nBet v 1-treated patients . No severe systemic adverse events were observed in the rBet v 1-treated group . CONCLUSION The rBet v 1-based vaccine was safe and effective in treating birch pollen allergy , and induced a highly specific immune response BACKGROUND Immunotherapy for allergic rhinoconjunctivitis ( ARC ) in North America is generally administered subcutaneously , but alternative formulations might be safer and more convenient . Trials of sublingual formulations in North America are needed to confirm European efficacy and safety data . OBJECTIVE We sought to investigate the efficacy and safety of timothy grass allergy immunotherapy tablet ( AIT ) treatment in North American subjects with ARC . METHODS Four hundred thirty-nine adults with grass pollen-induced ARC with or without asthma were r and omized to once-daily 2,800 bioequivalent allergen units of st and ardized grass AIT ( oral lyophilisate , Phleum pratense , 75,000 st and ardized quality tablet , containing approximately 15 μg of Phl p 5 ) or placebo approximately 16 weeks before the 2009 grass pollen season ( GPS ) . The primary end point was the average total combined score of the daily symptom score and the daily medication score during the GPS . Rhinoconjunctivitis Quality of Life Question naire with st and ardized activities ( RQLQ[S ] ) scores , Phl p 5-specific IgG4 levels , and IgE-blocking factor levels were additional end points . Adverse events ( AEs ) were monitored for safety . RESULTS Relative to placebo , grass AIT treatment improved total combined scores by 20 % ( P = .005 ) , daily symptom scores by 18 % ( P = .02 ) , and RQLQ(S ) scores by 17 % ( P = .02 ) . Daily medication scores were improved by 26 % and trended toward significance ( P = .08 ) . Phl p 5-specific IgG4 and IgE-blocking factor levels were higher after grass AIT treatment compared with those after placebo at the end of the GPS ( P < .001 ) . Grass AIT treatment was safe and well tolerated . The majority of AEs were transient mild local reactions with no investigator-diagnosed grass AIT-related serious AEs or reports of anaphylactic shock/respiratory compromise . In the grass AIT group , 1 subject received epinephrine after experiencing a possible grade 1 systemic reaction ( local site reactions , chest discomfort , and rash ) . CONCLUSIONS Timothy grass AIT treatment ( cross-reactive with related Pooideae grasses ) was demonstrated to be effective , generally safe , and well tolerated in North American adults with grass pollen-induced ARC Abstract Background : There is ample evidence to support the efficacy of sublingual immunotherapy ( SLIT ) on allergic rhinitis , while there is less solid data regarding asthma . We evaluated the effects of a high dose birch SLIT on birch-induced rhinitis and asthma in a controlled study . Methods : This double-blind , placebo-controlled , r and omised , single centre trial on SLIT with birch pollen allergen extract ( Stallergenes , Antony , France ) included 24 patients presenting severe rhinitis and slight to moderate asthma , 14 actively and 10 placebo treated . SLIT was performed by a pre-coseasonal protocol , and was repeated for 2 years . The study plan included a selection visit , a visit at the start of the first and the second treatment cycle , a follow-up visit after 1–3 months from the start of each cycle , and a final visit at the end of each yearly cycle . Results : A significant decrease ( p < 0.05 ) in rhinorrhoea and nasal obstruction occurred in actively treated patients . The median number of days with asthma at visit 3 was 10 ( 0–27 ) in the active ( SLIT ) group and 13 ( 0–29 ) in the placebo group . The median number of days with asthma at visit 6 was 2 ( 0–6 ) in the SLIT group and 7 ( 0–15 ) in the placebo group ( p < 0.05 between groups ) . A stepdown of asthma occurred in 77 % of actively treated vs. none of placebo treated patients ( p = 0.05 ) . No severe adverse events were observed . Conclusions : This pilot study suggests that SLIT with high dose birch extract may be able to step down seasonal pollen-induced asthma after prolonged treatment |
957 | 30,258,483 | Our meta- analysis may provide evidence that the presence of psychosis increases the risk of suicide in patients suffering from severe depression .
Conclusions The presence of psychosis in major depression should alert clinicians for the increased risk of completed suicide . | Background It remains unclear whether psychotic features increase the risk of completed suicides in unipolar depression .
The present systematic review coupled with a meta- analysis attempts to eluci date whether unipolar psychotic major depression ( PMD ) compared to non-PMD presents higher rates of suicides . | This article reports on the evidence for the validity of psychotic major depression as a distinct subtype based on cross-sectional and 1-year prospect i ve data from the Epidemiologic Catchment Area study . Consistent with findings from previous clinical studies , only about 14 % of major depressions were accompanied by psychotic features . Psychotic as compared with nonpsychotic depression had a more severe course , as reflected in increased risk of relapse , persistence over 1 year , suicide attempts , hospitalization , comorbidity , and financial dependency . These differences could not be explained by differences in demographic characteristics or by symptom severity , as assessed by symptom profile or number of symptoms . The boundary problem with schizophrenia and bipolar affective disorder that is seen in clinical studies was also found in this sample . To our knowledge , this is the first study to examine the validity of psychotic depression in a community sample ; the findings are consistent with those from clinical sample s. They support the clinical significance of psychotic depression and the continuation of its inclusion as a distinct subtype in DSM-IV OBJECTIVE To examine the association between baseline suicidality and outcome of major depression in a r and omized controlled trial of the pharmacotherapy of psychotic depression and to explore the interaction of suicidality , r and omized treatment assignment , and depression outcome . METHODS This study was a secondary analysis of data from 258 persons aged 18 years or older with DSM-IV-defined major depressive disorder with psychotic features who participated in a 12-week r and omized controlled trial ( RCT ) comparing olanzapine plus sertraline with olanzapine plus placebo ( the Study of the Pharmacotherapy of Psychotic Depression [ STOP-PD ] , which ran from 2002 to 2007 ) . The independent variable was baseline suicidality , defined by 4 groups ( suicide attempt in the current episode , active suicidal ideation , passive suicidal ideation , and no suicidality ) . The outcome variables were change in 16-item Hamilton Depression Rating Scale ( HDRS₁₆ ) total score ( excluding the suicide item ) over time and remission of psychotic depression over time . RESULTS Suicidality groups did not significantly differ on baseline HDRS₁₆ total score . Baseline suicidality group was significantly associated with change in HDRS₁₆ score over time in the sample as a whole ( F₃,₁₃₉₄ = 8.17 ; P < .0001 ) , but was not significantly associated with probability of remission over time . Among participants assigned to olanzapine and placebo , persons with no suicidality had a significantly greater reduction in HDRS₁₆ total score compared to those with passive suicidal ideation ( 7.5-point difference in change scores between the 2 groups ; 95 % CI , 4.3 - 10.7 t₁₃₉₄ = 4.61 , P < .0001 ) , active suicidal ideation ( 4.4 points ; 95 % CI , 1.4 - 7.4 ; t₁₃₉₄ = 2.85 , P = .0176 ) , or suicide attempts ( 6.1 points ; 95 % CI , 2.8 - 9.4 ; t₁₃₉₄ = 3.66 , P = .0015 ) . The 12-week change from baseline in HDRS₁₆ score for patients with no suicidality was not significantly different between the 2 treatment arms . However , the 12-week HDRS₁₆ improvement was significantly greater in the olanzapine plus sertraline arm , compared with the olanzapine plus placebo arm , for patients with suicide attempts ( 8.7-point difference in change scores between the 2 groups ; 95 % CI , 5.1 - 12.4 ; t₁₃₉₄ = 4.75 , P < .0001 ) , active suicidal ideation ( 8.1 points ; 95 % CI , 4.5 - 11.7 ; t₁₃₉₄ = 4.38 , P < .0001 ) , or passive suicidal ideation ( 5.7 points ; 95 % CI , 2.2 - 9.2 ; t₁₃₉₄ = 3.23 , P = .0012 ) , respectively . CONCLUSIONS Baseline suicidality predicted worse acute treatment outcome of psychotic depression . However , participants with suicidality had a better outcome when treated with the combination of olanzapine and sertraline than when treated with olanzapine plus placebo . TRIAL REGISTRATION Clinical Trials.gov identifier : Objective To compare the relative efficacy of electroconvulsive therapy ( ECT ) in psychotic and nonpsychotic patients with unipolar major depression . Methods The outcome of an acute ECT course in 253 patients with nonpsychotic ( n = 176 ) and psychotic ( n = 77 ) unipolar major depression was assessed in the first phase of an ongoing National Institute of Mental Health-supported four-hospital collaborative study of continuation treatments after successful ECT courses . ECT was administered with bilateral electrode placement at 50 % above the titrated seizure threshold . The remission criteria were rigorous : a score ≤10 on the 24-item Hamilton Rating Scale for Depression ( HRSD ) after 2 consecutive treatments , and a decrease of at least 60 % from baseline . Results The overall remission rate was 87 % for study completers . Among these , patients with psychotic depression had a remission rate of 95 % and those with nonpsychotic depression , 83 % . Improvement in symptomatology , measured by the HRSD , was more robust and appeared sooner in the psychotic patients compared with the nonpsychotic patients . Conclusion Bilateral ECT is effective in relieving severe major depression . Remission rates are higher and occur earlier in psychotic depressed patients than in nonpsychotic depressed patients . These data support the argument that psychotic depression is a distinguishable nosological entity that warrants separate treatment algorithms The authors report prospect i ve uniform clinical data differentiating 25 patients who committed suicide from 929 patients who did not in a group of 954 patients with major affective disorder followed for an average of 4 years in the Collaborative Program on the Psychobiology of Depression . Eight ( 32 % ) of the suicides occurred within 6 months and 13 ( 52 % ) within 1 year of entry into the study . Hopelessness , loss of pleasure or interest , and mood cycling during the index episode differentiated the suicide group . Diagnostic subcategories , suicidal ideation at entry to the study , suicide attempts during current or past episodes , and medical severity of prior attempts did not differentiate the suicide group OBJECTIVE The present study investigates how consistently DSM-IV major depressive disorder ( MDD ) with psychosis was diagnosed by research consensus across 10 years and the association of clinical characteristics with diagnostic consistency . METHOD The sample included 146 participants , part of a larger first-admission cohort ( N = 628 ) presenting to a psychiatric inpatient facility with psychosis , who were diagnosed with psychotic depression at least once across 4 assessment s spanning 10 years ( after first admission and at 6-month , 24-month , and 10-year follow-ups ) . The primary outcome of this prospect i ve epidemiologic study was retention of the best-estimate consensus diagnosis at each assessment . Diagnoses at each assessment were determined from semistructured interviews , medical records , and informant reports . The participants were recruited from 1989 to 1995 . RESULTS Fifty-five of the 146 participants ( 37.7 % ) were diagnosed with psychotic depression at each available assessment ; 13 ( 8.9 % ) switched from MDD to bipolar disorder , 24 ( 16.4 % ) switched from MDD to schizophrenia or schizoaffective disorder , and the remaining 54 ( 37.0 % ) had other patterns of diagnostic change . Only 47 of 80 participants ( 58.8 % ) diagnosed with MDD at baseline retained a mood disorder diagnosis 10 years later ( 36 [ 45.0 % ] had MDD and 11 [ 13.8 % ] had bipolar disorder ) , while 16 of 52 participants ( 30.8 % ) who ended the study with MDD were initially misdiagnosed . Compared to participants who were consistently diagnosed with MDD , those switching from MDD to bipolar disorder had better premorbid adjustment , more first-degree relatives with MDD , better functioning , and fewer negative symptoms at baseline , whereas those shifting to the schizophrenia spectrum had a more insidious onset , longer initial hospital stays , worse functioning , and more negative symptoms ( all P values < .05 ) . CONCLUSIONS The diagnosis of MDD with psychosis among in patients showed poor long-term consistency . For clinicians , results indicate that the diagnosis of MDD with psychosis based on a single assessment should be considered provisional OBJECTIVE Most efforts to describe the prognostic significance of psychotic features in depression have been limited to single assessment s 1 year or less after the initial evaluation . However , the various biological and treatment response differences between patients with psychotic and nonpsychotic depression suggest that prognostic differences may be very long-term . METHOD The 787 patients described here entered the study as they sought treatment at one of five academic medical centers ; they had either RDC major depressive disorder or schizo-affective depression ( other than the mainly schizophrenic subtype ) and completed at least 6 months of follow-up . Of these , 144 ( 18.3 % ) had psychotic depression as defined here . Patients provided follow-up interviews at 6-month intervals for 5 years and annually thereafter ; 98 of those with psychotic depression and 434 of those with non-psychotic depression were followed for 10 years . RESULTS Those who began follow-up with psychotic depression had fewer weeks with minimal symptoms in each of the 10 years of follow-up and reported more psychosocial impairment at both 5 and 10 years . Both the index episode and the first recurrence of psychotic depression lasted longer than nonpsychotic episodes , but nonpsychotic episodes among previously psychotic individuals were relatively brief . Intervals between episodes were significantly shorter for patients who had ever been psychotic . CONCLUSIONS Together with evidence that psychotic features are highly recurrent , these data show 1 ) that psychotic features denote a lifetime illness of greater severity and 2 ) that within individuals , psychotic features may emerge in only the more severe episodes To evaluate the role of severe depression , i.e. , depression with melancholic and /or psychotic features and alcohol dependence in suicide and undetermined death . The Lundby Study is a prospect i ve , longitudinal study of a population consisting of 3563 subjects . In a long-term follow up 1947–2006 there were 66 suicide cases , including 19 undetermined deaths . Depression and alcoholism were as expected the major contributors to suicide ( 44 % and 23 % respectively ) . Severe depression with psychotic and /or melancholic features was diagnosed in 66 % of all depressions and in 29 % of all suicide cases , as compared to 15 % for major depression only . Alcohol dependence was related to undetermined death . Major depressive disorder with melancholic and /or psychotic features appears to be an important contributor to accomplished suicide in the depression group , and alcohol dependence appears to be related to undetermined death This retrospective study compared the treatment responses of 34 primary , unipolar depressives without psychotic features and 30 with psychotic features . Patients were diagnosed by Research Diagnostic Criteria and received trials of tricyclic antidepressants , antipsychotics , the combination of the two , electroconvulsive therapy , or placebo and psychotherapy . Only three of 18 psychotic patients vs. 17 of 23 nonpsychotic patients responded to antidepressants alone . Electroconvulsive therapy and the combination of antipsychotic and antidepressant medication gave better responses . These data suggest that major depressive disorder with psychotic features is best considered as a distinct subtype rather than a severe variant of major depression OBJECTIVE The study explored the phenomenology and prognostic significance of delusions in major depressive disorder . METHOD From 452 patients with DSM-III major depression , we selected those with at least one belief fulfilling both DSM-III prerequisites for a delusion ( i.e. , being of " delusional proportions " and being maintained with " delusional intensity " ) . These patients were compared to the others with respect to demographic , historical , and index episode features ; time spent in a depressive episode during a prospect i ve observation period ; and 10-year outcome . The same comparisons were made between patients with mood-incongruent delusions and those with mood-congruent delusions only . The study covered the period between January 1 , 1978 , and December 31 , 2005 . RESULTS About 20 % of patients had at least one delusion in their index episode . An additional 5.3 % had a belief fulfilling only one of the DSM-III prerequisites for a delusion . In about one quarter of delusional patients , the index episode was not " severe . " Almost 10 % of delusional patients had both mood-congruent and mood-incongruent delusions . In patients with delusions , time to syndromal recovery from index episode was longer and antipsychotic medication was more frequently used ( both p < .0001 ) . The presence of delusions predicted a higher depressive morbidity during the prospect i ve observation period ( p < .05 ) , but not a poorer 10-year outcome . No variable discriminated patients with mood-incongruent delusions from those with mood-congruent delusions only . CONCLUSION The presence of delusions in a major depressive episode has significant therapeutic and short-term prognostic implication s. However , the boundary between delusions and nondelusional sustained preoccupations is somewhat fuzzy , and some DSM-IV assumptions concerning psychotic depression ( i.e. , that this depression is always " severe " ; that in an individual patient , delusions will be either all congruent or all incongruent with depressed mood ; and that mood-incongruent delusions are associated with a poorer prognosis ) may be unwarranted OBJECTIVE It is widely known that the risk of suicide is higher in cases of major depressive disorders in comparison to the general population . The purpose of this study was to examine which psychopathologic symptoms during the index episode are predictors for an increased risk of suicide in the further course of major depression . METHOD Mortality data were determined from a prospect i ve study of 280 patients with major depression ( DSM-III-R , single episode or recurrent ) during a follow-up period of 5 years . The predictive power of different depressive symptoms including psychotic symptoms for suicide risk was investigated . RESULTS Patients who committed suicide ( N = 16 ) during the follow-up period had reported significantly more often hypochondriacal preoccupations or delusions ( but not delusions or preoccupations of impoverishment , guilt or sin ) , suicidal thoughts and suicide attempts as well as feelings of severe hopelessness during the index episode than still living patients or patients who had died from natural causes . CONCLUSION These symptoms seem to be helpful early predictors for the risk of suicide during the further course of illness . This should be taken into account for suicide prevention in the course of major depression OBJECTIVE The purpose of this study was to investigate the prevalence and comorbidity of current mental disorders defined by DSM-III-R among a r and om sample of suicide victims from a nationwide suicide population . METHOD Using a psychological autopsy method , the authors collected comprehensive data on all suicide victims in Finl and during 1 year . Retrospective axis I-III consensus diagnoses were assigned to 229 ( 172 male , 57 female ) victims . RESULTS One or more diagnoses on axis I were made for 93 % of the victims . The most prevalent disorders were depressive disorders ( 59 % ) and alcohol dependence or abuse ( 43 % ) . The prevalence of major depression was higher among females ( 46 % ) than among males ( 26 % ) . Alcohol dependence was more common among the males ( 39 % versus 18 % for females ) . A diagnosis on axis II was made for 31 % and at least one diagnosis on axis III for 46 % of the cases . Only 12 % of the victims received one axis I diagnosis without any comorbidity . CONCLUSIONS The majority of suicide victims suffered from comorbid mental disorders . Comorbidity needs to be taken into account when analyzing the relationship between suicide and mental disorders and in planning treatment strategies for suicide prevention in clinical practice OBJECTIVE Early assessment can guide accurate diagnosis , prognosis , and treatment-planning for patients with major mental illnesses . Longitudinal studies in psychotic depression from onset are rare , encouraging the present study . METHOD We followed 56 DSM-IV MDD patients with psychotic features prospect ively and systematic ally to assess course and predictors of operationally-defined syndromal remission , syndromal recovery , symptomatic remission , functional recovery , and new episodes , and to evaluate diagnostic stability . RESULTS Among 49/56 cases followed for ≥2 years , 59 % retained the initial diagnosis and most achieved syndromal remission ( 86 % ) and recovery ( 84 % ) ; 58 % remitted symptomatically , and only 35 % ( 17/49 ) recovered functionally . Syndromal recovery was earlier following subacute onset , lower initial depression scores , and lack of moodincongruent psychotic features . Within 2 years , 45 % ( 22/49 ) experienced new episodes - earlier with younger onset and higher CGI scores . DSM diagnosis changed in 41 % , to bipolar ( 33 % ) , or schizoaffective disorders ( 12 % ) , which followed early mania-like or schizophrenia-like features , respectively . CONCLUSIONS Within 2 years of first-hospitalizations , 41 % of patients initially diagnosed with psychotic-depression met criteria for DSM-IV bipolar or schizoaffective disorders . Of the 59 % retaining the initial diagnosis for 2 years , nearly half experienced new episodes , 42 % remained symptomatic , and two-thirds failed to regain their own prior functional status |
958 | 31,335,695 | There is evidence , albeit of low quality , that added the TKIs to TRT or CRT may improve RR and survival outcomes in patients with EGFR mutant status unknown advanced or metastatic NSCLC relative to other studies of TKIs alone , TRT alone or CRT | BACKGROUND Pre clinical in vitro experiments demonstrated that epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitors ( TKIs ) might have synergistic effect in combination with radiotherapy on Non-small cell lung cancer ( NSCLC ) , but the clinical trials showed inconsistence results in NSCLC patients with EGFR status unknow or mutations .
This study aim ed to determine if added TKIs to Thoracic radiotherapy ( TRT ) improve primary disease response rate ( RR ) and survival outcomes in advanced or metastatic NSCLC . | A phase III r and omized trial was conducted to investigate whether induction chemotherapy followed by radiation can influence survival as compared with radiation alone in unresectable , locally advanced non-small-cell lung cancer ( LADNSCLC ) . A total of 101 patients with unresectable stage IIIA or IIIB NSCLC were enrolled . Patients were stratified by performance status , weight loss , histology and stage , and then r and omized to receive combined chemoradiotherapy or radiotherapy alone . Radiotherapy was administered in 1.8 Gy to 2.0 Gy st and ard fractions daily 5 times weekly for a total dose of 60 Gy to 65 Gy . The combined group received induction of cisplatin , etoposide , and vinblastine ( PEV ) chemotherapy with cisplatin 20 mg/m2 on days 1 to 5 , etoposide 100 mg/m2 on days 2 to 4 , and vinblastine 6 mg/m2 on day 1 , which wasrepeated every 3 weeks for 3 courses , after which time the patients underwent radiotherapy . Of 101 patients registered , 89 patients ( 43 combined , 46 radiotherapy alone ) were eligible for analysis . The response rates for the combined and radiotherapy groups were 65 % ( 28/43 ) and 70 % ( 32/46 ) , respectively . The median survival time ( MST ) showed a tendency to be more prolonged in the combined group than in the group receiving radiotherapy alone ( 13.8 vs. 8.5 months ) . The MST in patients with nonsquamous histology was strikingly prolonged in the combined group as compared with the radiotherapy group ( 14 vs. 3.6 months , p 0.027 ) . Likewise , the MST in patients with stage IIIB was significantly prolonged in the combined group as compared with the radiotherapy group ( 11.1 vs. 7.2 months , p 0.045 ) . Together , the MST of the high-risk group with nonsquamous or stage IIIB was significantly higher in the combined group than that seen in the radiotherapy group ( 11.6 vs. 8 months , p 0.046 ) , whereas the MST of the low-risk group , defined as having both squamous histology and stage IIIA , was similar in the two treatment groups ( 18.3 vs. 20.8 months , p = 0.293 ) . In conclusion , induction PEV chemotherapy plus radiotherapy is superior to radiotherapy alone in high-risk subsets of unresectable LAD-NSCLC and therapeutic strategy should be based on the identification of prognostic factors Background Gefitinib is an oral EGFR tyrosine kinase inhibitors which may act as a radiosensitizer . Patients and Methods This phase II study evaluated the efficacy of gefitinib 250 mg once daily in combination with thoracic radiotherapy ( 66 Gy in 6.5 weeks , 2 Gy/day , 5 fractions/week ) followed by consolidation chemotherapy ( IV cisplatin and vinorelbine ) as first line treatment in a population of unselected stage IIIB NSCLC patients according to EGFR mutation status . Results Due to a low accrual rate in this study , the sample size ( n = 50 ) was not reached . Sixteen patients were included in four centers , 50 % had adenocarcinoma and 75 % were male . Genomic alterations ( 7 patients studied ) retrieved TP53 mutation in 2 patients and no EGFR mutation . Four weeks after radiotherapy , 3 patients ( 19 % ) had a partial response , 6 ( 38 % ) had a stable disease , and 7 had a progression ( 44 % ) . Median overall survival was 11 months and median progression-free survival was 5 months . At the time of the last contact , 5 patients ( 31 % ) were still alive . Main toxicities were gastrointestinal ( 81 % ) , cutaneous ( 81 % ) , general ( 56 % ) , and respiratory ( 50 % ) . There were 12>G3 adverse events in 7 ( 47 % ) patients , and there was one toxic-death during the concomitant period due to an interstitial pneumonitis . There were two possible adverse events-related deaths during the chemotherapy period ( pulmonary embolism ( n = 1 ) and sudden death after the administration of the 3rd course of chemotherapy ( n = 1 ) ) . Conclusion The benefit of Gefitinib-RT could not be confirmed due to premature trial discontinuation . Further evaluation is required , especially in patients with EGFR mutated NSCLC BACKGROUND The efficacy of the ALK inhibitor crizotinib as compared with st and ard chemotherapy as first-line treatment for advanced ALK-positive non-small-cell lung cancer ( NSCLC ) is unknown . METHODS We conducted an open-label , phase 3 trial comparing crizotinib with chemotherapy in 343 patients with advanced ALK-positive nonsquamous NSCLC who had received no previous systemic treatment for advanced disease . Patients were r and omly assigned to receive oral crizotinib at a dose of 250 mg twice daily or to receive intravenous chemotherapy ( pemetrexed , 500 mg per square meter of body-surface area , plus either cisplatin , 75 mg per square meter , or carboplatin , target area under the curve of 5 to 6 mg per milliliter per minute ) every 3 weeks for up to six cycles . Crossover to crizotinib treatment after disease progression was permitted for patients receiving chemotherapy . The primary end point was progression-free survival as assessed by independent radiologic review . RESULTS Progression-free survival was significantly longer with crizotinib than with chemotherapy ( median , 10.9 months vs. 7.0 months ; hazard ratio for progression or death with crizotinib , 0.45 ; 95 % confidence interval [ CI ] , 0.35 to 0.60 ; P<0.001 ) . Objective response rates were 74 % and 45 % , respectively ( P<0.001 ) . Median overall survival was not reached in either group ( hazard ratio for death with crizotinib , 0.82 ; 95 % CI , 0.54 to 1.26 ; P=0.36 ) ; the probability of 1-year survival was 84 % with crizotinib and 79 % with chemotherapy . The most common adverse events with crizotinib were vision disorders , diarrhea , nausea , and edema , and the most common events with chemotherapy were nausea , fatigue , vomiting , and decreased appetite . As compared with chemotherapy , crizotinib was associated with greater reduction in lung cancer symptoms and greater improvement in quality of life . CONCLUSIONS Crizotinib was superior to st and ard first-line pemetrexed-plus-platinum chemotherapy in patients with previously untreated advanced ALK-positive NSCLC . ( Funded by Pfizer ; PROFILE 1014 Clinical Trials.gov number , NCT01154140 . ) BACKGROUND Activating mutations in EGFR are important markers of response to tyrosine kinase inhibitor ( TKI ) therapy in non-small-cell lung cancer ( NSCLC ) . The OPTIMAL study compared efficacy and tolerability of the TKI erlotinib versus st and ard chemotherapy in the first-line treatment of patients with advanced EGFR mutation-positive NSCLC . METHODS We undertook an open-label , r and omised , phase 3 trial at 22 centres in China . Patients older than 18 years with histologically confirmed stage IIIB or IV NSCLC and a confirmed activating mutation of EGFR ( exon 19 deletion or exon 21 L858R point mutation ) received either oral erlotinib ( 150 mg/day ) until disease progression or unacceptable toxic effects , or up to four cycles of gemcitabine plus carboplatin . Patients were r and omly assigned ( 1:1 ) with a minimisation procedure and were stratified according to EGFR mutation type , histological subtype ( adenocarcinoma vs non-adenocarcinoma ) , and smoking status . The primary outcome was progression-free survival , analysed in patients with confirmed disease who received at least one dose of study treatment . The trial is registered at Clinical Trials.gov , number NCT00874419 , and has completed enrolment ; patients are still in follow-up . FINDINGS 83 patients were r and omly assigned to receive erlotinib and 82 to receive gemcitabine plus carboplatin ; 82 in the erlotinib group and 72 in the chemotherapy group were included in analysis of the primary endpoint . Median progression-free survival was significantly longer in erlotinib-treated patients than in those on chemotherapy ( 13.1 [ 95 % CI 10.58 - 16.53 ] vs 4.6 [ 4.21 - 5.42 ] months ; hazard ratio 0.16 , 95 % CI 0.10 - 0.26 ; p<0.0001 ) . Chemotherapy was associated with more grade 3 or 4 toxic effects than was erlotinib ( including neutropenia in 30 [ 42 % ] of 72 patients and thrombocytopenia in 29 [ 40 % ] patients on chemotherapy vs no patients with either event on erlotinib ) ; the most common grade 3 or 4 toxic effects with erlotinib were increased alanine aminotransferase concentrations ( three [ 4 % ] of 83 patients ) and skin rash ( two [ 2 % ] patients ) . Chemotherapy was also associated with increased treatment-related serious adverse events ( ten [ 14 % ] of 72 patients [ decreased platelet count , n=8 ; decreased neutrophil count , n=1 ; hepatic dysfunction , n=1 ] vs two [ 2 % ] of 83 patients [ both hepatic dysfunction ] ) . INTERPRETATION Compared with st and ard chemotherapy , erlotinib conferred a significant progression-free survival benefit in patients with advanced EGFR mutation-positive NSCLC and was associated with more favourable tolerability . These findings suggest that erlotinib is important for first-line treatment of patients with advanced EGFR mutation-positive NSCLC . FUNDING F Hoffmann-La Roche Ltd ( China ) ; Science and Technology Commission of Shanghai Municipality Purpose Concurrent chemoradiotherapy ( CCRT ) is the st and ard care for stage III non-small cell lung cancer ( NSCLC ) patients ; however , a more effective regimen is needed to improve the outcome by better controlling occult metastases . We conducted two parallel r and omized phase II studies to incorporate erlotinib or irinotecan-cisplatin ( IP ) into CCRT for stage III NSCLC depending on epidermal growth factor receptor ( EGFR ) mutation status . Material s and Methods Patients with EGFR-mutant tumors were r and omized to receive three cycles of erlotinib first and then either CCRT with erlotinib followed by erlotinib ( arm A ) or CCRT with IP only ( arm B ) . Patients with EGFR unknown or wild-type tumors were r and omized to receive either three cycles of IP before ( arm C ) or after CCRT with IP ( arm D ) . Results Seventy-three patients were screened and the study was closed early because of slow accrual after 59 patients were r and omized . Overall , there were seven patients in arm A , five in arm B , 22 in arm C , and 25 in arm D. The response rate was 71.4 % and 80.0 % for arm A and B , and 70.0 % and 73.9 % for arm C and D. The median overall survival ( OS ) was 39.3 months versus 31.2 months for arm A and B ( p=0.442 ) , and 16.3 months versus 25.3 months for arm C and D ( p=0.050 ) . Patients with sensitive EGFR mutations had significantly longer OS than EGFR-wild patients ( 74.8 months vs. 25.3 months , p=0.034 ) . There were no unexpected toxicities . Conclusion Combined-modality treatment by molecular diagnostics is feasible in stage III NSCLC . EGFR-mutant patients appear to be a distinct subset with longer survival Background Concurrent chemoradiotherapy is the st and ard of care for inoperable stage III non-small cell lung cancer ( NSCLC ) for patients who can tolerate it . We explored if adding erlotinib would increase the effectiveness of chemoradiotherapy without increasing toxicity in a single-arm prospect i ve phase II trial . Methods Forty-eight patients with previously untreated NSCLC received intensity-modulated radiation therapy ( 63 Gy/35 fractions ) on Monday – Friday , with chemotherapy ( paclitaxel 45 mg/m2 , carboplatin AUC=2 ) on Mondays , for 7 weeks . All patients also received the epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor erlotinib ( 150 mg orally 1/day ) on Tuesday – Sunday for 7 weeks followed by consolidation paclitaxel – carboplatin . The primary endpoint was time to progression ; secondary endpoints were overall survival ( OS ) , toxicity , response , and disease control and whether any endpoint differed by EGFR mutation status . Results Of 46 patients evaluable for response , 40 were former or never-smokers and 41 were evaluable for EGFR mutations ( 37 wild-type [ wt ] and 4 [ mutated ; all adenocarcinoma ] ) . Median time to progression was 14.0 months and did not differ by EGFR status . Toxicity was acceptable ( no grade 5 , one grade 4 , eleven grade 3 ) . Twelve patients ( 26 % ) had complete responses ( 10 wt , 2 mutated ) , 27 ( 59 % ) partial ( 21 wt , 2 mutated , 4 unknown ) , and 7 ( 15 % ) none ( 6 wt , 2 mutated , 1 unknown ) ( P=0.610 ) . At 37.0 months ’ follow-up ( range 3.6–76.5 months ) for all patients , median OS time was 36.5 months and 1- , 2- , and 5-year OS rates were 82.6 % , 67.4 % , and 35.9 % ; none differed by mutation status . Twelve patients had no progression and 34 had local and /or distant failure . Eleven of 27 distant failures were in the brain ( 7 wt , 3 mutated , 1 unknown ) . Conclusions Toxicity and OS were promising , but time to progression did not meet expectations . The prevalence of distant failures underscores the need for effective systemic therapy BACKGROUND Non-small-cell lung cancer with sensitive mutations of the epidermal growth factor receptor ( EGFR ) is highly responsive to EGFR tyrosine kinase inhibitors such as gefitinib , but little is known about how its efficacy and safety profile compares with that of st and ard chemotherapy . METHODS We r and omly assigned 230 patients with metastatic , non-small-cell lung cancer and EGFR mutations who had not previously received chemotherapy to receive gefitinib or carboplatin-paclitaxel . The primary end point was progression-free survival ; secondary end points included overall survival , response rate , and toxic effects . RESULTS In the planned interim analysis of data for the first 200 patients , progression-free survival was significantly longer in the gefitinib group than in the st and ard-chemotherapy group ( hazard ratio for death or disease progression with gefitinib , 0.36 ; P<0.001 ) , result ing in early termination of the study . The gefitinib group had a significantly longer median progression-free survival ( 10.8 months , vs. 5.4 months in the chemotherapy group ; hazard ratio , 0.30 ; 95 % confidence interval , 0.22 to 0.41 ; P<0.001 ) , as well as a higher response rate ( 73.7 % vs. 30.7 % , P<0.001 ) . The median overall survival was 30.5 months in the gefitinib group and 23.6 months in the chemotherapy group ( P=0.31 ) . The most common adverse events in the gefitinib group were rash ( 71.1 % ) and elevated aminotransferase levels ( 55.3 % ) , and in the chemotherapy group , neutropenia ( 77.0 % ) , anemia ( 64.6 % ) , appetite loss ( 56.6 % ) , and sensory neuropathy ( 54.9 % ) . One patient receiving gefitinib died from interstitial lung disease . CONCLUSIONS First-line gefitinib for patients with advanced non-small-cell lung cancer who were selected on the basis of EGFR mutations improved progression-free survival , with acceptable toxicity , as compared with st and ard chemotherapy . ( UMIN-CTR number , C000000376 . Background : Disease progression remains the major challenge in the management of advanced ( stage IIIb or IV ) non – small cell lung cancer ( NSCLC ) after the failure of first-line or second-line chemotherapy , or even of targeted therapies such as gefitinib . The current study evaluated the tolerability and efficacy of stereotactic body radiation therapy ( SBRT ) in combined with gefitinib as a second-line or third-line treatment in patients with advanced NSCLC . Methods : Fourteen advanced NSCLC patients showing disease progression after platinum-based chemotherapy regimens were recruited . Eligible patients started taking gefitinib ( 250 mg/d ) 7 days before SBRT and continued for 1 year until disease progression , unacceptable toxicity or withdrawal of consent . SBRT was delivered in median 3 fractions within 3 to 5 days . Treatment-associated toxicity was assessed according to the Common Terminology Criteria for Adverse Events ( v.3.0 ) . Local control was assessed according to the Response Evaluation Criteria in Solid Tumors criteria and symptom assessment s were measured by the Functional Assessment of Cancer Therapy-Lung instrument ( V4.0 ) . Results : With an overall median follow-up of 15.5 months ( range , 4 to 27 mo ) , most patients were well tolerated with common side effects from grade 1 to 2 . No grade 4 or higher toxicity was encountered . The clinical disease-related symptom improvement rate was reached 57.1 % with the median duration of symptom improvement of 8.0 months . The 1-year local control and overall survival ( OS ) rates were 83.9 % and 69.6 % , respectively . The median progression-free survival and OS were 7.0 and 19.0 months , respectively . Conclusions : The SBRT combined with gefitinib is a promising treatment strategy for advanced ( stage IIIb or IV ) NSCLC after the failure of previously chemotherapy . This method improves local control and disease-related symptoms with tolerated toxicity , and even increases the progression-free survival and OS PURPOSE The aim of this prospect i ve multi-institutional phase 2 study was to investigate disease control , survival outcomes , and toxicity after thoracic three-dimensional radiation therapy ( 3D-RT ) with concurrent chemotherapy for newly diagnosed stage IV non-small cell lung cancer ( NSCLC ) . METHODS AND MATERIAL S Eligible patients were 18 to 80 years of age , had a Karnofsky performance status ( KPS ) score ≥70 % , and newly diagnosed stage IV NSCLC with limited metastatic disease ( defined as involving ≤3 organs ) . Patients received platinum-doublet chemotherapy with concurrent irradiation to the primary tumor . Primary endpoints were overall survival ( OS ) and acute toxicity . RESULTS From May 2008 to May 2012 , 198 eligible patients were enrolled from 7 cancer centers . Most patients died with distant metastasis ; only 10 % died with isolated primary recurrence . Median OS time was 13.0 months ( 95 % confidence interval [ CI ] : 11.7 - 14.3 ) ; OS rates were 53.5 % at 1 year , 15.8 % at 2 years , and 9.2 % at 3 years . Median progression-free survival ( PFS ) time was 9.0 months ( 95 % CI : 7.7 - 10.3 ) ; corresponding PFS rates were 30.8 % , 8.2 % , and 6.1 % . The 1-year , 2-year , and 3-year local ( primary tumor ) control rates were 78.8 % , 57.7 % , and 55.4 % . Multivariate analysis showed that delivery of ≥63 Gy to the primary tumor ( P=.014 ) , having a primary tumor volume < 134 cm(3 ) ( P=.008 ) , and having a stable or higher KPS score after treatment ( P=.01 ) were independent predictors of better OS . The most common severe ( grade s 3 - 4 ) acute toxicities were hematologic : leukopenia ( 37.9 % ) , thrombocytopenia ( 10.1 % ) , and anemia ( 6.9 % ) . No patients experienced grade 4 or 5 radiation-related toxicity ; 2.5 % had acute grade 3 pneumonitis , and 6.6 % had acute grade 3 radiation esophagitis . CONCLUSIONS Thoracic 3D-RT to the primary tumor with concurrent chemotherapy led to satisfactory survival outcomes with acceptable toxicity . Radiation dose , primary tumor volume , and PFS after treatment all predicted survival in these patients with limited-metastasis NSCLC BACKGROUND Erlotinib has been shown to improve progression-free survival compared with chemotherapy when given as first-line treatment for Asian patients with non-small-cell lung cancer ( NSCLC ) with activating EGFR mutations . We aim ed to assess the safety and efficacy of erlotinib compared with st and ard chemotherapy for first-line treatment of European patients with advanced EGFR-mutation positive NSCLC . METHODS We undertook the open-label , r and omised phase 3 EURTAC trial at 42 hospitals in France , Italy , and Spain . Eligible participants were adults ( > 18 years ) with NSCLC and EGFR mutations ( exon 19 deletion or L858R mutation in exon 21 ) with no history of chemotherapy for metastatic disease ( neoadjuvant or adjuvant chemotherapy ending ≥ 6 months before study entry was allowed ) . We r and omly allocated participants ( 1:1 ) according to a computer-generated allocation schedule to receive oral erlotinib 150 mg per day or 3 week cycles of st and ard intravenous chemotherapy of cisplatin 75 mg/m(2 ) on day 1 plus docetaxel ( 75 mg/m(2 ) on day 1 ) or gemcitabine ( 1250 mg/m(2 ) on days 1 and 8) . Carboplatin ( AUC 6 with docetaxel 75 mg/m(2 ) or AUC 5 with gemcitabine 1000 mg/m(2 ) ) was allowed in patients unable to have cisplatin . Patients were stratified by EGFR mutation type and Eastern Cooperative Oncology Group performance status ( 0 vs 1 vs 2 ) . The primary endpoint was progression-free survival ( PFS ) in the intention-to-treat population . We assessed safety in all patients who received study drug ( ≥ 1 dose ) . This study is registered with Clinical Trials.gov , number NCT00446225 . FINDINGS Between Feb 15 , 2007 , and Jan 4 , 2011 , 174 patients with EGFR mutations were enrolled . One patient received treatment before r and omisation and was thus withdrawn from the study ; of the remaining patients , 86 were r and omly assigned to receive erlotinib and 87 to receive st and ard chemotherapy . The preplanned interim analysis showed that the study met its primary endpoint ; enrolment was halted , and full evaluation of the results was recommended . At data cutoff ( Jan 26 , 2011 ) , median PFS was 9·7 months ( 95 % CI 8·4 - 12·3 ) in the erlotinib group , compared with 5·2 months ( 4·5 - 5·8 ) in the st and ard chemotherapy group ( hazard ratio 0·37 , 95 % CI 0·25 - 0·54 ; p < 0·0001 ) . Main grade 3 or 4 toxicities were rash ( 11 [ 13 % ] of 84 patients given erlotinib vs none of 82 patients in the chemotherapy group ) , neutropenia ( none vs 18 [ 22 % ] ) , anaemia ( one [ 1 % ] vs three [ 4 % ] ) , and increased amino-transferase concentrations ( two [ 2 % ] vs 0 ) . Five ( 6 % ) patients on erlotinib had treatment-related severe adverse events compared with 16 patients ( 20 % ) on chemotherapy . One patient in the erlotinib group and two in the st and ard chemotherapy group died from treatment-related causes . INTERPRETATION Our findings strengthen the rationale for routine baseline tissue-based assessment of EGFR mutations in patients with NSCLC and for treatment of mutation-positive patients with EGFR tyrosine-kinase inhibitors . FUNDING Spanish Lung Cancer Group , Roche Farma , Hoffmann-La Roche , and Red Temática de Investigacion Cooperativa en Cancer Background : Concurrent radiation and chemotherapy is the st and ard of care for good performance status patients with stage III non-small cell lung cancer . Locoregional control remains a significant factor relating to poor outcome . Pre clinical and early clinical data suggest that docetaxel and gefitinib have radiosensitizing activity . This study sought to define the maximum tolerated dose of weekly docetaxel that could be given with daily gefitinib and concurrent thoracic radiation therapy . Patients and Material s : Patients with histologically confirmed , inoperable stage III non-small cell lung cancer and good performance status ( Eastern Cooperative Oncology Group 0–1 ) were eligible for this study . Patients received three-dimensional conformal thoracic radiation to a dose of 70 Gy concurrently with oral gefitinib at a dose of 250 mg daily and intravenous , weekly docetaxel at escalating doses from 15 to 30 mg/m2 in cohorts of patients . Patients were given a 2-week rest period after the concurrent therapy , during which they received only gefitinib . After the 2-week rest period , patients received consolidation chemotherapy with docetaxel 75 mg/m2 given every 21 days for two cycles . Maintenance gefitinib was continued until disease progression or study completion . Results : Sixteen patients were enrolled on the study between December 2003 and April 2007 with the following characteristics : median age , 64 years ( range 43–79 years ) ; M/F : 9/7 ; and performance status 0/1 , 1/15 . Dose-limiting pulmonary toxicity and esophagitis were encountered at a weekly docetaxel dose of 25 mg/m2 , result ing in a maximum tolerated dose of 20 mg/m2/wk . Overall , grade 3/4 hematologic toxicity was observed in 27 % of patients . Grade 3/4 esophageal and pulmonary toxicities were reported in 27 % and 20 % of patients , respectively . The overall response rate was 46 % , and the median survival for all patients was 21 months . Conclusions : Concurrent thoracic radiation with weekly docetaxel and daily gefitinib is feasible but results in moderate toxicity . For further studies , the recommended weekly docetaxel dose for this chemoradiation regimen is 20 mg/m2 BACKGROUND Upfront tyrosine kinase inhibitor ( TKI ) has proved effective for selective advanced lung cancer patients in Taiwan . We hypothesized that early integration of radiotherapy during TKI treatment would decrease the chance of drug resistance and prolong progression-free survival ( PFS ) . METHODS This study included 25 patients with stage IIIb or IV non-squamous cell , non-small cell lung cancer ( NSqCLC ) who responded to upfront TKI treatment . Multi-target radiotherapy was administered during the TKI treatment course . Tomotherapy comprising a hypofractionated schedule with a dose of 40 - 50 Gy in 16 - 20 fractions was used for individual metastatic lesions . RESULTS The patients ' median follow-up duration was 30 months ( range , 9 - 62 months ) . Of the 23 patients who had stage IV disease , 9 had oligometastases ( ≤5 gross target volumes ) and 14 were in the more advanced stages of the disease . Twelve patients received more than 1 cycle of radiotherapy ( median , 3 ; range , 2 - 6 ) with TKI being the only systemic treatment before they were salvaged with chemotherapy . The overall response rate after radiotherapy was 84.0 % , and the median PFS was 16 months . The 3-year overall survival rate was 62.5 % ( 95 % confidence interval [ CI ] , 39.1 - 85.8 % ) . Toxicities were generally tolerated but it is necessary to prevent radiation-induced pneumonitis . CONCLUSION We showed that combined first-line TKI therapy and early multi-target radiotherapy are very effective in selected patients that respond to TKI , when the status of mutations in the epidermal growth factor receptor ( EGFR ) are not known before the treatment . Our data may aid expansion of the effectiveness of TKI treatment through radiotherapy in Asian patients with stage IV NSqCLC BACKGROUND Patients with non-small-cell lung cancer harbouring mutations in the epidermal growth factor receptor ( EGFR ) gene respond well to the EGFR-specific tyrosine kinase inhibitor gefitinib . However , whether gefitinib is better than st and ard platinum doublet chemotherapy in patients selected by EGFR mutation is uncertain . METHODS We did an open label , phase 3 study ( WJTOG3405 ) with recruitment between March 31 , 2006 , and June 22 , 2009 , at 36 centres in Japan . 177 chemotherapy-naive patients aged 75 years or younger and diagnosed with stage IIIB/IV non-small-cell lung cancer or postoperative recurrence harbouring EGFR mutations ( either the exon 19 deletion or L858R point mutation ) were r and omly assigned , using a minimisation technique , to receive either gefitinib ( 250 mg/day orally ; n=88 ) or cisplatin ( 80 mg/m(2 ) , intravenously ) plus docetaxel ( 60 mg/m(2 ) , intravenously ; n=89 ) , administered every 21 days for three to six cycles . The primary endpoint was progression-free survival . Survival analysis was done with the modified intention-to-treat population . This study is registered with UMIN ( University Hospital Medical Information Network in Japan ) , number 000000539 . FINDINGS Five patients were excluded ( two patients were found to have thyroid and colon cancer after r and omisation , one patient had an exon 18 mutation , one patient had insufficient consent , and one patient showed acute allergic reaction to docetaxel ) . Thus , 172 patients ( 86 in each group ) were included in the survival analyses . The gefitinib group had significantly longer progression-free survival compared with the cisplatin plus docetaxel goup , with a median progression-free survival time of 9.2 months ( 95 % CI 8.0 - 13.9 ) versus 6.3 months ( 5.8 - 7.8 ; HR 0.489 , 95 % CI 0.336 - 0.710 , log-rank p<0.0001 ) . Myelosuppression , alopecia , and fatigue were more frequent in the cisplatin plus docetaxel group , but skin toxicity , liver dysfunction , and diarrhoea were more frequent in the gefitinib group . Two patients in the gefitinib group developed interstitial lung disease ( incidence 2.3 % ) , one of whom died . INTERPRETATION Patients with lung cancer who are selected by EGFR mutations have longer progression-free survival if they are treated with gefitinib than if they are treated with cisplatin plus docetaxel . FUNDING West Japan Oncology Group ( WJOG ) : a non-profit organisation supported by unrestricted donations from several pharmaceutical companies PURPOSE The results of the Iressa Pan-Asia Study ( IPASS ) , which compared gefitinib and carboplatin/paclitaxel in previously untreated never-smokers and light ex-smokers with advanced pulmonary adenocarcinoma were published previously . This report presents overall survival ( OS ) and efficacy according to epidermal growth factor receptor ( EGFR ) biomarker status . PATIENTS AND METHODS In all , 1,217 patients were r and omly assigned . Biomarkers analyzed were EGFR mutation ( amplification mutation refractory system ; 437 patients evaluable ) , EGFR gene copy number ( fluorescent in situ hybridization ; 406 patients evaluable ) , and EGFR protein expression ( immunohistochemistry ; 365 patients evaluable ) . OS analysis was performed at 78 % maturity . A Cox proportional hazards model was used to assess biomarker status by r and omly assigned treatment interactions for progression-free survival ( PFS ) and OS . RESULTS OS ( 954 deaths ) was similar for gefitinib and carboplatin/paclitaxel with no significant difference between treatments overall ( hazard ratio [ HR ] , 0.90 ; 95 % CI , 0.79 to 1.02 ; P = .109 ) or in EGFR mutation-positive ( HR , 1.00 ; 95 % CI , 0.76 to 1.33 ; P = .990 ) or EGFR mutation-negative ( HR , 1.18 ; 95 % CI , 0.86 to 1.63 ; P = .309 ; treatment by EGFR mutation interaction P = .480 ) subgroups . A high proportion ( 64.3 % ) of EGFR mutation-positive patients r and omly assigned to carboplatin/paclitaxel received subsequent EGFR tyrosine kinase inhibitors . PFS was significantly longer with gefitinib for patients whose tumors had both high EGFR gene copy number and EGFR mutation ( HR , 0.48 ; 95 % CI , 0.34 to 0.67 ) but significantly shorter when high EGFR gene copy number was not accompanied by EGFR mutation ( HR , 3.85 ; 95 % CI , 2.09 to 7.09 ) . CONCLUSION EGFR mutations are the strongest predictive biomarker for PFS and tumor response to first-line gefitinib versus carboplatin/paclitaxel . The predictive value of EGFR gene copy number was driven by coexisting EGFR mutation ( post hoc analysis ) . Treatment-related differences observed for PFS in the EGFR mutation-positive subgroup were not apparent for OS . OS results were likely confounded by the high proportion of patients crossing over to the alternative treatment PURPOSE Patients with advanced stage IIIB or stage IV non-small cell lung carcinoma are typically treated with initial platinum-based chemotherapy . A variety of factors ( eg , performance status , gender , age , histology , weight loss , and smoking history ) are generally accepted as predictors of overall survival . Because uncontrolled pulmonary disease constitutes a major cause of death in these patients , we hypothesized that clinical and radiographic factors related to intrathoracic disease at diagnosis may be prognostically significant in addition to conventional factors . The results have implication s regarding the selection of patients for whom palliative thoracic radiation therapy may be of most benefit . METHODS AND MATERIAL S We conducted a pooled analysis of 189 patients enrolled at a single institution into 9 prospect i ve phase II and III clinical trials involving first-line , platinum-based chemotherapy . Baseline clinical and radiographic characteristics before trial enrollment were analyzed as possible predictors for subsequent overall survival . To assess the relationship between anatomic location and volume of disease within the thorax and its effect on survival , the pre-enrollment computed tomography images were also analyzed by contouring central and peripheral intrapulmonary disease . RESULTS On univariate survival analysis , multiple pulmonary-related factors were significantly associated with worse overall survival , including pulmonary symptoms at presentation ( P=.0046 ) , total volume of intrathoracic disease ( P=.0006 ) , and evidence of obstruction of major bronchi or vessels on prechemotherapy computed tomography ( P<.0001 ) . When partitioned into central and peripheral volumes , central ( P<.0001 ) but not peripheral ( P=.74 ) disease was associated with worse survival . On multivariate analysis with known factors , pulmonary symptoms ( hazard ratio , 1.46 ; P=.042 ) , central disease volume ( hazard ratio , 1.47 ; P=.042 ) , and bronchial/vascular compression ( hazard ratio , 1.54 ; P=.022 ) remained significant . CONCLUSIONS Patients with bulky central disease , bronchial/vascular compression , and /or pulmonary symptoms exhibited worse overall survival after first-line , platinum-based chemotherapy . A subset of these patients may be studied to determine whether early , planned palliative thoracic radiation could also be of benefit Introduction : Patients with stage III non – small-cell lung cancer and poor performance status and /or weight loss do not seem to benefit from st and ard therapy . Based on the pre clinical interaction between epidermal growth factor receptor inhibitors and radiation , we design ed a trial of induction chemotherapy followed by thoracic radiotherapy and concurrent erlotinib . Methods : Patients with poor-risk unresectable stage III non – small-cell lung cancer received two cycles of carboplatin at an AUC of 5 and nab-paclitaxel at 100 mg/m2 on days 1 and 8 every 21 days , followed by erlotinib administered concurrently with thoracic radiotherapy . Maintenance was not permitted . Molecular analysis was performed in available specimens . Seventy-two eligible patients were required to test whether the 1-year survival rate was less than 50 % or greater than or equal to 65 % with approximately 90 % power at a significance level of 0.10 . Results : From March 2008 to October 2011 , 78 patients were enrolled , three of whom were ineligible . The median age was 68 ( range , 39–88 ) and 32 % were aged greater than or equal to 75 years . Patients were evenly distributed between stages IIIA and IIIB and the majority had performance status 2 . The overall response rate was 67 % and the disease control rate was 93 % . Treatment was well tolerated . The median PFS and OS were 11 and 17 months , respectively . The overall 12-month OS was 57 % , which narrowly missed the prespecified target for significance . Conclusions : Patients with poor-risk stage III non – small-cell lung cancer had better than expected outcomes with a regimen of induction carboplatin/nab-paclitaxel followed by thoracic radiotherapy and erlotinib . However , as per the statistical design , the 12-month OS was not sufficiently high to warrant further studies Introduction : This study evaluated the addition of gefitinib to sequential or concurrent chemoradiotherapy ( CRT ) in unresectable stage III non-small cell lung cancer . Methods : Between May 2002 and April 2005 , 63 patients were entered before the study closing early . All received two cycles paclitaxel 200 mg/m2 and carboplatin area under the curve 6 intravenous plus gefitinib 250 mg daily . Poor risk stratum 1 ( ≥5 % weight loss and /or performance status 2 ) received radiotherapy 200 cGy for 33 fractions ( 6600 cGy ) and gefitinib 250 mg daily . Good-risk stratum 2 ( performance status : 0–1weight loss and < 5 % ) received the same RT with gefitinib 250 mg daily and weekly paclitaxel 50 mg/m2 plus carboplatin AUC 2 . Consolidation gefitinib until progression was started after all toxicities were grade ≤2 . Results : Acute high- grade infield toxicities were not clearly increased compared with historical CRT data . Poor-risk ( N = 21 ) median progression-free survival was 13.4 months ( 95 % confidence interval [ CI ] : 6.4–25.2 ) and median overall survival 19.0 months ( 95 % CI : 9.9–28.4 ) . Good-risk ( N = 39 ) median progression-free survival was 9.2 months ( 95 % CI : 6.7–12.2 ) , and median overall survival was 13 months ( 95 % CI : 8.5–17.2 ) . Thirteen of 45 tumors analyzed had activating epidermal growth factor receptor ( EGFR ) mutations , and 2 of 13 also had T790 M mutations . Seven tumors of 45 had KRAS mutations . There was no apparent survival difference with EGFR-activating mutations versus wild type or KRAS mutation versus wild type . Conclusions : Survival of poor-risk patients with wild type or mutated EGFR receiving sequential CRT with gefitinib was promising . Survival for good-risk patients receiving concurrent CRT plus gefitinib was disappointing even for tumors with activating EGFR mutations BACKGROUND We conducted a feasibility study of induction chemotherapy followed by gefitinib and thoracic radiotherapy ( TRT ) for unresectable locally advanced adenocarcinoma of the lung . PATIENTS AND METHODS Patients received induction chemotherapy with cisplatin ( 80 mg/m(2 ) , days 1 and 22 ) and vinorelbine ( 25 mg/m(2 ) , days 1 , 8 , 22 , and 29 ) followed by gefitinib ( 250 mg daily , beginning on day 43 , for 1 year ) and TRT ( 60 Gy/30 fractions , days 57 - 98 ) . The primary end point was feasibility , which was defined as the proportion of patients who completed 60 Gy of TRT and received > 75 % of the planned dose of gefitinib without developing grade 2 or worse pneumonitis . RESULTS Of the 38 enrolled patients , 23 patients [ 60.5 % ; 80 % confidence interval ( CI ) 48.8 - 71.3 ] completed treatment without experiencing grade 2 or worse pneumonitis . During the chemoradiation phase , grade 3 - 4 alanine aminotransferase elevations were observed in 37.1 % of the patients . The overall response rate was 73.0 % . The median survival time was 28.5 months ( 95 % CI 22.5 - 38.2 ) , and the 2-year survival rate was 65.4 % . CONCLUSIONS Although the results did not meet our criterion for feasibility , the toxicity was acceptable . This treatment warrants further evaluation among patients with locally advanced non-small-cell lung cancer harboring epidermal growth factor receptor mutations |
959 | 31,595,976 | Other outcome measures on the Female Sexual Function Index and the Female Sexual Distress Scale showed no significant differences between the two groups . | BACKGROUND Women who carry a pathogenic mutation in either a BRCA1 DNA repair associated or BRCA2 DNA repair associated ( BRCA1 or BRCA2 ) gene have a high lifetime risk of developing breast and tubo-ovarian cancer .
To manage this risk women may choose to undergo risk-reducing surgery to remove breast tissue , ovaries , and fallopian tubes .
Surgery should increase survival , but can impact women 's lives adversely at the psychological and psychosexual levels .
Interventions to facilitate psychological adjustment and improve quality of life post risk-reducing surgery are needed .
OBJECTIVES To examine psychosocial interventions in female BRCA carriers who have undergone risk-reducing surgery and to evaluate the effectiveness of such interventions on psychological adjustment and quality of life . | We characterized BRCA1 and BRCA2 status ( mutation/methylation ) in a consecutive series of cases of ovarian carcinoma in order to identify differences in clinicopathological features , molecular characteristics , and outcome between the pelvic high- grade serous cancers with ( i ) germline or somatic mutations in BRCA1 or BRCA2 , ( ii ) methylation of BRCA1 , and ( iii ) normal BRCA1 or BRCA2 . In all , 131 women were identified prospect ively , who were undergoing surgical staging and agreed to germline testing for BRCA1 and BRCA2 mutations . Histopathology , germline and somatic BRCA1 or BRCA2 mutations , BRCA1 methylation , and BRCA1 and BRCA2 mRNA expression levels distinguished four subgroups . In all , 103 cases were high- grade serous carcinoma and of these 31 ( 30 % ) had germline or somatic BRCA1 or BRCA2 mutations ( 20 % BRCA1 and 10 % BRCA2 ) ( group 1 ) , 21 ( 20 % ) had methylation of BRCA1 ( group 2 ) , and in 51 ( 50 % ) there was no BRCA loss ( group 3 ) . Group 4 consisted of 28 cases of non-high- grade serous , none of which had BRCA loss . BRCA1 and BRCA2 mRNA expression levels correlated with design ated group ( P=0.0008 ) . Among high- grade serous carcinomas , there were no differences between groups 1–3 with respect to stage , ascites , CA125 level , platinum sensitivity , cytoreduction rate , neoadjuvant chemotherapy , or survival . Tumors with BRCA1 or BRCA2 mutations had increased immune infiltrates ( CD20 and TIA-1 ) compared with high- grade serous without mutations ( P=0.034 , 0.027 ) . TP53 expression differed between groups ( P<0.0001 ) , with abnormal TP53 expression in 49/50 tumors from groups 1 and 2 . Wild-type TP53 expression was associated with worse outcome in high- grade serous ( P<0.001 ) . BRCA loss ( mutation/methylation ) is a common event in the pelvic high- grade serous ( 50 % ) . TP53 abnormalities and increased immune cell infiltrates are significantly more common in high- grade serous with germline and somatic mutations in BRCA1 or BRCA2 , compared with tumors lacking BRCA abnormalities This multi-centre UK study assesses the impact of predictive testing for breast and ovarian cancer predisposition genes ( BRCA1/2 ) in the clinical context . In the year following predictive testing , 261 adults ( 59 male ) from nine UK genetics centres participated ; 91 gene mutation carriers and 170 noncarriers . Self-report question naires were completed at baseline ( pre-genetic testing ) and 1 , 4 and 12 months following the genetic test result . Men were assessed for general mental health ( by general health question naire ( GHQ ) ) and women for general mental health , cancer-related worry , intrusive and avoidant thoughts , perception of risk and risk management behaviour . Main comparisons were between female carriers and noncarriers on all measures and men and women for general mental health . Female noncarriers benefited psychologically , with significant reductions in cancer-related worry following testing ( P<0.001 ) . However , younger female carriers ( < 50 years ) showed a rise in cancer-related worry 1 month post-testing ( P<0.05 ) . This returned to pre-testing baseline levels 12 months later , but worry remained significantly higher than noncarriers throughout ( P<0.01 ) . There were no significant differences in GHQ scores between males and females ( both carriers and noncarriers ) at any time point . Female carriers engaged in significantly more risk management strategies than noncarriers in the year following testing ( e.g. mammograms ; 92 % carriers vs 30 % noncarriers ) . In the 12 months post-testing , 28 % carriers had bilateral risk-reducing mastectomy and 31 % oophorectomy . Oophorectomy was confined to older ( mean 41 yrs ) women who already had children . However , worry about cancer was not assuaged by surgery following genetic testing , and this requires further investigation . In all , 20 % of female carriers reported insurance problems . The data show persistent worry in younger female gene carriers and confirm changes in risk management consistent with carrier status . Men were not adversely affected by genetic testing in terms of their general mental health This prospect i ve multicentre study assesses long-term impact of genetic testing for breast/ovarian cancer predisposition in a clinical cohort . Areas evaluated include risk management , distress and insurance problems 3 years post-testing . Participants are adults unaffected with cancer from families with a known BRCA1/2 mutation . One hundred and ninety-three out of 285 ( 70 % response ) participants at nine UK clinical genetics centres completed assessment s at 3 years : 80 % female ; 37 % carriers of a BRCA1/2 mutation . In the 3 years , post-genetic testing carriers reported more risk management activities than non-carriers . Fifty-five per cent of female carriers opted for risk reducing surgery ; 43 % oophorectomy ; and 34 % mastectomy . Eighty-nine per cent had mammograms compared with 47 % non-carriers . Thirty-six per cent non-carriers ⩾50 years did not have a mammogram post-test . Twenty-two per cent male carriers had colorectal and 44 % prostate screening compared with 5 and 19 % non-carriers respectively . Seven per cent carriers and 1 % non-carriers developed cancer . Distress levels did not differ in carriers and non-carriers at 3-year follow-up . Forty per cent of female carriers reported difficulties with life and /or health insurance . Given the return to pre-test levels of concern among female non-carriers at 3 years and a substantial minority not engaging in recommended screening , there appears to be a need to help some women underst and the meaning of their genetic status Objective Opportunistic bilateral salpingectomy is now promoted for women at the time of hysterectomy for a benign disease , consequent to the fimbrial end of the fallopian tube emerging as the primary site for carcinogenesis in high- grade serous carcinomas . In high-risk women with an identified germ line mutation , bilateral salpingo-oophorectomy offers the greatest risk reduction for ovarian cancer . Currently , no prospect i ve evidence exists with respect to the effectiveness of opportunistic salpingectomy alone in preventing ovarian cancer . Although it is thought that there is no direct connection between the ovary and its adjacent fallopian tube , we often find remnants of the fimbria adherent to the ovary at the time of surgery . If this tubo-ovarian interface is not separate , then practice s such as salpingectomy and radical fimbriectomy may be incomplete , and the effectiveness of this technique as a prophylactic strategy may need reconsideration . We aim ed to establish whether there might exist a direct attachment of the fimbria to the ovary by examining this interface in surgically removed specimens . Methods The tubes and ovaries of 20 women undergoing risk-reducing salpingo-oophorectomy were examined using the Sectioning and Extensively Examining the Fimbriated End of the Tubes protocol and p53 immunohistochemistry for lesions suspicious of serous intraepithelial tubal carcinoma . Results Three specimens showed fimbria adherent to the ovary at the histopathological analysis . One p53 signature was identified , but there were no occult cancers or serous intraepithelial tubal carcinomas . Conclusions Although only a small study , the findings show that microscopic fimbriae are adherent to the ovary . This relationship challenges the recommendation for bilateral salpingectomy alone for risk-reducing surgery because the primary site of carcinogenesis may be left on the ovary to later develop into a high- grade serous carcinoma . A larger study is needed to assess our findings related to the tubo-ovarian interface and its implication s for long-term ovarian cancer development . Until then , caution on using this technique alone in the high-risk patient should be adopted OBJECTIVES Considerable morbidity persists among survivors of breast cancer ( BC ) including high levels of psychological stress , anxiety , depression , fear of recurrence , and physical symptoms including pain , fatigue , and sleep disturbances , and impaired quality of life . Effective interventions are needed during this difficult transitional period . METHODS We conducted a r and omized controlled trial of 84 female BC survivors ( Stages 0-III ) recruited from the H. Lee Moffitt Cancer and Research Institute . All subjects were within 18 months of treatment completion with surgery and adjuvant radiation and /or chemotherapy . Subjects were r and omly assigned to a 6-week Mindfulness-Based Stress Reduction ( MBSR ) program design ed to self-regulate arousal to stressful circumstances or symptoms ( n=41 ) or to usual care ( n=43 ) . Outcome measures compared at 6 weeks by r and om assignment included vali date d measures of psychological status ( depression , anxiety , perceived stress , fear of recurrence , optimism , social support ) and psychological and physical subscales of quality of life ( SF-36 ) . RESULTS Compared with usual care , subjects assigned to MBSR(BC ) had significantly lower ( two-sided p<0.05 ) adjusted mean levels of depression ( 6.3 vs 9.6 ) , anxiety ( 28.3 vs 33.0 ) , and fear of recurrence ( 9.3 vs 11.6 ) at 6 weeks , along with higher energy ( 53.5 vs 49.2 ) , physical functioning ( 50.1 vs 47.0 ) , and physical role functioning ( 49.1 vs 42.8 ) . In stratified analyses , subjects more compliant with MBSR tended to experience greater improvements in measures of energy and physical functioning . CONCLUSIONS Among BC survivors within 18 months of treatment completion , a 6-week MBSR(BC ) program result ed in significant improvements in psychological status and quality of life compared with usual care BACKGROUND Reliable estimates of cancer risk are critical for guiding management of BRCA1 and BRCA2 mutation carriers . The aims of this study were to derive penetrance estimates for breast cancer , ovarian cancer , and contralateral breast cancer in a prospect i ve series of mutation carriers and to assess how these risks are modified by common breast cancer susceptibility alleles . METHODS Prospect i ve cancer risks were estimated using a cohort of 978 BRCA1 and 909 BRCA2 carriers from the United Kingdom . Nine hundred eighty-eight women had no breast or ovarian cancer diagnosis at baseline , 1509 women were unaffected by ovarian cancer , and 651 had been diagnosed with unilateral breast cancer . Cumulative risks were obtained using Kaplan-Meier estimates . Associations between cancer risk and covariables of interest were evaluated using Cox regression . All statistical tests were two-sided . RESULTS The average cumulative risks by age 70 years for BRCA1 carriers were estimated to be 60 % ( 95 % confidence interval [ CI ] = 44 % to 75 % ) for breast cancer , 59 % ( 95 % CI = 43 % to 76 % ) for ovarian cancer , and 83 % ( 95 % CI = 69 % to 94 % ) for contralateral breast cancer . For BRCA2 carriers , the corresponding risks were 55 % ( 95 % CI = 41 % to 70 % ) for breast cancer , 16.5 % ( 95 % CI = 7.5 % to 34 % ) for ovarian cancer , and 62 % ( 95 % CI = 44 % to 79.5 % ) for contralateral breast cancer . BRCA2 carriers in the highest tertile of risk , defined by the joint genotype distribution of seven single nucleotide polymorphisms associated with breast cancer risk , were at statistically significantly higher risk of developing breast cancer than those in the lowest tertile ( hazard ratio = 4.1 , 95 % CI = 1.2 to 14.5 ; P = .02 ) . CONCLUSIONS Prospect i ve risk estimates confirm that BRCA1 and BRCA2 carriers are at high risk of developing breast , ovarian , and contralateral breast cancer . Our results confirm findings from retrospective studies that common breast cancer susceptibility alleles in combination are predictive of breast cancer risk for BRCA2 carriers Purpose : To investigate the medical and psychosocial factors determining the time to prophylactic surgery of unaffected women carriers of a deleterious BRCA1/2 mutation . Methods : Prospect i ve study on a French national cohort of unaffected BRCA1/2 carriers ( N = 244 ) ; multivariate Cox proportional hazard modeling . Results : Median follow-up time was 2.33 years ( range , 0.04–6.84 years ) . Time to surgery was shorter when the psychological impact of BRCA1/2 result disclosure was stated to be higher ( P ≤ 0.01 ) . Those who intended to opt for prophylactic surgery before being tested did so faster and more frequently after test disclosure than those who were undecided/opposed . The older the women were , the faster their uptake of risk-reducing salpingo-oophorectomy ( adjusted hazard ratio > 2.95 ; P < 0.001 ) was ; the uptake of those with at least two children was also faster ( adjusted hazard ratio = 2.51 ; [ 1.38–4.55 ] ) . Those who opted most quickly for risk-reducing mastectomy more frequently had a younger child at the time of testing ( adjusted hazard ratio = 4.63 [ 1.56–13.74 ] ) . Time to surgery was shorter when there was a first-degree relative with ovarian/breast cancer ( P ≤ 0.01 ) . Conclusion : Time to prophylactic surgery depends on the stated psychological impact of disclosure and on women 's cognitive anticipation of surgery after adjusting on sociodemographic characteristics Non-metastatic breast cancer patients often experience psychological distress which may influence disease progression and survival . Cognitive-behavioral stress management ( CBSM ) improves psychological adaptation and lowers distress during breast cancer treatment and long-term follow-ups . We examined whether breast cancer patients r and omized to CBSM had improved survival and recurrence 8–15 years post-enrollment . From 1998 to 2005 , women ( N = 240 ) 2–10 weeks post-surgery for non-metastatic Stage 0–IIIb breast cancer were r and omized to a 10-week , group-based CBSM intervention ( n = 120 ) or a 1-day psychoeducational seminar control ( n = 120 ) . In 2013 , 8–15 years post- study enrollment ( 11-year median ) , recurrence and survival data were collected . Cox Proportional Hazards Models and Weibull Accelerated Failure Time tests were used to assess group differences in all-cause mortality , breast cancer-specific mortality , and disease-free interval , controlling for biomedical confounders . Relative to the control , the CBSM group was found to have a reduced risk of all-cause mortality ( HR = 0.21 ; 95 % CI [ 0.05 , 0.93 ] ; p = .040 ) . Restricting analyses to women with invasive disease revealed significant effects of CBSM on breast cancer-related mortality ( p = .006 ) and disease-free interval ( p = .011 ) . CBSM intervention delivered post-surgery may provide long-term clinical benefit for non-metastatic breast cancer patients in addition to previously established psychological benefits . Results should be interpreted with caution ; however , the findings contribute to the limited evidence regarding physical benefits of psychosocial intervention post-surgery for non-metastatic breast cancer . Additional research is necessary to confirm these results and investigate potential explanatory mechanisms , including physiological pathways , health behaviors , and treatment adherence changes 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 The grading of recommendation , assessment , development and evaluation ( GRADE ) approach is widely implemented in health technology assessment and guideline development organisations throughout the world . GRADE provides a transparent approach to reaching judgements about the quality of evidence on the effects of a health care intervention , but is complex and therefore challenging to apply in a consistent manner . Methods We developed a checklist to guide the research er to extract the data required to make a GRADE assessment . We applied the checklist to 29 meta-analyses of r and omised controlled trials on the effectiveness of health care interventions . Two review ers used the checklist for each paper and used these data to rate the quality of evidence for a particular outcome . Results For most ( 70 % ) checklist items , there was good agreement between review ers . The main problems were for items relating to indirectness where considerable judgement is required . Conclusions There was consistent agreement between review ers on most items in the checklist . The use of this checklist may be an aid to improving the consistency and reproducibility of GRADE assessment s , particularly for inexperienced users or in rapid review s without the re sources to conduct assessment s by two research ers independently The outcome of bilateral prophylactic mastectomy with breast reconstruction ( BPM-IBR ) in healthy BRCA1/2 mutation carriers can be potentially burdensome for body image and the intimate relationship . Therefore , in the current analysis the impact on body image , sexual and partner relationship satisfaction was prospect ively investigated in women opting for BPM-IBR as well as cancer distress and general quality of life . Healthy women undergoing BPM-IBR completed question naires preoperatively ( T0 , n = 48 ) , at 6 months ( T1 , n = 44 ) and after finishing breast reconstruction ( median 21 months , range 12–35 ) ( T2 , n = 36 ) . With multi-level regression analyses the course of outcome variables was investigated and a statistically significant change in body image and /or sexual and partner relationship satisfaction was predicted by baseline covariates . Body image significantly decreased at T1 . At T2 sexual relationship satisfaction and body image tended to be lower compared to baseline . The overall partner relationship satisfaction did not significantly change . At T2 , 37 % of the women reported that their breasts felt unpleasantly , 29 % was not satisfied with their breast appearance and 21 % felt embarrassed for their naked body . Most body image issues remained unchanged in 30 % of the women . A negative body image was predicted by high preoperative cancer distress . BPM-IBR was associated with adverse impact on body image in a substantial subgroup , but satisfaction with the overall sexual and partner relationship did not significantly change in time . The psychosocial impact of BPM-IBR in unaffected women should not be underestimated . Psychological support should ideally be integrated both before and after BPM-IBR OBJECTIVE The primary objective of the study was to prospect ively assess quality of life ( QOL ) among women at increased risk of ovarian cancer who are undergoing risk-reducing salpingo-oophorectomy ( RRSO ) or serial screening . METHODS Women at increased risk of ovarian cancer who were undergoing RRSO were recruited into the study . At-risk women undergoing serial screening for early detection of ovarian cancer served as a comparison group . Participants completed measures of QOL , sexual functioning , body image , depressive symptoms , and a symptom checklist at baseline ( prior to surgery for women obtaining RRSO ) , and then at 1-month , 6-months , and 12-months post baseline . RESULTS Women who underwent surgery reported poorer physical functioning , more physical role limitations , greater pain , less vitality , poorer social functioning , and greater discomfort and less satisfaction with sexual activities at 1-month assessment compared to baseline . In contrast , women undergoing screening experienced no significant decrements in QOL or sexual functioning at 1-month assessment . Most QOL deficits observed in the surgical group were no longer apparent by 6-month assessment . Women in the surgery group were more likely to report hot flashes and vaginal dryness , but over time , symptoms of vaginal discomfort decreased to a greater extent in women who had RRSO compared to women undergoing screening . No differences in body image or depressive symptoms were observed between the two groups at any time point . CONCLUSIONS Short-term deficits in physical functioning and other specific domains of QOL were observed following RRSO , but most women recovered baseline functioning by 6- and 12-month assessment s. Issues regarding the potential impact of surgery on short-term sexual functioning should be considered and weighed carefully , particularly among younger women Recent consensus-based characterizations of female sexual dysfunction have emphasized personal distress as an essential component of their definition . To assist research ers and clinicians , we developed a new scale , the Female Sexual Distress Scale , to measure sexually related personal distress in women . In this article , we describe the initial stages in the development and validation of this instrument . Three studies involving a total of approximately 500 women were performed to evaluate the reliability and validity of the scale in different sample s of sexually functional and dysfunctional women . Results indicated a unidimensional factor structure in both the original 20-item version and in a " polished " 12-item version . We observed a high degree of internal consistency and test-retest reliability in both versions across all three studies . Additionally , the scale showed a high degree of discriminative ability to distinguish between sexually dysfunctional and functional women in each of the studies . One study also showed a strong sensitivity to treatment response . Finally , we observed moderate positive correlations with other conceptually related nonsexual measures of distress , supporting the construct validity of the scale . Overall , these findings provide solid support for the FSDS as a valid and reliable measure for assessing sexually related personal distress in women OBJECTIVES To develop the 1996 MENQOL question naire further with advice regarding summary score computation , missing- data management , readability , recall period and assessment of the vasomotor domain reliability and construct validity . To develop a modified version , the MENQOL-Intervention question naire , for use where certain treatment side effects could negatively impact the quality of life . METHODS MENQOL-Intervention modifications involved the addition of three items to the physical domain . For both question naires , psychometric property assessment was embedded in two r and omized controlled trials of menopause interventions . Test-retest reliability and Cronbach 's alpha were computed for all domains as was construct validity of the vasomotor domain for both question naires . RESULTS The vasomotor intraclass correlation coefficient was 0.73 for the MENQOL-Intervention over 1 week and 0.78 for the MENQOL over 1 month . The altered physical domain of the MENQOL-Intervention question naire continued to show strong test-retest reliability and Cronbach 's alpha consistent with the MENQOL . The MENQOL-Intervention demonstrated excellent face validity with high construct validity for the vasomotor domain of 0.78 - 0.80 . For both instruments , comparisons of the vasomotor domains to hot flash scores , although statistically significant , were only moderate at 0.56 and 0.49 . CONCLUSIONS Both the MENQOL and the MENQOL-Intervention question naires show strong psychometric properties . We recommend using the MENQOL-Intervention question naire where intervention side effects might negatively impact a woman 's quality of life . For both question naires , a summary score can be calculated INTRODUCTION Women at high risk for ovarian cancer due to BRCA1 or BRCA2 mutation or family history are recommended to undergo risk-reducing salpingo-oophorectomy ( RRSO ) after age 35 or completion of childbearing . This potentially life-saving surgery leads to premature menopause , frequently result ing in distressing and unaddressed sexual dysfunction . AIM To pilot a novel sexual health intervention for women with BRCA1/2 mutations who previously underwent RRSO a using a single-arm trial . Feasibility and primary outcomes including sexual dysfunction and psychological distress were assessed . METHODS This single-arm trial included a one-time , half-day educational session comprised of targeted sexual health education , body awareness and relaxation training , and mindfulness-based cognitive therapy strategies , followed by two sessions of tailored telephone counseling . Assessment s were completed at baseline and 2 months postintervention . MAIN OUTCOME MEASURE Study end points include feasibility and effectiveness as reported by the participant . RESULTS Thirty-seven women completed baseline and postintervention assessment s. At baseline , participants had a mean age of 44.4 ( st and ard deviation [ SD ] = 3.9 ) years and mean duration of 3.8 ( SD = 2.7 ) years since RRSO . Overall sexual functioning ( P = 0.018 ) , as well as desire ( P = 0.003 ) , arousal ( P = 0.003 ) , satisfaction ( P = 0.028 ) , and pain ( P = 0.018 ) , improved significantly . There were significant reductions in somatization ( P = 0.029 ) and anxiety scores ( P < 0.001 ) , and , overall , for the Global Severity Index ( P < 0.001 ) of the Brief Symptom Inventory . Sexual self-efficacy and sexual knowledge also improved significantly from baseline to postintervention ( both P < 0.001 ) . Women were highly satisfied with the intervention content and reported utilizing new skills to manage sexual dysfunction . CONCLUSIONS This intervention integrates elements of cognitive behavioral therapy with sexual health education to address a much-neglected problem after RRSO . Results from this promising single-arm study provide preliminary data to move toward conducting a r and omized , controlled trial Background Bilateral prophylactic mastectomy in women with increased breast cancer risk dramatically reduces breast cancer occurrence but little is known about psychosocial outcomes . Methods To examine long-term quality of life after bilateral prophylactic mastectomy , we mailed surveys to 195 women who had the procedure from 1979 to 1999 and to a r and om sample of 117 women at increased breast cancer risk who did not have the procedure . Measures were modeled on or drawn directly from vali date d instruments design ed to assess quality of life , body image , sexuality , breast cancer concerns , depression , health perception , and demographic characteristics . We used logistic regression to examine associations between quality of life and other domains . Results The response rate was 58 % , with 106 women with and 62 women without prophylactic mastectomy returning complete surveys . Among women who underwent bilateral prophylactic mastectomy , 84 % were satisfied with their decision to have the procedure ; 61 % reported high contentment with quality of life compared with an identical 61 % of women who did not have the procedure ( P = 1.0 ) . Among all subjects , diminished contentment with quality of life was not associated with bilateral prophylactic mastectomy but with dissatisfaction with sex life ( adjusted ratio [ OR ] = 2.5 , 95 % confidence interval [ CI ] = 1.0–6.2 ) , possible depression ( CES-D > 16 , OR = 4.9 , CI = 2.0–11.8 ) , and poor or fair general health perception ( OR = 8.3 , 95 % CI = 2.4–29.0 ) . Conclusions The majority of women reported satisfaction with bilateral prophylactic mastectomy and experienced psychosocial outcomes similar to women with similarly elevated breast cancer risk who did not undergo prophylactic mastectomy . Bilateral prophylactic mastectomy appears to neither positively nor negatively impact long-term psychosocial outcomes Background : Whether oophorectomy reduces breast cancer risk among BRCA mutation carriers is a matter of debate . We undertook a prospect i ve analysis of bilateral oophorectomy and breast cancer risk in BRCA mutation carriers . Methods : Subjects had no history of cancer , had both breasts intact , and had information on oophorectomy status ( n = 3722 ) . Women were followed until breast cancer diagnosis , prophylactic bilateral mastectomy , or death . A Cox regression model was used to estimate the hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) of breast cancer associated with oophorectomy ( coded as a time-dependent variable ) . All statistical tests were two-sided . Results : Over a mean follow-up of 5.6 years , 350 new breast cancers were diagnosed . Among women with a BRCA1 or BRCA2 mutation , oophorectomy was not associated with breast cancer risk compared with women who did not undergo an oophorectomy . The age-adjusted hazard ratio associated with oophorectomy was 0.96 ( 95 % CI = 0.73 to 1.26 , P = .76 ) for BRCA1 and was 0.65 ( 95 % CI = 0.37 to 1.16 , P = .14 ) for BRCA2 mutation carriers . In stratified analyses , the effect of oophorectomy was statistically significant for breast cancer in BRCA2 mutation carriers diagnosed prior to age 50 years ( age-adjusted HR = 0.18 , 95 % CI = 0.05 to 0.63 , P = .007 ) . Oophorectomy was not associated with risk of breast cancer prior to age 50 years among BRCA1 mutation carriers ( age-adjusted HR = 0.79 , 95 % CI = 0.55 to 1.13 , P = .51 ) . Conclusions : Findings from this large prospect i ve study support a role of oophorectomy for the prevention of premenopausal breast cancer in BRCA2 , but not BRCA1 mutation carriers . These findings warrant further evaluation PURPOSE To prospect ively evaluate body image , sexuality , emotional reactions ( anxiety , depression ) , and quality of life in a sample of women having increased risk for breast cancer before and 6 months and 1 year after bilateral prophylactic mastectomy ( BPM ) , and to compare preoperative expectations of the operation with postoperative reactions concerning the impact on six areas of the women 's lives . PATIENTS AND METHODS A total of 90 of 98 consecutive women who underwent BPM during October 1997 to December 2005 were included . Data were collected by self-administered question naires ( eg , Hospital Anxiety and Depression scale , Swedish Short Term-36 Health Survey , Body Image Scale , Sexual Activity Question naire ) before the operation ( n = 81 ) , and 6 ( n = 71 ) and 12 months ( n = 65 ) after BPM . RESULTS Anxiety decreased over time ( P = .0004 ) . No corresponding difference was found for depression . No differences in health-related quality of life over time were found , with one exception . A substantial proportion of the women reported problems with body image 1 year after BPM ( eg , self consciousness , 48 % ; feeling less sexually attractive , 48 % ; and dissatisfaction with the scars , 44 % ) . Sexual pleasure was rated lower 1-year post-BPM as compared with before operation ( P = .005 ) , but no differences over time in habit , discomfort , or activity were found . CONCLUSION No negative effects on anxiety , depression , and quality of life were found . Anxiety and social activities improved . Negative impact on sexuality and body image was reported The dem and for risk-reducing mastectomy ( RRM ) to avoid breast cancer has increased over the last several years , and knowledge of the outcome after this prophylactic surgical procedure is important . The primary aim of this study was to prospect ively compare breast sensibility before and after RRM in a consecutive series of women . The study also investigated whether the nipples were less numb if the nipple areola complexes ( NACs ) were spared compared with regrafted nipple tips . Forty-six women who selected bilateral RRM with immediate reconstruction using implants at the Karolinska University Hospital , Solna , Stockholm , Sweden , were included in the study . The median patient age at the time of surgery was 39 years ( range 26 - 58 ) . All patients were evaluated preoperatively and at least 2 years postoperatively ( median 29 months ) . Tactile , thermal and nociceptive cutaneous sensibilities were studied with quantitative techniques . The patients at the postoperative evaluation completed a question naire about subjective feelings in both breasts . The results showed that breast sensibility is significantly impaired after RRM . Additionally , the ability to experience sexual sensations in the breast is often lost . An NAC-sparing surgery did not result in better nipple sensibility PURPOSE The association between radiotherapy for gynecological carcinoma and sexual dysfunction is well established . Regular vaginal dilation is widely recommended to these women as a way for them to maintain vaginal health and good sexual functioning . However , the compliance rate with this recommendation is low . The purpose of this study was to test the effectiveness of a group psychoeducational program based on the " information-motivation-behavioral skills " model of behavior change in increasing the rate of compliance . METHODS AND MATERIAL S Thirty-two women with Stage I or II cervical or endometrial carcinoma who were being treated with radiotherapy were r and omized and received either the experimental group program or the control intervention that consisted of written information and brief counseling . Outcome measures included global sexual health , knowledge about sexuality and cancer , fears about sexuality after cancer , and vaginal dilation compliance . RESULTS Younger women attending the experimental program ( 44.4 % ) were significantly more likely to follow recommendations for vaginal dilation than those who received the control intervention ( 5.6 % ) . Women , regardless of age , who received the experimental intervention reported less fear about sex after cancer treatment . The older women who received the experimental intervention gained more sexual knowledge . There was no evidence that the experimental intervention improved global sexual health . CONCLUSIONS This is the first controlled study to provide evidence of an intervention 's effectiveness 1 . in increasing women 's vaginal dilation following radiotherapy for gynecological carcinoma and 2 . in reducing their fears about sex after cancer . Most women , particularly younger women , are unlikely to follow the recommendation to dilate unless they are given assistance in overcoming their fears and taught behavioral skills Background Although bilateral prophylactic mastectomy ( BPM ) can reduce the risk of breast cancer , the decision to proceed surgically can have significant consequences and requires careful deliberation . To facilitate decision making for women at high risk for breast carcinoma , the risks and benefits of BPM should be well-eluci date d. We sought to determine the effects of BPM and immediate reconstruction on health-related quality -of-life outcomes among a multisite cohort of women at high risk for breast carcinoma . Methods Patient-reported outcome data were prospect ively collected as part of the Mastectomy Reconstruction Outcomes Consortium Study , and data on a subgroup of 204 high-risk women who elected to have BPM and immediate reconstruction were evaluated . Baseline scores were compared with scores at 1 or 2 years after reconstruction . Results Satisfaction with breasts and psychosocial well-being were significantly higher at both 1 and 2 years ( p < 0.01 ) ; however , anxiety was significantly lower at 1 or 2 years ( p < 0.01 ) and physical well-being of the chest and upper body was significantly worse at 1 year ( p < 0.01 ) . Conclusion Our results highlight the impact of BPM and immediate reconstruction on health-related quality -of-life outcomes in this setting . BPM and reconstruction can result in significant , positive , lasting changes in a woman ’s satisfaction with her breasts , as well as her psychosocial well-being . Furthermore , presurgery anxiety was significantly reduced by 1 year post-reconstruction and remained reduced at 2 years . With this knowledge , women at high risk for breast carcinoma , and their providers , will be better equipped to make the best individualized treatment decisions IMPORTANCE BRCA testing is recommended for young women diagnosed as having breast cancer , but little is known about decisions surrounding testing and how results may influence treatment decisions in young patients . OBJECTIVES To describe the use of BRCA testing and to evaluate how concerns about genetic risk and use of genetic information affect subsequent treatment decisions in young women with breast cancer . DESIGN , SETTING , AND PARTICIPANTS Cross-sectional analysis of data collected following the opening of the study to accrual from October 10 , 2006 , through December 31 , 2014 , as part of the Helping Ourselves , Helping Others : Young Women 's Breast Cancer Study , an ongoing prospect i ve cohort study . Study participants included 897 women aged 40 years and younger at breast cancer diagnosis from 11 academic and community medical centers . MAIN OUTCOMES AND MEASURES Frequency and trends in the use of BRCA testing and how genetic information is used to make treatment decisions among women who test positive vs negative for a BRCA mutation . RESULTS A total of 780 ( 87.0 % ) of 897 women reported BRCA testing by 1 year after breast cancer diagnosis ( mean age at diagnosis , 35.3 vs 36.9 years for untested women ; P < .001 ) , with the frequency of testing increasing among women diagnosed from August 1 , 2006 , through December 31 , 2013 . Of 39 women who were diagnosed as having breast cancer in 2006 , 30 ( 76.9 % ) reported testing . In 2007 , a slightly lower percentage of women ( 87 of 124 [ 70.2 % ] ) reported testing ; however , the proportion tested increased each subsequent year , with 141 ( 96.6 % ) of 146 and 123 ( 95.3 % ) of 129 women diagnosed as having breast cancer in 2012 and 2013 , respectively , reporting BRCA testing ( P < .001 ) . Among untested women , 37 ( 31.6 % ) of 117 did not report discussion of the possibility that they might have a mutation with a physician and /or genetic counselor , and 43 ( 36.8 % ) of 117 were thinking of testing in the future . A total of 248 ( 29.8 % ) of 831 women said that knowledge or concern about genetic risk influenced treatment decisions ; among these women , 76 ( 86.4 % ) of 88 mutation carriers and 82 ( 51.2 % ) of 160 noncarriers chose bilateral mastectomy ( P < .001 ) . Fewer women reported that systemic treatment decisions were influenced by genetic risk concern . CONCLUSIONS AND RELEVANCE Rates of BRCA1 and BRCA2 mutation testing are increasing in young women with breast cancer . Given that knowledge and concern about genetic risk influence surgical decisions and may affect systemic therapy trial eligibility , all young women with breast cancer should be counseled and offered genetic testing , consistent with the National Comprehensive Cancer Network guidelines Background Risk-reducing salpingo-oophorectomy ( RRSO ) around the age of 40 is currently recommended to BRCA1/2 mutation carriers . This procedure decreases the elevated ovarian cancer risk by 80–96 % but it initiates premature menopause as well . The latter is associated with short-term and long-term morbidity , potentially affecting quality of life ( QoL ) . Based on recent insights into the Fallopian tube as possible site of origin of serous ovarian carcinomas , an alternative preventive strategy has been put forward : early risk-reducing salpingectomy ( RRS ) and delayed oophorectomy ( RRO ) . However , efficacy and safety of this alternative strategy have to be investigated . Methods A multicentre non-r and omised trial in 11 Dutch centres for hereditary cancer will be conducted . Eligible patients are premenopausal BRCA1/2 mutation carriers after completing childbearing without ( a history of ) ovarian carcinoma . Participants choose between st and ard RRSO at age 35–40 ( BRCA1 ) or 40–45 ( BRCA2 ) and the alternative strategy ( RRS upon completion of childbearing and RRO at age 40–45 ( BRCA1 ) or 45–50 ( BRCA2 ) ) . Women who opt for RRS but do not want to postpone RRO beyond the currently recommended age are included as well . Primary outcome measure is menopause-related QoL. Secondary outcome measures are ovarian/breast cancer incidence , surgery-related morbidity , histopathology , cardiovascular risk factors and diseases , and cost-effectiveness . Mixed model data analysis will be performed . Discussion The exact role of the Fallopian tube in ovarian carcinogenesis is still unclear . It is not expected that further fundamental research will eluci date this role in the near future . Therefore , this clinical trial is essential to investigate RRS with delayed RRO as alternative risk-reducing strategy in order to improve QoL.Trial registration Clinical Trials.gov ( NCT02321228 |
960 | 28,068,454 | We did not find any evidence for or against the effectiveness of non-surgical interventions for the treatment of an internal hordeolum . | BACKGROUND A hordeolum is a common , painful inflammation of the eyelid margin that is usually caused by a bacterial infection .
The infection affects oil gl and s of the eyelid and can be either internal or external .
In many cases , the lesion drains spontaneously and resolves without treatment ; however , the inflammation can spread to other ocular gl and s or tissues , and recurrences are common .
If unresolved , an acute internal hordeolum can become chronic , or can develop into a chalazion .
External hordeola , also known as styes , were not included in the scope of this review .
OBJECTIVES The objective of this review was to investigate the effectiveness , and when possible , the safety , of non-surgical treatments for acute internal hordeola compared with observation or placebo . | Patients with chalazia were r and omly allocated to treatment by intralesional triamcinolone injection or incision and curettage . Incision and curettage result ed in a significantly higher rate of resolution by two weeks after treatment OBJECTIVE The research ers sought to assess whether the widely used 1994 Cochrane Highly Sensitive Search Strategy ( HSSS ) for r and omized controlled trials ( RCTs ) in MEDLINE could be improved in terms of sensitivity , precision , or parsimony . METHODS A gold st and ard of 1,347 RCT records and a comparison group of 2,400 non-trials were r and omly selected from MEDLINE . Terms occurring in at least 1 % of RCT records were identified . Fifty percent of the RCT and comparison group records were r and omly selected , and the ability of the terms to discriminate RCTs from non-trial records was determined using logistic regression . The best performing combinations of terms were tested on the remaining records and in MEDLINE . RESULTS The best discriminating term was " Clinical Trial " ( Publication Type ) . In years where the Cochrane assessment of MEDLINE records had taken place , the strategies identified few additional unindexed records of trials . In years where Cochrane assessment has yet to take place , " R and omized Controlled Trial " ( Publication Type ) proved highly sensitive and precise . Adding six more search terms identified further , unindexed trials at reasonable levels of precision and with sensitivity almost equal to the Cochrane HSSS . CONCLUSIONS Most reports of RCTs in MEDLINE can now be identified easily using " R and omized Controlled Trial " ( Publication Type ) . More sensitive search es can be achieved by a brief strategy , the Centre for Review s and Dissemination/Cochrane Highly Sensitive Search Strategy ( 2005 revision ) We evaluated the safety and efficacy of tobramycin and gentamicin sulfate ophthalmic solutions in the treatment of patients with bacterial infections of the conjunctivas . In this double-masked study involving 66 patients , the two aminoglycosides were found to be equally safe and effective , although the in vitro data suggested that tobramycin may be more efficacious against Pseudomonas infections . Staphylococcus aureus and S. epidermidis were the most frequent isolates from the infected eyes ( 59.8 % and 20.6 % , respectively ) The presented pilot study compared the effectiveness of combined antibiotic ophthalmic solution ( neomycin sulfate , polymyxin B sulfate and gramicidin ) with a placebo ( artificial tear ) in the treatment of hordeolum after incision and curettage ( I&C ) . A r and omized , placebo-controlled trial with patients and investigators blinded from the start started from June 2002 to May 2003 . Subjects were patients with untreated hordeolum who subsequently underwent I&C at the Ophthalmology Department . The patients were r and omized into 2 groups : group A for combined antibiotic ophthalmic solution , and group B for artificial tear containing the antibiotic solution base . Pain score , mass size and duration of cure were recorded before and on the 3rd and 7th day after treatment . The study included 14 patients in each group . Two subjects in group A and three subjects in group B dropped out . There were no statistically significant differences of all outcomes in both groups , even with the intention-to-treat analysis . The conclusion is combined antibiotic ophthalmic solution is not more effective than placebo in the treatment of hordeolum after Background Loteprednol etabonate 0.5 % and tobramycin 0.3 % ophthalmic suspension ( LE/T ) is indicated for steroid-responsive inflammatory ocular conditions where superficial bacterial ocular infection or a risk of bacterial ocular infection exists . LE/T was shown to be safe in healthy volunteers and patients aged 18 years and older with minimal effect on intraocular pressure ( IOP ) . Objective The aim of the study was to evaluate the safety of LE/T in pediatric subjects by examining data from two clinical studies . Methods Two r and omized , multicenter , double-masked , parallel-group ( one two-arm , the other four-arm ) studies were conducted in subjects aged 0–6 years ( N = 245 ) . One study assessed LE/T compared with vehicle in the management of lid inflammation ( n = 108 ) and the other compared LE/T with loteprednol etabonate ophthalmic suspension 0.5 % ( LE ) , tobramycin ophthalmic solution 0.3 % ( tobramycin ) , and vehicle in the treatment of blepharoconjunctivitis ( n = 137 ) . In the first study , subjects were r and omized to LE/T or vehicle administered four times daily ( qid ) for the first 7 days followed by twice daily ( bid ) for 7 days along with warm compresses bid for the entire 2 weeks . In the second study , subjects were r and omized to LE/T , LE , tobramycin , or vehicle administered qid for 14 days . Treatment-emergent ocular and non-ocular adverse events ( AEs ) and bilateral vision were assessed at all study visits in both studies . In addition , in the lid inflammation study , IOP was assessed at all visits . The primary safety endpoint in both studies was the incidence of treatment-emergent AEs . Results The incidence of LE/T treatment-emergent AEs was low . A total of four ocular AEs were reported for three LE/T-treated subjects in the first study ( conjunctivitis [ two events ] , meibomian gl and dysfunction , and corneal staining ) , and one ocular AE was reported for an LE/T-treated subject in the second study ( eye pain ) . A total of 13 non-ocular AEs were reported for eight LE/T-treated subjects in the two trials . The most prevalent non-ocular AEs were pyrexia ( three events ) and rash ( two events ) . There were no differences in the incidence of specific ocular and non-ocular AEs between the LE/T group and the comparator treatment group . In both studies , there were no clinical ly meaningful reductions in vision at follow-up visits . Mean IOP and IOP changes from baseline , assessed in the lid inflammation study , were not different between LE/T and vehicle treatment groups at any study visits . Conclusion The results of these two clinical trials demonstrate the short-term safety of treatment with topical LE/T in pediatric subjects ( 0–6 years of age ) with lid inflammation or blepharoconjunctivitis We tested an over-the-counter ophthalmic ointment , yellow mercuric oxide 1 % , for safety and efficacy in decreasing eyelid-margin bacterial-colony counts . Of 150 patients screened for high bacterial levels , 78 were r and omized in double-blind fashion to either yellow mercuric oxide bid ( 41 patients or 53 % ) or a placebo ( 37 patients or 47 % ) . Bacterial-colony counts were determined at outset and at days 4 and 7 of treatment . At the conclusion of treatment on day 7 , 87 % of patients in the mercuric oxide group were successful in decreasing bacterial counts , compared with 59 % of patients treated with placebo ( P = .01 ) . Side effects were no higher in the active group than in the placebo group . We have shown mercuric oxide 1 % to be safe and effective in reducing eyelid bacterial-colony counts in patients with hordeolum and blepharitis A trial was conducted to compare the efficacy of the treatment of chalazions by injection of triamcinolone acetonide with conventional incision and curettage . Of the 39 injected cases 77 % resolved completely , though 54 % of the injected cases required a second injection . Of the 30 surgically treated cases 90 % resolved , but 27 % required a second operation . Injection of chalazions with a steroid suspension is a convenient and reasonably effective alternative to the st and ard surgical management of this common condition |
961 | 18,174,500 | RESULTS Cognitive-behavioural therapy or group psychoeducation may be effective for relapse prevention in stable individuals .
Family therapy was no more or less effective than individual psychosocial therapy or crisis management .
There is no evidence that care management or integrated group therapy is effective in the prevention of relapse .
CONCLUSIONS Cognitive-behavioural therapy , group psychoeducation and possibly family therapy may be beneficial as adjuncts to pharmacological maintenance treatments | BACKGROUND Pharmacological interventions alone do not provide sufficient benefit for some individuals with bipolar disorder .
AIMS To determine the effectiveness of psychosocial interventions for the prevention of relapse in bipolar disorder . | BACKGROUND Efficacy trials suggest that structured psychological therapies may significantly reduce recurrence rates of major mood episodes in individuals with bipolar disorders . AIMS To compare the effectiveness of treatment as usual with an additional 22 sessions of cognitive-behavioural therapy ( CBT ) . METHOD We undertook a multicentre , pragmatic , r and omised controlled treatment trial ( n=253 ) . Patients were assessed every 8 weeks for 18 months . RESULTS More than half of the patients had a recurrence by 18 months , with no significant differences between groups ( hazard ratio=1.05 ; 95 % CI 0.74 - 1.50 ) . Post hoc analysis demonstrated a significant interaction ( P=0.04 ) such that adjunctive CBT was significantly more effective than treatment as usual in those with fewer than 12 previous episodes , but less effective in those with more episodes . CONCLUSIONS People with bipolar disorder and comparatively fewer previous mood episodes may benefit from CBT . However , such cases form the minority of those receiving mental healthcare BACKGROUND The efficacy and effectiveness of cognitive therapy ( CT ) is well established for unipolar disorders , but little is known about its utility in bipolar disorders . This study aim ed to explore the feasibility and efficacy of using CT as an adjunct to usual psychiatric treatment in this patient population . METHOD Subjects referred by general adult psychiatrists were assessed by and independent rater and then r and omly allocated to immediate CT ( N = 21 ) or 6-month waiting-list control , which was then followed by CT ( N = 21 ) . Observer and self-ratings of symptoms and functioning were undertaken immediately prior to CT , after a 6-month course of CT and a further 6-months later . Data on relapse and hospitalization rates in the 18 months before and after commencing CT were also collected . RESULTS At 6-month follow-up , subjects allocated to CT showed statistically significantly greater improvements in symptoms and functioning as measured on the Beck Depression Inventory , the Internal State Scale , and the Global Assessment of Functioning than those in the waiting-list control group . In the 29 patients who eventually received CT , relapse rates in the 1 8 months after commencing CT showed a 60 % reduction in comparison with the 18 months prior to commencing CT . Seventy per cent of subjects who commenced therapy viewed CT as highly acceptable . CONCLUSION Although the results of this study are encouraging , the use of CT in subjects with bipolar disorders is more complex than in unipolar disorders and requires a high level of therapist expertise . The therapy may prove to be particularly useful in the treatment of bipolar depression Recently hospitalized bipolar , manic patients ( N = 53 ) were r and omly assigned to a 9-month , manual-based , family-focused psychoeducational therapy ( n = 28 ) or to an individually focused patient treatment ( n = 25 ) . All patients received concurrent treatment with mood-stabilizing medications . Structured follow-up assessment s were conducted at 3-month intervals for a 1-year period ofactive treatment and a 1-year period of posttreatment follow-up . Compared with patients in individual therapy , those in family-focused treatment were less likely to be rehospitalized during the 2-year study period . Patients in family treatment also experienced fewer mood disorder relapses over the 2 years , although they did not differ from patients in individual treatment in their likelihood of a first relapse . Results suggest that family psychoeducational treatment is a useful adjunct to pharmacotherapy in decreasing the risk of relapse and hospitalization frequently associated with bipolar disorder Abstract Objective : To determine the efficacy of teaching patients with bipolar disorder ( manic-depressive psychosis ) to identify early symptoms of relapse and seek prompt treatment from health services . Design : Single blind r and omised controlled trial with matching on four baseline variables using a minimisation algorithm . Setting : Mental health services in four NHS trusts ( one teaching , three non-teaching ) . Subjects : 69 patients with bipolar disorder who had had a relapse in the previous 12 months . Interventions : Seven to 12individual treatment sessions from a research psychologist plus routine care or routine care alone . Main outcome measures : Time to first manic or depressive relapse , number of manic or depressive relapses , and social functioning examined by st and ardised interviews every six months for 18 months . Results : 25th centile time to first manic relapse in experimental group was 65weeks compared with 17weeks in the control group . Event curves of time to first manic relapse significantly differed between experimental and control groups ( log rank 7.04 , df=1 , P=0.008 ) , with significant reductions in the number of manic relapses over 18months ( median difference 30 % ( 95 % confidence interval 8 % to 52 % ) , P=0.013 ) . The experimental treatment had no effect on time to first relapse or number of relapses with depression , but it significantly improved overall social functioning ( mean difference 2.0(0.7to 3.2 ) , P=0.003 ) and employment ( mean difference 0.7(0.1to 1.3 ) , P=0.030 ) by 18months . Conclusion : Teaching patients to recognise early symptoms of manic relapse and seek early treatment is associated with important clinical improvements in time to first manic relapse , social functioning , and employment BACKGROUND Despite the availability of efficacious medications and psychotherapies , care of bipolar disorder in everyday practice is often deficient . This trial evaluated the effectiveness of a multi-component care management program in a population -based sample of people with bipolar disorder . METHOD Four hundred and forty-one patients treated for bipolar disorder during the prior year were r and omly assigned to continued usual care or usual care plus a systematic care management program including : initial assessment and care planning , monthly telephone monitoring including brief symptom assessment and medication monitoring , feedback to and coordination with the mental health treatment team , and a structured group psychoeducational program -- all provided by a nurse care manager . Blinded quarterly assessment s generated week-by-week ratings of severity of depression and mania symptoms using the Longitudinal Interval Follow-Up Evaluation . RESULTS Participants assigned to the intervention group had significantly lower mean mania ratings averaged across the 12-month follow-up period ( Z= 2.44 , p=0.015 ) and approximately one-third less time in hypomanic or manic episode ( 2.59 weeks v. 1.69 weeks ) . Mean depression ratings across the entire follow-up period did not differ significantly between the two groups , but the intervention group showed a greater decline in depression ratings over time ( Z statistic for group-by-time interaction = 1.98 , p = 0.048 ) . CONCLUSIONS A systematic care program for bipolar disorder significantly reduces risk of mania over 12 months . Preliminary results suggest a growing effect on depression over time , but longer follow-up will be needed BACKGROUND The authors ' goal was to pilot test a newly developed manual-based group psychotherapy , called Integrated Group Therapy ( IGT ) , for patients with bipolar disorder and substance dependence . METHOD In this open trial , patients with DSM-IV bipolar disorder and substance dependence ( N = 45 ) were recruited in sequential blocks to receive either group therapy ( N = 21 ) or 6 monthly assessment s , but no experimental treatment ( N = 24 ) . RESULTS When compared with patients who did not receive group therapy , patients who received IGT had significantly better outcomes on the Addiction Severity Index drug composite score ( p < .03 ) , percentage of months abstinent ( p < .01 ) , and likelihood of achieving 2 ( p < .002 ) or 3 ( p < .004 ) consecutive abstinent months . CONCLUSION IGT is a promising treatment for patients with bipolar disorder and substance dependence , who have traditionally had poor outcomes . It is unclear , however , how much of the improvement among the group therapy patients is attributable to the specific content of the treatment . A study comparing this treatment with another active psychotherapy treatment is warranted CONTEXT Psychosocial interventions have been shown to enhance pharmacotherapy outcomes in bipolar disorder . OBJECTIVE To examine the benefits of 4 disorder-specific psychotherapies in conjunction with pharmacotherapy on time to recovery and the likelihood of remaining well after an episode of bipolar depression . DESIGN R and omized controlled trial . SETTING Fifteen clinics affiliated with the Systematic Treatment Enhancement Program for Bipolar Disorder . Patients A total of 293 referred out patients with bipolar I or II disorder and depression treated with protocol pharmacotherapy were r and omly assigned to intensive psychotherapy ( n = 163 ) or collaborative care ( n = 130 ) , a brief psychoeducational intervention . INTERVENTIONS Intensive psychotherapy was given weekly and biweekly for up to 30 sessions in 9 months according to protocol s for family-focused therapy , interpersonal and social rhythm therapy , and cognitive behavior therapy . Collaborative care consisted of 3 sessions in 6 weeks . MAIN OUTCOME MEASURES Outcome assessment s were performed by psychiatrists at each pharmacotherapy visit . Primary outcomes included time to recovery and the proportion of patients classified as well during each of 12 study months . RESULTS All analyses were by intention to treat . Rates of attrition did not differ across the intensive psychotherapy ( 35.6 % ) and collaborative care ( 30.8 % ) conditions . Patients receiving intensive psychotherapy had significantly higher year-end recovery rates ( 64.4 % vs 51.5 % ) and shorter times to recovery than patients in collaborative care ( hazard ratio , 1.47 ; 95 % confidence interval , 1.08 - 2.00 ; P = .01 ) . Patients in intensive psychotherapy were 1.58 times ( 95 % confidence interval , 1.17 - 2.13 ) more likely to be clinical ly well during any study month than those in collaborative care ( P = .003 ) . No statistically significant differences were observed in the outcomes of the 3 intensive psychotherapies . CONCLUSIONS Intensive psychosocial treatment as an adjunct to pharmacotherapy was more beneficial than brief treatment in enhancing stabilization from bipolar depression . Future studies should compare the cost-effectiveness of models of psychotherapy for bipolar disorder . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00012558 OBJECTIVE In a previous r and omized controlled study , the authors reported significant beneficial effects of cognitive therapy for relapse prevention in bipolar disorder patients up to 1 year . This study reports additional 18-month follow-up data and presents an overview of the effect of therapy over 30 months . METHOD Patients with DSM-IV bipolar I disorder ( N=103 ) suffering from frequent relapses were r and omly assigned into a cognitive therapy plus medication group or a control condition of medication only . Independent raters , who were blind to patient group status , assessed patients at 6-month intervals . RESULTS Over 30 months , the cognitive therapy group had significantly better outcome in terms of time to relapse . However , the effect of relapse prevention was mainly in the first year . The cognitive therapy group also spent 110 fewer days ( 95 % CI=32 to 189 ) in bipolar episodes out of a total of 900 for the whole 30 months and 54 fewer days ( 95 % CI=3 to 105 ) in bipolar episodes out of a total of 450 for the last 18 months . Multivariate analyses of variance showed that over the last 18 months , the cognitive therapy group exhibited significantly better mood ratings , social functioning , coping with bipolar prodromes , and dysfunctional goal attainment cognition . CONCLUSIONS Patients in the cognitive therapy group had significantly fewer days in bipolar episodes after the effect of medication compliance was controlled . However , the results showed that cognitive therapy had no significant effect in relapse reduction over the last 18 months of the study period . Further studies should explore the effect of booster sessions or maintenance therapy BACKGROUND Several previous studies have established that low treatment adherence is common among bipolar patients and may explain high rates of recurrence . On the other h and , some patients keep relapsing even when they strictly follow their prescribed somatic treatments . Psychological interventions such as psychoeducation may foster early recognition of prodromal symptoms and minimize the risk of relapse . To date , studies assessing the usefulness of psychoeducation in fully compliant patients are lacking . METHOD This was a single-blind , r and omized , prospect i ve clinical trial on the efficacy of group psychoeducation in remitted fully compliant DSM-IV bipolar I patients ( N = 25 ) who were compared with a group with similar characteristics ( N = 25 ) who did not receive psychoeducation . All patients received naturalistic pharmacologic treatment . Recruitment began in 1997 and follow-up was completed in January 2002 . The follow-up phase comprised 2 years during which all patients continued receiving naturalistic treatment without psychological intervention and were assessed monthly on several outcome measures . RESULTS At the end of the 2-year follow-up , 23 subjects ( 92 % ) in the control group fulfilled criteria for recurrence versus 15 patients ( 60 % ) in the psychoeducation group ( p < .01 ) . The number of total recurrences and the number of depressive episodes were significantly lower in psychoeducated patients . CONCLUSION Although the present study has the limitation of small sample size , psychoeducation showed its efficacy in preventing relapses in bipolar I patients who were adherent to drug treatment . The action of psychoeducation seems to go beyond compliance enhancement and may support a tripod model composed by lifestyle regularity and healthy habits , early detection of prodromal signs followed by prompt drug intervention , and finally treatment compliance BACKGROUND Bipolar patients are at risk for relapses of their illness even when undergoing optimal pharmacotherapy . This study was performed to determine whether combining family-focused therapy ( FFT ) with pharmacotherapy during a postepisode interval enhances patients ' mood stability during maintenance treatment . METHODS In a r and omized controlled trial , 101 bipolar patients were assigned to FFT and pharmacotherapy or a less intensive crisis management ( CM ) intervention and pharmacotherapy . Outcome assessment s were conducted every 3 to 6 months for 2 years . Participants ( mean + /- SD age , 35.6 + /- 10.2 years ) were referred from inpatient or outpatient clinics after onset of a manic , mixed , or depressed episode . FFT consisted of 21 sessions of psychoeducation , communication training , and problem-solving skills training . Crisis management consisted of 2 sessions of family education plus crisis intervention sessions as needed . Both protocol s lasted 9 months . Patients received pharmacotherapy for 2 study years . Main outcome measures included time to relapse , depressive and manic symptoms , and medication adherence . RESULTS Rates of study completion did not differ across the FFT ( 22/31 , 71 % ) and CM groups ( 43/70 , 61 % ) . Patients undergoing FFT had fewer relapses ( 11/31 , 35 % ) and longer survival intervals ( mean + /- SD , 73.5 + /- 28.8 weeks ) than patients undergoing CM ( 38/70 , 54 % ; mean + /- SD , 53.2 + /- 39.6 weeks ; hazard ratio , 0.38 ; 95 % confidence interval , 0.20 - 0.75 ; P = .003 ; intent to treat ) . Patients undergoing FFT showed greater reductions in mood disorder symptoms and better medication adherence during the 2 years than patients undergoing CM . CONCLUSION Combining family psychoeducation with pharmacotherapy enhances the postepisode symptomatic adjustment and drug adherence of bipolar patients R and omised controlled trials are widely accepted as the most reliable method of determining effectiveness , but most trials have evaluated the effects of a single intervention such as a drug . Recognition is increasing that other , non-pharmacological interventions should also be rigorously evaluated.1 - 3 This paper examines the design and execution of research required to address the additional problems result ing from evaluation of complex interventions —that is , those “ made up of various interconnecting parts.”4 The issues dealt with are discussed in a longer Medical Research Council paper ( www.mrc.ac.uk/complex_packages.html ) . We focus on r and omised trials but believe that this approach could be adapted to other design s when they are more appropriate . # # # # Summary points Complex interventions are those that include several components The evaluation of complex interventions is difficult because of problems of developing , identifying , documenting , and reproducing the intervention A phased approach to the development and evaluation of complex interventions is proposed to help research ers define clearly where they are in the research process Evaluation of complex interventions requires use of qualitative and quantitative evidence There are specific difficulties in defining , developing , documenting , and reproducing complex interventions that are subject to more variation than a drug . A typical example would be the design of a trial to evaluate the benefits of specialist stroke units . Such a trial would have to consider the expertise of various health professionals as well as investigations , drugs , treatment guidelines , and arrangements for discharge and follow up . Stroke units may also vary in terms of organisation , management , and skill mix . The active components of the stroke unit may be difficult to specify , making it difficult to replicate the intervention . The box gives other examples of complex interventions . # # # # Examples of complex interventions Service delivery and organisation : Stroke units Hospital at home Interventions directed at health professionals ' behaviour : Strategies for implementing guidelines Computerised decision support Community interventions : Community BACKGROUND Studies on individual psychotherapy indicate that some interventions may reduce the number of recurrences in bipolar patients . However , there has been a lack of structured , well- design ed , blinded , controlled studies demonstrating the efficacy of group psychoeducation to prevent recurrences in patients with bipolar I and II disorder . METHODS One hundred twenty bipolar I and II out patients in remission ( Young Mania Rating Scale score < 6 , Hamilton Depression Rating Scale-17 score < 8) for at least 6 months prior to inclusion in the study , who were receiving st and ard pharmacologic treatment , were included in a controlled trial . Subjects were matched for age and sex and r and omized to receive , in addition to st and ard psychiatric care , 21 sessions of group psychoeducation or 21 sessions of nonstructured group meetings . Subjects were assessed monthly during the 21-week treatment period and throughout the 2-year follow-up . RESULTS Group psychoeducation significantly reduced the number of relapsed patients and the number of recurrences per patient , and increased the time to depressive , manic , hypomanic , and mixed recurrences . The number and length of hospitalizations per patient were also lower in patients who received psychoeducation . CONCLUSION Group psychoeducation is an efficacious intervention to prevent recurrence in pharmacologically treated patients with bipolar I and II disorder |
962 | 23,803,497 | In conclusion , the longitudinal studies were generally consistent in showing that adaptation to night work was complete within one to two weeks of work , while re-adaptation to a daytime schedule was slower .
Shift workers reported more sleep problems than day workers . | Shift and night work are associated with several negative outcomes .
The aim of this study was to make a systematic review of all studies which examine effects of shift and night work in the offshore petroleum industry , to synthesize the knowledge of how shift work offshore may affect the workers . | STUDY OBJECTIVES To study the adaptation and readaptation processes to 1 week of night work ( 6:30 PM to 6:30 AM ) followed by 1 week of day work ( 6:30 AM to 6:30 PM ) . DESIGN Part of a r and omized , placebo-controlled , crossover field study . Here , data from the placebo arm are presented . SETTING Oil rig in the North Sea . Work schedule : 2 weeks on a 12-hour shift , with the first week on the night shift and the second week on the day shift . PARTICIPANTS Subjects complaining about problems with adjusting to shift work . Seventeen workers completed the study . INTERVENTIONS N/A. MEASUREMENTS Subjective and objective measures of sleepiness ( Karolinska Sleepiness Scale and simple serial reaction time test ) and sleep ( diary and actigraphy ) . RESULTS Both subjective and objective measures improved gradually during night work . The return to day work after 1 week on the night shift led to a clear increase in subjective sleepiness and worsening of sleep parameters . During the week on the day shift , sleepiness and sleep gradually improved , similar to the improvement seen during night work . The workers indicated that the day shift was worse than the night shift on some of the measures , e.g. , sleep length was significantly longer during the night-shift period . CONCLUSIONS This is one of few studies showing how shift workers in a real-life setting adjust to night work . Both subjective and objective sleepiness and subjective sleep improved across days . The effects were especially pronounced for the subjective data Previously we have shown that the 6-sulphatoxymelatonin rhythm of oil rig workers on a 2-week night shift ( 1800 - 0600 h ) adapts to the shift via a phase delay . We now report the findings of a study on two offshore drill crews working a 1 week day ( 1200 - 0000 h ) , 1 week night ( 0000 - 1200 h ) swing shift . Urine sample s were collected every 2 - 3 h throughout the subjective days , with over-sleep collection s , for the measurement of 6-sulphatoxymelatonin by radioimmunoassay . One crew ( n = 11 ) , studied in November , showed no change in their 6-sulphatoxymelatonin rhythm during night shift . The other crew ( n = 7 ) , studied in March , showed a significant phase advance of the rhythm during night shift . The data indicate that both the type of shift and the season influence the direction and degree of adaptation Background : Melatonin shows potential oncostatic activity and is acutely suppressed by light exposure . Some evidence suggests an association between night work and breast cancer risk , possibly through the melatonin pathway . Methods : In a cohort of premenopausal nurses , we prospect ively studied the relation between rotating night shift work and breast cancer risk . Total number of months during which the nurses worked rotating night shifts was first assessed at baseline in 1989 and periodically up date d thereafter . We used Cox proportional hazards models to calculate relative risks ( RRs ) and 95 % confidence intervals ( CIs ) . Results : Among 115,022 women without cancer at baseline , 1,352 developed invasive breast cancer during 12 years of follow up . Women who reported more than 20 years of rotating night shift work experienced an elevated relative risk of breast cancer compared with women who did not report any rotating night shift work ( multivariate RR = 1.79 ; 95 % CI = 1.06–3.01 ) . There was no increase in risk associated with fewer years of rotating night work . Conclusion : Our results suggest a modestly elevated risk of breast cancer after longer periods of rotating night work . Additional studies are warranted to rule out small sample size or uncontrolled sources for confounding as alternative explanations Previous research indicates that night workers ' circadian rhythms do not adapt to night work and that disturbed sleep and wakefulness persist , even after weeks of working on night shift . We studied adjustment to 14 days of consecutive night work at an oil platform and the readjustment to day life at home , using the Karolinska sleep/wake diary . The platform workers adapted to night work within a few days , as indicated by the rapid reduction of night-work sleepiness , and by the gradual delay of bedtime to an hour commensurate with the behavior of day workers . Readaptation to day life was slower and more difficult , adding evidence of a complete adaptation to night work . We conclude that the lack of conflicting exposure to daylight in the morning may have facilitated the rapid adjustment to night work STUDY OBJECTIVES Although there are considerable data demonstrating the impact of shift work on sleep and alertness , little research has examined the prevalence and consequences of shift work sleep disorder in comparison to the difficulties with insomnia and excessive sleepiness experienced by day workers . The present study was design ed to determine the relative prevalence and negative consequences associated with shift work sleep disorder in a representative sample drawn from the working population of metropolitan Detroit . DESIGN R and om-digit dialing techniques were used to assess individuals regarding their current work schedules and a variety of sleep- and non-sleep-related outcomes . SETTING Detroit tricounty population . PARTICIPANTS A total of 2,570 individuals aged 18 to 65 years from a representative community-based sample including 360 people working rotating shifts , 174 people working nights , and 2036 working days . MEASUREMENTS AND RESULTS Using st and ardized techniques , individuals were assessed for the presence of insomnia and excessive sleepiness , based on DSM-IV and ICSD criteria . Those individuals with either insomnia or excessive sleepiness and who were currently working rotating or night schedules were classified as having shift work sleep disorder . Occupational , behavioral , and health-related outcomes were also measured . Individuals who met criteria for shift work sleep disorder had significantly higher rates of ulcers ( odds ratio = 4.18 , 95 % confidence interval = 2.00 - 8.72 ) , sleepiness-related accidents , absenteeism , depression , and missed family and social activities more frequently compared to those shift workers who did not meet criteria ( P < .05 ) . Importantly , in most cases , the morbidity associated with shift work sleep disorder was significantly greater than that experienced by day workers with identical symptoms . CONCLUSION These findings suggest that individuals with shift work sleep disorder are at risk for significant behavioral and health-related morbidity associated with their sleep-wake symptomatology . Further , it suggests that the prevalence of shift work sleep disorder is approximately 10 % of the night and rotating shift work population OBJECTIVES This study evaluated the effects of bright light and melatonin on adaptation to night work on an oil rig in the North Sea . METHODS Seventeen persons working a schedule of 2 weeks on a 12-hour shift , with the first week on night shift and the second week on day shift ( ie , the swing shift schedule ) participated . In a r and omized controlled crossover design , the shift workers received a placebo , melatonin ( 3 mg , 1 hour before bedtime ) , or bright light ( 30-minute exposure , individually scheduled ) during the first 4 days on the night shift and during the first 4 days on the day shift . Subjective and objective measures of sleepiness ( Karolinska Sleepiness Scale and a simple serial reaction-time test ) and sleep ( diary and actigraphy ) were recorded . RESULTS Subjective measures indicated that melatonin modestly reduced sleepiness at work during the day shift and increased sleep by 15 - 20 minutes per day . Bright light gave values in between those of melatonin and the placebo , but with few significant results . According to the objective measures , bright light improved sleep to a minor degree during the night shift . Hardly any side-effects were reported . CONCLUSIONS Melatonin and bright light modestly improved sleep and sleepiness in this field study . In well-controlled simulated nightwork studies , both melatonin and bright light are more effective in alleviating sleepiness and sleep problems . The less effect in this field study may be due to competing or conflicting factors present in real life or to an inoptimal timing and duration of the treatments |
963 | 26,341,170 | INTERPRETATION Glycaemic efficacy of Technosphere inhaled insulin is lower than that of subcutaneous insulin , but inhaled insulin has a lower risk of severe hypoglycaemia and weight gain . | BACKGROUND Technosphere inhaled insulin is a non-invasive alternative to subcutaneous injectable insulin for adults with type 1 or 2 diabetes .
In this systematic review and meta- analysis of r and omised controlled trials , we aim ed to establish the efficacy , safety , and patient acceptability of Technosphere inhaled insulin in patients with diabetes . | Clinical investigators are increasingly testing treatments that have the primary benefit of decreased burden or harms relative to an existing st and ard . The goal of the result ing r and omized trials -- called noninferiority trials -- is to establish that the novel treatment 's effectiveness is not substantially less than the existing st and ard . Conclusions from these trials are , however , based on noninferiority thresholds specified by authors whose judgments may not coincide with those of patients and clinicians . This article highlights issues related to validity , interpretation , and applicability of results specific to noninferiority trials . Suboptimal administration of st and ard treatment or exclusive reliance on the analyze-as-r and omized approach that is st and ard for conventional superiority trials may produce misleading results in noninferiority trials . Clinicians should judge whether the novel treatment 's impact on effectiveness outcomes --the prime reason for wanting to prescribe it -- is sufficiently close to that of st and ard treatment that they are comfortable substituting it for the existing st and ard . Trading off desirable and undesirable consequences is an individual decision : given the benefits of a novel treatment , some patients may perceive the uncertainty regarding a reduction in treatment effectiveness as acceptable while others may not Background : Individuals with type 2 diabetes mellitus have impairments in early insulin release , result ing in increased postpr and ial glucose excursions and suboptimal glycemic control . Studies with Technosphere ® Insulin ( TI ) indicate that it has rapid systemic absorption and a short duration of glucose-lowering activity , making it well suited for controlling postpr and ial glucose levels . Methods : The goal of this phase 2b , prospect i ve , multicenter , double-blind , placebo-controlled study was to characterize the dose response of four different doses ( equivalent to 3.6 , 7.3 , 10.9 , and 14.6 U subcutaneous regular human insulin ) of pr and ial TI or Technosphere powder alone administered before each of three meals daily , in combination with insulin glargine over an 11-week treatment period , in patients with type 2 diabetes and suboptimal glycemic control . Conclusions : This study demonstrated that , over 11 weeks , TI plus basal insulin glargine is well tolerated and results in dose-dependent reductions in postpr and ial glucose and HbA1c levels . Results : The study enrolled 227 patients . In all dose groups , TI demonstrated statistically significant dose-dependent reductions in hemoglobin A1c ( HbAlc ) versus baseline ( −0.4 , −0.5 , −0.5 , and −0.6 for 3.6 , 7.3 , 10.9 , and 14.6 U equivalents , respectively ; p < 0.05 in all groups ) , as well as versus placebo or Technosphere powder alone ( −0.40 , −0.67 , −0.70 , and −0.78 for 3.6 , 7.3 , 10.9 , and 14.6 U equivalents , respectively ; p < 0.04 in all groups ) . It reduced the postpr and ial maximum glucose concentration within each treatment group ( statistically significant in all but the TI 3.6 U-equivalent group ) and reduced the postpr and ial area under the glucose curve ( statistically significant for the TI 10.9 and 14.6 U-equivalent groups ) versus placebo . There were no cases of severe hypoglycemia , while mild/moderate hypoglycemia was observed most frequently in the highest dosage groups , as expected . Rates of cough were low and comparable among all groups . No clinical ly relevant changes in pulmonary function tests , body weight , or high-resolution computerized axial tomography and magnetic resonance imaging were observed 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 development of pulmonary insulin formulation offers an attractive alternative to the current requirement of repeated subcutaneous ( s.c . ) injections for insulin administration . Technosphere/Insulin is a formulation of regular human insulin that was design ed to produce an efficient transport of insulin across the respiratory epithelium into the systemic circulation . Several studies using the euglycemic clamp technique were performed in healthy volunteers and patients with Type 2 diabetes to assess the pharmacokinetic and pharmacodynamic properties of Technosphere/Insulin . The investigations revealed a very rapid systemic insulin uptake ( insulin T(max ) approximately 12 - 14 min ) , a fast onset of action ( maximum activity approximately 20 - 30 min ) , and a short duration of action ( approximately 2 - 3 h ) in healthy volunteers and in patients with Type 2 diabetes . In the first study , employing a commercially available inhaler , the relative bioavailability ( compared with s.c . injections ) was initially reported to be 26 % for the first 3 h and 16 % for the entire observation period of 6 h. With the development of a specific inhaler adapted to the physical properties of Technosphere/Insulin , the MedTone Inhaler , relative bioavailability was 50 % for the first 3 h and 30 % over the entire 6-h period . A clear linearity of systemic insulin uptake was observed in a study employing 12 healthy volunteers inhaling doses of 25 , 50 , and 100 IU . Repeated inhalation of 100 IU of Technosphere/Insulin by 12 patients with Type 2 diabetes revealed a lower variability in comparison with published s.c . injection data from healthy volunteers . This new Technosphere/Insulin formulation was well tolerated , and no serious adverse events were reported in any of the investigations . Given its attractive time-action profile , Technosphere/Insulin may become a suitable alternative to s.c . injection for pr and ial insulin delivery , especially in patients with Type 2 diabetes , if the long-term safety , tolerability , and efficacy of this pulmonary insulin are established and confirmed in future studies AIMS This study assessed patient-reported outcomes in a multicenter study of adults with type 2 diabetes taking mealtime Technosphere ( ® ) inhaled insulin ( MannKind Corp. , Valencia , CA ) and basal insulin ( insulin glargine ) or premixed aspart insulin 70/30 . METHODS Subjects were 618 non-smoking adults with starting hemoglobin A1c > 7.0 % : 302 in the Technosphere+glargine ( TI+G ) arm and 316 in the biphasic rapid-acting insulin arm ( premixed aspart insulin 70/30 ) . Subjects ( 47 % male ; mean age , 56 years ; mean duration of diagnosed diabetes , 13.4 years ) completed a measure of health-related quality of life ( the SF-36 ) and a measure of treatment satisfaction ( the Inhaled Insulin Treatment Question naire [ IITQ ] ) before starting insulin treatment and approximately 45 weeks later . RESULTS There were no significant changes in either treatment arm for SF-36 Physical or Mental Component Summary measures . IITQ Diabetes Worries declined significantly in the TI+G arm ( P=0.008 ) , and Perceptions of Insulin Therapy , Treatment Satisfaction , and Treatment Preference improved in both arms ( all P<0.001 ) ; there were no significant between-arm differences in change on any of these measures . CONCLUSIONS Treatment with inhaled Technosphere insulin was implemented without a negative impact on health-related quality of life and with a reduction in diabetes worries . Improvements in perceptions of insulin therapy , treatment satisfaction , and treatment preference did not differ from treatment with premixed aspart insulin AIMS Development of inhaled insulin has increased the need to underst and its pulmonary safety . This study evaluated pulmonary function changes in diabetes patients receiving inhaled Technosphere Insulin ( TI ) or usual antidiabetes treatment ( usual care ) . METHODS This r and omized , open-label study was conducted at 220 sites ( 25 July 2005 to 29 August 2008 ) . Pulmonary function tests [ forced expiratory volume in 1 s ( FEV(1 ) ) , forced vital capacity ( FVC ) , total lung capacity ( TLC ) and lung diffusion capacity for carbon monoxide ( DL(CO ) ) ] were prospect ively followed over 2 years in patients with type 1 or type 2 diabetes receiving TI ( n = 730 ) or usual care ( n = 824 ) , along with a cohort without diabetes not receiving any specific therapy ( n = 145 ) . RESULTS Baseline demographics and pulmonary function were similar between diabetes treatment groups . Lung function declined from baseline in all groups . TI was non-inferior to usual care for mean change in FEV(1 ) from baseline to month 24 [ mean ( s.e.m . ) 0.037 ( 0.0119 ) l ; 95 % CI 0.014 to 0.060 ] using mixed-model repeated-measure with a pre-specified non-inferiority margin of 50 ml/year . After a greater initial decline at month 3 with TI , rate of change ( slope ) in FEV(1 ) , FVC and DL(CO ) ( months 3 - 24 ) was not statistically different between treatment groups . TI was well tolerated ; no serious safety concerns emerged . The most common respiratory event associated with TI was mild , transient cough , occurring within minutes of inhalation . CONCLUSIONS Observed changes in lung function with TI were small , occurred early after therapy initiation , remained non-progressive over 2 years and were unlikely to be clinical ly meaningful Background : Technosphere ® [ Bis-3 , 6(4-fumarylaminobutyl)-2 , 5-diketopiperazine ( FDKP ) ] microparticles , the integral component of the Technosphere inhalation system , deliver drugs to the deep lung and have been used to administer insulin and glucagon-like peptide-1 via inhalation in clinical studies . Three studies were conducted to characterize FDKP pharmacokinetics , including assessment s in subjects with diabetic nephropathy ( DNP ) , in subjects with chronic liver disease ( CLD ) , and in healthy subjects . Methods : An open-label , nonr and omized , two-period , fixed-sequence crossover absorption , distribution , metabolism , and excretion ( ADME ) study was conducted in six healthy nonsmoking men who received single intravenous and oral doses of [14C]FDKP solution , with serial sampling of blood , urine , feces , and expired air . Additionally , two single-dose , open-label , parallel- design studies with 20 mg of inhaled FDKP were conducted in ( 1 ) 12 diabetic subjects with normal renal function and 24 DNP subjects and ( 2 ) 12 healthy subjects and 21 CLD subjects . Results : In the ADME study , > 95 % of the intravenous dose and <3 % of the oral dose were recovered in urine , with no evidence of metabolism . No significant pharmacokinetic differences were observed between healthy subjects and CLD subjects [ geometric mean ( % coefficient of variation ) area under the curve from time 0 to 480 minutes ( AUC0 - 480 ) : 26,710 ( 34.8 ) and 31,477 ( 28.8 ) ng/ml·min , respectively ] . Maximum observed drug concentration ( C max ) and AUC0 - 480 were higher in DNP subjects than in subjects with normal renal function [ C max : 159.9 ( 59.4 ) ng/ml versus 147.0 ( 44.3 ) ng/ml ; AUC0 - 480 : 36,869 ( 47.2 ) ng/ml·min versus 30,474 ( 31.8 ) ng/ml·min ] . None of the differences observed were considered clinical ly significant . Conclusions : Fumaryl diketopiperazine is predominantly cleared unchanged by the kidney with essentially no oral bioavailability . Technosphere is a safe delivery vehicle for medications administered via inhalation AIM AFRESA [ Technosphere Insulin ( TI ) ; MannKind Corporation , Valencia , CA ] , a dry powder preparation of regular human insulin ( RHI ) , utilizes a novel and versatile drug carrier platform that enables pulmonary administration of medications typically administered by injection . The aim of this study was to compare the pharmacokinetic ( PK ) and pharmacodynamic ( PD ) parameters of three different inhaled doses of TI with those of subcutaneous ( s.c . ) RHI . METHODS This r and omized , open-label , four-way crossover study of 11 healthy , non-smoking volunteers evaluated PK and PD profiles following single inhalations of 25 , 50 or 100 U TI and 10 IU RHI administered subcutaneously using a euglycaemic clamp technique . RESULTS Following inhalation of TI , peak insulin concentrations ( C(max ) ) were achieved approximately 2 h earlier than with RHI ( 12 - 17 min for TI vs. 134 min for RHI ) . Area under the insulin concentration-time curve ( AUC ) and insulin C(max ) values increased with increasing TI dose . Insulin exposure , as measured by AUC , was found to be linear over the dose range studied . Compared with s.c . RHI , TI at doses of 25 , 50 and 100 U showed a relative bioavailability of 25 , 23 and 21 % , respectively . The maximum bioeffect , as measured by the glucose infusion rate , occurred approximately 2 h earlier for all three TI doses ( 42 , 50 and 58 min , respectively ) than for s.c . RHI ( 171 min ) . No treatment-related adverse events were reported with TI . CONCLUSION TI is an inhaled insulin with a more rapid absorption and a more rapid elimination than subcutaneously administered RHI , result ing in a quick onset and short duration of action . Insulin exposure following TI administration was found to be linear over the dose range of 25 - 100 Confidence in evidence summarized in meta-analyses depends on the strength of the underlying studies . This inherent limitation of syntheses appears in the case of a meta- analysis of sodium-glucose cotransporter 2 inhibitors for the treatment of type 2 diabetes because many of the pertinent r and omized trials did not h and le patient dropout and " rescue " medication properly . Repudiated statistical methods , such as last observation carried forward , and unsophisticated methods for h and ling postrescue data produce unreliable summary estimates . Future reports of r and omized studies and meta-analyses of those studies must focus on posing precise questions about the treatment effect of interest and then implement appropriate statistical methods to account for missing data , patient dropout , and use of rescue medication BACKGROUND Insulin therapy is often a delayed strategy in patients with type 2 diabetes mellitus because it is associated with weight gain , hypoglycaemia , and the need for subcutaneous injections . We aim ed to assess the efficacy and safety of pr and ial Technosphere inhaled insulin compared with twice daily biaspart insulin . METHODS In this r and omised , open-label , parallel-group study , adult patients with type 2 diabetes mellitus and poor glycaemic control despite insulin therapy , with or without oral antidiabetes drugs , were enrolled from ten countries between Feb 23 , 2006 , and Aug 8 , 2007 . Patients were r and omly allocated in a 1:1 ratio to receive 52 weeks ' treatment with : pr and ial Technosphere inhaled insulin powder plus bedtime insulin glargine ; or twice daily premixed biaspart insulin ( 70 % insulin aspart protamine suspension and 30 % insulin aspart of rDNA origin ) . The primary endpoint was a comparison of change in glycosylated haemoglobin ( HbA(1c ) ) from baseline to week 52 between treatment groups ; the non-inferiority margin was 0.4 % . Analysis was by per protocol for non-inferiority testing of the primary endpoint . This study is registered with Clinical Trials.gov , number NCT00309244 . FINDINGS 334 patients were allocated to inhaled insulin plus insulin glargine , and 343 to biaspart insulin ; 107 patients on inhaled insulin plus insulin glargine and 85 on biaspart insulin discontinued the trial . 211 patients on inhaled insulin plus insulin glargine and 237 on biaspart insulin were included in per- protocol analyses . Change in HbA(1c ) with inhaled insulin plus insulin glargine ( -0.68 % , SE 0.077 , 95 % CI -0.83 to -0.53 ) was similar and non-inferior to that with biaspart insulin ( -0.76 % , 0.071 , -0.90 to -0.62 ) . The between-group difference was 0.07 % ( SE 0.102 , 95 % CI -0.13 to 0.27 ) . Patients had significantly lower weight gain and had fewer mild-to-moderate and severe hypoglycaemic events on inhaled insulin plus insulin glargine than on biaspart insulin . The safety and tolerability profile was similar for both treatments , apart from increased occurrence of cough and change in pulmonary function in the group receiving inhaled insulin plus insulin glargine . INTERPRETATION This study is part of a large clinical development programme addressing the efficacy and tolerability of use of Technosphere inhaled insulin in a wide variety of patients . FUNDING MannKind |
964 | 25,070,054 | : Soluble fiber is effective in treating IBS .
Bran did not appear to be of benefit , although we did not uncover any evidence of harm from this intervention , as others have speculated from uncontrolled data | OBJECTIVES : Fiber has been used for many years to treat irritable bowel syndrome ( IBS ) .
This approach had fallen out of favor until a recent resurgence , which was based on new r and omized controlled trial ( RCT ) data that suggested it might be effective .
We have previously conducted a systematic review of fiber in IBS , but new RCT data for fiber therapy necessitate a new analysis ; thus , we have conducted a systematic review of this intervention . | A double-blind controlled therapeutic trial of factorial design was used to study the therapeutic effects of lorazepam , hyoscine butylbromide , and ispaghula husk in 12 r and omised blocks of eight patients with the irritable bowel syndrome ( IBS ) . Each of the three agents caused a sustained symptomatic improvement in some of the patients , although only with ispaghula was the difference between the real and dummy preparation statistically significant . When the eight possible combinations of treatment were analysed none of the 12 patients who received only dummy preparations of the three agents had maintained any improvement over the three months of the trial . Seven patients improved among the 12 who received potent preparations of all three agents , and between four and six patients improved in the groups receiving one or two of the potent preparations . These therapeutic results , though far from perfect , show that the types of drug commonly used to treat IBS are of some value and may be additive in their effects . Similar combinations of other therapeutic agents may be more effective , but it will be possible to determine this only by carrying out factorial therapeutic trials This placebo controlled , double-blind , cross-over trial involving 20 patients was conducted to assess the effect of ispaghula husk on the major bowel symptoms and the whole gut transit time in irritable bowel syndrome ( IBS ) and to determine if changes in these parameters were related to global improvement . All 20 patients were interviewed at the end of the treatment periods and 14 patients kept concurrent daily records . Ispaghula therapy result ed in improvement in global symptoms and satisfying bowel movements ( P less than 0.001 ) but produced no change in abdominal pain or flatulence . There was a correlation between the improvement of well-being and the number of days of satisfying bowel movements ( P less than 0.001 ) but not with the indexes of pain , stool frequency or changes in the transit time . The easing of bowel dissatisfaction appears to be a major reason for the therapeutic success of ispaghula in IBS A double blind placebo controlled trial of ispaghula husk in 80 patients with irritable bowel syndrome is reported . Global assessment judged treatment to be satisfactory in 82 % of patients receiving ispaghula and 53 % of the placebo group ( p less than 0.02 ) . Bowel habit was unchanged in the placebo group , while constipation significantly improved in patients taking ispaghula ( p = 0.026 ) . Transit time decreased significantly in those taking ispaghula compared with placebo ( p = 0.001 ) , especially in patients with initially high transit times . Abdominal pain and bloating improved in both groups , with no significant differences between ispaghula and placebo . Four of the eight withdrawals on ispaghula and 10 of the 15 withdrawals on placebo were because of treatment failure . Ispaghula significantly improves overall well being in patients with irritable bowel syndrome , and in those with constipation favourably affects bowel habit and transit time Comment Our results confirm that the natural defences of the peritoneum can deal successfully with infection if unhampered by the dialysis fluid . ' Temporary interruption of dialysis avoids protein loss and fluid retention due to peritoneal inflammation , limits the use of costly or toxic antibiotics , and preserves remaining renal function . We found that our patients , having been treated by interruption of dialysis once , subsequently tended to refer themselves early in the hope of being able to receive this short treatment again . The treatment avoids the loss of phagocytic cells and opsonins that occurs during dialysis and allows these cells to be concentrated into a small volume of peritoneal fluid , thus increasing the chance of phagocytosis . It also avoids the detrimental effect of dialysis fluid on phagocytic cells,2 which may enhance survival of bacteria within leucocytes,3 and on the mesothelial cells.4 Interruption of dialysis was regularly effective and was not detrimental to peritoneal function . We believe that this was because of our careful selection of cases and recommend that the treatment is used only in the absence of contraindications . Immediate failure of this treatment was unusual . If not due to the presence of unusual pathogens it would suggest persisting infection from colonisation of the catheter or , if infection were present at the exit site , covert infection around the catheter . In either case the catheter should be removed , as in relapse of peritonitis after conventional A r and omized , double-blind trial of a psyllium preparation was initiated in 77 patients with painful irritable bowel syndrome . Sixty- patients finished and su bmi tted symptom data for 8 weeks while taking placebo ( n = 34 ) or psyllium ( n = 26 ) . Increase in normal stools and decrease in pain severity ( p less than 0.05 ) occurred equally in both groups . Subjective improvement was reported by 24 of 34 patients on placebo and 20 or 26 on psyllium ( p greater than 0.05 ) . Five symptom variables were significantly correlated ( p less than 0.05 ) with patient 's subjective global assessment ( R = 0.64 ) . Discriminant analysis of Minnesota Multiphasic Personality Inventory variables yielded overall rates of correct prediction of 66.1 % for whether patients got " much better " and 77.9 % for whether they voluntarily dropped from the study . A major placebo effect occurs in patients with painful irritable bowel syndrome and is probably responsible for the efficacy of psyllium . Personality factors influence the magnitude of therapeutic response and whether patients discontinue treatment within 8 weeks |
965 | 16,229,742 | There were , however , many adverse effects .
Chlorpromazine is sedating ( n = 1242 , 18 RCTs , RR 2.3 CI 1.7 to 3.1 , NNH 6 CI 5 to 8) , increases a person 's chances of experiencing acute movement disorders , Parkinsonism and causes low blood pressure with dizziness and dry mouth .
Conclusion It is underst and able why the World Health Organization ( WHO ) have endorsed and included chlorpromazine in their list of essential drugs for use in schizophrenia . | Background Chlorpromazine ( CPZ ) remains one of the most common drugs used for people with schizophrenia worldwide , and a benchmark against which other treatments can be evaluated .
Quantitative review s are rare ; this one evaluates the effects of chlorpromazine in the treatment of schizophrenia in comparison with placebo . | To evaluate the clinical effectiveness of chlorpromazine in comparison with placebo over a brief period of hospitalization , the authors conducted a double-blind study of the drug in 44 acutely ill schizophrenic patients . These patients had been newly admitted to a brief treatment unit where the average length of stay was 7 to 10 days . The results of this study indicate that chlorpromazine had no more calming or antipsychotic effect than placebo during the first 5 days of treatment . The authors suggest that 5 days is too short a time for a clinical trial to gauge patient response to chlorpromazine 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 In a series of 6 separate controlled clinical trials of antipsychotic agents in chronic schizophrenic patients , it was shown repeatedly that chlorpromazine ( CPZ ) exhibited hypercholesterolemic activity . In the analysis of covariance , the adjusted final mean difference in serum cholesterol concentrations between the placebo and CPZ groups ranged from 14 to 28 mg . per 100 ml . This activity was dose related in that it occurred with a fixed daily dose of 600 mg . administered for 24 weeks , but not with a fixed daily dose of 150 mg . or 300 mg . over the same period of time . The serum concentration of triglycerides remained unaffected under similar experimental conditions . This action of CPZ appeared unrelated to thyroid function and liver function as presently measured in the clinical laboratory . A consistent relationship to body weight changes could not be demonstrated even though increased body weight was noted to be a consistent result of CPZ therapy . In view of its extensive use as long‐term therapy , the possible role of CPZ as an atherogenic agent deserves consideration A double-blind placebo-controlled trial of chlorpromazine , using a cross-over design , is reported . There were 28 patients , showing chronic defect states , mostly schizophrenic . They lived in an isolated community , and were selected because they had had no specific therapy for at least five years , and had had no previous treatment with psychotropic drugs of any kind . Pre caution s were taken to keep their environment constant , and medication was not started until the end of a six-month observation period , in which all the procedures of a therapeutic trial , including administration of placebo , were carried out . Only one patient out of 28 showed a definite therapeutic response . Analysis of ratings for the main psychopathological symptoms did not disclose any significant changes in the group as a whole . It is argued that the value of chlorpromazine in chronic schizophrenia has been accepted without sufficient evidence of the effect of the drug in different clinical states and the specific indications for its use . Further study of the clinical features of cases which do or do not respond to phenothiazines is required |
966 | 28,775,189 | All drugs were significantly more effective than placebo apart from sertraline , nefiracetam and fluoxetine .
After weighing the efficacy and acceptability , we conclude that paroxetine might be the best choice when starting acute treatment for PSD , and fluoxetine might be the worst choice . | OBJECTIVE The aim of this study is to create a rank order of the comparative efficacy and acceptability ( risk of all-cause discontinuation ) of antidepressant treatment in poststroke depression ( PSD ) by integrating direct and indirect evidence . | The impact of clinical ly diagnosed depression on recovery in activities of daily living over a 2-year follow-up was examined in a prospect i ve study of 63 stroke patients . Although impairment in activities of daily living , neurologic diagnoses and findings , lesion location and volume as measured on computed tomographic scan , demographic variables , cognitive impairment , and social functioning were comparable between depressed ( n = 25 ) and nondepressed ( n = 38 ) patients during their acute hospitalization , the two groups had different patterns of recovery in activities of daily living . At 2 years after suffering a stroke , patients with an in-hospital diagnosis of depression ( either major or minor depression ) were significantly more impaired in both physical activities and language functioning than were non-depressed patients . Among patients with major depression , this disparity in the recovery profile was present even after the depression had remitted . This study emphasizes the need for early recognition and treatment of poststroke depression The efficacy of nortriptyline in the treatment of post-stroke depression was assessed by a double-blind study in thirty-four patients . Half of the patients had major depression . There was a significantly greater improvement in depression in patients treated with nortriptyline than in a similar group of placebo-treated patients . Depression was measured by the Hamilton depression scale , Zung depression scale , present state examination , and an overall depression scale . Successfully treated patients had serum nortriptyline levels in the therapeutic range . Post-stroke depressions are common , severe , and longst and ing , and the demonstrated efficacy of nortriptyline provides an important addition to the treatments available for stroke patients The authors sought to determine the relative efficacy and tolerability of duloxetine versus citalopram and sertraline in the treatment of poststroke depression ( PSD ) , anxiety , and fatigue . A group of 60 patients with PSD were assigned to receive duloxetine , citalopram , or sertraline and were assessed over a 3-month period for depression , anxiety , and fatigue . Improvement of depression and anxiety , but not fatigue , was observed in all study groups . Duloxetine was well tolerated and significantly more effective than citalopram and sertraline for the treatment of anxiety symptoms in PSD patients . None of the antidepressants used was effective for reducing symptoms of fatigue BACKGROUND AND PURPOSE Patients with poststroke major depression have a greater severity of cognitive impairment than nondepressed patients even when matched for size and location of stroke lesion . Prior treatment studies have consistently failed to show an improvement in cognitive function even when poststroke mood disorders responded to antidepressant therapy . We examined the response of cognitive function to treatment with nortriptyline or placebo in a double-blind trial . METHODS Patients with major ( n=33 ) or minor ( n=14 ) depression participated in a double-blind treatment study with nortriptyline or placebo . They were examined for change in depressive mood , measured by the Hamilton Rating Scale for Depression ( HAM-D ) , and change in cognitive impairment , assessed by the Mini-Mental State Examination ( MMSE ) , after treatment with nortriptyline or placebo . Cognitive treatment response , as measured by the MMSE , was compared between patients whose depression did and did not respond to treatment . RESULTS Patients whose poststroke depression remitted ( predominantly associated with nortriptyline treatment ) had significantly greater recovery in cognitive function over the course of the treatment study than patients whose mood disorder did not remit ( predominantly associated with placebo treatment ) . CONCLUSIONS Our findings support the contention that poststroke major depression leads to a " dementia of depression . " Prior studies failed to show an effect of treatment because the effect size was too small . Successful treatment of depression may constitute one of the major methods of promoting cognitive recovery in victims of stroke BACKGROUND AND PURPOSE Early poststroke depression ( PSD ) is a frequent and specific entity that impairs the rehabilitation and functional recovery of hemiplegic patients . This trial was design ed to study the efficacy and tolerance of fluoxetine ( FLX ) in the treatment of early PSD . METHODS This was a multicenter , double-blind , placebo-controlled study . Recent hemiplegic patients ( <3 months ) suffering from major depressive disorder ( determined by International Classification of Diseases , 10th Revision , and Montgomery-Asberg Depression Rating Scale [ MADRS ] > 19 ) were r and omized to receive either 20 mg/d fluoxetine ( FLX ) or placebo for 6 weeks . Patients were evaluated by use of the Motricity Index , Mini-Mental State Examination , Functional Independence Measure , and MADRS . Statistical analysis was performed by using an intent-to-treat approach comparing the 2 groups at day 0 ( baseline ) and days 15 , 30 , and 45 ( end point ) . RESULTS Of 121 patients screened , 31 were included in the study , 16 in the FLX group and 15 in the placebo group . There were no significant differences in baseline characteristics among the 2 groups . The FLX-treated patients compared with placebo-treated patients demonstrated significant improvement in mean MADRS scores at end point ( 11.8+/-6 . 7 [ mean+/-SD ] versus 18.7+/-10.0 , respectively ; P=0.05 ) . FLX-treated patients compared with placebo-treated patients also demonstrated greater response rate ( 62.5 % versus 33.3 % , respectively ) and greater mean decrease of MADRS ( 16.6 versus 8.4 , respectively ; P=0.02 ) . There were no differences in motor , cognitive , or functional improvement and no significant side effects after FLX treatment , except for a patient with a moderate and transient increase of transaminases . CONCLUSIONS FLX is an efficacious and well-tolerated treatment for early PSD . Further research is needed to evaluate the efficacy and safety of long-term treatment in this population OBJECTIVE This study compared nortriptyline and fluoxetine with placebo in the treatment of depression and in recovery from physical and cognitive impairments after stroke . METHOD A total of 104 patients with acute stroke enrolled between 1991 and 1997 entered a double-blind r and omized study comparing nortriptyline , fluoxetine , and placebo over 12 weeks of treatment . The majority of patients were recruited from a rehabilitation hospital in Des Moines , Iowa , but other enrollment sites were also used . Both depressed and nondepressed patients were enrolled to determine whether improved recovery could be mediated by mechanisms unrelated to depression . Nortriptyline in doses of 25 mg/day gradually increased to 100 mg/day or fluoxetine in doses of 10 mg/day gradually increased to 40 mg/day or identical placebo were given over 12 weeks . Response to treatment of depression for individual patients was defined as a greater-than-50 % reduction in scores on the Hamilton Rating Scale for Depression and no longer fulfilling diagnostic criteria for major or minor depression . Improved recovery for a treatment group was defined as a significantly higher mean score from baseline to end of the treatment trial , compared with patients treated with placebo , on measures of impairment in activities of daily living and levels of cognitive and social functioning . RESULTS Nortriptyline produced a significantly higher response rate than fluoxetine or placebo in treating poststroke depression , in improving anxiety symptoms , and in improving recovery of activities of daily living as measured by the Functional Independence Measure . There was no effect of nortriptyline or fluoxetine on recovery of cognitive or social functioning among depressed or nondepressed patients . Fluoxetine in increasing doses of 10 - 40 mg/day led to an average weight loss of 15 . 1 pounds ( 8 % of initial body weight ) over 12 weeks of treatment that was not seen with nortriptyline or placebo . CONCLUSIONS Given the doses of medication used in this study , nortriptyline was superior to fluoxetine in the treatment of poststroke depression . Demonstrating a benefit of antidepressant treatment in recovery from stroke may require the identification of specific subgroups of patients , alternative measurement scales , or the optimal time of treatment OBJECTIVE Poststroke depression is a frequent psychiatric complication after stroke that may have strong negative impact on rehabilitation therapy and functional recovery . This study was conducted to show the efficacy and safety of early treatment with the selective serotonin reuptake inhibitor fluoxetine in post-stroke depressed patients . METHODS This double-blind , r and omized placebo-controlled study was of patients within two weeks after stroke . Moderate to severe depressed patients ( determined by Hamilton Depression Scale ( HDS ) > 15 , the Beck Depression Inventory ( BDI ) and the Clinical Global Impression ( CGI ) Scale ) were r and omized to receive either 20 mg/d fluoxetine or placebo for 3 months . Beside the psychiatric assessment , patients were evaluated by use of the Sc and inavian Stroke Scale ( SSS ) , the Mini-Mental-State-Examination ( MMSE ) and the Barthel-Index ( BI ) . An open-label long-term follow up was done 18 months after the initial assessment . RESULTS 54 depressed patients of an inpatient population of 242 consecutive stroke patients aged 25 to 85 years entered the trial within the first two weeks post-stroke . 50 patients completed the trial per- protocol . The initial severity of depression was comparable in the two groups ( mean baseline HDS score 32.8 in the fluoxetine vs. 30.3 in the placebo group ) , as were neurological symptom severity and demographic parameters . Significant improvement was seen in both groups within 4 weeks of treatment , whereas no advantages of fluoxetine could be observed at this time . This indicates a high degree of spontaneous recovery during early rehabilitation therapy . BDI scores of patients treated with fluoxetine further decreased until the follow-up at 12 weeks , whereas the scores increased again in the placebo group . This depressive relapse of the placebo patients after the end of most rehabilitation efforts was evident at a long-term follow-up 18 months after inclusion , when patients who had been treated with fluoxetine were significantly less depressed . No side effects of fluoxetine treatment were detected . CONCLUSIONS The advantages of fluoxetine were obvious at the follow-up 18 months after inclusion , but could not be demonstrated within the first three months of controlled treatment . The multitude of therapeutic efforts that take place in the early phase of rehabilitation might have facilitated spontaneous recovery from depression and might have hindered benefits of antidepressant treatment to become obvious . Fluoxetine treatment was well tolerated and safe Background and Purpose The aim of the study was to investigate the efficacy and safety of the selective serotonin reuptake inhibitor citalopram in treating poststroke depression , since available treatments are usually poorly tolerated . Methods A 6-week double-blind , placebo-controlled trial was undertaken . Diagnosis and outcome were determined using the Hamilton Depression Scale , and unwanted effects were measured using the UKU side effect rating scale . Sixtysix consecutive depressed patients from an unselected population of 285 stroke patients aged 25 to 80 years entered the trial 2 to 52 weeks after stroke . They were assigned to equally sized treatment and placebo groups . The initial level of depression was comparable in the two groups ( mean baseline Hamilton Depression scores , 19.4 and 18.9 , respectively ) . Demographic parameters were also comparable in the two groups . Results Significantly greater improvement was seen in patients treated with citalopram ( 10 to 40 mg/d ) for 3 and 6 weeks , both when including all patients ( intention-to-treat analysis , p<.05 ) and excluding patients who dropped out during the first 3 weeks ( efficacy analysis , P<.005 ) . Half of the 28 patients who entered the trial 2 to 6 weeks after stroke recovered within 1 month , independent of the treatment given . This indicates a high degree of spontaneous recovery in the early phase after stroke . In contrast , recovery was infrequent in placebo group patients who became depressed 7 weeks or more after stroke . No serious side effects related to the treatment were detected ; those present were mild and usually transient . Conclusions This trial demonstrates that the selective serotonin reuptake inhibitor citalopram offers an advantageous new treatment of poststroke depression that is both safe and effective The incidence of depression following a hemispheric stroke ranges from 25 to 60 % . The benefit of antidepressant therapy on the outcome of rehabilitation in the subacute post-stroke phase is well known . We studied subjects both with and without evidence of depression , as indicated by any one of three criteria : ( i ) Clinical diagnosis of depression , ( ii ) Abnormal Zung-depression score . ( iii ) Abnormal dexamethasone suppression test ( DST ) . Patients in a stroke rehabilitation program ( 22 ) were r and omized to receive either placebo or 300 mg/day trazodone-HCl , beginning 30 days after the stroke . Patients with either a clinical diagnosis of depression or abnormal Zung depression scores showed a consistent trend towards greater improvement in Barthel activities of daily living ( ADL ) scores , with antidepressant therapy , as compared to patients receiving placebo . An abnormal DST was associated with significant improvement in the ADL scores in subjects receiving trazodone , i.e. , in post-stroke depression such a treatment seems to be beneficial BACKGROUND Poststroke depression is a frequent condition and important to treat . The aim of this trial was to study the efficacy and tolerability of sertraline . METHOD In 4 Swedish stroke centers , 123 patients ( aged 70.7 + /- 9.9 years ) were enrolled during the period September 1998 to January 2001 in a r and omized , double-blind , placebo-controlled 26-week trial , at a mean of 128 + /- 97 days ( range , 3 - 375 days ) after stroke , if they fulfilled DSM-IV criteria of major depressive episode ( N = 76 ) or minor depressive disorder ( N = 47 ) . The primary efficacy variable was a change in depression assessed by the Montgomery-Asberg Depression Rating Scale . The Emotional Distress Scale ( EDS ) was administered and the occurrence of emotionalism and quality of life ( QoL ) were assessed , as well as neurologic recovery . Efficacy analyses were intention-to-treat , short-term ( week 6 ) and long-term ( week 26 ) . RESULTS Of the 123 patients , 62 were treated with sertraline ( 50 - 100 mg/day ) and 61 with placebo . Both groups improved substantially , with no differences between the treatments , either for major depressive episode or minor depressive disorder , or for short- or long-term antidepressant effect and neurologic outcome . EDS revealed a better outcome with sertraline at week 6 ( p < .05 ) . At week 26 , the improvement in QoL was better in sertraline patients ( p < .05 ) and there was a trend for emotionalism ( p = .07 ) . No serious side effects were seen . CONCLUSION Poststroke depression as measured by a conventional depression rating scale improved over time irrespective of treatment . Positive effects specific to sertraline were identified in emotional distress , emotionalism , and QoL. The study indicates that poststroke emotional reactions comprise depression and other domains susceptible to pharmacologic therapy In a double-blind , placebo-controlled study , the therapeutic efficacy of two antidepressants with different neurochemical mechanisms of action , amitriptyline and amineptine , was investigated in patients affected by anxious depression . Sixty-six patients with the primary diagnosis of major depression or bipolar affective disorder ( DSM-III-R ) and meeting additional operational clinical criteria such as anxiety , trepidation , restlessness , early and /or late insomnia , impulsivity , hostility , dysphoria , compulsivity , hyperperspiration , palpitation , pollakiuria and phobias were included . They were r and omly assigned to three groups ( n = 22 ) and treated either with placebo , amitriptyline ( up to 100 mg/day ) or amineptine ( up to 200 mg/day ) for 6 weeks . Patients showed better response to amitriptyline , a preferential inhibitor of serotonin reuptake , than to amineptine , a selective inhibitor of dopamine reuptake . The present results suggest that alterations in serotonergic rather than dopaminergic transmission contribute to the pathophysiology of anxious depression Depression occurs frequently in post-stroke patients and appears to be associated with an impairment in their rehabilitation and functional recovery . Although selective serotonin reuptake inhibitors ( SSRI ) are often used in post-stroke depression ( PSD ) , it has been observed that only a subset of patients is responsive to this treatment . Other patients respond to tricyclic antidepressants or MAO inhibitors , which , however , may not have a favorable profile of safety and tolerability in post-stroke patients . In this double-blinded , placebo-controlled study , we evaluated the efficacy and tolerability of the noradrenaline reuptake inhibitor , reboxetine , in a subset of PSD patients classified as affected by " retarded " depression . Reboxetine ( 4 mg , twice daily , for 16 weeks ) was administered to patients that developed depression after a single ischaemic or hemorrhagic stroke . We assessed the severity of depressive symptoms by the Beck Depression Inventory ( BDI ) and Hamilton Depression Rating Scale ( HDRS ) . HDRS and BDI scores ( mean+/-S.D. ) at baseline were , respectively , 24+/-1.31 and 19.87+/-1.46 in the placebo group , 24.06+/-1.52 and 20.56+/-2.16 in the reboxetine group . After 16 weeks , HDRS and BDI mean scores were respectively 22.73+/-2.4 and 18.4+/-3.33 in the placebo group , 9.26+/-2.15 and 8.06+/-3.43 in the reboxetine group [ p<0.01 versus the respective baseline ( paired t-test ) ; (#)p<0.01 versus retarded depressed patients treated with placebo ( one-way analysis of variance ( ANOVA ) applied to the difference from baseline , associated with Dunnett 's t-test to isolate the differences ) ] . Reboxetine showed a good efficacy , safety and tolerability in PSD patients affected by " retarded " depression . We conclude that reboxetine is well tolerated and may be a useful therapeutic option in PSD patients with " retarded " depression We assessed the therapeutical efficacy of various antidepressants ( amineptine , minaprine and clomipramine ) in patients affected by retarded depression . All patients exhibited symptoms of retardation , including hypokinesia , anergia , reduction of speech , increased salivation , hypersomnia , Parinaud 's syndrome , reduced sexual activity , slowness , hypomimia , orthostatic hypotension , dysphagia and drowsiness . Antidepressant drugs were administered for a 6‐week period in a r and omized double‐blind vs placebo design . The rank order of clinical effectiveness ( amineptine > > minaprine > clomipramine > placebo ) paralleled the specificity of antidepressants as dopaminomimetic agents . These results support the view that a reduced dopaminergic transmission contributes to the pathophysiology of retarded depression |
967 | 19,236,609 | Data from 958 patients in 4 trials , recruiting between 1972 and 1984 , showed that addition of an anthracycline reduced bone marrow relapse and , non-significantly , non-bone marrow relapse , result ing in an increased relapse-free interval .
The limited data from trials did not demonstrate differences in clinical ly evident cardiotoxicity .
Anthracyclines are effective against bone marrow relapse but have not been shown to significantly increase event free survival in childhood ALL . | Anthracyclines are used to treat childhood acute lymphoblastic leukaemia ( ALL ) but non-r and omized studies suggest that cardiotoxicity may be a problem . | Fifty-six untreated patients with childhood with acute lymphoblastic leukemia ( ALL ) were r and omized to receive one of three remission induction regimens : vincristine and prednisone ( VP ) , vincristine , prednisone and daunorubicin ( VPD ) , or vincristine , prednisone and adriamycin ( VPA ) . The complete remission rate was similar for all three groups . Although the anthracycline regimens caused somewhat more rapid leukemic cell reduction than the VP only group , this difference was not significant . Labeling index reduction between study days 1 and 5 was significantly greater ( p less than 0.001 ) with an anthracycline than for the VP group , but there was no difference between the two anthracyclines . Granulocytopenia during induction was significantly increased ( p less than 0.05 ) in both the VPD and VPA groups as compared with VP alone . A significantly higher rate of infectious morbidity ( p less than 0.01 ) was associated with the addition of either anthracycline , but to date no significant differences in remission duration or survival have been observed . The addition of anthracyclines to VP for remission induction in childhood ALL has theoretical advantages , but may be undesirable because of increased morbidity Two groups of children with acute lymphoblastic leukemia or non-Hodgkin lymphoma , treated with anthracyclines ( ANT ) , were studied : group I , consisting of 10 patients , with coenzyme Q10 ( CoQ ) therapy ; group II , consisting of 10 patients without CoQ therapy . The ANT cumulative dose was 240 + /- 20.0 mg/m2 in group I and 252.0 + /- 20.1 mg/m2 in group II . Echocardiographic study was performed at the beginning , at the cumulative dose of 180 mg/m2 and at the end of therapy with ANT . Percentage left ventricular fractional shortening ( % LVFS ) decreased from baseline ( 40.36 + /- 4.6 ) to end value ( 35.82 + /- 5.02 ) ( P < 0.05 ) in group I ; % LVFS decreased from baseline ( 39.89 + /- 4.37 ) to end value ( 33.43 + /- 3.46 ) ( P < 0.002 ) in group II . Interventricular septum wall thickening decreased only in group II from baseline ( 46.10 + /- 10.1 ) to end therapy ( 27.00 + /- 18.54 ) ( P < 0.01 ) . Septum wall motion abnormalities were detected only in 2 patients of group II . These data demonstrate a protective effect of CoQ on cardiac function during therapy with ANT The Dana-Farber Cancer Institute ( DFCI ) acute lymphoblastic leukemia ( ALL ) Consortium Protocol 91 - 01 was design ed to improve the outcome of children with newly diagnosed ALL while minimizing toxicity . Compared with prior protocol s , post-remission therapy was intensified by substituting dexamethasone for prednisone and prolonging the asparaginase intensification from 20 to 30 weeks . Between 1991 and 1995 , 377 patients ( age , 0 - 18 years ) were enrolled ; 137 patients were considered st and ard risk ( SR ) , and 240 patients were high risk ( HR ) . Following a 5.0-year median follow-up , the estimated 5-year event-free survival ( EFS ) + /- SE for all patients was 83 % + /- 2 % , which is superior to prior DFCI ALL Consortium protocol s conducted between 1981 and 1991 ( P = .03 ) . There was no significant difference in 5-year EFS based upon risk group ( 87 % + /- 3 % for SR and 81 % + /- 3 % for HR , P = .24 ) . Age at diagnosis was a statistically significant prognostic factor ( P = .03 ) , with inferior outcomes observed in infants and children 9 years or older . Patients who tolerated 25 or fewer weeks of asparaginase had a significantly worse outcome than those who received at least 26 weeks of asparaginase ( P < .01 , both univariate and multivariate ) . Older children ( at least 9 years of age ) were significantly more likely to have tolerated 25 or fewer weeks of asparaginase ( P < .01 ) . Treatment on Protocol 91 - 01 significantly improved the outcome of children with ALL , perhaps due to the prolonged asparaginase intensification and /or the use of dexamethasone . The inferior outcome of older children may be due , in part , to increased intolerance of intensive therapy BACKGROUND Doxorubicin chemotherapy is very effective in children with acute lymphoblastic leukemia ( ALL ) but also injures myocardial cells . Dexrazoxane , a free-radical scavenger , may protect the heart from doxorubicin-associated damage . METHODS To determine whether dexrazoxane decreases doxorubicin-associated injury of cardiomyocytes , we r and omly assigned 101 children with ALL to receive doxorubicin alone ( 30 mg per square meter of body-surface area every three weeks for 10 doses ) and 105 to receive dexrazoxane ( 300 mg per square meter ) followed immediately by doxorubicin . Serial measurements of serum cardiac troponin T were obtained in 76 of 101 patients in the doxorubicin group and 82 of 105 patients in the group given dexrazoxane and doxorubicin . A total of 2377 serum sample s ( mean , 15.1 sample s per patient ) were obtained before , during , and after treatment with doxorubicin . Troponin T levels were evaluated in a blinded fashion to determine whether they were elevated ( > 0.01 ng per milliliter)--the primary end point -- or extremely elevated ( > 0.025 ng per milliliter ) . RESULTS Elevations of troponin T occurred in 35 percent of the patients ( 55 of 158 ) . Patients treated with doxorubicin alone were more likely than those who received dexrazoxane and doxorubicin to have elevated troponin T levels ( 50 percent vs. 21 percent , P<0.001 ) and extremely elevated troponin T levels ( 32 percent vs. 10 percent , P<0.001 ) . The median follow-up was 2.7 years . The rate of event-free survival at 2.5 years was 83 percent in both groups ( P=0.87 by the log-rank test ) . CONCLUSIONS Dexrazoxane prevents or reduces cardiac injury , as reflected by elevations in troponin T , that is associated with the use of doxorubicin for childhood ALL without compromising the antileukemic efficacy of doxorubicin . Longer follow-up will be necessary to determine the influence of dexrazoxane on echocardiographic findings at four years and on event-free survival Summary During the 1970s , despite apparently similar treatment , the prognosis for children with lymphoblastic leukaemia ( ALL ) improved more in some countries , notably the United States and West Germany , than in others . To find out why , the first phase of the United Kingdom ( UK ) Medical Research Council ( MRC ) childhood ALL trial , UKALL VIII , was design ed to see whether similar results to the United States Children 's Cancer Study Group ( CCSG ) could be obtained in the U.K. using an identical protocol ( CCG 162 ) . Protocol 162 was one of a series of regimens devised by the American Children 's Cancer Study Group in the 1970s and was used specifically for their average risk patients ( all children with ALL with an initial white cell count up to 50 × 109/l except those aged 3–6 years with white cell counts under 10 × 109/l ) . One arm ( 1A ) of their study was adopted by the MRC for all children in the U.K. aged 0–14 years with confirmed ALL PURPOSE Acute doxorubicin-induced cardiotoxicity can be prevented in adults by continuous infusion of the drug , but mechanisms of cardiotoxicity are different in children . We compared cardiac outcomes in children receiving bolus or continuous infusion of doxorubicin . PATIENTS AND METHODS In a r and omized study , children with high-risk acute lymphoblastic leukemia received doxorubicin 360 mg/m(2 ) in 30-mg/m(2 ) doses every 3 weeks either by bolus ( within 1 hour , n = 57 ) or by continuous infusion ( over 48 hours , n = 64 ) . Echocardiograms obtained before doxorubicin and at longest follow-up times were central ly remeasured , and z scores of cardiac measurements were calculated based on a healthy population . RESULTS The groups were similar in age , sex distribution , doxorubicin dose , and duration of follow-up . Before treatment , measures of left ventricular ( LV ) structure and function did not reveal dilated cardiomyopathy and were not statistically different between bolus and continuous-infusion groups . The follow-up echocardiograms demonstrated no significant difference between the two groups for any cardiac characteristic , but both groups showed significant abnormalities of LV structure and function compared with normal and with baseline . For example , the mean LV fractional shortening fell by approximately two SD in both groups between the two echocardiograms . LV contractility was depressed in both groups ( for bolus patients , median z score = -0.70 SD , P = .006 ; for continuous-infusion patients , median z score = -0.765 , P = .005 ) . Dilated cardiomyopathy and inadequate LV hypertrophy were noted in both groups . Clinical cardiac manifestations and event-free survival did not differ . CONCLUSION Continuous doxorubicin infusion over 48 hours for childhood leukemia did not offer a cardioprotective advantage over bolus infusion . Both regimens were associated with progressive sub clinical cardiotoxicity . Other cardioprotective strategies should be explored BACKGROUND Daunorubicin ( DNR ) is one of the most important drugs in treatment of acute lymphoblastic leukemia ( ALL ) . Prolonged infusions of anthracyclines are less cardiotoxic but it has not been investigated whether the in vivo leukemic cell kill is equivalent to short-term infusions . PROCEDURE In the cooperative treatment study COALL-92 for childhood ALL 178 patients were r and omized to receive in a therapeutic window a single dose of 36 mg/m ( 2 ) DNR either as a 1-h ( 85 patients ) or 24-h infusion ( 93 patients ) . Daily measurements of white blood cell count ( WBC ) and peripheral blood smears for seven days could be evaluated central ly in 101 patients ( 1-h : 43 patients , 24-h : 58 patients ) . RESULTS The proportional decline of blasts at day 7 after DNR infusion showed no statistically significant difference between the two treatment arms . At day 3 the median percentage of blasts was less than 10 % , at day 7 less than 2 % for either the 1-h or 24-h infusion . Twelve patients ( 1-h : 5 patients , 24-h : 7 patients ) had an absolute number of more than 1000 blasts per mul peripheral blood ( PB ) at day 7 after DNR infusion ( DNR poor responders ) . Kaplan-Meier analysis showed an equal probability of EFS for the short- and long-term infusion group ( 24-h : 83%+/-5 ; 1-h : 81+/-6 ) after a median observation time of 12.3 years . CONCLUSIONS We conclude that in children with ALL a 24-h infusion of DNR has the same in vivo cytotoxicity for leukemic cells as a 1-h infusion . This offers the possibility to use prolonged infusions with hopefully less cardiotoxicity without loss of efficacy Background . Improved survival of children with acute lymphoblastic leukemia ( ALL ) has made it more difficult to develop new protocol s to further improve results . The authors report the pilot experience with the Memorial Sloan‐Kettering‐New York‐II ( MSK‐NY‐II ) protocol , based on the New York regimen with changes made in an attempt to improve efficacy while reducing toxicity PURPOSE Dexrazoxane is a drug used to prevent anthracycline-induced cardiotoxicity . A recent report found an association between the use of dexrazoxane and the risk of developing secondary malignant neoplasms ( SMNs ) in children with Hodgkin 's disease . We report the absence of an association of SMNs in children with acute lymphoblastic leukemia ( ALL ) treated on Dana-Farber Cancer Institute ALL Consortium Protocol 95 - 01 . PATIENTS AND METHODS Two hundred five children with high-risk ( HR ) ALL were r and omly assigned to receive doxorubicin alone ( n = 100 ) or doxorubicin with dexrazoxane ( n = 105 ) during the induction and intensification phases of multiagent chemotherapy . We compared incidence of SMNs in these two groups . RESULTS With a median follow-up of 6.2 years , no differences in the incidence of SMNs were noted between the group that received dexrazoxane and the group that did not ( P = .66 ) . One SMN ( a melanoma located outside of the cranial radiation field ) occurred in a patient who was r and omly assigned to doxorubicin alone . No SMNs were observed in patients r and omly assigned to receive dexrazoxane . CONCLUSION Dexrazoxane was not associated with an increased risk of SMNs in children treated for HR ALL . Given the potential importance of dexrazoxane as a cardioprotectant , we recommend that dexrazoxane continue to be used and studied in doxorubicin-containing pediatric regimens The Dutch Childhood Leukemia Study Group ( DCLSG ) performed a phase III study - Study ( ALL ) V-to evaluate the effectiveness of rubidomycin in induction therapy with vincristine , prednisone , and L-asparaginase for children ( 0 - 15 years ) with st and ard risk acute lymphoblastic leukemia ( ALL ) ( white blood cell [ WBC ] counts less than 50.10(9)/L , absence of mediastinal mass , and /or cerebromeningeal leukemia ) . Furthermore , the influence of initial patient and disease characteristics on the outcome was analyzed . Between May 1979 and December 1982 , 240 patients entered the study and were r and omized into two groups : group A ( n = 122 ) received induction treatment with vincristine ( VCR ) , prednisone ( Pred ) , and L-asparaginase ( L-Asp ) ; for group B ( n = 118 ) , induction therapy consisted of VCR , Pred , L-Asp , and rubidomycin ( Rub ) . All patients subsequently underwent cranial irradiation ( doses adjusted to age ) in combination with intrathecal methotrexate ; maintenance therapy of 6-mercaptopurine and methotrexate for 5 weeks followed by vincristine and prednisone for 2 weeks was given for 24 months . The complete remission ( CR ) rate was similar in both groups ( 94.5 % ) . Event-free survival ( EFS ) 5 years after diagnosis was higher in group B ( 62.5 + /- 4.5 % ) than in group A ( 54.7 + /- 4.5 % ) , although the difference is not significant ( p = 0.20 ) . A high initial WBC ( greater than or equal to 10.10(9)/L ) , age ( greater than or equal to 10 years ) , a low platelet count ( less than 100.10(9)/L ) , and a positive acid phosphatase reaction of the leukemic cells were unfavorable prognostic factors ( p less than 0.05 ) . Sex , French-American-British ( FAB ) classification group , immunophenotype , and treatment in specialized centers did not have a significant impact on event-free survival Doxorubicin or daunorubicin are routinely used to induce remission in acute lymphoblastic leukemia ( ALL ) . Efficacy of epirubicin ( an analog of doxorubicin ) , however , has not been adequately evaluated in ALL management . This r and omized study was undertaken to compare the relative efficacy of epirubicin vs. doxorubicin as part of induction chemotherapy in adult ALL . Between January 1990 and June 1998 , 79 previously untreated adult ALL patients ( age 11–55 years , median 20 years ) were r and omized to receive either doxorubicin ( Group A , n = 39 ) or epirubicin ( Group B , n = 40 ) as a part of induction therapy . Vincristine and prednisolone were common in each group . The induction treatment was followed by identical consolidation and maintenance therapy . The two groups were compared as regards pretherapy clinical and laboratory parameters , dose intensity of therapy , therapeutic efficacy , myelotoxicity , and survival . Epirubicin was as effective as doxorubicin in terms of complete remission rate ( 80 % vs. 78.3 % ; P = 0.87 ) and relapse rate ( 57.1 % vs. 51.7 % ; P = 0.68 ) . Five‐year overall survival ( 30 % vs. 30 % , P = 0.98 ) and disease‐free survival ( 40 % vs. 39 % , P = 0.92 ) at median follow‐up of 68 months was also similar in the two groups . The incidence of Grade 4 myelotoxicity was comparable in the two groups . Patients 20 years of age or less had better CR rates ( 90 % vs. 65 % ; P = 0.011 ) and median overall survival ( 39 vs. 11 months ; P = 0.008 ) compared to those who were older . From this study epirubicin appears as effective as doxorubicin as part of induction therapy for adult ALL . However , the results need to be vali date d on the basis of immunophenotype and cytogenetic prognostic characterization . Am . J. Hematol . 71:241–247 , 2002 . © 2002 Wiley‐Liss , |
968 | 17,574,803 | Three types of interventions ( group counseling , contingency management , and residential dual diagnosis treatment ) show consistent positive effects on substance use disorder , whereas other interventions have significant impacts on other areas of adjustment ( e.g. , case management enhances community tenure and legal interventions increase treatment participation ) . | This report review s studies of psychosocial interventions for people with co-occurring substance use disorder and severe mental illness . | We recently concluded the third decade of large-scale public funding for community-based drug abuse treatment in the United States . Over these years , basic and applied research in this arena has been carried out and reported at an unprecedented rate , based in part on the requirements of federal agencies to evaluate the effectiveness of our national drug abuse treatment system . Beginning in the early 1970s with the Drug Abuse Reporting Program ( DARP ) , followed by the Treatment Outcome Prospect i ve Study ( TOPS ) a decade later , and continuing through the 1990s with the Drug Abuse Treatment Outcome Studies ( DATOS ) , national evaluations have examined over 65,000 admissions to 272 treatment programs using multimodality and multisite sampling plans that allow the study of treatment in natural setting s. These national projects comprise only part of the large body of evidence accumulated over the past 30 years that supports the general effectiveness of drug treatment.1 - Integrated mental health and substance abuse treatment within an assertive community treatment ( ACT ) approach was compared to that within a st and ard case management approach for 223 patients with dual disorders over three years . ACT patients showed greater improvements on some measures of substance abuse and quality of life , but the groups were equivalent on most measures , including stable community days , hospital days , psychiatric symptoms , and remission of substance use disorder Jail recidivists with serious mental illness and substance use disorders were treated in an in-custody setting and then r and omly assigned to either a high fidelity Integrated Dual Disorders Treatment program ( 103 participants ) or to service as usual ( 79 participants ) . Outcomes were tracked an average of 18 months from program entry at the termination of the initial incarceration . A reduction in jail days from baseline to study period was significant for both groups . The pre to post reduction for arrests and total convictions was significant in the experimental group but not the control group . However , during the study period , differences between experimental and control groups in arrests , convictions and jail days were not statistically significant . Experimental participants had lower study period psychiatric inpatient and crisis utilization and greater outpatient utilization than did control group participants . The groups did not differ with regard to total institutional days . Experimental group attrition was relatively high BACKGROUND Few r and omised controlled trials have been aim ed specifically at substance use reduction among people with psychotic disorders . AIMS To investigate whether a 10-session intervention consisting of motivational interviewing and cognitive-behavioural therapy ( CBT ) was more efficacious than routine treatment in reducing substance use and improving symptomatology and general functioning . METHOD A community sample of people with a psychotic disorder and who reported hazardous alcohol , cannabis and /or amphetamine use during the preceding month was recruited . Participants were r and omly allocated to motivational interviewing/CBT ( n = 65 ) or treatment as usual ( n = 65 ) , and were assessed on multiple outcomes at baseline , 15 weeks , 6 months and 12 months . RESULTS There was a short-term improvement in depression and a similar trend with regard to cannabis use among participants who received the motivational interviewing/CBT intervention , together with effects on general functioning at 12 months . There was no differential benefit of the intervention on substance use at 12 months , except for a potentially clinical ly important effect on amphetamine use . CONCLUSIONS The motivational interviewing/CBT intervention was associated with modest improvements This study evaluated the efficacy of adding contingency management techniques to vocational rehabilitation ( VR ) to improve treatment outcome as measured by entry into competitive employment . Nineteen dually diagnosed veterans who entered VR in the Veterans ' Administration 's compensated work therapy ( CWT ) program were r and omly assigned to CWT ( n = 8) or to CWT with enhanced incentives ( n = 11 ) . Over the first 16 weeks of rehabilitation , those in the incentives condition could earn up to dollar 1,006 in cash for meeting two sets of clinical goals : ( a ) remaining abstinent from drugs and alcohol and ( b ) taking steps to obtain and maintain a competitive job . Results indicate that relative to participants in the CWT-only group , those in the incentives condition engaged in more job- search activities , were more likely to remain abstinent from drugs and alcohol , were more likely to obtain competitive employment , and earned an average of 68 % more in wages . These results suggest that rehabilitation outcomes may be enhanced by restructuring traditional work-for-pay contingencies to include direct financial rewards for meeting clinical goals This study examined the effects of integrating mental health , substance abuse , and housing interventions for homeless persons with co-occurring severe mental illness and substance use disorder . With the use of a quasi-experimental design , integrated treatment was compared with st and ard treatment for 217 homeless , dually diagnosed adults over an 18-month period . The integrated treatment group had fewer institutional days and more days in stable housing , made more progress toward recovery from substance abuse , and showed greater improvement of alcohol use disorders than the st and ard treatment group . Abuse of drugs other than alcohol ( primarily cocaine ) improved similarly for both groups . Secondary outcomes , such as psychiatric symptoms , functional status , and quality of life , also improved for both groups , with minimal group differences favoring integrated treatment In adaptive treatment strategies , the treatment level and type is repeatedly adjusted according to ongoing individual response . Since past treatment may have delayed effects , the development of these treatment strategies is challenging . This paper advocates the use of sequential multiple assignment r and omized trials in the development of adaptive treatment strategies . Both a simple ad hoc method for ascertaining sample sizes and simple analysis methods are provided OBJECTIVE Comorbidity of substance abuse disorders with schizophrenia is associated with a greater risk for serious illness complications and poorer outcome . Method ologically sound studies investigating treatment approaches for patients with these disorders are rare , although recommendations for integrated and comprehensive treatment programs abound . This study investigates the relative benefit of adding an integrated psychological and psychosocial treatment program to routine psychiatric care for patients with schizophrenia and substance use disorders . METHOD The authors conducted a r and omized , single-blind controlled comparison of routine care with a program of routine care integrated with motivational interviewing , cognitive behavior therapy , and family or caregiver intervention . RESULTS The integrated treatment program result ed in significantly greater improvement in patients ' general functioning than routine care alone at the end of treatment and 12 months after the beginning of the study . Other benefits of the program included a reduction in positive symptoms and in symptom exacerbations and an increase in the percent of days of abstinence from drugs or alcohol over the 12-month period from baseline to follow-up . CONCLUSIONS These findings demonstrate the effectiveness of a program of routine care integrated with motivational interviewing , cognitive behavior therapy , and family intervention over routine psychiatric care alone for patients with comorbid schizophrenia and alcohol or drug abuse or dependence OBJECTIVES The feasibility and effectiveness of treating homeless mentally ill chemical abusers in community residences compared with a therapeutic community were evaluated . METHODS A total of 694 homeless mentally ill chemical abusers were r and omly referred to two community residences or a therapeutic community . All programs were enhanced to treat persons with dual diagnoses . Subjects ' attrition , substance use , and psychopathology were measured at two , six , and 12 months . RESULTS Forty-two percent of the 694 referred subjects were admitted to their assigned program and showed up for treatment , and 13 percent completed 12 months or more . Clients retained at both types of program showed reductions in substance use and psychopathology , but reductions were greater at the therapeutic community . Compared with subjects in the community residences , those in the therapeutic community were more likely to be drug free , as measured by urine analysis and self-reports , and showed greater improvement in psychiatric symptoms , as measured by the Center for Epidemiological Studies --Depression Scale and the Brief Psychiatric Rating Scale . Their functioning also improved , as measured by the Global Assessment of Functioning scale . CONCLUSIONS Homeless mentally ill chemical abusers who are retained in community-based residential programs , especially in therapeutic communities , can be successfully treated Homeless adults with both a serious mental illness and substance dependence ( N = 276 ) were r and omly assigned to : ( 1 ) a social model residential program providing integrated mental health and substance abuse treatment ; ( 2 ) a community-based nonresidential program using the same social model approach ; or ( 3 ) a control group receiving no intervention but free to access other community services . Interventions were design ed to provide 3 months of intensive treatment , followed by 3 months of nonresidential maintenance . Subjects completed baseline interviews prior to r and omization and reinterviews 3 , 6 , and 9 months later . Results showed that , while substance use , mental health , and housing outcomes improved from baseline , subjects assigned to treatment conditions differed little from control subjects . Examination of the relationship between length of treatment exposure and outcomes suggested that residential treatment had positive effects on outcomes at 3 months , but that these effects were eroded by 6 months BACKGROUND There is a well-recognized association between substance use and psychotic disorders , sometimes described as ' dual diagnosis ' . The use of substances by people with psychosis has a negative impact in terms of symptoms , longitudinal course of illness and psychosocial adjustment . There are few vali date d treatments for such individuals , and those that do exist are usually impracticable in routine clinical setting s. The present study employs a r and omized controlled experimental design to examine the effectiveness of a manualized group-based intervention in helping patients with dual diagnosis reduce their substance use . METHOD The active intervention consisted of weekly 90-min sessions over 6 weeks . The manualized intervention was tailored to participants ' stage of change and motivations for drug use . The control condition was a single educational session . RESULTS Sixty-three subjects participated , of whom 58 ( 92 % ) completed a 3-month follow-up assessment of psychopathology , medication and substance use . Significant reductions in favour of the treatment condition were observed for psychopathology , chlorpromazine equivalent dose of antipsychotics , alcohol and illicit substance use , severity of dependence and hospitalization . CONCLUSIONS It is possible to reduce substance use in individuals with psychotic disorders , using a targeted group-based approach . This has important implication s for clinicians who wish to improve the long-term outcome of their patients The effect of motivational interviewing on outpatient treatment adherence among psychiatric and dually diagnosed in patients was investigated . Subjects were 121 psychiatric in patients , 93 ( 77 % ) of whom had concomitant substance abuse/dependence disorders , who were r and omly assigned to : a ) st and ard treatment ( ST ) , including pharmacotherapy , individual and group psychotherapy , activities therapy , milieu treatment , and discharge planning ; or b ) ST plus motivational interviewing ( ST+MI ) , which involved 15 minutes of feedback on the results of a motivational assessment early in the hospitalization , and a 1-hour motivational interview just before discharge . Interviewers utilized motivational techniques described in Miller and Rollnick ( 1991 ) , such as reflective listening , discussion of treatment obstacles , and elicitation of motivational statements . Results indicated that the proportion of patients who attended their first outpatient appointment was significantly higher for the ST+MI group ( 47 % ) than for the ST group ( 21 % ; chi2 = 8.87 , df = 1 , p<.01 ) overall , and for dually diagnosed patients ( 42 % for ST+MI vs. 16 % for ST only ; chi2 = 7.68 , df = 1 , p<.01 ) . Therefore , brief motivational interventions show promise in improving outpatient treatment adherence among psychiatric and dually diagnosed patients OBJECTIVE Clients with co-occurring severe mental and substance use disorders are at high risk of institutionalization and other adverse outcomes . Although integrated mental health and substance abuse treatment is becoming a st and ard clinical approach for such clients , the optimal method for delivering integrated treatment remains unclear . METHOD This study compared integrated treatment delivered within two different models of community-based case management ( assertive community treatment and st and ard clinical case management ) . A total of 198 clients in two urban sites who had co-occurring disorders and were homeless or unstably housed were r and omly assigned to one of two treatment conditions and were followed for three years . RESULTS Participants in both treatment conditions improved over time in multiple outcome domains , and few differences were found between the two models . Decreases in substance use were greater than would be expected given time alone . At the site that had higher rates of institutionalization , clients who received st and ard case management were more likely to be institutionalized . However , in the site that had lower rates of institutionalization , no differences in the rate of institutionalization were found between the two treatment conditions . CONCLUSIONS Integrated treatment can be successfully delivered either by assertive community treatment or by st and ard clinical case management OBJECTIVE Uncertainty regarding the degree to which persons with schizophrenia may lack decision-making capacity , and what the predictors of capacity may be led us to examine the relationship between psychopathology , neurocognitive functioning , and decision-making capacity in a large sample of persons with schizophrenia at entry into a clinical trial . METHOD In the Clinical Antipsychotic Trials of Intervention Effectiveness ( CATIE ) schizophrenia trial , a clinical trial sponsored by the National Institute of Mental Health design ed to compare the effectiveness of antipsychotic drugs , subjects were administered the MacArthur Competence Assessment Tool- Clinical Research ( MacCAT-CR ) and had to demonstrate adequate decision-making capacity before r and omization . The MacCAT-CR , the Positive and Negative Syndrome Scale ( PANSS ) , and an extensive neurocognitive battery were completed for 1447 study participants . RESULTS The neurocognitive composite score and all 5 neurocognitive subscores ( verbal memory , vigilance , processing speed , reasoning , and working memory ) were positive correlates of the MacCAT-CR underst and ing , appreciation , and reasoning scales at baseline . Higher levels of negative symptoms , but not positive symptoms , were inversely correlated with these three MacCAT-CR scales . Linear regression models of all three MacCAT-CR scales identified working memory as a predictor ; negative symptoms made a small contribution to the underst and ing and appreciation scores . CONCLUSIONS Negative symptoms and aspects of neurocognitive functioning were correlated with decision-making capacity in this large sample of moderately ill subjects with schizophrenia . In multiple regression models predicting performance on the MacCAT-CR scales , working memory was the only consistent predictor of the components of decision-making capacity . Individuals with schizophrenia who have prominent cognitive dysfunction , especially memory impairment , may warrant particular attention when participating in research Thirty subjects with comorbid schizophrenia and alcohol use disorders were r and omly assigned to receive either a Motivational Interviewing ( MI ) or Educational Treatment ( ET ) intervention with treatment goals of abstinence and /or decreased alcohol use . Subjects were followed up at 4 , 8 and 24-weeks upon completion of the interventions . Outcome measures included number of drinking days , abstinence rates , average blood alcohol concentration and st and ard ethanol content per drinking day . Subjects r and omized to the MI intervention had a significant reduction in drinking days and an increase in abstinence rates when compared to subjects receiving ET . Motivational Interviewing may be a useful treatment intervention for individuals with schizophrenia and alcoholism BACKGROUND People with severe mental illness and substance use disorders ( dual disorder ) often have considerable contact with the criminal justice system . AIMS To test the effects of client characteristics on six criminal justice outcomes among homeless ( at intake ) people with mental illness and substance misuse disorders . METHODS The sample was of participants in a r and omized controlled trial comparing st and ard treatment , assertive community treatment ( ACT ) and integrated treatment ( IT ) . Data were analysed using hierarchical logistic regression . RESULTS Half the sample was arrested and a quarter incarcerated during the two-year follow-up period . The regression models explained between 22 % and 35 % of the variance of the following criminal justice measures : ( 1 ) major offences , ( 2 ) minor offences , ( 3 ) substance-use-related offences , ( 4 ) incarcerations , ( 5 ) arrests , and ( 6 ) summons . Prior criminal behaviour was the strongest predictor of all of the dependent variables ; in general , demographic and diagnostic variables were not . Similarly , neither the type nor the amount of mental health treatment received predicted subsequent criminal behaviour . CONCLUSION Elsewhere the authors have shown that ACT and IT had advantages for health and stability of accommodation but these analyses suggest that more specialized interventions are needed to reduce criminal behaviour in dual disorder individuals The rate of substance-use disorders in patients with mental illnesses within the psychotic spectrum , such as schizophrenia , schizoaffective disorder , and bipolar disorder , is higher than the rate observed in the general population and is associated with significant morbidity and mortality . Although there are currently 3 medications approved by the Food and Drug Administration for the treatment of alcohol dependence , no medications have been approved for the specific treatment of dually diagnosed patients . A small but growing body of literature supports the use of 2 of these medications , disulfiram and naltrexone , in dually diagnosed individuals . This article outlines a review of the literature about the use of disulfiram and naltrexone for alcoholism and in patients with comorbid mental illness . In addition , results are presented of a 12-week r and omized clinical trial of disulfiram and naltrexone alone and in combination for individuals with Axis I disorders and alcohol dependence who were also receiving intensive psychosocial treatment . Individuals with a psychotic spectrum disorder , including schizophrenia , schizoaffective disorder , and bipolar disorder , had worse alcohol outcomes than those without a psychotic spectrum disorder . Individuals with a psychotic spectrum disorder had better alcohol-use outcomes on an active medication compared with placebo , but there was no clear advantage of disulfiram or naltrexone or of the combination . Retention rates and medication compliance in the study were high and exceeded 80 % . Pharmacotherapeutic strategies should take into account the advantages and disadvantages of each medication . Future directions of pharmacotherapeutic options are also discussed This study examines the rationale for and relative effectiveness of three intervention models for treating people with severe mental illness and substance abuse disorders : Twelve Step recovery , behavioral skills training , and intensive case management . Using clinical trial methods , 132 dually diagnosed clients were assigned to three service approaches . Changes in client psychosocial outcomes , and psychiatric and substance abuse symptomatology were tracked over a 24-month period . Differential effectiveness was evident , with clients in the behavioral skills group demonstrating the most positive and significant differences in psychosocial functioning and symptomatology , compared with the Twelve Step recovery approach . However , the case management intervention also result ed in several positive and important differences compared with the Twelve Step recovery approach . We also found significant changes over time , not only at 6 months but increasingly positive changes in psychosocial functioning at 12 and 18 months as well . These results underscore the need for clinical trials to further examine the relative cost effectiveness of treatment approaches for dually disordered clients and to incorporate means of assessing subgroup differences so that the interventions being tested can be further refined and targeted to a broad set of needs among the dually diagnosed CONTEXT Drug abuse by people with severe mental disorder is a significant public health problem for which there is no empirically vali date d treatment . OBJECTIVE To evaluate the efficacy of a new behavioral treatment for drug abuse in this population : Behavioral Treatment for Substance Abuse in Severe and Persistent Mental Illness ( BTSAS ) . DESIGN Participants were r and omly assigned to 6 months of treatment in either BTSAS or a manualized control condition : Supportive Treatment for Addiction Recovery ( STAR ) . SETTING Treatment was conducted in community-based outpatient clinics and a Veterans Affairs medical center in Baltimore , Md. PARTICIPANTS Participants were 129 stabilized out patients meeting DSM criteria for drug dependence ( cocaine , heroin , or cannabis ) and serious mental illness : 39.5 % met DSM-IV criteria for schizophrenia or schizoaffective disorder ; 55.8 % , for major affective disorders ; and the remainder met criteria for severe and persistent mental illness and other Axis I disorders . INTERVENTIONS Both treatments were administered by trained health care professionals in small groups , twice a week for 6 months . The BTSAS program is a social learning intervention that includes motivational interviewing , a urinalysis contingency , and social skills training . The control condition , STAR , is a supportive group discussion treatment . Main Outcome Measure The primary outcome measure was urinalysis results from twice-weekly treatment sessions . RESULTS The BTSAS program was significantly more effective than STAR in percentage of clean urine test results , survival in treatment , and attendance at sessions . The BTSAS program also had significant effects on important community-functioning variables , including hospitalization ; money available for living expenses ; and quality of life . CONCLUSIONS The BTSAS program is an efficacious treatment . Further work needs to be done to increase the proportion of eligible patients who are able to become engaged in treatment AIMS This study examined general and substance-specific coping skills and their relationship to treatment climate , continuing care and 1-year post-treatment functioning among dual diagnosis patients ( i.e. co-occurrence of substance use and psychiatric disorders ) . DESIGN In a prospect i ve multi-site study , dual diagnosis patients participating in substance abuse treatment were assessed at intake , discharge and at a 1-year follow-up . SETTING Patients were recruited from 15 substance abuse treatment programs , which were selected from a larger pool of 174 inpatient treatment programs in the Department of Veterans Affairs Health Care System . PARTICIPANTS A total of 981 male dual diagnosis patients participated in the study . MEASUREMENTS Assessment s included general and substance-specific coping skills , treatment climate , continuing outpatient care , abstinence and clinical ly significant psychiatric symptoms . FINDINGS Dual diagnosis patients modestly improved on general and substance-specific coping skills over the 1-year follow-up period . Patients who were in programs with a ' dual diagnosis treatment climate ' and who participated in more 12-Step self-help groups showed slightly more gains in adaptive coping . Both general and substance-specific coping were associated with abstinence , but only general coping was associated with freedom from significant psychiatric symptoms . CONCLUSIONS Enhancing general and substance-specific coping skills in substance abuse treatment may reduce dual diagnosis patients ' post-treatment substance use and improve their psychological functioning Faced with many patients with comorbid severe mental illness and substance use disorders , a university-affiliated , inner-city community mental health center and a psychosocial rehabilitation center initiated this clinical trial assessing a program to care for these patients . Fifty-four patients , age 18 to 10 , with either schizophrenia or major affective disorder and a substance use disorder were r and omly assigned to usual community mental health center and rehabilitation services with or without an innovative group and intensive case management program . One-year follow-ups detected no significant advantages on patient outcomes for adding the innovative program to usual services . Failure to engage patients in the experimental program posed a major and enduring barrier to treatment , despite intensive case management . Future efforts must give greater consideration to effective engagement techniques and patients ' readiness for active treatment OBJECTIVES This study examined a strategy to prevent homelessness among individuals with severe mental illness by providing a bridge between institutional and community care . METHODS Ninety-six men with severe mental illness who were entering community housing from a shelter institution were r and omized to receive 9 months of a " critical time " intervention plus usual services or usual services only . The primary analysis compared the mean number of homeless nights for the two groups during the 18-month follow-up period . To eluci date time trends , survival curves were used . RESULTS Over the 18-month follow-up period , the average number of homeless nights was 30 for the critical time intervention group and 91 for the usual services group . Survival curves showed that after the 9-month period of active intervention , the difference between the two groups did not diminish . CONCLUSIONS Strategies that focus on a critical time of transition may contribute to the prevention of recurrent homelessness among individuals with mental illness , even after the period of active intervention BACKGROUND The authors ' goal was to pilot test a newly developed manual-based group psychotherapy , called Integrated Group Therapy ( IGT ) , for patients with bipolar disorder and substance dependence . METHOD In this open trial , patients with DSM-IV bipolar disorder and substance dependence ( N = 45 ) were recruited in sequential blocks to receive either group therapy ( N = 21 ) or 6 monthly assessment s , but no experimental treatment ( N = 24 ) . RESULTS When compared with patients who did not receive group therapy , patients who received IGT had significantly better outcomes on the Addiction Severity Index drug composite score ( p < .03 ) , percentage of months abstinent ( p < .01 ) , and likelihood of achieving 2 ( p < .002 ) or 3 ( p < .004 ) consecutive abstinent months . CONCLUSION IGT is a promising treatment for patients with bipolar disorder and substance dependence , who have traditionally had poor outcomes . It is unclear , however , how much of the improvement among the group therapy patients is attributable to the specific content of the treatment . A study comparing this treatment with another active psychotherapy treatment is warranted Although substantial evidence favors the efficacy of contingency management ( CM ) for substance use disorders , few studies have examined the effect of CM on one 's motivation to change substance use . One way of conceptualizing motivation to change is by using the stages of change model [ Prochaska , J.O. , DiClemente , C.C. , 1983 . Stages and processes of self-change of smoking : toward an integrative model of change . J. Consult . Clin . Psychol . 51 , 390 - 395 ] . We assessed motivation to change substance use as conceptualized by the stages of change model using the University of Rhode Isl and Change Assessment ( URICA [ McConnaughy , E.A. , Prochaska , J.O. , Velicer , W.F. , 1983 . Stages of change in psychotherapy : measurement and sample profiles . Psychother . Theor . Res . 20 , 368 - 375 ] ) in 115 patients in community treatment clinics before they were r and omized to receive st and ard treatment or st and ard treatment plus CM . Motivation was also assessed 3 months later . Patients in both conditions evidence d significant decreases in their motivation scores from pre- to post-treatment . CM neither increased nor decreased motivation relative to the st and ard treatment condition . Pre-treatment motivation scores were also not related to treatment outcome . Assignment to the CM condition was associated with better treatment outcome as defined by longest duration of abstinence during treatment ( LDA ) . Higher post-treatment motivation was also modestly associated with LDA , but not in all analyses . These findings suggest that CM neither increases nor decreases motivation to change substance use in out patients receiving treatment at community-based drug-free clinics . Future studies should further examine motivation change in CM treatment using different assessment tools and conceptualizations of motivation , extending these effects to other treatment setting s and population The objective of this study was to evaluate the 6-month outcomes of a brief intervention to reduce alcohol consumption by psychiatric in- patients in the general hospital setting and following resolution of psychiatric morbidity . Patients from the psychiatric wards of three general hospitals were screened using the Alcohol Use Disorders Identification Test . Of 144 people approached who matched the study criteria , 120 ( 83 % ) people aged 18 - 64 years ( mean 31.7 ) were recruited . Participants were r and omized to either a brief motivational interview or an information package to reduce alcohol consumption . Alcohol consumption was assessed as total weekly consumption and categorized on Australian National Health and Medical Research Council ( NH&MRC ) criteria . We delivered 62 motivational interviews and 58 information packages . At the 6-month follow-up 83 ( 69 % ) , participants were reassessed . Both groups had significantly reduced alcohol consumption . However , the motivation group had a significantly greater reduction in weekly consumption than the information group ( F = 6.8 , ( 1,65 ) p < 0.025 ) after controlling for age , sex , SCL-90-R GSI and alcohol dependence ( and baseline alcohol consumption ) . A greater proportion of the motivation group compared to the information group also ' improved ' in their classification on NH&MRC criteria ( chi(2 ) = 7.3 , df 1 , p < 0.01 ) . Brief interventions , especially motivational interviews , are effective in reducing alcohol use in persons with psychiatric disorders . They are effective across the mid-range of GSI severity scores for in- patients . Screening and brief interventions can and should be incorporated into the routine assessment and management in psychiatric units Substance misuse is common in early psychosis , and impacts negatively on outcomes . Little is known about effective interventions for this population . We report a pilot study of brief intervention for substance misuse in early psychosis ( Start Over and Survive : SOS ) , comparing it with St and ard Care ( SC ) . Twenty-five in- patients aged 18 - 35 years with early psychosis and current misuse of non-opioid drugs were allocated r and omly to conditions . Substance use and related problems were assessed at baseline , 6 weeks and 3 , 6 and 12 months . Final assessment s were blind to condition . All 13 SOS participants who proceeded to motivational interviewing reported less substance use at 6 months , compared with 58 % ( 7/12 ) in SC alone . Effects were well maintained to 12 months . However , more SOS participants lived with a relative or partner , and this also was associated with better outcomes . Engagement remained challenging : 39 % ( 16/41 ) declined participation and 38 % ( 5/13 ) in SOS only received rapport building . Further research will increase sample size , and address both engagement and potential confounds OBJECTIVE The study examined the association between fidelity of programs to the assertive community treatment model and client outcomes in dual disorders programs . METHODS Assertive community treatment programs in the New Hampshire dual disorders study were classified as low-fidelity programs ( three programs ) or high-fidelity programs ( four programs ) based on extensive longitudinal process data . The study included 87 clients with a dual diagnosis of severe mental illness and a comorbid substance use disorder . Sixty-one clients were in the high-fidelity programs , and 26 were in the low-fidelity programs . Client outcomes were examined in the domains of substance abuse , housing , psychiatric symptoms , functional status , and quality of life , based on interviews conducted every six months for three years . RESULTS Clients in the high-fidelity assertive community treatment programs showed greater reductions in alcohol and drug use and attained higher rates of remission from substance use disorders than clients in the low-fidelity programs . Clients in high-fidelity programs had higher rates of retention in treatment and fewer hospital admissions than those in low-fidelity programs . No differences between groups were found in length of hospital stays and other residential measures , psychiatric symptoms , family and social relations , satisfaction with services , and overall life satisfaction . CONCLUSIONS Faithful implementation of , and adherence to , the assertive community treatment model for persons with dual disorders was associated with superior outcomes in the substance use domain . The findings underscore the value of measures of model fidelity , and they suggest that local modifications of the assertive community treatment model or failure to comply with it may jeopardize program success The study r and omly assigned male inmates with co-occurring serious mental illness and chemical abuse ( MICA ) disorders to either modified therapeutic community ( MTC ) or mental health ( MH ) treatment programs . On their release from prison , MICA inmates who completed the prison MTC program could enter the MTC aftercare program . The results , obtained from an intent-to-treat analysis of all study entries , showed that inmates r and omized into the MTC group had significantly lower rates of reincarceration compared with those in the MH group . The results also show that differences between the MTC + aftercare and comparison group across a variety of crime outcomes ( i.e. any criminal activity , and alcohol or drug related criminal activity ) are consistent and significant , and persist after an examination of various threats to validity ( e.g. initial motivation , duration of treatment , exposure to risk ) . This study provides some support for the effectiveness of the prison TC only condition . The findings are encouraging and consonant with other studies of integrated prison and aftercare TC programs for substance abusing non-MICA offenders , although qualified by the possibility that selection bias ( i.e. differences in motivation on entry into aftercare ) may be operating . Nevertheless , given the available evidence and the need for effective programming for MICA offenders , program and policy makers should strongly consider developing integrated prison and aftercare modified TC programs for MICA offenders ABSTRACT This study compared the costs and outcomes associated with three treatment programs that served 149 individuals with dual disorders ( i.e. , individuals with co-occurring severe mental illness and substance use disorders ) who were homeless at baseline . The three treatment programs were : Integrated Assertive Community Treatment ( IACT ) , Assertive Community Treatment only ( ACTO ) , and st and ard care ( Control ) . Participants were r and omly assigned to treatment and followed for a period of 24 months . Clients in the IACT and ACTO programs were more satisfied with their treatment program and reported more days in stable housing than clients in the Control condition . There were no significant differences between treatment groups on psychiatric symptoms and substance use . The average total costs associated with the IACT and Control conditions were significantly less than the average total costs for the ACTO condition Baker A , Lewin T , Reichler H , Clancy R , Carr V , Garrett R , Sly K , Devir H , Terry M. Motivational interviewing among psychiatric in‐ patients with substance use disorders . Acta Psychiatr Sc and 2002 : 106 : 233–240 . © Blackwell Munksgaard 2002 AIMS To assess the effectiveness of a motivational interview among hospitalized psychiatric patients with comorbid substance use disorder in reducing alcohol and other drug ( AOD ) use . DESIGN Subjects were assigned r and omly to receive an individual motivational interview ( n=79 ) or a self-help booklet ( control condition ; n=81 ) . SETTING Subjects were volunteers recruited from a major public psychiatric hospital . PARTICIPANTS Subjects met abuse or dependence criteria on the structured clinical interview for diagnosis ( SCID ) for alcohol , cannabis or amphetamine or they reported hazardous use during the last month of one or more of these drug types on the opiate treatment index ( OTI ) . INTERVENTION Either one 30 - 45-minute motivational interview or brief advice . MEASUREMENTS The SCID and OTI were the main measures . FINDINGS There was a modest short-term effect of the motivational interview on an aggregate index of alcohol and other drug use ( polydrug use on the OTI ) . Cannabis use remained high among the sample over the 12-month follow-up period . CONCLUSION Although motivational interviewing appears feasible among in- patients in psychiatric hospital with comorbid substance use disorders , more extensive interventions are recommended , continuing on an out-patient basis , particularly for cannabis use To evaluate the feasibility and efficacy of a program to manage Social Security disability benefits in a clinical sample of patients with severe mental illness and co-occurring substance dependence , 41 patients were r and omly assigned to have their benefits either contingently or noncontingently managed through their mental health center . Contingent management involved adjustments to the type or frequency ( not amount ) of disability benefits and payments for study participation based on ratings of substance use , money management , and treatment follow-through . The patients with contingent management used significantly less alcohol and drugs and showed much better money management than those with noncontingent management . Patients and case managers who participated in the study reported that they found the management strategy to be acceptable and useful In recent years , jail diversion programs for people with serious mental illness and co-occurring substance use disorders have received increasing attention and have rapidly grown in number . Previous studies suggest that jail diversion programs have the potential to achieve positive outcomes . The present study reports findings from 6 jail diversion programs ( 3 pre-booking and 3 post-booking ) participating in a federally-funded research initiative to assess the effectiveness of jail diversion programs for people with co-occurring disorders . Diverted and non-diverted groups were compared on self-reported outcomes at 12 months following diversion . The findings suggest that jail diversion reduces time spent in jail without increasing the public safety risk , while linking participants to community-based services . Jail diversion costs and the implication s of these results for jail diversion programs and future research are discussed |
969 | 20,156,703 | This review concluded that VEGF may have a strategic role in the pathophysiology of PCOS and is the key mediator in the pathogenesis of ovarian hyperstimulation syndrome ( OHSS ) in women undergoing assisted reproductive procedures . | The aim of this study was to investigate the strategic role of vascular endothelial growth factor ( VEGF ) in the pathophysiology of polycystic ovary syndrome ( PCOS ) and to critically review the published trials that have evaluated VEGF in women with PCOS . | CONTEXT Vascular endothelial growth factor A ( VEGF-A ) is a potent cytokine that promotes angiogenesis and vascular permeability . After controlled ovarian stimulation ( COS ) for in vitro fertilization ( IVF ) , excessive VEGF-A production can occur , particularly in women with polycystic ovarian syndrome ( PCOS ) ; however , it is unclear whether the regulation of VEGF-A production is different between PCOS and non-PCOS women . OBJECTIVE The aim of this study was to determine whether there were differences in the dose- and time-dependent effects of insulin and IGFs on VEGF-A production by luteinized granulosa cells ( LGCs ) from women with and without PCOS . DESIGN AND SETTING A prospect i ve comparative experimental study was conducted at an institutional practice . PATIENTS Patients included six PCOS and six non-PCOS women undergoing COS and IVF . INTERVENTIONS Interventions included COS for IVF . MAIN OUTCOME MEASURES VEGF-A levels in culture media were collected daily for 3 d from LGCs after incubation with variable doses of insulin , IGF-I , and IGF-II in the presence and absence of LH . RESULTS In both study groups , exposure to LH alone did not alter VEGF-A levels . However , insulin or IGF increased VEGF-A levels within 1 d and appeared to synergize with LH at 3 d. VEGF-A production by non-PCOS LGCs was more sensitive to IGF exposure , whereas PCOS cells were more sensitive to insulin . Although an increase in DNA content ( P < 0.05 ) was noted in cultures of PCOS cells , progesterone levels were lower compared with non-PCOS LGCs . CONCLUSION Insulin and IGFs promote VEGF-A production in LGCs , but the response patterns are different when cells from PCOS and non-PCOS women are compared BACKGROUND The aim of this study was to determine whether , in polycystic ovarian syndrome ( PCOS ) patients , HCG action prolonged for 4 h improves the action of angiogenic substances [ ovarian renin angiotensin system and vascular endothelial growth factor ( VEGF ) ] , and consequently follicular maturation , oocyte quality and oocyte fertilization competence . METHODS In this prospect i ve study 20 patients with PCOS undergoing IVF were included . Oocyte retrieval was carried out either 34 or 38 h after HCG administration . Each follicle was analysed for prorenin , active renin , VEGF and estradiol . Oocytes were evaluated for quality ( mature , immature , degenerated oocytes ) , as were the embryos ( low or high ) . RESULTS In the HCG + 38 h group there were 245 follicles , and in the HCG + 34 h group 240 follicles . In the HCG + 38 h group , log active renin was lower ( 2.78 + /- 0.20 versus 2.91 + /- 0.25 ; P < 0.001 ) and VEGF higher ( 2276.0 + /- 790.1 versus 1946.6 + /- 954.5 pg/ml ; P < 0.001 ) . The odds ratio for obtaining oocytes from follicles was 1.6 [ 95 % confidence interval ( CI ) 1.1 - 2.6 ; P = 0.02 ] , and for developing high quality embryos 7.6 ( 95 % CI 2.8 - 20.9 ; P < 0.001 ) in favour of the HCG + 38 h group . CONCLUSIONS Follicular maturation and oocyte quality are related to the intrafollicular influences of active renin and VEGF in a time-dependent manner after HCG administration , whereas fertilization competence is related to VEGF only OBJECTIVE To determine the concentration of angiogenic factors ( vascular endothelial growth factor [ VEGF ] , basic fibroblast growth factor [ bFGF ] , and angiogenin ) in the follicular fluid ( FF ) and oocyte-cumulus complex culture medium ( CM ) of women undergoing IVF and to investigate the association of the concentrations with the maturity and fertilization of the oocyte . DESIGN Prospect i ve study . SETTING Academic tertiary-care institution . PATIENT(S ) IVF patients with unexplained or tubal factor infertility . INTERVENTION(S ) Analysis of VEGF , bFGF , and angiogenin FF and CM concentrations . MAIN OUTCOME MEASURE(S ) Oocyte maturity and fertilization and FF and CM angiogenic factor concentrations . RESULT ( S ) VEGF , bFGF , and angiogenin were determined in FF and CM . FF angiogenin concentrations were significantly higher when the oocyte was mature versus immature . CM VEGF concentrations were significantly higher when the oocyte was nonfertilized versus fertilized . Positive correlations were observed between angiogenic factors in CM . CONCLUSION ( S ) VEGF , bFGF , and angiogenin ( determined for the first time ) are secreted in the FF and CM . Elevated CM VEGF concentrations , probably implying oocyte-cumulus complex hypoxia , are negatively associated with oocyte fertilization . Elevated FF angiogenin concentrations are positively associated with oocyte maturity , possibly indicating angiogenin 's biological role beyond neovascularization To test the hypothesis that increased serum levels of vascular endothelial growth factor ( VEGF ) in women with polycystic ovaries or the polycystic ovary syndrome ( PCOS ) result from excess release by ovarian granulosa cells . Prospect i ve study . Academic research setting . Twenty women undergoing IVF treatment , of whom 10 had normal ovaries and 10 had polycystic ovaries . Human granulosa lutein cells were isolated from follicular fluid obtained on the day of oocyte retrieval . Release of VEGF was assessed after co-incubation of granulosa lutein cells with gonadotropins and insulin . Serum and follicular fluid concentrations of VEGF were measured . Release of VEGF from granulosa lutein cells and serum levels of VEGF . Incubation with human hCG , and luteinizing hormone increased release of VEGF into the culture medium . Insulin alone did not increase release of VEGF , but addition of insulin increased hCG-stimulated release of VEGF . Serum and follicular fluid VEGF concentrations and the amount VEGF released from granulosa lutein cells obtained from women with polycystic ovaries or PCOS and those who developed the ovarian hyperstimulation syndrome were greater than those from granulosa lutein cells obtained from women with normal ovaries and those who did not develop the ovarian hyperstimulation syndrome . The amount of VEGF released by granulosa lutein cells is gonadotropin dependent and is augmented by insulin . The increased circulating concentrations of VEGF in women with PCOS may not only be due to an increased number of actively secreting granulosa lutein cells but also due to increased secretory capacity of each granulosa cell The multicentric study regroups 128 cases of the ovarian hyperstimulation syndrome ( OHSS ) in in-vitro fertilization ( IVF ) and 256 selected controls . Values of serum oestradiol obtained from different laboratories were found to be normally distributed after logarithmic transformation . Comparative study of clinical and biological characteristics indicates that among OHSS patients ( i ) mean age was lower ; ( ii ) tubal indications for IVF were less frequent ; ( iii ) polycystic ovary-like conditions ( i.e. hyper and rogenism , anovulation , luteinizing hormone/follicle stimulating hormone ratio > 2 ) were more frequent . OHSS patients displayed ovarian hypersensitivity reflected by higher oestradiol peak concentrations in response to lower dosage of human menopausal gonadotrophin and by a steeper slope of oestradiol increment during stimulation . In these patients , the collection of greater numbers of fertilizable oocytes allowed replacement of more embryos with a good vitality score . Ongoing pregnancy rate was found to be higher among the OHSS patients . The following complications were recorded among OHSS cases : abdominal fluid at echographic examination or clinical ascites ( 86.7 and 71.1 % , respectively ) ; pleural and pericardial effusion ( 21 and 3 % , respectively ) ; haemoconcentration ( 71.1 % ) ; electrolytic disorders ( 6.2 % ) . Although significantly different between groups , clinical and biological parameters under study showed considerable overlap of their distributions in control and OHSS cases . Therefore , these data must be su bmi tted to discriminant analysis in order to derive a formula predictive of the risk of OHSS OBJECTIVE To study the serum levels and correlation of vascular endothelial growth factor ( VEGF ) , insulin-like growth factor 1 ( IGF-1 ) , hormonal profile , and Doppler blood flow changes within the ovarian stroma before and after laparoscopic ovarian drilling ( LOD ) in women with clomiphene-resistant polycystic ovary syndrome ( PCOS ) . DESIGN Prospect i ve controlled study . SETTING University teaching hospital . PATIENT(S ) Twenty-five women with clomiphene-resistant PCOS ( group 1 ) and 20 women with regular menstrual cycles as a comparison group ( group 2 ) . INTERVENTION(S ) Laparoscopic ovarian drilling . MAIN OUTCOME MEASURE(S ) Serum levels of VEGF , IGF-1 , and Doppler indices of ovarian stromal blood flow . RESULT ( S ) The serum levels of VEGF , IGF-1 , T , and LH were significantly higher in group 1 before LOD than in group 2 . The Doppler indices ( pulsatility index and resistance index ) of ovarian stromal blood flow were also significantly lower in group 1 before LOD than in group 2 . The serum levels of VEGF , T , and LH were significantly reduced in group 1 after LOD compared with in group 1 before LOD . Doppler indices ( pulsatility index and resistance index ) of ovarian stromal blood flow were significantly increased after LOD . The VEGF levels before LOD were positively correlated with IGF-1 , LH , and T. After LOD , the VEGF levels were positively correlated with LH and T. CONCLUSION ( S ) Higher serum levels of VEGF and IGF-1 may explain the increased vascularity that was demonstrated by Doppler blood flow measurements in PCOS . Laparoscopic ovarian drilling reduced serum VEGF , IGF-1 , T , and LH and reduced ovarian blood flow velocities , which may explain the reduction of ovarian hyperstimulation syndrome in women with PCOS after LOD OBJECTIVE To evaluate the serum vascular endothelial growth factor concentrations and insulin responses to the oral glucose tolerance test before and after laparoscopic ovarian drilling in women with PCOS . DESIGN Prospect i ve study . SETTING University teaching center . PATIENT(S ) Twenty-seven women with clomiphene citrate-resistant polycystic ovary syndrome . INTERVENTION(S ) Laparoscopic ovarian drilling . MAIN OUTCOME MEASURE(S ) VEGF levels and insulin responses to OGTT before and after ovarian drilling . RESULT ( S ) No difference was found in VEGF levels in women with PCOS before ( 6.0 + /- 1.2 ng/mL ) and after ovarian drilling ( 5.5 + /- 1.2 ng/mL ) . VEGF levels before and after ovarian drilling in women who conceived were , respectively , 5.9 + /- 1.0 and 5.1 + /- 0.9 ng/mL and in those who did not conceive were 6.0 + /- 1.3 and 5.7 + /- 1.2 ng/mL. No correlation was found between baseline serum insulin and VEGF levels . VEGF concentrations in women with normal ovaries ( 4.5 + /- 1.7 ng/mL ) were significantly lower than in women with PCOS . There was no difference in glucose and insulin responses to OGTT before and after ovarian drilling . CONCLUSION ( S ) VEGF levels in women with PCOS are higher than in normal women , and ovarian drilling does not affect these levels . The procedure does not change insulin responses to OGTT The aim of this study was to determine whether follicular oestradiol and vascular endothelial growth factor ( VEGF ) concentrations in women with polycystic ovarian syndrome ( PCOS ) differ according to the use of gonadotrophin-releasing hormone ( GnRH ) antagonists or GnRH agonists . Furthermore , the effect of follicular oestradiol and VEGF concentrations on oocyte and embryo quality was investigated . In this prospect i ve clinical study , 20 women with PCOS undergoing intracytoplasmic sperm injection for male factor infertility were included using a GnRH antagonist or a GnRH agonist protocol . In each follicle , oestradiol and VEGF concentrations were determined . In the GnRH antagonist group 254 follicles and in the GnRH agonist group 245 follicles , were aspirated . Fewer metaphase II ( MII ) and more immature and degenerative oocytes were registered in the GnRH antagonist group . Follicular oestradiol and VEGF were lower in the GnRH antagonist group ( P = 0.014 and P < 0.001 , respectively ) . Moreover , higher oestradiol concentrations were related to embryos of higher quality ( P = 0.037 ) . It is concluded that GnRH antagonists decrease follicular oestradiol and VEGF concentrations and the number of retrieved MII oocytes in women with PCOS OBJECTIVE To determine whether serum levels of vascular permeability factor ( VPF ) are elevated in patients with ovarian hyperstimulation syndrome ( OHSS ) and to determine if luteinizing granulosa cells may be a source of VPF . DESIGN Prospect i ve observational study . SETTING University IVF and GIFT program . PATIENTS Eight consecutive IVF and GIFT patients at high risk for OHSS . MAIN OUTCOME MEASURES Vascular permeability factor concentration in serum and follicular fluid . RESULTS Serum VPF was significantly higher ( 15.2 + /- 4.0 pM ; mean + /- SEM ) on day + 14 in the group who developed severe OHSS compared with those who did not . Follicular fluid VPF ( 171.5 + /- 18.5 pM ) was approximately 100-fold greater than serum ( 1.7 + /- 1.3 pM ) or peritoneal fluid ( 2.5 + /- 1.3 pM ) 36 hours after hCG administration . CONCLUSION Vascular permeability factor is elevated in patients with severe OHSS and the ovary may be a source of VPF secretion Background . Polycystic ovary syndrome ( PCOS ) is a common endocrine disorder that causes anovulation and consequent subfertility . It is well established that increased ovarian mass , supported by new blood vessel proliferation in stroma and theca , is a key feature of PCOS . Recent studies suggest a role for angiogenetic factors in this phenomenon . Aim . To evaluate of levels of vascular endothelial growth factor ( VEGF ) and basic fibroblast growth factor ( bFGF ) in serum and follicular fluid of PCOS patients during a controlled ovarian hyperstimulation . Methods . In 52 patients undergoing in vitro fertilization treatments , 26 PCOS patients and 26 controls , serum VEGF and bFGF levels were assessed before starting administration of follicle-stimulating hormone ( FSH ) ( day 0 ) , on the day of administration of human chorionic gonadotropin ( hCG ) and on the day of oocyte retrieval . Follicular fluid levels of the two growth factors were detected on the day of oocyte retrieval . Results . PCOS patients showed higher serum VEGF levels than controls before starting FSH administration , on the day of hCG administration and on the day of oocyte retrieval . Serum VEGF levels showed a rise after hCG administration only in the PCOS patients . In addition , serum bFGF levels were higher in PCOS patients than in controls on the day of hCG administration and the day of oocyte retrieval . Furthermore , on the day of hCG administration , serum bFGF levels were directly correlated to the amount of FSH previously administered ( p < 0.0001 ) . In follicular fluid , higher VEGF and bFGF levels were found in PCOS patients than in controls . Furthermore , follicular-fluid bFGF concentrations were inversely correlated with the percentage of mature oocytes collected ( p < 0.05 ) . Conclusions . The present study revealed elevated levels of VEGF and bFGF in serum and follicular fluid in PCOS patients compared with controls . bFGF seems to be an FSH-dependent growth factor and its levels in follicular fluid are inversely correlated with the percentage of mature oocytes collected OBJECTIVE To relate changes in serum and follicular fluid vascular endothelial growth factor ( VEGF ) concentrations to Doppler blood flow velocities within ovarian and uterine blood vessels during IVF cycles and to assess their relation to ovarian hyperstimulation syndrome ( OHSS ) and polycystic ovaries (PCO)/polycystic ovary syndrome ( PCOS ) . DESIGN Prospect i ve descriptive study . SETTING The London Women 's Clinic . PATIENT(S ) One hundred seven patients receiving a " long " stimulation protocol of IVF . INTERVENTION(S ) Doppler blood flows were recorded in ovarian stromal and uterine arteries ; serum VEGF was measured in the early follicular phase , after pituitary desensitization , on the day of hCG administration , on the day of oocyte retrieval , and on the day of ET . MAIN OUTCOME MEASURE(S ) Serum and follicular fluid VEGF concentrations and Doppler blood flow measurements . RESULT ( S ) Serum VEGF concentrations rose after hCG administration . The rise was higher in women in whom OHSS developed . Women with PCO/PCOS had higher serum VEGF concentrations throughout the IVF cycle irrespective of whether OHSS developed . Follicular fluid VEGF concentrations were higher in women in whom OHSS developed and in women with PCO/PCOS . Doppler blood flow velocities in the ovarian blood vessels were higher in women in whom OHSS developed . Within ovarian and uterine blood vessels , blood flow velocities were higher in the early follicular phase and on the day of hCG administration in women with PCO/PCOS . A positive correlation was observed between the serum VEGF and E2 concentrations on the days of hCG administration and oocyte retrieval and between the serum VEGF concentration and Doppler blood flow velocities throughout the IVF cycle . CONCLUSION ( S ) Our results support the role of VEGF as a mediator of OHSS and establish a possible link between VEGF , OHSS , and PCO The considerable overlap of distributions of values for different parameters between control and ovarian hyperstimulation syndrome ( OHSS ) population s makes any single variable inefficient for risk prediction . Combinations of variables were studied in a discriminant function in order to increase predictivity and decrease the false negative rate . Such analyses were performed on two groups of in-vitro fertilization ( IVF ) patients : all OHSS cases ( n = 128 ) ( group A ) and only severe OHSS cases ( n = 92 ) ( group B ) . Progressive introduction and automated stepwise selection of variables were applied to both groups . The best prediction ( 78.5 % ) was obtained in group A under post-oocyte retrieval conditions using log oestradiol , slope of log oestradiol increment , human menopausal gonadotrophin ( HMG ) dosage , number of oocytes retrieved and ratio of luteinizing hormone/follicle stimulating hormone ( LH/FSH ) , in the formula . The corresponding false negative rate was 18.1 % . However , effective prevention of OHSS implies the ability to withhold human chorionic gonadotrophin injection . Therefore a formula for pre-oocyte retrieval conditions was established yielding a prediction rate of 76.1 % with a false negative rate of 18.1 % . To be vali date d , such formulae have to be applied to another population of IVF cases used as a ' testing-set ' The outcome of in-vitro fertilization and embryo transfer ( IVF-ET ) was compared in 76 patients with polycystic ovaries ( PCO ) diagnosed on pre-treatment ultrasound scan , and 76 control patients who had normal ovaries and were matched for age , cause of infertility and stimulation regimen . Despite receiving significantly less human menopausal gonadotrophin ( HMG ) , patients with PCO , as compared with controls , had significantly higher serum oestradiol levels on the day of human chorionic gonadotrophin administration ( 5940 + /- 255 versus 4370 + /- 240 pmol/l , P < 0.001 ) , developed more follicles ( 14.9 + /- 0.7 versus 9.8 + /- 0.6 , P < 0.001 ) and produced more oocytes ( 9.3 + /- 0.6 versus 6.8 + /- 0.5 , P = 0.003 ) . However , fertilization rates were reduced in the PCO patients ( 52.8 + /- 3.4 % versus 66.1 + /- 3.4 % , P = 0.007 ) . There was no significant difference in cleavage rates . The pregnancy rate/embryo transfer was 25.4 % in the PCO group and 23.0 % in the group with normal ovaries . There were three high order multiple pregnancies in the PCO group compared with none in the group with normal ovaries . Of the PCO patients , 10.5 % developed moderate/severe ovarian hyperstimulation syndrome ( OHSS ) compared with none of the controls ( P = 0.006 ) . Patients with and without PCO undergoing IVF have comparable pregnancy and livebirth rates . However , it is important to diagnose PCO before ovarian stimulation is initiated as these patients are more likely to develop moderate or severe OHSS following IVF-ET OBJECTIVE To evaluate plasma and follicular fluid levels of vascular endothelial growth factor ( VEGF ) in women undergoing controlled ovarian hyperstimulation to establish the possible role of this growth factor as a predictive marker of ovarian hyperstimulation syndrome ( OHSS ) . DESIGN Prospect i ve observational study . SETTING University hospital infertility unit . PATIENT(S ) Fifteen women at risk of OHSS and 15 controls . INTERVENTION(S ) An IM injection of hCG was administered ; plasma and follicular fluid sample s were collected 34 - 38 hours after administration of hCG . MAIN OUTCOME MEASURE(S ) VEGF levels in plasma and in follicular fluid . RESULT ( S ) VEGF levels increased after hCG administration in the patients at risk of developing OHSS and in those who developed OHSS . Further , on the day of the oocyte retrieval the increase in the VEGF levels in the plasma of the patients who developed OHSS was statistically significant compared with the increase in the levels in the women who did not . On the same day , the levels of VEGF in follicular fluid were 10 times greater than those in plasma . CONCLUSION ( S ) Plasma levels of VEGF peak after hCG administration and are related to the risk of developing OHSS OBJECTIVE To determine blood flow characteristics of ovarian and uterine arteries in patients with endocrinologically and clinical ly confirmed polycystic ovary disease ( PCOD ) in comparison with blood flow parameters observed in patients with spontaneous ovulatory cycles . DESIGN Controlled clinical study . SETTING Patients from Infertility Service in a tertiary care institution . PATIENTS Forty patients with confirmed PCOD and 50 control patients in various phases of spontaneous menstrual cycles . MAIN OUTCOME MEASURE Using transvaginal color Doppler sonography to determine ovarian morphology , ovarian blood vessel visualization rates , and ovarian and uterine arteries blood flow parameters ( resistance index , pulsatility index , and maximal peak velocity ) . These parameters were correlated with serum hormone levels . RESULTS Polycystic ovaries showed typical vascular pattern : increased stromal vascularity , a positive correlation between increased blood velocities and serum LH levels , and a trend toward lower resistance index and pulsatility index values , whereas uterine arteries revealed significantly increased resistance index and pulsatility index values . CONCLUSIONS The observed specific intraovarian and uterine vascular pattern in PCOD patients may provide additional data for conventional endocrinologic and ultrasonic diagnostic methods for PCOD BACKGROUND We aim ed to examine the serum levels of inhibin A , vascular endothelial growth factor ( VEGF ) , tumour necrosis factor alpha ( TNFalpha ) , estradiol ( E2 ) and progesterone levels after triggering of final oocyte maturation with GnRH agonist compared with HCG in patients with polycystic ovaries ( PCO ) and to investigate the relationship between these markers and ovarian hyperstimulation syndrome ( OHSS ) . METHODS Twenty-eight patients with PCO , undergoing controlled ovarian hyperstimulation with FSH and GnRH antagonist for IVF-embryo transfer treatment , were r and omized for triggering of final oocyte maturation with GnRH agonist ( GnRH agonist group , n = 15 ) or HCG ( HCG group , n = 13 ) . Blood sample s were obtained on the day of r and omization and thereafter every 2 - 7 days . Serum levels of inhibin A , VEGF , TNFalpha , E2 and progesterone , the incidence of OHSS , ovarian size and pelvic fluid accumulation were evaluated . RESULTS Serum inhibin A , E2 and progesterone levels were significantly lower in the GnRH agonist group compared with the HCG group , particularly on the day of embryo transfer ( P < 0.0001 ) . Serum VEGF and TNFalpha levels were similar between the two groups . Four patients in the HCG group developed severe OHSS , whereas no patient had any symptoms or signs of OHSS in the GnRH-agonist group ( P < 0.05 ) . CONCLUSIONS In patients with PCO treated with FSH/GnRH antagonist , final oocyte maturation with GnRH agonist instead of HCG reduces significantly inhibin A , E2 and progesterone levels during the luteal phase . This phenomenon reflects the inhibition of the corpus luteum function and may explain , at least in part , the mechanism of OHSS prevention in high-risk patients . Our results do not support a crucial role for VEGF or TNFalpha in OHSS |
970 | 16,394,751 | Electrotherapy or hydrotherapy does not enhance recovery and joint mobilization has limited evidence of its efficacy .
The best available evidence for shoulder rehabilitation emphasizes using advice , exercise , and mobilization of limited joints to restore upper limb function .
Placing controlled stresses throughout the fracture site at an early stage will optimize bone repair without increasing complication rates .
This approach requires cooperation between the referring surgeon and therapist and will optimize the patient 's shoulder function and maintain their functional independence . | UNLABELLED The occurrence of proximal humerus fractures will continue to rise with the increasing elderly population .
Many patients with proximal humerus fractures have osteoporosis and have poor neuromuscular control mechanisms .
This predisposes them to future falls and additional fractures .
Patients continue to have shoulder problems as a result of the fracture for many years after the injury .
Rehabilitation is central to addressing the problems caused by the fracture .
In the United Kingdom most patients are immobilized routinely for 3 weeks or longer and are referred for physical therapy . | STUDY DESIGN A prospect i ve r and omized clinical trial . OBJECTIVE To compare the effectiveness of 2 physical therapy treatment approaches for impingement syndrome of the shoulder . BACKGROUND Manual physical therapy combined with exercise is a commonly applied but currently unproven clinical treatment for impingement syndrome of the shoulder . METHODS AND MEASURES Thirty men and 22 women ( age 43 years + /- 9.1 ) diagnosed with shoulder impingement syndrome were r and omly assigned to 1 of 2 treatment groups . The exercise group performed supervised flexibility and strengthening exercises . The manual therapy group performed the same program and received manual physical therapy treatment . Both groups received the selected intervention 6 times over a 3-week period . The testers , who were blinded to group assignment , measured strength , pain , and function before treatment and after 6 physical therapy visits . Strength was a composite score of isometric strength tests for internal rotation , external rotation , and abduction . Pain was a composite score of visual analog scale measures during resisted break tests , active abduction , and functional activities . Function was measured with a functional assessment question naire . The visual analog scale used to measure pain with functional activities and the functional assessment question naire were also measured 2 months after the initiation of treatment . RESULTS Subjects in both groups experienced significant decreases in pain and increases in function , but there was significantly more improvement in the manual therapy group compared to the exercise group . For example , pain in the manual therapy group was reduced from a pretreatment mean ( + /- SD ) of 575.8 ( + /- 220.0 ) to a posttreatment mean of 174.4 ( + /- 183.1 ) . In contrast , pain in the exercise group was reduced from a pretreatment mean of 557.1 ( + /- 237.2 ) to a posttreatment mean of 360.6 ( + /- 272.3 ) . Strength in the manual therapy group improved significantly while strength in the exercise group did not . CONCLUSION Manual physical therapy applied by experienced physical therapists combined with supervised exercise in a brief clinical trial is better than exercise alone for increasing strength , decreasing pain , and improving function in patients with shoulder impingement syndrome This paper provides an up-to- date overview of the occurrence , diagnosis , risk factors , prognostic indicators and outcome of shoulder disorder ( SD ) , and of the validity and reproducibility of diagnostic classifications and diagnostic imaging techniques for SD . Furthermore , the available evidence on the effectiveness of non-steroidal anti-inflammatory drugs ( NSAIDs ) , corticosteroid injections and physiotherapy for SD is summarized on the basis of r and omized controlled trials with an acceptable quality of their methods . The annual incidence of SD is estimated at about 7 % , its 1-year period prevalence at about 51 % and its lifetime prevalence at about 10 % . While approximately 50 % of all patients with SD seek medical care , about 95 % are treated in primary health care . Of all new episodes of SD presenting to primary care , approximately 50 % seem to resolve within 6 months , while about 40 % seem to persist for up to 12 months . Several prognostic indicators for a favourable or a poor outcome of SD have been identified , but a comprehensive prognostic model is not available . While evidence for the prognostic validity of popular diagnostic classifications of SD is lacking , their reproducibility has been shown to be poor . The accuracy and clinical usefulness of diagnostic imaging techniques appear to be sufficiently verified for SD in secondary care , while their clinical usefulness in primary care and prognostic validity are not . NSAIDs and steroid injections for SD have been shown to be effective within 6 weeks , but their effect on long-term outcome remains unclear . There is very limited evidence for the effectiveness in SD of physiotherapy , including exercise therapy , ultrasound , electrotherapy , laser , mobilization and manipulation This paper reports a prospect i ve study of 72 consecutive patients with fractures or fracture-dislocations of the upper end of the humerus , treated during 1981 . Most were elderly and treatment was conservative . Of the 72 patients 64 were followed up for a period of six months . Observations were made on the type of fracture , the speed and pattern of recovery of shoulder movements , on the time of commencement of physiotherapy , and on its duration . We found that with conservative treatment alone , 94 % of our patients had good or satisfactory results at six months from injury . The criteria for manipulation are discussed and the literature is review ed Current knowledge of the clinical course and efficacy of treatment for shoulder pain comes mainly from studies of hospital patients . However , only a few patients experiencing such pain require referral to a specialist . Although shoulder pain is common in the general population , the outcome of patients presenting in general practice is unknown.1 We conducted a prospect i ve cohort study to determine the outcome of shoulder pain in primary care . Twelve general practitioners recruited 166 patients who consulted with a new episode of shoulder pain during one year . They recorded demographic information , diagnosis , management , and an assessment of passive elevation of the shoulder ; patients assessed the disability associated with their symptoms with a vali date d 22 item disability question naire.2 To assess outcome , identical disability question naires were sent to patients six and 18 months after consultation , together with a question measuring self assessed change in symptoms Primary shoulder impingement syndrome is a common shoulder problem which , if treated ineffectively , can lead to more serious pathology and expensive treatment . This study examined whether subjects receiving joint mobilization and comprehensive treatment ( hot packs , active range of motion , physiologic stretching , muscle strengthening , soft tissue mobilization , and patient education ) would have improved pain , mobility , and function compared with similar patients receiving comprehensive treatment alone . Subjects were eight men and six women ( mean age = 52.9 years ) with primary shoulder impingement syndrome ( superolateral shoulder pain , decreased active humeral elevation , limited overhead function ) . Following r and om assignment to experimental ( N = 7 ) and control groups ( N = 7 ) , three blinded evaluators tested 24-hour pain ( visual analog scale ) , pain with subacromial compression test ( visual analog scale ) , active range of motion ( goniometry ) , and function ( reaching forward , behind the head , and across the body in an overhead position ) before and after nine treatments . One-tailed analyses of covariance ( baseline values as covariates ) showed that the experimental group had less 24-hour pain and pain with subacromial compression test but no differences in range of motion and function ( Mann-Whitney U ) compared with controls . The experimental group improved on all variables , while the control group improved only on mobility and function ( one-tailed , paired t tests ; Wilcoxon matched pairs ) . Age , side of dominance , duration of symptoms , treatment attendance , exercise quality , and adherence had no effect on the outcomes . Results may be affected by inadequate sample size , minimal capsular tightness , insensitive functional scale , nonspecific motion measurements , position at which mobilization treatment was given , or a strong effect of comprehensive treatment . Mobilization decreased 24-hour pain and pain with subacromial compression test in patients with primary shoulder impingement syndrome , but larger replication studies are needed to assess more clearly mobilization 's influence on motion and function OBJECTIVE To determine the natural history of shoulder pain in the population , and predictors of outcome on the basis of clinical and individual factors . In addition , to determine whether outcome is influenced by the definition of shoulder pain used . METHODS A prospect i ve cohort study , over a 3 year period , of subjects recruited from a cross sectional population screening study of shoulder pain , conducted in the Greater Manchester area of the UK . RESULTS Of 92 subjects classified as having shoulder pain in the cross sectional study , 50 ( 54 % ) reported shoulder pain at followup about 3 years later . In 90 % of cases this was accompanied by some disability specifically relating to the symptoms . Baseline factors that predicted symptoms at followup were : pain ( indicated on a manikin ) within a more narrowly defined shoulder region , shoulder pain related disability , pain on the day of examination , symptoms lasting more than one year , and a high score on the General Health Question naire , a measure of psychological distress . CONCLUSION Shoulder pain in the population is a longterm disabling symptom , although many subjects do not seek early medical consultation . Disability ( independent of whether there was restriction of movement on examination ) is a strong predictor of continuing symptoms . The outcome observed in epidemiological studies of shoulder pain will be influenced by the initial definition of symptoms Abstract Relatively little is known about outcomes following clinical osteoporotic fractures at nonhip , nonvertebral skeletal sites . To address this issue , we prospect ively assessed post-fracture disability at multiple skeletal sites in a population of 909 older ( aged 55–81 years ) , community-dwelling women with low femoral neck bone mineral density who had experienced a fracture while enrolled in the Fracture Intervention Trial ( FIT ) . FIT is a r and omized , double-masked , placebo-controlled trial that was design ed to determine the effect of alendronate on fracture incidence , and the current study was conducted as a secondary analysis of FIT data . Following incident clinical fractures , FIT participants were followed prospect ively for assessment of site-specific , fracture-related disability . Measures of disability were self-reported days hospitalized or confined to bed because of the fracture ( ` bed days ' ) and days of reduced usual activities because of the fracture ( ` limited activity days ' ) . Of fracture types evaluated , those of the hip result ed in the highest percentage of subjects with any bed days or limited activity days after fracture ( 94 % with any bed days and 100 % with any limited activity days ) , though the mean number of bed days and limited activity days appeared highest after lumbar vertebral fractures ( 25.8 mean bed days and 158.5 mean limited activity days ) . Substantial disability also was reported after fractures of thoracic vertebrae , humerus , distal forearm , ankle and foot . Within fracture types , post-fracture disability was highly variable , ranging from none to more than 6 months BACKGROUND AND PURPOSE The aim of this study was to evaluate the efficacy of a physical therapy approach to the treatment of shoulder pain . Subjects . Sixty-six volunteers with shoulder pain believed to be of local mechanical origin were r and omly allocated to either a treatment group or a control group . METHODS Subjects in the treatment group received 1 month of physical therapy aim ed at restoring function of their shoulder muscles . Subjects in the control group received no treatment . Outcome measurements of pain intensity , range of motion ( ROM ) , isometric muscle force , functional impairment , and self-perception of improvement were obtained by blinded assessment . RESULTS Subjects in the treatment group showed improvement in pain-free abduction and flexion ROM , functional impairment , and self-perception of improvement . The control group deteriorated slightly over the experimental period in ROM and functional impairment measures . CONCLUSION AND DISCUSSION These results suggest that the physical therapy approach used in this study is effective in improving shoulder function in subjects experiencing pain of mechanical origin . The results also provide little evidence of spontaneous recovery over a 1-month period The effectiveness of arthroscopic surgery , supervised exercises , and placebo was compared in 125 patients with rotator cuff disease ( impingement syndrome stage II ) in a r and omized clinical trial . The median age was 48 years , and the median duration of complications was 1 to 2 years . The treatments were arthroscopic subacromial decompression performed by 2 experienced surgeons , an exercise regimen supervised for 3 to 6 months by 1 experienced physiotherapist , or 12 sessions of detuned soft laser ( placebo ) for 6 weeks . The criterion for success was a Neer shoulder score > 80 . Fifteen ( 50 % ) and 11 ( 22 % ) of the patients r and omized to placebo and exercises , respectively , had surgery during the 2 1/2-year follow-up period and were classified as having failure with the treatments . The success rate was higher ( P < .01 ) for patients r and omized to surgery ( 26 of 38 ) and exercises ( 27 of 44 ) compared with the placebo group ( 7 of 28 ) . The odds ratio for success after surgery compared with exercises was 1.5 ( 95 % confidence interval 0.6 to 3.7 ; P = .49 ) . Including all patients who underwent operation , the success rate in those not on sick leave ( 19 of 21 ) before surgery was higher compared with those on sick leave ( 18 of 36 ) ( adjusted odds ratio 5.6 [ 1.2 to 29.2 ] ) . Similar results were observed for patients not receiving versus those receiving regular pain medication before surgery ( adjusted odds ratio 4.2 [ 1.2 to 15.8 ] ) A poor outcome arising from a minimally displaced fracture of the neck of the humerus may be the result of a contracture of the capsule of the glenohumoral joint . Pulsed high frequency electromagnetic energy ( PHFE ) is an electrotherapy to reduce pain and swelling and to enhance healing . If PHFE is effective , early mobilization of the injured shoulder will be possible , reducing the risk of joint capsule contracture . We therefore conducted a double-blind trial of PHFE in minimally displaced fractures of the neck of the humerus . Early physiotherapy produced an excellent outcome in all cases . The functional outcome depended on age rather than time of starting treatment , although a relationship was found between the time of starting treatment and the duration of therapy required . The use of PHFE did not improve the result further We undertook a prospect i ve , controlled trial which compared two rehabilitation programmes for 86 patients who sustained two-part fractures of the proximal humerus . Patients were r and omised either to receive immediate physiotherapy within one week ( group A ) or delayed physiotherapy after three weeks of immobilisation in a collar and cuff sling ( group B ) . At 16 weeks after the fracture , patients in group A had less pain ( p < 0.01 ) and had greater shoulder function ( p < 0.001 ) than those in group B. At 52 weeks , the differences between the groups had reduced . Although group A still had greater shoulder function and less pain , there was no statistical difference when compared with group B. By analysis of the area under the curve , an overall measure up to the 52-week period , group A experienced less pain as measured by the SF36 general health question naire and had improved shoulder function . Our results show that patients with two-part fractures of the proximal humerus who begin immediate physiotherapy , experience less pain . The gains in shoulder function persist at 52 weeks which suggests that patients do not benefit from immobilisation before beginning physiotherapy |
971 | 30,253,707 | Evidence supports the use of rituximab in moderate-to-severe refractory systemic lupus erythematosus , diffuse skin involvement in systemic sclerosis and systemic involvement in primary Sjögren syndrome .
In addition , there is a consensus about the use of rituximab in refractory myositis .
Conclusion : Rituximab is a treatment option in several SARDs . | ABSTRACT Objectives : To review the therapeutic option of Rituximab , a chimeric anti-CD20 antibody , in systemic autoimmune rheumatic diseases ( SARDs ) such as systemic lupus erythematosus , systemic sclerosis , primary Sjögren syndrome and idiopathic inflammatory myopathy .
Results : The specific role and indication of rituximab in SARDs has been the subject of multiple trials in recent years .
Several guidelines have adopted these indications . | Objective . To assess the efficacy of rituximab ( RTX ) in SSc . Methods . Fourteen patients with SSc were evaluated . Eight patients were r and omized to receive two cycles of RTX at baseline and 24 weeks [ each cycle consisted of four weekly RTX infusions ( 375 mg/m2 ) ] in addition to st and ard treatment , whereas six patients ( control group ) received st and ard treatment alone . Lung involvement was assessed by pulmonary function tests ( PFTs ) and chest high-resolution CT ( H RCT ) . Skin involvement was assessed both clinical ly and histologically . Results . There was a significant increase of forced vital capacity ( FVC ) in the RTX group compared with baseline ( mean ± s.d . : 68.13 ± 19.69 vs 75.63 ± 19.73 , at baseline vs 1-year , respectively , P = 0.0018 ) . The median percentage of improvement of FVC in the RTX group was 10.25 % , whereas that of deterioration in the controls was 5.04 % ( P = 0.002 ) . Similarly , diffusing capacity of carbon monoxide ( DLCO ) increased significantly in the RTX group compared with baseline ( mean ± s.d . : 52.25 ± 20.71 vs 62 ± 23.21 , at baseline vs 1-year respectively , P = 0.017 ) . The median percentage of improvement of DLCO in the RTX group was 19.46 % , whereas that of deterioration in the control group was 7.5 % ( P = 0.023 ) . Skin thickening , assessed with the Modified Rodnan Skin Score ( MRSS ) , improved significantly in the RTX group compared with the baseline score ( mean ± s.d . : 13.5 ± 6.84 vs 8.37 ± 6.45 at baseline vs 1-year , respectively , P < 0.001 ) . Conclusion . Our results indicate that RTX may improve lung function in patients with SSc . To confirm our encouraging results we propose that larger scale , multicentre studies with longer evaluation periods are needed Objectives ( 1 ) Hypothesis testing of the potency of rituximab ( RTX ) in preventing fibrotic complications and ( 2 ) assessing acceptability and feasibility of RTX in early systemic sclerosis ( SSc ) . Methods A small , 24-month , r and omised , double-blind , placebo-controlled , single-centre trial in patients with SSc diagnosed < 2 years was conducted . Patients received RTX or placebo infusions at t=0 , t=15 days and t=6 months . Patients were clinical ly evaluated every 3 months , with lung function tests and high-resolution CT every other visit . Skin biopsies were taken at baseline and month 3 . Immunophenotyping of peripheral blood mononuclear cells was performed at every visit , except at months 9 and 18 . Adverse events , course of skin and pulmonary involvement and B cell population s in skin and peripheral blood were evaluated . Results In total 16 , patients ( rituximab n=8 , placebo n=8 ) were included . Twelve patients had diffuse cutaneous SSc . Eighty-eight adverse events ( RTX n=53 , placebo n=35 , p=0.22 ) and 11 serious adverse events ( RTX n=7 , placebo n=4 , p=0.36 ) occurred . No unexpected RTX-related events were observed . Mean skin score over time did not differ between the groups . Over time , forced vital capacity and extent of lung involvement slightly improved with RTX , but this difference was insignificant . In peripheral blood B cells depletion was demonstrated . Conclusions No unexpected safety issues were observed with RTX in early SSc . Although this small trial could not confirm or reject potential efficacy of RTX in these patients , future placebo-controlled trials are warranted , specifically in the subgroup of patients with pulmonary involvement . Trial registration number EudraCT 2008 - 07180 - 16 ; Results OBJECTIVE B cells are likely to contribute to the pathogenesis of systemic lupus erythematosus ( SLE ) , and rituximab induces depletion of B cells . The Exploratory Phase II/III SLE Evaluation of Rituximab ( EXPLORER ) trial tested the efficacy and safety of rituximab versus placebo in patients with moderately-to-severely active extrarenal SLE . METHODS Patients entered with > or=1 British Isles Lupus Assessment Group ( BILAG ) A score or > or=2 BILAG B scores despite background immunosuppressant therapy , which was continued during the trial . Prednisone was added and subsequently tapered . Patients were r and omized at a ratio of 2:1 to receive rituximab ( 1,000 mg ) or placebo on days 1 , 15 , 168 , and 182 . RESULTS In the intent-to-treat analysis of 257 patients , background treatment was evenly distributed among azathioprine , mycophenolate mofetil , and methotrexate . Fifty-three percent of the patients had > or=1 BILAG A score at entry , and 57 % of the patients were categorized as being steroid dependent . No differences were observed between placebo and rituximab in the primary and secondary efficacy end points , including the BILAG-defined response , in terms of both area under the curve and l and mark analyses . A beneficial effect of rituximab on the primary end point was observed in the African American and Hispanic subgroups . Safety and tolerability were similar in patients receiving placebo and those receiving rituximab . CONCLUSION The EXPLORER trial enrolled patients with moderately-to-severely active SLE and used aggressive background treatment and sensitive cutoffs for nonresponse . No differences were noted between placebo and rituximab in the primary and secondary end points . Further evaluation of patient subsets , biomarkers , and exploratory outcome models may improve the design of future SLE clinical trials Objective . The aim was to assess the efficacy of rituximab for the cutaneous manifestations of adult DM and JDM . Methods . Patients with refractory adult DM ( n = 72 ) and JDM ( n = 48 ) were treated with rituximab in a r and omized placebo-phase-controlled trial [ either rituximab early drug ( week 0/1 ) or rituximab late arms ( week 8/9 ) , such that all subjects received study drug ] . Stable concomitant therapy was allowed . Cutaneous disease activity was assessed using the Myositis Disease Activity Assessment Tool , which grade s cutaneous disease activity on a visual analog scale . A myositis damage assessment tool , termed the Myositis Damage Index , was used to assess cutaneous damage . Improvement post-rituximab was evaluated in individual rashes as well as in cutaneous disease activity and damage scores . The & khgr;2 test , Student ’s paired t-test and Wilcoxon test were used for analysis . Results . There were significant improvements in cutaneous disease activity from baseline to the end of the trial after rituximab administration in both adult DM and JDM subsets . The cutaneous visual analog scale activity improved in adult DM ( 3.22–1.72 , P = 0.0002 ) and JDM ( 3.26–1.56 , P < 0.0001 ) , with erythroderma , erythematous rashes without secondary changes of ulceration or necrosis , heliotrope , Gottron sign and papules improving most significantly . Adult DM subjects receiving rituximab earlier in the trial demonstrated a trend for faster cutaneous response ( 20 % relative improvement from baseline ) compared with those receiving B cell depletion later ( P = 0.052 ) . Conclusion . Refractory skin rashes in adult DM and JDM showed improvement after the addition of rituximab to the st and ard therapy in a clinical trial Introduction An over-expression of CD19 has been shown in B cells of systemic sclerosis ( SSc ) and B cells are thought to contribute to the induction of skin fibrosis in the tight skin mouse model . The aim was to define the outcome on safety and the change in skin score after rituximab therapy in SSc patients and to correlate the clinical characteristics with the levels of interleukin (IL)-6 and with the immune cell infiltrate detected by immunohistochemistry . Methods Nine patients with SSc with mean age 40.9 ± 11.1 years were treated with anti-CD20 , 1 g at time 0 and after 14 days . Skin biopsy was performed at baseline and during the follow-up . B-cell activating factor ( BAFF ) and IL-6 levels were also determined at the follow-up times . Results After 6 months patients presented a median decrease of the skin score of 43.3 % ( range 21.1 - 64.0 % ) , and a decrease in disease activity index and disease severity index . IL-6 levels decreased permanently during the follow up . After treatment , a complete depletion of peripheral blood B cells was observed in all but 2 patients . Only 3 patients presented CD20 positive cells in the biopsy of the involved skin at baseline . Conclusions Anti-CD20 treatment has been well tolerated and SSc patients experienced an improvement of the skin score and of clinical symptoms . The clear fall in IL-6 levels could contribute to the skin fibrosis improvement , while the presence of B cells in the skin seems to be irrelevant with respect to the outcome after B cell depletion . Trial registration IS RCT N77554566 OBJECTIVE To study the efficacy and safety of B cell depletion with rituximab , a chimeric murine/human anti-CD20 monoclonal antibody , in patients with primary Sjögren 's syndrome ( SS ) in a double-blind , r and omized , placebo-controlled trial . METHODS Patients with active primary SS , as determined by the revised American-European Consensus Group criteria , and a rate of stimulated whole saliva secretion of > or = 0.15 ml/minute were treated with either rituximab ( 1,000 mg ) or placebo infusions on days 1 and 15 . Patients were assigned r and omly to a treatment group in a ratio of 2:1 ( rituximab : placebo ) . Followup was conducted at 5 , 12 , 24 , 36 , and 48 weeks . The primary end point was the stimulated whole saliva flow rate , while secondary end points included functional , laboratory , and subjective variables . RESULTS Thirty patients with primary SS ( 29 female ) were r and omly allocated to a treatment group . The mean + /- SD age of the patients receiving rituximab was 43 + /- 11 years and the disease duration was 63 + /- 50 months , while patients in the placebo group were age 43 + /- 17 years and had a disease duration of 67 + /- 63 months . In the rituximab group , significant improvements , in terms of the mean change from baseline compared with that in the placebo group , were found for the primary end point of the stimulated whole saliva flow rate ( P = 0.038 versus placebo ) and also for various laboratory parameters ( B cell and rheumatoid factor [ RF ] levels ) , subjective parameters ( Multidimensional Fatigue Inventory [ MFI ] scores and visual analog scale [ VAS ] scores for sicca symptoms ) , and extragl and ular manifestations . Moreover , in comparison with baseline values , rituximab treatment significantly improved the stimulated whole saliva flow rate ( P = 0.004 ) and several other variables ( e.g. , B cell and RF levels , unstimulated whole saliva flow rate , lacrimal gl and function on the lissamine green test , MFI scores , Short Form 36 health survey scores , and VAS scores for sicca symptoms ) . One patient in the rituximab group developed mild serum sickness-like disease . CONCLUSION These results indicate that rituximab is an effective and safe treatment strategy for patients with primary SS In the United States , approximately 35 % of adults with Systemic Lupus Erythematosus ( SLE ) have clinical evidence of nephritis at the time of diagnosis ; with an estimated total of 50–60 % developing nephritis during the first 10 years of disease [ 1–4 ] . The prevalence of nephritis is significantly higher in African Americans and Hispanics than in Caucasians , and is higher in men than in women . Renal damage is more likely to develop in non-Caucasian groups [ 2–4 ] . Overall survival in patients with SLE is approximately 95 % at 5 years after diagnosis and 92 % at 10 years [ 5 , 6 ] . The presence of lupus nephritis significantly reduces survival , to approximately 88 % at 10 years , with even lower survival in African Americans [ 5 , 6 ] . The American College of Rheumatology ( ACR ) last published guidelines for management of systemic lupus erythematosus ( SLE ) in 1999 [ 7 ] . That publication was design ed primarily for education of primary care physicians and recommended therapeutic and management approaches for many manifestations of SLE . Recommendations for management of lupus nephritis ( LN ) consisted of pulse glucocorticoids followed by high dose daily glucocorticoids in addition to an immunosuppressive medication , with cyclophosphamide viewed as the most effective immunosuppressive medication for diffuse proliferative glomerulonephritis . Mycophenolate mofetil was not yet in use for lupus nephritis and was not mentioned . Since that time , many clinical trials of glucocorticoids-plus-immunosuppressive interventions have been published , some of which are high quality prospect i ve trials , and some not only prospect i ve but also r and omized . Thus , the ACR determined that a new set of management recommendations was in order . A combination of extensive literature review and the opinions of highly qualified experts , including rheumatologists , nephrologists and pathologists , has been used to reach the recommendations . The management strategies discussed here apply to lupus nephritis in adults , particularly to those receiving care in the United States of America , and include interventions that were available in the United States as of April 2011 . While these recommendations were developed using rigorous methodology , guidelines do have inherent limitations in informing individual patient care ; hence the selection of the term “ recommendations . ” While they should not supplant clinical judgment or limit clinical judgment , they do provide expert advice to the practicing physician managing patients with lupus nephritis OBJECTIVES To assess the safety and efficacy of long-term treatment with rituximab ( RTX ) in patients with systemic sclerosis ( SSc ) . METHODS Eight patients with SSc-associated interstitial lung disease ( ILD ) received 4 cycles of RTX and had a follow-up of 2 years . Lung involvement was assessed by pulmonary function tests and chest H RCT . Skin involvement was assessed both clinical ly and histologically . RESULTS We found a linear improvement of lung function and skin thickening over the 2 years of RTX treatment . There was a significant increase of FVC at 2 years compared to baseline ( mean ± SEM : 77.13±7.13 vs. 68.13±6.96 , respectively , p<0.0001 ) . Similarly , DLco increased significantly at 2 years compared to baseline ( mean ± SEM : 63.13±7.65 vs. 52.25±7.32 , respectively , p<0.001 ) . Skin thickening , assessed with the MRSS , improved significantly at 2 years compared to baseline ( mean ± SEM : 4.87±0.83 vs. 13.5±2.42 , respectively , p<0.0001 ) . A reduction in myofibroblast score was seen histologically following RTX treatment . CONCLUSIONS Our results indicate that long-term treatment with RTX may favourably affect lung function and skin fibrosis in patients with SSc . Larger scale , multicentre , r and omised , controlled studies are needed to further explore the efficacy of RTX in SSc Objective : Primary Sjögren syndrome ( pSS ) causes significant systemic symptoms including fatigue as well as gl and ular dysfunction . There are currently no effective systemic therapies ; however , open label series have suggested that rituximab may be beneficial for systemic and gl and ular manifestations . Therefore , we performed a double blind , placebo-controlled , r and omised pilot study of the efficacy of rituximab in reducing fatigue in pSS . Methods : A total of 17 patients with pSS and a score on fatigue visual analogue scale ( VAS ) > 50 were r and omised to receive either 2 infusions of rituximab 1 g or placebo ; patients also received oral and intravenous steroids . Outcome measures included : the proportion of patients with > 20 % reduction in fatigue VAS , changes in pSS related symptoms , health related quality of life and immunological parameters of pSS . These were measured 6 months after therapy . Results : There was significant improvement from baseline in fatigue VAS in the rituximab group ( p<0.001 ) in contrast to the placebo group ( p = 0.147 ) . There was a significant difference between the groups at 6 months in the social functioning score of SF-36 ( p = 0.01 ) and a trend to significant difference in the mental health domain score of SF-36 ( p = 0.06 ) . There was one episode of serum sickness in the rituximab treated group . Conclusions : This is the first double blind study of rituximab in pSS to show benefit ; further studies are justified BACKGROUND The combination of cyclophosphamide and glucocorticoids leads to remission in most patients with antineutrophil cytoplasm antibody (ANCA)-associated vasculitides . However , even when patients receive maintenance treatment with azathioprine or methotrexate , the relapse rate remains high . Rituximab may help to maintain remission . METHODS Patients with newly diagnosed or relapsing granulomatosis with polyangiitis , microscopic polyangiitis , or renal-limited ANCA-associated vasculitis in complete remission after a cyclophosphamide-glucocorticoid regimen were r and omly assigned to receive either 500 mg of rituximab on days 0 and 14 and at months 6 , 12 , and 18 after study entry or daily azathioprine until month 22 . The primary end point at month 28 was the rate of major relapse ( the reappearance of disease activity or worsening , with a Birmingham Vasculitis Activity Score > 0 , and involvement of one or more major organs , disease-related life-threatening events , or both ) . RESULTS The 115 enrolled patients ( 87 with granulomatosis with polyangiitis , 23 with microscopic polyangiitis , and 5 with renal-limited ANCA-associated vasculitis ) received azathioprine ( 58 patients ) or rituximab ( 57 patients ) . At month 28 , major relapse had occurred in 17 patients in the azathioprine group ( 29 % ) and in 3 patients in the rituximab group ( 5 % ) ( hazard ratio for relapse , 6.61 ; 95 % confidence interval , 1.56 to 27.96 ; P=0.002 ) . The frequencies of severe adverse events were similar in the two groups . Twenty-five patients in each group ( P=0.92 ) had severe adverse events ; there were 44 events in the azathioprine group and 45 in the rituximab group . Eight patients in the azathioprine group and 11 in the rituximab group had severe infections , and cancer developed in 2 patients in the azathioprine group and 1 in the rituximab group . Two patients in the azathioprine group died ( 1 from sepsis and 1 from pancreatic cancer ) . CONCLUSIONS More patients with ANCA-associated vasculitides had sustained remission at month 28 with rituximab than with azathioprine . ( Funded by the French Ministry of Health ; MAINRITSAN Clinical Trials.gov number , NCT00748644 ; EudraCT number , 2008 - 002846 - 51 . ) Objectives To evaluate the efficacy and safety of rituximab in patients with primary Sjögren 's syndrome ( pSS ) . Methods The AutoImmune and Rituximab registry has included 86 patients with pSS treated with rituximab , prospect ivey followed up every 6 months for 5 years . Results Seventy-eight patients with pSS ( 11 men , 67 women ) , who already had at least one follow-up visit , were analysed . Median age was 59.8 years ( 29–83 ) , median duration of disease was 11.9 years ( 3–32 ) . Indications for treatment were systemic involvement for 74 patients and only severe gl and ular involvement in four patients . The median European Sjögren 's Syndrome disease activity index ( ESSDAI ) was 11 ( 2–31 ) . 17 patients were concomitantly treated with another immunosuppressant agent . Median follow-up was 34.9 months ( 6–81.4 ) ( 226 patient-years ) . Overall efficacy according to the treating physician was observed in 47 patients ( 60 % ) after the first cycle of rituximab . Median ESSDAI decreased from 11 ( 2–31 ) to 7.5 ( 0–26 ) ( p<0.0001 ) . Median dosage of corticosteroid decreased from 17.6 mg/day ( 3–60 ) to 10.8 mg/day ( p=0.1 ) . Forty-one patients were retreated with rituximab . Four infusion reactions and one delayed serum sickness-like disease result ed in rituximab discontinuation . Three serious infections ( 1.3/100 patient-years ) and two cancer-related deaths occurred . Conclusions In common practice , the use of rituximab in pSS is mostly restricted to patients with systemic involvement . This prospect i ve study shows good efficacy and tolerance of rituximab in patients with pSS and systemic involvement OBJECTIVES To evaluate the efficacy of rituximab in central nervous system ( CNS ) manifestations of patients with primary Sjögren 's syndrome ( pSS ) . METHODS Prospect i ve data from patients with pSS and CNS involvement included in the French AutoImmunity and Rituximab registry were analysed . All patients had diffuse white matter T2-weigted hypersignals . Neurological response was defined as improvement or disappearance of neurological signs . RESULTS Eleven patients ( mean age 55 years [ 38 - 77 ] ) were treated with rituximab for their neurological involvement . The mean duration of pSS was 9 years ( 4 - 24 ) . Mean baseline ESSDAI score was 17 ( 5 - 25 ) . Neurological features were progressive multiple sclerosis-like manifestations ( n=6 ) , transverse myelitis ( n=1 ) , anxiety and depression disorder ( n=1 ) and cognitive dysfunction ( n=3 ) . Mean Exp and ed Disability Status Score ( EDSS ) before rituximab was 4 ( 3 - 5.5 ) . The mean follow-up was of 13 months ( 6 - 58 ) . No neurological change occurred in all 6 patients with multiple sclerosis-like symptoms , in 2/3 patients with cognitive dysfunction or in the patient with anxiety-depression . One patient with depression and cognitive dysfunction disclosed subjective improvement . One patient with transverse myelitis , refractory to cyclophosphamide had an improvement of his walk perimeter ( 160 meters vs. 116 ) . Mean EDSS score and ESSDAI remained stable . CONCLUSIONS Rituximab does not seem to be effective in progressive multiple sclerosis-like manifestations of patients with pSS-related CNS involvement The EXPLORER study was design ed to assess the response to rituximab versus placebo in patients with moderate to severe extrarenal systemic lupus erythematosus ( SLE ) receiving background immunosuppression . The definition of response required reduced clinical activity without subsequent flares over 52 weeks , and the study did not meet its efficacy endpoint . The current exploratory analysis assessed flare rates in patients who achieved initial low disease activity response ( British Isles Lupus Assessment Group [ BILAG ] C or better in all organs ) during the study . Exploratory re analysis of data from the EXPLORER trial was conducted , considering alternative definitions for flare . No difference was found between rituximab and placebo in preventing or delaying moderate to severe flares . However , when severe ( BILAG A ) flares alone were examined , rituximab reduced the risk of a subsequent first A flare ( hazard ratio = 0.61 ; p = 0.052 ) and lowered mean ± SD annualized A flare rates ( 0.86 ± 1.47 vs. 1.41 ± 2.14 ; p = 0.038 ) . Eighty-four ( 49.7 % ) rituximab-treated patients achieved low disease activity without subsequent A flares versus 31 ( 35.2 % ) placebo-treated patients ( p = 0.027 ) . Prednisone rescue for A flares was similar in rituximab- ( 24 % ) and placebo-treated ( 14 % ) patients ( p = 0.204 ) . This post hoc analysis evaluates the hypothesis that assessment of BILAG A flares may distinguish potential treatment effects with greater sensitivity than assessment of BILAG B flares OBJECTIVE To assess the safety and efficacy of rituximab in a r and omized , double-blind , placebo-phase trial in adult and pediatric myositis patients . METHODS Adults with refractory polymyositis ( PM ) and adults and children with refractory dermatomyositis ( DM ) were enrolled . Entry criteria included muscle weakness and ≥2 additional abnormal values on core set measures ( CSMs ) for adults . Juvenile DM patients required ≥3 abnormal CSMs , with or without muscle weakness . Patients were r and omized to receive either rituximab early or rituximab late , and glucocorticoid or immunosuppressive therapy was allowed at study entry . The primary end point compared the time to achieve the International Myositis Assessment and Clinical Studies Group preliminary definition of improvement ( DOI ) between the 2 groups . The secondary end points were the time to achieve ≥20 % improvement in muscle strength and the proportions of patients in the early and late rituximab groups achieving the DOI at week 8 . RESULTS Among 200 r and omized patients ( 76 with PM , 76 with DM , and 48 with juvenile DM ) , 195 showed no difference in the time to achieving the DOI between the rituximab late ( n = 102 ) and rituximab early ( n = 93 ) groups ( P = 0.74 by log rank test ) , with a median time to achieving a DOI of 20.2 weeks and 20.0 weeks , respectively . The secondary end points also did not significantly differ between the 2 treatment groups . However , 161 ( 83 % ) of the r and omized patients met the DOI , and individual CSMs improved in both groups throughout the 44-week trial . CONCLUSION Although there were no significant differences in the 2 treatment arms for the primary and secondary end points , 83 % of adult and juvenile myositis patients with refractory disease met the DOI . The role of B cell-depleting therapies in myositis warrants further study , with consideration for a different trial design Objectives : The safety and potential efficacy of rituximab was examined in diffuse cutaneous systemic sclerosis ( dc-SSc ) . Methods : A 24 week open-label study in which eight patients with dc-SSc received an infusion of 1000 mg rituximab administered at baseline and day 15 , together with 100 mg methylprednisolone at each infusion . Assessment included CD19 + peripheral blood lymphocyte number , skin sclerosis score , indices of internal organ functioning , the health assessment question naire disability index , the 36-item Short Form health survey and histopathological evaluation of the skin . Results : Ritixumab induced effective B-cell depletion in all patients ( < 5 CD19 + cells/μl blood ) . There was a significant change in skin score at week 24 ( p<0.001 ) . Also , significant improvements were measured in the dermal hyalinised collagen content ( p = 0.014 ) and dermal myofibroblast numbers ( p = 0.011 ) . Two serious adverse events occurred , which were thought to be unrelated to the rituximab treatment . Conclusions : Rituximab appears to be well tolerated and may have potential efficacy for skin disease in dc-SSc . This study is registered with Clinical Trials.gov , number NCT00379431 OBJECTIVES Rituximab ( RTX ) may favorably affect lung function and skin fibrosis in patients with systemic sclerosis ( SSc ) . We aim ed to assess long-term efficacy and safety of RTX in SSc compared to st and ard treatment . METHODS A total of 51 patients with SSc-associated interstitial lung disease were recruited and treated with RTX ( n = 33 ) or conventional treatment ( n = 18 ) . Median follow-up was 4 years ( range : 1 - 7 ) . Conventional treatment consisted of azathioprine ( n = 2 ) , methotrexate ( n = 6 ) , and mycophenolate mofetil ( n = 10 ) . RESULTS Patients in the RTX group showed an increase in FVC at 2 years ( mean ± SD of FVC : 80.60 ± 21.21 vs 86.90 ± 20.56 at baseline vs 2 years , respectively , p = 0.041 compared to baseline ) . In sharp contrast , patients in the control group had no change in FVC during the first 2 years of follow-up . At the 7 year time point the remaining patients in the RTX group ( n = 5 ) had higher FVC compared to baseline ( mean ± SD of FVC : 91.60 ± 14.81 , p = 0.158 compared to baseline ) in contrast to patients in the control group ( n = 9 ) where FVC deteriorated ( p < 0.01 , compared to baseline ) . Direct comparison between the 2 groups showed a significant benefit for the RTX group in FVC ( p = 0.013 ) . Improvement of skin thickening was found in both the RTX and the st and ard treatment group ; however , direct comparison between groups strongly favored RTX at all-time points . Adverse events were comparable between groups . CONCLUSIONS Our data indicate that RTX has a beneficial effect on lung function and skin fibrosis in patients with SSc . R and omized controlled studies are highly needed OBJECTIVE To determine the safety of rituximab , to provide preliminary data regarding the potential efficacy of rituximab , and to investigate the effects of rituximab on autoimmunity and fibrosis in patients with diffuse cutaneous systemic sclerosis ( dcSSc ) . METHODS Fifteen patients with dcSSc , all of whom experienced their first non-Raynaud 's disease-associated disease manifestation within 18 months of trial entry , were recruited to receive 2 intravenous doses of rituximab ( 1,000 mg ) , administered 2 weeks apart . Safety , clinical , and exploratory outcomes were evaluated at baseline and at 6 months . The primary outcome was the change in the modified Rodnan skin thickness score ( MRSS ) at 6 months compared with baseline . RESULTS Adverse events included frequent infusion reactions and rare infections ( urinary tract infection and dental abscess occurred in 1 patient each ) . The mean change in the MRSS between baseline and 6 months was not significant . Results of pulmonary function tests and other measures of major organ involvement were stable . The modest B cell infiltrates that were present in most skin biopsy specimens at baseline were completely depleted at 6 months in most patients . Autoantibody titers showed only modest and variable changes after treatment . CONCLUSION In this pilot study , treatment with rituximab appeared to be safe and well tolerated among patients with dcSSc . Rituximab treatment result ed in both depletion of circulating B cells and depletion of dermal B cells but had little effect on the levels of SSc-associated autoantibodies . Rituximab treatment did not appear to result in a significant beneficial effect on skin disease . The potential efficacy of rituximab in other organs such as the lung could not be clearly evaluated in this small open-label trial OBJECTIVE To evaluate the efficacy and safety of rituximab in a r and omized , double-blind , placebo-controlled phase III trial in patients with lupus nephritis treated concomitantly with mycophenolate mofetil ( MMF ) and corticosteroids . METHODS Patients ( n = 144 ) with class III or class IV lupus nephritis were r and omized 1:1 to receive rituximab ( 1,000 mg ) or placebo on days 1 , 15 , 168 , and 182 . The primary end point was renal response status at week 52 . RESULTS Rituximab depleted peripheral CD19 + B cells in 71 of 72 patients . The overall ( complete and partial ) renal response rates were 45.8 % among the 72 patients receiving placebo and 56.9 % among the 72 patients receiving rituximab ( P = 0.18 ) ; partial responses accounted for most of the difference . The primary end point ( superior response rate with rituximab ) was not achieved . Eight placebo-treated patients and no rituximab-treated patients required cyclophosphamide rescue therapy through week 52 . Statistically significant improvements in serum complement C3 , C4 , and anti-double-str and ed DNA ( anti-dsDNA ) levels were observed among patients treated with rituximab . In both treatment groups , a reduction in anti-dsDNA levels greater than the median reduction was associated with reduced proteinuria . The rates of serious adverse events , including infections , were similar in both groups . Neutropenia , leukopenia , and hypotension occurred more frequently in the rituximab group . CONCLUSION Although rituximab therapy led to more responders and greater reductions in anti-dsDNA and C3/C4 levels , it did not improve clinical outcomes after 1 year of treatment . The combination of rituximab with MMF and corticosteroids did not result in any new or unexpected safety signals |
972 | 31,009,468 | Our study indicates that although preoperative cTn and perioperative change in cTn might be valuable predictors of MACE and /or all-cause mortality in adult noncardiac surgical patients , its overall prognostic performance remains uncertain . | BACKGROUND Increased postoperative cardiac troponin ( cTn ) independently predicts short-term mortality .
Previous studies suggest that preoperative cTn also predicts major adverse cardiovascular events ( MACE ) and mortality after noncardiac surgery .
The value of preoperative and perioperative changes in cTn as a prognostic tool for adverse outcomes has been sparsely investigated . | CONTEXT Of the 200 million adults worldwide who undergo noncardiac surgery each year , more than 1 million will die within 30 days . OBJECTIVE To determine the relationship between the peak fourth-generation troponin T ( TnT ) measurement in the first 3 days after noncardiac surgery and 30-day mortality . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve , international cohort study that enrolled patients from August 6 , 2007 , to January 11 , 2011 . Eligible patients were aged 45 years and older and required at least an overnight hospital admission after having noncardiac surgery . MAIN OUTCOME MEASURES Patients ' TnT levels were measured 6 to 12 hours after surgery and on days 1 , 2 , and 3 after surgery . We undertook Cox regression analysis in which the dependent variable was mortality until 30 days after surgery , and the independent variables included 24 preoperative variables . We repeated this analysis , adding the peak TnT measurement during the first 3 postoperative days as an independent variable and used a minimum P value approach to determine if there were TnT thresholds that independently altered patients ' risk of death . RESULTS A total of 15,133 patients were included in this study . The 30-day mortality rate was 1.9 % ( 95 % CI , 1.7%-2.1 % ) . Multivariable analysis demonstrated that peak TnT values of at least 0.02 ng/mL , occurring in 11.6 % of patients , were associated with higher 30-day mortality compared with the reference group ( peak TnT ≤ 0.01 ng/mL ) : peak TnT of 0.02 ng/mL ( adjusted hazard ratio [ aHR ] , 2.41 ; 95 % CI , 1.33 - 3.77 ) ; 0.03 to 0.29 ng/mL ( aHR , 5.00 ; 95 % CI , 3.72 - 6.76 ) ; and 0.30 ng/mL or greater ( aHR , 10.48 ; 95 % CI , 6.25 - 16.62 ) . Patients with a peak TnT value of 0.01 ng/mL or less , 0.02 , 0.03 - 0.29 , and 0.30 or greater had 30-day mortality rates of 1.0 % , 4.0 % , 9.3 % , and 16.9 % , respectively . Peak TnT measurement added incremental prognostic value to discriminate those likely to die within 30 days for the model with peak TnT measurement vs without ( C index = 0.85 vs 0.81 ; difference , 0.4 ; 95 % CI , 0.2 - 0.5 ; P < .001 for difference between C index values ) . The net reclassification improvement with TnT was 25.0 % ( P < .001 ) . CONCLUSION Among patients undergoing noncardiac surgery , the peak postoperative TnT measurement during the first 3 days after surgery was significantly associated with 30-day mortality BACKGROUND Cardiac complications are important causes of morbidity after noncardiac surgery . The purpose of this prospect i ve cohort study was to develop and vali date an index for risk of cardiac complications . METHODS AND RESULTS We studied 4315 patients aged > or = 50 years undergoing elective major noncardiac procedures in a tertiary-care teaching hospital . The main outcome measures were major cardiac complications . Major cardiac complications occurred in 56 ( 2 % ) of 2893 patients assigned to the derivation cohort . Six independent predictors of complications were identified and included in a Revised Cardiac Risk Index : high-risk type of surgery , history of ischemic heart disease , history of congestive heart failure , history of cerebrovascular disease , preoperative treatment with insulin , and preoperative serum creatinine > 2.0 mg/dL. Rates of major cardiac complication with 0 , 1 , 2 , or > or = 3 of these factors were 0.5 % , 1.3 % , 4 % , and 9 % , respectively , in the derivation cohort and 0.4 % , 0.9 % , 7 % , and 11 % , respectively , among 1422 patients in the validation cohort . Receiver operating characteristic curve analysis in the validation cohort indicated that the diagnostic performance of the Revised Cardiac Risk Index was superior to other published risk-prediction indexes . CONCLUSIONS In stable patients undergoing nonurgent major noncardiac surgery , this index can identify patients at higher risk for complications . This index may be useful for identification of c and i date s for further risk stratification with noninvasive technologies or other management strategies , as well as low-risk patients in whom additional evaluation is unlikely to be helpful OBJECTIVES To determine if troponin I and NT-proBNP were predictors of 6-month mortality after emergency orthopedic-geriatric surgery in a frail population . DESIGN Prospect i ve observational study . SETTING Orthopedic-geriatric unit of a metropolitan hospital in Australia . PARTICIPANTS A total of 383 patients were screened ; 44 were eligible for this study of which 33 patients consented who were receiving high-level care or had severe dementia or an illness with a prognosis of less than 12 months . MEASUREMENTS Troponin I and NT-proBNP were tested on one preoperative sample and at least one postoperative blood sample . Cardiac events were defined as acute myocardial infa rct ion , congestive cardiac failure , new onset or rapid atrial fibrillation , major arrhythmia , or cardiac arrest . RESULTS The mean age of the patients was 85.8 + /- 9.6 years and 93.9 % had a fractured neck of femur . Premorbid cardiac conditions were common ( 24.2 % had ischemic heart disease and 21.2 % congestive cardiac failure ) . A third of patients had a preoperative troponin elevation and 60.6 % had a postoperative elevation . The mortality within 30 days of surgery was 15.2 % ( 5/33 patients ) , rising to 39.4 % ( 13/33 ) at 6 months with 46.2 % ( 6/13 ) dying of a cardiac cause . The Kaplan-Meier survival curve was not significantly different between patients with and without a troponin elevation . A third of patients sustained a cardiac event at 6 months . The median preoperative NT-proBNP was 1651.50 pg/L , range 25 to 31,227 , and median postoperative NT-proBNP was 3038.50pg/L , range 44 to 27,348 . Troponin I and NT pro-BNP did not predict 6-month mortality or cardiac complications . Predictors of 6-month mortality using univariate analysis were number of comorbidities OR 2.0 ( 95 % CI 1.1 - 3.8 , P = .033 ) and premorbid atrial fibrillation OR 7.7 ( 95 % CI 1.2 - 47.8 , P = .028 ) . CONCLUSION Troponin I and NT-proBNP were not predictors of 6-month mortality or cardiac events in an older frailer population of patients undergoing orthopedic surgery . These patients sustained substantial cardiac morbidity and mortality at 6 months after surgery . The control of symptoms , rather than prolongation of life with cardiological intervention , may be more appropriate for this patient group : The purpose of this up date of the European Society of Anaesthesiology ( ESA ) guidelines on the pre-operative evaluation of the adult undergoing noncardiac surgery is to present recommendations based on the available relevant clinical evidence . Well performed r and omised studies on the topic are limited and therefore many recommendations rely to a large extent on expert opinion and may need to be adapted specifically to the healthcare systems of individual countries . This article aims to provide an overview of current knowledge on the subject with an assessment of the quality of the evidence in order to allow anaesthesiologists all over Europe to integrate - wherever possible - this knowledge into daily patient care . The Guidelines Committee of the ESA formed a task force comprising members of the previous task force , members of ESA scientific subcommittees and an open call for volunteers was made to all individual active members of the ESA and national societies . Electronic data bases were search ed from July 2010 ( end of the literature search of the previous ESA guidelines on pre-operative evaluation ) to May 2016 without language restrictions . A total of 34 066 abtracts were screened from which 2536 were included for further analysis . Relevant systematic review s with meta-analyses , r and omised controlled trials , cohort studies , case-control studies and cross-sectional surveys were selected . The Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) system was used to assess the level of evidence and to grade recommendations . The final draft guideline was posted on the ESA website for 4 weeks and the link was sent to all ESA members , individual or national ( thus including most European national anaesthesia societies ) . Comments were collated and the guidelines amended as appropriate . When the final draft was complete , the Guidelines Committee and ESA Board ratified the guidelines INTRODUCTION The relationship between electrocardiograph ( ECG ) changes and troponin levels after the emergency orthopaedic surgery are not well characterised . The aim of this study was to determine the correlation between ECG changes ( ischaemia or arrhythmia ) , troponin elevations perioperatively and cardiac complications . MATERIAL S AND METHODS One hundred and eighty-seven orthopaedic patients over 60 years of age were prospect ively tested for troponin I and ECGs were performed on the fi rst 3 postoperative mornings or until discharge . RESULTS The incidences of pre- and postoperative troponin elevation were 15.5 % and 37.4 % respectively , the majority were asymptomatically detected . Most of the patients who sustained a troponin rise did not have any concomitant ECG changes ( 51/70 or 72.9 % ) . Postoperative ECG changes were noted in 18.4 % ( 34/185 ) and of those with ECG changes , slightly more than half ( 55.9 % ) had a troponin elevation . Most ECG changes occurred on postoperative day 1 and were non-ST elevation in type . ECG changes occurred more frequently with higher troponin levels . Postoperative troponin elevation ( P = 0.018 ) and not preoperative troponin level ( P = 0.060 ) was associated with ECG changes on univariate analysis . Two premorbid factors were predictors of postoperative ECG changes using multivariate logistical regression ; age [ odds ratio ( OR ) , 1.05 ; 95 % CI , 1.005 to 1.100 , P = 0.029 ) and sex OR , 2.4 ; 95 % CI , 1.069 to 5.446 , P = 0.034 ) . Twenty patients sustained postoperative cardiac complications ; 9 ( 45 % ) were associated with ECG changes and 16 ( 80 % ) with postoperative troponin elevation . Pre- or postoperative troponin elevation better predicted cardiac complications compared with preoperative ECG changes . CONCLUSION Electrocardiograph changes do not necessarily accompany troponin elevations after the emergency orthopaedic surgery but are more likely to have higher troponin levels . The best predictor of postoperative cardiac complications is troponin elevation AIMS We aim ed to evaluate the incremental value of high-sensitive troponin T ( hsTnT ) for risk prediction prior to non-cardiac surgery in comparison with the established revised cardiac index . METHODS AND RESULTS In this prospect i ve , international multicentre observational study , 979 patients prior to non-cardiac surgery were enrolled . The endpoints were in-hospital mortality , the combination of death , acute myocardial infa rct ion , cardiac arrest , cardio-pulmonary resuscitation , and acute decompensated heart failure . Twenty-five patients ( 2.6 % ) deceased and 36 ( 3.7 % ) of the patients experienced the combined endpoint . Cardiac markers were elevated in those patients who died when compared with survivors ( hsTnT : 21 ng/L vs. 7 ng/L ; P < 0.001 ; NT-proBNP : 576 pg/mL vs. 166 pg/mL ; P < 0.001 ) . Applying a cut-off for hsTnT of 14 ng/L and for NT-proBNP of 300 pg/mL , those patients with elevated hsTnT had a mortality of 6.9 vs. 1.2 % ( P < 0.001 ) and with elevated NT-proBNP 4.8 vs. 1.4 % ( P = 0.002 ) . The highest AUC of the ROC curve was found for hsTnT as a predictor for mortality of 0.809 . In a multivariate Cox regression analyses , hsTnT was the strongest independent predictor for the combined endpoint [ HR 2.6 ( 95 % CI : 1.3 - 5.3 ) ; P = 0.01 ] . CONCLUSION High-sensitive troponin T provides strong prognostic information in patients undergoing non-cardiac surgery incremental to the widely accepted revised cardiac index OBJECTIVES The objective of this study was to ascertain the benefit of routine pre-operative cardiac troponin I ( cTnI ) measurement in patients undergoing major lower extremity amputation for critical limb ischaemia . DESIGN This was a prospect i ve , blinded observational study . METHODS All patients scheduled for lower extremity amputation , without evidence of unstable coronary artery disease were recruited prospect ively over a period of 1 year . In addition to routine pre-operative evaluation , a blood sample was taken for measurement of serum cTnI. Post-operative screening was conducted for cardiac events with patients followed up to 6 weeks . RESULTS Ten of the 44 patients included suffered a non-fatal myocardial infa rct ion or died from a cardiac cause post-operatively . A rise in pre-operative cTnI was associated with a very poor outcome ( two cardiac deaths and one post-operative myocardial infa rct ion ) and was the only significant predictor of post-operative cardiac events . CONCLUSION Routine pre-operative cTnI measurement may be of use to identify patients at high risk of cardiac complication who would benefit from optimization of cardiac status or in whom surgery could be deferred BACKGROUND Perioperative myocardial infa rct ion ( MI ) is a serious complication after noncardiac surgery . We hypothesized that preoperative cardiac troponin T detected with a novel high-sensitivity ( hs-cTnT ) assay will identify patients at risk for acute MI and long-term mortality after major noncardiac surgery . METHODS This was a prospect i ve cohort study within the VINO trial ( n = 608 ) . Patients had been diagnosed with or had multiple risk factors for coronary artery disease and underwent major noncardiac surgery . Cardiac troponin I ( contemporary assay ) and troponin T ( high-sensitivity assay ) and 12-lead electrocardiograms were obtained before and immediately after surgery and on postoperative days 1 , 2 , and 3 . RESULTS At baseline before surgery , 599 patients ( 98.5 % ) had a detectable hs-cTnT concentration , and 247 ( 41 % ) were > 14 ng/L ( 99th percentile ) . After surgery , 497 patients ( 82 % ) had a rise in hs-cTnT ( median change in hs-cTnT + 2.7 ng/L [ interquartile range 0.7 - 6.8 ] ) . During the first 3 postoperative days , there were 9 patients ( 2.5 % ) with a preoperative hs-cTnT < 14 ng/L with acute MI , compared with 21 patients ( 8.6 % ) with a preoperative hs-cTnT > 14 ng/L ( odds ratio 3.67 , 95 % CI 1.65 - 8.15 ) . During long-term follow-up , 80 deaths occurred . The 3-year mortality rate was 11 % in patients with a preoperative hs-cTnT concentration < 14 ng/L compared with 25 % in patients with a preoperative hs-cTnT > 14 ng/L ( adjusted hazard ratio 2.17 , 95 % CI 1.19 - 3.96 ) . CONCLUSIONS In this cohort of high-risk patients , preoperative hs-cTnT concentrations were significantly associated with postoperative MI and long-term mortality after noncardiac surgery BACKGROUND : Even small elevations in preoperative troponin levels have been shown to be associated with adverse outcomes . However , there are currently limited data on the relationship between troponin increase and timing of surgery . METHODS : We performed a single-institution , retrospective cohort study of 6030 individuals with a troponin measurement made during the 30 days preceding a noncardiac surgical procedure . Subjects with detectable troponin levels were separated into terciles based on both the magnitude of the value and the time elapsed between this value and the surgery . For those undergoing nonemergent procedures , these 9 cohorts were compared with the group of individuals with undetectable preoperative troponin levels using bivariable and multivariable logistic regression . RESULTS : Thirty-day mortality was 4.7 % in the group with undetectable troponin levels and increased with higher concentrations , with rates of 8.9 % , 12.7 % , and 12.7 % in the low , medium , and high tercile groups , respectively . Unadjusted risk of 30-day mortality was highest in those with the highest troponin levels and shortest duration between the measurement and surgery ( odds ratio , 4.497 ; 95 % confidence interval , 2.058–9.825 ) . After adjusting for subject characteristics , troponin remained associated with 30-day mortality in several groups , including individuals with troponin levels in the normal range . CONCLUSIONS : Higher levels of preoperative cardiac troponin I were associated with higher postoperative mortality , and longer time to surgery appeared to reduce this risk for individuals with mild preoperative troponin elevations . Prospect i ve studies are needed to determine whether delaying surgery in patients with elevated preoperative troponin levels improves postoperative outcomes Objectives : Myocardial infa rct ion after major surgery is frequent , drives outcome , and consumes health re sources . Specific prediction and detection of perioperative myocardial infa rct ion is an unmet clinical need . With the widespread use of high-sensitive cardiac troponin T assays , positive tests become frequent , but their diagnostic or prognostic impact is arguable . We , therefore , studied the association of routinely determined pre- and postoperative high-sensitive cardiac troponin T with the occurrence of major adverse cardiac events . Design : This study was a prospect i ve noninterventional trial . Setting : This study was conducted at Hannover Medical School in Germany . Patients : A total of 455 patients undergoing open vascular surgery were followed for 30 days for the occurrence of major adverse cardiac events . Interventions : None . Measurements and Main Results : Preoperative and 24-hour postoperative high-sensitive cardiac troponin T measurements and the respective changes were correlated to medical history and the occurrence of major adverse cardiac events ( cardiovascular death , myocardial infa rct ion , and ischemia ) . Pre- and postoperative high-sensitive cardiac troponin T measurements demonstrated a majority of patients with detectable troponin levels preoperatively and an increase over the 24 hours after surgery . The level of high-sensitive cardiac troponin T was significantly associated with preexisting diseases that constitute the Lee ’s Revised Cardiac Risk Index . A preoperative high-sensitive cardiac troponin T greater than or equal to 17.8 ng/L and a perioperative high-sensitive cardiac troponin T change greater than or equal to 6.3 ng/L are independently associated with the occurrence of major adverse cardiac events . Adding high-sensitive cardiac troponin T absolute change to the Revised Cardiac Risk Index improves the risk predictive accuracy of the score as evidence d by increased area under receiver operating characteristic and significant reclassification effects . Conclusions : The risk predictive power of high-sensitive cardiac troponin T change in addition to the Revised Cardiac Risk Index could facilitate 1 ) detection of patients at highest risk for perioperative myocardial ischemia , 2 ) evaluation and development of cardioprotective therapeutic strategies , and 3 ) decisions for admission to and discharge from high-density care units Although brain natriuretic peptide has been shown to be superior to the revised cardiac risk index for risk stratification of vascular surgical patients , it remains unknown whether it is superior to alternative dynamic risk predictors , such as other pre‐operative biomarkers ( C‐reactive protein and troponins ) or myocardial ischaemia monitoring . The aim of this prospect i ve observational study was to determine the relative clinical utility of these risk predictors for the prediction of postoperative cardiac events in elective vascular surgical patients . Only pre‐operative troponin elevation ( OR 56.8 , 95 % CI 6.5–496.0 , p < 0.001 ) and brain natriuretic peptide above the optimal discriminatory point ( OR 6.0 , 95 % CI 2.7–12.9 , p < 0.001 ) were independently associated with cardiac events . Both brain natriuretic peptide and troponin risk stratification significantly improved overall net reclassification ( 74.6 % ( 95 % CI 51.6%–97.5 % ) and 38.5 % ( 95 % CI 22.4–54.6 % , respectively ) ) ; however , troponin stratification decreased the correct classification of patients with cardiac complications ( −59 % , p < 0.001 ) . Pre‐operative brain natriuretic peptide evaluation was the only clinical ly useful predictor of postoperative cardiac complications Background — Perioperative myocardial infa rct ion or cardiac arrest is associated with significant morbidity and mortality . The Revised Cardiac Risk Index is currently the most commonly used cardiac risk stratification tool ; however , it has several limitations , one of which is its relatively low discriminative ability . The objective of the present study was to develop and vali date a predictive cardiac risk calculator . Methods and Results — Patients who underwent surgery were identified from the American College of Surgeons ' 2007 National Surgical Quality Improvement Program data base , a multicenter ( > 250 hospitals ) prospect i ve data base . Of the 211 410 patients , 1371 ( 0.65 % ) developed perioperative myocardial infa rct ion or cardiac arrest . On multivariate logistic regression analysis , 5 predictors of perioperative myocardial infa rct ion or cardiac arrest were identified : type of surgery , dependent functional status , abnormal creatinine , American Society of Anesthesiologists ' class , and increasing age . The risk model based on the 2007 data set was subsequently vali date d on the 2008 data set ( n=257 385 ) . The model performance was very similar between the 2007 and 2008 data sets , with C statistics ( also known as area under the receiver operating characteristic curve ) of 0.884 and 0.874 , respectively . Application of the Revised Cardiac Risk Index to the 2008 National Surgical Quality Improvement Program data set yielded a relatively lower C statistic ( 0.747 ) . The risk model was used to develop an interactive risk calculator . Conclusions — The cardiac risk calculator provides a risk estimate of perioperative myocardial infa rct ion or cardiac arrest and is anticipated to simplify the informed consent process . Its predictive performance surpasses that of the Revised Cardiac Risk Index Objective Cardiovascular complications are important causes of morbidity and mortality in elective non-cardiac surgery . Although difficult to diagnose , perioperative myocardial infa rct ion ( MI ) remains prognostically important . High-sensitivity troponin T ( hs-TnT ) assays allow detection of very minor damage to cardiac muscle . These assays are yet to be fully evaluated in the perioperative setting . Our aim was to determine the incidence and predictors of myocardial necrosis in patients at high cardiovascular risk undergoing elective non-cardiac surgery using hs-TnT. Design Prospect i ve observational cohort study . Patients 352 consecutive patients undergoing elective major non-cardiac surgery prescribed antiplatelet therapy for primary or secondary cardiovascular event prevention . Main outcome measure The incidence of elevated preoperative hs-TnT ( ≥14 ng/litre ) , hs-TnT-defined perioperative myocardial necrosis ( ≥ 14ng/litre and 50 % increase from preoperative level ) , and perioperative MI were determined in relation to patient and surgical factors . Results Preoperative hs-TnT was elevated in 31 % and postoperative myocardial necrosis occurred in 22 % of patients . Predictors of elevated baseline hs-TnT included age ( OR 1.10 , p<0.001 ) , male gender ( OR 2.91 , p<0.001 ) , diabetes requiring insulin therapy ( OR 4.85 , p=0.004 ) and chronic kidney disease ( OR 3.60 , p<0.001 ) . Independent predictors of perioperative myocardial necrosis were age ( OR 1.07 , p<0.001 ) , intraoperative hypotension ( OR 3.67 , p=0.001 ) and orthopaedic surgery ( OR 2.46 , p=0.005 ) . Only 2 % of patients suffered clinical ly apparent MI . Elevated preoperative hs-TnT did not predict perioperative myocardial necrosis or MI . Conclusions Perioperative myocardial damage occurs frequently in patients undergoing elective non-cardiac surgery , although the majority of events are clinical ly undetected . Age and intraoperative hypotension are independent predictors of myocardial necrosis in this setting Importance Little is known about the relationship between perioperative high-sensitivity troponin T ( hsTnT ) measurements and 30-day mortality and myocardial injury after noncardiac surgery ( MINS ) . Objective To determine the association between perioperative hsTnT measurements and 30-day mortality and potential diagnostic criteria for MINS ( ie , myocardial injury due to ischemia associated with 30-day mortality ) . Design , Setting , and Participants Prospect i ve cohort study of patients aged 45 years or older who underwent inpatient noncardiac surgery and had a postoperative hsTnT measurement . Starting in October 2008 , participants were recruited at 23 centers in 13 countries ; follow-up finished in December 2013 . Exposures Patients had hsTnT measurements 6 to 12 hours after surgery and daily for 3 days ; 40.4 % had a preoperative hsTnT measurement . Main Outcomes and Measures A modified Mazumdar approach ( an iterative process ) was used to determine if there were hsTnT thresholds associated with risk of death and had an adjusted hazard ratio ( HR ) of 3.0 or higher and a risk of 30-day mortality of 3 % or higher . To determine potential diagnostic criteria for MINS , regression analyses ascertained if postoperative hsTnT elevations required an ischemic feature ( eg , ischemic symptom or electrocardiography finding ) to be associated with 30-day mortality . Results Among 21 842 participants , the mean age was 63.1 ( SD , 10.7 ) years and 49.1 % were female . Death within 30 days after surgery occurred in 266 patients ( 1.2 % ; 95 % CI , 1.1%-1.4 % ) . Multivariable analysis demonstrated that compared with the reference group ( peak hsTnT < 5 ng/L ) , peak postoperative hsTnT levels of 20 to less than 65 ng/L , 65 to less than 1000 ng/L , and 1000 ng/L or higher had 30-day mortality rates of 3.0 % ( 123/4049 ; 95 % CI , 2.6%-3.6 % ) , 9.1 % ( 102/1118 ; 95 % CI , 7.6%-11.0 % ) , and 29.6 % ( 16/54 ; 95 % CI , 19.1%-42.8 % ) , with corresponding adjusted HRs of 23.63 ( 95 % CI , 10.32 - 54.09 ) , 70.34 ( 95 % CI , 30.60 - 161.71 ) , and 227.01 ( 95 % CI , 87.35 - 589.92 ) , respectively . An absolute hsTnT change of 5 ng/L or higher was associated with an increased risk of 30-day mortality ( adjusted HR , 4.69 ; 95 % CI , 3.52 - 6.25 ) . An elevated postoperative hsTnT ( ie , 20 to < 65 ng/L with an absolute change ≥5 ng/L or hsTnT ≥65 ng/L ) without an ischemic feature was associated with 30-day mortality ( adjusted HR , 3.20 ; 95 % CI , 2.37 - 4.32 ) . Among the 3904 patients ( 17.9 % ; 95 % CI , 17.4%-18.4 % ) with MINS , 3633 ( 93.1 % ; 95 % CI , 92.2%-93.8 % ) did not experience an ischemic symptom . Conclusions and Relevance Among patients undergoing noncardiac surgery , peak postoperative hsTnT during the first 3 days after surgery was significantly associated with 30-day mortality . Elevated postoperative hsTnT without an ischemic feature was also associated with 30-day mortality Background : Myocardial injury after noncardiac surgery ( MINS ) was defined as prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days after noncardiac surgery . The study ’s four objectives were to determine the diagnostic criteria , characteristics , predictors , and 30-day outcomes of MINS . Methods : In this international , prospect i ve cohort study of 15,065 patients aged 45 yr or older who underwent in-patient noncardiac surgery , troponin T was measured during the first 3 postoperative days . Patients with a troponin T level of 0.04 ng/ml or greater ( elevated “ abnormal ” laboratory threshold ) were assessed for ischemic features ( i.e. , ischemic symptoms and electrocardiography findings ) . Patients adjudicated as having a nonischemic troponin elevation ( e.g. , sepsis ) were excluded . To establish diagnostic criteria for MINS , the authors used Cox regression analyses in which the dependent variable was 30-day mortality ( 260 deaths ) and independent variables included preoperative variables , perioperative complications , and potential MINS diagnostic criteria . Results : An elevated troponin after noncardiac surgery , irrespective of the presence of an ischemic feature , independently predicted 30-day mortality . Therefore , the authors ’ diagnostic criterion for MINS was a peak troponin T level of 0.03 ng/ml or greater judged due to myocardial ischemia . MINS was an independent predictor of 30-day mortality ( adjusted hazard ratio , 3.87 ; 95 % CI , 2.96–5.08 ) and had the highest population -attributable risk ( 34.0 % , 95 % CI , 26.6–41.5 ) of the perioperative complications . Twelve hundred patients ( 8.0 % ) suffered MINS , and 58.2 % of these patients would not have fulfilled the universal definition of myocardial infa rct ion . Only 15.8 % of patients with MINS experienced an ischemic symptom . Conclusion : Among adults undergoing noncardiac surgery , MINS is common and associated with substantial mortality Background : Perioperative myocardial injury ( PMI ) seems to be a contributor to mortality after noncardiac surgery . Because the vast majority of PMIs are asymptomatic , PMI usually is missed in the absence of systematic screening . Methods : We performed a prospect i ve diagnostic study enrolling consecutive patients undergoing noncardiac surgery who had a planned postoperative stay of ≥24 hours and were considered at increased cardiovascular risk . All patients received a systematic screening using serial measurements of high-sensitivity cardiac troponin T in clinical routine . PMI was defined as an absolute high-sensitivity cardiac troponin T increase of ≥14 ng/L from preoperative to postoperative measurements . Furthermore , mortality was compared among patients with PMI not fulfilling additional criteria ( ischemic symptoms , new ECG changes , or imaging evidence of loss of viable myocardium ) required for the diagnosis of spontaneous acute myocardial infa rct ion versus those that did . Results : From 2014 to 2015 we included 2018 consecutive patients undergoing 2546 surgeries . Patients had a median age of 74 years and 42 % were women . PMI occurred after 397 of 2546 surgeries ( 16 % ; 95 % confidence interval , 14%–17 % ) and was accompanied by typical chest pain in 24 of 397 patients ( 6 % ) and any ischemic symptoms in 72 of 397 ( 18 % ) . Crude 30-day mortality was 8.9 % ( 95 % confidence interval [ CI ] , 5.7–12.0 ) in patients with PMI versus 1.5 % ( 95 % CI , 0.9–2.0 ) in patients without PMI ( P<0.001 ) . Multivariable regression analysis showed an adjusted hazard ratio of 2.7 ( 95 % CI , 1.5–4.8 ) for 30-day mortality . The difference was retained at 1 year with mortality rates of 22.5 % ( 95 % CI , 17.6–27.4 ) versus 9.3 % ( 95 % CI , 7.9–10.7 ) . Thirty-day mortality was comparable among patients with PMI not fulfilling any other of the additional criteria required for spontaneous acute myocardial infa rct ion ( 280/397 , 71 % ) versus those with at least 1 additional criterion ( 10.4 % ; 95 % CI , 6.7–15.7 , versus 8.7 % ; 95 % CI , 4.2–16.7 ; P=0.684 ) . Conclusions : PMI is a common complication after noncardiac surgery and , despite early detection during routine clinical screening , is associated with substantial short- and long-term mortality . Mortality seems comparable in patients with PMI not fulfilling any other of the additional criteria required for spontaneous acute myocardial infa rct ion versus those patients who do . Clinical Trial Registration : URL : https://www . clinical trials.gov . Unique identifier : NCT02573532 |
973 | 31,656,589 | Conclusions : This systematic review showed that CPGs could be useful to improve the process and structure of health care and , to a lesser extent , to improve the results in patients .
There are probably still undiscovered variables that interfere with the use of the CPGs and , therefore , with their impact . | Background : The development of clinical practice guidelines ( CPGs ) has increasing global growth ; however , the certainty of impact on patients and health systems , as well as the magnitude of the impact , is not apparent .
The objective of this systematic review was to assess the effectiveness of the application of CPGs for the improvement of the quality of health care in three domains : structure , process and results in the patient for the management of cardiovascular disease . | Background . The influence of an opinion leader intervention on adherence to Unstable Angina ( UA ) guidelines compared with a traditional quality improvement model was investigated . Research Design . A group-r and omized controlled trial with 2210 patients from 21 hospitals was design ed . There were three intervention arms : ( 1 ) no intervention ( NI ) ; ( 2 ) a traditional Health Care Quality Improvement Program ( HCQIP ) ; and ( 3 ) a physician opinion leader in addition to the HCQIP model ( OL ) . Quality indicators included : electrocardiogram within 20 minutes , antiplatelet therapy within 24 hours and at discharge , and heparin and & bgr;-blockers during hospitalization . Hospitals could determine the specific indicators they wished to target . Potential cases of UA were identified from Medicare cl aims data . UA confirmation was determined by a clinical algorithm based on data abstract ed from medical records . Data analyses included both hospital level analysis ( analysis of variance ) and patient level analysis ( generalized linear models ) . Results . The only statistically significant postintervention difference in percentage compliant was greater improvement for the OL group in the use of antiplatelet therapy at 24 hours in both hospital level ( P = 0.01 ) and patient level analyses ( P < 0.05 ) compared with the HCQIP and NI groups . When analyses were confined to hospitals that targeted specific indicators , compared with the HCQIP hospitals , the OL hospitals showed significantly greater change in percentage compliant postintervention in both antiplatelet therapy during the first 24 hours ( 20.2 % vs. −3.9 % , P = 0.02 ) and heparin ( 31.0 % vs.9.1 % , P = 0.05 ) . Conclusions . The influence of physician opinion leaders was unequivocally positive for only one of five quality indicators . To maximize adherence to best practice s through physician opinion leaders , more research on how these physicians influence health care delivery in their organizations will be required BACKGROUND Public agencies responsible for implementing health care policies often adapt and disseminate clinical practice guidelines , but the effectiveness of mass dissemination of guidelines is unknown . AIM To study the effects of guideline dissemination on physicians ' prescribing practice s for the treatment of stable angina pectoris . DESIGN R and omized controlled trial . METHODS A sample of 3293 Quebec physicians were r and omly assigned to receive a one-page summary of clinical practice guidelines on the treatment of stable angina ( in February 1999 ) , to receive the summary and a reminder ( in February and March 1999 , respectively ) , or to receive no intervention ( controls ) . The prescribing profiles of participants , as well as sociodemographic characteristics of the physicians and their patients , were examined for June-December 1999 . RESULTS The intervention had no effect on prescription rates of beta-blockers , antiplatelet agents , or hypolipaemic drugs . Compared to 1997 data for the same physicians , there was an overall 10 % increase in appropriate prescription rates , irrespective of the intervention . DISCUSSION In-house production and dissemination of clinical practice guidelines may not improve physicians ' practice patterns if there is pre-existing substantial scientific consensus on the issue Abstract Objective : To study the efficacy of case method learning , for general practitioners , on patients ' lipid concentrations in the secondary prevention of coronary artery disease . Design : Prospect i ve controlled trial . Setting : Södertälje , Stockholm County , Sweden . Participants : 255 consecutive patients with coronary artery disease . Intervention : Guidelines were mailed to all general practitioners ( n=54 ) and presented at a common lecture . General practitioners who were r and omised to the intervention group participated in recurrent case method learning dialogues at their primary healthcare centres during a two year period . A locally well known cardiologist served as a facilitator . Main outcome measure : Concentration of low density lipoprotein cholesterol at baseline and after two years . Analysis according to intention to treat ( intervention and control groups ( n=88 ) ) was based on group affiliation at baseline . Results : Low density lipoprotein cholesterol was reduced by 0.5 mmol/l ( 95 % confidence interval 0.2 to 0.8 mmol/l ) ( 9.3 % ( 2.9 % to 15.8 % ) ) from baseline in patients in the intervention group and by 0.5 ( 0.1 to 0.9 ) mmol/l compared with controls ( P<0.05 ) . No change occurred in the control group ( 0.0 ( −0.2 to 0.2 ) mmol/l ) . Low density lipoprotein cholesterol decreased by 0.6 ( 0.4 to 0.8 ) mmol/l in a group of patients who received specialist care . Conclusion : Case method learning result ed in a lowering of low density lipoprotein cholesterol in the primary care patients with coronary artery disease comparable to that achieved at a specialist clinic . Conventional presentation of practice guidelines had no effect PURPOSE To assess the effects of an intervention involving dissemination of treatment recommendations to primary care physicians treating out patients with acute myocardial infa rct ion or heart failure . METHODS The study comprised 509 patients with myocardial infa rct ion and 323 patients with heart failure who were discharged from hospital . The primary care physicians caring for these patients were assigned r and omly to either the intervention or control group ; the intervention group was mailed practice guidelines immediately after patient discharge , and patients were cited by name . During a 6-month assessment period , the records of primary care physicians ( and cardiologists , if any ) were review ed to assess mean conformance with the guidelines , using seven measures of care for myocardial infa rct ion and eight measures of care for heart failure . RESULTS After adjusting for demographic and clinical characteristics of patients , and the number of eligible measures per patient , we observed no effect of the intervention on care of patients with myocardial infa rct ion ( odds ratio [ OR ] = 0.98 ; 95 % confidence interval [ CI ] : 0.81 to 1.17 ) or heart failure ( OR = 1.25 ; 95 % CI : 0.96 to 1.59 ) . However , there was a higher likelihood of conformance with measures for patients with infa rct ion ( OR = 1.56 ; 95 % CI : 1.29 to 1.87 ) or heart failure ( OR = 1.71 ; 95 % CI : 1.29 to 2.23 ) who had also been seen by a cardiologist during the 6-month assessment period . CONCLUSION Mailing treatment recommendations did not improve the quality of care of recently discharged patients with myocardial infa rct ion or heart failure . However , efforts to include cardiologists in the care of these patients might be worthwhile Background — Hypertension control rates remain suboptimal . Pharmacists ’ scope of practice is evolving , and their position in the community may be ideal for improving hypertension care . We aim ed to study the impact of pharmacist prescribing on blood pressure ( BP ) control in community-dwelling patients . Methods and Results — We design ed a patient-level , r and omized , controlled trial , enrolling adults with above-target BP ( as defined by Canadian guidelines ) through community pharmacies , hospitals , or primary care teams in 23 communities in Alberta . Intervention group patients received an assessment of BP and cardiovascular risk , education on hypertension , prescribing of antihypertensive medications , laboratory monitoring , and monthly follow-up visits for 6 months ( all by their pharmacist ) . Control group patients received a wallet card for BP recording , written hypertension information , and usual care from their pharmacist and physician . Primary outcome was the change in systolic BP at 6 months . A total of 248 patients ( mean age , 64 years ; 49 % male ) were enrolled . Baseline mean±SD systolic/diastolic BP was 150±14/84±11 mm Hg . The intervention group had a mean±SE reduction in systolic BP at 6 months of 18.3±1.2 compared with 11.8±1.9 mm Hg in the control group , an adjusted difference of 6.6±1.9 mm Hg ( P=0.0006 ) . The adjusted odds of patients achieving BP targets was 2.32 ( 95 % confidence interval , 1.17–4.15 in favor of the intervention ) . Conclusions — Pharmacist prescribing for patients with hypertension result ed in a clinical ly important and statistically significant reduction in BP . Policy makers should consider an exp and ed role for pharmacists , including prescribing , to address the burden of hypertension . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00878566 Background : The 2007 American College of Cardiologists/American Heart Association Guidelines on Perioperative Cardiac Evaluation and Care for Noncardiac Surgery is the st and ard for perioperative cardiac evaluation . Recent work has shown that residents and anesthesiologists do not apply these guidelines when tested . This research hypothesized that a decision support tool would improve adherence to this consensus guideline . Methods : Anesthesiology residents at four training programs participated in an unblinded , prospect i ve , r and omized , cross-over trial in which they completed two tests covering clinical scenarios . One quiz was completed from memory and one with the aid of an electronic decision support tool . Performance was evaluated by overall score ( % correct ) , number of incorrect answers with possibly increased cost or risk of care , and the amount of time required to complete the quizzes both with and without the cognitive aid . The primary outcome was the proportion of correct responses attributable to the use of the decision support tool . Results : All anesthesiology residents at four institutions were recruited and 111 residents participated . Use of the decision support tool result ed in a 25 % improvement in adherence to guidelines compared with memory alone ( P < 0.0001 ) , and participants made 77 % fewer incorrect responses that would have result ed in increased costs . Use of the tool was associated with a 3.4-min increase in time to complete the test ( P < 0.001 ) . Conclusions : Use of an electronic decision support tool significantly improved adherence to the guidelines as compared with memory alone . The decision support tool also prevented inappropriate management steps possibly associated with increased healthcare costs BACKGROUND : Electronic information systems have been proposed as one means to reduce medical errors of commission ( doing the wrong thing ) and omission ( not providing indicated care ) . OBJECTIVE : To assess the effects of computer-based cardiac care suggestions . DESIGN : A r and omized , controlled trial targeting primary care physicians and pharmacists . SUBJECTS : A total of 706 out patients with heart failure and /or ischemic heart disease . INTERVENTIONS : Evidence -based cardiac care suggestions , approved by a panel of local cardiologists and general internists , were displayed to physicians and pharmacists as they cared for enrolled patients . MEASUREMENTS : Adherence with the care suggestions , generic and condition-specific quality of life , acute exacerbations of their cardiac disease , medication compliance , health care costs , satisfaction with care , and physicians ’ attitudes toward guidelines . RESULTS : Subjects were followed for 1 year during which they made 3,419 primary care visits and were eligible for 2,609 separate cardiac care suggestions . The intervention had no effect on physicians ’ adherence to the care suggestions ( 23 % for intervention patients vs 22 % for controls ) . There were no intervention-control differences in quality of life , medication compliance , health care utilization , costs , or satisfaction with care . Physicians viewed guidelines as providing helpful information but constraining their practice and not helpful in making decisions for individual patients . CONCLUSIONS : Care suggestions generated by a sophisticated electronic medical record system failed to improve adherence to accepted practice guidelines or outcomes for patients with heart disease . Future studies must weigh the benefits and costs of different ( and perhaps more Draconian ) methods of affecting clinician behavior AIM OF THE STUDY The European Resuscitation Council ( ERC ) guidelines changed in 2005 . We investigated the impact of these changes on no flow time and on the quality of cardiopulmonary resuscitation ( CPR ) . MATERIAL S AND METHODS Simulated cardiac arrest ( CA ) scenarios were managed r and omly in manikins using ERC 2000 or 2005 guidelines . Pairs of paramedics/paramedic students treated 34 scenarios with 10min of continuous ventricular fibrillation . The rhythm was analysed and defibrillation shocks were delivered with a semi-automatic defibrillator , and breathing was assisted with a bag-valve-mask ; no intravenous medication was given . Time factors related to human intervention and time factors related to device , rhythm analysis , charging and defibrillation were analysed for their contribution to no flow time ( time without chest compression ) . Chest compression quality was also analysed . RESULTS No flow time ( mean+/-S.D. ) was 66+/-3 % of CA time with ERC 2000 and 32+/-4 % with ERC 2005 guidelines ( P<0.001 ) . Human factor interventions occupied 114+/-4s ( ERC 2000 ) versus 107+/-4s ( ERC 2005 ) during 600-s scenarios ( P=0.237 ) . Device factor interventions took longer using ERC 2000 guidelines : 290+/-19s versus 92+/-15s ( P<0.001 ) . The total number of chest compressions was higher with ERC 2005 guidelines ( 808+/-92s versus 458+/-90s , P<0.001 ) , but the quality of CPR did not differ between the groups . CONCLUSIONS The use of a single shock sequence with guidelines 2005 has decreased the no flow time during CPR when compared with guidelines 2000 with multiple shocks We examined the impact of ambulatory care clinical pharmacist interventions on clinical and economic outcomes of 208 patients with dyslipidemia and 229 controls treated at nine Veterans Affairs medical centers . This was a r and omized , controlled trial involving patients at high risk of drug-related problems . Only those with dyslipidemia are reported here . In addition to usual medical care , clinical pharmacists were responsible for providing pharmaceutical care for patients in the intervention group . The control group did not receive pharmaceutical care . Seventy-two percent of the intervention group and 70 % of controls required secondary prevention according to the National Cholesterol Education Program guidelines . Significantly more patients in the intervention group had a fasting lipid profile compared with controls ( p=0.021 ) . The absolute change in total cholesterol ( 17.7 vs 7.4 mg/dl , p=0.028 ) and low-density lipoprotein ( 23.4 vs 12.8 mg/dl , p=0.042 ) was greater in the intervention than in the control group . There were no differences in patients achieving goal lipid values or in overall costs despite increased visits to pharmacists . Ambulatory care clinical pharmacists can significantly improve dyslipidemia in a practice setting design ed to manage many medical and drug-related problems |
974 | 25,131,812 | Multiple and flexible strategies targeting providers and participants at provider sites and within communities might be needed to enroll underrepresented population s into clinical trials | BACKGROUND Underrepresentation of racial and ethnic minorities in clinical trials remains a reality while they have disproportionately higher rates of health disparities .
OBJECTIVE The purpose of this study was to identify successful community-engaged interventions that included health care providers as a key strategy in addressing barriers to clinical trial enrollment of underrepresented patients . | We are conducting a community-based cluster-r and omized trial in rural Alabama , testing a peer-support intervention design ed to improve diabetes self-care behaviors . We describe recruitment and data collection approaches used , focusing on strategies that created community partnerships and facilitated recruitment in underserved , rural , largely minority communities . Key recruitment and data collection strategies included early community engagement ; pilot testing of procedures ; inclusion of community members as study team members , recruiters , and data collectors ; data collection at community venues to minimize participant travel requirements ; and provision of a multi-disciplinary diabetes education program to both intervention and control participants . A total of 424 participants were recruited and enrolled ( 400 targeted ) . Of the 759 referrals received , 78.9 % ( n=599 ) successfully completed telephone screening . Of these , 78.8 % ( n=472 ) were eligible and scheduled for a local enrollment day , and 81.4 % ( n=384 ) attended and enrolled in the study . In addition , community members who walked in and expressed interest were screened , and 40 eligible and willing individuals were consented and enrolled . We exceeded recruitment goals in underserved , rural communities in Alabama . This success was due in large part to community partnerships that facilitated community involvement on several levels : engaging the community early in study proposal and design ; hiring community members to fill various capacities as research team members , recruiters , and data collectors ; conducting data collection within communities ; and collecting additional contact information to maintain communication . Providing diabetes education to all participants , including intervention and control , helped ensure that everyone stood to benefit and likely enhanced overall participation Purpose To describe methods used to recruit and retain low-income Latinos in a r and omized clinical trial ( RCT ) of a diabetes self-management intervention at 5 community health centers ( CHCs ) in Massachusetts . Methods Consent from primary care providers ( PCPs ) was obtained to screen their patients . Trained site research coordinators ( SRCs ) screened , recruited , and enrolled participants following a multistep process ( medical record review s , PCP approval , a patient eligibility interview ) and provided support for retention efforts . Assessment staff were trained in motivational strategies to facilitate retention and received ongoing support from a retention coordinator . Electronic tracking systems facilitated recruitment and retention activities . Results Of an initial pool of 1176 patients , 1034 were active at the time of screening , 592 ( 57 % ) were eligible by medical record review , and 487 received PCP approval ( 92 % of review ed patients ) . Of these , 293 patients completed the patient screening interview ( 60 % of patients with PCP approval , and 76 % of those reached ) , and 276 were eligible . Sixteen percent of all active patients refused participation , and 8 % of contacted patients were unreachable . Two hundred fifty-two patients were r and omized after completion of baseline assessment s. Clinical , behavioral , and psychosocial assessment completion rates were 92 % , 77 % , and 86 % at 12-month follow-up , respectively , and 93 % of patients completed at least one study assessment at 12 months . Conclusions CHCs are a prime setting for translation research aim ed to eliminate diabetes health disparities . Successful recruitment and retention efforts must address institutional/organizational , research team , and patient-related challenges . References 1 . US Department of Health and Human Services , Centers for Disease Control and Prevention . Age-adjusted prevalence of diagnosed diabetes by race/ethnicity and sex in the United States , 1980 - 2005 . Available at : www.cdc.gov/diabetes/statistics/prev/ national/figraceethsex.htm . Accessed January 21 , 2010 . 2 . US Census Bureau . Annual estimates of the population by sex , race , and Hispanic or Latino origin for the United States : April 1 , 2000 to July 1 , 2006 . Available at : www.census.gov/popest/ national/asrh/NC-EST2006-srh.html . Accessed January 21 , 2010 . 3 . National Center for Health Statistics . Early release of selected estimates based on data from the January-September 2006 National Health Interview Survey . Available at : http://www . cdc.gov/nchs/about/major/nhis/released200703.htm . Accessed January 12 , 2010 . 4 . Centers for Disease Control and Prevention . Self-reported prevalence of diabetes among Hispanics : United States , 1994 - 1997 . MMWR . 1999;48:8 - 12 . 5 . Harris MI , Klein R , Cowie CC , Rowl and M , Byrd-Holt DD . Is the risk of diabetic retinopathy greater in non-Hispanic blacks and Mexican Americans than in non-Hispanic whites with type 2 diabetes ? A U.S. population study . Diabetes Care . 1998 ; 21:1230 - 1235 . 6 . Franklin GM , Kahn LB , Baxter J , Marshall JA , Hamman RF . Sensory neuropathy in non-insulin-dependent diabetes mellitus : the San Luis Valley Diabetes Study . Am J Epidemiol . 1990;131:633 - 643 . 7 . Agency for Healthcare Research and Quality . National Healthcare Disparities Report , 2006 . Rockville , MD : Agency for Healthcare Research and Quality ; 2006 . Available at : http://www.ahrq.gov/ qual/nhdr06/nhdr06.htm . Accessed January 12 , 2010 . 8 . National Institute of Diabetes and Digestive and Kidney Diseases , National Diabetes Information Clearinghouse ( NDIC ) . National diabetes statistics . Available at : http://diabetes.niddk.nih.gov/dm/ pubs/statistics/index.htm . Accessed January 12 , 2010 . 9 . US Department of Health and Human Services , Office of Minority Research . Diabetes and Hispanic Americans . Available at : http://www.omhrc.gov/templates/content.aspx?lvl=2&lvllD= 54&ID=3324 . Accessed December 10 , 2009 . 10 . The Diabetes Control and Complications Trial Research Group . The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus . N Engl J Med . 1993;329 : 977 - 986 . 11 . UK Prospect i ve Diabetes Study ( UKPDS ) Group . Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes ( UKPDS 33 ) . Lancet . 1998;352:837 - 853 . 12 . Norris SL , Engelgau MM , Narayan KM . Effectiveness of self-management training in type 2 diabetes : a systematic review of r and omized controlled trials . Diabetes Care . 2001;24:561 - 587 . 13 . Brown SA , Garcia AA , Kouzekanani K , Hanis CL . Culturally competent diabetes self-management education for Mexican Americans : the Starr County border health initiative . Diabetes Care . 2002;25:259 - 268 . 14 . Lorig K , Ritter PL , Villa F , Piette JD . Spanish diabetes self-management with and without automated telephone reinforcement : two r and omized trials . Diabetes Care . 2008 ; 31:408 - 414 . 15 . Rosal MC , Olendzki B , Reed GW , Gumieniak O , Scavron J , Ockene IS . Diabetes self-management among low-income Spanish speaking patients : a pilot study . Ann Behav Med . 2005;29:225 - 235 . 16 . Mauldon M , Melkus GD , Cagganello M. Tom and o Control : a culturally appropriate diabetes education program for Spanish-speaking individuals with type 2 diabetes mellitus . Evaluation of a pilot project . Diabetes Educ . 2006;32:751 - 760 . 17 . Centers for Disease Control and Prevention , National Center for Health Statistics . Age-adjusted percentage of civilian , noninstitutionalized population with diagnosed diabetes , Hispanics , United States , 1980 - 2007 . Available at : http://www.ced.gov/diabetes/ statistics/prev/national/figbyhispanic.htm . Accessed March 31 , 2010 . 18 . Flegal KM , Ezzati TM , Harris MI . Prevalence of diabetes in Mexican Americans , Cubans , and Puerto Ricans from the Hispanic health and nutrition examination survey 1982 - 1984 . Diabetes Care . 1991;14(7 Suppl):528 - 538 . 19 . Lemon SC , Zapka JG , Estabrook B , Benjamin E. Challenges to research in urban community health centers . Am J Public Health . 2006;96:626 - 628 . 20 . H and ley MA , Hammer H , Schillinger D. Navigating the terrain between research and practice : a Collaborative Research Network ( CRN ) case study in diabetes research . J Am Board Fam Med . 2006;19:85 - 92 . 21 . Piatt GA , Orchard TJ , Emerson S. Translating the chronic care model into the community : results from a r and omized controlled trial of a multifaceted diabetes care intervention . Diabetes Care . 2006;29:811 - 817 . 22 . Frayne SM , Burns RB , Hardt EJ , Rosen AK , Moskowitz MA . The exclusion of non-English-speaking persons from research . J Gen Intern Med . 1996;11:39 - 43 . 23 . Durant RW , Davis RB , St George M , Williams IC , Blumenthal C , Corbie-Smith GM . Participation in research studies : factors associated with failing to meet minority recruitment goals . Ann Epidemiol . 2007;17:634 - 642 . 24 . Centers for Disease Control and Prevention , Department of Health and Human Services . Diabetes data and trends . Available at : http : www.cdc.gov/diabetes/statistics/prev/national/. Accessed March 31 , 2010 . 25 . Surani S , Aguillar R , Komari V , Surani A , Subramanian S. Influence of Hispanic ethnicity in prevalence of diabetes mellitus in sleep apnea and relationship to sleep phase . Postgrad Med . 2009;121:108 - 112 . 26 . Link CL , McKinlay JB . Disparities in the prevalence of diabetes : is it race/ethnicity or socioeconomic status ? Results from the Boston Area Community Health ( BACH ) survey . Ethn Dis . 2009;19:288 - 292 . 27 . Bryson CL , Ross HJ , Boyko EJ , Young BA . Racial and ethnic variations in albuminuria in the US Third National Health and Nutrition Examination Survey ( NHANES III ) population : associations with diabetes and level of CKD . Am J Kidney Dis . 2006 ; 48:720 - 726 . 28 . Gross R , Olfson M , Gameroff MJ . Depression and glycemic control in Hispanic primary care patients with diabetes . J Gen Intern Med . 2005;20:460 - 466 . 29 . Trief PM , Morin PC , Izquierdo R. Depression and glycemic control in elderly ethnically diverse patients with diabetes : the IDEATel project . Diabetes Care . 2006 ; 29:830 - 835 . 30 . McCarthy CR . Historical background of clinical trials involving women and minorities . Acad Med . 1994;69:695 - 698 . 31 . Rosal MC , Benjamin EM , Pekow PS , Lemon SC , von Goeler D. Opportunities and challenges for diabetes prevention at two community health centers . Diabetes Care . 2008 ; 31:247 - 254 . 32 . Blumenthal DS , Sung J , Coates R , Williams J , Liff J. Recruitment and retention of subjects for a longitudinal cancer prevention study in an inner-city black community . Health Serv Res . 1995;30(1 Pt 2):197 - 205 . 33 . UyBico SJ , Pavel S , Gross CP . Recruiting vulnerable population s into research : a systematic review of recruitment interventions . J Gen Intern Med . 2007;22:852 - 863 . 34 . Corbie-Smith GM . Minority recruitment and participation in health research . N C Med J. 2004 ; 65:385 - 387 . 35 . Bruner DW , Jones M , Buchanan D , Russo J. Reducing cancer disparities for minorities : a multidisciplinary research agenda to improve patient access to health systems , clinical trials , and effective cancer therapy . J Clin Oncol . 2006;24:2209 - 2215 . 36 . Blumenthal DS , Lukomnik JE , Hawkins DR , Jr. A proposal to provide care to the uninsured through a network of community health centers . J Health Care Poor Underserved . 1993;4:272 - 279 . 37 . Davis SK , Collins KS , Hall A. Community health centers in a changing U.S. health care system . Policy Brief Commonw Fund . 1999;(300):1 - 13 . 38 . US Department of Health and Human Services , Health Re sources and Services Administration . Bureau of Primary Health Care . America ’s health centers : models for quality primary health care . Available at : http://bphc.hrsa.gov/chc/charts/healthcenters.htm . Accessed January 8 , 2010 . 39 . Rosal MC , White MJ , Restrepo A. Design and methods for a r and omized clinical trial of a diabetes self-management intervention for low-income Latinos : Latinos en Control . BMC Med Res Method ol . 2009;9:81 . 40 . Miller WR , Rollnick S. Motivational Interviewing : Preparing People for Change . PURPOSE The purpose of this article was to describe effective recruitment and retention strategies used in a community-based intervention study for older , rural African American women with type 2 diabetes . METHODS The study 's design was a r and omized control test using a 3-group experimental design in a sample of 180 older , rural African American women ( 55 years of age and older ) , with type 2 diabetes . The study employed a range of strategies to successfully recruit and retain older African American women . These strategies were initially developed based on a review of the literature and the investigators ' prior experience . They were modified as the research progressed . RESULTS More than a quarter of the participants were recruited from outpatient clinics . In-person outreach to health care providers was essential to engage and retain their help in recruiting patients . The research team made it easy and rewarding for women to participate in the study by providing a toll-free phone number , culturally appropriate intervention material s , intervention in the home , and incentives . Developing a relationship of trust with participants and the community was critical throughout the study period . Through the use of these strategies , the target enrollment of 180 women was met with 91 % retention rate at the completion of the study . CONCLUSION The use of multiple strategies can enhance recruitment and retention of rural , older African American women into a research study . Strategies are most effective when they build a relationship of trust with participants and the community and make it easy and rewarding for women to participate Background Obesity and hypertension and their associated health complications disproportionately affect communities of color and people of lower socioeconomic status . Recruitment and retention of these population s in research trials , and retention in weight loss trials has been an ongoing challenge . Methods Be Fit , Be Well was a pragmatic r and omized weight loss and hypertension management trial of patients attending one of three community health centers in Boston , Massachusetts . Participants were asked to complete follow-up assessment s every 6-months for two years . We describe challenges encountered and strategies implemented to recruit and retain trial participants over the 24-month intervention . We also identify baseline participant characteristics associated with retention status . Retention strategies included financial incentives , contact between assessment visits , building relationships with health center primary care providers ( PCPs ) and staff , and putting participant convenience first . Results Active refusal rates were low with 130 of 2,631 patients refusing participation ( 4.9 % ) . Of 474 eligible persons completing telephone screening , 365 ( 77.0 % ) completed their baseline visit and were r and omized into the study . The study population was predominantly non-Hispanic Black ( 71.2 % ) , female ( 68.5 % ) and reported annual household income of less than $ 35,000 ( 70.1 % ) . Recruitment strategies included use of passive approval of potential participants by PCPs , use of part-time staff , and outsourcing calls to a call center . A total of 314 ( 86.0 % ) people completed the 24-month visit . Retention levels varied across study visits and intervention condition . Most participants completed three or more visits ( 69.6 % ) , with 205 ( 56.2 % ) completing all four . At 24-months , lower retention was observed for males and the intervention condition . Retention strategies included building strong relationships with clinic staff , flexibility in overcoming participant barriers through use of taxi vouchers , night and weekend appointments , and keeping participants engaged via newsletters and social gatherings . Conclusion We were able to retain 86.0 % of participants at 24-months . Recruitment and retention of high percentages of racial/ethnic minorities and lower income sample s is possible with planning , coordination with a trusted community setting and staff ( e.g. community health centers and RAs ) , adaptability and building strong relationships . Trial registration Clinical trials.gov Identifier : Background One of the first chemoprevention trials conducted in the western hemisphere , the National Surgical Adjuvant Breast and Bowel Project ’s ( NSABP ) Breast Cancer Prevention Trial ( BCPT ) , demonstrated the need to evaluate all aspects of recruitment in real time and to implement strategies to enroll racial and ethnic minority women . Purpose The purpose of this report is to review various patient recruitment efforts the NSABP developed to enhance the participation of racial and ethnic minority women in the Study of Tamoxifen and Raloxifene ( STAR ) trial and to describe the role that the recruitment process played in the implementation and underst and ing of breast cancer risk assessment in minority communities . Methods The NSABP STAR trial was a r and omized , double-blinded study comparing the use of tamoxifen 20 mg/day to raloxifene 60 mg/day , for a 5-year period , to reduce the risk of developing invasive breast cancer . Eligible postmenopausal women were required to have a 5-year predicted breast cancer risk of 1.66 % based on the modified Gail Model . For the current report , eligibility and enrollment data were tabulated by race/ethnicity for women who su bmi tted STAR risk assessment forms ( RAFs ) . Results A total of 184,460 RAFs were received , 145,550 ( 78.9 % ) from white women and 38,910 ( 21.1 % ) from minority women . Of the latter group , 21,444 ( 11.6 % ) were from African Americans/blacks , 7913 ( 4.5 % ) from Hispanics/Latinas , and 9553 ( 5.2 % ) from other racial or ethnic groups . The percentages of risk-eligible women among African Americans , Hispanics/Latinas , others , and whites were 14.2 % , 23.3 % , 13.7 % , and 57.4 % , respectively . Programs targeting minority enrollment su bmi tted large numbers of RAFs , but the eligibility rates of the women referred from those groups tended to be lower than the rates among women referred outside of those programs . The average number of completed risk assessment s increased among minority women over the course of the recruitment period compared to those from whites . Limitations We have not addressed all identified barriers to the recruitment of minorities in clinical research . Our risk assessment s and recruitment results do not reflect the modified Gail Model for African Americans . Conclusions Recruitment strategies used in STAR for racial and ethnic minorities contributed to doubling the minority enrollment compared to that in the BCPT and increased the awareness of breast cancer risk assessment in minority communities . Incorporation of new information into models to improve the risk estimation of diverse population s should prove beneficial Background Latinos comprise the largest racial/ethnic group in the United States and have 2–3 times the prevalence of type 2 diabetes mellitus as Caucasians . Methods and design The Lawrence Latino Diabetes Prevention Project ( LLDPP ) is a community-based translational research study which aims to reduce the risk of diabetes among Latinos who have a ≥ 30 % probability of developing diabetes in the next 7.5 years per a predictive equation . The project was conducted in Lawrence , Massachusetts , a predominantly Caribbean-origin urban Latino community . Individuals were identified primarily from a community health center 's patient panel , screened for study eligibility , r and omized to either a usual care or a lifestyle intervention condition , and followed for one year . Like the efficacious Diabetes Prevention Program ( DPP ) , the LLDPP intervention targeted weight loss through dietary change and increased physical activity . However , unlike the DPP , the LLDPP intervention was less intensive , tailored to literacy needs and cultural preferences , and delivered in Spanish . The group format of the intervention ( 13 group sessions over 1 year ) was complemented by 3 individual home visits and was implemented by individuals from the community with training and supervision by a clinical research nutritionist and a behavioral psychologist . Study measures included demographics , Stern predictive equation components ( age , gender , ethnicity , fasting glucose , systolic blood pressure , HDL-cholesterol , body mass index , and family history of diabetes ) , glycosylated hemoglobin , dietary intake , physical activity , depressive symptoms , social support , quality of life , and medication use . Body weight was measured at baseline , 6-months , and one-year ; all other measures were assessed at baseline and one-year . All surveys were orally administered in Spanish . Results A community-academic partnership enabled the successful recruitment , intervention , and assessment of Latinos at risk of diabetes with a one-year study retention rate of 93%.Trial registration Purpose To assess cancer clinical trial recruitment and reasons for nonaccrual among a rural , medically underserved population served by a community-based cancer care center . Methods We prospect ively tracked clinical trial enrollment incidence among all new patients presenting at the Rapid City Regional Cancer Care Institute . Evaluating physicians completed question naires for each patient regarding clinical trial enrollment status and primary reasons for nonenrollment . Patients who identified as American Indian were referred to a program where patients were assisted in navigating the medical system by trained , culturally competent staff . Results Between September 2006 and January 2008 , 891 new cancer patients were evaluated . Seventy-eight patients ( 9 % ; 95 % confidence intervals , 7—11 % ) were enrolled on a clinical treatment trial . For 73 % ( 95 % confidence intervals , 69—75 % ) of patients ( 646 of 891 ) lack of relevant protocol availability or protocol inclusion criteria restrictiveness was the reason for nonenrollment . Only 45 ( 5 % ; 95 % confidence intervals , 4—7 % ) patients refused enrollment on a trial . Of the 78 enrolled on a trial , 6 ( 8 % ; 95 % confidence intervals , 3—16 % ) were American Indian . Three additional American Indian patients were enrolled under a nontreatment cancer control trial , bringing the total percentage enrolled of the 94 American Indians who presented to the clinic to 10 % ( 95 % confidence intervals , 5—17 % ) . Limitations Eligibility rates were unable to be calculated and cross validation of the number in the cohort via registries or ICD-9 codes was not performed . Conclusion Clinical trial participation in this medically underserved population was low overall , but approximately 3-fold higher than reported national accrual rates . Lack of availability of protocol s for common cancer sites as well as stringent protocol inclusion criteria were the primary obstacles to clinical trial enrollment . Targeted interventions using a Patient Navigation program were used to engage AI patients and may have result ed in higher clinical trial enrollment among this racial/ethnic group . Clinical Trials 2009 ; 6 : 610—617 . PURPOSE " Physicians-recruiting-physicians " is the preferred recruitment approach for practice -based research . However , yields are variable ; and the approach can be costly and lead to biased , unrepresentative sample s. We sought to explore the potential efficiency of alternative methods . METHODS We conducted a retrospective analysis of the yield and cost of 10 recruitment strategies used to recruit primary care practice s to a r and omized trial to improve cardiovascular disease risk factor management . We measured response and recruitment yields and the re sources used to estimate the value of each strategy . Providers at recruited practice s were surveyed about motivation for participation . RESULTS Response to 6 opt-in marketing strategies was 0.40 % ( 53/13290 ) , ranging from 0 % to 2.86 % by strategy ; 33.96 % ( 18/53 ) of responders were recruited to the study . Of those recruited from opt-out strategies , 8.68 % joined the study , ranging from 5.35 % to 41.67 % per strategy . A strategy that combined both opt-in and opt-out approaches result ed in a 51.14 % ( 90/176 ) response and a 10.80 % ( 19/90 ) recruitment rate . Cost of recruitment was $ 613 per recruited practice . Recruitment approaches based on in-person meetings ( 41.67 % ) , previous relationships ( 33.33 % ) , and borrowing an Area Health Education Center 's established networks ( 10.80 % ) , yielded the most recruited practice s per effort and were most cost efficient . Individual providers who chose to participate were motivated by interest in improving their clinical practice ( 80.5 % ) ; contributing to CVD primary prevention ( 54.4 % ) ; and invigorating their practice with new ideas ( 42.1 % ) . CONCLUSIONS This analysis provides suggestions for future recruitment efforts and research . Translational studies with limited funds could consider multi-modal recruitment approaches including in-person presentations to practice groups and exploitation of previous relationships , which require the providers to opt-out , and interactive opt-in approaches which rely on borrowed networks . These approaches can be supplemented with non-relationship-based opt-out strategies such as cold calls strategically targeted to underrepresented provider groups M and ates to include women and minority population s in research have heightened the need to identify successful recruitment strategies . This paper describes the recruitment and retention strategies used as part of a r and omized controlled trial ( RCT ) of a physical activity and dietary intervention targeting low-income , predominantly Latino patients in a primary health care clinic . Data on the recruitment and retention rates and the representativeness of participants are presented . Strategies included hiring bilingual staff , translating and culturally adapting intervention material s and soliciting ongoing consultation from patients , clinicians and organizations providing services to the Latino community . The primary recruitment procedure involved letters from physicians followed by phone calls from project staff to patients identified from electronic medical records . Two hundred patients were recruited into the RCT ( 78 % of those reached and eligible ) , with 69 and 81 % reached for the 6-week and 6-month follow-ups , respectively . Women were more likely to both participate and remain in the trial , and there was a trend toward greater recruitment and retention of Spanish speakers . By engaging the community , clinicians and patients , this study was able to successfully recruit and retain a large proportion of this often difficult to reach Latino sub- population of patients with multiple chronic conditions Background Clinical trials ( CTs ) are the mechanism by which research is translated into st and ards of care . Low recruitment among underserved and minority population s may result in inequity in access to the latest technology and treatments , compromise the generalizability , and lead to failure in identification of important positive or negative treatment effects among under-represented population s. Methods Data were collected over a 39-month period on patient eligibility for available therapeutic cancer CTs . Reasons for in eligibility and refusal were collected . The data were captured using an automated software tool for tracking eligibility pre-enrollment . We examined characteristics associated with being evaluated for a trial , and reasons for in eligibility and refusal , overall and by patient race . Results African-Americans ( AAs ) were more likely than Whites to be ineligible ( odds ratio , ( OR ) = 1.26 , 95 % confidence interval ( CI ) = 1.0–1.58 ) and if eligible , to refuse participation ( OR = 1.79 , 95 % CI = 1.27–2.52 ) , even after adjusting for insurance , age , gender , study phase , and cancer type . White patients were more likely to be ineligible due to study -specific or cancer characteristics . AAs were more likely to be ineligible due to mental status or perceived noncompliance . Whites were more likely to refuse due to extra burden , due to concerns with r and omization and toxicity , or because they express a positive treatment preference . AAs were more likely to refuse because they were not interested in CTs , because of family pressures , or they felt overwhelmed ( NS ) ) . Discussion This study is the first to directly compare in eligibility and refusal rates and reasons captured prospect ively in AA and White cancer patients . The data are consistent with earlier studies that indicated that AA patients more often are deemed ineligible and , when eligible , more often refuse participation . However , differences in reasons for in eligibility and refusal by race have implication s for a cancer center to participate in CTs appropriate for the population of patients served . On a broader scale , consideration should be given to modifying eligibility criteria and other design aspects to permit broader participation of minority and other underserved groups BACKGROUND Several sickle cell clinical trials have closed due to inability to enroll patients . To limit the early cessation of a proposed clinical trial due to low accrual rates , we sought to better underst and barriers and facilitators to enrolling parents of children with sickle cell anemia ( SCD ) into clinical trials . PROCEDURE Focus groups ( n = 3 ) were conducted with parents/guardians ( n = 14 ) who had not previously been recruited for a clinical trial and were not administering hydroxyurea to their children . RESULTS Three main themes related to barriers to clinical trial enrollment were identified during analysis of focus groups : general barriers to health related research ( general mistrust of research studies , emotional and practical concerns ) , barriers to trial design ( r and omization ) , and barriers to hydroxyurea ( long term unknown risks , cancer , myelosuppressive effects ) . Facilitators identified were need for more education , including request for peer education , and improved explanation of clinical trials or study rationale . CONCLUSION Engagement of parents/guardians of children with SCD in identifying barriers and facilitators to clinical trial enrollment may be critical to the development of strategies to enhance SCD trial completion OBJECTIVES We tested the effectiveness of a community-based , literacy-sensitive , and culturally tailored lifestyle intervention on weight loss and diabetes risk reduction among low-income , Spanish-speaking Latinos at increased diabetes risk . METHODS Three hundred twelve participants from Lawrence , Massachusetts , were r and omly assigned to lifestyle intervention care ( IC ) or usual care ( UC ) between 2004 and 2007 . The intervention was implemented by trained Spanish-speaking individuals from the community . Each participant was followed for 1 year . RESULTS The participants ' mean age was 52 years ; 59 % had less than a high school education . The 1-year retention rate was 94 % . Compared with the UC group , the IC group had a modest but significant weight reduction ( -2.5 vs 0.63 lb ; P = .04 ) and a clinical ly meaningful reduction in hemoglobin A1c ( -0.10 % vs -0.04 % ; P = .009 ) . Likewise , insulin resistance improved significantly in the IC compared with the UC group . The IC group also had greater reductions in percentage of calories from total and saturated fat . CONCLUSIONS We developed an inexpensive , culturally sensitive diabetes prevention program that result ed in weight loss , improved HbA1c , and improved insulin resistance in a high-risk Latino population Despite the large burden of chronic kidney disease ( CKD ) in Hispanics , this population has been underrepresented in research studies . We describe the recruitment strategies employed by the Hispanic Chronic Renal Insufficiency Cohort Study , which led to the successful enrollment of a large population of Hispanic adults with CKD into a prospect i ve observational cohort study . Recruitment efforts by bilingual staff focused on community clinics with Hispanic providers in high-density Hispanic neighborhoods in Chicago , academic medical centers , and private nephrology practice s. Methods of publicizing the study included church meetings , local Hispanic print media , Spanish television and radio stations , and local health fairs . From October 2005 to July 2008 , we recruited 327 Hispanics aged 21 - 74 years with mild-to-moderate CKD as determined by age-specific estimated glomerular filtration rate ( eGFR ) . Of 716 individuals completing a screening visit , 49 % did not meet eGFR inclusion criteria and 46 % completed a baseline visit . The mean age at enrollment was 57.1 and 67.1 % of participants were male . Approximately 75 % of enrolled individuals were Mexican American , 15 % Puerto Rican , and 10 % had other Latin American ancestry . Eighty two percent of participants were Spanish-speakers . Community-based and academic primary care clinics yielded the highest percentage of participants screened ( 45.9 % and 22.4 % ) and enrolled ( 38.2 % and 24.5 % ) . However , academic and community-based specialty clinics achieved the highest enrollment yield from individuals screened ( 61.9 % to 71.4 % ) . A strategy focused on primary care and nephrology clinics and the use of bilingual recruiters allowed us to overcome barriers to the recruitment of Hispanics with CKD Women are disproportionately affected by the sexually transmitted infections ( STI ) epidemic , with African-Americans and Latinos at significantly higher risk for STIs than Caucasians . Successful recruitment and retention strategies used with young minority women in community-based STI prevention or intervention research have not been previously reported . This communication presents eight key strategies learned in the recruitment and retention of 16- to 21-year-old urban women participating in a 12-month r and omized clinical trial design ed to promote STI screening to decrease the duration of untreated chlamydia and gonorrhea infection . Strategies learned include : ( 1 ) Educate clinic staff on the rigors of study design ; ( 2 ) Facilitate a team effort between clinical and research staff ; modify recruitment procedures , as needed ; ( 3 ) Provide prospect i ve participants the option of enrolling by return appointment ; ( 4 ) Anticipate a diminishing recruitment pool over time ; ( 5 ) Set positive recruitment tone at the beginning of each clinic session ; ( 6 ) Consider participants ' mothers as important points of contact ; ( 7 ) Match communication styles to participant contacts ; and ( 8) Consider a variety of retention techniques . Together , these strategies helped to reinforce participant 's commitment to the project , facilitated their attendance at interviews , and encouraged them to adhere to the treatment protocol Objectives . To assess the usefulness of three sources ( faith-based organizations ( FBOs ) health system and community ) for recruitment of African Americans with type 2 diabetes to a r and omized controlled trial ( RCT ) . Design . African Americans with type 2 diabetes were recruited to a diabetes self-management program at four FBO sites . An observational study of a multifaceted recruitment strategy to enroll subjects in the RCT that evaluated the effectiveness of a diabetes self-management program and the effect of recruitment source on retention after enrollment . Self-administered demographic surveys and weekly class attendance records were collected . Results . Of 184 interested individuals 109 ( 59.2 % ) were enrolled . Of those enrolled 60.6 % recruited through the health system 13.8 % FBOs and 19.2 % the community . The highest yield was achieved through the health system . However for both the intervention ( I ) and control ( C ) groups respectively participants recruited from FBOs ( 85.7 % I ; 62.5 % C ) were more likely to attend four or more sessions than those from the health system ( 75.0 % I ; 43.3 % C ) and community ( 55.6 % I ; 25.0 % C ) . Despite similar class size participants in the intervention group ( 74.5 % ; n = 41 ) were more likely to attend four or more of the seven classes than those in the delayed intervention ( control group ) ( 40.7 % ; n = 22 ) . Conclusions . The findings suggest that African American adults with diabetes can be successfully recruited and retained in a racially targeted RCT conducted in FBOs . Key elements to consider are the use of a multifaceted approach for participant recruitment particularly the benefit of health system physician involvement in recruitment since the highest yield was achieved through health system providers and importance of site location for retention |
975 | 31,812,239 | INTERPRETATION We found evidence that individual-level interventions can assist disadvantaged smokers with quitting , but there were no large moderating effects of tailoring for disadvantaged smokers .
Improvements in tailored intervention development might be necessary to achieve equity-positive smoking cessation outcomes . | BACKGROUND Socioeconomic inequalities in smoking cessation have led to development of interventions that are specifically tailored for smokers from disadvantaged groups .
We aim ed to assess whether the effectiveness of interventions for disadvantaged groups is moderated by tailoring for socioeconomic position . | BACKGROUND This study tested the impact of free nicotine patches plus proactive telephone peer support to help low-income women stop smoking . METHODS A total of 214 Medicaid-eligible women smokers of childbearing age were r and omized to receive free nicotine patches through the mail or free nicotine patches through the mail plus the provision of proactive support by telephone from a woman ex-smoker for up to 3 months . Assessment s were conducted by telephone at baseline , 10 days , and 3 and 6 months after enrollment . RESULTS At the 3-month follow-up , significantly more women in the patch plus proactive telephone support condition were abstinent ( 42 % ) compared to the patch only condition ( 28 % ) ( P = 0.03 ) . Similarly , more women in the experimental condition were abstinent at both the 10-day and 3-month assessment s ( 32 v 19 % , P = 0.02 ) . However , differences were not found at the 6-month follow-up , suggesting that the addition of proactive telephone peer support enhanced short-term , but not long-term cessation . CONCLUSIONS This is the first study to demonstrate a beneficial effect for the addition of proactive telephone support as an adjunct to free nicotine replacement in a low-income population Smoking-cessation services are an unmet need among the homeless , who smoke at rates more than 4 times the national estimate . Successful interventions have high potential for improving tobacco-related health disparities among homeless smokers . Contingency management ( CM ) is a behavioral intervention with efficacy in a number of substance-use disorder population s , including smokers . However , no r and omized studies have evaluated the effect of CM in homeless smokers . We examined smoking-related outcomes in homeless smokers ( N = 70 ) r and omized to st and ard-care ( SC ) smoking cessation involving transdermal nicotine-replacement therapy ( NRT ) , st and ard counseling , and carbon monoxide ( CO ) monitoring or the same SC plus CM for negative CO sample su bmi ssions . Participants r and omized to CM achieved significantly longer duration s of consecutive abstinence and su bmi tted a significantly higher proportion of CO-negative sample s relative to st and ard-care participants . At 4 weeks postquit day , 22 % were abstinent in the CM condition and 9 % were abstinent in the SC condition . At the 6-month follow-up , about 10 % of smokers in both conditions were abstinent . This study demonstrates that CM is an efficacious option to increase initial quit rates in homeless smokers , but methods to extend effects are needed INTRODUCTION Evidence -based treatments for tobacco dependence are significantly less effective for smokers of lower socioeconomic status which contributes to socioeconomic disparities in smoking prevalence rates and health . We aim ed to reduce the socioeconomic gradient in treatment outcomes by systematic ally adapting evidence -based , cognitive-behavioral treatment for tobacco dependence for diverse lower socioeconomic smokers . METHODS Participants were r and omized to adapted or st and ard treatment , received six 1-h group treatment sessions , and were followed for six months . We examined the effectiveness of the adapted treatment to improve treatment outcomes for lower socioeconomic groups . RESULTS Participants ( n=227 ) were ethnically , racially , and socioeconomically diverse . The adapted treatment significantly reduced the days to relapse for the two lowest socioeconomic groups : SES1 : M=76.6 ( SD 72.9 ) vs. 38.3 ( SD 60.1 ) days to relapse ( RR=0.63 95 % CI , 0.45 , 0.88 , p=0.0013 ) ; SES2 : M=88.2 ( SD 67.3 ) vs. 40.1 ( SD 62.6 days to relapse ( RR=0.57 95 % CI , 0.18 , 0.70 , p=0.0024 ) . Interactions between socioeconomic status and condition were significant for initial abstinence ( OR=1.26 , 95 % CI 1.09 , 1.46 , p=0.002 ) , approached significance for 3-month abstinence ( OR=0.90 , 95 % CI 0.80 , 1.01 , p<0.071 ) , and were not significant for 6-month abstinence ( OR=0.99 95 % CI 0.88 , 1.10 , p=0.795 ) . No significant differences in long-term abstinence were observed . CONCLUSION Systematic adaption of evidence -based treatment for tobacco dependence can significantly improve initial and short-term treatment outcomes for diverse lower socioeconomic smokers and reduce inequities in days to relapse . Novel methods of providing targeted extended support are needed to improve long-term outcomes Background Lower rates of smoking cessation are a major reason for the higher prevalence of smoking among socioeconomically disadvantaged adults . Because barriers to quitting are both more numerous and severe , socioeconomically disadvantaged smokers may benefit from more intensive intervention . We sought to determine whether a smoking cessation intervention delivered by public housing residents trained as Tobacco Treatment Advocates ( TTAs ) could increase utilization of cessation re sources and increase abstinence . Methods We conducted a group-r and omized trial among Boston public housing residents who were interested in quitting smoking . Participants at control sites received st and ard cessation material s and a one-time visit from a TTA who provided basic counseling and information about cessation re sources . Participants at intervention sites were eligible for multiple visits by a TTA who employed motivational interviewing , cessation counseling , and navigation to encourage smokers to utilize cessation treatment ( Smokers ' Quitline and clinic-based programs ) . Utilization and 7-day and 30-day point prevalence abstinence were assessed at 12 months . Self-reported abstinence was biochemically verified . Results Intervention participants ( n = 121 ) were more likely than control participants ( n = 129 ) to both utilize treatment programs ( adjusted odds ratio [ aOR ] : 2.15 ; 95 % confidence interval [ CI ] : 0.93 - 4.91 ) and 7-day and 30-day point prevalence abstinence ( aOR : 2.60 ( 1.72 - 3.94 ) ; 2.98 ( 1.56 - 5.68 ) , respectively ) . Mediation analysis indicated that the higher level of utilization did not explain the intervention effect . Conclusions An intervention delivered by peer health advocates was able to increase utilization of treatment programs and smoking abstinence among public housing residents . Future studies of similar types of interventions should identify the key mechanisms responsible for success . Implication s In order to narrow the large and growing socioeconomic disparity in smoking rates , more effective cessation interventions are needed for low-income smokers . Individual culturally-relevant coaching provided in smokers ' residences may help overcome the heightened barriers to cessation experienced by this group of smokers . In this study among smokers residing in public housing , an intervention delivered by peer health advocates trained in motivational interviewing , basic smoking cessation skills , and client navigation significantly increased abstinence at 12 months . Future research should address whether these findings are replicable in other setting s both within and outside of public housing OBJECTIVE To evaluate the effectiveness of a community based participatory research ( CBPR ) developed , multi-level smoking cessation intervention among women in subsidized housing neighborhoods in the Southeastern US . METHODS A total of n=409 women in 14 subsidized housing neighborhoods in Georgia and South Carolina participated in this group r and omized controlled trial conducted from 2009 to 2013 . Intervention neighborhoods received a 24-week intervention with 1:1 community health worker contact , behavioral peer group sessions , and nicotine replacement . Control neighborhoods received written cessation material s at weeks 1 , 6 , 12 , 18 . R and om coefficient models were used to compare smoking abstinence outcomes at 6 and 12months . Significance was set a p<0.05 . RESULTS The majority of participants ( 91.2 % ) were retained during the 12-month intervention period . Smoking abstinence rates at 12months for intervention vs. control were 9 % vs. 4.3 % , p=0.05 . Additional analyses accounting for passive smoke exposure in these multi-unit housing setting s demonstrated 12month abstinence rates of 12 % vs. 5.3 % , p=0.016 . However , in the multivariate regression analyses , there was no significant effect of the intervention on the odds of being a non-smoker ( OR=0.44 , 95 % CI : 0.18 - 1.07 ) . Intervention participants who kept coach visits , attended group sessions , and used patches were more likely to remain abstinent . CONCLUSIONS This CBPR developed intervention showed potential to engage smokers and reduce smoking among women in these high-poverty neighborhoods . Effectiveness in promoting cessation in communities burdened with fiscal , environmental and social inequities remains a public health priority Objectives To assess the effects of a novel oral health promotion program ( Oral Health 4 Life ; OH4L ) delivered through state-funded tobacco quitlines . Methods Using a semipragmatic design to balance experimental control and generalizability , we r and omized US quitline callers ( n = 718 ) to st and ard care or st and ard care plus OH4L . We followed participants for 6 months to assess effects on professional dental care and smoking abstinence . We collected data between 2015 and 2017 . Results Participants were racially diverse ( 42 % non-White ) and socioeconomically disadvantaged . Most ( 71 % ) reported fair or poor oral health , and all were overdue for routine dental care . At 6 months , professional dental care and abstinence did not significantly differ between arms , but abstinence favored the experimental arm and was significantly higher among experimental participants at 2 months in a complete case sensitivity analysis . Conclusions OH4L was not effective for promoting dental care , but integrating oral health counseling with quitline counseling may offer some advantage for smoking cessation . Public Health Implication s We offer a model for conducting semipragmatic trials and partnering with tobacco quitlines to evaluate population -level public health interventions OBJECTIVES There remains a need to identify effective smoking cessation interventions in severely disadvantaged population s. This trial aim ed to examine the effectiveness of an intervention ( Call it Quits ) developed to promote smoking cessation and delivered by community social service case-workers . METHODS Call it Quits was a pragmatic , parallel r and omised trial of a case-worker delivered smoking cessation intervention conducted in a non-government community social service organisation in New South Wales ( NSW ) , Australia . Adult smokers requiring financial assistance were r and omly assigned to the five-session Call it Quits intervention or usual care control group . Of the 618 eligible individuals , 300 were r and omised to the intervention group , of whom 187 ( 62 % ) consented and 318 were r and omised to the control group , of whom 244 ( 77 % ) consented , result ing in 431 participants . The primary outcome measure was self-reported continuous abstinence up to 6-month follow-up with biochemical verification . Primary analysis was performed using all the available data from participants under the assumption the data is missing completely at r and om , followed by sensitivity analyses . RESULTS No statistically significant differences in the primary outcome were found ( 1.4 % in the control group versus 1.0 % in the intervention group , OR = 0.77 , p = 0.828 ) . CONCLUSIONS A multi-component smoking cessation intervention delivering motivational interviewing-based counselling and free NRT by a trained case-worker within a community social service setting was not effective at achieving abstinence in a highly disadvantaged sample of smokers but increased attempts to stop and led to a reduction in number of cigarettes smoked daily Background Tobacco use kills half a million people every month , most in low – middle income countries ( LMICs ) . There is an urgent need to identify potentially low-cost , scalable tobacco cessation interventions for these countries . Objective To evaluate a brief community outreach intervention delivered by health workers to promote tobacco cessation in India . Design Cluster-r and omised controlled trial . Setting 32 low-income administrative blocks in Delhi , half government authorised ( ‘ resettlement colony ’ ) and half unauthorised ( ‘ J.J. cluster ’ ) communities . Participants 1213 adult tobacco users . Interventions Administrative blocks were computer r and omised in a 1:1 ratio , to the intervention ( 16 clusters ; n=611 ) or control treatment ( 16 clusters ; n=602 ) , delivered and assessed at individual level between 07/2012 and 11/2013 . The intervention was single session quit advice ( 15 min ) plus a single training session in yogic breathing exercises ; the control condition comprised very brief quit advice ( 1 min ) alone . Both were delivered via outreach , with contact made though household visits . Measurements The primary outcome was 6-month sustained abstinence from all tobacco , assessed 7 months post intervention delivery , biochemically verified with salivary cotinine . Results The smoking cessation rate was higher in the intervention group ( 2.6 % ( 16/611 ) ) than in the control group ( 0.5 % ( 3/602 ) ) ( relative risk=5.32 , 95 % CI 1.43 to 19.74 , p=0.013 ) . There was no interaction with type of tobacco use ( smoked vs smokeless ) . Results did not change material ly in adjusted analyses , controlling for participant characteristics . Conclusions A single session community outreach intervention can increase tobacco cessation in LMIC . The effect size , while small , could impact public health if scaled up with high coverage . Trial registration number IS RCT CN23362894 Community college students represent 44 % of all students enrolled in U.S. higher education facilities . To our knowledge , no previous smoking cessation intervention has targeted community college students . Previous studies suggest that a motivational smoking cessation intervention could be successful for young adult smokers . Combining motivational interviewing sessions with personalized health feedback is likely to increase participants ' motivation to quit and movement through the stages of change . The purpose of this study was to evaluate the impact of a smoking cessation program based on these premises . We design ed a computer-assisted , counselor-delivered smoking cessation program that addresses personal health risks and readiness to change smoking behavior among community college students . A group-r and omized , controlled trial was used to assess the intervention in a sample of 426 students ( 58.5 % females ; mean age , 22.8+/-4.7 years ) from 15 pair-matched campuses . At the 10-month follow-up assessment , the cotinine-vali date d smoking cessation rates were 16.6 % in the experimental condition and 10.1 % in the st and ard care condition ( p=0.07 ) . Our results indicate that our computer-assisted intervention holds considerable promise in reducing smoking among community college students Smoking continues to take an enormous toll on society , and although most smokers would like to quit , most are unsuccessful using existing therapies . These findings call on research ers to develop and test therapies that provide higher rates of long-term smoking abstinence . We report results of a r and omized controlled trial comparing a novel smoking cessation treatment using mindfulness training to a matched control based on the American Lung Association 's Freedom From Smoking program . Data were collected on 175 low socioeconomic status smokers in 2011 - 2012 in a medium sized midwestern city . A significant difference was not found in the primary outcome ; intent-to-treat biochemically confirmed 6-month smoking abstinence rates were mindfulness=25.0 % , control=17.9 % ( p=0.35 ) . Differences favoring the mindfulness condition were found on measures of urges and changes in mindfulness , perceived stress , and experiential avoidance . While no significant differences were found in quit rates , the mindfulness intervention result ed in positive outcomes Background Novel interventions tailored to blue collar workers are needed to reduce the disparities in smoking rates among occupational groups . Objective The main objective of this study was to evaluate the efficacy and usage of the Web-enhanced “ Tobacco Tactics ” intervention targeting operating engineers ( heavy equipment operators ) compared to the “ 1 - 800-QUIT-NOW ” telephone line . Methods Operating engineers ( N=145 ) attending one of 25 safety training sessions from 2010 through 2012 were r and omized to either the Tobacco Tactics website with nurse counseling by phone and access to nicotine replacement therapy ( NRT ) or to the 1 - 800-QUIT-NOW telephone line , which provided an equal number of phone calls and NRT . The primary outcome was self-reported 7-day abstinence at 30-day and 6-month follow-up . The outcomes were compared using chi-square tests , t tests , generalized mixed models , and logistic regression models . Results The average age was 42 years and most were male ( 115/145 , 79.3 % ) and white ( 125/145 , 86.2 % ) . Using an intent-to-treat analysis , the Tobacco Tactics website group showed significantly higher quit rates ( 18/67 , 27 % ) than the 1 - 800-QUIT NOW group ( 6/78 , 8 % ) at 30-day follow-up ( P=.003 ) , but this difference was no longer significant at 6-month follow-up . There were significantly more positive changes in harm reduction measures ( quit attempts , number of cigarettes smoked per day , and nicotine dependence ) at both 30-day and 6-month follow-up in the Tobacco Tactics group compared to the 1 - 800-QUIT-NOW group . Compared to participants in the 1 - 800-QUIT NOW group , significantly more of those in the Tobacco Tactics website group participated in the interventions , received phone calls and NRT , and found the intervention helpful . Conclusions The Web-enhanced Tobacco Tactics website with telephone support showed higher efficacy and reach than the 1 - 800-QUIT-NOW intervention . Longer counseling sessions may be needed to improve 6-month cessation rates . Trial Registration Clinical trials.gov NCT01124110 ; http:// clinical trials.gov/ct2/show/NCT01124110 ( Archived by WebCite at http://www.webcitation.org/6TfKN5iNL ) Summary Background Smoking cessation programmes delivered via mobile phone text messaging show increases in self-reported quitting in the short term . We assessed the effect of an automated smoking cessation programme delivered via mobile phone text messaging on continuous abstinence , which was biochemically verified at 6 months . Methods In this single-blind , r and omised trial , undertaken in the UK , smokers willing to make a quit attempt were r and omly allocated , using an independent telephone r and omisation system , to a mobile phone text messaging smoking cessation programme ( txt2stop ) , comprising motivational messages and behavioural-change support , or to a control group that received text messages unrelated to quitting . The system automatically generated intervention or control group texts according to the allocation . Outcome assessors were masked to treatment allocation . The primary outcome was self-reported continuous smoking abstinence , biochemically verified at 6 months . All analyses were by intention to treat . This study is registered , number IS RCT N 80978588 . Findings We assessed 11 914 participants for eligibility . 5800 participants were r and omised , of whom 2915 smokers were allocated to the txt2stop intervention and 2885 were allocated to the control group ; eight were excluded because they were r and omised more than once . Primary outcome data were available for 5524 ( 95 % ) participants . Biochemically verified continuous abstinence at 6 months was significantly increased in the txt2stop group ( 10·7 % txt2stop vs 4·9 % control , relative risk [ RR ] 2·20 , 95 % CI 1·80–2·68 ; p<0·0001 ) . Similar results were obtained when participants that were lost to follow-up were treated as smokers ( 268 [ 9 % ] of 2911 txt2stop vs 124 [ 4 % ] of 2881 control [ RR 2·14 , 95 % CI 1·74–2·63 ; p<0·0001 ] ) , and when they were excluded ( 268 [ 10 % ] of 2735 txt2stop vs 124 [ 4 % ] of 2789 control [ 2·20 , 1·79–2·71 ; p<0·0001 ] ) . No significant heterogeneity was shown in any of the prespecified subgroups . Interpretation The txt2stop smoking cessation programme significantly improved smoking cessation rates at 6 months and should be considered for inclusion in smoking cessation services . Funding UK Medical Research Council , Primary Care Research Networks Objectives Novel approaches to worksite health promotion are needed for high-risk workers who change job sites frequently , and thus may have limited access to worksite health promotion efforts . The objective of this study was to test a behavioral intervention among construction laborers . Methods Using a r and omized-controlled design , we tested the efficacy of a tailored telephone-delivered and mailed intervention to promote smoking cessation and increased fruit and vegetable consumption ( n = 582 ) . Results At baseline , 40 % of control group participants and 45 % of intervention group participants reported using any tobacco in the last seven days . At final , 8 % of baseline cigarette smokers in the control group had quit , compared to 19 % in the intervention group ( p = 0.03 ) . In both groups , the mean consumption of fruits and vegetables at baseline was over five servings per day . At final , the intervention group had increased consumption by approximately one and one-half servings , compared to a slight decrease in consumption in the control group ( p < 0.001 ) . Conclusions A tailored intervention can be efficacious in promoting tobacco use cessation and increased fruit and vegetable consumption among construction laborers , a high-risk , mobile workforce Background Systematic review s of behaviour change interventions for smoking cessation vary in scope , quality , and applicability . The current review aims to generate more accurate and useful findings by ( 1 ) a detailed analysis of intervention elements that change behaviour ( i.e. behaviour change techniques ( BCTs ) ) and potential moderators of behaviour change ( i.e. other intervention and sample characteristics ) and ( 2 ) assessing and controlling for variability in support provided to comparison groups in smoking cessation trials . Methods A systematic review will be conducted of r and omized controlled trials of behaviour change interventions for smoking cessation in adults ( with or without pharmacological support ) , with a minimum follow-up of 6 months , published after 1995 . Eligible articles will be identified through the Cochrane Tobacco Addiction Group Specialized Register . Study authors will be asked for detailed descriptions of smoking cessation support provided to intervention and comparison groups . All data will be independently coded by two research ers . The BCT taxonomy v1 ( tailored to smoking cessation interventions ) and template for intervention description and replication criteria will be used to code intervention characteristics . Data collection will further include sample and trial characteristics and outcome data ( smoking cessation rates ) . Multilevel mixed-effects meta-regression models will be used to examine which BCTs and /or BCT clusters delivered to intervention and comparison groups explain smoking cessation rates in treatment arms ( and effect sizes ) and what key moderators of behaviour change are . Predicted effect sizes of each intervention will be computed assuming all interventions are compared against comparison groups receiving the same levels of behavioural support ( i.e. low , medium , and high levels ) . Multi-disciplinary advisory board members ( policymakers , health care providers , and (ex-)smokers ) will provide strategic input throughout the project to ensure the review ’s applicability to policy and practice . Discussion By capturing BCTs in intervention and comparison groups , this systematic review will provide more accurate estimates of the effectiveness of smoking cessation interventions , the most promising BCTs and /or BCT clusters associated with smoking cessation rates in intervention and comparison arms , and important moderators of behaviour change . The results could set new st and ards for conducting meta-analyses of behaviour change interventions and improve research , service delivery , and training in the area of smoking cessation . Systematic review registration PROSPERO Background Tobacco is still the number one life style risk factor for ill health and premature death and also one of the major contributors to oral problems and diseases . Dentistry may be a potential setting for several aspects of clinical public health interventions and there is a growing interest in several countries to develop tobacco cessation support in dentistry setting . The aim of the present study was to assess the relative effectiveness of a high intensity intervention compared with a low intensity intervention for smoking cessation support in a dental clinic setting . Methods 300 smokers attending dental or general health care were r and omly assigned to two arms and referred to the local dental clinic for smoking cessation support . One arm received support with low intensity treatment ( LIT ) , whereas the other group was assigned to high intensity treatment ( HIT ) support . The main outcome measures included self-reported point prevalence and continuous abstinence ( ≥ 183 days ) at the 12-month follow-up . Results Follow-up question naires were returned from 86 % of the participants . People in the HIT-arm were twice as likely to report continuous abstinence compared with the LIT-arm ( 18 % vs. 9 % , p = 0.02 ) . There was a difference ( not significant ) between the arms in point prevalence abstinence in favour of the HIT- protocol ( 23 % vs. 16 % ) . However , point prevalence cessation rates in the LIT-arm reporting additional support were relatively high ( 23 % ) compared with available data assessing abstinence in smokers trying to quit without professional support . ConclusionS creening for willingness to quit smoking within the health care system and offering smoking cessation support within dentistry may be an effective model for smoking cessation support in Sweden . The LIT approach is less expensive and time consuming and may be appropriate as a first treatment option , but should be integrated with other forms of available support in the community . The more extensive and expensive HIT- protocol should be offered to those who are unable to quit with the LIT approach in combination with other support . Trial Registration Trial registration number : Background Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease ( COPD ) . But a fewer smoking cessation measures were conducted in communities for smokers with COPD in China . The aim of our study was to assess the preventive effects of behavioral interventions for smoking cessation and potential impact factors in smokers with COPD in China . Methods In a r and omised controlled smoking cessation trial 3562 patients with COPD who were current smoker were allocated to intervention group received behavioral intervention and control group received the usual care for two years . The primary efficacy endpoint was the complete and continuous abstinence from smoking from the beginning of month 24 to the end of month 30 . Participants were followed up at month 48 . Results Continuous smoking abstinence rates from month 24 to 30 were significantly higher in participants receiving behavioral intervention than in those receiving usual care ( 46.4 % vs 3.4 % , p < 0.001 ) . Continuous abstinence rates from months 24 to 36 ( 45.8 % vs 4.0 % ) and months 24 to 48 ( 44.3 % vs 5.1 % ) were also higher in participants receiving behavioral intervention than in those control group . Family members or family physicians/nurses smoking were first identified to influence smoking cessation . Conclusions Behavioral intervention doubled the smoking cessation rate in patients with COPD and was complied well by the general practitioners . The family members and family physicians/nurses smoking were the main risk factors for smoking cessation . Trial registration Chinese Clinical Trials Registration ( ChiCTR-TRC-12001958 ) IMPORTANCE Widening socioeconomic disparities in mortality in the United States are largely explained by slower declines in tobacco use among smokers of low socioeconomic status ( SES ) than among those of higher SES , which points to the need for targeted tobacco cessation interventions . Documentation of smoking status in electronic health records ( EHRs ) provides the tools for health systems to proactively offer tobacco treatment to socioeconomically disadvantaged smokers . OBJECTIVE To evaluate a proactive tobacco cessation strategy that addresses socio context ual mediators of tobacco use for low-SES smokers . DESIGN , SETTING , AND PARTICIPANTS This prospect i ve , r and omized clinical trial included low-SES adult smokers who described their race and /or ethnicity as black , Hispanic , or white and received primary care at 1 of 13 practice s in the greater Boston area ( intervention group , n = 399 ; control group , n = 308 ) . INTERVENTIONS We analyzed EHRs to identify potentially eligible participants and then used interactive voice response ( IVR ) techniques to reach out to them . Consenting patients were r and omized to either receive usual care from their own health care team or enter an intervention program that included ( 1 ) telephone-based motivational counseling , ( 2 ) free nicotine replacement therapy ( NRT ) for 6 weeks , ( 3 ) access to community-based referrals to address socio context ual mediators of tobacco use , and ( 4 ) integration of all these components into their normal health care through the EHR system . MAIN OUTCOMES AND MEASURES Self-reported past-7-day tobacco abstinence 9 months after r and omization ( " quitting " ) , assessed by automated caller or blinded study staff . RESULTS The intervention group had a higher quit rate than the usual care group ( 17.8 % vs 8.1 % ; odds ratio , 2.5 ; 95 % CI , 1.5 - 4.0 ; number needed to treat , 10 ) . We examined whether use of intervention components was associated with quitting among individuals in the intervention group : individuals who participated in the telephone counseling were more likely to quit than those who did not ( 21.2 % vs 10.4 % ; P < .001 ) . There was no difference in quitting by use of NRT . Quitting did not differ by a request for a community referral , but individuals who used their referral were more likely to quit than those who did not ( 43.6 % vs 15.3 % ; P < .001 ) . CONCLUSIONS AND RELEVANCE Proactive , IVR-facilitated outreach enables engagement with low-SES smokers . Providing counseling , NRT , and access to community-based re sources to address socio context ual mediators among smokers reached in this setting is effective . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01156610 Background Evidence d-based tobacco cessation treatments are underused , especially by socioeconomically disadvantaged smokers . This contributes to widening socioeconomic disparities in tobacco-related morbidity and mortality . Methods The Offering Proactive Treatment Intervention trial tested the effects of a proactive outreach tobacco treatment intervention on population -level smoking abstinence and tobacco treatment use among a population -based sample of socioeconomically disadvantaged smokers . Current smokers ( n=2406 ) , regardless of interest in quitting , who were enrolled in the Minnesota Health Care Programs , the state 's publicly funded healthcare programmes for low-income population s , were r and omly assigned to proactive outreach or usual care . The intervention comprised proactive outreach ( tailored mailings and telephone calls ) and free cessation treatment ( nicotine replacement therapy and intensive , telephone counselling ) . Usual care comprised access to a primary care physician , insurance coverage of Food and Drug Administration-approved smoking cessation medications , and the state 's telephone quitline . The primary outcome was self-reported 6-month prolonged smoking abstinence at 1 year and was assessed by follow-up survey . Findings The proactive intervention group had a higher prolonged abstinence rate at 1 year than usual care ( 16.5 % vs 12.1 % , OR 1.47 , 95 % CI 1.12 to 1.93 ) . The effect of the proactive intervention on prolonged abstinence persisted in selection models accounting for non-response . In analysis of secondary outcomes , use of evidence -based tobacco cessation treatments were significantly greater among proactive outreach participants compared with usual care , particularly combination counselling and medications ( 17.4 % vs 3.6 % , OR 5.69 , 95 % CI 3.85 to 8.40 ) . Interpretation Population -based proactive tobacco treatment increases engagement in evidence -based treatment and is effective in long-term smoking cessation among socioeconomically disadvantaged smokers . Findings suggest that dissemination of population -based proactive treatment approaches is an effective strategy to reduce the prevalence of smoking and socioeconomic disparities in tobacco use . Trial registration number NCT01123967 BACKGROUND Continued high rates of smoking among socioeconomically disadvantaged women lead to increases in children 's health problems associated with exposure to tobacco smoke . The pediatric clinic is a " teachable setting " in which to provide advice and assistance to parents who smoke . OBJECTIVE To evaluate a smoking cessation intervention for women . DESIGN Two-arm ( usual care vs intervention ) r and omized trial . SETTING Pediatric clinics serving an ethnically diverse population of low-income families in the greater Seattle , Wash , area . INTERVENTION During the clinic visit , women received a motivational message from the child 's clinician , a guide to quitting smoking , and a 10-minute motivational interview with a nurse or study interventionist . Women received as many as 3 outreach telephone counseling calls from the clinic nurse or interventionist in the 3 months following the visit . PARTICIPANTS Self-identified women smokers ( n = 303 ) whose children received care at participating clinics . MAIN OUTCOME MEASURE Self-reported abstinence from smoking 12 months after enrollment in the study , defined as not smoking , even a puff , during the 7 days prior to assessment . RESULTS Response rates at 3 and 12 months were 80 % and 81 % . At both follow-ups , abstinence rates were twice as great in the intervention group as in the control group ( 7.7 % vs 3.4 % and 13.5 % vs 6.9 % , respectively ) . The 12-month difference was statistically significant . CONCLUSIONS A pediatric clinic smoking cessation intervention has long-term effects in a socioeconomically disadvantaged sample of women smokers . The results encourage implementation of evidence -based clinical guidelines for smoking cessation in pediatric practice The purpose of this study was to examine the associations between individual and neighborhood social context ual factors and smoking prevalence among African-American women in subsidized neighborhoods . We r and omly sample d 663 adult women in 17 subsidized neighborhoods in two Southeastern US states . The smoking prevalence among participants was 37.6 % , with an estimated neighborhood household prevalence ranging from 30 to 68 % . Smokers were more likely to be older , have lower incomes , have lower BMI , and live with other smokers . Women with high social cohesion were less likely to smoke , although living in neighborhoods with higher social cohesion was not associated with smoking prevalence . Women with higher social cohesion were more likely to be older and had lived in the neighborhood longer . Women with high stress ( related to violence and disorder ) and who lived in neighborhoods with higher stress were more likely to smoke . Younger women were more likely to have higher stress than older women . There were no statistically significant associations with objective neighborhood crime data in any model . This is the first study to examine both individual and neighborhood social context ual correlates among African-American women in subsidized neighborhoods . This study extends findings about smoking behaviors and neighborhood social context s in this high-risk , urban population . Future research is needed to explore age and residential stability differences and perceptions of social cohesion , neighborhood disorder , and perceived violence in subsidized housing . Further research is also warranted on African-American women , subsidized housing , smoking , social context , health disparities ’ effective strategies to address these individual and context ual factors to better inform future ecological-based multilevel prevention , and cessation intervention strategies Objective : Evaluate the effectiveness of monetary incentives for increasing engagement in smoking cessation treatment and improving 6-month abstinence in low-income pregnant smokers . Method : Two-group r and omized clinical trial recruiting low-income ( Medicaid-registered ) pregnant smokers receiving assistance through a perinatal support program . Participants were r and omized to either an incentive ( n = 505 ) or control condition ( n = 509 ) . All participants were offered identical smoking cessation counseling at contacts . Incentive condition participants received incentives for attending pre- and postbirth treatment contacts : $ 25 for each of 6 prebirth provider visits , $ 25–40 for each of 4 postbirth home visits at Weeks 1 , 2 , 4 , and 6 ( total = $ 130 ) , $ 20 for each of 5 postbirth counseling calls and $ 40 for biochemically verified abstinence at the Week 1 and 6-month visits . Control condition participants received only $ 40 for attendance at the Week 1 and 6-month postbirth visits ( $ 40 each ) . Main outcomes : Primary outcome was biochemically confirmed 7-day point-prevalence abstinence at 6-month postbirth follow-up . Secondary outcomes included number of home visits and phone calls taken over the first 6 months postbirth ; biochemically confirmed abstinence at postbirth Week 1 visit ; and self-reported smoking status at 2- and 4-month visits . Results : Incentive condition participants had a higher biochemically confirmed abstinence rate at 6-month postbirth than controls ( 14.7 % vs. 9.2 % , respectively : p < .01 ) . This effect was mediated by incentive condition participants ’ greater acceptance of postbirth home visits and counseling calls . Conclusions : Moderate incentive payments for smoking treatment engagement ( a mean of ≈$214 paid ) increased low-income pregnant smokers ’ engagement and success in smoking cessation treatment BACKGROUND Although smoking cessation programs significantly reduce smoking rates in the general population , some sectors are poorly motivated by them , especially healthy men from lower socioeconomic classes . METHODS By using a significant life event ( approaching birth of a child ) we exploited a time of increased receptiveness to smoking cessation influences . A multicomponent intervention was conducted and evaluated using a stratified , r and omised control trial , with an intention to treat analysis . RESULTS Five hundred and sixty-one men were enrolled and 505 ( 90 % ) followed to the end of their partners ' pregnancy . At 6-month follow-up 16.5 % of 291 smokers of the intervention group and 9.3 % of 270 in the control group reported they had stopped smoking ( P=0.011 , OR=0.52 , 95 % CI 0.31 - 0.86 ) . The strongest predictors of smoking cessation were being in a skilled occupation , having a higher number of quit attempts in the previous year and having the first cigarette of the day relatively later . CONCLUSIONS The number of smoking men who had to be treated to achieve one stopping smoking ( NNT ) during their partner 's pregnancy was 13 to 14 . Innovative antismoking population health measures for the partners of antenatal patients are effective and perhaps should be more widely adopted INTRODUCTION Low-income population s are especially likely to smoke and have difficulty quitting . This study evaluated a monetary incentive intended to increase smoking treatment engagement and abstinence among Medicaid recipients who smoke . STUDY DESIGN Two-group r and omized clinical trial of Incentive ( n=948 ) and Control interventions ( n=952 ) for smoking . SETTING / PARTICIPANTS Medicaid recipients recruited from primary care patients ( n=920 ) and callers to the Wisconsin Tobacco Quit Line ( n=980 ) . INTERVENTION Participants were offered five quitline cessation calls and were encouraged to obtain cessation medication ( covered by Medicaid ) . All participants received payment for completing a baseline assessment and a 6-month smoking test . Only Incentive condition participants received compensation for taking counseling calls ( $ 30 per call ) and for biochemically verified abstinence at the 6-month visit ( $ 40 ) . MAIN OUTCOME MEASURES Seven-day point-prevalence smoking abstinence 6-months post study entry and cost/quit . RESULTS Incentive condition participants had significantly higher biochemically determined 7-day point-prevalence smoking abstinence rates 6 months after study induction than did Controls ( 21.6 % vs 13.8 % , respectively , p<0.0001 ) . A positive treatment effect of incentives was present across other abstinence indices , but the size of effects and levels of abstinence varied considerably across indices . Incentive condition participants were also significantly more likely than non-incentivized Control participants to accept Wisconsin Tobacco Quit Line treatment calls and their acceptance of calls mediated their attainment of higher abstinence rates at 6-month follow-up . The cost/quit/participant averaged $ 4,268.26 for the Control participants and $ 3,601.37 for the Incentive participants . CONCLUSIONS This study shows that fairly moderate levels of incentive payments for treatment engagement and abstinence ( a total possible payment of $ 190 ) increased very low-income smokers ' engagement and success in smoking cessation treatment . CLINICAL REGISTRATION This study is registered at www . clinical trials.gov : NCT02713594 BACKGROUND Text messaging programs on mobile phones have shown some promise in helping people quit smoking . Text2Quit is an automated , personalized , interactive mobile health program that sends text messages to offer advice , support , and reminders about quitting smoking . PURPOSE To evaluate the effect of Text2Quit on biochemically confirmed repeated point prevalence abstinence in the context of an RCT conducted in the U.S. METHODS Participants ( n=503 ) were recruited on the Internet and r and omized to receive Text2Quit or self-help material . Between 2011 and 2013 , participants were surveyed at baseline and at 1 , 3 , and 6 months post-enrollment to assess smoking status . Saliva was collected from participants who reported not smoking in the past 7 days at the 6-month follow-up . An intent to treat analysis was used , and those lost to follow-up were categorized as smokers . All analyses were completed in 2013 . RESULTS Biochemically confirmed repeated point prevalence abstinence favored the intervention group , with 11.1 % abstinent compared to 5.0 % of the control group ( relative risk=2.22 , 95 % CI=1.16 , 4.26 , p<0.05 ) . Similarly , self-reported repeated point prevalence abstinence was higher in the intervention group ( 19.9 % ) than in the control group ( 10.0 % ) ( p<0.01 ) . Effects were found to be uniform across the analyzed demographic subgroups , although suggestive of a larger effect for non-whites than whites . CONCLUSIONS These results provide initial support for the relative efficacy of the Text2Quit program OBJECTIVES To determine if mothers receiving a smoking cessation intervention emphasizing health risks of environmental tobacco smoke ( ETS ) for their children have a higher quit rate than mothers who received routine smoking cessation advice , which focused on their own health , or a control group of mothers . SETTING Tertiary referral centre . METHODS R and omized control trial . A total of 363 mothers were r and omly assigned to a smoking cessation intervention either aim ed at their children 's health ( n = 111 ) or their own health ( n = 131 ) , or to a control group receiving no smoking cessation advice ( n = 121 ) . RESULTS Provision to mothers of both groups of health risks of tobacco smoke result ed in significantly higher rate of cessation of smoking and smoking location change than those of the control group , with child intervention group having significantly higher rate of cessation of smoking and smoking location change than those of the maternal intervention group ( P < 0.05 ) . Post-intervention knowledge scores differed significantly for all groups ; however , child intervention group was the only significantly better group than the others ( P < 0.05 ) . According to the multivariate analysis results , intervention grouping and presence of smoking friends were independent factors determining smoking cessation ( P < 0.05 ) . Intervention grouping , post-intervention knowledge , presence of other household members who smoked and family income were independent factors determining smoking location change ( P < 0.05 ) . Family income , intervention grouping and presence of smoking friends were significant independent factors influencing post-intervention knowledge ( P < 0.05 ) . CONCLUSION Discussion during short paediatric visits on effects of smoking on child 's or maternal health may result in a significant smoking cessation , smoking location change rate or knowledge change . Those who can not give up smoking usually change their location of smoking . Provision of information on effects of smoking on child 's health , rather than maternal , may result in more significant changes in behaviour or knowledge . Maternal education on smoking should include information on effects of smoking on both child 's and maternal health , but should be especially focused on child 's health BACKGROUND This article describes the process and results of a smoking cessation intervention r and omized clinical trial ( RCT ) that was conducted as a community-based participatory research project . This RCT tested whether outcomes are improved by adding social justice and tobacco industry targeting messages to a smoking cessation program conducted among African American adults within a low-income community in San Francisco , California . This study provides lessons for future similar research projects that focus on urban low-income population s. METHODS Participants were r and omly allocated to receive a smoking-cessation program ( control group [ CG ] ) or CG care plus tobacco industry and media ( IAM ) messages . Primary interventions were behavioral . At intake , participants reporting severe withdrawal or smoking > or = 25 cigarettes daily were offered free nicotine replacement therapy . Baseline data were from an in-person interview . Outcome measures included self-reported smoking status ; validation of quitting was by salivary cotinine assays . RESULTS Of 87 participants providing baseline data , 31 % ( 27 ) did not join the RCT . Proportions quitting in the CG and IAM group were 11.5 % and 13.6 % at 6 months and 5.3 % and 15.8 % at 12 months , respectively . CONCLUSION African Americans in underserved inner-city neighborhoods can be recruited into RCTs with community participatory approaches . Differences between the CG and IAM in proportions who quit were 2.1 % and 10.5 % at 6 and 12 months , respectively . More than 3 years with adequate funding , high staffing ratios , and intense outreach and follow-up schedules are needed to achieve recruitment and study goals OBJECTIVES We sought to compare the effectiveness of a dental practitioner advice and brief counseling intervention to quit tobacco use versus usual care for patients in community health centers on tobacco cessation , reduction in tobacco use , number of quit attempts , and change in readiness to quit . METHODS We r and omized 14 federally funded community health center dental clinics that serve diverse racial/ethnic groups in 3 states ( Mississippi , New York , and Oregon ) to the intervention ( brief advice and assistance , including nicotine replacement therapy ) or usual care group . RESULTS We enrolled 2549 smokers . Participants in the intervention group reported significantly higher abstinence rates at the 7.5-month follow-up , for both point prevalence ( F(1,12 ) = 6.84 ; P < .05 ) and prolonged abstinence ( F(1,12 ) = 14.62 ; P < .01 ) than did those in the usual care group . CONCLUSIONS The results of our study suggest the viability and effectiveness of tobacco cessation services delivered to low-income smokers via their dental health care practitioner in community health centers . Tobacco cessation services delivered in public dental clinics have the potential to improve the health and well-being of millions of Americans BACKGROUND It is not known whether large financial incentives enhance long-term smoking cessation rates outside clinical or workplace setting s. OBJECTIVES The goal of this study was to test whether large financial incentives improved long-term smoking cessation rates in low-income smokers , in a general population setting , without face-to-face or telephone counseling . METHODS This was a 2-arm , parallel group , individually r and omized controlled trial , with follow-up after 3 , 6 , and 18 months . Participants were 805 low-income smokers enrolled between 2011 and 2013 from the general population in Geneva , Switzerl and . We r and omly assigned participants to receive either booklets plus access to a smoking cessation website ( control group , n = 404 ) , or the same intervention plus financial incentives ( intervention group , n = 401 ) . Incremental financial rewards , to a maximum of U.S. $ 1,650 , were offered for biochemically verified abstinence at 1 , 2 , and 3 weeks , and 1 , 3 , and 6 months . No in-person counseling , telephone counseling , or medications were provided . The primary outcome was continuous abstinence between 6 months ( end of incentives ) and 18 months ( 12 months after the incentives ended ) , verified by expired carbon monoxide and salivary cotinine . We also assessed biochemically verified 7-day abstinence at 3 , 6 , and 18 months . RESULTS Rates of continuous abstinence between months 6 and 18 were 9.5 % in the incentive group and 3.7 % in the control group ( p = 0.001 ) . Rates of 7-day abstinence were higher in the incentive group than in the control group at 3 ( 54.9 % vs. 11.9 % ; p < 0.001 ) , 6 ( 44.6 % vs. 11.1 % ; p < 0.001 ) , and 18 months ( 18.2 % vs. 11.4 % ; p = 0.006 ) . CONCLUSIONS In low-income smokers who did not receive face-to-face or telephone smoking cessation counseling , large financial incentives increased long-term rates of smoking cessation . ( Financial incentives for smoking cessation in low-income smokers ; IS RCT N04019434 ) OBJECTIVES The purpose of this study was to evaluate a brief smoking cessation intervention for women 15 to 35 years of age attending Planned Parenthood clinics . METHODS Female smokers ( n = 1154 ) were r and omly assigned either to advice only or to a brief intervention that involved a 9-minute video , 12 to 15 minutes of behavioral counseling , clinician advice to quit , and follow-up telephone calls . RESULTS Seventy-six percent of those eligible participated . Results revealed a clear , short-term intervention effect at the 6-week follow-up ( 7-day self-reported abstinence : 10.2 % vs 6.9 % for advice only , P < .05 ) and a more ambiguous effect at 6 months ( 30-day biochemically vali date d abstinence : 6.4 % vs 3.8 % , NS ) . CONCLUSIONS This brief , clinic-based intervention appears to be effective in reaching and enhancing cessation among female smokers , a traditionally underserved population BACKGROUND In western countries , smoking prevalence rates are high among smokers unmotivated to quit and those with a lower socioeconomic status ( LSES ) . Multiple computer tailoring and the use of audio-visual aids may improve such interventions and increase cessation in LSES smokers . This study assessed the 12-month effectiveness of a video- and text-based computer-tailored intervention . METHODS A r and omized controlled trial in the Netherl and s was used in which smokers were allocated to the video-based condition ( VC ) ( N=670 ) , the text-based condition ( TC ) ( N=708 ) or the control condition ( CC ) ( brief generic text advice ) ( N=721 ) . After 12months , self-reported prolonged abstinence was assessed and biochemically verified in respondents indicating to have quit smoking . Three analysis strategies were used to assess the effects : ( 1 ) multiple imputation ( MI ) ; ( 2 ) intention-to-treat ( ITT ) ; ( 3 ) complete case analysis ( CC ) . RESULTS VC was more effective in prolonged abstinence compared to CC ( odds ratio (OR)=1.90 , p=.005 ) and the text-based condition ( OR=1.71 , p=.01 ) . VC was furthermore more effective than TC . No differences were found for SES and motivational levels . Results were similar when using ITT and CC . For our secondary outcome seven-day point prevalence abstinence ; however , neither VC ( OR=1.17 , p=.34 ) or TC ( OR=0.91 , p=.52 ) outperformed the CC . CONCLUSION The video-based computer-tailored intervention was effective in obtaining substantial long-term abstinence compared to the text-based version and a brief generic text advice BACKGROUND Internet-based interventions for smoking cessation could help millions of people stop smoking at very low unit costs ; however , long-term biochemically verified evidence is scarce and such interventions might be less effective for smokers with low socioeconomic status than for those with high status because of lower online literacy to engage with websites . We aim ed to assess a new interactive internet-based intervention ( StopAdvisor ) for smoking cessation that was design ed with particular attention directed to people with low socioeconomic status . METHODS We did this online r and omised controlled trial between Dec 6 , 2011 , and Oct 11 , 2013 , in the UK . Participants aged 18 years and older who smoked every day were r and omly assigned ( 1:1 ) to receive treatment with StopAdvisor or an information-only website . R and omisation was automated with an unseen r and om number function embedded in the website to establish which treatment was revealed after the online baseline assessment . Recruitment continued until the required sample size had been achieved from both high and low socioeconomic status sub population s. Participants , and research ers who obtained data and did laboratory analyses , were masked to treatment allocation . The primary outcome was 6 month sustained , biochemically verified abstinence . The main secondary outcome was 6 month , 7 day biochemically verified point prevalence . Analysis was by intention to treat . Homogeneity of intervention effect across the socioeconomic sub sample s was first assessed to establish whether overall or separate sub sample analyses were appropriate . The study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N99820519 . FINDINGS We r and omly assigned 4613 participants to the StopAdvisor group ( n=2321 ) or the control group ( n=2292 ) ; 2142 participants were of low socioeconomic status and 2471 participants were of high status . The overall rate of smoking cessation was similar between participants in the StopAdvisor and control groups for the primary ( 237 [ 10 % ] vs 220 [ 10 % ] participants ; relative risk [ RR ] 1·06 , 95 % CI 0·89 - 1·27 ; p=0·49 ) and the secondary ( 358 [ 15 % ] vs 332 [ 15 % ] participants ; 1·06 , 0·93 - 1·22 ; p=0·37 ) outcomes ; however , the intervention effect differed across socioeconomic status sub sample s ( 1·44 , 0·99 - 2·09 ; p=0·0562 and 1·37 , 1·02 - 1·84 ; p=0·0360 , respectively ) . StopAdvisor helped participants with low socioeconomic status stop smoking compared with the information-only website ( primary outcome : 90 [ 8 % ] of 1088 vs 64 [ 6 % ] of 1054 participants ; RR 1·36 , 95 % CI 1·00 - 1·86 ; p=0·0499 ; secondary outcome : 136 [ 13 % ] vs 100 [ 10 % ] participants ; 1·32 , 1·03 - 1·68 , p=0·0267 ) , but did not improve cessation rates in those with high socioeconomic status ( 147 [ 12 % ] of 1233 vs 156 [ 13 % ] of 1238 participants ; 0·95 , 0·77 - 1·17 ; p=0·61 and 222 [ 18 % ] vs 232 [ 19 % ] participants ; 0·96 , 0·81 - 1·13 , p=0·64 , respectively ) . INTERPRETATION StopAdvisor was more effective than an information-only website in smokers of low , but not high , socioeconomic status . StopAdvisor could be implemented easily and made freely available , which would probably improve the success rates of smokers with low socioeconomic status who are seeking online support . FUNDING National Prevention Research Initiative BACKGROUND Initial trials of web-based smoking-cessation programs have generally been promising . The active components of these programs , however , are not well understood . This study aim ed to ( 1 ) identify active psychosocial and communication components of a web-based smoking-cessation intervention and ( 2 ) examine the impact of increasing the tailoring depth on smoking cessation . DESIGN R and omized fractional factorial design . SETTING Two HMOs : Group Health in Washington State and Henry Ford Health System in Michigan . PARTICIPANTS 1866 smokers . INTERVENTION A web-based smoking-cessation program plus nicotine patch . Five components of the intervention were r and omized using a fractional factorial design : high- versus low-depth tailored success story , outcome expectation , and efficacy expectation messages ; high- versus low-personalized source ; and multiple versus single exposure to the intervention components . MEASUREMENTS Primary outcome was 7 day point-prevalence abstinence at the 6-month follow-up . FINDINGS Abstinence was most influenced by high-depth tailored success stories and a high-personalized message source . The cumulative assignment of the three tailoring depth factors also result ed in increasing the rates of 6-month cessation , demonstrating an effect of tailoring depth . CONCLUSIONS The study identified relevant components of smoking-cessation interventions that should be generalizable to other cessation interventions . The study also demonstrated the importance of higher-depth tailoring in smoking-cessation programs . Finally , the use of a novel fractional factorial design allowed efficient examination of the study aims . The rapidly changing interfaces , software , and capabilities of eHealth are likely to require such dynamic experimental approaches to intervention discovery OBJECTIVES To evaluate the effect of a provider counseling and office systems intervention in obstetric , pediatric , and Special Supplemental Nutrition Program for Women , Infants and Children ( WIC ) clinics on smoking and relapse rates in pregnant and postpartum women . METHODS Five community health centers were r and omized to special intervention ( SI ) or usual care ( UC ) . Subjects ( n = 601 ) were current smokers or had quit with pregnancy . Prenatal and postpartum interviews assessed smoking status and related factors . Data were collected between May 1997 and November 2000 . RESULTS There was a statistically significant difference in 30-day abstinence rates between SI ( 26 % ) and UC ( 12 % ) conditions at the end of pregnancy among women who had not quit spontaneously with pregnancy ( odds ratio [OR]=2.57 , p = 0.05 ) . This effect remained at 1 month postpartum but was lost at 3- and 6-month postpartum follow-ups . CONCLUSIONS Brief interventions delivered by healthcare providers during routine prenatal care increased smoking abstinence during pregnancy among women who did not quit spontaneously . Interventions extended into postpartum care did not affect relapse and smoking rates postdelivery OBJECTIVES Low-income women have high rates of smoking during pregnancy , but little is known about the costs , benefits , and cost-effectiveness of motivational interviewing ( MI ) , focused on the medical and psychosocial needs of this population , as an intervention for smoking cessation and relapse prevention . METHODS A sample of 302 low-income pregnant women was recruited from multiple obstetrical sites in the Boston metropolitan area into a r and omized controlled trial of a motivational intervention for smoking cessation and relapse prevention versus usual care ( UC ) . The findings of this clinical trial were used to estimate the costs , benefits , and cost-effectiveness of the intervention from a societal perspective , incorporating published quality -adjusted life-year ( QALY ) and life-year ( LY ) estimates . Outcomes included smoking cessation and relapse , maternal and infant outcomes , economic costs , LYs and QALYs saved , and incremental cost-effectiveness ratios . RESULTS The cost-effectiveness of MI for relapse prevention compared to UC was estimated to be $ 851/LY saved and $ 628/QALY saved . Including savings in maternal medical costs in sensitivity analyses result ed in cost savings for MI for relapse prevention compared to UC . For smoking cessation , MI cost more but did not provide additional benefit compared to UC . In one-way sensitivity analyses , the incremental cost-effectiveness of MI versus UC would have been $ 117,100/LY saved and $ 86,300/QALY saved if 8 % of smokers had quit . In two-way sensitivity analyses , MI was still relatively cost-effective for relapse prevention ( $ 17,300/QALY saved ) even if it cost as much as $ 2000/participant and was less effective . For smoking cessation , however , a higher level of effectiveness ( 9/110 ) and higher cost ( $ 400/participant ) result ed in higher incremental cost-effectiveness ratios ( $ 112,000/QALY ) . CONCLUSIONS Among low-income pregnant women , MI helps prevent relapse at relatively low cost , and may be cost-saving when net medical cost savings are considered . For smoking cessation , MI cost more but provided no additional benefit compared to UC , but might offer benefits at costs comparable to other clinical preventive interventions if 8 - 10 % of smokers are induced to quit Despite high smoking rates among those living in poverty , few cessation studies are conducted in these population s. This cluster-r and omized trial tested nicotine gum plus motivational interviewing ( MI ) for smoking cessation in 20 low-income housing developments ( HDs ) . Intervention participants ( 10 HDs , n = 66 ) received educational material s , 8 weeks of 4 mg nicotine gum , and 5 MI sessions on quitting smoking . Comparison participants ( 10 HDs , n = 107 ) received 5 MI sessions and educational material s addressing fruit and vegetable consumption . Participants had a mean age of 46.3 years and were predominantly female ( 70 % ) and African American ( 83 % ) . Biochemically-verified 7-day abstinence rates at 8 weeks were 6.1 % and 5.6 % in the intervention and comparison arms , respectively ( p = ns ) ; and at 26 weeks were 7.6 % and 9.3 % , respectively ( p = ns ) . Results suggest that nicotine gum plus MI were not effective for smoking cessation in low-income housing . Programs are needed to enhance the effectiveness of pharmacotherapy and counseling in underserved population BACKGROUND NHS Stop Smoking Services ( SSSs ) provide free at the point of use treatment for smokers who would like to stop . Since their inception in 1999 they have evolved to offer a variety of support options . Given the changes that have happened in the provision of services and the ongoing need for evidence on effectiveness , the Evaluating Long-term Outcomes for NHS Stop Smoking Services ( ELONS ) study was commissioned . OBJECTIVES The main aim of the study was to explore the factors that determine longer-term abstinence from smoking following intervention by SSSs . There were also a number of additional objectives . DESIGN The ELONS study was an observational study with two main stages : secondary analysis of routine data collected by SSSs and a prospect i ve cohort study of service clients . The prospect i ve study had additional elements on client satisfaction , well-being and longer-term nicotine replacement therapy ( NRT ) use . SETTING The setting for the study was SSSs in Engl and . For the secondary analysis , routine data from 49 services were obtained . For the prospect i ve study and its added elements , nine services were involved . The target population was clients of these services . PARTICIPANTS There were 202,804 cases included in secondary analysis and 3075 in the prospect i ve study . INTERVENTIONS A combination of behavioural support and stop smoking medication delivered by SSS practitioners . MAIN OUTCOME MEASURES Abstinence from smoking at 4 and 52 weeks after setting a quit date , vali date d by a carbon monoxide ( CO ) breath test . RESULTS Just over 4 in 10 smokers ( 41 % ) recruited to the prospect i ve study were biochemically vali date d as abstinent from smoking at 4 weeks ( which was broadly comparable with findings from the secondary analysis of routine service data , where self-reported 4-week quit rates were 48 % , falling to 34 % when biochemical validation had occurred ) . At the 1-year follow-up , 8 % of prospect i ve study clients were CO vali date d as abstinent from smoking . Clients who received specialist one-to-one behavioural support were twice as likely to have remained abstinent than those who were seen by a general practitioner ( GP ) practice and pharmacy providers [ odds ratio ( OR ) 2.3 , 95 % confidence interval ( CI ) 1.2 to 4.6 ] . Clients who received group behavioural support ( either closed or rolling groups ) were three times more likely to stop smoking than those who were seen by a GP practice or pharmacy providers ( OR 3.4 , 95 % CI 1.7 to 6.7 ) . Satisfaction with services was high and well-being at baseline was found to be a predictor of abstinence from smoking at longer-term follow-up . Continued use of NRT at 1 year was rare , but no evidence of harm from longer-term use was identified from the data collected . CONCLUSIONS Stop Smoking Services in Engl and are effective in helping smokers to move away from tobacco use . Using the 52-week CO-vali date d quit rate of 8 % found in this study , we estimate that in the year 2012 - 13 the services supported 36,249 clients to become non-smokers for the remainder of their lives . This is a substantial figure and provides one indicator of the ongoing value of the treatment that the services provide . The study raises a number of issues for future research including ( 1 ) examining the role of electronic cigarettes ( e-cigarettes ) in smoking cessation for service clients [ this study did not look at e-cigarette use ( except briefly in the longer-term NRT study ) but this is a priority for future studies ] ; ( 2 ) more detailed comparisons of rolling groups with other forms of behavioural support ; ( 3 ) further exploration of the role of practitioner knowledge , skills and use of effective behaviour change techniques in supporting service clients to stop smoking ; ( 4 ) surveillance of the impact of structural and funding changes on the future development and sustainability of SSSs ; and ( 5 ) more detailed analysis of well-being over time between those who successfully stop smoking and those who relapse . Further research on longer-term use of non-combustible nicotine products that measures a wider array of biomarkers of smoking-related harm such as lung function tests or carcinogen metabolites . FUNDING The National Institute for Health Research Health Technology Assessment programme . The UK Centre for Tobacco and Alcohol Studies provided funding for the longer-term NRT study Importance While the proportion of adults who smoke cigarettes has declined substantially in the past decade , socioeconomic disparities in cigarette smoking remain . Few interventions have targeted low socioeconomic status ( SES ) and minority smokers in primary care setting s. Objective To evaluate a multicomponent intervention to promote smoking cessation among low-SES and minority smokers . Design , Setting , and Participants For this prospect i ve , unblinded , r and omized clinical trial conducted between May 1 , 2015 , and September 4 , 2017 , adults 18 years and older who spoke English , smoked 10 or more cigarettes per day in the past week , were contemplating or preparing to quit smoking , and had a primary care clinician were recruited from general internal medicine and family medicine practice s at 1 large safety-net hospital in Boston , Massachusetts . Interventions Patients were r and omized to a control group that received an enhancement of usual care ( n = 175 participants ) or to an intervention group that received up to 4 hours of patient navigation delivered over 6 months in addition to usual care , as well as financial incentives for biochemically confirmed smoking cessation at 6 and 12 months following enrollment ( n = 177 participants ) . Main Outcomes and Measures The primary outcome determined a priori was biochemically confirmed smoking cessation at 12 months . Results Among 352 patients who were r and omized ( mean [ SD ] age , 50.0 [ 11.0 ] years ; 191 women [ 54.3 % ] ; 197 participants who identified as non – Hispanic black [ 56.0 % ] ; 40 participants who identified as Hispanic of any race [ 11.4 % ] ) , all were included in the intention-to-treat analysis . At 12 months following enrollment , 21 participants [ 11.9 % ] in the navigation and incentives group , compared with 4 participants [ 2.3 % ] in the control group , had quit smoking ( odds ratio , 5.8 ; 95 % CI , 1.9 - 17.1 ; number needed to treat , 10.4 ; P < .001 ) . In prespecified subgroup analyses , the intervention was particularly beneficial for older participants ( 19 [ 19.8 % ] vs 1 [ 1.0 % ] ; P < .001 ) , women ( 17 [ 16.8 % ] vs 2 [ 2.2 % ] ; P < .001 ) , participants with household yearly income of $ 20 000 or less ( 15 [ 15.5 % ] vs 3 [ 3.1 % ] ; P = .003 ) , and nonwhite participants ( 21 [ 15.2 % ] vs 4 [ 3.0 % ] ; P < .001 ) . Conclusions and Relevance In this study of adult daily smokers at 1 large urban safety-net hospital , patient navigation and financial incentives for smoking cessation significantly increased the rates of smoking cessation . Trial Registration clinical trials.gov Identifier : Background : Pediatricians following clinical practice guidelines for tobacco intervention ( “ Ask , Advise , and Refer ” [ AAR ] ) can motivate parents to reduce child tobacco smoke exposure ( TSE ) . However , brief clinic interventions are unable to provide the more intensive , evidence -based behavioral treatments that facilitate the knowledge , skills , and confidence that parents need to both reduce child TSE and quit smoking . We hypothesized that a multilevel treatment model integrating pediatric clinic-level AAR with individual-level , telephone counseling would promote greater long-term ( 12-month ) child TSE reduction and parent smoking cessation than clinic-level AAR alone . Methods : Pediatricians were trained to implement AAR with parents during clinic visits and reminded via prompts embedded in electronic health records . Following AAR , parents were r and omized to intervention ( AAR + counseling ) or nutrition education attention control ( AAR + control ) . Child TSE and parent quit status were bioverified . Results : Participants ( n = 327 ) were 83 % female , 83 % African American , and 79 % below the poverty level . Child TSE ( urine cotinine ) declined significantly in both conditions from baseline to 12 months ( p = 0.001 ) , with no between-group differences . The intervention had a statistically significant effect on 12-month bioverified quit status ( p = 0.029 ) : those in the intervention group were 2.47 times more likely to quit smoking than those in the control . Child age was negatively associated with 12-month log-cotinine ( p = 0.01 ) , whereas nicotine dependence was positively associated with 12-month log-cotinine levels ( p = 0.001 ) and negatively associated with bioverified quit status ( p = 0.006 ) . Conclusions : Pediatrician advice alone may be sufficient to increase parent protections of children from TSE . Integrating clinic-level intervention with more intensive individual-level smoking intervention is necessary to promote parent cessation INTRODUCTION Population -based smoking-cessation services tend to preferentially benefit high-SES smokers , potentially exacerbating disparities . Interventions that include proactive outreach , telephone counseling , and free or low-cost cessation medications may be more likely to help low-SES smokers quit . This analysis evaluated the role of SES in smokers ' response to a population -based proactive smoking-cessation intervention . METHODS This study , conducted in 2016 and 2017 , was a secondary analysis of the Veterans Victory Over Tobacco Study , a multicenter pragmatic RCT of a proactive smoking-cessation intervention conducted from 2009 to 2011 . Logistic regression modeling was used to test the effect of income or education level on 6-month prolonged abstinence at 1-year follow-up . RESULTS Of the 5,123 eligible , r and omized participants , 2,565 ( 50 % ) reported their education level and 2,430 ( 47 % ) reported their income level . The interactions between education ( p=0.07 ) or income ( p=0.74 ) X treatment arm were not statistically significant at the 0.05 level . The largest effect sizes for the intervention were found among smokers in the lowest education category ( ≤11th grade ) , with a quit rate of 17.3 % as compared with 5.7 % in usual care ( OR=3.5 , 95 % CI=1.4 , 8.6 ) and in the lowest income range ( < $ 10,000 ) , with a quit rate of 18.7 % as compared with 9.4 % in usual care ( OR=2.2 , 95 % CI=1.2 , 4.0 ) . CONCLUSIONS In a large , multicenter smoking-cessation trial , proactive outreach was associated with higher rates of prolonged abstinence among smokers at all SES levels . Proactive outreach interventions that integrate telephone-based care and facilitated cessation medication access have the potential to reduce socioeconomic disparities in quitting . TRIAL REGISTRATION This study is registered at www . clinical trials.gov NCT00608426 Importance Limited evidence supports mobile phone – delivered cessation interventions for socioeconomically disadvantaged individuals . Objective To assess the efficacy of mobile phone – delivered cessation interventions targeted to smokers at neighborhood sites serving racial/ethnic minority and socioeconomically disadvantaged individuals . Design , Setting , and Participants This group-r and omized clinical trial with neighborhood site serving as the sampling unit compared smoking cessation interventions that included ( 1 ) nicotine replacement therapy ( NRT ) , ( 2 ) NRT plus text messaging , and ( 3 ) NRT plus text messaging plus proactive counseling via mobile phone . Recruitment took place at churches , public housing complexes , and community centers located throughout the Houston , Texas , area . A total of 624 current cigarette smokers 18 years or older were enrolled at neighborhood sites from August 13 , 2011 , through December 12 , 2014 . Final follow-up was completed on June 12 , 2015 , and data were analyzed from August 17 , 2017 , through May 10 , 2018 , based on intention to treat . Interventions Nicotine replacement therapy consisted of transdermal nicotine patches ; NRT plus text messages , transdermal nicotine patches and individually tailored mobile phone text messages ; and NRT plus text plus call , transdermal patches , individually tailored mobile phone text messages , and proactive counseling via mobile phone . Main Outcomes and Measures The primary outcome was smoking abstinence at 6 months , defined as ( 1 ) biochemically verified smoking abstinence ( calculated among a subgroup of 377 participants ) as determined by saliva cotinine level ; and ( 2 ) self-reported 30-day abstinence ( calculated among all 624 participants ) . Results The study sample included 624 current cigarette smokers ( 50.6 % female ; mean [ SD ] age , 45.8 [ 12.8 ] years ) . Among the 377 participants eligible for biochemical verification , 127 self-reported 30-day abstinence and were asked to provide saliva sample s. Of these , 98 sample s were returned ( participants who did not return sample s were coded as smoking ) . Biochemically verified abstinence rates were 12.0 % for NRT , 12.0 % for NRT plus text , and 25.5 % for NRT plus text plus call . Participants in the NRT plus text plus call group were 2.11 ( 95 % CI , 1.00 - 4.48 ) times more likely to be biochemically verified as abstinent compared with the NRT group . No differences in biochemically verified abstinence between the NRT plus text group and the NRT group were observed . Similar associations were observed with the self-report cessation outcomes . Conclusions and Relevance Findings indicate that assignment to an intervention consisting of text messaging alone may not increase cessation rates for socioeconomically disadvantaged smokers . However , text messaging plus proactive counseling may be an efficacious option . Trial Registration Clinical Trials.gov identifier : OBJECTIVES To determine the cost-effectiveness of an incentive-based stop-smoking intervention that paid Medicaid recipients who smoke to take calls from a tobacco quit line . METHODS A cost-effectiveness analysis was conducted alongside a r and omized controlled trial . The analysis was conducted from a health care systems perspective on the basis of costs and effectiveness over a 6-month follow-up . Participants ( n = 1900 ) were recruited from May 2013 to June 2015 through quit line ( n = 980 ) , clinic-based ( n = 444 ) , or community-based ( n = 476 ) referrals . Incentive group participants ( n = 948 ) received $ 30 a call for taking up to five tobacco quit line calls and $ 40 for biochemically verified tobacco abstinence at 6 months . Control group participants ( n = 952 ) did not receive financial incentives for taking quit line calls . Intervention re source costs included incentive payments to participants , counselor and administrative staff time , and smoking cessation medications . Smoking status at baseline and 6 months was determined for all study participants via carbon monoxide ( CO ) breath tests ( abstinence : CO < 7 ppm ) . Cost-effectiveness analysis calculated the incremental cost-effectiveness ratio ( ICER ) . RESULTS Incentive treatment produced higher 6-month CO-confirmed 7-day point-prevalence abstinence than did the control treatment ( 21.6 vs. 13.8 % ; P < 0.001 ) . The ICER of the financial incentives intervention was $ 2316 ( 95 % confidence interval $ 1582-$4270 ) per additional person who quit . The study ICER compares favorably with other smoking treatments , such as varenicline combined with proactive telephone counseling , whose ICER has been estimated at $ 2600 per additional smoker who quits . CONCLUSIONS Use of financial incentives to engage with tobacco quit line treatment is a cost-effective option to enhance smoking cessation rates for low-income smokers AIMS AND OBJECTIVES The aim of this study is to describe and compare three statistical methods to allow for therapist effects in individually r and omised controlled trials . BACKGROUND In an individually r and omised controlled trial where the intervention is delivered by a health professional it seems likely that the effectiveness of the intervention , independent of any treatment effect , could depend on the skill of the health professional delivering it . This leads to a potential clustering of the outcomes for the patients being treated by the same health professional . DESIGN Retrospective statistical analysis of outcomes from four example r and omised controlled trial data sets with potential clustering by health professional . METHODS Three methods to allow for clustering are described : cluster level analysis ; r and om effects models and marginal models . These models were fitted to continuous outcome data from four example r and omised controlled trial data sets with potential clustering by health professional . RESULTS The cluster level models produced the widest confidence intervals . Little difference was found between the estimates of the regression coefficients for the treatment effect and confidence intervals between the individual patient level models for the data sets . The conclusions reached for each data set match those published in the original papers . The intracluster correlation coefficient ranged from < 0.001 - 0.04 for the outcomes , which shows only minor levels of clustering within the data sets . CONCLUSIONS The models , which use individual level data are to be preferred . Treatment coefficients from these models have different interpretations . The choice of model should depend on the scientific question being asked . RELEVANCE TO CLINICAL PRACTICE We recommend that research ers should be aware of any potential clustering , by health professional , in their r and omised controlled trial and use appropriate methods to account for this clustering in the statistical analysis of the data Background Without assistance , smokers being admitted to the hospital for coronary heart disease often return to regular smoking within a year . Objective This study assessed the 12-month effectiveness of a telephone and a face-to-face counselling intervention on smoking abstinence among cardiac patients . Differential effects for subgroups varying in their socioeconomic status and intention to quit smoking were also studied . Methods A r and omised controlled trial was used . During hospital stay , smokers hospitalised for coronary heart disease were assigned to usual care ( n = 245 ) , telephone counselling ( n = 223 ) or face-to-face counselling ( n = 157 ) . Eligible patients were allocated to an intervention counselling group and received nicotine patches . After 12 months , self-reported continued abstinence was assessed and biochemically verified in quitters . Effects on smoking abstinence were tested using multilevel logistic regression analyses applying the intention-to-treat approach . Results Compared with usual care , differential effects of telephone and face-to-face counselling on continued abstinence were found in patients with a low socioeconomic status and in patients with a low quit intention . For these patients , telephone counselling increased the likelihood of abstinence threefold ( OR = 3.10 , 95 % CI 1.32–7.31 , p = 0.01 ) , whereas face-to-face counselling increased this likelihood fivefold ( OR = 5.30 , 95 % CI 2.13–13.17 , p < 0.001 ) . Considering the total sample , the interventions did not result in stronger effects than usual care . Conclusion Post-discharge telephone and face-to-face counselling interventions increased smoking abstinence rates at 12 months compared with usual care among cardiac patients of low socioeconomic status and low quit intentions . The present study indicates that patients of high socioeconomic status and high quit motivation require different cessation approaches |
976 | 32,285,160 | High-intermediate or high-risk untreated patients with DLBCL only achieved short-term survival benefit with the upfront ASCT | To assess the survival outcomes and adverse events ( AEs ) of high-intermediate- or high-risk patients with diffuse large B cell lymphoma ( DLBCL ) who underwent conventional chemotherapy plus rituximab with or without first-line autologous stem cell transplantation ( ASCT ) . | Purpose The benefit of high-dose chemotherapy with autologous stem-cell transplantation ( ASCT ) as first-line treatment in patients with diffuse large B-cell lymphomas is still a matter of debate . To address this point , we design ed a r and omized phase III trial to compare rituximab plus cyclophosphamide , doxorubicin , vincristine , and prednisone (R-CHOP)-14 ( eight cycles ) with rituximab plus high-dose sequential chemotherapy ( R-HDS ) with ASCT . Patients and Methods From June 2005 to June 2011 , 246 high-risk patients with a high-intermediate ( 56 % ) or high ( 44 % ) International Prognostic Index score were r and omly assigned to the R-CHOP or R-HDS arm , and 235 were analyzed by intent to treat . The primary efficacy end point of the study was 3-year event-free survival , and results were analyzed on an intent-to-treat basis . Results Clinical response ( complete response , 78 % v 76 % ; partial response , 5 % v 9 % ) and failures ( no response , 15 % v 11 % ; and early treatment-related mortality , 2 % v 3 % ) were similar after R-CHOP versus R-HDS , respectively . After a median follow-up of 5 years , the 3-year event-free survival was 62 % versus 65 % ( P = .83 ) . At 3 years , compared with the R-CHOP arm , the R-HDS arm had better disease-free survival ( 79 % v 91 % , respectively ; P = .034 ) , but this subsequently vanished because of late-occurring treatment-related deaths . No difference was detected in terms of progression-free survival ( 65 % v 75 % , respectively ; P = .12 ) , or overall survival ( 74 % v 77 % , respectively ; P = .64 ) . Significantly higher hematologic toxicity ( P < .001 ) and more infectious complications ( P < .001 ) were observed in the R-HDS arm . Conclusion In this study , front-line intensive R-HDS chemotherapy with ASCT did not improve the outcome of high-risk patients with diffuse large B-cell lymphomas BACKGROUND High-dose therapy ( HDT ) followed by transplantation of autologous haemopoietic stem cells is frequently done as part of first-line therapy in young patients with high-risk aggressive B-cell lymphoma . We investigated whether HDT with cytotoxic agents identical to those used for conventional therapy followed by autologous stem-cell transplantation ( ASCT ) improved survival outcome compared with conventional chemotherapy when rituximab was added to both modalities . METHODS We did an open-label , r and omised trial comparing conventional chemotherapy ( cyclophosphamide , doxorubicin , vincristine , etoposide , prednisone ) and rituximab ( R-CHOEP-14 ) with dose-escalated sequential HDT and rituximab ( R-MegaCHOEP ) followed by repetitive ASCT in high-risk ( age-adjusted International Prognostic Index [ IPI ] 2 or 3 ) patients aged 18 - 60 years with aggressive B-cell lymphoma . Eligible patients received radiotherapy for bulky , extranodal disease , or both . R and omisation ( 1:1 ) used the Pocock minimisation algorithm ; patients were stratified by age-adjusted IPI factors , bulky disease , and centre . The primary endpoint was event-free survival . All analyses were done on the intention-to-treat population . This trial is registered with Clinical Trials.gov , number NCT00129090 . FINDINGS 136 patients were r and omly assigned to R-CHOEP-14 and 139 to R-MegaCHOEP . 130 patients in the R-CHOEP-14 group and 132 in the R-MegaCHOEP group were included in the intention-to-treat population . After a median of 42 months ( IQR 29 - 59 ) , 3-year event-free survival was 69·5 % ( 95 % CI 61·3 - 77·7 ) in the R-CHOEP-14 group and 61·4 % ( 52·8 - 70·0 ) in the R-MegaCHOEP group ( p=0·14 ; hazard ratio 1·3 , 95 % CI 0·9 - 2·0 ) . All 128 evaluable patients treated with R-MegaCHOEP had grade 4 leucopenia , as did 48 ( 58·5 % ) of 82 patients with documented blood counts in the R-CHOEP-14 group . All 128 evaluable patients in the R-MegaCHOEP group had grade 3 - 4 thrombocytopenia , as did 26 ( 33·8 % ) of 77 patients in the R-CHOEP-14 group with documented blood counts . The most important non-haematological grade 3 or 4 adverse event was infection , which occurred in 96 ( 75·0 % ) of 128 patients treated with R-MegaCHOEP and in 40 ( 31·3 % ) of 128 patients treated with R-CHOEP-14 . INTERPRETATION In young patients with high-risk aggressive B-cell lymphoma , R-MegaCHOEP was not superior to conventional R-CHOEP therapy and was associated with significantly more toxic effects . R-CHOEP-14 with or without radiotherapy remains a treatment option for these patients , with encouraging efficacy . FUNDING Deutsche Krebshilfe PURPOSE Salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation ( ASCT ) is the st and ard treatment for relapsed diffuse large B-cell lymphoma ( DLBCL ) . Salvage regimens have never been compared ; their efficacy in the rituximab era is unknown . PATIENTS AND METHODS Patients with CD20(+ ) DLBCL in first relapse or who were refractory after first-line therapy were r and omly assigned to either rituximab , ifosfamide , etoposide , and carboplatin ( R-ICE ) or rituximab , dexamethasone , high-dose cytarabine , and cisplatin ( R-DHAP ) . Responding patients received high-dose chemotherapy and ASCT . RESULTS The median age of the 396 patients enrolled ( R-ICE , n = 202 ; R-DHAP , n = 194 ) was 55 years . Similar response rates were observed after three cycles of R-ICE ( 63.5 % ; 95 % CI , 56 % to 70 % ) and R-DHAP ( 62.8 % ; 95 CI , 55 % to 69 % ) . Factors affecting response rates ( P < .001 ) were refractory disease/relapse less than versus more than 12 months after diagnosis ( 46 % v 88 % , respectively ) , International Prognostic Index ( IPI ) of more than 1 versus 0 to 1 ( 52 % v 71 % , respectively ) , and prior rituximab treatment versus no prior rituximab ( 51 % v 83 % , respectively ) . There was no significant difference between R-ICE and R-DHAP for 3-year event-free survival ( EFS ) or overall survival . Three-year EFS was affected by prior rituximab treatment versus no rituximab ( 21 % v 47 % , respectively ) , relapse less than versus more than 12 months after diagnosis ( 20 % v 45 % , respectively ) , and IPI of 2 to 3 versus 0 to 1 ( 18 % v 40 % , respectively ) . In the Cox model , these parameters were significant ( P < .001 ) . CONCLUSION In patients who experience relapse more than 12 months after diagnosis , prior rituximab treatment does not affect EFS . Patients with early relapses after rituximab-containing first-line therapy have a poor prognosis , with no difference between the effects of R-ICE and R-DHAP 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 Lack of appropriate reporting of method ological details has previously been shown to distort risk of bias assessment s in r and omized controlled trials . The same might be true for observational studies . The goal of this study was to compare the Newcastle-Ottawa Scale ( NOS ) assessment for risk of bias between review ers and authors of cohort studies included in a published systematic review on risk factors for severe outcomes in patients infected with influenza . Methods Cohort studies included in the systematic review and published between 2008–2011 were included . The corresponding or first authors completed a survey covering all NOS items . Results were compared with the NOS assessment applied by review ers of the systematic review . Inter-rater reliability was calculated using kappa ( K ) statistics . Results Authors of 65/182 ( 36 % ) studies completed the survey . The overall NOS score was significantly higher ( p < 0.001 ) in the review ers ’ assessment ( median = 6 ; interquartile range [ IQR ] 6–6 ) compared with those by authors ( median = 5 , IQR 4–6 ) . Inter-rater reliability by item ranged from slight ( K = 0.15 , 95 % confidence interval [ CI ] = −0.19 , 0.48 ) to poor ( K = −0.06 , 95 % CI = −0.22 , 0.10 ) . Reliability for the overall score was poor ( K = −0.004 , 95 % CI = −0.11 , 0.11 ) . Conclusions Differences in assessment and low agreement between review ers and authors suggest the need to contact authors for information not published in studies when applying the NOS in systematic review BACKGROUND The efficacy of first-line intensive chemotherapy plus transplantation of autologous hematopoietic stem cells in adults with disseminated aggressive lymphoma is unknown . METHODS We compared high-dose therapy plus autologous stem-cell support with the st and ard regimen of cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) in a r and omized trial . The patients were 15 to 60 years of age , had untreated aggressive lymphoma , and were at low , low intermediate , or high intermediate risk of death ( i.e. , a maximum of two adverse prognostic factors ) according to the age-adjusted International Prognostic Index . The primary outcome was event-free survival at five years . RESULTS Of 207 consecutive patients , 197 underwent r and omization ; 99 were assigned to receive CHOP , and 98 to receive high-dose chemotherapy plus stem-cell transplantation . Overall , 78 percent of the patients completed the assigned treatment ; the median follow-up was four years . The estimated event-free survival rate ( + /-SD ) at five years was significantly higher among patients who received high-dose therapy than among patients who received CHOP ( 55+/-5 percent vs. 37+/-5 percent , P=0.037 ) . Among patients with a high intermediate risk of death , according to the age-adjusted International Prognostic Index , the five-year survival rate was significantly higher after high-dose therapy than after CHOP ( 74+/-6 percent vs. 44+/-7 percent , P=0.001 ) . CONCLUSIONS High-dose chemotherapy with autologous stem-cell support is superior to CHOP in adults with disseminated aggressive lymphoma BACKGROUND The MInT study was the first to show improved 3-year outcomes with the addition of rituximab to a CHOP ( cyclophosphamide , doxorubicin , vincristine , and prednisone)-like regimen in young patients with good-prognosis diffuse large-B-cell lymphoma . Extended follow-up was needed to establish long-term effects . METHODS In the r and omised open-label MInT study , patients from 18 countries ( aged 18 - 60 years with none or one risk factor according to the age-adjusted International Prognostic Index [ IPI ] , stage II-IV disease or stage I disease with bulk ) were r and omly assigned to receive six cycles of a CHOP-like chemotherapy with or without rituximab . Bulky and extranodal sites received additional radiotherapy . R and omisation was done central ly with a computer-based tool and was stratified by centre , bulky disease , age-adjusted IPI , and chemotherapy regimen by use of a modified minimisation algorithm that incorporated a stochastic component . Patients and investigators were not masked to treatment allocation . The primary endpoint was event-free survival . Analyses were by intention to treat . This observational study is a follow-up of the MInT trial , which was stopped in 2003 , and is registered at Clinical Trials.gov , number NCT00400907 . FINDINGS The intention-to-treat population included 410 patients assigned to chemotherapy alone and 413 assigned to chemotherapy plus rituximab . After a median follow-up of 72 months ( range 0·03 - 119 ) , 6-year event-free survival was 55·8 % ( 95 % CI 50·4 - 60·9 ; 166 events ) for patients assigned to chemotherapy alone and 74·3 % ( 69·3 - 78·6 ; 98 events ) for those assigned to chemotherapy plus rituximab ( difference between groups 18·5 % , 11·5 - 25·4 , log-rank p<0·0001 ) . Multivariable analyses showed that event-free survival was affected by treatment group , presence of bulky disease , and age-adjusted IPI and that overall survival was affected by treatment group and presence of bulky disease only . After chemotherapy and rituximab , a favourable subgroup ( IPI=0 , no bulk ) could be defined from a less favourable subgroup ( IPI=1 or bulk , or both ; event-free survival 84·3 % [ 95 % CI 74·2 - 90·7 ] vs 71·0 % [ 65·1 - 76·1 ] , log-rank p=0·005 ) . 18 ( 4·4 % , 95 % CI 2·6 - 6·9 ) second malignancies occurred in the chemotherapy-alone group and 16 ( 3·9 % , 2·2 - 6·2 ) in the chemotherapy and rituximab group ( Fisher 's exact p=0·730 ) . INTERPRETATION Rituximab added to six cycles of CHOP-like chemotherapy improved long-term outcomes for young patients with good-prognosis diffuse large-B-cell lymphoma . The definition of two prognostic subgroups allows a more refined therapeutic approach to these patients than does assessment by IPI alone . FUNDING Hoffmann-La Roche BACKGROUND The prognosis of young patients with diffuse large B-cell lymphoma at high risk ( age-adjusted International Prognostic Index [ aa-IPI ] score 2 or 3 ) treated with R-CHOP ( rituximab , cyclophosphamide , vincristine , doxorubicin , and prednisone ) is poor . The aim of this study was to investigate the possible benefit of intensification with high-dose chemotherapy and autologous stem-cell transplantation as part of first-line treatment in these patients . METHODS We did a multicentre , open-label , r and omised , controlled , phase 3 trial with a 2 × 2 factorial design to compare , at two different R-CHOP dose levels , a full course of rituximab-dose-dense chemotherapy ( no transplantation group ) versus an abbreviated course of rituximab-dose-dense chemotherapy followed by consolidation with R-MAD ( rituximab plus high-dose cytarabine plus mitoxantrone plus dexamethasone ) and high-dose BEAM chemotherapy ( carmustine , etoposide , cytarabine , and melphalan ) plus autologous stem-cell transplantation ( transplantation group ) in young patients ( 18 - 65 years ) with untreated high-risk diffuse large B-cell lymphoma ( aa-IPI score 2 - 3 ) . At enrolment , patients were stratified according to aa-IPI score and r and omly assigned ( 1:1:1:1 ) to receive R-CHOP ( intravenous rituximab 375 mg/m2 , cyclophosphamide 750 mg/m2 , doxorubicin 50 mg/m2 , and vincristine 1·4 mg/m2 on day 1 , plus oral prednisone 100 mg on days 1 - 5 ) delivered in a 14-day cycle ( R-CHOP-14 ) for eight cycles ; high-dose R-CHOP-14 ( R-MegaCHOP-14 ; R-CHOP-14 except for cyclophosphamide 1200 mg/m2 and doxorubicin 70 mg/m2 ) for six cycles ; R-CHOP-14 for four cycles followed by R-MAD ( intravenous rituximab 375 mg/m2 on day 1 or 4 plus intravenous cytarabine 2000 mg/m2 and dexamethasone 4 mg/m2 every 12 h on days 1 - 3 plus intravenous mitoxantrone 8 mg/m2 on days 1 - 3 ) plus BEAM ( intravenous carmustine 300 mg/m2 on day -7 , intravenous cytarabine 200 mg/m2 twice a day on days -6 to -3 , intravenous etoposide 100 mg/m2 twice a day on days -6 to -3 , plus intravenous melphalan 140 mg/m2 on day -2 ) and autologous stem-cell transplantation ( day 0 ) ; or R-MegaCHOP-14 for four cycles followed by R-MAD plus BEAM and autologous stem-cell transplantation . The primary endpoint was failure-free survival at 2 years in the intention-to-treat population . This study is registered with EudraCT ( 2005 - 002181 - 14 ; 2007 - 000275 - 42 ) and with Clinical Trials.gov , number NCT00499018 . FINDINGS Between Jan 10 , 2006 , and Sept 8 , 2010 , 399 patients were r and omly assigned to receive transplantation ( n=199 ) or no transplantation ( n=200 ) ; 203 patients were assigned to receive R-CHOP-14 and 196 were assigned to receive R-MegaCHOP-14 . With a median follow-up of 72 months ( IQR 57 - 88 ) , 2-year failure-free survival was 71 % ( 95 % CI 64 - 77 ) in the transplantation group versus 62 % ( 95 % CI 55 - 68 ) in the no transplantation group ( hazard ratio [ HR ] 0·65 [ 95 % CI 0·47 - 0·91 ] ; stratified log-rank test p=0·012 ) . No difference in 5-year overall survival was observed between these groups ( 78 % [ 95 % CI 71 - 83 ] versus 77 % [ 71 - 83 ] ; HR 0·98 [ 0·65 - 1·48 ] ; stratified log-rank test p=0·91 ) . Grade 3 or worse haematological adverse events were reported in 183 ( 92 % ) of 199 patients in the transplantation group versus 135 ( 68 % ) of 200 patients in the no transplantation group . Grade 3 or worse non-haematological adverse events were reported in 90 ( 45 % ) versus 31 ( 16 % ) ; the most common grade 3 or worse non-haematological adverse event was gastrointestinal ( 49 [ 25 % ] vs 19 [ 10 % ] ) . Treatment-related deaths occurred in 13 ( 3 % ) patients ; eight in the transplantation group and five in the no transplantation group . INTERPRETATION Abbreviated rituximab-dose-dense chemotherapy plus R-MAD plus BEAM and autologous stem-cell transplantation reduced the risk of treatment failure compared with full course rituximab-dose-dense chemotherapy in young patients with diffuse large B-cell lymphoma at high risk . However , these results might not be clinical ly meaningful , since this improvement did not reflect an improvement in overall survival . These results do not support further consideration of the use of intensification of R-CHOP as an upfront strategy in patients with diffuse large B-cell lymphoma with poor prognosis . FUNDING Fondazione Italiana Linfomi PURPOSE R and omized trial LNH93 - 3 was conducted on patients who had poor-prognosis aggressive lymphoma and were younger than 60 years with two to three factors of the age-adjusted International Prognostic Index to evaluate the benefit of early high-dose therapy ( HDT ) with autologous stem-cell transplantation ( ASCT ) . PATIENTS AND METHODS Patients were r and omized between doxorubicin , cyclophosphamide , vindesine , bleomycin , and prednisone ( ACVBP ) chemotherapy followed by sequential consolidation and an experimental shortened treatment consisting of three cycles with escalated doses of cyclophosphamide , epirubicin , vindesine , bleomycin , and prednisone and collection of peripheral-blood stem cells . On day 60 , HDT was administered with 1,3-bis(2-chloroethyl)-1-nitrosourea , etoposide , cytarabine , and melphalan followed by ASCT . RESULTS Eligible patients ( n = 370 ) with aggressive lymphoma were analyzed . For ACVBP ( 181 patients ) and HDT ( 189 patients ) , respective complete remission rates were 64 % and 63 % . With a median follow-up of 60 months , 5-year overall survival and event-free survival for ACVBP and HDT were 60 % + /- 8 % and 46 % + /- 8 % ( P = .007 ) and 52 + /- 8 % and 39 + /- 8 % ( P = .01 ) , respectively . Survival was independently affected by age greater than 40 years ( P = .0003 ) , T-cell phenotype ( P = .009 ) , bone marrow involvement ( P = .003 ) , and HDT treatment group ( P = .04 ) . CONCLUSION Early HDT with ASCT in high-risk patients was inferior to the ACVBP chemotherapy regimen . These results indicate that the received dose-intensity before HDT was too low when compared with ACVBP and HDT and was given too early Salvage chemotherapy followed by autologous stem cell transplant ( ASCT ) remains the current st and ard of care for patients with relapsed or refractory diffuse large B‐cell lymphoma ( DLBCL ) with chemosensitive disease . The addition of rituximab results in improved overall survival ( OS ) after first‐line treatment , but cure rates of salvage therapy with ASCT are inferior when compared to historical controls . Historically , patients with DLBCL with disease progression following ASCT have had an extremely poor prognosis with a median OS of 3 months . However , there are little data regarding outcomes in the rituximab era . We performed a retrospective study of 56 patients with relapsed or refractory DLBCL with prior exposure to rituximab who had disease progression following ASCT . The median OS from progression following ASCT for the cohort was 9.9 months ( 95 % CI : 5.3–13.1 months ) . Patients who progressed less than 1 year from ASCT had a significantly shorter OS than those who progressed at 1 year or greater from ASCT ( 8.2 vs. 26.7 months , P = 0.01 ) . Patients with at least stable disease following ASCT had a longer OS than those who progressed immediately after ASCT ( 12.3 vs. 5.3 months , P = 0.01 ) . Other factors associated with OS were International Prognostic Index ( IPI ) ( P = 0.01 ) and LDH level ( P = 0.0003 ) at the time of progression following ASCT . In the rituximab era , the prognosis for patients with disease progression following ASCT remains poor , but is improved when compared with historical controls . Ultimately , more work needs to be done to develop novel therapeutic strategies tailored to individual patients in this heterogeneous population . Am . J. Hematol . 88:890–894 , 2013 . © 2013 Wiley Periodicals , PURPOSE To evaluate the role of early intensification with high-dose therapy ( HDT ) and autologous stem-cell transplantation ( ASCT ) as front-line chemotherapy for patients with high-risk , histologically aggressive non-Hodgkin 's lymphoma ( NHL ) . PATIENTS AND METHODS We planned a multicenter , r and omized trial to compare a conventional chemotherapy regimen of methotrexate with leucovorin rescue , doxorubicin , cyclophosphamide , vincristine , prednisone , and bleomycin ( MACOP-B ; arm A ) with an abbreviated regimen of MACOP-B ( 8 weeks ) followed by HDT and ASCT ( arm B ) for intermediate-high-risk/high-risk patients ( according to the age-adjusted International Prognostic Index ) . From September 1994 to April 1998 , 150 patients with aggressive lymphoma were enrolled onto the trial . Seventy-five patients were r and omly assigned to arm A and 75 patients were r and omly assigned to arm B. In both arms , involved-field radiation therapy ( 36 Gy ) was delivered to the site of bulky disease . RESULTS The rate of complete response was 68 % in arm A and 76 % in arm B ( P = not significant [ NS ] ) . Three toxic deaths ( 4 % ) occurred in arm B and one ( 1 % ) occurred in arm A ( P = NS ) . In arm B , 30 patients ( 40 % ) did not undergo HDT and ASCT . According to the intention-to-treat analysis at a median follow-up of 24 months , 5-year overall survival probability in arms A and B was 65 % and 64 % ( P = .95 ) , 5-year progression-free survival was 49 % and 61 % ( P = .21 ) , and 5-year relapse-free survival was 65 % and 77 % ( P = .22 ) , respectively . CONCLUSION Abbreviated chemotherapy followed by intensification with HDT-ASCT is not superior to conventional chemotherapy in patients with high-risk , aggressive NHL . Additional r and omized trials will clarify whether HDT-ASCT as front-line therapy after a complete course of conventional chemotherapy improves survival in this group of patients Background This study aim ed to investigate the association of pre-treatment inflammatory status with survival time and to develop a prognostic nomogram incorporating inflammatory cytokines in non-Hodgkin 's lymphoma . Methods A total of 228 patients with diffuse large B-cell lymphoma ( DLBCL ) received R-CHOP-based regimens from a prospect i ve r and omized study ( NCT01852435 ) were included as a training cohort . Other cohorts of 886 lymphoma patients were served as validation cohorts . Lymphocyte-monocyte ratio ( LMR ) , serum levels of soluble interleukin s(IL)-2R , IL-6 , IL-8 , IL-10 and tumor necrosis factor-α ( TNF-α ) , were assessed before treatment . Least absolute shrinkage and selection operator ( LASSO ) regression were used to select variables for nomogram of overall survival ( OS ) . The predictive accuracy of the nomogram was determined by concordance index ( C-index ) . Findings The nomogram included lactate dehydrogenase ( LDH ) , sIL-2R , TNF-α and decreased LMR . The C-index of the nomogram for OS prediction were range from 0.61 to 0.86 for training cohort of DLBCL and validation cohorts of DLBCL , PTCL , NKTCL and ASCT , which were superior to the predictive power of International Prognostic Index ( IPI , 0.67 to 0.84 ) or NCCN-IPI ( 0.59 to 0.78 ) , but not in those of indolent lymphoma like FL and MALT . Interpretations The nomogram incorporating inflammatory cytokines provides a useful tool for risk stratification in aggressive non-Hodgkin 's lymphomas . Fund National Natural Science Foundation of China , the Shanghai Commission of Science and Technology , Multicenter Clinical Research Project by Shanghai Jiao Tong University School of Medicine , Clinical Research Plan of SHDC , and Chang Jiang Scholars Program PURPOSE Lenalidomide has significant single-agent activity in relapsed diffuse large B-cell lymphoma ( DLBCL ) . We demonstrated that lenalidomide can be safely combined with R-CHOP ( rituximab plus cyclophosphamide , doxorubicin , vincristine , and prednisone ) ; this new combination is known as R2CHOP . The goal of this phase II study was to evaluate the efficacy of this combination in newly diagnosed DLBCL . PATIENTS AND METHODS Eligible patients were adults with newly diagnosed untreated stages II to IV CD20(+ ) DLBCL . Patients received lenalidomide 25 mg orally per day on days 1 through 10 with st and ard-dose R-CHOP every 21 days for six cycles . All patients received pegfilgrastim on day 2 of each cycle and aspirin prophylaxis throughout . DLBCL molecular subtype was determined by tumor immunohistochemistry and classified as germinal center B-cell ( GCB ) versus non-GCB in the R2CHOP patients and 87 control patients with DLBCL from the Lymphoma Data base who were treated with conventional R-CHOP . RESULTS In all , 64 patients with DLBCL were enrolled , and 60 were evaluable for response . The overall response rate was 98 % ( 59 of 60 ) with 80 % ( 48 of 60 ) achieving complete response . Event-free survival and overall survival ( OS ) rates at 24 months were 59 % ( 95 % CI , 48 % to 74 % ) and 78 % ( 95 % CI , 68 % to 90 % ) , respectively . In R-CHOP patients , 24-month progression-free survival ( PFS ) and OS were 28 % versus 64 % ( P < .001 ) and 46 % versus 78 % ( P < .001 ) in non-GCB DLBCL versus GCB DLBCL , respectively . In contrast , there was no difference in 24-month PFS or OS for R2CHOP patients on the basis of non-GCB and GCB subtype ( 60 % v 59 % [ P = .83 ] and 83 % v 75 % [ P = .61 ] at 2 years , respectively ) . CONCLUSION R2CHOP shows promising efficacy in DLBCL . The addition of lenalidomide appears to mitigate a negative impact of non-GCB phenotype on patient outcome |
977 | 26,895,896 | The benefits of robotic surgery lacked robustness on RCT -sensitivity analyses .
Conclusions Our results showed that robotic surgery contributed positively to some perioperative outcomes but longer operative times remained a shortcoming . | Background Robotic surgery has been in existence for 30 years .
This study aim ed to evaluate the overall perioperative outcomes of robotic surgery compared with open surgery ( OS ) and conventional minimally invasive surgery ( MIS ) across various surgical procedures . | OBJECTIVES To compare intraoperative blood loss , perioperative hematocrit , and transfusion requirements in patients undergoing radical retropubic prostatectomy ( RRP ) versus robotic-assisted laparoscopic prostatectomy ( RALP ) by a single surgeon . METHODS During a 14-month period , 279 patients with localized carcinoma of the prostate were prospect ively enrolled in this comparative study . The decision of which surgical approach to use was by patient choice . Of the 279 patients , 176 underwent RALP and 103 underwent RRP . The serum hematocrit was obtained preoperatively and 24 hours postoperatively in all patients . The intraoperative blood loss was recorded , and transfusion requirements were noted . RESULTS Patients in the RALP group had significantly less intraoperative blood loss compared with the RRP group ( mean 191 mL versus 664 mL , P < 0.001 ) . Additionally , the difference in the discharge hematocrit ( 36.8 % versus 32.8 % , P < 0.001 ) and the mean perioperative change in hematocrit ( 8.0 % decrease versus 10.7 % decrease , P < 0.001 ) were significant between the RALP and RRP groups , respectively . Three patients in the RRP group ( 2.9 % ) and one in the RALP group ( 0.5 % ) required transfusion of blood products ( P = 0.14 ) . CONCLUSIONS The results of this study have shown that RALP is associated with less intraoperative bleeding than RRP , and patients undergoing RALP have a greater serum hematocrit at hospital discharge . The lack of a statistically significant difference in blood transfusion was partially attributable to the low transfusion rate in both groups in this series Computer-assisted telesurgical devices have recently been approved in the United States for general surgery . To determine the safety and efficacy of these procedures , we performed a prospect i ve trial of computer-enhanced “ robotic ” fundoplication compared to st and ard laparoscopic control procedures . Consecutive patients undergoing surgical treatment for gastroesophageal reflux were included . The operating surgeon worked at a console using a three-dimensional image and manipulated h and controls . Operative times , complications , and length of hospital stay were recorded . A st and ardized question naire was administered to evaluate symptoms . Twenty patients were entered into each group . There were no differences in age , preoperative weight , or sex . Operative times were significantly longer in the robot group ( 97 vs. 141 minutes ) . There were no complications and most patients went home the first postoperative day . At follow-up , symptoms were similar in both groups ; however , there was a significant difference in the number of patients taking antisecretory medication — none in the robotic group but six in the laparoscopic group reported regular use . Computer-assisted laparoscopic antireflux surgery is safe . However , operative times are longer , with little difference in outcomes . At the current level of technology and experience , robotic antireflux surgery appears to offer little advantage over st and ard laparoscopic approaches The background of this study is to compare prospect ively the oncological and functional results of open radical prostatectomy ( OP ) and robotic prostatectomy ( RP ) from the experience of a single surgeon . Between June 2002 and June 2007 , 422 patients underwent radical prostatectomy ( OP 199 , RP 223 ) . We divided OP patients into 89 early cases ( OP-I ) and 110 late cases ( OP-II ) before and after introduction of a robotic system , and RP patients into 35 early cases ( RP-I ) and 188 late cases ( RP-II ) . Functional outcomes were measured by use of vali date d question naires completed by the patients . There were no significant differences in preoperative characteristics among the four groups , except that RP-I patients had lower biopsy Gleason scores . In the RP groups the mean estimated blood loss was lower and mean duration s of hospital stay and bladder catheterization were shorter compared to those of the OP groups . The frequency of intraoperative complications was significantly lower in the RP-II group . The positive surgical margin rates in the RP-II group were similar to or lower than those in the OP groups when stratified by pathologic stage T2 and T3 . From one month after surgery , RP-II patients had higher continence rates than OP-II patients . For patients ≥60 years old , recovery of potency was better in the RP-II group . To conclude , RP by an experienced surgeon may have a similar or lower positive surgical margin rate than OP . Additionally , RP may lead to a shorter duration of bladder catheterization and hospital stay and better recovery of continence and potency than obtainable by OP Background — The incidence of silent cerebral lesions ( SCL ) after atrial fibrillation ( AF ) ablation is highly variable , depending on the technology used . Recently , an increased risk for SCL has been described for a novel , nonirrigated ablation tool using multielectrode phased radiofrequency ( PVAC ) . The aim of this prospect i ve study was to evaluate the incidence and long-term follow-up of SCL in patients undergoing robotically assisted pulmonary vein isolation ( RA-PVI ) as compared with manual PVI . Methods and Results — Circumferential PVI using irrigated radiofrequency current was performed on 70 patients ( 41 patients with paroxysmal AF , 59 % ) . Fifty patients underwent RA-PVI and 20 patients underwent a manual approach . Cerebral MRI was performed the day before and the day after the ablation procedure ; follow-up MRI was performed on 9 of 12 ( 75 % ) patients after a follow-up period of 21 months . SCLs were found in 12 of 70 ( 17 % ) patients in this study ; the incidence of SCLs was similar in patients undergoing RA-PVI as compared with manually ablated patients ( n=9 , 18 % versus n=3 , 15 % ; probability value=1.0 ) . In 1 patient undergoing manual PVI ( 1 % ) , an SCL with asymptomatic subarachnoid hemorrhage was detected ; the bleeding completely resolved within 1 month . Transient ischemic attack occurred in 1 ( 1 % ) patient 2 days after manual PVI . After a median follow-up period of 21 months , no residual SCLs were detected . Conclusions — The incidence of SCL using the robotic navigation system was 18 % in this study . Incidence and size of SCL appears to be similar after RA-PVI as compared with manual PVI . Repeat MRI showed no residual SCLs at long-term follow-up INTRODUCTION Lack of r and omized controlled trials ( RCTs ) that compare pure laparoscopic radical prostatectomy ( LRP ) with robot-assisted laparoscopic radical prostatectomy ( RALRP ) is an important gap of the literature related to the surgical treatment of the clinical ly localized prostate cancer ( PCa ) . AIM To provide the first prospect i ve r and omized comparison on the functional and oncological outcomes of LRP and RALRP for the treatment of the clinical ly localized PCa . METHODS Between 2007 and 2008 , 128 consecutive male patients were r and omized in two groups and treated by a single experienced surgeon with traditional LRP ( Group I-64 patients ) or RALRP ( Group II-64 patients ) in all cases with intent of bilateral intrafascial nerve sparing . MAIN OUTCOME MEASURES Primary end point was to compare the 12 months erectile function ( EF ) outcomes . Complication rates , continence outcomes , and oncological results were also compared . The sample size of our study was able , with an adequate power ( 1-beta > 0.90 ) , to recognize as significant large differences ( above 0.30 ) between incidence proportions of considered outcomes . RESULTS No statistically significant differences were observed for operating time , estimated blood loss , transfusion rate , complications , rates of positive surgical margins , rates of biochemical recurrence , continence , and time to continence . However , the 12-month evaluation of capability for intercourse ( with or without phosphodiesterase type 5 inhibitors ) showed a clear and significant advantage of RALRP ( 32 % vs. 77 % , P < 0.0001 ) . Time to capability for intercourse was significantly shorter for RALRP . Rates of return to baseline International Index of Erectile Function ( IIEF-6 ) EF domain score question naires ( questions 1 - 5 and 15 ) ( 25 % vs. 58 % ) and to IIEF-6 > 17 ( 38 % vs. 63 % ) were also significantly higher for RALRP ( P = 0.0002 and P = 0.008 , respectively ) . CONCLUSIONS Our study offers the first high-level evidence that RALRP provides significantly better EF recovery than LRP without hindering the oncologic radicality of the procedure . Larger RCTs are needed to confirm if a new gold-st and ard treatment in the field of RP has risen Background and aims Laparoscopic surgery has become the treatment of choice for cholecystectomy . Many studies showed that while this approach benefits the patient , the surgeon faces such distinct disadvantages as a poor ergonomic situation and limited degrees of freedom with limited motion as a consequence . Robots have the potential to overcome these problems . To evaluate the efficiency and feasibility of robotically assisted surgery ( RAC ) , we design ed a prospect i ve study to compare it with st and ard laparoscopic cholecystectomy ( SLC ) . Material s and methods Between 2001 and 2003 , 26 patients underwent SLC and 20 patients underwent RAC using the ZEUS system . The feasibility , safety , and possible advantages were evaluated . To assess the efficacy , the total time in the operating room was divided into preoperative , operative , and postoperative time frames . Results For RAC in comparison with SLC , the preoperative phase including equipment setup was significantly longer . In the intraoperative phase , the cut-closure time and camera and trocar insertion times were significantly longer . It is interesting to note that the net dissection time for the cystic artery , duct , and the gall bladder was not different from SLC . Conclusions The study demonstrates the feasibility of robotically assisted cholecystectomy without system-specific morbidity . There is time loss in several phases of robotic surgery due to equipment setup and deinstallation and therefore , presents no benefit in using the robot in laparoscopic cholecystectomy PURPOSE Robotic assisted laparoscopic radical cystectomy for bladder cancer has been reported with potential for improvement in perioperative morbidity compared to the open approach . However , most studies are retrospective with significant selection bias . MATERIAL S AND METHODS A pilot prospect i ve r and omized trial evaluating perioperative outcomes and oncologic efficacy of open vs robotic assisted laparoscopic radical cystectomy for consecutive patients was performed from July 2009 to June 2011 . RESULTS To date 47 patients have been r and omized with data available on 40 patients for analysis . Each group was similar with regard to age , gender , race , body mass index and comorbidities , as well as previous surgeries , operative time , postoperative complications and final pathological stage . We observed no significant differences between oncologic outcomes of positive margins ( 5 % each , p = 0.50 ) or number of lymph nodes removed for open radical cystectomy ( 23 , IQR 15 - 28 ) vs robotic assisted laparoscopic radical cystectomy ( 11 , IQR 8.75 - 21.5 ) groups ( p = 0.135 ) . The robotic assisted laparoscopic radical cystectomy group ( 400 ml , IQR 300 - 762.5 ) was noted to have decreased estimated blood loss compared to the open radical cystectomy group ( 800 ml , IQR 400 - 1,100 ) and trended toward a decreased rate of excessive length of stay ( greater than 5 days ) ( 65 % vs 90 % , p = 0.11 ) compared to the open radical cystectomy group . The robotic group also trended toward fewer transfusions ( 40 % vs 50 % , p = 0.26 ) . CONCLUSIONS Our study vali date s the concept of r and omizing patients with bladder cancer undergoing radical cystectomy to an open or robotic approach . Our results suggest no significant differences in surrogates of oncologic efficacy . Robotic assisted laparoscopic radical cystectomy demonstrates potential benefits of decreased estimated blood loss and decreased hospital stay compared to open radical cystectomy . Our results need to be vali date d in a larger multicenter prospect i ve r and omized clinical trial Current options for minimally invasive surgical treatment of single-vessel coronary artery disease include beating heart procedures without cardiopulmonary bypass ( CPB ) via mini-thoracotomy ( MIDCAB ) and totally endoscopic robot-assisted techniques ( TECAB ) with CPB . Both procedures are associated with potential myocardial stress before revascularization , such as single-lung ventilation ( SLV ) , temporary coronary artery occlusion , cardiac luxation , intrathoracic carbon dioxide insufflation , and extended CPB and operating time . In this echocardiographic study we sought to evaluate the extent of intraoperative segmental wall motion abnormalities ( SWMA ) during MIDCAB and TECAB surgery and to identify factors affecting SWMA . Forty-six patients with single-vessel coronary artery disease were studied . Sixteen patients were operated using the MIDCAB technique and 30 patients with TECAB . In both groups sequential transesophageal echocardiograms were recorded during the entire procedure . Hemodynamic data and oxygenation variables were acquired simultaneously . In both groups , mild but obvious perioperative SWMA were identified and noted to increase during the course of the operation . These SWMA were more pronounced in the TECAB group . Independent of operating time , these changes disappeared completely after revascularization . No significant hemodynamic compromise was observed . We conclude that MIDCAB and TECAB techniques are associated with significant perioperative SWMA . The appearance of more profound SWMA in the TECAB group compared with the MIDCAB patients might have been the result of intrathoracic CO2 insufflation , as SLV was used in both groups . No persistent SWMA or post-CPB SWMA were apparent in either group . More extensive intraoperative ventricular SWMA was detected in the TECAB group , suggesting that a more frequent risk for right ventricular dysfunction may exist during TECAB procedures BACKGROUND Recently , a nonmagnetic robotic navigation system ( RN , Hansen-Sensei ) has been introduced for remote catheter manipulation . OBJECTIVE To investigate the influence of RN combined with intuitive 3-dimensional mapping on the fluoroscopy exposure to operator and patient during pulmonary vein isolation ( PVI ) for paroxysmal atrial fibrillation ( PAF ) in a prospect i ve r and omized trial . METHODS Sixty patients were r and omly assigned to undergo PVI either using a RN guided ( group 1 ; n = 30 , 20 male , 62 + /- 7.7 years ) or conventional ablation approach ( group 2 ; n = 30 , 14 male , 61 + /- 7.6 years ) . A 3-dimensional mapping system ( NavX ) was used in both groups . RESULTS Electrical disconnection of the ipsilateral pulmonary veins ( PVs ) was achieved in all patients . Use of RN significantly lowered the overall fluoroscopy time ( 9 + /- 3.4 vs 22 + /- 6.5 minutes ; P < 0.001 ) and reduced the operator 's fluoroscopy exposure ( 7 + /- 2.1 vs 22 + /- 6.5 minutes ; P < 0.001 ) . The difference in fluoroscopy duration between both groups was most pronounced during the ablation part of the procedure ( 3 + /- 2.4 vs 17 + /- 6.3 minutes ; P < 0.001 ) . The overall procedure duration tended to be prolonged using RN without reaching statistical significance ( 156 + /- 44.4 vs 134 + /- 12 minutes , P = 0.099 ) . No difference regarding outcome was found during a midterm follow-up of 6 months ( AF freedom group 1 = 73 % vs 77 % in group 2 [ P = 0.345 ] ) . CONCLUSION The use of RN for PVI seems to be effective and significantly reduces overall fluoroscopy time and operator 's fluoroscopy exposure without affecting mid-term outcome after 6-month follow-up OBJECTIVES Robotic assistance may enhance the precision of anatomic dissection and increase the feasibility of performing laparoscopic radical prostatectomy for most surgeons . We performed a prospect i ve comparison of 30 consecutive patients undergoing conventional radical retropubic prostatectomy ( RRP ) and 30 initial patients undergoing robot-assisted anatomic prostatectomy ( RAP ) at our institution . METHODS The study design was a prospect i ve nonr and omized comparison of anatomic RRP performed using the technique of Walsh and RAP performed with the da Vinci surgical system . We evaluated the baseline patient and tumor characteristics ( age , body mass index , serum prostate-specific antigen , Gleason score , and clinical stage ) , intraoperative parameters ( operative time , blood loss , and need for transfusion ) , postoperative parameters ( pain score , hospitalization duration , catheter duration ) , histopathologic parameters , and complications in the two groups . RESULTS The preoperative parameters were comparable for both groups of patients . The mean setup time for RAP was 0.95 hours . The mean operating time was 2.3 hours for RRP and 4.8 hours for RAP ( P < 0.001 ) . One patient required conversion from RAP to RRP because of a lack of progress . The mean blood loss was 970 mL for RRP and 329 mL for RAP ( P < 0.001 ) . The drop in hemoglobin was greater in the RRP group ( 4.4 versus 1.2 g in RAP ; P < 0.05 ) . The mean pain score on postoperative day 1 was 7 in the RRP group and 4 in RAP group ( P = 0.05 ) . The mean hospital stay was 56 hours in the RRP group and 36 hours in the RAP group ( P value not significant ) . Sixty-three percent of the RAP and 0 % of the RRP groups were discharged within 23 hours ( P < 0.001 ) . The mean duration of postoperative catheterization was 14 days for the RRP and 11 days for the RAP groups ( difference not significant ) . The pathologic stage , margin status , and prostate-specific antigen values were not different between the two groups . The setup time , operative time , blood loss amount , and catheterization duration were significantly reduced after the first 20 patients . CONCLUSIONS Currently , RAP is a longer procedure than RRP . However , the blood loss is minimal and patients feel less pain and are discharged earlier from the hospital . In our h and s , the margin status and complication rates were comparable for both techniques INTRODUCTION Robotic-assisted surgery is playing an increasingly important role in the last few years in the treatment of colorectal oncological disease . However , there are still no studies that objective ly demonstrate the advantages of this type of surgery . We present a prospect i ve r and omised study in order to compare the short-term results between colorectal robotic surgery and laparoscopic surgery . MATERIAL AND METHOD A total of 56 patients diagnosed with colorectal cancer between January 2008 and January 2009 , were r and omised and assigned to the robotic or laparoscopic group . Age , body mass index , tumour location , conversions in each group , complications during and after surgery , and histological characteristics of the specimens obtained , were all compared . RESULTS There were no significant differences between age ( P=.055 ) , body mass index ( P=.12 ) , or tumour location ( P=.91 ) . Only one patient in the robotic group required a transfusion and none in the laparoscopic group . The percentage of conversions was the same in both groups , however , the preparation times and operating times were significantly longer in patients intervened using the robotic device ( P=.0001 and P=.017 , respectively ) . There were no differences as regards the rate of complications or in the percentage of re- interventions ( 14.2 % and 7.1 % ) . The mean hospital stay of the patients was 9.3 ( 8.1 ) days in the robotic group and 9.2 ( 6.8 ) days in the laparoscopic ( P=.79 ) . The distal resection margin was greater in the specimen obtained using robotic surgery ( P = .003 ) as well as the number of lymph nodes obtained in the specimen ( P = .23 ) . CONCLUSION Robotic colorectal was performed safely and effectively , and with similar clinical results . International Trial Number for this study is : IS RCT N60866560 Background Robotic thyroidectomy using a gasless transaxillary approach , first described in 2008 , has become popular . This study compared outcomes , including postoperative distress and patient satisfaction , for patients undergoing robotic thyroidectomy with those for patients treated by conventional open thyroidectomy . Methods Of 84 prospect ively enrolled patients , 41 underwent robotic thyroidectomy ( the robot group ) , and 43 received conventional open thyroidectomy ( the open group ) . All the patients were followed up for at least 3 months after surgery . Videolaryngostroboscopic examinations were performed preoperatively and after 1 week and after 3 months postoperatively . Postoperative pain and discomfort were evaluated using a symptom scale . Subjective voice and swallowing changes were assessed by question naires ; and satisfaction with cosmetic outcome was measured by verbal response at 3 months . Results The two groups were similar in age , gender , type of operation , and final pathologic diagnosis . Although the mean operating time was significantly longer with the robotic technique than with open surgery , there were no between-group differences in postoperative pain or duration of hospital stay . No patient in either group experienced any major postoperative complication . Postoperative discomfort in the neck and swallowing disturbances were significantly more frequent in the open group than in the robot group , both at 1 week and at 3 months after surgery . However , there was no significant between-group difference in subjective voice parameters . At 3 months , the mean cosmetic satisfaction score was significantly higher in the robotic than in the open group . Conclusion Although postoperative pain levels and complications were comparable in the two groups , conventional open thyroidectomy requires a shorter operative time . The robotic technique , however , offers several distinct advantages including very good to excellent cosmetic results , reduced postoperative neck discomfort , and fewer adverse swallowing symptoms PURPOSE Minimally invasive surgery has been shown to decrease postoperative morbidity and length of stay for a number of surgical procedures . Furthermore , length of stay after open radical prostatectomy has decreased dramatically during the last decade . We examined differences in length of stay between a prospect ively evaluated cohort of patients who underwent radical retropubic prostatectomy and robot assisted laparoscopic prostatectomy . MATERIAL S AND METHODS Between January 2003 and March 2006 , 1,003 radical prostatectomies were performed at our hospital . Data were collected in prospect i ve fashion and a comparison was made between 374 patients who underwent radical retropubic prostatectomy and 629 who underwent robot assisted laparoscopic prostatectomy . Length of stay , factors influencing length of stay , readmission rates and unscheduled clinic or emergency room visits were evaluated . Patients in the 2 groups were treated using the same clinical care pathway . RESULTS Overall 94.3 % of patients in the radical retropubic prostatectomy group and 97.5 % in the robot assisted laparoscopic prostatectomy group were discharged home on or before postoperative day 1 . Mean length of stay in the radical retropubic and robot assisted laparoscopic prostatectomy groups was 1.25 ( median 1.09 ) and 1.17 days ( median 1.03 ) , which was similar and not statistically different ( p=0.27 ) . Readmission rates were similar in robot assisted laparoscopic and radical retropubic prostatectomy patients ( 7 % and 5 % , respectively , p=0.12 ) . Unscheduled clinic or emergency room visits were the same in the robot assisted laparoscopic and radical retropubic prostatectomy groups ( 10 % , p=0.95 ) . CONCLUSIONS Patients who underwent radical retropubic prostatectomy or robot assisted laparoscopic prostatectomy can be treated on the same clinical pathway . A targeted hospital discharge date of postoperative day 1 can be achieved in the majority of patients who underwent radical prostatectomy . Readmission rates or unscheduled hospital visits are necessary in a small percent of patients treated with an early discharge program , of which the majority are caused by ileus In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias BACKGROUND Perioperative short-term outcomes could be improved after totally robotic Roux-en-Y gastric bypass ( TR-RYGBP ) compared with conventional laparoscopic gastric bypass . METHODS This is a nonr and omized controlled prospect i ve study ( N = 200 ) to evaluate perioperative short-term outcomes . The primary endpoint was to investigate risk factors for 30-day surgical complications . RESULTS Mean total operative time was shorter in patients who underwent TR-RYGBP ( 130 vs 147 minutes ; P < .0001 ) . However , postoperative surgical complications rate ( 13 % vs 1 % ; P = .001 ) , and mean overall hospital stay ( 9.3 vs 6.7 days ; P < .0001 ) were higher after TR-RYGBP . By multivariate analysis , robotic surgery ( hazard ratio [ HR ] = 15.1 ; 95 % confidence interval [ CI ] , 2.8 to 280 ; P = .01 ) , and conversion to laparotomy ( HR = 18.8 ; 95 % CI , 1.7 to 250.8 ; P = .014 ) were independent risk factors for 30-day surgical complications . CONCLUSIONS Although robotic gastric bypass reduces mean operative time , TR-RYGBP is associated with an increased postoperative surgical complications rate and longer hospitalization Background : Traditional laparoscopic anterior rectal resection ( TLAR ) has recently been used for rectal cancer , offering good functional results compared with open anterior resection and result ing in a better postoperative early outcome . However , laparoscopic rectal resection can be technically dem and ing , especially when a total mesorectal excision is required . The aim of this study was to verify whether robot-assisted anterior rectal resection ( RLAR ) could overcome limitations of the laparoscopic approach . Methods : Sixty-six patients with rectal cancer were enrolled in the study . Twenty-nine patients underwent RLAR and 37 TLAR . Groups were matched for age , BMI , sex ratio , ASA status , and TNM stage , and were followed up for a mean time of 12 months . Results : Robot-assisted laparoscopic rectal resection results in shorter operative time when a total mesorectal excision is performed ( 165.9±10 vs 210±37 minutes ; P<0.05 ) . The conversion rate is significantly lower for RLAR ( P<0.05 ) . Postoperative morbidity was comparable between groups . Overall survival and disease-free survival were comparable between groups , even though a trend towards better disease-free survival in the RLAR group was observed . Conclusion : RLAR is a safe and feasible procedure that facilitates laparoscopic total mesorectal excision . R and omized clinical trials and longer follow-ups are needed to evaluate a possible influence of RLAR on patient survival This study was aim ed to compare robotic-assisted implantation of a total knee arthroplasty with conventional manual implantation . We controlled , r and omized , and review ed 72 patients for total knee arthroplasty assigned to undergo either conventional manual implantation ( excluding navigation-assisted implantation cases ) of a Zimmer LPS prosthesis ( Zimmer , Warsaw , Ind ) ( 30 patients : group 1 ) or robotic-assisted implantation of such a prosthesis ( 32 patients : group 2 ) . The femoral flexion angle ( gamma angle ) and tibial angle ( delta angle ) in the lateral x-ray of group 1 were 4.19 + /- 3.28 degrees and 89.7 + /- 1.7 degrees , and those of group 2 were 0.17 + /- 0.65 degrees and 85.5 + /- 0.92 degrees . The major complications were from improper small skin incision during a constraint attempt of minimally invasive surgery and during bulk fixation frame pins insertion . Robotic-assisted technology had definite advantages in terms of preoperative planning , accuracy of the intraoperative procedure , and postoperative follow-up , especially in the femoral flexion angle ( gamma angle ) and tibial flexion angle ( delta angle ) in the lateral x-ray , and in the femoral flexion angle ( alpha angle ) in the anteroposterior x-ray . But a disadvantage was the high complication rate in early stage OBJECTIVE : To compare conventional laparoscopic and robotic-assisted laparoscopic sacrocolpopexy for vaginal apex prolapse . METHODS : This single-center , blinded r and omized trial included participants with stage 2–4 posthysterectomy vaginal prolapse . Participants were r and omized to laparoscopic or robotic sacrocolpopexy . The primary outcome was total operative time from incision to closure . Secondary outcomes were postoperative pain , functional activity , bowel and bladder symptoms , quality of life , anatomic vaginal support , and cost from a health care system perspective . RESULTS : A total of 78 patients enrolled and were r and omized ( laparoscopic n=38 ; robotic n=40 ) . Total operative time was significantly longer in the robotic group compared with the laparoscopic group ( + 67-minute difference ; 95 % confidence interval [ CI ] 43–89 ; P<.001 ) . Anesthesia time , total time in the operating room , total sacrocolpopexy time , and total suturing time were all significantly longer in the robotic group . Participants in the robotic group also had significantly higher pain at rest and with activity during weeks 3 through 5 after surgery and required longer use of nonsteroidal anti-inflammatory drugs ( median , 20 compared with 11 days , P<.005 ) . The robotic group incurred greater cost than the laparoscopic group ( mean difference + $ 1,936 ; 95 % CI $ 417–$3,454 ; P=.008 ) . Both groups demonstrated significant improvement in vaginal support and functional outcomes 1 year after surgery with no differences between groups . CONCLUSION : Robotic-assisted sacrocolpopexy results in longer operating time and increased pain and cost compared with the conventional laparoscopic approach . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00551993 . LEVEL OF EVIDENCE : INTRODUCTION Pulmonary venous antra isolation ( PVAI ) is the cornerstone of catheter ablation procedure for drug refractory paroxysmal atrial fibrillation ( AF ) . However , the procedure is technically challenging . Robotic navigation has a potential to expedite and facilitate the procedure . METHODS A robotic catheter control system was used for remote navigation-supported PVAI in 22 patients ( mean age = 55 + /- 9 years , 16 males , study group ) . An irrigated-tip catheter with estimate of catheter force on the tissue was used . This was compared in nonr and omized fashion with conventional h and -controlled catheter ablation in 16 patients ( mean age = 55 + /- 9 years , 13 males , control group ) . The procedures were performed under guidance of Ensite NavX navigation system ( St. Jude Medical , St. Paul , MN , USA ) and intracardiac echocardiography . RESULTS Robotic navigation was associated with significantly shorter overall duration of radiofrequency delivery ( 1,641 + /- 609 vs 2,188 + /- 865 seconds , P < 0.01 ) , shorter total procedural time ( 207 + /- 29 vs 250 + /- 62 minutes , P = 0.007 ) , fluoroscopy exposure ( 15 + /- 5 vs 27 + /- 9 minutes , P < 0.001 ) , and lower radiation dose ( 1,119 + /- 596 vs 3,048 + /- 2,029 mGy/m(2 ) , P < 0.001 ) . No complication was observed in either the study or the control group . During the 5 + /- 1 months follow-up in the study group and 9 + /- 3 months in the control group , 91 % and 81 % of patients , respectively , were AF free . CONCLUSIONS In our early clinical experience , PVAI using a remote robotic catheter navigation was effective , safe , and associated with shorter procedural and fluoroscopic times than conventional PVAI BACKGROUND There are scant data in the literature regarding the role of robotic liver surgery . The aim of the present study was to develop techniques for robotic liver tumour resection and to draw a comparison with laparoscopic resection . METHODS Over a 1-year period , nine patients underwent robotic resection of peripherally located malignant lesions measuring < 5 cm . These patients were compared prospect ively with 23 patients who underwent laparoscopic resection of similar tumours at the same institution . Statistical analyses were performed using Student 's t-test , χ(2 ) -test and Kaplan-Meier survival . All data are expressed as mean ± SEM . RESULTS The groups were similar with regards to age , gender and tumour type ( P= NS ) . Tumour size was similar in both groups ( robotic -3.2 ± 1.3 cm vs. laparoscopic -2.9 ± 1.3 cm , P= 0.6 ) . Skin-to-skin operative time was 259 ± 28 min in the robotic vs. 234 ± 17 min in the laparoscopic group ( P= 0.4 ) . There was no difference between the two groups regarding estimated blood loss ( EBL ) and resection margin status . Conversion to an open operation was only necessary in one patient in the robotic group . Complications were observed in one patient in the robotic and four patients in the laparoscopic groups . The patients were followed up for a mean of 14 months and disease-free survival ( DFS ) was equivalent in both groups ( P= 0.6 ) . CONCLUSION The results of this initial study suggest that , for selected liver lesions , a robotic approach provides similar peri-operative outcomes compared with laparoscopic liver resection ( LLR ) PURPOSE To demonstrate the feasibility of robot-assisted staging surgery using three arms in patients with endometrial cancer . METHODS One hundred nine patients with clinical stage I endometrial cancer who underwent staging surgery at Yonsei University Health System were enrolled from May 2006 to January 2009 . Patient demographics and operative outcomes were prospect ively collected . RESULTS Robotic surgery using three arms was performed in 28 patients , laparoscopy in 25 , and laparotomy in 56 . There were no differences among the three groups in terms of patient demographics . The number of harvested pelvic lymph nodes was lower in the laparoscopy group than in the laparotomy group ( 18.36 + /- 7.25 vs. 24.39 + /- 10.08 , respectively , P = 0.025 ) , but there was no difference between the robot and laparotomy groups . The number of resected para-aortic lymph nodes and operative time did not differ among the three groups . The average hospital stay was longer for the laparotomy group than the robot and laparoscopy groups ( 10.78 days vs. 7.92 days vs. 7.67 days , respectively , P < 0.001 ) . Operative complications and transfusions developed more frequently in the laparotomy group than in the robot and laparoscopy groups ( 25.0 % vs. 7.1 % vs. 8.0 % , respectively , P = 0.049 ; 42.9 % vs. 14.3 % vs. 16.0 % , respectively , P = 0.006 ) . CONCLUSION Robot-assisted surgery using three arms is a feasible method for surgical staging in patients with clinical stage I endometrial cancer BACKGROUND Early studies reported comparative results of functional outcomes between robot-assisted ( RARP ) and retropubic radical prostatectomy ( RRP ) . However , well-controlled single-surgeon prospect i ve studies comparing the outcomes are rare . OBJECTIVE To compare functional outcomes after RARP and RRP performed by a single surgeon , and to identify factors predictive of early return of continence and potency . DESIGN , SETTING , AND PARTICIPANTS A total of 763 consecutive patients undergoing RP between 2007 and 2010 were prospect ively included and serially followed postoperatively for comparative analysis . INTERVENTION RARP was performed in 528 patients , and 235 underwent RRP . MEASUREMENTS Continence was defined as being completely pad free . Potency was defined as having erection sufficient for intercourse with or without a phosphodiesterase type 5 inhibitor . Continence and potency recovery were checked serially by interview and question naire at 1 , 3 , 6 , 9 , 12 , 18 , and 24 mo postoperatively . Cox proportional hazards method analyses was performed to determine predictive factors for early recovery . RESULTS AND LIMITATIONS After the initial 132 cases , patients who underwent RARP demonstrated faster recovery of urinary continence compared to RRP patients . Potency recovery was more rapid in the RARP group at all evaluation time points , beginning from the initial cases . In multivariate analysis , younger age and longer preoperative membranous urethral length seen by prostate magnetic resonance imaging ( MRI ) demonstrated statistical significance as independent prognostic factors for continence recovery ; younger age , surgical method ( RARP vs RRP ) , and higher preoperative serum testosterone were independent prognostic factors for potency recovery . The limitations of the present study were that it was nonr and omized and used interview to evaluate potency recovery . CONCLUSIONS Patients after RARP demonstrated superior functional recovery . Moreover , membranous urethral length on preoperative MRI and patient age were factors independently predictive of continence recovery , while patient age and higher preoperative serum testosterone were independent prognostic factors for potency recovery 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 Robotic-assisted radical prostatectomy ( RARP ) shows measurable advantages , compared to conventional open surgery , even if some aspects are , still , under debate . The aim of this study was to compare the potency recovery rate of patients with clinical ly localised prostate cancer treated by bilateral nerve-sparing ( BNS ) RARP or retropubic radical prostatectomy ( RRP ) , and secondarily , the urinary continence recovery evaluation and the oncological efficacy . All patients treated with BNS-RARP or BNS-RRP for clinical ly localised prostate cancer , performed by a single dedicated surgeon , between January 2004 and December 2008 , were enrolled in this non-r and omised prospect i ve comparative study . The International Index of Erectile Function ( IIEF ) and erection hardness score ( EHS ) , in the form of a question naire , were self-administered to each patient pre-operatively and after 12 months . The presence of surgical margins was considered as oncological outcome measure . Eighty-two patients underwent BNS-RARP while 48 underwent BNS-RRP . For BNS-RARP and BNS-RRP the median operative time was 221 and 103 min , respectively ( P<0.001 ; df=128 ; t=721.43 ) , and intra-operative blood loss was 280 and 565 ml , respectively ( P<0.001 ; df=128 ; t=1742.44 ) . At a mean follow-up period of 12.4±2.3 months , 12 patients ( 25 % ) in the BNS-RRP group and 22 ( 26.8 % ) in the BNS-RARP group were considered potent with or without drugs ( P=0.81 ) . Moreover , we did not find any statistically significant difference between the 2 groups in terms of IEFF and EHS scores after treatment ( 17.21 vs. 16.98 ; P=0.16 and 2.1 vs. 2.0 ; P=0.54 ) . On the other h and , statistically significant differences between the 2 groups were found in terms of faster urinary continence recovery and the presence of positive surgical margins ( P<0.001 , P=0.009 ) . Shorter catheterization duration ( 7 vs. 3 days ) and post-operative hospital stays ( 8 vs. 4 days ; P<0.001 ) were found in the BNS-RARP group compared to the BNS-RRP group . In conclusion , our results demonstrate that BNS-RARP does not improve erectile function recovery compared to open radical prostatectomy ; however , it significantly improves urinary continence and decreases the presence of positive surgical margins AIMS Recurrent arrhythmias after ablation procedures are often caused by recovery of ablated tissue . Robotic catheter manipulation systems increase catheter tip stability which improves energy delivery and could produce more transmural lesions . We tested this assertion using bipolar voltage attenuation as a marker of lesion quality comparing robotic and manual circumferential pulmonary vein ablation for atrial fibrillation ( AF ) . METHODS AND RESULTS Twenty patients were r and omly assigned to robotic or manual AF ablation at st and ard radiofrequency ( RF ) setting s for our institution ( 30 W 60 s manual , 25 W 30 s robotic , R30 ) . A separate group of 10 consecutive patients underwent robotic ablation at increased RF duration , 25 W for 60 s ( R60 ) . Lesions were marked on an electroanatomic map before and after ablation to measure distance moved and change in bipolar electrogram amplitude during RF . A total of 1108 lesions were studied ( 761 robotic , 347 manual ) . A correlation was identified between voltage attenuation and catheter movement during RF ( Spearman 's rho -0.929 , P < 0.001 ) . The ablation catheter was more stable during robotic RF ; 2.9 ± 2.3 mm ( R30 ) and 2.6 ± 2.2 mm ( R60 ) , both significantly less than the manual group ( 4.3 ± 3.0 mm , P < 0.001 ) . Despite improved stability , there was no difference in signal attenuation between the manual and R30 group . However , there was increased signal attenuation in the R60 group ( 52.4 ± 19.4 % ) compared with manual ( 47.7 ± 25.4 % , P = 0.01 ) . When procedures under general anaesthesia ( GA ) and conscious sedation were analysed separately , the improvement in signal attenuation in the R60 group was only significant in the procedures under GA . CONCLUSIONS Robotically assisted ablation has the capability to deliver greater bipolar voltage attenuation compared with manual ablation with appropriate selection of RF parameters . General anaesthesia confers additional benefits of catheter stability and greater signal attenuation . These findings may have a significant impact on outcomes from AF ablation procedures Background The benefits of robotic techniques for implanting femoral components during THA are still controversial . Questions / Purpose sThe purpose of this study was to prospect ively compare the results and complications of robotic-assisted and h and -rasping stem implantation techniques . Method The minimum followup was 5 years ( mean , 67 months ; range , 60–85 months ) . One hundred forty-six primary THAs on 130 patients were included in this study . Robot-assisted primary THA was performed on 75 hips and a h and -rasping technique was used on 71 hips . Results At 2 and 3 years postoperatively , the Japanese Orthopaedic Association ( JOA ) clinical score was slightly better in the robotic-assisted group . At 5 years followup , however , the differences were not significant . Postoperative limb lengths of the robotic-milling group had significantly less variance than the h and -rasping group . At 2 years postoperatively , there was significantly more stress shielding of the proximal femur in the h and -rasping group ; this difference was more significant 5 years postoperatively . Conclusions Substantially more precise implant positioning seems to have led to less variance in limb-length ine quality and less stress shielding of the proximal femur 5 years postoperatively . Level of Evidence Level II , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence Study Design . Single-center prospect i ve r and omized controlled study . Objective . To evaluate the accuracy of robot-assisted ( RO ) implantation of lumbar/sacral pedicle screws in comparison with the freeh and ( FH ) conventional technique . Summary of Background Data . SpineAssist is a miniature robot for the implantation of thoracic , lumbar , and sacral pedicle screws . The system , studied in cadaver and cohort studies , revealed a high accuracy , so far . A direct comparison of the robot assistance with the FH technique is missing . Methods . Patients requiring mono- or bisegmental lumbar or lumbosacral stabilization were r and omized in a 1:1 ratio to FH or RO pedicle screw implantation . Instrumentation was performed using fluoroscopic guidance ( FH ) or robot assistance . The primary end point screw position was assessed by a postoperative computed tomography , and screw position was classified ( A : no cortical violation ; B : cortical breach < 2 mm ; C : ≥2 mm to < 4 mm ; D : ≥4 mm to < 6 mm ; E : ≥6 mm ) . Secondary end points as radiation exposure , duration of surgery/planning , and hospital stay were assessed . Results . A total of 298 pedicle screws were implanted in 60 patients ( FH , 152 ; RO , 146 ) . Ninety-three percent had good positions ( A or B ) in FH , and 85 % in RO . Preparation time in the operating room ( OR ) , overall OR time , and intraoperative radiation time were not different for both groups . Surgical time for screw placement was significantly shorter for FH ( 84 minutes ) than for RO ( 95 minutes ) . Ten RO screws required an intraoperative conversion to the FH . One FH screw needed a secondary revision . Conclusion . In this study , the accuracy of the conventional FH technique was superior to the RO technique . Most malpositioned screws of the RO group showed a lateral deviation . Attachment of the robot to the spine seems a vulnerable aspect potentially leading to screw malposition as well as slipping of the implantation cannula at the screw entrance point The ROBODOC ® system was design ed to address potential human errors in performing cementless total hip replacement . The system consists of a preoperative planning computer workstation ( called ORTHODOC ) and a five-axis robotic arm with a high speed milling device as an end effector . The combined experience of the United States Food and Drug Administration multicenter trial and the German postmarket use of the system are reported . The United States study is controlled and r and omized with 136 hip replacements performed at three centers ( 65 ROBODOC ® and 62 control ) . Followup was 1 year on 127 hip replacements and 2 years on 93 hip replacements . No differences were found in the Harris hip scores or the Short Form Health Survey outcomes question naire . Length of stay also was not different , but the surgical time and blood loss were greater in the ROBODOC ® group . This was attributed to a learning curve at each center . Radiographs were evaluated by an independent bone radiologist and showed statistically better fit and positioning of the femoral component in the ROBODOC ® group . Complications were not different , except for three cases of intraoperative femoral fracture in the control group and none in the ROBODOC ® group . The German study reports on 858 patients , 42 with bilateral hip replacements and this includes 30 revision cases for a total of 900 hip replacements . The Harris hip score rose from 43.7 to 91.5 . In these cases the surgical time declined quickly from 240 minutes for the first case to 90 minutes . No intraoperative femoral fractures occurred in 900 cases . Other complications were comparable with total hip replacements performed using conventional techniques . The ROBODOC ® system is thought to be safe and effective in producing radiographically superior implant fit and positioning while eliminating femoral fractures AIM Robotic assisted total hip arthroplasty remains controversial , since wider exposure of the proximal femur and placement of the leg in maximal hip adduction and external rotation using a rigid leg-holder apparatus may impair significantly the hip abductors . Consequently , it is the purpose of this study to analyse and report both clinical outcome and hip abductor function following robotic assisted versus conventional total hip arthroplasty . MATERIAL AND METHODS 36 robotic-assisted ( CASPAR , Orto-Maquet , Rastatt , Germany ) and 35 conventional cementless total hip arthroplasties were followed on average for 18 months regarding incidence of complications , Harris hip score , the scoring system according to Merle d'Aubigné and Postel , hip abductor function ( using a spring-balance ) , and incidence of Trendelenburg 's sign ( according to the Kuhfuss-classification ) . Statistical analysis was performed in case of continuous data using the t test and the Mann-Whitney test , respectively , and in case of categorical data using Fisher 's exact test and the chi-squared test , respectively . The level of significance was set as p < 0.05 . RESULTS Average duration of surgery ( CASPAR : 100.6 min ; conventional : 51.5 min ; p < 0.0001 ) as well as average loss of haemoglobin ( CASPAR : 4.5 mg/dL ; conventional : 3.3 mg/dL ; p = 0.0002 ) differed significantly , whereas the incidence of complications ( CASPAR : two dislocations , one sciatic paresis , one deep infection ; conventional : one dislocation , two fissures ) , revision rate ( CASPAR : 5.6 % ; conventional : 2.9 % ) , and incidence of heterotopic ossifications ( CASPAR : 30.6 % ; conventional : 17.1 % ) was comparable following both procedures ( p > 0.05 ) . Improvement of the Harris hip score also was comparable in both groups ( CASPAR : 40.9 to 86.1 points ; conventional : 39.5 to 88.0 points ; p = 0.21 ) , whereas improvement of the score according to Merle d'Aubigné and Postel was significantly greater following the manual procedure ( CASPAR : 10.1 to 16.0 points ; conventional : 8.3 to 16.6 points ; p < 0.0001 ) . Differences between the two groups were also significant regarding hip abductor function ( CASPAR : 76.1 % ; conventional : 93.8 % of the contralateral hip ; p < 0.0001 ) and incidence of Trendelenburg 's sign ( CASPAR : 61.1 % ; conventional : 25.7 % ; p = 0.0014 ) . CONCLUSION The significant functional impairment following robotic assisted THA should be taken critically into consideration prior to initiating such procedure BACKGROUND It is not clear if robotically assisted surgery ( providing articulating instruments , 3-dimensional vision , intuitive ergonomics ) performed in pediatric patients offers the same advantages over conventional surgery as in adult patients . In the laboratory setting , robots require less time to perform certain tasks . Accordingly , we tested the hypothesis that the time required to perform a robotically assisted laparoscopic Thal semifundoplication is different compared with a conventional laparoscopic procedure in children . METHODS The time required to perform single operative steps was prospect ively recorded in 10 consecutively performed Thal semifundoplications with the use of a robot ( da Vinci ) and in 10 consecutively performed operations done by conventional laparoscopy . RESULTS No conversion to an open operation was necessary , and there were no intraoperative complications throughout the study and no postoperative complications up to 14 months after surgery . Total operative time was similar in both groups . In the robotically assisted group , time for setup was significantly longer ( 20.8 + /- 7.5 vs 34.6 + /- 9.2 minutes , P < .05 ) , but dissection of the hiatal region as the most challenging operative step was accomplished 34 % faster in the robotically assisted group ( 30.8 + /- 8.7 vs 20.2 + /- 5.3 minutes , P < .05 ) . CONCLUSION At the current level of technology , the robotic system is superior compared with established st and ard laparoscopic techniques requiring tissue preparation ; however , the potential benefit in operating time is counterbalanced by the increased complexity of setting up the system Background The aim of this study is to compare the short-term results between robotic-assisted low anterior resection ( R-LAR ) , using the da Vinci ® Surgical System , and st and ard laparoscopic low anterior resection ( L-LAR ) in rectal cancer patients . Methods 113 patients were assigned to receive either R-LAR ( n = 56 ) or L-LAR ( n = 57 ) between April 2006 and September 2007 . Patient characteristics , perioperative clinical results , complications , and pathologic details were compared between the groups . Moreover , macroscopic grading of the specimen was evaluated . Results Patient characteristics were not significantly different between the groups . The mean operation time was 190.1 ± 45.0 min in the R-LAR group and 191.1 ± 65.3 min in the L-LAR group ( P = 0.924 ) . The conversion rate was 0.0 % in the R-LAR groups and 10.5 % in the L-LAR group ( P = 0.013 ) . The serious complication rate was 5.4 % in the R-LAR group and 19.3 % in the L-LAR group ( P = 0.025 ) . The specimen quality was acceptable in both groups . However , the mesorectal grade was complete ( n = 52 ) and nearly complete ( n = 4 ) in the R-LAR group and complete ( n = 43 ) , nearly complete ( n = 12 ) , and incomplete ( n = 2 ) in the L-LAR group ( P = 0.033 ) . Conclusion R-LAR was performed safely and effectively , using the da Vinci ® Surgical System . The use of the system result ed in acceptable perioperative outcomes compared to L-LAR BACKGROUND Although open resection using a sphincter-saving operation ( SSO ) remains the st and ard of care for rectal cancer , few studies have compared open and robot-assisted ( RA ) SSOs . This study aim ed to compare the operative features , functional outcomes , and oncological validity of open and RA SSO for rectal cancer . METHODS A total of 200 rectal cancer patients undergoing curative SSO were enrolled prospect ively . The open and RA groups ( n = 100 , respectively ) were matched for clinical stage and operation type . RESULTS The mean operation time was significantly longer in the RA group than in the open group ( 188 vs. 103 min , P < 0.001 ) , but it was significantly reduced in the latter half of the RA patients compared with that in the first half ( 164 vs. 214 min , P < 0.001 ) . The mean distal resection margin was significantly longer in the RA than in the open group ( 2.7 vs. 1.9 cm ; P = 0.001 ) , but only one patient in either group had positive circumferential resection margin . Bowel peristalsis returned one day earlier in the RA than in the open group ( P < 0.001 ) . Postoperative complication rates and anorectal functional outcomes were comparable between the two groups . The operator 's physical discomfort , assessed on a visual analog scale , was significantly lower in the RA than in the open group ( P < 0.001 ) . CONCLUSIONS According to this short-term study , the RA SSO showed equivalent oncological safety , functional outcome , and morbidities to open SSO . Although the operation takes longer , the robotic system enables a technically versatile SSO with fine dissection in a limited surgical field OBJECTIVE : To compare postoperative pain after conventional laparoscopic and robotically assisted laparoscopic surgery in gynecology . METHODS : This is a prospect i ve nonr and omized analysis of patients undergoing conventional laparoscopy or robotically assisted laparoscopy in a university-affiliated hospital between March 2011 and March 2012 . Postoperative pain was measured using the Numeric Rating Scale and the narcotic use converted to morphine sulfate equivalents . The primary outcome was the Numeric Rating Scale pain score obtained on the first postoperative day . RESULTS : One hundred ten patients were enrolled ; 91 were included in the statistical analysis . Both groups were similar with regard to race , history of abdominopelvic surgeries , psychiatric history , and substance abuse . Patients undergoing robotically assisted laparoscopy were 6 years older and had a body mass index 6 points higher . Median length of hospital stay for conventional laparoscopy and robotically assisted laparoscopy was 2 days and 3 days , respectively ( P<.001 ) ; median to being off narcotics was 4 days and 4.5 days , respectively ( P=.336 ) ; and median return to normal activities was 13 days and 21 days , respectively ( P=.021 ) . There were no significant differences in mean Numeric Rating Scale pain scores over time ( P=.499 ) or mean narcotic requirements ( P=.393 ) between groups . CONCLUSION : Robotically assisted laparoscopy is equivalent to conventional laparoscopy in terms of subjective and objective measures of postoperative pain . LEVEL OF EVIDENCE : Objectives We prospect ively evaluated the safety , feasibility , and efficiency of robotic radical nephrectomy ( RRN ) for localized renal tumors ( T1 - 2N0M0 ) and compared this with laparoscopic radical nephrectomy ( LRN ) . Material s and methods Between October 2006 to August 2007 , a prospect i ve data analysis of 15 cases of renal cell carcinoma ( RCC ) stage T1 - 2N0M0 , undergoing RRN was done . These patients were compared with a contemporary cohort of 15 patients of RCC with clinical stage T1 - 2N0M0 , undergoing LRN . To keep comparison robust , all cases were performed by a single surgeon . Demographic , intra-operative , post-operative outcomes , pathological characteristics and follow-up data of the two groups were recorded and analyzed statistically . Results Patients in group A ( RRN ) experienced significantly ( P = 0.001 ) long operating time than group B ( LRN ) . However , mean estimated blood loss , intra-operative and post-operative complications , blood transfusion rate , analgesic requirement , hospital stay and convalescence were comparable in two groups ( P < 0.05 ) . There was one conversion to open surgery in group A , and none in group B. The mean follow-up was comparable in two groups ( 8.3 and 9.1 months , respectively , in group A and B , P = 0.09 ) . There were no local , port-site or distal recurrences in either group . Conclusions Robotic radical nephrectomy is a safe , feasible and effective for performing radical nephrectomy for localized RCC . Both groups ( RRN and LRN ) had comparable intra-operative , peri-operative , post-operative and oncological outcomes except for longer operating time with increased cost for RRN . In this comparative study , there were no outst and ing benefits of RRN observed over LRN for localized RCC PURPOSE We report our initial experience with laparoscopy- and robot-assisted partial nephrectomy ( RAPN ) operations . MATERIAL S AND METHODS Between November 2003 and April 2009 , laparoscopic partial nephrectomy ( LPN ) was performed in 20 patients ( h and -assisted procedure in one patient ) and RAPN in 11 patients . Transperitoneal approach was used in both groups . RESULTS The patient demographics were similar in both groups . The groups were statistically comparable for body mass index ( BMI ) , gender , and American Society of Auesthesiologists ( ASA ) scores . The mean tumor size was 32.1 mm ( range 20 - 41 mm ) in the RAPN group and 31.45 mm ( range 15 - 70 mm ) in the LPN group . The operative time was 226 minutes ( range 120 - 420 ) in the LPN group and 185 minutes ( range 120 - 270 ) in the RAPN group ; the difference was not statistically significant ( p = 0.07 ) . The mean warm ischemia time was significantly shorter in the RAPN group ( 27.3 minutes for the RAPN group and 35.8 for the LPN group ) ( p = 0.02 ) . The mean estimated blood loss was 286.4 mL in the RAPN group and 387.5 mL in the LPN group ( p = 0.3 ) . One patient ( 5 % ) had focal positive margin in the LPN group . No patient had positive surgical margins in the RAPN group . CONCLUSIONS In this pilot study , we found that RAPN and LPN are feasible and safe operations in T1 renal tumors . The advantages for RAPN are excision of the tumor under three-dimensional vision and easy suturing with the articulated instruments of the robotic system . The cost and the need for two experienced laparoscopic surgeons are the disadvantages of robotic surgery . Larger r and omized studies are needed to evaluate whether RAPN has any advantages over LPN BACKGROUND Evaluation of the impact of a new robotic surgery programme on perioperative outcomes for endometrial cancer METHODS A prospect i ve data base of all patients undergoing staging for endometrial cancer during July 2007-July 2008 was collected and analysed . Demographic data and perioperative outcomes were compared between cases performed via laparotomy , laparoscopy and robotics . RESULTS Sixty-five patients underwent staging during the time of data collection ( LAP-26 , LSC-7 , ROB-32 ) . No difference in surgical volume in the year before vs. after robotics was identified . Median operative time for robotics and laparotomy was significantly less than for laparoscopy ( p = 0.023 ) . There was no significant difference in lymph node yields between the three groups ( p = 0.92 ) . Robotics was associated with significantly less blood loss ( p < 0.0001 ) . Complication rates were significantly lower in the robotic group compared to the laparotomy group ( p = 0.05 ) . Median hospital stay was 1 day for the minimally invasive groups . Total number of perioperative inpatient days decreased from 331 to 150 in one year . Practice management of endometrial cancer transitioned from a predominantly open approach ( 5.6 % LSC ) to robotics ( 11 % LSC , 49 % ROB ) within 12 months . CONCLUSIONS Robotic surgery dramatically altered our management of endometrial cancer and was associated with a significant improvement in several perioperative outcomes when compared to laparotomy and laparoscopy OBJECTIVE The purpose of this study was to compare operative time and intra- and postoperative complications between total laparoscopic hysterectomy and robotic-assisted total laparoscopic hysterectomy . STUDY DESIGN This study was a blinded , prospect i ve r and omized controlled trial conducted at 2 institutions . Subjects consisted of women who planned laparoscopic hysterectomy for benign indications . Preoperative r and omization to total laparoscopic hysterectomy or robotic-assisted total laparoscopic hysterectomy was stratified by surgeon and uterine size ( > or ≤12 weeks ) . Vali date d question naires , activity assessment scales , and visual analogue scales were administered at baseline and during follow-up evaluation . RESULTS Sixty-two women gave consent and were enrolled and r and omly assigned ; 53 women underwent surgery ( laparoscopic , 27 women ; robot-assisted , 26 women ) . There were no demographic differences between groups . Compared with laparoscopic hysterectomy , total case time ( skin incision to skin closure ) was significantly longer in the robot-assisted group ( mean difference , + 77 minutes ; 95 % confidence interval , 33 - 121 ; P < .001 ] as was total operating room time ( entry into operating room to exit ; mean difference , + 72 minutes ; 95 % confidence interval , 14 - 130 ; P = .016 ) . Mean docking time was 6 ± 4 minutes . There were no significant differences between groups in estimated blood loss , pre- and postoperative hematocrit change , and length of stay . There were very few complications , with no difference in individual complication types or total complications between groups . Postoperative pain and return to daily activities were no different between groups . CONCLUSION Although laparoscopic and robotic-assisted hysterectomies are safe approaches to hysterectomy , robotic-assisted hysterectomy requires a significantly longer operative time Background A new technical tool was developed and introduced into the therapeutic field of videoscopic surgery — robotic telemanipulation surgery . The aim of this study is to investigate in a prospect i ve r and omized trial the feasibility of the Nissen procedure using the da Vinci and to evaluate the benefits and the costs of this new technique compared with the conventional laparoscopic approach . Material s and methods Twenty patients with gastro-esophageal reflux disease ( GERD ) were r and omized into laparoscopic Nissen versus robot-assisted Nissen fundoplication . All the patients signed an informed consent document . The time data of the procedure , the efficacy of the instruments , the intra-operative incidents , postoperative morbidity , and cost minimization are presented . Results Nine patients were assigned to the robot , and 11 to the laparoscopic procedure . Both groups were similar in age , male/female ratio , and body mass index . The robot procedure time was significantly longer . The hospital stay and the alimentation day were similar . The number of postoperative complaints was similar after the 1st , 6th , and 12th postoperative months . However , on the 3rd postoperative month , the number of complaints was significantly higher in the robot group . The robot procedure was more expensive with regard to the instrumentation and reusable material , the nursing costs , the investment costs , and the maintenance costs . Conclusions No clear advantage of using robotics in the Nissen procedure was observed . The procedure seems to be feasible and safe . The technique is limited because of unadapted instruments . The disadvantages are the high costs and prolonged operative time BACKGROUND Robot-assisted radical prostatectomy ( RALP ) is performed worldwide , even in institutions with limited caseloads . However , although the results of large RALP series are available , oncologic and functional outcomes as well as complications from low-caseload centres are lacking . OBJECTIVE To compare perioperative , oncologic , and functional outcomes from two consecutive series of patients with localised prostate cancer treated by retropubic radical prostatectomy ( RRP ) or recently established RALP in our hospital , which has a limited caseload . DESIGN , SETTING , AND PARTICIPANTS One hundred fifty consecutive patients were enrolled . Their data and outcomes were collected and extensively evaluated . INTERVENTION Seventy-five consecutive patients underwent RRP , and 75 consecutive patients underwent RALP , including all patients of the learning curve . MEASUREMENTS Patient baseline characteristics , perioperative and postoperative outcomes , and complications were evaluated . End points were oncologic data ( positive margins , prostate-specific antigen [ PSA ] ) , perioperative complications , urinary continence , and erectile function at 3- and 12-mo follow-up . RESULTS AND LIMITATIONS The preoperative parameters from the two groups were comparable . The positive surgical margin ( PSM ) rates were 32 % for RRP and 16 % for RALP ( p=0.002 ) . For RRP and RALP , the PSA value was < 0.2 ng/ml in 91 % and 88 % of patients 3 mo postoperatively ( p=0.708 ) and in 87 % and 89 % of patients 12 mo postoperatively ( p=0.36 ) , respectively . Continence rates for RRP and RALP were 83 % and 95 % at 3-mo follow-up ( p=0.003 ) and 80 % and 89 % after 12-mo follow-up ( p=0.092 ) , respectively . Among patients who were potent without phosphodiesterase type 5 inhibitors ( PDE5-I ) before RRP and RALP , recovery of erectile function with and without PDE5-Is was achieved in 25 % ( 12 of 49 patients ) and 68 % ( 25 of 37 patients ) 3 mo postoperatively ( p=0.009 ) and in 26 % ( 12 of 47 patients ) and 55 % ( 12 of 22 patients ) 12 mo postoperatively ( p=0.009 ) , respectively . Minimal follow-up for RRP was 12 mo ; median follow-up for the RALP group was 12 mo ( range : 3 - 12 ) . According to the modified Clavien system , major complication rates for RRP and RALP were 28 % and 7 % ( p=0.025 ) , respectively ; minor complication rates were 24 % and 35 % ( p=0.744 ) , respectively . CONCLUSIONS Despite a limited caseload and including the learning curve , RALP offers slightly better results than RRP in terms of PSM , major complications , urinary continence , and erectile function Background Laparoscopic adrenalectomy offers distinct benefits to patients and has now become the gold st and ard for the removal of adrenal lesions . Nonetheless , the procedure poses a challenge for surgeons in regards to the maneuverability of instruments , the two-dimensional operating field and the counterintuitive movements . This study reports our experience using the Zeus robotic surgical system in laparoscopic adrenalectomy compared with traditional laparoscopic adrenalectomy . Patients and Methods From January 2003 to February 2005 , a total of 12 patients were prospect ively enrolled to receive robot-assisted laparoscopic adrenalectomy ( RALA ) or traditional laparoscopic adrenalectomy ( TLA ) . The time necessary for robotic setup and operation was recorded , as well as complications , technical problems , postoperative hospital stay , morbidity , and mortality . Results Five RALA procedures and seven TLA were successfully completed . There was no significant difference between the groups in terms of age , body mass index , and tumor size . Resection times were longer in the RALA group ( 168.0 ± 30.7 min vs. 131.4 ± 29.0 min , p = 0.05 ) . There were no perioperative complications . There was neither postoperative mortality nor morbidity at the time of discharge and during one year follow-up . Conclusions RALA is as safe and technically feasible as TLA , It provides a real benefit for the surgeon with the three dimensional view , a comfortable sitting position , the elimination of the surgeon ’s tremor , and increased degrees of freedom of the operative instruments compared with TLA . However , patient outcomes and operative costs should be evaluated further BACKGROUND Laparoscopically assisted aortic aneurysm resection requiring a minilaparotomy can be performed as a routine procedure . It was the purpose of our study to evaluate whether a total laparoscopic operation can be offered to aneurysm patients as a minimally invasive alternative . We also wanted to test whether a master-slave robot could facilitate the total laparoscopic procedure . METHODS A prospect i ve , consecutive number of 50 patients was evaluated . A transperitoneal left retrocolic access was used to expose the aorta . If possible , a tube graft repair was performed . The aortic anastomosis was sutured totally laparoscopically , with the surgeon st and ing on the right side of the operating table . In 10 consecutive patients , the anastomosis was sutured with the help of the Zeus robot . RESULTS After excluding 3 cases that required suprarenal cross-clamping , 47 patients were operated using a total laparoscopic approach . A totally laparoscopic operation could be performed successfully in 39 patients with aneurysms . In 8 patients ( 17 % ) , conversion to a laparoscopic h and -assisted operation with a 7-cm minilaparotomy was required . The robot was used to perform the aortic anastomosis in 10 patients . In 8 patients , a tube graft repair could successfully be performed totally laparoscopically . In the remaining patients , a bifurcated graft was implanted laparoscopically . The mean operating time was 227 minutes in the laparoscopy group and was 242 minutes in those patients in whom the anastomosis was sutured with the help of the Zeus Robot . Mean cross-clamping time , + /- SD , was 81.4 + 31 minutes . None of the patients died perioperatively . Major complications occurred in three patients ( 6.3 % ) . The overall morbidity was 14.8 % , including one patient who required temporary hemodialysis postoperatively . The time to suture the aortic anastomosis was significantly shorter in the robotic-assistance group ( 40.8 + /- 4 minutes ) , yet total operating time was longer in this group because of the technical complexity of the robotic device . Patients with a total laparoscopic procedure asked for significantly fewer analgesics and could regain full mobility earlier compared with those patients for whom a minilaparotomy after conversion to the laparoscopic h and -assist procedure was required . CONCLUSIONS Total laparoscopic aneurysm resection can be offered to the majority of patients in our institution . The robot still requires further refinements to reduce operating times and the aortic cross-clamping period . We now have the technique and the instrumentation to offer laparoscopic aneurysm surgery as a minimally invasive alternative for patients whose conditions are unsuitable for endovascular aneurysm repair Background Robotic technology represents the latest development in minimally-invasive surgery . Nevertheless , robotic-assisted surgery seems to have specific disadvantages such as an increase in costs and prolongation of operative time . A general clinical implementation of the technique would only be justified if a relevant improvement in outcome could be demonstrated . This is also true for laparoscopic fundoplication . The present study was design ed to compare robotic-assisted ( RALF ) and conventional laparoscopic fundoplication ( CLF ) with the focus on operative time , costs und perioperative outcome . Methods Forty patients with gastro-esophageal reflux disease were r and omized to either RALF by use of the daVinci ® Surgical System or CLF . Nissen fundoplication was the st and ard anti-reflux procedure . Peri-operative data such as length of operative procedure , intra- and postoperative complications , length of hospital stay , overall costs and symptomatic short-term outcome were compared . Results The total operative time was shorter for RALF compared to CLF ( 88 vs. 102 min ; p = 0.033 ) consisting of a longer set-up ( 23 vs. 20 min ; p = 0.050 ) but a shorter effective operative time ( 65 vs. 82 min ; p = 0.006 ) . Intraoperative complications included one pneumothorax and two technical problems in the RALF group and two bleedings in the CLF group . There were no conversions to an open approach . Mean length of hospital stay ( 2.8 vs. 3.3 days ; p = 0.086 ) and symptomatic outcome thirty days postoperatively ( 10 % vs. 15 % with ongoing PPI therapy ; p = 1.0 and 25 % vs. 20 % with persisting mild dysphagia ; p = 1.0 ) was similar in both groups . Costs were higher for RALF than for CLF ( € 3244 vs. € 2743 , p = 0.003 ) . Conclusion In comparison with CLF , operative time can be shorter for RALF if performed by an experienced team . However , costs are higher and short-term outcome is similar . Thus , RALF can not be favoured over CLF regarding perioperative outcome Background Several studies have shown mechanical alignment influences the outcome of TKA . Robotic systems have been developed to improve the precision and accuracy of achieving component position and mechanical alignment . Questions / purpose sWe determined whether robotic-assisted implantation for TKA ( 1 ) improved clinical outcome ; ( 2 ) improved mechanical axis alignment and implant inclination in the coronal and sagittal planes ; ( 3 ) improved the balance ( flexion and extension gaps ) ; and ( 4 ) reduced complications , postoperative drainage , and operative time when compared to conventionally implanted TKA over an intermediate-term ( minimum 3-year ) followup period . Methods We prospect ively r and omized 100 patients who underwent unilateral TKA into one of two groups : 50 using a robotic-assisted procedure and 50 using conventional manual techniques . Outcome variables considered were postoperative ROM , WOMAC scores , Hospital for Special Surgery ( HSS ) knee scores , mechanical axis alignment , flexion/extension gap balance , complications , postoperative drainage , and operative time . Minimum followup was 41 months ( mean , 65 months ; range , 41–81 months ) . Results There were no differences in postoperative ROM , WOMAC scores , and HSS knee scores . The robotic-assisted group result ed in no mechanical axis outliers ( > ± 3 ° from neutral ) compared to 24 % in the conventional group . There were fewer robotic-assisted knees where the flexion gap exceeded the extension gap by 2 mm . The robotic-assisted procedures took an average of 25 minutes longer than the conventional procedures but had less postoperative blood drainage . There were no differences in complications between groups . Conclusions Robotic-assisted TKA appears to reduce the number of mechanical axis alignment outliers and improve the ability to achieve flexion-extension gap balance , without any differences in clinical scores or complications when compared to conventional manual techniques . Level of Evidence Level I , therapeutic study . See Instructions for Authors for a complete description of levels of evidence OBJECTIVES To quantify complications to surgery in patients treated with robot-assisted radical prostatectomy ( RARP ) and open retropubic radical prostatectomy ( RRP ) at our institution . Radical prostatectomy is associated with specific complications that can affect outcome results in patients . METHODS Between January 2002 and August 2007 , a series of 1738 consecutive patients underwent RARP ( n = 1253 ) or RRP ( n = 485 ) for clinical ly localized prostate cancer . Surgery-related complications were assessed using a prospect i ve hospital-based complication registry . The baseline characteristics of all patients were documented preoperatively . RESULTS Overall , 170 patients required blood transfusions ( 9.7 % ) , 112 patients ( 23 % ) in the RRP group compared with 58 patients ( 4.8 % ) in the RARP group . Infectious complications occurred in 44 RRP patients ( 9 % ) compared with 18 ( 1 % ) in the RARP group . Bladder neck contracture was treated in 22 ( 4.5 % ) patients who had undergone RRP compared with 3 ( 0.2 % ) in the RARP group . Clavien grade IIIb-V complications were more common in RRP patients ( n = 63 ; 12.9 % ) than in RARP patients ( n = 46 ; 3.7 % ) . CONCLUSIONS The introduction of RARP at our institution has result ed in decreased number of patients with Clavien grade IIIb-V complications , such as bladder neck contractures , a decrease in the number of patients who require blood transfusions , and decreased numbers of patients with postoperative wound infections BACKGROUND Conventional catheter ablation for common-type atrial flutter ( AFL ) is a widely established therapy but has not been compared with the use of a robotic navigation system ( RNS ) thus far . OBJECTIVES The purpose of this study was to investigate the feasibility of a new , nonmagnetic RNS with regard to safety , efficacy , and X-ray exposure to investigator and patient compared with the conventional ablation approach in patients with AFL . METHODS Fifty patients ( 65.7 + /- 9.3 years , 40 male ) undergoing de novo catheter ablation for AFL were r and omly assigned to conventional or RNS-guided cavotricuspid isthmus ( CTI ) ablation . RESULTS Complete bidirectional isthmus block was achieved for all patients without occurrence of procedure-related complications . The fluoroscopy time and the investigator X-ray exposure ( 8.2 + /- 4.6 vs. 5.8 + /- 3.6 , P = .038 ; and 8.2 + /- 4.6 vs. 1.9 + /- 1.1 minutes , P<.001 ) as well as the mean radiofrequency ( RF ) duration and the energy delivered were significantly higher in the conventional than in the RNS group ( 321.7 + /- 214.6 vs. 496.4 + /- 213.9 seconds , P = .006 ; 8279 + /- 5767 vs. 16,308 + /- 6870 J , P<.001 , respectively ) . The overall procedure time in the RNS group was significantly longer than in the conventional group ( 79.2 + /- 30.6 vs. 58.4 + /- 17.7 minutes ; P = .04 ) but significantly decreased comparing the first 10 with the last 10 patients in the RNS group ( 105.3 + /- 34.8 vs. 60.6 + /- 6.3 minutes ; P = .003 ) . Starting ablation during AFL , bidirectional block instantly after termination was observed in 90 % of the RNS and 50 % of the conventionally treated patients ( P = .03 ) . CONCLUSION The present study demonstrates the safety and feasibility of RNS for performing CTI ablation in patients with common-type AFL for use in the clinical routine . As a result of the remote navigation , X-ray exposure and RF duration to achieve bidirectional block were significantly decreased and occurred more often immediately after AFL termination . These findings are consistent with increased catheter stability and RF application efficacy using RNS compared with conventional catheter manipulation BACKGROUND The robotic surgical system overcomes many technological obstacles of conventional laparoscopic surgery , and possesses enormous clinical applied potential . The aim of this study was to compare the efficacy of Zeus robot-assisted laparoscopic cholecystectomy with conventional laparoscopic cholecystectomy . METHODS Forty patients undergoing elective cholecystectomy were r and omly divided into two groups . Patients in group A ( n=20 ) underwent Zeus robot-assisted laparoscopic cholecystectomy , and patients in group B ( n=20 ) received conventional laparoscopic cholecystectomy . The parameters on operative field , operative time , the number of actions , the rate of operative errors and minimal trauma were evaluated and compared between the two groups . RESULTS The number of clearing camera ( 1.1+/-1.0 times ) and the time of adjusting the operative field ( 2.2+/-0.7 minutes ) in group A were significantly less than those ( 4.5+/-1.5 times ) and ( 7.5+/-1.2 minutes ) in group B. The number of dissection actions ( 337+/-86 times ) and the rate of operative errors ( 10 % ) in group A were less than those ( 389+/-94 times ) , ( 25 % ) in group B. The total operation time ( 104.9+/-20.5 minutes ) and setup time ( 29.5+/-9.8 minutes ) in group A were significantly longer than those ( 78.6+/-17.1 minutes ) , ( 12.6+/-2.5 minutes ) in group B. Blood loss and postoperative hospitalization were similar . No postoperative complications occurred in both groups , and open cholecystectomy was performed in each group . CONCLUSIONS Zeus robot-assisted cholecystectomy inherits the benefits of minimally invasive surgery . The Zeus robotic surgical system is better than conventional laparoscopic technique in controlling the operative field and can be manipulated precisely and stably though it requires more operative time Background : The efficacy of conventional laparoscopic cholecystectomy ( CLC ) was compared with robot-assisted laparoscopic cholecystectomy ( RLC ) . Surgical trainees performed the LC to avoid the surgeon ’s experience bias . Methods : Two surgical trainees performed 10 CLCs and 10 RLCs at r and om with a Zeus-Aesop Surgical Robotic System . The primary efficacy parameters were the total time and the number of actions involved in the procedure . The secondary parameters were setup and dissection times , and the number of grasping and dissection actions . Surgical complications were evaluated . Results : For CLC and RLC , respectively , the total times were 95.4 ± 28 min and 123.5 ± 33.3 min and the total actions were 420 ± 176.3 and 363.5 ± 158.2 . For CLC , the times required for setup ( 21 ± 10.4 min ) and dissection ( 50.2 ± 17.7 min ) were less than for RLC ( 33.8 ± 11.3 min and 72 ± 24.3 min , respectively ) . The numbers of grasping and dissection actions were not significantly different : 41.4 ± 26.5 and 378 ± 173.7 , respectively , for CLC versus 48.9 ± 27 and 314.6 ± 141.9 , respectively , for RLC . Conclusion : Although feasible , RLC requires significantly more time than CLC because of slower performed actions Microsurgical vasectomy reversal is a technically dem and ing procedure . Previous studies have shown the possible benefit of robotic assistance during such procedures . Our goal was to compare robotic assisted vasovasostomy and vasoepididymostomy to st and ard microsurgical vasovasostomy ( MVV ) and vasoepididymostomy ( MVE ) . The use of robotic assistance for vasectomy reversal may provide the microsurgeon with improved visualization , elimination of tremor , and decreased fatigue and obviate the need for a skilled microsurgical assistant . This study provides the first clinical prospect i ve control trial of robotic assisted versus pure microsurgical vasectomy reversal . The use of robotic assistance in microsurgical vasovasostomy and vasoepididymostomy may have benefit over MVV and MVE with regards to decreasing operative duration and improving the rate of recovery of postoperative total motile sperm counts based on our study OBJECTIVE We sought to compare recovery of activity and pain control after robotic ( ROB ) vs abdominal ( ABD ) sacral colpopexy . STUDY DESIGN Women undergoing ROB and ABD sacral colpopexy wore accelerometers for 7 days preoperatively and the first 10 days postoperatively . They completed postoperative pain diaries and Short Form-36 question naires before and after surgery . RESULTS At 5 days postoperatively , none of the 14 subjects in the ABD group and 4 of 28 ( 14.3 % ) in the ROB group achieved 50 % total baseline activity counts ( P = .283 ) . At 10 days , 5 of 14 ( 35.7 % ) in the ABD group and 8 of 26 ( 30.8 % ) in the ROB group ( P = .972 ) achieved 50 % . Postoperative pain was similar in both groups . Short Form-36 vitality scores were lower ( P = .017 ) after surgery in the ABD group , but not in the ROB group . CONCLUSION Women undergoing ROB vs ABD sacral colpopexy do not recover physical activity faster , and pain control is not improved BACKGROUND The aim of this study was to evaluate postoperative pain levels after endoscopic versus conventional internal thoracic artery ( ITA ) dissection for minimally invasive direct coronary artery bypass graft surgery ( MIDCABG ) surgery . Results were compared with pain levels associated with conventional cardiac bypass operations through a median sternotomy . METHODS Of 190 patients included in this prospect i ve study , 24 patients had endoscopic ITA takedown ( MIDCABG-endo ) using the da Vinci telemanipulator followed by a manual coronary anastomosis through a left minithoracotomy . A conventional MIDCABG operation ( MIDCABG-conv ) was performed in 73 patients with ITA preparation under direct vision . Postoperative pain levels after conventional CABG through a median sternotomy ( CABG-conv , n = 93 ) served as controls . A st and arized question naire including visual analog scale ( VAS ) was used for prospect i ve pain assessment from POD 1 to 7 . RESULTS Pain levels ( VAS ) declined in all groups from POD 1 to 7 . Overall pain levels were significantly lower in the MIDCABG-endo group as compared with MIDCABG-conv and CABG-conv groups , respectively ( p < 0.001 , general linear model ) . There was no significant difference between the MIDCABG-conv and CABG-conv ( p = not significant , general linear model ) groups . Furthermore , patients after MIDCABG-endo required fewer nonsteroidal anti-inflammatory drugs and opioid medications , postoperatively . CONCLUSIONS An endoscopic ITA takedown in MIDCABG surgery leads to significantly reduced postoperative pain levels possibly because of less rib retraction BACKGROUND Robotic cystectomy is an emerging alternative for treatment of invasive bladder cancer ( BCa ) . However , reduction in postoperative morbidity relative to the open approach has not been demonstrated . OBJECTIVE To compare complication rates in patients undergoing robotic versus open radical cystectomy ( RC ) . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve cohort study of 187 consecutive patients undergoing RC at our institution-104 open RC , 83 robotic RC . INTERVENTION Open or robotic RC with urinary diversion . MEASUREMENTS Demographic , perioperative , and complication data were recorded prospect ively . Thirty-day and 90-d complication rates were assessed using the modified Clavien complication scale . Data were evaluated using chi(2 ) and multivariate logistic regression analyses . RESULTS AND LIMITATIONS At 30 d , the open group demonstrated a higher overall complication rate ( 59 % vs 41 % ; p=0.04 ) as well as more major complications ( 30 % vs 10 % ; p=0.007 ) . At 90 d , the overall complication rate was greater in the open group , but this was not statistically significant ( 62 % vs 48 % ; p=0.07 ) . However , there was a significantly higher major complication rate in the open cohort ( 31 % vs 17 % ; p=0.03 ) . When subjected to logistic regression analysis , robotic cystectomy was an independent predictor of fewer overall and major complications at 30 and 90 d. High American Society of Anesthesiologists ( ASA ) score ( 3 - 4 ) and longer surgical time were independent predictors of major complications . Though this is one of the largest published RC series , the sample size is relatively small . Moreover , despite the two patient cohorts being similarly matched , the study was not performed in a r and omized fashion . CONCLUSIONS Patients undergoing robotic cystectomy experienced fewer postoperative complications than those undergoing open cystectomy . Robotic cystectomy is an independent predictor of fewer overall and major complications . Until long-term oncologic results are available , robotic cystectomy should still be considered investigational STUDY AIM The goal of this study was to report the early results of unilateral transperitoneal adrenalectomy using robotic Da Vinci system , and to compare them to the results of the laparoscopic st and ard adrenalectomy . METHODS Prospect i ve study included all patients operated on for unilateral laparoscopic or robotic adrenalectomy from November 2000 to November 2002 . RESULTS Twenty-eight patients underwent unilateral adrenalectomy using either st and ard laparoscopy ( 14 patients ) or robotic Da Vinci system ( 14 patients ) . Mean duration of robotic adrenalectomy seemed to be longer than st and ard laparoscopy ( 111 vs. 83 min ; P = 0.057 ) . This tendency decreased while surgeons ' experience was increasing . Mean duration of operating room activity was similar for both types of surgery . Peroperative events without conversion , conversion rate ( 7 % ) , drainage , morbidity ( 21 % ) , duration of hospitalisation were similar for both types of surgery . Duration of st and ard laparoscopic adrenalectomy was positively correlated to patients body mass index . This correlation was absent in patients operated on by robotic Da Vinci system . CONCLUSION This preliminary study found no objective data demonstrating that robotic Da Vinci system was superior to st and ard laparoscopic approach for unilateral adrenalectomy . However , we think that it is necessary to continue further evaluation of this system to demonstrate its possible superiority Objective To prospect ively compare short-term functional outcomes achieved by laparoscopic or robot-assisted sacrocolpopexy for pelvic organ prolapse . Material s and methods We prospect ively collected clinical and operative data over 24 months for female patients who underwent either pure laparoscopic sacrocolpopexy ( LSCP ) or robot-assisted laparoscopic sacrocolpopexy ( RALSCP ) . Clinical data included age , BMI and assessment of PFDI-20 score . Perioperative data included operative time and complications . Post-operative outcomes included hospital stay , length of catheterisation , pain and functional outcomes as assessed by clinical examination and PFDI-20 score assessment . Results Overall , 67 women with a median age of 65 were included : 47 in the LSCP arm and 20 in the RALSCP arm . RALSCP was superior in terms of blood loss ( median 55mls vs. 280 ; P = 0.03 ) and strict operative time ( median 125 min vs. 220 ; P < 0.0001 ) , but this time advantage was nullified when comparing overall operating room time ( 215 min vs. 220 ) . With a median follow-up of 16 months , the overall anatomic repair rate was 98.5 % , and there was an improvement in overall PFDI-20 score before and after surgery ( P = 0.001 ) but with no difference between the two surgical approaches . Conclusions RALSCP allows for a safe and effective repair of pelvic organ prolapse in female patients . Whilst being equivalent to LSCP in terms of functional outcome , it is superior in terms of blood loss and strict operative time . These results are based on short-term assessment , and further studies of larger population s with longer follow-up and objective assessment s of outcome are needed to make any definitive statement OBJECTIVE : Laparoscopic and robotic sacrocolpopexy are widely used for pelvic organ prolapse ( POP ) treatment . Evidence comparing outcomes and costs is lacking . We compared costs and clinical ly relevant outcomes in women r and omized to laparoscopic sacrocolpopexy compared with robotic sacrocolpopexy . METHODS : Participants with symptomatic stage POP II or greater , including significant apical support loss , were r and omized to either laparoscopic or robotic sacrocolpopexy . We compared surgical costs ( including costs for robot , initial hospitalization ) and rehospitalization within 6 weeks . Secondary outcomes included postoperative pain , POP quantification , symptom severity and quality of life , and adverse events . RESULTS : We r and omized 78 women ( mean age 59 years ) : laparoscopic ( n=38 ) and robotic ( n=40 ) . The robotic sacrocolpopexy group had higher initial hospital costs ( $ 19,616 compared with $ 11,573 , P<.001 ) and over 6 weeks , hospital costs remained higher for robotic sacrocolpopexy ( $ 20,898 compared with $ 12,170 , P<.001 ) . When we excluded costs of robot purchase and maintenance , we did not detect a statistical difference in initial day of surgery costs of robotic compared with laparoscopic ( $ 12,586 compared with $ 11,573 ; P=.160 ) or hospital costs over 6 weeks ( $ 13,867 compared with $ 12,170 ; P=.060 ) . The robotic group had longer operating room times ( 202.8 minutes compared with 178.4 minutes , P=.030 ) and higher pain scores 1 week after surgery ( 3.5±2.1 compared with 2.6±2.2 ; P=.044 ) . There were no group differences in symptom bother by Pelvic Floor Distress Inventory , POP stage , or rate of adverse events . CONCLUSION : Costs of robotic sacrocolpopexy are higher than laparoscopic , whereas short-term outcomes and complications are similar . Primary cost differences result ed from robot maintenance and purchase costs . CLINICAL TRIAL REGISTRATION : Clinical trials.gov , www . clinical trials.gov , NCT01124916 . LEVEL OF EVIDENCE : OBJECTIVES To perform a complete cost analysis comparing robot assisted radical cystectomy ( RARC ) versus open radical cystectomy ( ORC ) . MATERIAL AND METHODS After institutional review board approval for data collection , we prospect ively recorded perioperative outcomes and costs , such as hospital stay , transfusion rate , readmission rate , and medications for consecutive patients undergoing RARC or ORC . Using actual cost data , we developed a cost decision tree model to determine typical perioperative costs for both RARC and ORC . Multivariate sensitivity analysis was performed to eluci date which variables had the greatest impact on overall cost . Breakeven points with ORC were calculated using our model to better evaluate variable influence . In addition to the above modeled analysis , actual patient costs , including complications 30 days from surgery , were also compared for each procedure . RESULTS Our model analysis showed that operative time and length of stay had the greatest impact on perioperative costs . Robotic cystectomy became more expensive than open cystectomy at the following break-even points : operating room ( OR ) time greater than 361 minutes , length of stay greater than 6.6 days , or robotic OR supply cost exceeding $ 5853 . RARC was 16 % more expensive when only comparing direct operative costs . Interestingly , actual total patient costs revealed a 38 % cost advantage favoring RARC due to increased hospitalization costs for ORC in our cohort . CONCLUSIONS RARC can provide a cost-effective alternative to ORC with operative time and length of stay being the most critical cost determinants . Higher complication rates with ORC make total actual costs much higher than RARC Background The aim of this study was to compare conventional open thyroidectomy with robotic thyroidectomy in terms of postoperative pain . Methods We compared the intensity of postoperative pain experienced by patients who received conventional open thyroidectomy ( n = 45 ) versus those who underwent robotic thyroidectomy ( n = 45 ) . During surgery , we carefully controlled the anesthetic conditions . All the patients underwent a total thyroidectomy with ipsilateral central compartment node dissection . Postoperative pain in the 2 groups was compared using a visual analog scale and the amount of rescue analgesic at 30 min , 4 h , 1 , 2 , 3 , and 10 days after surgery . Results The postoperative pain at 30 min and 4 h after surgery were 3.0 ± 0.9 and 2.6 ± 0.9 ( p = .066 ) and 4.9 ± 1.3 and 4.4 ± 1.3 ( p = .055 ) in the conventional open group and the robotic group , respectively . The mean pain scores at 1 , 2 , 3 , and 10 days after surgery were 3.8 ± 1.3 and 3.0 ± 1.3 ( p = .001 ) , 2.6 ± 1.2 and 2.0 ± 0.9 ( p = .005 ) , 1.7 ± 0.9 and 1.3 ± 0.6 ( p = .034 ) , and 0.9 ± 0.7 and 1.2 ± 1.1 ( p = .093 ) , respectively . No significant differences were observed between the 2 groups in terms of postoperative rescue analgesic use ( 1.1 ± 1.1 and 0.8 ± 0.9 , p = .264 ) . Conclusions Even though robotic thyroidectomy using the transaxillary technique requires a more extensive subcutaneous dissection than conventional open thyroidectomy , robotic thyroidectomy does not result in more postoperative pain or use of analgesic when compared with open thyroidectomy Nephron‐sparing surgery has become the st and ard of care for small renal masses because it allows for the same oncological control as radical nephrectomy and achieves better overall survival , while lowering the risk of subsequent chronic renal failure . Mini‐invasive surgical approaches have also been developed , e.g. laparoscopic partial nephrectomy ( LPN ) and robot‐assisted laparoscopic PN ( RAPN ) , which result in less bleeding , reduced postoperative pain , shorter length of stay ( LOS ) and shorter recovery time . LPN requires advanced surgical skill , has a longer learning curve and requires perseverance , which limits its large diffusion . From this prospect i ve comparative study , we can now cl aim that RAPN is not inferior to pure LPN in terms of perioperative outcomes ( i.e. blood loss , operative duration , warm ischaemia time , LOS ) PURPOSE To compare operating room times between retroperitoneal robot-assisted laparoscopic radical prostatectomy ( RALRP ) and pure retroperitoneal laparoscopic radical prostatectomy ( LRP ) . PATIENTS AND METHODS From March 2007 to April 2008 , 288 patients underwent an extraperitoneal LRP in our institution . Eighty-three LRPs were performed with robot assistance using the da Vinci Surgical System ( RALRP ) whereas 205 pure LRPs were performed . Operating room times were compared between the two groups . RESULTS Both groups were statistically equal concerning age ( P = 0.95 ) , body mass index ( P = 0.52 ) , prostate-specific antigen level ( P = 0.40 ) , prostate volume ( P = 0.49 ) , clinical stage ( P = 0.11 ) , and Gleason score on biopsy ( P = 0.57 ) . Total operating room time was not significantly different between the two groups ( 223.6 vs 215.7 minutes in LRP and RALRP groups , respectively ; P = 0.23 ) . Mean patient installation was longer in the RALRP group ( 33.2 vs 24.0 minutes , P < 0.01 ) . Mean operative time was significantly shorter by about 20 minutes in the RALRP group ( 145.6 vs 164.7 minutes , P < 0.01 ) . Mean estimated blood loss was significantly lower in the RALRP group ( 469 mL vs 889 mL in the LRP group , P < 0.01 ) . No statistical differences were observed regarding hospital stay , bladder catheterization , and complication rate between the two groups . CONCLUSION Occupation times of the operating room are equivalent during pure retroperitoneal LRP and RALRP . For a trained team performing four procedures per week , the use of the robot for LRP with no lymph node dissection decreases actual operative time at the expense of an increase in installation time , compared with pure laparoscopy INTRODUCTION The role of minimally invasive radical cystectomy as opposed to open surgery for bladder cancer is not yet established . We present comparative outcomes of open , laparoscopic and robotic-assisted radical cystectomy MATERIAL AND METHODS Prospect i ve cohort comparison of 158 patients from 2003 - 2008 undergoing open radical cystectomy ( ORC ) ( n = 52 ) , laparoscopic radical cystectomy ( LRC ) ( n = 58 ) or robotic-assisted radical cystectomy ( RARC ) ( n = 48 ) performed by a team of three surgeons at two hospitals . Peri-operative data , complication rates , length of hospital stay , oncological outcome ( including lymph node status ) and survival were recorded . Statistical analyses were adjusted to account for potential confounding factors such as ASA grade , gender , age , diversion type and final histology . RESULTS RARC took longer than LRC and ORC . Patients were about 30 times more likely to have a transfusion if they had ORC than if they had RARC ( p < 0.0001 ) and about eight times more likely to have a transfusion if they had LRC compared with RARC ( p < 0.006 ) . Patients were four times more likely to have a transfusion if they had ORC as compared with LRC ( p < 0.007 ) . Patients were four times more likely to have complications if they had ORC than RARC ( p = 0.006 ) and about three times more likely to have complications with LRC than with RARC ( p = 0.02 ) . Hospital stay was mean 19 days after ORC , 16 days after LRC and 10 days after RARC . CONCLUSIONS Despite study limitations , RARC had the lowest transfusion and complication rates and the shortest length of stay , although taking the longest to perform We performed a prospect i ve , r and omised controlled trial of unicompartmental knee arthroplasty comparing the performance of the Acrobot system with conventional surgery . A total of 27 patients ( 28 knees ) awaiting unicompartmental knee arthroplasty were r and omly allocated to have the operation performed conventionally or with the assistance of the Acrobot . The primary outcome measurement was the angle of tibiofemoral alignment in the coronal plane , measured by CT . Other secondary parameters were evaluated and are reported . All of the Acrobot group had tibiofemoral alignment in the coronal plane within 2 degrees of the planned position , while only 40 % of the conventional group achieved this level of accuracy . While the operations took longer , no adverse effects were noted , and there was a trend towards improvement in performance with increasing accuracy based on the Western Ontario and McMaster Universities Osteoarthritis Index and American Knee Society scores at six weeks and three months . The Acrobot device allows the surgeon to reproduce a pre-operative plan more reliably than is possible using conventional techniques which may have clinical advantages BACKGROUND In recent years , surgeons have begun to report case series of minimally invasive approaches to radical cystectomy , including robotic-assisted techniques demonstrating the surgical feasibility of this procedure with the potential of lower blood loss and more rapid return of bowel function and hospital discharge . Despite these experiences and observations , at this point high levels of clinical evidence with regard to the benefits of robotic cystectomy are absent , and the current experiences represent case series with limited comparisons to historical controls at best . OBJECTIVE We report our results on a prospect i ve r and omized trial of open versus robotic-assisted laparoscopic radical cystectomy with regard to perioperative outcomes , complications , and short-term narcotic usage . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve r and omized single-center noninferiority study comparing open versus robotic approaches to cystectomy in patients who are c and i date s for radical cystectomy for urothelial carcinoma of the bladder . Of the 41 patients who underwent surgery , 21 were r and omized to the robotic approach and 20 to the open technique . INTERVENTION Radical cystectomy , bilateral pelvic lymphadenectomy , and urinary diversion by either an open approach or by a robotic-assisted laparoscopic technique . MEASUREMENTS The primary end point was lymph node ( LN ) yield with a noninferiority margin of four LNs . Secondary end points included demographic characteristics , perioperative outcomes , pathologic results , and short-term narcotic use . RESULTS AND LIMITATIONS On univariate analysis , no significant differences were found between the two groups with regard to age , sex , body mass index , American Society of Anesthesiologists classification , anticoagulation regimen of aspirin , clinical stage , or diversion type . Significant differences were noted in operating room time , estimated blood loss , time to flatus , time to bowel movement , and use of inpatient morphine sulfate equivalents . There was no significant difference in regard to overall complication rate or hospital stay . On surgical pathology , in the robotic group 14 patients had pT2 disease or higher ; 3 patients had pT3/T4 disease ; and 4 patients had node-positive disease . In the open group , eight patients had pT2 disease or higher ; five patients had pT3/T4 disease ; and seven patients had node-positive disease . The mean number of LNs removed was 19 in the robotic group versus18 in the open group . Potential study limitations include the limited clinical and oncologic follow-up and the relatively small and single-institution nature of the study . CONCLUSIONS We present the results of a prospect i ve r and omized controlled noninferiority study with a primary end point of LN yield , demonstrating the robotic approach to be noninferior to the open approach . The robotic approach also compares favorably with the open approach in several perioperative parameters All new interventions and procedures must be properly assessed in comparison to the currently accepted method ( s ) . It is unethical not to do so . The optimum method is by R and omised Controlled Trial ( RCT ) . This is ideally suited to the testing of drugs because the trial can usually be double blind and placebo controlled . RCTs are less commonly used for the evaluation of new surgical techniques . There are valid and invalid reasons for this and these are discussed Background The aim of this study was to assess the benefits and disadvantages of robot-assisted laparoscopic surgery for disorders of the adrenal gl and in terms of feasibility , safety , and length of hospitalization . Methods Twenty consecutive patients with benign lesions of adrenal gl and were r and omized into two groups : Patients in the laparoscopic group underwent traditional laparoscopic adrenalectomy ( LAP ) , whereas those in the robotic group underwent robot-assisted adrenalectomy ( ROBOT ) using the da Vinci robotic system . Results There was no significant difference between the groups in terms of age , sex , body mass index , and size or locations of lesions . Operative times were significant longer in the ROBOT group ( total operative time , 169.2 min [ range , 136–215 ] vs 115.3 min ( range , 95–155 ) p < 0.001 . Skin-to-skin time was 107 m ( range , 77–154 ) vs 82.1 min ( range , 55–120 ) ( p < 0.001 ) . There were no conversions to open surgery . However , conversion to st and ard laparoscopic surgery was necessary in four of 10 ROBOT patients ( 40 % ; left , one right ) . Perioperative morbidity was higher in the ROBOT group ( 20 % vs 0 % ) . There was no difference in length of hospital stay . In the following ROBOT group , hospital stay was 5.7 days ( range , 4–9 ) vs 5.4 days ( range , 4–8 ) in the LAP group ( p = NS ) . The total cost of the ROBOT procedure ( $ 3,467 ) was significantly higher than that for LAP ( $ 2,737 ) ( p < 0.01 ) . Conclusion Laparoscopic adrenalectomy is superior to robot-assisted adrenalectomy in terms of feasibility , morbidity , and cost BACKGROUND The advantages of robot-assisted radical prostatectomy ( RARP ) over laparoscopic radical prostatectomy ( LRP ) have rarely been investigated in r and omised controlled trials . OBJECTIVE To compare RARP and LRP in terms of the functional , perioperative , and oncologic outcomes . The main end point of the study was changes in continence 3 mo after surgery . DESIGN , SETTING , AND PARTICIPANTS From January 2010 to January 2011 , 120 patients with organ-confined prostate cancer were enrolled and r and omly assigned ( using a r and omisation plan ) to one of two groups based on surgical approach : the RARP group and the LRP group . INTERVENTION All RARP and LRP interventions were performed with the same technique by the same single surgeon . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The demographic , perioperative , and pathologic results , such as the complications and prostate-specific antigen ( PSA ) measurements , were recorded and compared . Continence was evaluated at the time of catheter removal and 48 h later , and continence and potency were evaluated after 1 , 3 , 6 , and 12 mo . The student t test , Mann-Whitney test , χ(2 ) test , Pearson χ(2 ) test , and multiple regression analysis were used for statistics . RESULTS AND LIMITATIONS The two groups ( RARP : n=60 ; LRP : n=60 ) were comparable in terms of demographic data . No differences were recorded in terms of perioperative and pathologic results , complication rate , or PSA measurements . The continence rate was higher in the RARP group at every time point : Continence after 3 mo was 80 % in the RARP group and 61.6 % in the LRP group ( p=0.044 ) , and after 1 yr , the continence rate was 95.0 % and 83.3 % , respectively ( p=0.042 ) . Among preoperative potent patients treated with nerve-sparing techniques , the rate of erection recovery was 80.0 % and 54.2 % , respectively ( p=0.020 ) . The limitations included the small number of patients . CONCLUSIONS RARP provided better functional results in terms of the recovery of continence and potency . Further studies are needed to confirm our results BACKGROUND Laparoscopic gastric bypass is a technically dem and ing operation , especially when h and -sewing is required . Robotics may help facilitate the performance of this difficult operation . This study was undertaken to compare a single surgeon 's results using the daVinci Surgical System with those using traditional laparoscopic Roux-en-Y gastric bypass ( LRYGB ) when the techniques were learned simultaneously . METHODS From July 2004 to April 2005 , the new laparoscopic fellow 's first 50 patients were r and omized to undergo either LRYGB or totally robotic laparoscopic Roux-en-Y gastric bypass ( TRRYGB ) . Data were collected on patient age , gender , body mass index ( BMI ) , co-morbidities , operative time , complication rates , and length of stay . Student 's t test with unequal variances was used for statistical analysis . RESULTS No significant differences in age , gender , co-morbidities , complication rates , or length of stay were found between the two groups . The mean operating time was significantly shorter for TRRYGB than for LRYGB ( 130.8 versus 149.4 minutes ; P = 0.02 ) , with a significant difference in minutes per BMI ( 2.94 versus 3.47 min/ BMI ; P = 0.02 ) . The largest difference was in patients with a BMI > 43 kg/m(2 ) , for whom the difference in procedure time was 29.6 minutes ( 123.5 minutes for TRRYGB versus 153.2 minutes for LRYGB ; P = 0.009 ) and a significant difference in minutes per BMI ( 2.49 versus 3.24 min/ BMI ; P = 0.009 ) . CONCLUSION Our data indicate that the use of the daVinci Surgical System for TRRYGB is safe and feasible . The operating room time is shorter with the use of the robotic system during a surgeon 's learning curve , and that decrease is maximized in patients with a larger BMI . TRRYGB may be a better approach to gastric bypass when h and -sewing is required , especially early in a surgeon 's experience OBJECTIVE : To compare surgical outcome and quality of life of robot-assisted laparoscopic hysterectomy with conventional laparoscopic hysterectomy . METHODS : For this controlled clinical trial , patients with benign indications for hysterectomy were r and omized to receive either a robotic ( robotic group ) or conventional laparoscopic hysterectomy ( conventional group ) . The primary end point was total operating time ; secondary end points were perioperative outcome , blood loss , and the change in quality of life . RESULTS : Ninety-five patients out of 100 r and omized patients completed the study . Patient age , body mass index , and uterus weight showed no significant differences between both groups . All results are given as mean ( ±st and ard deviation ; median ) . Total operating time for the robotic group was significantly higher with 106 ( ±29 ; 103 ) compared with 75 ( ±21 ; 74 ) ( conventional group ) minutes . Blood loss , complications , analgesics use , and return to activity for both groups were comparable . The change in preoperative to postoperative quality -of-life index ( quality of life measured on a linear scale from 0 to 100 ) was significantly higher in the robotic group , with 13 ( ±10 ; 13 ) compared with 5 ( ±14 ; 5 ) ( conventional group ) . CONCLUSION : Robot-assisted laparoscopic hysterectomy and conventional laparoscopy compare well in most surgical aspects , but the robotic procedure is associated with longer operating times . Postoperative quality -of-life index was better ; however , long-term , there was no difference . However , subjective postoperative parameters such as analgesic use and return to activity showed no significant difference between both groups . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00683293 . LEVEL OF EVIDENCE : OBJECTIVES To prospect ively compare the relevant in-hospital and postdischarge short-term health outcomes in a contemporary group of patients undergoing either robotic or conventional radical prostatectomy . METHODS A total of 117 robotic and 89 conventional radical prostatectomy patients participated in a prospect i ve study evaluating short-term postoperative recovery . A vali date d short-term health outcomes question naire was self-administered at 2 and 6 weeks postoperatively . All patients were given the same preoperative and postoperative instructions . RESULTS The significant differences in short-term health outcome measures between the two groups were that robotic patients had less mean narcotic use during the first 24 hours of admission ( 32 versus 52 mg morphine sulfate equivalents , P = 0.001 ) and a shorter mean length of hospital stay ( 1.2 versus 1.3 days , P = 0.048 ) . No difference was found between the robotic and conventional radical prostatectomy groups regarding the median time to normal activity , 100 % activity , and time to driving ( 9 and 8 , 21 and 28 , and 13 and 14 days , respectively ) . No difference was found in the postdischarge pain levels at 2 and 6 weeks , as reflected in the equivalent time of narcotic use between the two groups ( 10.6 and 9 days for the robotic and conventional radical prostatectomy groups , respectively ) . CONCLUSIONS The results of this prospect i ve study have shown that both robotic and conventional radical prostatectomy provide comparable short-term postdischarge recovery , including time to normal and full activity , driving , and postdischarge narcotic use BACKGROUND The purpose of this study was to compare the quality of left internal thoracic arteries harvested by the conventional open approach versus minimally invasive videoscopic and robotic-assisted telesurgical techniques . METHODS One hundred and fifty consecutive patients with single vessel coronary artery disease were prospect ively studied . The left internal thoracic artery was harvested using three different approaches , with 50 patients consecutively assigned to each group . The off-pump coronary artery bypass ( OPCAB ) group underwent median sternotomy with direct visualization . The automated endoscopic system for optimal positioning ( AESOP ) group employed the AESOP 3000 system ( Computer Motion Inc , Goleta , CA ) for robotic-assisted visualization with endoscopic manual left internal thoracic artery harvesting . The Zeus group used the Zeus robotic telesurgical system ( Computer Motion Inc ) and internal thoracic artery harvesting was performed remotely from a surgical console . Postanastomotic left internal thoracic artery flows and day one postoperative angiography were used to assess internal thoracic artery quality and patency . RESULTS Average left internal thoracic artery harvest times were 23 + /- 2.5 , 63.3 + /- 20.3 , and 66.1 + /- 17.9 minutes in the OPCAB , AESOP , and Zeus groups , respectively ( p < 0.001 , OPCAB vs AESOP and Zeus ) . Intraoperative graft flows averaged 28.1 + /- 11.9 , 33.7 + /- 19.3 , and 36.9 + /- 24.6 mL/minute , respectively in the OPCAB , AESOP , and Zeus groups ( p = 0.317 , OPCAB vs AESOP and Zeus ) . There was no significant angiographic difference in the patency rate of the harvested left internal thoracic arteries in the three groups ( p = 0.685 , overall ) . CONCLUSIONS The left internal thoracic artery can be harvested safely and effectively using minimally invasive videoscopic and robotic-assisted telesurgical techniques . Although the less invasive approaches require specialized equipment and training as well as increased operative time , they offer the potential for less traumatic myocardial revascularization through smaller incisions and reduced postoperative morbidity Background The laparoscopic surgical approach has proven its benefit for the patient . There are however several short-comings , which have triggered considerable research for improvement . One improvement may be the introduction of telesurgery by the interposition of a computer interface between surgeon and patient . Material and Methods : A prospect i ve r and omized study was conducted in an advanced laparoscopic procedure . Nissen fundoplication . The control group underwent the conventional laparoscopic approach , while the investigational group underwent the telesurgical approach . Results Feasibility was 100 % . The procedure was more time consuming in the Telesurgical group , at all stages of the operation . Mortality was nil and morbidity was comparable in both groups . Conclusion The telesurgical approach is feasible in advanced laparoscopic procedures like Nissen fundoplication . At the present time there is however no obvious added benefit from this new technique OBJECTIVE To prospect ively evaluate quality of life ( QoL ) evolution after robotic-assisted thoracoscopic or open anterior mediastinal tumour resection with the European Organisation for Research and Treatment of Cancer ( EORTC ) QoL Question naire-C30 and the lung cancer-specific module , LC-13 . METHODS From January 2004 to December 2008 , QoL was prospect ively recorded in all patients undergoing surgery for mediastinal tumours . A total of 14 patients underwent thoracoscopic resection using the da Vinci robotic system ( Intuitive Surgical , Inc. , Mountain View , CA , USA ) , and 22 patients open resection through sternotomy . Question naires were administered before surgery and 1 , 3 , 6 and 12 months , postoperatively , with response rates of 100 % , 86.1 % , 94.4 % ; 75.0 % and 86.1 % , respectively . RESULTS Both approaches had comparable preoperative patients ' characteristics and QoL subscales . Open resection by sternotomy was characterised by a significant decrease in general functioning 1 month after surgery ( physical functioning p=0.001 , role functioning p=0.001 , and social functioning p=0.044 ) . Patients also complained of increased thoracic pain in the first 3 months after surgery ( p=0.017 ) . After a da Vinci robotic resection QoL scores approximated baseline preoperative values 1 month after surgery , with the exception of increase in thoracic and shoulder pain the first 3 months after surgery ( p=0.028 and 0.029 , respectively ) . CONCLUSIONS Numerous techniques have been published with different degrees of invasiveness , generating the existing controversy as to which is the best surgical approach for anterior mediastinal tumours . The high burden of decreased physical functioning reported after sternotomy is not seen after a da Vinci robotic-assisted thoracoscopic resection . The initial experience and postoperative QoL data are excellent and , therefore , the da Vinci robot will stay our future technique of choice for the treatment of resectable mediastinal tumours smaller than 4 cm on imaging techniques OBJECTIVE To prospect ively compare surgical and pathologic outcomes obtained by elective robot-assisted ( RAPN ) or open partial nephrectomy ( OPN ) for small renal cell carcinoma ( RCC ) . MATERIAL S AND METHODS Between 2008 and 2010 , after protocol design and patient consent , we prospect ively collected clinical data for 100 patients who concurrently underwent either OPN ( 58 ) or RAPN ( 42 ) by an individual experienced surgeon . Clinical data included age , BMI , and past medical history . Operative data included operative time , warm ischemia time ( WIT ) , and estimated blood loss ( EBL ) . Postoperative outcomes included hospital stay ( LOS ) , creatinine variation , Clavien complications , pathologic results , and survival . We stratified the complexity of the renal tumor using the R.E.N.A.L Nephrometry score . RESULTS Of note , RAPN was superior to OPN in terms of EBL ( median 143 mL vs. 415 ; P < 0.001 ) and LOS ( median 3.8 days vs. 6.8 ; P < 0.0001 ) . The median WIT for the RAPN group was 17.5 minutes ( vs. 17.1 OPN ; P = 0.3 ) ) and the mean strict operative time was 134.8 minutes ( vs. 128.4 OPN ; P = 0.097 ) . Regarding immediate , early , and short-term complications , variation of creatinine levels , and pathologic margins , the rates were equivalent for both groups ( P > 0.05 ) . According to the R.E.N.A.L nephrometry scores , both groups ( RAPN/OPN ) had similar rates ( % ) of low ( 81/72.4 ) and intermediate ( 19/20.7 ) complexity tumors , though there were 4 high complexity tumors in OPN group ( vs. 0 ; P = 0.03 ) . CONCLUSION We found that RAPN is superior to the reference st and ard ( OPN ) surgical treatment of small RCCs in terms of blood loss and length of hospital stay with equivalent complications , warm ischemia time , and effect on renal function . Larger r and omized trials with longer follow-up will give us further information and insight into the oncologic equivalence BACKGROUND Robotic-assisted total hip replacement has become a common method of implantation , especially in Europe . It frequently has been postulated that robotic reaming would result in an improved clinical outcome due to the better fit of the prosthesis , but that has never been demonstrated in a prospect i ve study , to our knowledge . The purpose of this study was to compare robotic-assisted implantation of a total hip replacement with conventional manual implantation . METHODS One hundred and fifty-four patients scheduled for total hip replacement were r and omly assigned to undergo either conventional manual implantation of an S-ROM prosthesis ( eighty patients ) or robotic-assisted implantation of such a prosthesis ( seventy-four patients ) . The five-axis ROBODOC was used for the robotic-assisted procedures . Preoperatively as well as at three , six , twelve , and twenty-four months after surgery , the scores according to the Harris and Merle d'Aubigné systems and the Mayo clinical score were determined . Radiographs made at these intervals were analyzed for evidence of loosening , prosthetic alignment , and heterotopic ossification . RESULTS Thirteen ( 18 % ) of the seventy-four attempted robotic implantations had to be converted to manual implantations as a result of failure of the system . The duration of the robotic procedures was longer than that of the manual procedures ( mean and st and ard deviation,107.1 + /- 29.1 compared with 82.4 + /- 23.4 minutes , p < 0.001 ) . Limb-length e quality ( mean discrepancy , 0.18 + /- 0.30 compared with 0.96 + /- 0.93 cm , p < 0.001 ) and varus-valgus orientation of the stem ( mean angle between the femur and the shaft of the prosthesis , 0.34 degrees + /- 0.67 degrees compared with 0.84 degrees + /- 1.23 degrees , p < 0.001 ) were better after the robotic procedures . At six months , slightly more heterotopic ossification was seen in the group treated with robotic implantation . The group treated with robotic implantation had a better Mayo clinical score at six and twelve months and a better Harris score at twelve months ; however , by twenty-four months , no difference was found between the groups with regard to any of the three scores . Dislocation was more frequent in the group treated with robotic implantation : it occurred in eleven of the sixty-one patients in that group compared with three of eighty in the other group ( p < 0.001 ) . Recurrent dislocation and pronounced limping were indications for revision surgery in eight of the sixty-one patients treated with robotic implantation compared with none of the seventy-eight ( excluding two with revision for infection ) treated with manual insertion ( p < 0.001 ) . Rupture of the gluteus medius tendon was observed during all of the revision operations . CONCLUSIONS The robotic-assisted technology had advantages in terms of preoperative planning and the accuracy of the intraoperative procedure . Disadvantages were the high revision rate ; the amount of muscle damage , which we believe was responsible for the higher dislocation rate ; and the longer duration of surgery . This technology must be further developed before its widespread usage can be justified The authors from the Vattikuti Institute in the USA report a prospect i ve comparison of radical prostatectomy and robot‐assisted prostatectomy . They found that the robot‐assisted procedure was safer , and yielded favourable oncological and functional results . They also present work in association with the Department of Urology in Mansoura into robot‐assisted radical cystoprostatectomy and urinary diversion , and point out the advantages and disadvantages associated with performing the most complex types of urinary diversion OBJECTIVE We compared the outcomes of same sitting robotic-assisted hybrid coronary artery revascularization ( HCR ) with off-pump coronary artery bypass grafting ( OPCABG ) in similar patients with multivessel coronary artery disease . BACKGROUND HCR is a novel procedure in selected patients with multivessel coronary artery disease ( CAD ) . Although there are some data on staged HCR , the data on same sitting HCR are limited . METHODS We conducted a prospect i ve study comparing same sitting robotic-assisted HCR patients ( n = 25 ) to a group of consecutive low to moderate risk OPCABG patients ( n = 27 ) during the study period . HCR patients underwent robotic internal mammary artery takedown followed by OPCABG via minithoracotomy . After confirming graft patency , immediate percutaneous coronary intervention on the nonbypass arteries was performed . Comparative analyses were performed on in-hospital and 30 day outcomes . RESULTS The baseline characteristics were similar for both groups including the severity of CAD ( Syntax score 33.5+/-8.2 vs. 34.9+/-8.2 , P = 0.556 ) . Overall MACE was similar between both groups ; however , the HCR group showed improved hospital outcomes with lower need for postoperative transfusions ( 12 % vs. 67 % , P < 0.001 ) , and shorter length of hospital stay ( 5.1+/-2.8 vs. 8.2+/-5.4 days , P < 0.01 ) . Despite lower postoperative costs , the HCR group had higher overall hospital costs due to higher procedural costs ( $ 33,984 + /-$4,806 vs. $ 27,816+/-$11,172 , P < 0.0001 ) . Propensity model analysis showed similar findings . The HCR group showed improved quality of life measures with shorter time to return to work ( 5.3+/-3.0 vs. 8.2+/- 4.6 weeks , P = 0.01 ) . CONCLUSIONS Same sitting HCR appears to be feasible and may offer superior outcomes to st and ard OPCABG , further studies are warranted BACKGROUND Robotic catheter navigation and ablation either with magnetic catheter driving or with electromechanical guidance have emerged in the recent years for the treatment of atrial fibrillation . OBJECTIVE The aim of this study was to compare our center 's experience of atrial fibrillation ablation using the Hansen Robotic Medical System with our current manual ablation technique in terms of acute and chronic success , as well as procedure time and radiation exposure to both the patient and the operator . METHODS A total of 390 consecutive patients with symptomatic and drug-resistant atrial fibrillation ( 289 males , 62 + /- 11 years ) were prospect ively enrolled in the study . All patients underwent the procedure either with conventional manual ablation ( group 1 , n = 197 ) or with the robotic navigation system ( RNS ) ( group 2 , n = 193 ) . RESULTS The success rate for RNS was 85 % ( 164 patients ) , while for manual ablation it was 81 % ( 159 patients ) ( p = 0.264 ) at 14.1 + /- 1.3 months with AADs previously ineffective . Fluoroscopy time was significantly lower for RNS ( 48.9 + /- 24.6 minutes for RNS vs. 58.4 + /- 20.1 minutes for manual ablation , P < 0.001 ) . Mean fluoroscopy time was statistically reduced after 50 procedures ( 61.8 + /- 23.2 minutes for first 50 cases vs. 44.5 + /- 23.6 minutes for subsequent procedures , P < 0.0001 ) . CONCLUSION Robotic navigation and ablation of atrial fibrillation is safe and effective . Fluoroscopy time decreases with experience A robotics surgery program was introduced into the division of gynecologic oncology at Northwestern University Feinberg School of Medicine in June 2007 . A prospect i ve data base of all patients undergoing a type III radical hysterectomy for stage IB1 cervical cancer between July 2007 and June 2008 was collected and analyzed . Demographic data and perioperative outcomes were analyzed between a traditional and robot-assisted approach . A total of 14 patients were identified who underwent a type III radical hysterectomy for stage IB1 cervical cancer . Seven patients underwent robotic surgery and seven patients underwent traditional surgery . There were no significant differences in median age or body mass index between the two groups . A significant difference in blood loss between robotic ( 75 cc ) and traditional ( 700 cc ) surgery was detected ( P = 0.002 ) . A significant difference in hospital stay between robotic ( 1 day ) and traditional ( 5 days ) surgery was observed ( P = 0.0007 ) . No significant difference in operative time ( 260 vs. 264 min ) or lymph node yield ( 19 and 14 ) was identified between the robotic and traditional approaches . No major operative complications occurred with robotic radical hysterectomy . Robot-assisted radical hysterectomy was associated with a significant reduction in blood loss and hospital stay . Improved nodal yields , fewer operative complications , and less pain was observed with the robotic approach . Robot-assisted radical hysterectomy appears safe and feasible and further investigation is warranted in a prospect i ve fashion BACKGROUND Minimally invasive coronary artery bypass grafting ( miniCABG ) decreases in-hospital morbidity versus traditional sternotomy CABG . We performed a prospect i ve cohort study ( NCT00481806 ) to assess the impact of miniCABG on costs and metrics that influence quality of life after hospital discharge . METHODS One hundred consecutive miniCABG cases performed using internal mammary artery ( IMA ) grafting + /- coronary stenting were compared with a matched group of 100 sternotomy CABG patients using IMA and saphenous veins , both treating equivalent number of target coronaries ( 2.7 vs. 2.9 ) , off-pump . We compared perioperative costs , time to return to work/normal activity , and risk of major adverse cardiac/cerebrovascular events ( MACCE ) at 1 year : myocardial infa rct ion ( elevated troponin or EKG changes ) , target vessel occlusion ( CT angiography at 1 year ) , stroke , or death . RESULTS For miniCABG , robotic instruments and stents increased intraoperative costs ; postoperative costs were decreased from significantly less intubation time ( 4.80 + /- 6.35 vs. 12.24 + /- 6.24 hours ) , hospital stay ( 3.77 + /- 1.51 vs. 6.38 + /- 2.23 days ) , and transfusion ( 0.16 + /- 0.37 vs. 1.37 + /- 1.35 U ) leading to no significant differences in total costs . Undergoing miniCABG independently predicted earlier return to work after adjusting for confounders ( t = -2.15 ; P = 0.04 ) , whereas sternotomy CABG increased MACCE ( HR , 3.9 ; 95 % CI , 1.4 - 7.6 ) , largely from lower target-vessel patency . CONCLUSIONS MiniCABG shortens patient recovery time , minimizes MACCE risk at 1 year , and showed superior quality and outcome metrics versus st and ard-of-care CABG . These findings occurred without increasing costs and with superior target vessel graft patency |
978 | 25,875,432 | Our three-layered trust model provides a new lens for conceptualizing the variability of trust in automation . | OBJECTIVE We systematic ally review recent empirical research on factors that influence trust in automation to present a three-layered trust model that synthesizes existing knowledge .
BACKGROUND Much of the existing research on factors that guide human-automation interaction is centered around trust , a variable that often determines the willingness of human operators to rely on automation .
Studies have utilized a variety of different automated systems in diverse experimental paradigms to identify factors that impact operators ' trust . | Objective : The aim of this study was to evaluate display formats for an automated combat identification ( CID ) aid . Background : Verbally informing users of automation reliability improves reliance on automated CID systems . A display can provide reliability information in real time . Method : We developed and tested four visual displays that showed both target identity and system reliability information . Display type ( pie , r and om mesh ) and display proximity ( integrated , separated ) of identity and reliability information were manipulated . In Experiment 1 , participants used the displays while engaging targets in a simulated combat environment . In Experiment 2 , participants briefly viewed still scenes from the simulation . Results : Participants relied on the automation more appropriately with the integrated display than with the separated display . Participants using the r and om mesh display showed greater sensitivity than those using a pie chart . However , in Experiment 2 , the sensitivity effects were limited to lower reliability levels . Conclusion : The integrated display format and the r and om mesh display were the most effective displays tested . Application : We recommend the use of the integrated format and a r and om mesh display to indicate identity and reliability information with an automated CID system Objective : This study examined whether benefits of conflict probe automation would occur in a future air traffic scenario in which air traffic service providers ( ATSPs ) are not directly responsible for freely maneuvering aircraft but are controlling other nonequipped aircraft ( mixed-equipage environment ) . The objective was to examine how the type of automation imperfection ( miss vs. false alarm ) affects ATSP performance and attention allocation . Background : Research has shown that the type of automation imperfection leads to differential human performance costs . Method : Participating in four 30-min scenarios were 12 full-performance-level ATSPs . Dependent variables included conflict detection and resolution performance , eye movements , and subjective ratings of trust and self confidence . Results : ATSPs detected conflicts faster and more accurately with reliable automation , as compared with manual performance . When the conflict probe automation was unreliable , conflict detection performance declined with both miss ( 25 % conflicts detected ) and false alarm automation ( 50 % conflicts detected ) . Conclusion : When the primary task of conflict detection was automated , even highly reliable yet imperfect automation ( miss or false alarm ) result ed in serious negative effects on operator performance . Application : The further in advance that conflict probe automation predicts a conflict , the greater the uncertainty of prediction ; thus , design ers should provide users with feedback on the state of the automation or other tools that allow for inspection and analysis of the data underlying the conflict probe algorithm |
979 | 18,947,284 | Surgical correction of skeletal Class III malocclusion after combined maxillary and m and ibular procedures appears to be stable for maxillary advancements up to 5 mm and for the correction of presurgical sagittal intermaxillary discrepancies smaller than 7 mm | OBJECTIVE To identify the stability factors of skeletal Class III malocclusion after double-jaw surgery by a systematic review of the literature . | In this paper preliminary results are presented of a prospect i ve study design ed to examine the effect of maxillary fixation methods on postoperative stability . The purpose of this study was to evaluate the stability of Le Fort I osteotomy stabilized with semirigid fixation of the maxilla ( SRMF ) or rigid fixation of the maxilla ( RMF ) . All patients had skeletal Class III malocclusion and underwent bimaxillary surgery ( Le Fort I maxillary advancement with or without superior repositioning and bilateral sagittal split osteotomies of the m and ible ) . St and ardized cephalometric analysis was performed on serial radiographs of 42 patients immediately before surgery , 1 week after surgery , after release of fixation , and 1 year postoperatively . The patients were r and omized into 2 treatment groups : 23 patients received RMF ( group A ) , and 19 patients received SRMF ( group B ) . Within the groups , patients showed good stability with regard to their baseline characteristics . To show the therapeutic equivalence of the 2 treatments , analysis of the recorded data followed the approach for an equivalence trial . The mean surgical advancement was 5.34 + /- 1.50 mm for group A and 4.51 + /- 1.37 mm for group B. The mean amount of postsurgical relapse was 0.98 + /- 1.27 mm for group A and 0.30 + /- 1.04 mm for group B. Group A patients experienced 93 % of their relapse ( 0.92 mm ) during fixation , while group B patients experienced 96 % of their relapse ( 0.29 mm ) after release of fixation . RMF provided better stability than SRMF for all maxillary l and marks in the vertical plane . All considered points both in horizontal and vertical plane exhibited full equivalence for 95 % confidence intervals , which seems to indicate equivalent stability between the surgical procedures The aim of this study was to select a model of cephalometric variables to predict the results of early treatment of Class III malocclusion with rapid maxillary expansion and facemask therapy followed by comprehensive treatment with fixed appliances . Lateral cephalograms of 42 patients ( 20 boys , 22 girls ) with Class III malocclusion were analyzed at the start of treatment ( mean age 8 years 6 months + /- 2 years , at stage I in cervical vertebral maturation ) . All patients were reevaluated after a mean period of 6 years 6 months ( at stage IV or V in cervical vertebral maturation ) that included active treatment plus retention . At this time , the sample was divided into 2 groups according to occlusal criteria : a successful group ( 30 patients ) and an unsuccessful group ( 12 patients ) . Discriminant analysis was applied to select pretreatment predictive variables of long-term treatment outcome . Stepwise variable selection of the cephalometric measurements at the first observation identified 3 predictive variables . Orthopedic treatment of Class III malocclusion might be unfavorable over the long term when a patient 's pretreatment cephalometric records exhibit a long m and ibular ramus ( ie , increased posterior facial height ) , an acute cranial base angle , and a steep m and ibular plane angle . On the basis of the equation generated by the multivariate statistical method , the outcome of interceptive orthopedic treatment for each new patient with Class III malocclusion can be predicted with a probability error of 16.7 % The purpose of this study was to evaluate long-term dentofacial stability after bimaxillary surgery in skeletal Class III open bite patients . Twenty-three Japanese adults ( 5 males , 18 females ) were r and omly selected as the experimental group from the files of Tohoku University Dental Hospital according to the following criteria : ( 1 ) skeletal Class III malocclusion with anterior open bite , ( 2 ) simultaneous Le Fort I and sagittal split ramus osteotomies , and ( 3 ) complete set of cephalograms taken at predetermined intervals until 5 years after debonding . Based on the manner of maxillary surgical repositioning , they were divided into the following 2 groups : ( 1 ) impaction group of 13 subjects ( 2 males , 11 females ) who had maxillary superior repositioning without rotation of the palatal plane , and ( 2 ) rotation group of 10 subjects ( 3 males , 7 females ) who had maxillary repositioning with clockwise rotation of the palatal plane . These patients were compared to a control group of 11 adults ( 1 male , 10 females ) with skeletal Class III malocclusion without open bite who underwent bimaxillary surgery by the same techniques . Our data showed that overbite stability in the rotation group was better than that in the impaction group . This suggests that clockwise rotation of the palatal plane , which moves the anterior maxillary structures down , is an effective way to produce a reasonably stable correction of the anterior open bite . In contrast , superior repositioning of the maxilla that significantly rotates the m and ible in the closing direction should be applied with caution PURPOSE The aim of this study was to evaluate skeletal stability after double-jaw surgery for correction of skeletal Class III malocclusion to assess whether there were any differences between wire and rigid fixation of the m and ible . PATIENTS AND METHODS Thirty-seven Class III patients had Le Fort I osteotomy stabilized with plate and screws for maxillary advancement . Bilateral sagittal split osteotomy for m and ibular setback was stabilized with wire osteo synthesis and maxillom and ibular fixation for 6 weeks in 20 patients ( group 1 ) and with rigid internal fixation in 17 patients ( group 2 ) . Lateral cephalograms were taken before surgery , immediately after surgery , 8 weeks after surgery , and 1 year after surgery . RESULTS Before surgery , both groups were balanced with respect to linear and angular measurements of craniofacial morphology . One year after surgery , maxillary sagittal stability was excellent in both groups , and bilateral sagittal split osteotomy accounted for most of the total horizontal relapse observed . In group 1 , significant correlations were found between maxillary advancement and relapse at the posterior maxilla and between m and ibular setback and postoperative counterclockwise rotation of the ramus and m and ibular relapse . In group 2 , significant correlations were found between m and ibular setback and intraoperative clockwise rotation of the ramus and between m and ibular setback and postoperative counterclockwise rotation of the ramus and m and ibular relapse . No significant differences in postoperative skeletal and dental stability between groups were observed except for maxillary posterior vertical position . CONCLUSIONS Surgical correction of Class III malocclusion after combined maxillary and m and ibular procedures appears to be a fairly stable procedure independent of the type of fixation used to stabilize the m and ible PURPOSE The aim of this report was to compare the clinical and radiographic findings observed at the 12-month follow-up in 2 groups of 15 patients who underwent Le Fort I and bilateral sagittal split osteotomy for the correction of dental-skeletal Class III . In the first group , the condylar positioning devices were used , whereas in the second group , an alternative method was used for the intraoperative assessment of m and ibular repositioning . MATERIAL S AND METHODS All of the patients of our study in the immediate presurgical period were without temporom and ibular joint disorders and with a normal anatomic relationship between condyle and fossae . The condyle position and morphology were examined at the 12-month follow-up through cephalometric measurements and the postsurgical findings in both groups were compared with those observed in the presurgical period . RESULTS In all of the 30 patients in our study , no relapse or postsurgical temporom and ibular joint disturbance was observed at the 12-month follow-up . Variations in condyle position of more than 2 mm or 2 degrees were not observed in the 15 patients treated with condylar positioning devices . Changes in condyle position between 2 and 4 mm and 2 degrees and 4 degrees were observed in 6 of the 15 patients treated without the devices . CONCLUSIONS The use of condylar positioning devices can be avoided in patients with dental-skeletal Class III without presurgical temporom and ibular dysfunction . The manual positioning of the m and ibular condyle is easier , but it requires the utmost care and an experienced operator The criteria and scoring method for a system to evaluate the quality of r and omized control trials ( RCTs ) in dental research based on published reports is presented . This sytem is based on one devised for evaluation of RCTs in medicine . Items assessed in this system include r and omization and blinding procedures , subject selection criteria , treatment protocol s , and statistical analyses . Assessing the quality of RCTs can contribute to improved study design , implementation and reporting by investigators , and evaluation of reports by referees and editors of scientific journals |
980 | 23,955,385 | Conclusion A wide range of severity assessment tools are used in the literature .
Developing a basis of comparison between tools would potentially be helpful in comparing findings across studies . | Background Prescribing errors are common .
It has been suggested that the severity as well as the frequency of errors should be assessed when measuring prescribing error rates .
This would provide more clinical ly relevant information , and allow more complete evaluation of the effectiveness of interventions design ed to reduce errors .
Objective The objective of this systematic review was to describe the tools used to assess prescribing error severity in studies reporting hospital prescribing error rates . | Background To prevent medication errors in prescribing , one needs to know their types and relative occurrence . Such errors are a great cause of concern as they have the potential to cause patient harm . The aim of this study was to determine the nature and types of medication prescribing errors in an Indian setting . Methods The medication errors were analyzed in a prospect i ve observational study conducted in 3 medical wards of a public teaching hospital in India . The medication errors were analyzed by means of Micromedex Drug-Reax data base . Results Out of 312 patients , only 304 were included in the study . Of the 304 cases , 103 ( 34 % ) cases had at least one error . The total number of errors found was 157 . The drug-drug interactions were the most frequently ( 68.2 % ) occurring type of error , which was followed by incorrect dosing interval ( 12 % ) and dosing errors ( 9.5 % ) . The medication classes involved most were antimicrobial agents ( 29.4 % ) , cardiovascular agents ( 15.4 % ) , GI agents ( 8.6 % ) and CNS agents ( 8.2 % ) . The moderate errors contributed maximum ( 61.8 % ) to the total errors when compared to the major ( 25.5 % ) and minor ( 12.7 % ) errors . The results showed that the number of errors increases with age and number of medicines prescribed . Conclusion The results point to the establishment of medication error reporting at each hospital and to share the data with other hospitals . The role of clinical pharmacist in this situation appears to be a strong intervention ; and the clinical pharmacist , initially , could confine to identification of the medication errors Objective To evaluate a matrix for determining the predominant type , cause category , and rate of medication prescribing errors , and to explore the effectiveness of hospital-based improvement initiatives among pediatric intensive care units ( PICUs ) . Design This study involved the prospect i ve identification of medication errors for categorization and evaluation by using a matrix methodology . A pretest-posttest design without a control group was used to explore the impact of initiatives employed to reduce medication error rates and severity . Setting PICUs in nine freest and ing , collaborating tertiary care children ’s hospitals that participated in both baseline and postintervention analyses . Methods We evaluated 12,026 PICU medication orders at baseline and 9,187 orders postintervention for prescribing errors , excluding resuscitation orders . A st and ardized tool and process captured error type , cause category , and severity for 2 wks before and after intervention . Three levels of error detection were used and included pharmacy order entry , PICU nurse order transcription , and team-based overview . Site-specific interventions were implemented , which included predominantly provider education as well as informational ( 47 % ) and dosing “ assists ” via preprinted orders , forcing functions , or prompts ( 39 % ) . Results Of baseline orders , 11.1 % had at least one prescribing error . The interception of prescribing errors improved 30.9 % ( 1.6 % of all orders at baseline , 2.0 % post intervention ) . Preventable adverse drug events were uncommon ( 0.6 % of all medication errors ) and of low severity at baseline ; most were wrong dose errors . The implementation of improvement initiatives , specific for each facility , result ed in a 31.6 % reduction in prescribing errors from 11.1 % to 7.6 % . However , site results varied considerably . Conclusions A benchmark for medication prescribing errors in the PICU was identified among nine children ’s hospitals . The methodology was successful in accounting for site-specific differences with regard to identifying and documenting errors as well as reporting results of improvement initiatives . Furthermore , the methodology employed was generalizable in the identification of predominant prescribing error types , which helped to track individual hospital improvement initiative development and implementation . Overall improvement in prescribing error rates was noted ; however , considerable variation in the success of improvement initiatives was noted and bears further attention Background : Medication errors at the time of hospital admission and discharge are common and can lead to preventable adverse drug events . The objective of this study was to describe the potential impact of a medication reconciliation process to identify and rectify medication errors at the time of hospital admission and discharge . Methods : Sixty r and omly selected patients were prospect ively enrolled at the time of admission to a Canadian community hospital . At admission , patients ’ medication orders were compared with pre-admission medication use based on medication vials and interviews with patients , caregivers , and /or outpatient healthcare providers . At discharge , pre-admission and in-patient medications were compared with discharge orders and written instructions . All variances were discussed with the prescribing physician and classified as intended or unintended ; unintended variances were considered to be medication errors . An internist classified the clinical importance of each unintended variance . Results : Overall , 60 % ( 95 % CI 48 to 72 ) of patients had at least one unintended variance and 18 % ( 95 % CI 9 to 28 ) had at least one clinical ly important unintended variance . None of the variances had been detected by usual clinical practice before reconciliation was conducted . Of the 20 clinical ly important variances , 75 % ( 95 % CI 56 to 94 ) were intercepted by medication reconciliation before patients were harmed . Discussion : Unintended medication variances at the time of hospital admission and discharge are common and clinical ly important . The medication reconciliation process identified and addressed most of these unintended variances before harm occurred . In this small study , medication reconciliation was a useful method for identifying and rectifying medication errors at times of transition . Reconciliation warrants broader evaluation Abstract Background : Medication safety research and clinical pharmacy practice today is primarily focused on managing preventable adverse drug events ( pADEs ) . Determinants of both pADEs and non-preventable adverse drug reactions ( ADRs ) have been identified . However , relatively little is known on the overlap between these determinants and the balance of preventable and non-preventable harm in patients experience in modern computerized hospitals . Objective : The aim of this study was to analyse the prevalence of pADEs and non-preventable ADRs as well as the determinants , including multimorbidity , of these ADEs , i.e. both pADEs and ADRs . Methods : Adverse events experienced by patients admitted to two Dutch hospitals with functioning computerized physician order entry ( CPOE ) systems were prospect ively identified through chart review . Adverse events were divided into pADEs ( i.e. as a result of a medication error ) and non-preventable ADRs . In both cases , a causal relationship between adverse events and patients ’ drugs was established using the simplified Yale algorithm . Study data were collected anytime between April 2006 and May 2008 over a 5-month period at each hospital ward included in the study , beginning from 8 weeks after CPOE was implemented at the ward . Results : pADEs and non-preventable ADRs were experienced by 349 ( 58 % ) patients , of whom 307 ( 88 % ) had non-preventable ADRs . Multimorbidity ( adjusted odds ratio [ ORadj ] 1.90 ; 95 % CI 1.44,2.50 ; ORadj 1.28 ; 95 % CI 1.14 , 1.45 , respectively ) , length of stay ( ORadj 1.13 ; 95 % CI 1.06 , 1.21 ; ORadj 1.11 ; 95 % CI 1.07 , 1.16 , respectively ) , admission to the geriatric ward ( ORadj 7.78 ; 95 % CI 2.15 , 28.13 ; ORadj 3.82 ; 95 % CI 1.73 , 8.45 , respectively ) and number of medication orders ( ORadj 1.25 ; 95 % CI 1.16,1.35 ; ORadj 1.13 ; 95 % CI 1.06 , 1.21 , respectively ) were statistically significantly associated with pADEs and ADRs . Admission to the gastroenterology/rheumatology ward ( ORadj 0.22 ; 95 % CI 0.06 , 0.77 ; ORadj 0.40 ; 95 % CI 0.24 , 0.65 , respectively ) was inversely related to both pADEs and ADRs . Other determinants for ADRs only were female sex ( ORadj 1.77 ; 95 % CI 1.12 , 2.80 ) and use of drugs affecting the nervous system ( ORadj 1.83 ; 95 % CI 1.09 , 3.07 ) . Age was a significant determinant for pADEs only ( ORadj 1.07 ; 95 % CI 1.03 , 1.11 ) . Conclusions : In this study more than half of the patients admitted to the hospitals are harmed by drugs , of which most are non-serious , non-preventable ADRs ( after the introduction of CPOE ) . Determinants of both pADEs and ADRs overlap to a large extent . Our results imply the need for signalling early potential adverse events that occur during the normal use of drugs in multimorbid patients or those in geriatric wards . Subsequent therapeutic interventions may improve the well-being of hospitalized patients to a greater extent than focusing on errors in the medication process only Objective . The purpose of this study was to record prospect ively the frequency of medication order errors in a general hospital in Israel with the objective of assessing the impact of pharmacist intervention in preventing potential harm . Methods . The study was conducted during a 6‐month period . A total of 160 medication order errors were detected at the hospital of which 60.6 % were prescription errors and 39.4 % were therapy ones . Principal types of errors detected were incorrect dosage ( 27.5 % ) , interactions between drugs ( 20 % ) , incorrect drug ( 12.5 % ) , route ( 11.2 % ) and frequency ( 11.2 % ) . Medication error rate by degree of severity was calculated per 100 patient days . The highest rate was found in Hemato‐Oncology ( 2.48 ) , followed by Intensive Care ( 0.82 ) , Surgery ( 0.48 ) and Internal Medicine ( 0.26 ) . Anti‐infective drugs were the most prevalent class of drugs in which errors occurred ( 38.7 % ) followed by total parenteral nutrition preparations ( 21.8 % ) , antineoplastics ( 15.6 % ) and anticoagulants ( 11.3 % ) . Changes in medication orders due to pharmacists ' intervention only occurred in 73.8 % of error cases , most referring to dosage or route change ( 37.5 % ) . Conclusion . This study underestimates the actual number of medication errors . However , it identified problem areas and trends so that better measures to improve drug use could be implemented CONTEXT Iatrogenic injuries , including medication errors , are an important problem in all hospitalized population s. However , few epidemiological data are available regarding medication errors in the pediatric inpatient setting . OBJECTIVES To assess the rates of medication errors , adverse drug events ( ADEs ) , and potential ADEs ; to compare pediatric rates with previously reported adult rates ; to analyze the major types of errors ; and to evaluate the potential impact of prevention strategies . DESIGN , SETTING , AND PATIENTS Prospect i ve cohort study of 1120 patients admitted to 2 academic institutions during 6 weeks in April and May of 1999 . MAIN OUTCOME MEASURES Medication errors , potential ADEs , and ADEs were identified by clinical staff reports and review of medication order sheets , medication administration records , and patient charts . RESULTS We review ed 10 778 medication orders and found 616 medication errors ( 5.7 % ) , 115 potential ADEs ( 1.1 % ) , and 26 ADEs ( 0.24 % ) . Of the 26 ADEs , 5 ( 19 % ) were preventable . While the preventable ADE rate was similar to that of a previous adult hospital study , the potential ADE rate was 3 times higher . The rate of potential ADEs was significantly higher in neonates in the neonatal intensive care unit . Most potential ADEs occurred at the stage of drug ordering ( 79 % ) and involved incorrect dosing ( 34 % ) , anti-infective drugs ( 28 % ) , and intravenous medications ( 54 % ) . Physician review ers judged that computerized physician order entry could potentially have prevented 93 % and ward-based clinical pharmacists 94 % of potential ADEs . CONCLUSIONS Medication errors are common in pediatric inpatient setting s , and further efforts are needed to reduce them Introduction Medication errors in the intensive care unit ( ICU ) are frequent and lead to attributable patient morbidity and mortality , increased length of ICU stay and substantial extra costs . We investigated if the introduction of a computerized ICU system ( Centricity Critical Care Clinisoft , GE Healthcare ) reduced the incidence and severity of medication prescription errors ( MPEs ) . Methods A prospect i ve trial was conducted in a paper-based unit ( PB-U ) versus a computerized unit ( C-U ) in a 22-bed ICU of a tertiary university hospital . Every medication order and medication prescription error was vali date d by a clinical pharmacist . The registration of different classes of MPE was done according to the National Coordinating Council for Medication Error Reporting and Prevention guidelines . An independent panel evaluated the severity of MPEs . We identified three groups : minor MPEs ( no potential to cause harm ) ; intercepted MPEs ( potential to cause harm but intercepted on time ) ; and serious MPEs ( non-intercepted potential adverse drug events ( ADE ) or ADEs , being MPEs with potential to cause , or actually causing , patient harm ) . Results The C-U and the PB-U each contained 80 patient-days , and a total of 2,510 medication prescriptions were evaluated . The clinical pharmacist identified 375 MPEs . The incidence of MPEs was significantly lower in the C-U compared with the PB-U ( 44/1286 ( 3.4 % ) versus 331/1224 ( 27.0 % ) ; P < 0.001 ) . There were significantly less minor MPEs in the C-U than in the PB-U ( 9 versus 225 ; P < 0.001 ) . Intercepted MPEs were also lower in the C-U ( 12 versus 46 ; P < 0.001 ) , as well as the non-intercepted potential ADEs ( 21 versus 48 ; P < 0.001 ) . There was also a reduction of ADEs ( 2 in the C-U versus 12 in the PB-U ; P < 0.01 ) . No fatal errors occurred . The most frequent drug classes involved were cardiovascular medication and antibiotics in both groups . Patients with renal failure experienced less dosing errors in the C-U versus the PB-U ( 12 versus 35 serious MPEs ; P < 0.001 ) . Conclusion The ICU computerization , including the medication order entry , result ed in a significant decrease in the occurrence and severity of medication errors in the ICU Introduction The study aim ed to compare the impact of computerised physician order entry ( CPOE ) without decision support with h and -written prescribing ( HWP ) on the frequency , type and outcome of medication errors ( MEs ) in the intensive care unit . Methods Details of MEs were collected before , and at several time points after , the change from HWP to CPOE . The study was conducted in a London teaching hospital 's 22-bedded general ICU . The sampling periods were 28 weeks before and 2 , 10 , 25 and 37 weeks after introduction of CPOE . The unit pharmacist prospect ively recorded details of MEs and the total number of drugs prescribed daily during the data collection periods , during the course of his normal chart review . Results The total proportion of MEs was significantly lower with CPOE ( 117 errors from 2429 prescriptions , 4.8 % ) than with HWP ( 69 errors from 1036 prescriptions , 6.7 % ) ( p < 0.04 ) . The proportion of errors reduced with time following the introduction of CPOE ( p < 0.001 ) . Two errors with CPOE led to patient harm requiring an increase in length of stay and , if administered , three prescriptions with CPOE could potentially have led to permanent harm or death . Differences in the types of error between systems were noted . There was a reduction in major/moderate patient outcomes with CPOE when non-intercepted and intercepted errors were combined ( p = 0.01 ) . The mean baseline APACHE II score did not differ significantly between the HWP and the CPOE periods ( 19.4 versus 20.0 , respectively , p = 0.71 ) . Conclusion Introduction of CPOE was associated with a reduction in the proportion of MEs and an improvement in the overall patient outcome score ( if intercepted errors were included ) . Moderate and major errors , however , remain a significant concern with CPOE The effect of an automated bedside dispensing machine on medication errors was studied on a 32-bed surgical unit of an 848-bed hospital . The experimental system ( McLaughlin Dispensing System ) included at each patient 's bedside a locked medication cabinet that was electronically programmed to allow the nurse access to doses due at a particular time . The control system was a de central ized unit dose system . A crossover study design with r and om assignment of subjects and treatments was used . In the 14-day study period , nurses were observed by a pharmacist for 28 five-hour periods as they administered medications on the day and evening shifts . The mean error rates were significantly different--10.6 % for the experimental system and 15.9 % for the control system . Wrong time errors were the most common type . No significant differences were found between day and evening shifts or workloads of individual nurses . There was no treatment order effect . The error rate was significantly lower for the automated dispensing system than for the system using unit doses dispensed from a satellite pharmacy . Automated dispensing systems may be useful in reducing errors in administration time and dose omissions AIMS AND OBJECTIVES To examine the incidence of prescribing errors in a main public hospital in Pakistan and to assess the impact of introducing electronic prescribing system on the reduction of their incidence . BACKGROUND Medication errors are persistent in today 's healthcare system . The impact of electronic prescribing on reducing errors has not been tested in developing world . DESIGN Prospect i ve review of medication and discharge medication charts before and after the introduction of an electronic inpatient record and prescribing system . METHODS Inpatient records ( n = 3300 ) and 1100 discharge medication sheets were review ed for prescribing errors before and after the installation of electronic prescribing system in 11 wards . RESULTS Medications ( 13,328 and 14,064 ) were prescribed for in patients , among which 3008 and 1147 prescribing errors were identified , giving an overall error rate of 22·6 % and 8·2 % throughout paper-based and electronic prescribing , respectively . Medications ( 2480 and 2790 ) were prescribed for discharge patients , among which 418 and 123 errors were detected , giving an overall error rate of 16·9 % and 4·4 % during paper-based and electronic prescribing , respectively . CONCLUSION Electronic prescribing has a significant effect on the reduction of prescribing errors . RELEVANCE TO CLINICAL PRACTICE Prescribing errors are commonplace in Pakistan public hospitals . The study evaluated the impact of introducing electronic inpatient records and electronic prescribing in the reduction of prescribing errors in a public hospital in Pakistan Medication errors are an important cause of patient morbidity and mortality , of which there have been few reports in psychiatry , especially in the UK . Our aim was to examine the nature , frequency and potential severity of prescribing errors in UK mental health units in a prospect i ve , 1 week survey of errors detected by pharmacy staff in nine NHS trusts . Pharmacists checked 22036 prescription items . In total , 523 errors meeting the study definition were detected ( 2.4 % of prescription items checked ) . Prescription writing errors ( 77.4 % ) were most common , while decision-making errors accounted for 22.6 % of errors . In 280 ( 53.5 % ) cases the prescribed drug had been administered before the error was detected . Most errors were of doubtful or minor importance but 22 ( 4.3 % ) were deemed likely to result in serious adverse effects or death . The error detection rate varied fourfold between trusts . Prescribing errors are fairly common in psychiatry . A small proportion of errors have the potential for serious harm . Pharmacy staff have an important role to play in their management Background Drug prescribing errors are frequent in the hospital setting and pharmacists play an important role in detection of these errors . The objectives of this study are ( 1 ) to describe the drug prescribing errors rate during the patient 's stay , ( 2 ) to find which characteristics for a prescribing error are the most predictive of their reproduction the next day despite pharmacist 's alert ( i.e. override the alert ) . Methods We prospect ively collected all medication order lines and prescribing errors during 18 days in 7 medical wards ' using computerized physician order entry . We described and modelled the errors rate according to the chronology of hospital stay . We performed a classification and regression tree analysis to find which characteristics of alerts were predictive of their overriding ( i.e. prescribing error repeated ) . Results 12 533 order lines were review ed , 117 errors ( errors rate 0.9 % ) were observed and 51 % of these errors occurred on the first day of the hospital stay . The risk of a prescribing error decreased over time . 52 % of the alerts were overridden ( i.e error uncorrected by prescribers on the following day . Drug omissions were the most frequently taken into account by prescribers . The classification and regression tree analysis showed that overriding pharmacist 's alerts is first related to the ward of the prescriber and then to either Anatomical Therapeutic Chemical class of the drug or the type of error . Conclusions Since 51 % of prescribing errors occurred on the first day of stay , pharmacist should concentrate his analysis of drug prescriptions on this day . The difference of overriding behavior between wards and according drug Anatomical Therapeutic Chemical class or type of error could also guide the validation tasks and programming of electronic alerts CONTEXT Pharmacist review of medication orders in the intensive care unit ( ICU ) has been shown to prevent errors , and pharmacist consultation has reduced drug costs . However , whether pharmacist participation in the ICU at the time of drug prescribing reduces adverse events has not been studied . OBJECTIVE To measure the effect of pharmacist participation on medical rounds in the ICU on the rate of preventable adverse drug events ( ADEs ) caused by ordering errors . DESIGN Before-after comparison between phase 1 ( baseline ) and phase 2 ( after intervention implemented ) and phase 2 comparison with a control unit that did not receive the intervention . SETTING A medical ICU ( study unit ) and a coronary care unit ( control unit ) in a large urban teaching hospital . PATIENTS Seventy-five patients r and omly selected from each of 3 groups : all admissions to the study unit from February 1 , 1993 , through July 31 , 1993 ( baseline ) and all admissions to the study unit ( postintervention ) and control unit from October 1 , 1994 , through July 7 , 1995 . In addition , 50 patients were selected at r and om from the control unit during the baseline period . INTERVENTION A senior pharmacist made rounds with the ICU team and remained in the ICU for consultation in the morning , and was available on call throughout the day . MAIN OUTCOME MEASURES Preventable ADEs due to ordering ( prescribing ) errors and the number , type , and acceptance of interventions made by the pharmacist . Preventable ADEs were identified by review of medical records of the r and omly selected patients during both preintervention and postintervention phases . Pharmacists recorded all recommendations , which were then analyzed by type and acceptance . RESULTS The rate of preventable ordering ADEs decreased by 66 % from 10.4 per 1000 patient-days ( 95 % confidence interval [ CI ] , 7 - 14 ) before the intervention to 3.5 ( 95 % CI , 1 - 5 ; P<.001 ) after the intervention . In the control unit , the rate was essentially unchanged during the same time periods : 10.9 ( 95 % CI , 6 - 16 ) and 12.4 ( 95 % CI , 8 - 17 ) per 1000 patient-days . The pharmacist made 366 recommendations related to drug ordering , of which 362 ( 99 % ) were accepted by physicians . CONCLUSIONS The presence of a pharmacist on rounds as a full member of the patient care team in a medical ICU was associated with a substantially lower rate of ADEs caused by prescribing errors . Nearly all the changes were readily accepted by physicians OBJECTIVE To investigate the frequency , type , and consequences of medication errors in more stages of the medication process , including discharge summaries . DESIGN A cross-sectional study using three methods to detect errors in the medication process : direct observations , unannounced control visits , and chart review s. With the exception of errors in discharge summaries all potential medication error consequences were evaluated by physicians and pharmacists . SETTING A r and omly selected medical and surgical department at Aarhus University Hospital , Denmark . STUDY PARTICIPANTS Eligible in-hospital patients aged 18 or over ( n = 64 ) , physicians prescribing drugs and nurses dispensing and administering drugs . MAIN OUTCOME MEASURES Frequency , type , and potential clinical consequences of all detected errors compared with the total number of opportunities for error . RESULTS We detected a total of 1065 errors in 2467 opportunities for errors ( 43 % ) . In worst case scenario 20 - 30 % of all evaluated medication errors were assessed as potential adverse drug events . In each stage the frequency of medication errors were-ordering : 167/433 ( 39 % ) , transcription : 310/558 ( 56 % ) , dispensing : 22/538 ( 4 % ) , administration : 166/412 ( 41 % ) , and finally discharge summaries : 401/526 ( 76 % ) . The most common types of error throughout the medication process were : lack of drug form , unordered drug , omission of drug/dose , and lack of identity control . CONCLUSION There is a need for quality improvement , as almost 50 % of all errors in doses and prescriptions in the medication process were caused by missing actions . We assume that the number of errors could be reduced by simple changes of existing procedures or by implementing automated technologies in the medication process Objective : To investigate the prevalence of prescribing errors identified by pharmacists in hospital in patients and the factors influencing error identification rates by pharmacists throughout hospital admission . Setting : 880-bed university teaching hospital in North-west Engl and . Methods : Data about prescribing errors identified by pharmacists ( median : 9 ( range 4–17 ) collecting data per day ) when conducting routine work were prospect ively recorded on 38 r and omly selected days over 18 months . Main outcome measures : Proportion of new medication orders in which an error was identified ; predictors of error identification rate , adjusted for workload and seniority of pharmacist , day of week , type of ward or stage of patient admission . Results : 33,012 new medication orders were review ed for 5,199 patients ; 3,455 errors ( in 10.5 % of orders ) were identified for 2,040 patients ( 39.2 % ; median 1 , range 1–12 ) . Most were problem orders ( 1,456 , 42.1 % ) or potentially significant errors ( 1,748 , 50.6 % ) ; 197 ( 5.7 % ) were potentially serious ; 1.6 % ( n = 54 ) were potentially severe or fatal . Errors were 41 % ( CI : 28–56 % ) more likely to be identified at patient ’s admission than at other times , independent of confounders . Workload was the strongest predictor of error identification rates , with 40 % ( 33–46 % ) less errors identified on the busiest days than at other times . Errors identified fell by 1.9 % ( 1.5–2.3 % ) for every additional chart checked , independent of confounders . Conclusions : Pharmacists routinely identify errors but increasing workload may reduce identification rates . Where re sources are limited , they may be better spent on identifying and addressing errors immediately after admission to hospital Background : Medication errors ( MEs ) affect patient safety to a significant extent . Because these errors can lead to preventable adverse drug events ( pADEs ) , it is important to know what type of ME is the most prevalent cause of these pADEs . This study determined the impact of the various types of prescribing ( administrative , dosing and therapeutic ) and transcribing errors on pADEs in hospitalised patients . Methods : During a 5-month period , data for patients admitted to a total of five internal medicine wards of one university and one teaching hospital in The Netherl and s were prospect ively collected by chart review . In each hospital , MEs were detected and classified by the same pharmacist , using the classification scheme for MEs developed by The Netherl and s Association of Hospital Pharmacists . The primary outcome measure was the prevalence of pADEs during hospital stay . In consensus meetings , five pharmacists assessed the causal relationship between MEs and pADEs . The association between type of ME and pADEs was determined by a multivariate regression analysis taking into account potential confounders . Results : The study included 592 hospital admissions with 7286 medication orders ( MOs ) , of which 60 % contained at least one prescribing or transcribing error . 1.4 % of all MOs led to pADEs , concerning 14.8 % of all admitted patients . The total number of pADEs was 103 , and in 92 of these cases patients experienced temporary harm , in eight cases hospital admission was prolongued , two cases were life-threatening , and one was fatal . Therapeutic errors were most strongly associated with pADEs ( OR 1.98 ; 95 % CI 1.53 to 2.56 ) . Conclusions : Although many prescribing and transcribing errors occur in the process of medication use of hospitalised patients , a minority lead to pADEs . In particular , therapeutic errors are the cause of these pADEs and are therefore clinical ly relevant . Intervention and prevention programmes should primarily focus on this type of medication error Background : The impact of pharmacy residents ' interventions on medical rounds has not been well evaluated . Objective : To assess the impact of a resident 's interventions on hospital length of stay , describe the types of interventions , and assess drug-related cost savings . Methods : Using a matched control design , we conducted an evaluative study of adults admitted to a general internal medicine unit over one month . The study group consisted of patients admitted to the service of a medical team that included a pharmacy resident and medical residents . The pharmacy resident prospect ively collected data on patient demographics and interventions made during patient admission and follow-up rounds . The control group consisted of patients admitted to the service of a team consisting of medical residents only , over the same period . The medical records of the control group were retrospectively evaluated for potential interventions . Results : Forty patients were enrolled in each group ( aged 63 ± 17 y , mean ± SD ) . In the study group , 250 of 271 interventions were accepted and fulfilled . In the control group , 321 potential interventions were identified . The mean length of stay of the study group was significantly lower than that of the control group ( 7.9 ± 7.2 days vs 10.9 ± 7.9 days , respectively ; p = 0.008 ) . In the study group and the control group , the total interventions were related to prescribing errors ( 51.3 % vs 45.4 % ) , preventable adverse drug events ( 32.9 % vs 42.3 % ) , patient monitoring ( 14 % vs 7 % ) , and drug interactions ( 1.8 % vs 5.3 % ) . In the study group , the net drug-related cost savings totaled $ 2087 . Conclusions : Our study demonstrates the positive impact of a pharmacy resident on reducing the hospital length of stay and producing drug-related cost savings . Most interventions prevented adverse drug events and prescribing errors Abstract The objective was to assess the incidence and consequences of medication errors , highlight sources of recurrent error and institute changes in practice to prevent their recurrence . Utilising a continuous quality improvement approach , a 2-year prospect i ve cohort study was undertaken using an adverse incident reporting scheme . A multidisciplinary committee analysed medication error reports , classifying them according to type ( prescription , supply or administration ) , severity ( serious or not serious ) and clinical outcome . Changes in policy and practice were implemented to reduce the frequency of errors . There were 441 reported medication errors in the study period , during which 682 patients were admitted for 5315 inpatient days . Errors were more seven times likely to occur in the intensive care setting . Doctors accounted for 72 % of errors and prescription errors doubled when new doctors joined the rotation . Most errors ( 68 % ) were detected prior to drug administration . Twenty-four serious medication errors were not detected in advance , but only 4 had overt clinical consequences . Excluding prevented errors and appropriate deviations from prescribed therapy , there were 117 actual medication errors ( 1/5.8 admissions , or 1/45 inpatient days ) . During the 2nd year of the scheme , the incidence of all reported errors , administration errors and serious errors fell , but the prescription error rate remained constant . Conclusions Medication errors occurred commonly in this study , but adverse consequences were rare . The non-punitive , multidisciplinary approach to medication errors utilised in this study increased staff vigilance , highlighted sources of recurrent error , and led to changes in drug policies and staff training , which result ed in improved patient safety and quality of care OBJECTIVE Medication errors are a common cause of iatrogenic morbidity and mortality . The incidence of medication errors in pediatric emergency departments ( EDs ) has not been described . The objective of this study was to describe the incidence and type of drug errors in a pediatric ED and determine factors associated with risk of errors . METHODS A retrospective cohort study was conducted of the charts of 1532 children who were treated in the ED of a pediatric tertiary care hospital during 12 r and omly selected days from the summer of 2000 . Two pediatricians , blinded to other study variables , independently decided whether a medication error occurred and ranked it according to a severity score . Disagreement was resolved by consensus . RESULTS Prescribing errors were identified in 10.1 % of the charts . The following variables were associated in univariate analysis with an increased proportion of errors : patients seen between 4 AM and 8 AM ( odds ratio [ OR ] : 2.45 ; 95 % confidence interval [ CI ] : 1.10 - 5.50 ) , patients with severe disease ( OR : 2.53 ; 95 % CI : 1.18 - 5.41 ) , medication ordered by a trainee ( OR : 1.48 ; 95 % CI : 1.03 - 2.11 ) , and patients seen during weekends ( OR : 1.48 ; 95 % CI : 1.04 - 2.11 ) . Among trainees , there was a higher rate of errors at the beginning of the academic year ( OR : 1.67 ; 95 % CI : 1.06 - 2.64 ) . Logistic regression revealed increased risk for errors when a medication was ordered by a trainee ( OR : 1.64 ; 95 % CI : 1.06 - 2.52 ) and in seriously ill patients ( OR : 1.55 ; 95 % CI : 1.06 - 2.26 ) . CONCLUSIONS In the pediatric ED , trainees are more likely to commit prescribing errors , and the most seriously ill patients are more likely to be subjected to prescribing errors PURPOSE The interrater agreement for and reliability of the National Coordinating Council for Medication Error Reporting and Prevention ( NCC MERP ) index for categorizing medication errors were determined . METHODS A letter was sent by the U.S. Pharmacopeia to all 550 contacts in the MEDMARX system user data base . Participants were asked to categorize 27 medication scenarios using the NCC MERP index and were r and omly assigned to one of three tools ( the index alone , a paper-based algorithm , or a computer-based algorithm ) to assist in categorization . Because the NCC MERP index accounts for harm and cost , and because categories could be interpreted as substantially similar , study results were analyzed after the nine error categories were collapsed to six . The interrater agreement was measured using Cohen 's kappa value . RESULTS Of 119 positive responses , 101 completed surveys were returned for a response rate of 85 % . There were no significant differences in baseline demographics among the three groups . The overall interrater agreement for the participants , regardless of group assignment , was substantial at 0.61 ( 95 % confidence interval [ CI ] , 0.41 - 0.81 ) . There was no difference among the kappa values of the three study groups and the tools used to aid in medication error classification . When the index was condensed from nine categories to six , the interrater agreement increased with a kappa value of 0.74 ( 95 % CI , 0.56 - 0.90 ) . CONCLUSION Overall interrater agreement for the NCC MERP index for categorizing medication errors was substantial . The tool provided to assist with categorization did not influence overall categorization . Further refining of the scale could improve the usefulness and validity of medication error categorization Objective : To evaluate the incidence and preventability of adverse drug events ( ADEs ) and to determine the yield of several strategies for identifying them . Design : Prospect i ve cohort study . Setting : Seven units , including two medical , two surgical , and two obstetric general care units and a coronary intensive care unit in an urban tertiary care hospital . Patients : All patients on these units over a 37-day period ( 2,967 patient-days ) . Interventions : None . Methods : Events were identified in three ways : 1 ) logs were placed on each unit and satellite pharmacy for nurses and pharmacists to record incidents ; 2 ) a research nurse solicited reports of incidents twice daily on each unit ; and 3 ) the nurse review ed all charts at least daily . Incidents were classified by two independent review ers as ADEs or potential ADEs . Results : The rate of drug-related incidents was 73 in 2,967 patient-days ; 27 incidents were judged ADEs , 34 potential ADEs , and 12 problem orders . Fifty different drugs were involved . Physicians were primarily responsible for 72 % of the incidents , with the remainder divided evenly between nursing , pharmacy , and clerical personnel . Of the 27 ADEs , five were life-threatening , nine were serious , and 13 were significant . Fifteen ( 56 % ) of the 27 were judged definitely or probably preventable . Incidents were discovered about equally often from the logs and by chart review . However , when the incidents in which an ADE was present were compared with the remainder of incidents , the authors found that 67 % ( 18 of 27 ) of the ADEs were identified only by chart review ( p<0.001 ) , and physicians were more often judged responsible than other personnel ( p<0.001 ) . Conclusions : The authors conclude that ADEs are not infrequent , often preventable , and usually caused by physician decisions . In this study , solicited reporting by nurses and pharmacists was inferior to chart review for identifying ADEs , but was effective for identifying potential ADEs . Optimal prevention strategies should cover many types of drugs and target physicians ’ ordering practice Background : It has been estimated that 1–2 % of US in patients are harmed by medication errors , the majority of which are errors in prescribing . The UK Department of Health has recommended that serious errors in the use of prescribed drugs should be reduced by 40 % by 2005 ; however , little is known about the current incidence of prescribing errors in the UK . This pilot study sought to investigate their incidence in one UK hospital . Methods : Pharmacists prospect ively recorded details of all prescribing errors identified in non-obstetric in patients during a 4 week period . The number of medication orders written was estimated from a 1 in 5 sample of in patients . Potential clinical significance was assessed by a pharmacist and a clinical pharmacologist . Results : About 36 200 medication orders were written during the study period , and a prescribing error was identified in 1.5 % ( 95 % confidence interval ( CI ) 1.4 to 1.6 ) . A potentially serious error occurred in 0.4 % ( 95 % CI 0.3 to 0.5 ) . Most of the errors ( 54 % ) were associated with choice of dose . Error rates were significantly different for different stages of patient stay ( p<0.0001 ) with a higher error rate for medication orders written during the inpatient stay than for those written on admission or discharge . While the majority of all errors ( 61 % ) originated in medication order writing , most serious errors ( 58 % ) originated in the prescribing decision . Conclusions : There were about 135 prescribing errors identified each week , of which 34 were potentially serious . Knowing where and when errors are most likely to occur will be helpful in design ing initiatives to reduce them . The methods developed could be used to evaluate such initiatives The purpose of this study was to record prospect ively the frequency of and potential harm caused by errant medication orders at two large pediatric hospitals . The objective of the study was to assess the impact of pharmacist intervention in preventing potential harm . The study was conducted during a 6-month period . A total of 281 and 198 errors were detected at the institutions . The overall error rates for the two hospitals were 1.35 and 1.77 per 100-patient days , and 4.9 and 4.5 per 1,000 medication orders , respectively . Pediatric patients aged 2 years and less and pediatric intensive care unit patients received the greatest proportion of errant orders . Neonatal patients received the lowest rate of errant orders . The most common type of error was incorrect dosage , and the most prevalent type of error was overdosage . Antibiotics was the class of drugs for which errant orders were most common . Orders for theophylline , analgesics , and fluid and electrolytes , including hyperalimentation , were also frequently in error . In general , the error rate was greatest among physicians with the least training , but no physician group was error free . Involving pharmacists in review ing drug orders significantly reduced the potential harm result ing from errant medication orders |
981 | 22,028,824 | The meta- analysis of published data did not show an overall association between any of the tested LEPR variants and overweight .
However , the choice of a BMI cut-off value to distinguish cases from controls was crucial to explain heterogeneity in Q223R .
Differences in allele frequencies across ethnic groups are compatible with natural selection of derived alleles in Q223R and K109R and of the ancient allele in K656N in Asians .
In CoLaus , the rs10128072 , rs3790438 and rs3790437 variants showed interaction with sex for their association with overweight , waist circumference and fat mass in linear regressions .
Conclusions Our systematic review and analysis of primary data from the CoLaus study did not show an overall association between LEPR SNPs and overweight . | Background Three non-synonymous single nucleotide polymorphisms ( Q223R , K109R and K656N ) of the leptin receptor gene ( LEPR ) have been tested for association with obesity-related outcomes in multiple studies , showing inconclusive results .
We performed a systematic review and meta- analysis on the association of the three LEPR variants with BMI . | Obesity has a heritable component ; however , the heterogeneity of obesity complicates dissection of its genetic background . In this study , we therefore focused on eating patterns as specific traits within obesity . These traits have a heritable component ; genes associated with a specific eating pattern have not yet been reported at the population level . In this study , we determined whether genetic variations in cholecystokinin ( CCK ) and leptin genes underlie specific eating patterns . We selected obese individuals showing extreme snacking behavior or use of excessive portion sizes from a large population -based sample ( n = 17,357 ) from the Prospect -EPIC ( European Prospect i ve Study into Cancer and Nutrition ) study . Using allele-specific PCRs , we tested several single nucleotide polymorphisms in the c and i date genes and performed haplotype analysis . Obese carriers of common allelic variations in leptin or the leptin receptor gene had an increased risk to display extreme snacking behavior . In contrast , obese carriers of common allelic variations in CCK had an increased risk to eating increased meal sizes . In conclusion , we identified common allelic variants specifically associated with distinctly different eating patterns , namely extreme snacking behavior or excessive portion size Recent animal studies indicate that leptin is involved in the regulation of blood pressure through the leptin receptor . Therefore , 51-yr-old men ( N = 284 ) were selected ; and anthropometric , endocrine , metabolic , and hemodynamic variables were examined in relation to polymorphisms of the leptin receptor gene ( LEPR ) , by restriction fragment length polymorphism technique . Three polymorphisms were examined : Lys109Arg in exon 4 , Gln223Arg in exon 6 , and Lys656Asn in exon 14 . In comparison with Lys109 homozygotes , Arg109 homozygotes ( 9 % ) showed lower body mass index ( BMI ) and abdominal sagittal diameter , as well as lower systolic ( 10.0 mm Hg ) and diastolic ( 7.8 mm Hg ) blood pressure . Additionally , Arg223 homozygotes ( 26.8 % ) showed lower blood pressure ( 7.6/5.7 mm Hg ) than Gln223 homozygotes . These lower blood pressure levels were independent of other variables . No differences were found with the Lys656Asn polymorphism . Measurements of body fat mass correlated with leptin concentration in Lys109 homozygotes and in Lys109 heterozygotes but not in Arg109 homozygotes . Blood pressure correlated with leptin only in men carrying the wild-type allele Lys109 . With both elevated BMI and leptin , Lys109 homozygotes had higher blood pressure than the Arg109 homozygous men ( 12.4/6.9 mm Hg ) . Men with blood pressure > or = 140/90 mm Hg had , in comparison with normotensive men , increased BMI and leptin levels , and Lys109 homozygotes were significantly more prevalent . These results suggest that leptin is associated with blood pressure regulation in men through the leptin receptor . When BMI and leptin are elevated , increased blood pressure is found only with the most prevalent LEPR genotype at codons 109 and 223 , whereas variants of this receptor seem to protect from hypertension . This might explain why not all obese men are hypertensive We performed extensive and realistic simulations of the colonization process of Europe by Neolithic farmers , as well as their potential admixture and competition with local Palaeolithic hunter – gatherers . We find that minute amounts of gene flow between Palaeolithic and Neolithic population s should lead to a massive Palaeolithic contribution to the current gene pool of Europeans . This large Palaeolithic contribution is not expected under the demic diffusion ( DD ) model , which postulates that agriculture diffused over Europe by a massive migration of individuals from the Near East . However , genetic evidence in favour of this model mainly consisted in the observation of allele frequency clines over Europe , which are shown here to be equally probable under a pure DD or a pure acculturation model . The examination of the consequence of range expansions on single nucleotide polymorphism ( SNP ) diversity reveals that an ascertainment bias consisting of selecting SNPs with high frequencies will promote the observation of genetic clines ( which are not expected for r and om SNPs ) and will lead to multimodal mismatch distributions . We conclude that the different patterns of molecular diversity observed for Y chromosome and mitochondrial DNA can be at least partly owing to an ascertainment bias when selecting Y chromosome SNPs for study ing European population |
982 | 25,883,789 | La plupart des essais traitant de prévention des néphropathies secondaire aux PCI ont été effectués en context e d’administration artérielle , comme par cathétérisme cardiaque , et non d’administration veineuse , comme par tomodensitométrie .
Les conclusions secondaires se rapportent à la sécurité et font part , entre autres , d’une comparaison des effets indésirables de l’administration orale d’eau salée et de l’administration intraveineuse de solution saline isotonique .
Discussion Les résultats de cet essai pilote fourniront de l’information cruciale pour la planification de l’essai définitif visant à tester l’efficacité des voies d’administration des traitements de prévention d’IRA après les tomodensitométries avec agent de contraste | Background Although intravenous saline is the accepted prophylactic measure for the prevention of contrast- induced acute kidney injury , the oral route could offer an equivalent , practical , and cost saving approach .
A systematic review of r and omized trials that compared oral versus intravenous volume expansion for the prevention of radiocontrast-induced nephropathy in patients receiving arterial contrast reported no significant difference in the risk of contrast induced acute kidney injury between the oral and intravenous arms .
Most trials for contrast nephropathy prevention have been in the setting of arterial contrast such as with cardiac catheterization , and not with venous contrast , such as computed tomography .
The aim of this paper is to describe the protocol of a pilot trial comparing the effect of oral salt and water versus intravenous saline on the prevention of Acute Kidney Injury following contrast-enhanced computed tomography .
Trial registration The trial is registered at the US National Institutes of Health ( Clinical Trials.gov ) # NCT02084771.Abrégé Context eL’administration prophylactique de solution saline par voie intraveineuse est utilisée pour la prévention de l’insuffisance rénale aiguë ( IRA ) secondaire aux produits de contraste iodés ( PCI ) .
Cependant , une administration par voie orale pourrait être un traitement alternatif équivalent , pratique et économique . | A reported 12 % incidence of acute renal failure after angiography prompted this prospect i ve study to substantiate or repudiate this seemingly excessive rate . In 537 consecutive patients undergoing cerebral , abdominal , or peripheral angiography , there was no instance of renal failure following the procedure . The results of this study indicate that when adequate hydration is maintained , angiography does not pose a " significant hazard " of renal failure as previously reported , even in patients with underlying medical problems BACKGROUND AND OBJECTIVES Most studies of contrast-induced acute kidney injury ( CIAKI ) have focused on patients undergoing angiographic procedures . The incidence and outcomes of CIAKI in patients undergoing nonemergent , contrast-enhanced computed tomography in the inpatient and outpatient setting were assessed . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Patients with estimated glomerular filtration rates ( GFRs ) < 60 ml/min per 1.73 m(2 ) undergoing nonemergent computed tomography with intravenous iodinated radiocontrast at an academic VA Medical Center were prospect ively identified . Serum creatinine was assessed 48 to 96 h postprocedure to quantify the incidence of CIAKI , and the need for postprocedure dialysis , hospital admission , and 30-d mortality was tracked to examine the associations of CIAKI with these medical outcomes . RESULTS A total of 421 patients with a median estimated GFR of 53 ml/min per 1.73 m(2 ) were enrolled . Overall , 6.5 % of patients developed an increase in serum creatinine > or=25 % , and 3.5 % demonstrated a rise in serum creatinine > or=0.5 mg/dl . Although only 6 % of out patients received preprocedure and postprocedure intravenous fluid , < 1 % of out patients with estimated GFRs > 45 ml/min per 1.73 m(2 ) manifested an increase in serum creatinine > or=0.5 mg/dl . None of the study participants required postprocedure dialysis . Forty-six patients ( 10.9 % ) were hospitalized and 10 ( 2.4 % ) died by 30-d follow-up ; however , CIAKI was not associated with these outcomes . CONCLUSIONS Clinical ly significant CIAKI following nonemergent computed tomography is uncommon among out patients with mild baseline kidney disease . These findings have important implication s for providers ordering and performing computed tomography and for future clinical trials of CIAKI BACKGROUND Contrast-induced nephropathy ( CIN ) is a serious complication of percutenous coronary interventions ( PCI ) . Proper hydration reduces the risk of PCI . Wheter oral hydration is as effective as intravenous one has not been well established . AIM To determine the effects of oral hydration with mineral water versus intravenous hydration with isotonic solution ( 0.9 % NaCl ) on renal function in diabetic patients undergoing coronary angiography and angioplasty . METHODS The study included 102 patients ( age 67 ± 7.8 years , 44 female/58 male ) . Eligible patients ( group 1 - 52 pts ) were hydrated intravenously ( 1 mL/kg/h ) 6 hours before and during 12 hours following PCI with isotonic solution ( 0.9 % NaCl ) . Fifty patients ( group 2 ) were r and omised to receive oral mineral water ( 1 mL/kg/h ) 6 - 12 hours before and during 12 hours following angiography or angioplasty . All patients during the procedure received contrast medium ioversol . Primary endpoint of the study was the evaluation of renal function before and 72 hours after contrast medium administration . RESULTS Baseline creatinine clearance was 70.3 ± 21.22 mL/min in group 1 and 78.69 ± 19.92 mL/min in group 2 ( NS ) . The mean volume of contrast medium was 101.1 ± 36.7 mL in group 1 and 110.4 ± 45.3 mL in group 2 ( NS ) . At 72 hours after the procedure , creatinine clearance was 65.3 ± 23.39 mL/min in group 1 and 73.5 ± 21.94 mL/min in group 2 ( NS ) . CONCLUSIONS Our study demonstrates that the oral hydration with mineral water and intravenous hydration with 0.9 % NaCl have similar effects on renal function in diabetic patients undergoing coronary angiography and angioplasty BACKGROUND Contrast nephropathy ( CN ) is a common cause of renal dysfunction that may be prevented by saline hydration and by drugs such as theophylline or furosemide . Whether oral saline hydration is as efficient as intravenous saline hydration is unknown . The preventive efficacy of theophylline and furosemide for CN remains controversial . The purpose of the current study was to evaluate the efficacy of oral saline hydration and of intravenous saline hydration plus theophylline or furosemide for the prevention of CN . METHODS We prospect ively studied 312 patients with chronic renal failure ( serum creatinine 201+/-81 micromol/l , Cockcroft clearance 37+/-12 ml/min/1.73 m(2 ) ) , who were undergoing various radiological procedures with a non-ionic , low osmolality contrast agent . Patients were r and omly assigned to four arms . In arm A , patients received 1 g/10 kg of body weight/day of sodium chloride per os for 2 days before the procedure . In arm B , patients received 0.9 % saline intravenously at a rate of 15 ml/kg for 6 h before the procedure . In arm C , patients received the same saline hydration as in arm B plus 5 mg/kg theophylline per os in one dose 1 h before the procedure . In arm D , patients received the same saline hydration as in arm B plus 3 mg/kg of furosemide intravenously just after the procedure . RESULTS Patients were well-matched with no significant differences at baseline in any measured parameters . Acute renal failure , defined as an increase in serum creatinine of 44 micromol/l ( 0.5 mg/dl ) , occurred in 27 out of 312 patients ( 8.7 % ) . There was no significant difference between the rate of renal failure in the different arms of the study : five out of 76 ( 6.6 % ) in arm A , four out of 77 ( 5.2 % ) in arm B , six out of 80 ( 7.5 % ) in arm C and 12 out of 79 ( 15.2 % ) in arm D. No patient had fluid overload or a significant increase in blood pressure in the 2 days following the radiological procedure . The independent predictors of CN were diabetes mellitus , high baseline serum creatinine and high systolic blood pressure . CONCLUSIONS Oral saline hydration was as efficient as intravenous saline hydration for the prevention of CN in patients with stage 3 renal diseases . Furosemide and theophylline were not protective CONTEXT Contrast-induced nephropathy remains a common complication of radiographic procedures . Pretreatment with sodium bicarbonate is more protective than sodium chloride in animal models of acute ischemic renal failure . Acute renal failure from both ischemia and contrast are postulated to occur from free-radical injury . However , no studies in humans or animals have evaluated the efficacy of sodium bicarbonate for prophylaxis against contrast-induced nephropathy . OBJECTIVE To examine the efficacy of sodium bicarbonate compared with sodium chloride for preventive hydration before and after radiographic contrast . DESIGN , SETTING , AND PATIENTS A prospect i ve , single-center , r and omized trial conducted from September 16 , 2002 , to June 17 , 2003 , of 119 patients with stable serum creatinine levels of at least 1.1 mg/dL ( > or = 97.2 micromol/L ) who were r and omized to receive a 154-mEq/L infusion of either sodium chloride ( n = 59 ) or sodium bicarbonate ( n = 60 ) before and after iopamidol administration ( 370 mg iodine/mL ) . Serum creatinine levels were measured at baseline and 1 and 2 days after contrast . INTERVENTIONS Patients received 154 mEq/L of either sodium chloride or sodium bicarbonate , as a bolus of 3 mL/kg per hour for 1 hour before iopamidol contrast , followed by an infusion of 1 mL/kg per hour for 6 hours after the procedure . MAIN OUTCOME MEASURE Contrast-induced nephropathy , defined as an increase of 25 % or more in serum creatinine within 2 days of contrast . RESULTS There were no significant group differences in age , sex , incidence of diabetes mellitus , ethnicity , or contrast volume . Baseline serum creatinine was slightly higher but not statistically different in patients receiving sodium bicarbonate treatment ( mean [ SD ] , 1.71 [ 0.42 ] mg/dL [ 151.2 [ 37.1 ] micromol/L ] for sodium chloride and 1.89 [ 0.69 ] mg/dL [ 167.1 [ 61.0 ] micromol/L ] for sodium bicarbonate ; P = .09 ) . The primary end point of contrast-induced nephropathy occurred in 8 patients ( 13.6 % ) infused with sodium chloride but in only 1 ( 1.7 % ) of those receiving sodium bicarbonate ( mean difference , 11.9 % ; 95 % confidence interval [ CI ] , 2.6%-21.2 % ; P = .02 ) . A follow-up registry of 191 consecutive patients receiving prophylactic sodium bicarbonate and meeting the same inclusion criteria as the study result ed in 3 cases of contrast-induced nephropathy ( 1.6 % ; 95 % CI , 0%-3.4 % ) . CONCLUSION Hydration with sodium bicarbonate before contrast exposure is more effective than hydration with sodium chloride for prophylaxis of contrast-induced renal failure OBJECTIVES The effects of an oral rehydration solution ( ORS ) on fatigue were studied in workers engaged in manual work during the summer . METHODS One hundred and fifty-three workers engaged in loading cargo onto aircraft at Tokyo International Airport who consented to participate in the study were the subjects . The study was carried out on two summer days with fine weather during the daytime shift . The subjects were r and omly divided into two groups : with one group restricted to ORS intake and the other group having free-choice of their favorite drink ( FAD ) in a r and omized crossover study . The subjects were asked about the amount of beverage that they consumed and the type of FAD that they chose on the days of the survey . The effects of the ORS and the FAD were compared using a visual analogue scale ( VAS ) to determine the degree of fatigue experienced immediately after completing work . RESULTS The average wet bulb globe temperature ( WBGT ) on the survey days was 30 degrees C. The beverage intake during work was 1,000 ml for most participants and the most commonly chosen types of FAD were tea and coffee . The fatigue VAS was significantly lower on the ORS intake days than on the FAD intake days ( 50.0 + /- 18.3 vs. 53.9 + /- 16.3 ) . CONCLUSIONS The results of this study suggest that the intake of ORS during outdoor work in a hot environment would be effective for preventing industrial accidents and heat stroke . It is important to select an appropriate drink to ensure adequate intake of water and electrolytes Despite myriad improvements in the care of hospitalized patients , a decline in renal function remains a common event . Renal function in 4,622 consecutive patients admitted to the medical and surgical services of an urban tertiary care hospital was followed up prospect ively from the time of admission . Some degree of renal insufficiency developed in 7.2 % of patients . Decreased renal perfusion , medications , surgery , and radiographic contrast media were the most common causes of hospital-acquired renal insufficiency ( HARI ) . The overall mortality rate was 19.4 % and was similar among patients for all causes of renal insufficiency , except sepsis . For patients with a greater than 3.0-mg/dL increase in serum creatinine level , the mortality rate was 37.8 % . As shown by previous investigators , age and preexisting renal insufficiency were risk factors for HARI . Women and blacks had less hospital-acquired renal failure . The increasing acuity of hospital admissions has been accompanied by a greater incidence of acute renal insufficiency in patients admitted to hospitals . There is a trend toward better survival in patients with a severe deterioration in renal function BACKGROUND AND OBJECTIVES No prospect i ve study has reported the incidence of contrast-induced nephropathy ( CIN ) or the associated morbidity and mortality after contrast-enhanced computed tomography ( CECT ) in the outpatient setting . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS We enrolled and followed a prospect i ve , consecutive cohort ( June 2007 through January 2009 ) of patients who received intravenous contrast for CECT in the emergency department of a large , academic , tertiary care center . Outcomes measured were as follows ( 1 ) CIN : An increase in serum creatinine > or = 0.5 mg/dl or > or = 25 % 2 to 7 d after contrast administration ; ( 2 ) severe renal failure : An increase in serum creatinine to > or = 3.0 mg/dl or the need for dialysis at 45 d ; and ( 3 ) renal failure as a contributing cause of death ( consensus of three independent physicians ) at 45 d. RESULTS The incidence of CIN was 11 % ( 70 of 633 ) among the 633 patients enrolled . Fifteen ( 2 % ) patients died within 45 d , including six deaths after study -defined CIN . Seven ( 1 % ) patients developed severe renal failure , six of whom had study -defined CIN . Of the six patients with CIN and severe renal failure , four died , and adjudicators determined that renal failure significantly contributed to all four deaths . Thus , CIN was associated with an increased risk for severe renal failure and death from renal failure . CONCLUSIONS CIN occurs in > 10 % of patients who undergo CECT in the outpatient setting and is associated with a significant risk for severe renal failure and death BACKGROUND AND OBJECTIVES The relationship of contrast-induced nephropathy ( CIN ) to long-term adverse events ( AEs ) is controversial . Although an association with AEs has been previously reported , it is unclear whether CIN is causally related to these AEs . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS We obtained long-term ( > or = 1 yr ) follow-up on 294 patients who participated in a r and omized , double-blind comparison of two prevention strategies for CIN ( iopamidol versus iodixanol ) . A difference in the incidence of AEs between patients who had developed CIN and those who had not was performed using a chi(2 ) test and Poisson regression analysis . A similar statistical approach was used for the differences in AEs between those who received iopamidol or iodixanol . Multiple definitions of CIN were used to strengthen and vali date the results and conclusions . RESULTS The rate of long-term AEs was higher in individuals with CIN ( all definitions of CIN ) . After adjustment for baseline comorbidities and risk factors , the adjusted incidence rate ratio for AEs was twice as high in those with CIN . R and omization to iopamidol reduced both the incidence of CIN and AEs . CONCLUSIONS The parallel decrease in the incidence of CIN and AEs in one arm of this r and omized trial supports a causal role for CIN OBJECTIVES Contrast-enhanced computed tomography ( CECT ) of the pulmonary arteries ( CTPA ) has become the mainstay to evaluate patients with suspected pulmonary embolism ( PE ) and is one of the most common CECT imaging studies performed in the emergency department ( ED ) . While contrast-induced nephropathy ( CIN ) is a known complication , this risk is not well defined in the ED or other ambulatory setting . The aim of this study was to define the risk of CIN following CTPA . METHODS The authors enrolled and followed a prospect i ve , consecutive cohort ( June 2007 through January 2009 ) of patients who received intravenous ( IV ) contrast for CTPA in the ED of a large , academic tertiary care center . Study outcomes included 1 ) CIN defined as an increase in serum creatinine ( sCr ) of ≥ 0.5 mg/dL or ≥ 25 % , 2 to 7 days following contrast administration ; and 2 ) severe renal failure defined as an increase in sCr to ≥ 3.0 mg/dL or the need for dialysis within 45 days and /or renal failure as a contributing cause of death at 45 days , determined by the consensus of three independent physicians . RESULTS A total of 174 patients underwent CTPA , which demonstrated acute PE in 12 ( 7 % , 95 % confidence interval [ CI ] = 3 % to 12 % ) . Twenty-five patients developed CIN ( 14 % , 95 % CI = 10 % to 20 % ) including one with acute PE . The development of CIN after CTPA significantly increased the risk of the composite outcome of severe renal failure or death from renal failure within 45 days ( relative risk = 36 , 95 % CI = 3 to 384 ) . No severe adverse outcomes were directly attributable to complications of venous thromboembolism ( VTE ) or its treatment . CONCLUSIONS In this population , CIN was at least as common as the diagnosis of PE after CTPA ; the development of CIN was associated with an increased risk of severe renal failure and death within the subsequent 45 days . Clinicians should consider the risk of CIN associated with CTPA and discuss this risk with patients Water drinking activates the autonomic nervous system and induces acute hemodynamic changes . The actual stimulus for these effects is undetermined but might be related to either gastric distension or to osmotic factors . In the present study , we tested whether the cardiovascular responses to water drinking are related to water 's relative hypoosmolality . Therefore , we compared the cardiovascular effects of a water drink ( 7.5 ml/kg body wt ) with an identical volume of a physiological ( 0.9 % ) saline solution in nine healthy subjects ( 6 male , 3 female , aged 26 + /- 2 years ) , while continuously monitoring beat-to-beat blood pressure ( finger plethysmography ) , cardiac intervals ( electrocardiography ) , and cardiac output ( thoracic impedance ) . Total peripheral resistance was calculated as mean blood pressure/cardiac output . Cardiac interval variability ( high-frequency power ) was assessed by spectral analysis as an index of cardiac vagal tone . Baroreceptor sensitivity was evaluated using the sequence technique . Drinking water , but not saline , decreased heart rate ( P = 0.01 ) and increased total peripheral resistance ( P < 0.01 ) , high-frequency cardiac interval variability ( P = 0.03 ) , and baroreceptor sensitivity ( P = 0.01 ) . Neither water nor saline substantially increased blood pressure . These responses suggest that water drinking simultaneously increases sympathetic vasoconstrictor activity and cardiac vagal tone . That these effects were absent after drinking physiological saline indicate that the cardiovascular responses to water drinking are influenced by its hypoosmotic properties The plasma sodium concentration has a direct effect on blood pressure in addition to its effects on extracellular volume regulated through changes in the endothelium . The mechanism for elevated blood pressure seen with habitually increased salt intake is unclear , especially the effect of salt in a single meal on plasma sodium concentration and blood pressure . To resolve this we compared the effect of soup with or without 6 g of salt ( an amount similar to that in a single meal ) on the plasma sodium concentration and blood pressure in 10 normotensive volunteers using a r and omized , crossover design . The plasma sodium concentration was significantly increased by 3.13±0.75 mmol/l with salted compared with unsalted soup . Blood pressure increased in volunteers ingesting soup with added salt , and there was a significant positive correlation between plasma sodium concentration and systolic blood pressure . A 1-mmol/l increase in plasma sodium was associated with a 1.91-mm Hg increase in systolic blood pressure by linear regression . Thus , changes in plasma sodium concentration occur each time a meal containing salt is consumed . A potential mechanism for the changes in blood pressure seen with salt intake may be through its effects on plasma sodium concentration Presently , only hydration and N-acetylcysteine have been shown to be effective in decreasing the incidence of radiographic contrast-induced nephropathy . We investigated the role of N-acetylcysteine and various hydration protocol s in vascular surgery patients undergoing angiography . A single-center , r and omized , placebo-controlled trial was conducted in patients with stable , preexisting renal dysfunction undergoing elective , outpatient angiography . Patients were r and omized to outpatient oral hydration and N-acetylcysteine , inpatient hydration plus N-acetylcysteine , or our st and ard therapy of inpatient intravenous hydration alone . Two of twenty-eight ( 7 % ) patients who received outpatient oral hydration and N-acetylcysteine developed contrast-induced nephropathy , while two of 25 ( 8 % ) who recieved inpatient hydration plus N-acetylcysteine developed contrast-induced nephropathy and two of 25 ( 8 % ) who received st and ard therapy of inpatient intravenous hydration alone developed contrast-induced nephropathy . There was no statistical difference in incidence of contrast-induced nephropathy between the groups . No statistically significant independent risk factors were identified among the patients who developed contrast-induced nephropathy . N-Acetylcysteine did not confer additional benefit to patients treated with inpatient intravenous hydration . Outpatient oral hydration plus N-acetylcysteine was as effective at preventing contrast-induced nephropathy as inpatient therapies and avoided costly hospital admission BACKGROUND IV hydration before and after cardiac catheterization is effective in preventing contrast-associated renal dysfunction for patients with mild-to-moderate renal insufficiency , but necessitates overnight hospital admission . We tested an outpatient oral precatheterization hydration strategy in comparison with overnight IV hydration . METHODS We r and omized 36 patients with renal dysfunction ( serum creatinine > or = 1.4 mg/dL ) undergoing elective cardiac catheterization to receive either overnight IV hydration ( 0.45 normal saline solution at 75 mL/h for both 12 h precatheterization and postcatheterization ; n = 18 ) or an outpatient hydration protocol including precatheterization oral hydration ( 1,000 mL clear liquid over 10 h ) followed by 6 h of IV hydration ( 0.45 normal saline solution at 300 mL/h ) beginning just before contrast exposure . The predefined primary end point was the maximal change in creatinine up to 48 h after cardiac catheterization . RESULTS The inpatient and outpatient groups were well matched for baseline characteristics and contrast volume . By protocol design , the outpatient group received a greater volume of hydration , although the net volume changes were comparable in the two groups . The maximal changes in serum creatinine in the inpatient ( 0.21+/-0.38 mg/dL ; 95 % confidence interval [ CI ] , 0.02 to 0.39 mg/dL ) and outpatient groups ( 0.12+/-0.23 mg/dL ; 95 % CI , 0.01 to 0.24 mg/dL ) were comparable ( p = not significant ) . There were no instances of protocol intolerance . CONCLUSIONS A hydration strategy compatible with outpatient cardiac catheterization is comparable to precatheterization and postcatheterization IV hydration in preventing contrast-associated changes in serum creatinine . Hospital admission for IV hydration is unnecessary before elective cardiac catheterization in the setting of mild-to-moderate renal dysfunction Though simple and attractive , the role of hydration for the prophylaxis of contrast nephrotoxicity has not been definitively established . We prospect ively evaluated the role of deliberate saline hydration in patients undergoing nonemergency cardiac catheterization . Patients ( n = 53 ) were r and omized on the day prior to scheduled catheterization to one of two groups – group 1 ( n = 27 ) received normal saline for 24 h ( at a rate of 1 ml/kg/h ) beginning 12 h prior to scheduled catheterization , and group 2 ( n = 26 ) were allowed unrestricted oral fluids . Serum creatinine measured 24 and 48 h postcardiac catheterization was compared to the pre-r and omization baseline value . The mean baseline calculated creatinine clearance was 79.6 ± 31.9 ml/min and the mean baseline creatinine was 106 ± 28 µmol/l . An increase in serum creatinine by at least 44.2 µmol/l ( 0.5 mg/dl ) , within 48 h of contrast exposure , was considered to represent clinical ly significant acute renal insufficiency . Ten subjects ( 18.9 % ) developed acute renal insufficiency . The incidence of acute renal insufficiency was significantly lower in group 1 ( 1 out of 27 ) as compared to group 2 ( 9 out of 26 ; p = 0.005 for comparison between groups ; relative risk 0.11 , 95 % confidence interval 0.015 to 0.79 ) . Twenty-four hours after contrast exposure , the mean increase in creatinine was less in group 1 vs. group 2 ( 8 ± 11 vs. 20 ± 21 µmol/l , p = 0.02 ) . The increase in creatinine was not significantly different in group 1 vs. group 2 48 h after contrast exposure ( 12 ± 21 vs. 29 ± 40 µmol/l , p = 0.17 ) . Deliberate saline hydration decreases the incidence of contrast-related acute renal failure and the severity of contrast-induced renal dysfunction in patients undergoing non-emergency cardiac catheterization |
983 | 24,695,806 | There was no valid evidence of MT on improving dysfunction .
With regard to follow-up effects , there was not enough evidence of MT for neck pain .
This systematic review found moderate evidence of MT on improving pain in patients with neck pain compared with inactive therapies and limited evidence compared with traditional Chinese medicine .
There were no valid lines of evidence of MT on improving dysfunction . | To systematic ally evaluate the evidence of whether massage therapy ( MT ) is effective for neck pain . | OBJECTIVE To compare the effects of manual therapy and stretching exercise on neck pain and disability . DESIGN An examiner-blinded r and omized cross-over trial . PATIENTS A total of 125 women with non-specific neck pain . METHODS PATIENTS were r and omized into 2 groups . Group 1 received manual therapy twice weekly and Group 2 performed stretching exercises 5 times a week . After 4 weeks the treatments were changed . The follow-up times were after 4 and 12 weeks . Neck pain ( visual analogue scale ) and disability indices were measured . RESULTS Mean value ( st and ard deviation ) for neck pain was 50 mm ( 22 ) and 49 mm ( 19 ) at baseline in Group 1 and Group 2 , respectively , and decreased during the first 4 weeks by 26 mm ( 95 % Confidence Interval 20 - 33 ) and 19 mm ( 12 - 27 ) , respectively . There was no significant difference between groups . Neck and shoulder pain and disability index decreased significantly more in Group 1 after manual therapy ( p=0.01 ) as well as neck stiffness ( p=0.01 ) . CONCLUSION Both stretching exercise and manual therapy considerably decreased neck pain and disability in women with non-specific neck pain . The difference in effectiveness between the 2 treatments was minor . Low-cost stretching exercises can be recommended in the first instance as an appropriate therapy intervention to relieve pain , at least in the short-term OBJECTIVE This study evaluates the effectiveness of traditional bone setting ( TBS ) in chronic neck pain ( cNP ) compared with conventional physiotherapy ( PT ) and massage ( M ) . METHODS This was a r and omized clinical trial . Working-aged employed subjects with cNP ( n = 105 ; 37 men and 68 women ; mean age , 41.5 years ) were r and omized into TBS , PT , and M groups . Follow-up times were 1 , 6 , and 12 months after the treatments . Neck pain intensity ( visual analog scale ) , perceived disability ( Neck Disability Index [ NDI ] ) , and neck spine mobility measurements were used as outcomes . Global assessment was evaluated by the subjects ( scale from -1 to + 10 ) . Data were analyzed using time ( pre and post ) by group ( TBS , PT and M ) , 2- way analysis of variance for repeated measures . RESULTS Neck pain decreased and NDI scores improved in all groups 1 month after the treatment ( P < .001 ) . The improvement of NDI and persons ' satisfaction were significantly better after TBS . Neck spine mobility in rotation movements tended to improve significantly better and the frons-knee distance improved more after TBS . One year later , both NDI and neck pain were significantly better after TBS than in reference groups . A significant improvement was reported by 40 % to 45.5 % of subjects in the PT and M groups and by 68.6 % in the TBS group . Bone setters ' ability to communicate and to interact with patients was evaluated significantly higher . In the TBS group , the number of sick days was minimal as was the use of painkillers during 1-year follow-up compared to that in the reference groups . CONCLUSIONS Traditional bone setting , which is a soft manual mobilization technique focusing on the muscles , joints , and ligaments , appears to be effective in cNP . Two thirds of subjects experienced it as beneficial , and it seems to be able to improve disability and pain in patients with cNP . Subjective and partially objective benefits of TBS were found in those patients more than after other interventions , and the effects lasted at least for 1 year The existing review s of massage therapy ( MT ) research are either limited to infants , adults , or were conducted prior to the publication of the most recent studies using pediatric sample s. R and omized controlled trials ( RCTs ) of pediatric MT are review ed . A literature search yielded 24 RCTs of pediatric MT , defined as the manual manipulation of soft tissue intended to promote health and well-being in recipients between 2 and 19 years of age . Because RCTs of pediatric MT varied considerably in the amount and types of data reported , quantitative and narrative review methods were both used . Singledose and multiple-dose effects were examined separately . Among single-dose effects , significant reductions of state anxiety were observed at the first session ( g 1⁄4 0.59 , P < 0.05 ) and the last session ( g 1⁄4 1.10 , P < 0.01 ) of a course of treatment . Effects for salivary cortisol ( g 1⁄4 0.28 ) , negative mood ( g 1⁄4 0.52 ) and behavior ( g 1⁄4 0.37 ) were non-significant . Three of eleven multiple-dose effects were statistically significant . These were trait anxiety ( g 1⁄4 0.94 , P < 0.05 ) , muscle tone ( g 1⁄4 0.90 , P < 0.01 ) and arthritis pain ( g1⁄4 1.33 , P < 0.01 ) . Results of studies not permitting effect size calculation were judged to be generally consistent with quantitative results . MT benefits pediatric recipients , though not as universally as sometimes reported . Numerous weaknesses endemic to MT research ( e.g. low statistical power , frequent failure to report basic descriptive statistics ) are identified , and recommendations for future pediatric MT research are discussed Abstract Objectives : To compare the efficacy of acupuncture and conventional massage for the treatment of chronic neck pain . Design : Prospect i ve , r and omised , placebo controlled trial . Setting : Three outpatient departments in Germany . Participants : 177 patients aged 18–85 years with chronic neck pain . Interventions : Patients were r and omly allocated to five treatments over three weeks with acupuncture ( 56 ) , massage ( 60 ) , or “ sham ” laser acupuncture ( 61 ) . Main outcome measures : Primary outcome measure : maximum pain related to motion ( visual analogue scale ) irrespective of direction of movement one week after treatment . Secondary outcome measures : range of motion ( 3D ultrasound real time motion analyser ) , pain related to movement in six directions ( visual analogue scale ) , pressure pain threshold ( pressure algometer ) , changes of spontaneous pain , motion related pain , global complaints ( seven point scale ) , and quality of life ( SF-36 ) . Assessment s were performed before , during , and one week and three months after treatment . Patients ' beliefs in treatment were assessed . Results : One week after five treatments the acupuncture group showed a significantly greater improvement in motion related pain compared with massage ( difference 24.22 ( 95 % confidence interval 16.5 to 31.9 ) , P=0.0052 ) but not compared with sham laser ( 17.28 ( 10.0 to 24.6 ) , P=0.327 ) . Differences between acupuncture and massage or sham laser were greater in the subgroup who had had pain for longer than five years ( n=75 ) and in patients with myofascial pain syndrome ( n=129 ) . The acupuncture group had the best results in most secondary outcome measures . There were no differences in patients ' beliefs in treatment . Conclusions : Acupuncture is an effective short term treatment for patients with chronic neck pain , but there is only limited evidence for long term effects after five treatments . What is already known on this topic Acupuncture is a widespread complementary treatment Evidence from trials have given conflicting results on its use in the treatment of neck pain because of method ological shortcomings and because effects were compared either with alternative treatments or with different sham procedures imitating acupuncture , but not both What this study adds Compared with sham laser acupuncture and massage , needle acupuncture has beneficial effects on mobility and pain related to motion in patients with chronic neck pain Acupuncture was clearly more effective than massage , but differences were not always significant compared with sham laser acupuncture Acupuncture was the best treatment for patients with the myofascial syndrome and those who had had pain for longer than five Objectives Little is known about the effectiveness of therapeutic massage , one of the most popular complementary medical treatments for neck pain . A r and omized controlled trial was conducted to evaluate whether therapeutic massage is more beneficial than a self-care book for patients with chronic neck pain . Methods Sixty-four such patients were r and omized to receive up to 10 massages over 10 weeks or a self-care book . Follow-up telephone interviews after 4 , 10 , and 26 weeks assessed outcomes including dysfunction and symptoms . Log-binomial regression was used to assess whether there were differences in the percentages of participants with clinical ly meaningful improvements in dysfunction and symptoms ( ie , > 5-point improvement on the Neck Disability Index ; > 30 % improvement from baseline on the symptom bothersomeness scale ) at each time point . Results At 10 weeks , more participants r and omized to massage experienced clinical ly significant improvement on the Neck Disability Index [ 39 % vs. 14 % of book group ; relative risk (RR)=2.7 ; 95 % confidence interval ( CI ) , 0.99 - 7.5 ] and on the symptom bothersomeness scale ( 55 % vs. 25 % of book group ; RR=2.2 ; 95 % CI , 1.04 - 4.2 ) . After 26 weeks , massage group members tended to be more likely to report improved function ( RR=1.8 ; 95 % CI , 0.97 - 3.5 ) , but not symptom bothersomeness ( RR=1.1 ; 95 % CI , 0.6 - 2.0 ) . Mean differences between groups were strongest at 4 weeks and not evident by 26 weeks . No serious adverse experiences were reported . Conclusions This study suggests that massage is safe and may have clinical benefits for treating chronic neck pain at least in the short term . A larger trial is warranted to confirm these results Study Design . Population ‐based , cross‐sectional mailed survey . Objective . To determine the lifetime , period , and point prevalence of neck pain and its related disability among Saskatchewan adults and investigate the presence and strength of nonresponse bias . Summary of Background Data . In Europe , the life‐time and point prevalence of neck pain is almost as high as the prevalence of low back pain . Similarly , chronic neck pain is highly prevalent and a common source of disability in the working‐age population . However , no studies specifically have documented the prevalence of neck pain and its related disability in North America . Methods . The Saskatchewan Health and Back Pain Survey was mailed to 2184 r and omly selected Saskatchewan adults aged 20‐69 years . Fifty‐five percent of the study population participated . The presence of nonresponse bias was investigated through logistic regression and wave analysis . The Chronic Pain Question naire was used to classify the severity of chronic neck pain . Results . The age‐st and ardized lifetime prevalence of neck pain is 66.7 % ( 95 % confidence interval , 63.8‐69.5 ) , and the point prevalence is 22.2 % ( 95 % confidence interval , 19.7‐24.7 ) . The age‐st and ardized 6‐month prevalence of low‐intensity and low‐disability neck pain is 39.7 % ( 95 % confidence interval , 36.7‐42.7 ) , whereas it is 10.1 % ( 95 % confidence interval , 8.2‐11.9 ) for high‐intensity and low‐disability neck pain and 4.6 % ( 95 % confidence interval , 3.3‐5.8 ) for significantly disabling neck pain . The prevalence of low‐intensity and low‐disability neck pain decreases with age . More women experience high‐disability neck pain than men . Wave analysis suggests that the point prevalence and 6‐month prevalence of high‐intensity and low‐disability neck pain are overestimated in this survey . Conclusion . This cross‐sectional study shows that neck pain is highly prevalent in Saskatchewan and that it significantly disables 4.6 % ( 95 % confidence interval , 3.3‐5.8 ) of the adult population BACKGROUND Neck pain is one of the most common musculoskeletal ailments . The aim of this study was to evaluate the effectiveness and impact of therapeutic massage on the range of motion in patients with neck pain . MATERIAL AND METHODS The study involved 60 patients aged 37 - 82 years ( mean age : 62.8 ± 9.86 years ) treated for neck pain at the Rehabilitation Department of Zamość University of Management and Administration . The patients were divided into two groups : one ( 30 persons ) received kinesiotherapy and physiotherapy , and the other group ( 30 persons ) additionally received therapeutic massage . The effectiveness of rehabilitation was assessed with a Saunders digital inclinometer , the Neck Disability Index ( NDI ) and a Visual Analogue Scale ( VAS ) . RESULTS Both groups did not differ significantly in terms of NDI and VAS scores at baseline ( NDI : p = 0.56 , VAS : P = 0.231 ) and after rehabilitation ( NDI : p = 0.203 ; VAS : P = 0.401 ) . The NDI question naire and VAS revealed a significant pain reduction ( p < 0.001 ) , and improved performance and function ( p < 0.001 ) after rehabilitation in both groups . Patients who had received massage demonstrated a statistically significant improvement in the range of flexion ( p = 0.022 ) , lateral bend to the right ( p = 0.018 ) , and lateral bend to the left ( p = 0.003 ) . CONCLUSIONS 1 . Therapeutic massage increases ranges of motion . 2 . The effectiveness of therapeutic massage is comparable to the effectiveness of rehabilitation based only on physical therapy and kinesiotherapy Abstract The purpose of this pilot study was to examine the immediate effects of a manual therapy technique called Inhibitive Distraction ( ID ) on active range of motion ( AROM ) for cervical flexion in patients with neck pain with or without concomitant headache . A secondary objective of this study was to see whether patient subgroups could be identified who might benefit more from ID by study ing variables such as age , pain intensity , presence of headache , or pre-intervention AROM . We also looked at patients ' ability to identify pre- to post-intervention changes in their ability to actively move through a range of motion . Forty subjects ( mean age 34.7 years ; range 16–48 years ) referred to a physical therapy clinic due to discomfort in the neck region were r and omly assigned to an experimental and a control group . We used the CROM goniometer to measure pre- and post-intervention cervical flexion AROM in the sagittal plane within a single treatment session . The between-group difference in AROM increase was not statistically significant at P<0.05 with a mean post-intervention increase in ROM of 2.4 ° ( SD 6.2 ° ) for the experimental group and 1.2 ° ( SD 5.8 ° ) for the placebo group . We were also unable to identify potential subgroups more likely to respond to ID , although a trend emerged for greater improvement in chronic patients with headaches , lower pain levels , and less pre-intervention AROM . In the experimental group and in both groups combined , subjects noting increased AROM indeed had a significantly greater increase in AROM than those subjects not noting improvement . In conclusion , this study did not confirm immediate effects of ID on cervical flexion AROM but did provide indications for potential subgroups likely to benefit from this technique . Recommendations are provided with regard to future research and clinical use of the technique studied 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 . Background The purpose of this report is to provide a succinct but comprehensive summary of the scientific evidence regarding the effectiveness of manual treatment for the management of a variety of musculoskeletal and non-musculoskeletal conditions . Methods The conclusions are based on the results of systematic review s of r and omized clinical trials ( RCTs ) , widely accepted and primarily UK and United States evidence -based clinical guidelines , plus the results of all RCTs not yet included in the first three categories . The strength/ quality of the evidence regarding effectiveness was based on an adapted version of the grading system developed by the US Preventive Services Task Force and a study risk of bias assessment tool for the recent RCTs . Results By September 2009 , 26 categories of conditions were located containing RCT evidence for the use of manual therapy : 13 musculoskeletal conditions , four types of chronic headache and nine non-musculoskeletal conditions . We identified 49 recent relevant systematic review s and 16 evidence -based clinical guidelines plus an additional 46 RCTs not yet included in systematic review s and guidelines .Additionally , brief references are made to other effective non-pharmacological , non-invasive physical treatments . Conclusions Spinal manipulation/mobilization is effective in adults for : acute , subacute , and chronic low back pain ; migraine and cervicogenic headache ; cervicogenic dizziness ; manipulation/mobilization is effective for several extremity joint conditions ; and thoracic manipulation/mobilization is effective for acute/subacute neck pain . The evidence is inconclusive for cervical manipulation/mobilization alone for neck pain of any duration , and for manipulation/mobilization for mid back pain , sciatica , tension-type headache , coccydynia , temporom and ibular joint disorders , fibromyalgia , premenstrual syndrome , and pneumonia in older adults . Spinal manipulation is not effective for asthma and dysmenorrhea when compared to sham manipulation , or for Stage 1 hypertension when added to an antihypertensive diet . In children , the evidence is inconclusive regarding the effectiveness for otitis media and enuresis , and it is not effective for infantile colic and asthma when compared to sham manipulation . Massage is effective in adults for chronic low back pain and chronic neck pain . The evidence is inconclusive for knee osteoarthritis , fibromyalgia , myofascial pain syndrome , migraine headache , and premenstrual syndrome . In children , the evidence is inconclusive for asthma and infantile colic AIM The aim of this study was to compare the effects of acupuncture on active motion of the cervical spine in patients with chronic neck pain with those of " sham " laser acupuncture and massage . MATERIAL AND METHODS 177 patients with chronic neck pain were included in this prospect i ve , r and omized , placebo-controlled study . The patients were allocated by external r and omization to five treatments over three weeks with acupuncture , massage and " sham " laser acupuncture . The range of active motion was measured by means of a 3D ultrasound real time motion analyzer . RESULTS The analysis of cervical motion in three directions showed the largest increase in range of motion 14 days after acupuncture . Compared to massage , a significant improvement in total range of motion was seen in those patients treated by acupuncture immediately ( p = 0,03 ) and one week ( p = 0,03 ) weeks after therapy . There was no significant difference in those patients treated by sham laser acupuncture . CONCLUSION The results of the study indicate that acupuncture is superior to conventional massage for improving active range of motion in patients with chronic neck pain . Because of its positive effects , its acceptance among patients and the lack of severe side effects , acupuncture can be recommended for the treatment of chronic neck pain , although there was no significant difference in results between " sham " laser acupuncture and acupuncture OBJECTIVE The purpose of this study was to determine the feasibility of a trial comparing cervical spine mobilization and massage as adjuncts to usual physical therapy treatments ( superficial heat and head and neck posture education ) for chronic neck pain . Specific objectives were to assess procedures and recruitment strategies and estimate the variability of the Neck Disability Index ( NDI ) and visual analog scale ( VAS ) in a population of subjects with chronic nonspecific neck pain and calculate a sample size for a definitive trial . METHODS Subjects with nonspecific chronic neck pain ( ≥3 months ) were r and omized to receive either sedative massage or cervical spine joint mobilization in addition to postural education and home exercises . Neck Disability Index ( primary outcome ) and pain VAS scores were recorded for pretreatment , posttreatment , and change scores within each group to estimate effect size . Recruitment and follow-up success rates were tracked . RESULTS Sixty potential subjects were screened : 34 were eligible and 23 were enrolled . The primary reason for not participating was the unwillingness to commit to the treatment schedule . Twenty subjects completed all ( 12 ) treatments . Three subjects discontinued treatment because they become asymptomatic . Pre and post mean NDI and VAS scores for the group receiving joint mobilization were 13.54/5.64 and 40.91/16.54 , respectively . Pre and post mean NDI and VAS for the group receiving massage were 12.75/8.08 and 29.42/20.91 , respectively . Several problems were encountered , and possible solutions were identified . Recruitment difficulties required alteration of the recruitment strategy . CONCLUSION A full scale trial is feasible if appropriate changes are made in recruitment strategy including recruiting from a wider referral base , direct recruitment from the community , and /or exp and ing the study to multiple sites . A clinical trial will require 66 subjects per group to have a power of 80 % to detect a 2-point difference in NDI score . This sample size will also provide more than 80 % power to detect a 10-point difference in pain ( VAS ) between groups . Recruitment goals will be 76 per group to allow for dropouts BACKGROUND AND PURPOSE Myofascial trigger points ( TPs ) are found among patients who have neck and upper back pain . The purpose of this study was to determine the effectiveness of a home program of ischemic pressure followed by sustained stretching for the treatment of myofascial TPs . SUBJECTS Forty adults ( 17 male , 23 female ) , aged 23 to 58 years ( mean=30.6 , SD=9.3 ) , with one or more TPs in the neck or upper back participated in this study . METHODS Subjects were r and omly divided into 2 groups receiving a 5-day home program of either ischemic pressure followed by general sustained stretching of the neck and upper back musculature or a control treatment of active range of motion . Measurements were obtained before the subjects received the home program instruction and on the third day after they discontinued treatment . Trigger point sensitivity was measured with a pressure algometer as pressure pain threshold ( PPT ) . Average pain intensity for a 24-hour period was scored on a visual analog scale ( VAS ) . Subjects also reported the percentage of time in pain over a 24-hour period . A multivariate analysis of covariance , with the pretests as the covariates , was performed and followed by 3 analyses of covariance , 1 for each variable . RESULTS Differences were found between the treatment and control groups for VAS scores and PPT . No difference was found between the groups for percentage of time in pain . CONCLUSION AND DISCUSSION A home program , consisting of ischemic pressure and sustained stretching , was shown to be effective in reducing TP sensitivity and pain intensity in individuals with neck and upper back pain . The results of this study indicate that clinicians can treat myofascial TPs through monitoring of a home program of ischemic pressure and stretching |
984 | 27,660,931 | RESULTS Both " strong " and " conditional " recommendations are given for management of h and , hip , and knee OA and nonpharmacological , pharmacological , and surgical modalities of treatment are presented according to the different levels of agreement . | OBJECTIVE The objective of this consensus is to up date the recommendations for the treatment of h and , hip , and knee osteoarthritis ( OA ) by agreeing on key propositions relating to the management of h and , hip , and knee OA , by identifying and critically appraising research evidence for the effectiveness of the treatments and by generating recommendations based on a combination of the available evidence and expert opinion of 18 countries of America . | Background Total hip or knee replacement is highly successful when judged by prosthesis-related outcomes . However , some people experience long-term pain . Objectives To review published studies in representative population s with total hip or knee replacement for the treatment of osteoarthritis reporting proportions of people by pain intensity . Data sources MEDLINE and EMBASE data bases search ed to January 2011 with no language restrictions . Citations of key articles in ISI Web of Science and reference lists were checked . Study eligibility criteria , participants and interventions Prospect i ve studies of consecutive , unselected osteoarthritis patients representative of the primary total hip or knee replacement population , with intensities of patient-centred pain measured after 3 months to 5-year follow-up . Study appraisal and synthesis methods Two authors screened titles and abstract s. Data extracted by one author were checked independently against original articles by a second . For each study , the authors summarised the proportions of people with different severities of pain in the operated joint . Results Search es identified 1308 articles of which 115 reported patient-centred pain outcomes . Fourteen articles describing 17 cohorts ( 6 with hip and 11 with knee replacement ) presented appropriate data on pain intensity . The proportion of people with an unfavourable long-term pain outcome in studies ranged from about 7 % to 23 % after hip and 10 % to 34 % after knee replacement . In the best quality studies , an unfavourable pain outcome was reported in 9 % or more of patients after hip and about 20 % of patients after knee replacement . Limitations Other studies reported mean values of pain outcomes . These and routine clinical studies are potential sources of relevant data . Conclusions and implication s of key findings After hip and knee replacement , a significant proportion of people have painful joints . There is an urgent need to improve general awareness of this possibility and to address determinants of good and bad outcomes OBJECTIVE To evaluate the association between vitamin C supplementation and the incidence and progression of radiographic knee osteoarthritis ( OA ) . DESIGN Prospect i ve cohort study . SETTING Clearwater Osteoarthritis Study ( COS ) : ( 1988 to the present ) a longitudinal study . SUBJECTS Male and female COS participants aged 40 years and above ( n 1023 ) . The study exposure was the participants ' self-reported history of vitamin C supplementation . The participants underwent biennial , sequential knee radiographs , which were assessed using the Kellgren-Lawrence ordinal scale to determine evidence of the study 2 outcomes : incident radiographic knee OA ( RKOA ) and progression of RKOA . RESULTS Individuals without baseline knee OA who self-reported vitamin C supplement usage were 11 % less likely to develop knee OA than were those individuals who self-reported no vitamin C supplement usage ( risk ratio (RR)=0.89 , 95 % CI 0.85 , 0.93 ) . Among those participants with RKOA at baseline , vitamin C supplement usage did not demonstrate an association with RKOA progression ( RR=0.94 , 95 % CI 0.79 , 1.22 ) . CONCLUSIONS In the present prospect i ve cohort study , we found no evidence to support a protective role of vitamin C in the progression of knee OA . However , after controlling for confounding variables , these data suggest that vitamin C supplementation may indeed be beneficial in preventing incident knee OA . Given the massive public health burden of OA , the use of a simple , widely available and inexpensive supplement to potentially reduce the impact of this disease merits further consideration OBJECTIVE To evaluate the symptomatic effects of highly purified chondroitin 4 and chondroitin 6 sulfate ( CS ) therapy in patients with osteoarthritis ( OA ) of the h and . METHODS This investigator-initiated , single-center , r and omized , double-blind , placebo-controlled clinical trial included 162 symptomatic patients with radiographic evidence of h and OA ( American College of Rheumatology criteria ) . Inclusion criteria included patient 's assessment of global spontaneous h and pain of at least 40 mm on a 0 - 100-mm visual analog scale ( VAS ) and functional impairment of at least 6 ( 0 - 30 scale ) on the Functional Index for H and OA ( FIHOA ) in the most symptomatic h and . Patients received either 800 mg of CS ( n = 80 patients ) or placebo ( n = 82 patients ) once daily for 6 months and were analyzed in an intent-to-treat approach . The two primary outcomes were the change in the patient 's assessment of global spontaneous h and pain and in h and function ( by FIHOA score ) from baseline to month 6 . Secondary outcomes were improvement in grip strength , duration of morning stiffness , acetaminophen consumption , and the investigator 's global impression of treatment efficacy . RESULTS There was a significantly more pronounced decrease in the patient 's global assessment of h and pain in the CS group than in the placebo group ( difference VAS scores -8.7 mm ; P = 0.016 ) . H and function improved significantly more in the CS group than in the placebo group ( difference in FIHOA scores -2.14 ; P = 0.008 ) . There was a statistically significant between-group difference in favor of CS for the duration of morning stiffness and for the investigator 's global impression of treatment efficacy . Changes in grip strength , acetaminophen consumption , and safety end points were not significantly different between the two groups . CONCLUSION This study demonstrates that CS improves h and pain and function in patients with symptomatic OA of the h and and shows a good safety profile OBJECTIVE To investigate whether early changes in biochemical markers of bone ( NTX-I ) and cartilage ( CTX-II [ C-terminal crosslinking telopeptide of type II collagen ] ) degradation are associated with radiological progression in patients with knee osteoarthritis ( OA ) receiving risedronate . DESIGN Two thous and four hundred and eighty three patients with medial compartment knee OA were r and omized in two 24-month studies in North America ( NA ) and European Union ( EU ) . Studies evaluated risedronate 5 mg/day , 35 mg/week ( EU ) , 50 mg/week ( NA ) , and 15 mg/day ( NA and EU ) , compared to placebo in reducing signs and symptoms and in slowing radiographic progression . One thous and eight hundred and eighty five patients from the pooled EU and NA studies with available NTX-I/CTX-II at both baseline and 6 months and radiographs at baseline and at 24 months were analyzed . RESULTS Risedronate produced a dose-dependent reduction of NTX-I and CTX-II observed at 6 months which continued up to 24 months . Patients who had CTX-II levels returned to low levels ( < 150 ng/mmol creatinine ) at 6 months had a lower risk of radiographic progression at 24 months than patients whose CTX-II levels were increased both at baseline and 6 months [ odds-ratio ( 95 % confidence interval ) : 0.57 ( 0.39 - 0.85 ) after adjustment for demographics and joint space width ] . The lowest risk of progression was observed in patients who had low CTX-II levels both at baseline and at 6 months [ odds-ratio 0.36 ( 0.21 - 0.63 ) ] . No significant association between NTX-I levels and radiological progression was observed . CONCLUSION CTX-II decreased with risedronate in patients with knee OA and levels reached after 6 months were associated with radiological progression at 24 months . Monitoring a marker of cartilage degradation 6 months after initiating treatment may be instructive in identifying patients with low progression Objective To determine the effect of chondroitin sulphate ( CS ) treatment on cartilage volume loss , subchondral bone marrow lesions ( BML ) , synovitis and disease symptoms in patients with knee osteoarthritis ( OA ) . Methods In this pilot multicentre , r and omised , double-blind , controlled trial in primary knee OA , 69 patients with clinical signs of synovitis were r and omised to receive CS 800 mg or placebo once daily for 6 months followed by an open-label phase of 6 months in which patients in both groups received CS 800 mg once daily . Cartilage volume and BML were assessed by MRI at baseline and at 6 and 12 months ; synovial membrane thickness was assessed at baseline and at 6 months . Results The CS group showed significantly less cartilage volume loss than the placebo group as early as 6 months for the global knee ( p=0.030 ) , lateral compartment ( p=0.015 ) and tibial plateaus ( p=0.002 ) , with significance persisting at 12 months . Significantly lower BML scores were found for the CS group at 12 months in the lateral compartment ( p=0.035 ) and the lateral femoral condyle ( p=0.044 ) . Disease symptoms were similar between the two groups . Conclusion CS treatment significantly reduced the cartilage volume loss in knee OA starting at 6 months of treatment , and BML at 12 months . These findings suggest a joint structure protective effect of CS and provide new in vivo information on its mode of action in knee OA Background Knee osteoarthritis ( OA ) is a major cause of pain and functional limitation in older adults , yet longer-term studies of medical treatment of OA are limited . Objective To evaluate the efficacy and safety of glucosamine and chondroitin sulphate ( CS ) , alone or in combination , as well as celecoxib and placebo on painful knee OA over 2 years . Methods A 24-month , double-blind , placebo-controlled study , conducted at nine sites in the US ancillary to the Glucosamine/chondroitin Arthritis Intervention Trial , enrolled 662 patients with knee OA who satisfied radiographic criteria ( Kellgren/Lawrence grade 2 or 3 changes and baseline joint space width of at least 2 mm ) . This subset continued to receive their r and omised treatment : glucosamine 500 mg three times daily , CS 400 mg three times daily , the combination of glucosamine and CS , celecoxib 200 mg daily , or placebo over 24 months . The primary outcome was a 20 % reduction in Western Ontario and McMaster University Osteoarthritis Index ( WOMAC ) pain over 24 months . Secondary outcomes included an Outcome Measures in Rheumatology/Osteoarthritis Research Society International response and change from baseline in WOMAC pain and function . Results Compared with placebo , the odds of achieving a 20 % reduction in WOMAC pain were celecoxib : 1.21 , glucosamine : 1.16 , combination glucosamine/CS : 0.83 and CS alone : 0.69 , and were not statistically significant . Conclusions Over 2 years , no treatment achieved a clinical ly important difference in WOMAC pain or function as compared with placebo . However , glucosamine and celecoxib showed beneficial but not significant trends . Adverse reactions were similar among treatment groups and serious adverse events were rare for all treatments Background The implementation of evidence based clinical practice guidelines on self-management interventions to patients with chronic diseases is a complex process . A multifaceted strategy may offer an effective knowledge translation ( KT ) intervention to promote knowledge uptake and improve adherence in an effective walking program based on the Ottawa Panel Evidence Based Clinical Practice Guidelines among individuals with moderate osteoarthritis ( OA ) . Methods A single-blind , r and omized control trial was conducted . Patients with mild to moderate ( OA ) of the knee ( n=222 ) were r and omized to one of three KT groups : 1 ) Walking and Behavioural intervention ( WB ) ( 18 males , 57 females ) which included the supervised community-based aerobic walking program combined with a behavioural intervention and an educational pamphlet on the benefits of walking for OA ; 2 ) Walking intervention ( W ) ( 24 males , 57 females ) wherein participants only received the supervised community-based aerobic walking program intervention and the educational pamphlet ; 3 ) Self-directed control ( C ) ( 32 males , 52 females ) wherein participants only received the educational pamphlet . One-way analyses of variance were used to test for differences in quality of life , adherence , confidence , and clinical outcomes among the study groups at each 3 month assessment during the 12-month intervention period and 6-month follow-up period . Results Short-term program adherence was greater in WB compared to C ( p<0.012 ) after 3 months . No statistical significance ( p > 0.05 ) was observed for long-term adherence ( 6 to 12 months ) , and total adherence between the three groups . The three knowledge translation strategies demonstrated equivalent long-term results for the implementation of a walking program for older individuals with moderate OA . Lower dropout rates as well as higher retention rates were observed for WB at 12 and 18 months . Conclusion The additional knowledge translation behavioural component facilitated the implementation of clinical practice guidelines on walking over a short-term period . More studies are needed to improve the long-term walking adherence or longer guidelines uptake on walking among participants with OA . Particular attention should be taken into account related to patient ’s characteristic and preference . OA can be managed through the implementation of a walking program based on clinical practice guidelines in existing community-based walking clubs as well as at home with the minimal support of an exercise therapist or a trained volunteer . Trial Registration Current Controlled Trials OBJECTIVE Synovitis is very common in knee OA and associated with pain . This open-label study evaluated an anti-synovitis therapy , MTX , for pain relief in knee OA . METHODS Inclusion criteria included pain visual analogue scale ( VAS ) > 40/100 mm , ACR clinical criteria for knee OA and intolerance/inefficacy of NSAID and opioids . US at baseline and 24 weeks assessed effusion and synovial thickness . Patients received MTX up to 20 mg/week for 24 weeks . RESULTS Thirty participants were recruited ; mean age 64.5 years , median pain VAS 68 mm . At 24 weeks , 13/30 ( 43 % ) achieved ≥30 % reduction in pain VAS , 7 ( 23 % ) achieved ≥50 % reduction and 4 ( 13 % ) had worsened . Thirteen achieved Osteoarthritis Research Society International ( OARSI ) responder criteria . All had effusion/synovitis at baseline . There was no correlation between change in imaging and change in pain scores at 24 weeks . CONCLUSION This open-label trial suggests analgesic efficacy for MTX in OA knee and suggests that a r and omized controlled trial is warranted . Trial Registration . Current controlled trials , http://www.controlled-trials.com/ , IS RCT N66676866 Background Platelet Rich Plasma ( PRP ) , a blood-derived product rich in growth factors , is a promising treatment for cartilage defects but there is still a lack of clinical evidence . The aim of this study is to show , through a r and omized double blind prospect i ve trial , the efficacy of this procedure , by comparing PRP to Hyaluronic Acid ( HA ) injections for the treatment of knee chondropathy or osteoarthritis ( OA ) . Methods 109 patients ( 55 treated with HA and 54 with PRP ) were treated and evaluated at 12 months of follow-up . The patients were enrolled according to the following inclusion criteria : age > 18 years , history of chronic ( at least 4 months ) pain or swelling of the knee and imaging findings of degenerative changes of the joint ( Kellgren-Lawrence Score up to 3 ) . A cycle of 3 weekly injections was administered blindly . All patients were prospect ively evaluated before and at 2 , 6 , and 12 months after the treatment by : IKDC , EQ-VAS , TEGNER , and KOOS scores . Range of motion and knee circumference changes were measured over time . Adverse events and patient satisfaction were also recorded . Results Only minor adverse events were detected in some patients , such as mild pain and effusion after the injections , in particular in the PRP group , where a significantly higher post-injective pain reaction was observed ( p=0.039 ) . At the follow-up evaluations , both groups presented a clinical improvement but the comparison between the two groups showed a not statistically significant difference in all scores evaluated . A trend favorable for the PRP group was only found in patients with low grade articular degeneration ( Kellgren-Lawrence score up to 2 ) . Conclusions Results suggest that PRP injections offer a significant clinical improvement up to one year of follow-up . However , conversely to what was shown by the current literature , for middle-aged patients with moderate signs of OA , PRP results were not better than those obtained with HA injections , and thus it should not be considered as first line treatment . More promising results are shown for its use in low grade degeneration , but they still have to be confirmed Objective To assess the ability of avocado – soybean unsaponifiable — Expanscience ( ASU-E ) to slow radiographic progression in symptomatic hip osteoarthritis ( OA ) . Methods Prospect i ve , r and omised , double blind , parallel group , placebo controlled 3 year trial . Patients with symptomatic ( painful ≥1 year , Lequesne Index between 3 and 10 ) hip OA ( American College of Rheumatology criteria ) and a minimum joint space width ( JSW ) of the target hip between 1 and 4 mm on a pelvic radiograph were r and omly assigned to 300 mg/day ASU-E or placebo . St and ing pelvis , target hip anteroposterior ( AP ) and oblique views were taken annually . The primary outcome was JSW change at year 3 , measured at the narrowest point on pelvic or target hip AP view ( manual measure using a 0.1 mm graduated magnifying glass ) . The full analysis data set ( FAS ) included all patients having at least two successive radiographs . An analysis of covariance Mixed Model for Repeated Measurements with Missing at R and om ( for missing data ) was performed to compare adjusted 3 year JSW changes ( primary outcome ) and the percentages of ‘ progressors ’ ( JSW loss≥0.5 mm ) between groups . Results 399 patients were r and omised ( 345 kept in the FAS ) , aged 62 ( 35–84 ) years , 54 % women , mean body mass index 27 ( SD 4 ) kg/m2 , mean symptom duration 4 ( SD 5 ) years , 0–100 normalised Lequesne Index 30 ( SD 9 ) and global pain visual analogue scale 37 ( SD 23 ) mm . Mean baseline JSW was 2.8 ( 0.9 ) mm . There was no significant difference on mean JSW loss ( −0.638 mm vs −0.672 mm , p=0.72 , in the ASU-E and placebo groups , respectively ) but there were 20 % less progressors in the ASU-E than in the placebo group ( 40 % vs 50 % , respectively , p=0.040 ) . No difference was observed on clinical outcomes . Safety was excellent . Conclusions 3 year treatment with ASU-E reduces the percentage of JSW progressors , indicating a potential structure modifying effect in hip OA to be confirmed , and the clinical relevance requires further assessment . Trial registration number on Clinical Trial.gov This study was conducted to investigate the efficacy of oral hyaluronic acid ( HA ) administration for osteoarthritis ( OA ) in knee joints . Sixty osteoarthritic subjects ( Kellgren-Lawrence grade 2 or 3 ) were r and omly assigned to the HA or placebo group . The subjects in the HA group were given 200 mg of HA once a day everyday for 12 months , while the subjects in the placebo group were given placebo . The subjects in both groups were requested to conduct quadriceps strengthening exercise everyday as part of the treatment . The subjects ' symptoms were evaluated by the Japanese Knee Osteoarthritis Measure ( JKOM ) score . The symptoms of the subjects as determined by the JKOM score improved with time in both the HA and placebo groups . This improvement tended to be more obvious with the HA group , and this trend was more obvious with the subjects aged 70 years or less . For these relatively younger subjects , the JKOM score was significantly better than the one for the placebo group at the 2nd and 4th months after the initiation of administration . Oral administration of HA may improve the symptoms of knee OA in patients aged 70 years or younger when combined with the quadriceps strengthening exercise Background Osteoarthritis ( OA ) is a common health issue worldwide in the aging population who are also commonly deficient in vitamin D. Our previous study suggested that higher serum 25-(OH)D levels were associated with reduced knee cartilage loss , implying that vitamin D supplementation may prevent the progression of knee OA . The aim of the VItamin D Effects on OA ( VIDEO ) study is to compare , over a 2- year period , the effects of vitamin D supplementation versus placebo on knee structural changes , knee pain , and lower limb muscle strength in patients with symptomatic knee OA . Methods / design R and omised , placebo-controlled , and double-blind clinical trial aim ing to recruit 400 subjects ( 200 from Tasmania and 200 from Victoria ) with both symptomatic knee OA and vitamin D deficiency ( serum [ 25-(OH)D ] level of > 12.5 nmol/liter and < 60 nmol/liter ) . Participants will be r and omly allocated to vitamin D supplementation ( 50,000 IU compounded vitamin D3 capsule monthly ) or identical inert placebo group for 2 years . The primary endpoint is loss of knee cartilage volume measured by magnetic resonance imaging ( MRI ) and Western Ontario and McMaster Universities Index of OA ( WOMAC ) knee pain score . The secondary endpoints will be other knee structural changes , and lower limb muscle strength . Several other outcome measures including core muscle images and central blood pressure will be recorded . Linear and logistic regression will be used to compare changes between groups using univariable and multivariable modeling analyses . Both intention to treat and per protocol analyses will be utilized . Discussion The trial is design ed to test if vitamin D supplementation will reduce loss of knee cartilage volume , prevent the progression of other knee structural abnormalities , reduce knee pain and strengthen lower limb muscle strength , thus modify disease progression in knee OA.Trial registration Clinical Trials.gov identifier : NCT01176344 ; Australian New Zeal and Clinical Trials Registry : BACKGROUND Arthroscopic partial meniscectomy is one of the most common orthopedic procedures , yet rigorous evidence of its efficacy is lacking . METHODS We conducted a multicenter , r and omized , double-blind , sham-controlled trial in 146 patients 35 to 65 years of age who had knee symptoms consistent with a degenerative medial meniscus tear and no knee osteoarthritis . Patients were r and omly assigned to arthroscopic partial meniscectomy or sham surgery . The primary outcomes were changes in the Lysholm and Western Ontario Meniscal Evaluation Tool ( WOMET ) scores ( each ranging from 0 to 100 , with lower scores indicating more severe symptoms ) and in knee pain after exercise ( rated on a scale from 0 to 10 , with 0 denoting no pain ) at 12 months after the procedure . RESULTS In the intention-to-treat analysis , there were no significant between-group differences in the change from baseline to 12 months in any primary outcome . The mean changes ( improvements ) in the primary outcome measures were as follows : Lysholm score , 21.7 points in the partial-meniscectomy group as compared with 23.3 points in the sham-surgery group ( between-group difference , -1.6 points ; 95 % confidence interval [ CI ] , -7.2 to 4.0 ) ; WOMET score , 24.6 and 27.1 points , respectively ( between-group difference , -2.5 points ; 95 % CI , -9.2 to 4.1 ) ; and score for knee pain after exercise , 3.1 and 3.3 points , respectively ( between-group difference , -0.1 ; 95 % CI , -0.9 to 0.7 ) . There were no significant differences between groups in the number of patients who required subsequent knee surgery ( two in the partial-meniscectomy group and five in the sham-surgery group ) or serious adverse events ( one and zero , respectively ) . CONCLUSIONS In this trial involving patients without knee osteoarthritis but with symptoms of a degenerative medial meniscus tear , the outcomes after arthroscopic partial meniscectomy were no better than those after a sham surgical procedure . ( Funded by the Sigrid Juselius Foundation and others ; Clinical Trials.gov number , NCT00549172 . ) OBJECTIVE The aim of the trial was to assess the efficacy of chondroitin sulphate ( CS ) on symptomatic knee osteoarthritis ( OA ) associated to psoriasis . METHODS In this r and omized , double-blind , placebo (PBO)-controlled clinical trial 129 patients with symptomatic knee OA and concomitant psoriasis were r and omized into two groups receiving 800 mg daily of CS or PBO for 3 months . The primary efficacy outcome for knee OA was the Huskisson 's visual analogue scale ( VAS ) and for psoriasis was the Psoriasis Area and Severity Index ( PASI ) . Additionally , other secondary efficacy criteria for both conditions were assessed . RESULTS After 3 months of treatment , CS was more effective than PBO , relieving pain VAS ( CS -26.9+/-24.8 vs PBO -14.23+/-20.8 mm , P<0.01 ) , decreasing the Lequesne index ( CS -4.8+/-3.4 vs PBO -3.3+/-3.5 , P<0.05 ) and reducing the number of patients using acetaminophen as rescue medication ( CS 43 % vs PBO 64 % , P<0.05 ) . Regarding PASI , Overall Lesion Severity Scale and Physician 's Global Assessment of Change no statistically significant changes were detected in front of PBO . However , CS improved plantar psoriasis compared to PBO ( CS 87 % vs PBO 27 % , P<0.05 ) . Quality of life improved significantly in CS-treated patients according to the Short Form-36 health survey and the Dermatology Life Quality Index ( DLQI ) . CS tolerability was excellent . Adverse events were infrequent and evenly distributed among groups . The incidence of psoriatic flares did not increase after treatments . CONCLUSIONS This study confirms the efficacy and safety of CS as a symptomatic slow-acting drug in patients with knee OA and shows that CS improves plantar psoriasis . The use of CS could represent a special benefit in patients with both pathologies since non-steroidal anti-inflammatory drugs have been reported to induce or exacerbate psoriasis Background : Degenerative Joint Disease ( DJD ) is the most common joint disease in human beings . Previous studies have explained that glucosamine is preferred as placebo and in efficacy compared with NSAID ’s in treatment of patients ’ knee osteoarthritis . Alendronate was used to treat osteoporotic patients and its efficacy was established . Objectives : The aim of this study was to compare the efficacy of administration of glucosamine alone and its combination with alendronate in osteoarthritis of the knee . Patients and Methods : The study included 130 patients with osteoarthritis who r and omly received glucosamine alone ( group II ) ( 500 mg TDS ) , or combination of glucosamine ( 500 mg TDS ) and alendronate ( 70 mg weekly ) ( group I ) for 12 weeks . Patients were evaluated on 1 , 3 , 6 and 12 weeks after beginning the treatment to evaluate efficacy of each treatment . Results : Statistically , there was no significant difference in pain index ( P > 0.05 ) but in the two groups the mean of pain index decreased in a similar fashion . The stiffness index in combination treatment group ( group I ) decreased more than glucosamine group ( group II ) ( P < 0.05 ) . The function of joints in combination treatment group ( group I ) improved after 12weeks . The bone mineral density ( BMD ) at 12weeks in combination therapy group improved . Conclusions : Combination therapy of glucosamine and alendronate indicated significant improvement of stiffness , function , BMD of osteoarthritis compared with glucosamine alone but there was no statistically significant decrease in pain index . It can be concluded that the combination of glucosamine and alendronate provide better and more rapid improvement in patients with osteoarthritis Introduction The medicinal treatment of osteoarthritis ( OA ) is mostly symptomatic to relieve pain and incapacity with analgesics and non-steroidal anti-inflammatory drugs ( NSAIDs ) , drugs with well-known risks . Complementary medicines might reduce the symptoms of OA and decrease the need for NSAIDs . This study tested the effects of a food supplement , Phytalgic ® , on pain and function in patients with osteoarthritis and their use of analgesic and NSAIDs . Methods A r and omized double-blind parallel-groups clinical trial compared Phytalgic ® ( fish-oil , vitamin E , Urtica dioica ) to a placebo for three months , in 81 patients with OA of the knee or hip using NSAIDs and /or analgesics regularly . The main outcome measures were use of NSAIDs ( in Defined Daily Doses per day - DDD/day ) or analgesics ( in 500 mg paracetamol-equivalent tablets per week ( PET/week ) measured each month , and Western Ontario-McMaster University Osteo-Arthritis Index ( WOMAC ) function scales . Results After three months of treatment , the mean use of analgesics in the active arm ( 6.5 PET/week ) vs. the placebo arm ( 16.5 ) was significantly different ( P < 0.001 ) with a group mean difference of -10.0 ( 95 % CI : -4.9 to -15.1 ) . That of NSAIDs in the active arm ( 0.4 DDD/day ) vs the placebo arm ( 1.0 DDD/day ) was significantly different ( P = 0.02 ) with a group mean difference of - 0.7 DDD/day ( 95 % CI : -0.2 to -1.2 ) . Mean WOMAC scores for pain , stiffness and function in the active arm ( respectively 86.5 , 41.4 and 301.6 ) vs the placebo arm ( resp . 235.3 , 96.3 and 746.5 ) were significantly different ( P < 0.001 ) with group mean differences respectively of -148.8 ( 95 % CI : -97.7 to -199.9 ) , -54.9 ( 95 % CI : -27.9 to -81.9 ) and -444.8 ( 95 % CI : -269.1 to -620.4 ) . Conclusions The food supplement tested appeared to decrease the need for analgesics and NSAIDs and improve the symptoms of osteoarthritis . Trial registration Clinical trials.gov NCT00666523 BACKGROUND pain is the leading symptom of osteoarthritis ( OA ) and is often chronic in nature , leading to significant morbidity and decreased quality of life . Duloxetine , a selective serotonin norepinephrine reuptake inhibitor has been demonstrated to have a central ly acting analgesic effect . OBJECTIVES the aim of the present study was to investigate the efficacy of duloxetine in reducing pain in older adults with knee OA . METHODS totally , 288 patients aged 65 years and above with primary knee OA were enrolled in this study . Patients were r and omised 1:1 . Totally , 144 received 60 mg/day of duloxetine HCL and 144 received placebo for 16 weeks . Outcome measures included pain reduction and improvement in physical functioning scores . Pain was assessed using the visual analogue pain scale ( VAS ; 0 - 100 mm ) . The Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) scores were used to assess function . RESULTS two-hundred and seventy four of the 288 patients completed the study . There was a statistically significant reduction in pain and a significant improvement in WOMAC scores at 16 weeks in the duloxetine group versus the placebo group . No serious side effects were reported . CONCLUSIONS the findings of the present study provide evidence for the efficacy and tolerability of duloxetine in reducing pain and subsequently improving function in older adults with knee OA . TRIAL REGISTRATION NCT01425827 Abstract Limitation in daily physical activity is one of the reasons for total hip arthroplasty ( THA ) or total knee arthroplasty ( TKA ) . However , studies of the effects of THA or TKA generally do not determine actual daily activity as part of physical functioning . We determined the effect of THA or TKA on patients ’ actual physical activity and body function ( pain , stiffness ) , capacity to perform tasks , and self-reported physical functioning . We also assessed whether there are differences in the effect of the surgery between patients undergoing THA or TKA and whether the improvements vary between these different outcome measures . We recruited patients with long-st and ing end-stage osteoarthritis of the hip or knee awaiting THA or TKA . Measurements were performed before surgery and 3 and 6 months after surgery . Actual physical activity improved by 0.7 % . Patients ’ body function , capacity , and self-reported physical functioning also improved . The effects of the surgery on these aspects of physical functioning were similar for THA and TKA . The effect on actual physical activity ( 8 % ) was smaller than on body function ( 80%–167 % ) , capacity ( 19%–36 % ) , and self-reported physical functioning ( 87%–112 % ) . Therefore , in contrast to the large effect on pain and stiffness , patients ’ capacity , and their self-reported physical functioning , the improvement in actual physical activity of our patients was less than expected 6 months after surgery . Level of Evidence : Level I , prospect i ve study . See the Guidelines for Authors for a complete description of levels of evidence Objective To determine whether older patients with chronic knee pain should be advised to use topical or oral non-steroidal anti-inflammatory drugs ( NSAIDs ) . Design R and omised controlled trial and patient preference study . Setting 26 general practice s. Participants People aged ≥50 with knee pain : 282 in r and omised trial and 303 in preference study . Interventions Advice to use topical or oral ibuprofen . Primary outcome measures WOMAC ( Western Ontario and McMaster Universities ) osteoarthritis index , major and minor adverse effects . Results Changes in global WOMAC scores at 12 months were equivalent . In the r and omised trial the difference ( topical minus oral ) was two points ( 95 % confidence interval −2 to 6 ) ; in the preference study , it was one point ( −4 to 6 ) . There were no differences in major adverse effects in the trial or study . The only significant differences in secondary outcomes were in the r and omised trial . The oral group had more respiratory adverse effects ( 17 % v 7%,95 % confidence interval for difference −17 % to −2 % ) , the change in serum creatinine was 3.7 mmol/l less favourable ( 0.9 µmol/l to 6.5 µmol/l ) ; and more participants changed treatments because of adverse effects ( 16 % v 1 % , −16 % to −5 % ) . In the topical group more participants had chronic pain grade III or IV at three months , and more participants changed treatment because of ineffectiveness . Conclusions Advice to use oral or topical preparations has an equivalent effect on knee pain over one year , and there are more minor side effects with oral NSAIDs . Topical NSAIDs may be a useful alternative to oral NSAIDs . Trial registration IS RCT N 79353052 Objective To determine if the dietary supplements , glucosamine and /or chondroitin , result in reduced joint space narrowing ( JSN ) and pain among people with symptomatic knee osteoarthritis . Methods A double-blind r and omised placebo-controlled clinical trial with 2-year follow-up . 605 participants , aged 45–75 years , reporting chronic knee pain and with evidence of medial tibio-femoral compartment narrowing ( but retaining > 2 mm medial joint space width ) were r and omised to once daily : glucosamine sulfate 1500 mg ( n=152 ) , chondroitin sulfate 800 mg ( n=151 ) , both dietary supplements ( n=151 ) or matching placebo capsules ( n=151 ) . JSN ( mm ) over 2 years was measured from digitised knee radiographs . Maximum knee pain ( 0–10 ) was self-reported in a participant diary for 7 days every 2 months over 1 year . Results After adjusting for factors associated with structural disease progression ( gender , body mass index ( BMI ) , baseline structural disease severity and Heberden 's nodes ) , allocation to the dietary supplement combination ( glucosamine – chondroitin ) result ed in a statistically significant ( p=0.046 ) reduction of 2-year JSN compared to placebo : mean difference 0.10 mm ( 95 % CI 0.002 mm to 0.20 mm ) ; no significant structural effect for the single treatment allocations was detected . All four allocation groups demonstrated reduced knee pain over the first year , but no significant between-group differences ( p=0.93 ) were detected . 34 ( 6 % ) participants reported possibly-related adverse medical events over the 2-year follow-up period . Conclusions Allocation to the glucosamine – chondroitin combination result ed in a statistically significant reduction in JSN at 2 years . While all allocation groups demonstrated reduced knee pain over the study period , none of the treatment allocation groups demonstrated significant symptomatic benefit above placebo . Trial Registration Clinical Trials.gov identifier : NCT00513422 ; http://www . clinical Objective This study aim ed to find a simple , cost-effective , and time-efficient method for the preparation of platelet-rich plasma ( PRP ) , so the acquired benefits will be readily available for multiple procedures in smaller outpatient clinics and to explore the safety and efficacy of the application of PRP in the treatment of degenerative lesions of articular cartilage of the knee . Design The study was design ed as a prospect i ve , cohort study with a control group . A total of 120 patients with Grade 1 , 2 , or 3 osteoarthritis according to the Kellgren and Lawrence grading scale were enrolled in the study . One group of patients was treated using three intra-articular applications of PRP , and the second group of patients was given three injections of hyaluronic acid . Outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index and the 11-point pain intensity Numeric Rating Scale . Results On average , a 4.5-fold increase in platelet concentration was obtained in the PRP group . No severe adverse events were observed . Statistically significantly better results in the Western Ontario and McMaster Universities Osteoarthritis Index and Numeric Rating Scale scores were recorded in a group of patients who received PRP injections after a 3- and 6-mo follow-up . Conclusions Our preliminary findings support the application of autologous PRP as an effective and safe method in the treatment of the initial stages of knee osteoarthritis . Further studies are needed to confirm these results and to investigate the persistence of the beneficial effects observed First carpometacarpal joint osteoarthritis ( 1(st ) CMCJ OA ) is a common condition with variable results reported from local corticosteroid injection . This study aims to explore the medium-term outcome with respect to pain relief , patient satisfaction and the need for subsequent surgical intervention . A prospect i ve review was performed of patients undergoing fluoroscopically guided corticosteroid injection by one surgeon , with postal question naires for medium-term follow-up . Forty-one patients were included . Thirty-one were female and ten male , with a mean age of 60 years . In the short term 76 % of patients reported pain relief with an average duration of four weeks and 69 % of the patients reported benefit from injection . After a median follow-up of 36 months 76 % of patients reported continuing pain but 59 % reported satisfaction with the outcome . Twenty-eight per cent of the patients had undergone surgery . Local corticosteroid injection of the CMCJ provides only short-term pain relief , but few patients go on to surgical intervention OBJECTIVE To determine the efficacy of fluoroscopically guided corticosteroid injection for hip osteoarthritis ( OA ) in a r and omized , double-blind , placebo-controlled trial . METHODS Fifty-two patients with symptomatic hip OA were r and omly allocated to receive placebo ( 10 mg bipuvicaine , 2 ml saline ) ( n = 21 ) or corticosteroid treatment ( 10 mg bipuvicaine , 40 mg triamcinolone hexacetonide ) ( n = 31 ) . Patients were followed up for 1 , 2 , 3 , and 6 months . The primary outcome measure was the pain improvement response , defined as a 20 % decrease in the Western Ontario and McMaster Universities OA Index ( WOMAC ) pain score ( on 5 100-mm visual analog scales [ VAS ] ) ( WOMAC20 ) from baseline to 2 months postinjection . Secondary outcomes were a 50 % decrease in the WOMAC pain score ( WOMAC50 ) , changes in other WOMAC subscale scores , patient 's global assessment of health ( on a 100-mm VAS ) , and Short Form 36 ( SF-36 ) quality of life indices . Analyses were based on the intent-to-treat principle . RESULTS The mean WOMAC pain score fell 49.2 % ( decreasing from 310.1 mm to 157.4 mm ) at 2 months postinjection in patients receiving corticosteroid , compared with a decrease of 2.5 % ( from 314.3 mm to 306.5 mm ) in the placebo group ( P < 0.0001 ) . The proportion of WOMAC20 responders at 2 months ' followup was significantly higher in the corticosteroid group ( 67.7 % ) compared with the placebo group ( 23.8 % ) ( P = 0.004 ) ; similar proportions of WOMAC50 responders were observed between groups ( 61.3 % in the corticosteroid group versus 14.3 % in the placebo group ; P = 0.001 ) . Response differences were maintained at 3 months ' followup ( 58.1 % responders in the corticosteroid group versus 9.5 % responders in the placebo group ; P = 0.004 ) . Significant differences in the WOMAC stiffness and physical function scores ( P < 0.0001 ) , patient 's global health scores ( P = 0.005 ) , and SF-36 physical component scores ( P = 0.04 ) were observed , with patients in the corticosteroid group showing greater improvements . There were no differences in the frequency of adverse events between groups . CONCLUSION This placebo-controlled trial confirms that corticosteroid injection can be an effective treatment of pain in hip OA , with benefits lasting up to 3 months in many cases . Future studies should address questions related to the benefits of repeated steroid injection and the effects of this treatment on disease modification OBJECTIVE To compare the safety and efficacy of acetaminophen extended-release ( APAP ER ) with rofecoxib for the management of pain associated with knee osteoarthritis ( OA ) . METHODS Four hundred and three adult patients with moderate pain secondary to knee OA were r and omized to receive APAP ER 1300 mg three times daily , rofecoxib 12.5 mg once daily , or rofecoxib 25 mg once daily . Primary end point was change from baseline at week 4 in the Western Ontario and McMaster Universities Osteoarthritis Index pain subscale score using a visual analog scale . This 4-week study was conducted at 23 US research sites from October 1999 to October 2000 . RESULTS APAP ER was noninferior to rofecoxib 12.5 mg because the upper 95 % confidence limit ( CL ) for the least squares mean ( LSM ) change from baseline ( 35.27 mm at week 4 ) did not exceed the prespecified noninferiority limit of 50 mm . The upper CL ( 57.39 mm ) exceeded the noninferiority limit for APAP ER compared with rofecoxib 25 mg at week 4 . There were no significant differences among groups in the overall incidence of adverse events . CONCLUSION APAP ER 3900 mg daily was noninferior to rofecoxib 12.5 mg daily , but noninferiority was not established to rofecoxib 25 mg daily . APAP ER was well tolerated and no safety issues were identified . Based on the results of this study , APAP ER 3900 mg daily is an alternative to nonsteroidal anti-inflammatory drugs ( NSAIDs ) , such as rofecoxib , in treating pain associated with knee OA BACKGROUND Knee osteoarthritis ( OA ) is prevalent and associated with both pain and functional disability . Current treatments aim to alleviate mild to moderate symptoms by various methods . Topical capsaicin ( 0.075 % and 0.05 % ) has been evaluated for the treatment of the painful joints . A burning sensation was the most common side effect at these strengths . Therefore , the authors aim ed to evaluate the efficacy of 0.0125 % capsaicin gel ( Capsika gel ) compared to a placebo ( the vehicle gel ) in patients with symptomatic OA knee . MATERIAL AND METHOD This was a cross-over ; double blinded , r and omized , controlled trial of 100 patients with mild to moderate knee OA . All of the patients received either capsaicin gel or placebo gel applied to the affected knee , three times daily for 4 weeks with one week washout period after which the treatment switched to either capsaicin gel or placebo gel for the next 4 weeks . A blinded examiner used the visual analog scale ( VAS ) and WOMAC score to do weekly assessment s. RESULTS Subjects averaged 61 years of age ( range , 44 to 82 ) . During the enrollment phase , only female farmers presented . Mean body weight and height was 62.97 + /- 10.25 kg and 1.54 + /- 0.053 m , respectively The respective baseline VAS and WOMAC score was 6.40 + /- 1.64 and 51.65 + /- 13.3 . The severity of OA , according to the KL criteria was : 83 patients with grade 2 and 16 with grade 3 . The respective mean difference of VAS and total WOMAC score in the capsaicin group vs. the placebo group was statistically significant ( p < 0.05 ) . The mean difference of the WOMAC pain , stiffness and functional subscales in the capsaicin vs. the placebo group was also significant ( p < 0.05 ) . The only adverse event reported was a burning sensation . During the 4-week treatment with capsaicin , approximately 67 % of patients had a burning sensation but none withdrew for this reason . CONCLUSION 0.0125 % capsaicin gel was an effective treatment in mildly to moderately painful OA knees . The burning sensation reported by patients in the capsaicin group was less disturbing than in previous studies and none of the present patients withdrew for this reason The objective of this study was to examine the effect of a nonsteroidal anti-inflammatory drug ( NSAID ) plaster for knee osteoarthritis among Japanese patients . An open-labeled , r and omized , controlled , multiclinic trial was performed involving outpatient clinic groups . Two comparative groups — plaster NSAIDs and oral NSAIDs — were r and omly allocated . The drugs used were limited to the current top three in both groups in Japan . Treatments were assessed after four weeks and compared with the baseline scores . Outcomes were evaluated by two psychometric measures : Japanese knee osteoarthritis measure , and pain with the visual analogue scale . The total number of patients included in the final evaluation was 165 ( 87 for the plaster group and 78 for the oral group ) . Between these two groups there were no significant differences in gender , age , body height and weight , body mass index , and X-ray grading . The subjects in both groups showed improvements in both scores at the end of intervention . The differences in the improvements in scores between the two groups were not significant , though the mean rank score and the 95 % CI of the plaster group were slightly better than those of the oral group . In conclusion , the local application of a plaster with NSAIDs leads to the same level of improvement in knee osteoarthritis as oral NSAIDs Objectives To compare the effect of a single infusion of zoledronic acid ( ZA ) with placebo on knee pain and bone marrow lesions ( BMLs ) . Methods Adults aged 50–80 years ( n=59 ) with clinical knee osteoarthritis and knee BMLs were r and omised to receive either ZA ( 5 mg/100 ml ) or placebo . BMLs were determined using proton density-weighted fat saturation MR images at baseline , 6 and 12 months . Pain and function were measured using a visual analogue scale ( VAS ) and the knee injury and osteoarthritis outcome score ( KOOS ) scale . Results At baseline , mean VAS score was 54 mm and mean total BML area was 468 mm2 . VAS pain scores were significantly reduced in the ZA group compared with placebo after 6 months ( −14.5 mm , 95 % CI −28.1 to −0.9 ) but not after 3 or 12 months . Changes on the KOOS scales were not significant at any time point . Reduction in total BML area was greater in the ZA group compared with placebo after 6 months ( −175.7 mm2 , 95 % CI −327.2 to −24.3 ) with a trend after 12 months ( −146.5 mm2 , 95 % CI −307.5 to + 14.5 ) . A greater proportion of those in the ZA group achieved a clinical ly significant reduction in BML size at 6 months ( 39 % vs 18 % , p=0.044 ) . Toxicity was as expected apart from a high rate of acute phase reactions in treatment and placebo arms . Conclusions ZA reduces knee pain and areal BML size and increases the proportion improving over 6 months . Treatment of osteoarthritis may benefit from a lesion specific therapeutic approach . Clinical trial registration number ACTRN 12609000399291 OBJECTIVE To assess the long-term effects of chondroitins 4 and 6 sulfate ( CS ) on the radiographic progression of , and symptom changes associated with , knee osteoarthritis ( OA ) . METHODS We performed an international , r and omized , double-blind , placebo-controlled trial in which 622 patients with knee OA were r and omly assigned to receive either 800 mg CS ( n = 309 patients ) or placebo ( n = 313 patients ) once daily for 2 years . Radiographs of the target knee , using the Lyon schuss view , were obtained at the time of enrollment and at 12 , 18 , and 24 months . The minimum joint space width ( JSW ) of the medial compartment of the tibiofemoral joint was assessed by digital image analysis . The primary outcome was the loss in minimum JSW over 2 years . RESULTS The intent-to-treat analysis demonstrated a significant reduction ( P < 0.0001 ) in minimum JSW loss in the CS group ( mean + /- SEM -0.07 + /- 0.03 mm ) as compared with the placebo group ( -0.31 + /- 0.04 mm ) . The percentage of patients with radiographic progression > or = 0.25 mm was significantly reduced in the CS group compared with the placebo group ( 28 % versus 41 % [ P < 0.0005 ] ; relative risk reduction 33 % [ 95 % confidence interval 16 - 46 % ] ) . The number of patients needed to treat was 8 ( 95 % confidence interval 5 - 17 ) . Pain improved significantly faster in the CS group than in the placebo group ( P < 0.01 ) . There were no differences in safety between groups . CONCLUSION The long-term combined structure-modifying and symptom-modifying effects of CS suggest that it could be a disease-modifying agent in patients with knee OA OBJECTIVE To determine the effectiveness of subsensory , pulsed electrical stimulation ( PES ) in the symptomatic management of osteoarthritis ( OA ) of the knee . METHODS This was a double-blind , r and omized , placebo-controlled , repeated- measures trial in 70 participants with clinical and radiographically diagnosed OA of the knee who were r and omized to either PES or placebo . The primary outcome was change in pain score over 26 weeks measured on a 100-mm visual analog scale ( VAS ) . Other measures included pain on the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) , function on the WOMAC , patient 's global assessment of disease activity ( on a 100-mm VAS ) , joint stiffness on the WOMAC , quality of life on the Medical Outcomes Study Short-Form 36 ( SF-36 ) health survey , physical activity ( using the Human Activity Profile and an accelerometer ) , and global perceived effect ( on an 11-point scale ) . RESULTS Thirty-four participants were r and omized to PES and 36 to placebo . Intent-to-treat analysis showed a statistically significant improvement in VAS pain score over 26 weeks in both groups , but no difference between groups ( mean change difference 0.9 mm [ 95 % confidence interval -11.7 , 13.4 ] ) . Similarly , there were no differences between groups for changes in WOMAC pain , function , and stiffness scores ( -5.6 [ 95 % confidence interval -14.9 , 3.6 ] , -1.9 [ 95 % confidence interval -9.7 , 5.9 ] , and 3.7 [ 95 % confidence interval -6.0 , 13.5 ] , respectively ) , SF-36 physical and mental component summary scores ( 1.7 [ 95 % confidence interval -1.5 , 4.8 ] and 1.2 [ 95 % confidence interval -2.9 , 5.4 ] , respectively ) , patient 's global assessment of disease activity ( -2.8 [ 95 % confidence interval -13.9 , 8.4 ] ) , or activity measures . Fifty-six percent of the PES-treated group achieved a clinical ly relevant 20-mm improvement in VAS pain score at 26 weeks compared with 44 % of controls ( 12 % [ 95 % confidence interval -11 % , 33 % ] ) . CONCLUSION In this sample of subjects with mild-to-moderate symptoms and moderate-to-severe radiographic OA of the knee , 26 weeks of PES was no more effective than placebo Guidelines are based on a scientific analysis from existing data of r and omized controlled trials ( RCTs ) , registry trials , simple registries , case reports , and the personal experience of the task force members . Furthermore , meta-analyses and subgroup analyses are used to derive the strengths of recommendations . Fortunately , the major cardiac societies , i.e. , the American College of Cardiology ( ACC ) , the American Heart Association ( AHA ) , and the European Society of Cardiology ( ESC ) , are essentially using the same definitions for the levels of recommendations . In the exp and ing field of cardiology , however , the overwhelming and increasing number of clinical studies reveals the limitations of the traditional ranking of these studies : Applying the st and ard definitions of the ACC/AHA/ESC criteria for the levels of recommendation , almost every PCI procedure would easily reach the level of evidence A , even with two small , underpowered studies and a surrogate endpoint . Although meta-analyses are important tools for creating an overview of major diagnostic or treatment modalities , they are bound to severe limitations . The compilation of several underpowered , small trials can generate a statistically artificial " significant " result . This is especially important because only two meta-analyses containing almost identical studies could easily yield an evidence level A. RCTs are usually design ed and conducted according to a power calculation , for which a primary clinical or surrogate endpoint can be chosen . Surrogate endpoints , however , do not necessarily correlate with the clinical outcome . The history of medicine is full of errors introduced by underpowered studies with surrogate endpoints . Many investigators and companies attempt to tease out treatment effects in specific sub population s of patients . These subgroup analyses are usually underpowered . Another major limitation of the ACC/AHA/ESC scoring system is that neither the power of a study nor the choice of a primary clinical endpoint is included in their definitions . Yet another limitation of the ACC/AHA/ESC grading system is that two " simple " registries may already lead to a level of evidence B. A new scoring system is presented addressing most of these limitations : a primary clinical endpoint receives three points , whereas all of the following receive one point : double-blind design , evaluation interval of primary endpoint > or = 6 months , multicenter ( at least three centers ) , independent data and safety monitoring , power of > or = 80 % for primary endpoint achieved , and follow-up > or = 80 % for a surrogate primary endpoint or follow-up of > or = 95 % for a clinical primary endpoint . Thus , the maximum achievable points is 10 . This scoring system can also be applied for high- quality registry controlled trials using a predefined control group and power calculation . For simple registry studies and subgroup analyses , a modified scoring system has been developed ( maximum achievable points is 5 ) . The advantage of the suggested new scoring system is its transparency , reproducibility , and ease of use by quickly answering the key quality questions for clinical trials . The new scoring system suggested here should help make decisions regarding which treatment to use and stimulate discussion Forty-two women with thumb base osteoarthritis referred to a joint protection programme ( JP ) were distributed into groups : one with only JP ( Control group ) and one with addition of splints day/night , hot pack/home exercise ( SE group ) . Assessment s of pain , stiffness , grip force , disabilities of daily activities were performed before treatment , 1 week and 1 year after treatment . The SE group had a significant decrease in pain , stiffness and an improvement in daily activities directly after the intervention and at 1-year follow-up compared to the Control group . In the SE group pain at night , pain on motion , and stiffness decreased . Grip force increased and daily activities improved . The Control group decreased in pain on motion and showed improvement in daily activities just after the intervention but not at 1-year follow up . This comparative study shows that when splinting and exercise regimen are added to a JP programme it gives a greater improvement of pain , stiffness , grip force and daily activities than the JP programme alone OBJECTIVE To obtain preliminary information about the effectiveness of intra-articular injections of an autologous preparation rich in growth factors ( PRGF ) for knee OA treatment to be explored further in future studies . METHODS We have characterized PRGF treatment by platelet count and concentration of relevant growth factors ( TGF-Beta1 , PDGF-AB , VEGF-A ; HGF and IGF-I ) involved in healing mechanisms . We have performed an observational retrospective cohort study using hyaluronan injections as a control . Each group included 30 patients with OA of the knee , matched according to age , sex , body mass index and radiographic severity . Both treatments were based on three weekly injections . Clinical outcome was examined using the WOMAC question naires prior to treatment and at 5 weeks after treatment . RESULTS The observed success rates by week 5 for the pain subscale reached 33.4 % for the PRGF group and 10 % for the hyaluronan group . The difference was attributed exclusively to the treatment modality , p = 0.004 . The percent reductions in the physical function subscale and overall WOMAC at 5 weeks were also associated solely with treatment modality in favour of PRGF , p = 0.043 and p = 0.010 respectively . CONCLUSIONS Although these preliminary results need to be evaluated in a r and omized clinical trial , they provide useful infomration about the safety of PRGF and open new perspectives on autologous treatments for joint diseases Sampson S , Reed M , Silvers H , Meng M , M and elbaum B : Injection of platelet-rich plasma in patients with primary and secondary knee osteoarthritis : A pilot study . Objective : To evaluate the clinical effects of intraarticular platelet-rich plasma ( PRP ) injections in a small group of patients with primary and secondary osteoarthritis . Most of the current treatments for osteoarthritis are palliative and attack the symptoms rather than influencing the biochemical environment of the joint . Autologous platelet-rich plasma has emerged as a treatment option for tendinopathies and chronic wounds . In addition to release of growth factors , platelet-rich plasma also promotes concentrated anti-inflammatory signals including interleukin-1ra , which has been a focus of emerging treatments for osteoarthritis . Design : In this single-center , uncontrolled , prospect i ve preliminary study , 14 patients with primary and secondary knee osteoarthritis who met the study criteria received three platelet-rich plasma injections in the affected knee at ∼4-wk intervals . Outcome measures included the Brittberg-Peterson Visual Pain ( Visual Analog Scale [ VAS ] ) , Activities , and Expectations score and the Knee Injury and Osteoarthritis Outcome Scores at preinjection visit at 2- , 5- , 11- , 18- , and 52-wk follow-up visits . Musculoskeletal ultrasound was used to measure cartilage thickness . Results : There were no adverse events reported . The study demonstrated significant and almost linear improvements in Knee Injury and Osteoarthritis Outcome Scores , including pain and symptom relief . Brittberg-Peterson VAS showed many improvements including reduced pain after knee movement and at rest . Cartilage assessment was limited because of the small sample size . The majority of the patients expressed a favorable outcome at 12 mos after treatment . Conclusions : The positive trends and safety profile demonstrated could potentially be used to inspire a larger , blinded , and r and omized clinical trial to determine whether platelet-rich plasma is safe and effective for the treatment of knee osteoarthritis OBJECTIVE Evaluation of the efficacy and safety of a single oral dose of a 1200 mg sachet of chondroitin 4&6 sulfate ( CS 1200 ) vs three daily capsules of chondroitin 4&6 sulfate 400 mg ( CS 3 * 400 ) ( equivalence study ) and vs placebo ( superiority study ) during 3 months , in patients with knee osteoarthritis ( OA ) . DESIGN Comparative , double-blind , r and omized , multicenter study , including 353 patients of both genders over 45 years with knee OA . Minimum inclusion criteria were a Lequesne index ( LI ) ≥ 7 and pain ≥ 40 mm on a visual analogue scale ( VAS ) . LI and VAS were assessed at baseline and after 1 - 3 months . Equivalence between CS was tested using the per- protocol procedure and superiority of CS vs placebo was tested using an intent-to-treat procedure . RESULTS After 3 months of follow-up , no significant difference was demonstrated between the oral daily single dose of CS 1200 formulation and the three daily capsules of CS 400 . Patients treated with CS 1200 or CS 3 * 400 were significantly improved compared to placebo after 3 months of follow-up in terms of LI ( < 0.001 ) and VAS ( P < 0.01 ) . No significant difference in terms of security and tolerability was observed between the three groups . CONCLUSION This study suggests that a daily administration of an oral sachet of 1200 mg of chondroitin 4&6 sulfate allows a significant clinical improvement compared to a placebo , and a similar improvement when compared to a regimen of three daily capsules of 400 mg of the same active ingredient STUDY DESIGN R and omized Clinical Trial . INTRODUCTION H and exercises have been recommended as treatment for h and osteoarthritis ( OA ) but research evidence is sparse . PURPOSE OF THE STUDY To investigate effects of daily 16-week home-based h and exercise among persons with h and OA . METHODS Forty-six older adults completed a crossover trial with washout between exercise and sham treatments . The AUSCAN physical function sub-scale served as the primary outcome measure . Other outcomes included pain and stiffness sub-scales , dexterity , and grip & pinch strengths . RESULTS Changes in AUSCAN sub-scales did not differ between exercise and sham treatments . No changes in dexterity were seen . Grip and pinch measures modestly improved after exercise but not sham . CONCLUSIONS It is possible that our exercise protocol may have been too ambitious for this age group . Future research will further the underst and ing of the role of h and exercise in h and OA symptomatology . LEVEL OF EVIDENCE 2b Background Current treatment for osteoarthritis ( OA ) is limited . Many patients with OA of the h and have areas of tender subcutaneous thickening in the forearm and upper scapular region . A pilot study showed an improvement in pain from OA at the first carpometacarpal joint after injection of such areas with 0.5 % sodium salicylate or saline , an inexpensive treatment that can be administered by general practitioners and nurses . The study indicated that a r and omised , sham-controlled trial was justified . Methods 40 patients with OA of the first carpometacarpal joint were r and omised to receive either injections of sodium salicylate into tender , thickened areas of subcutaneous tissue on the forearm ( baseline ) and upper scapular region ( week 1 ) or sham injections consisting of pressure without skin penetration . Blinded assessment s were made at weeks 3 , 7 and 13 after baseline . Results Pain and tenderness during follow-up were both significantly lower in the active treatment group compared with the sham group : 19 % and 14 % greater reduction in mean visual analogue scale ( VAS ) score , respectively ( p=0.007 and 0.02 , baseline mean 5.65 and 5.35 cm , average difference in change from baseline VAS 1.9 and 1.4 cm , 95 % CI 0.6 to 3.2 and 0.2 to 2.5 ) . Active and sham injections were painful , the former significantly more so ; however , there was no significant correlation between the pain of active injections and response . Conclusion The data show that subcutaneous sodium salicylate injections are an effective symptomatic treatment for OA of the thumb . The results provide a basis for further physiological and therapeutic research in this area ABSTRACT While topical non‐steroidal anti‐inflammatory drugs are considered safe , their long‐term efficacy for osteoarthritis has been suspect . We conducted a 12‐week , double‐blind , double‐dummy , r and omized controlled trial of topical diclofenac ( TDiclo ) in a vehicle solution containing dimethyl sulfoxide ( DMSO ) in 775 subjects with radiologically confirmed , symptomatic primary osteoarthritis of the knee . This 5‐arm study compared TDiclo with a placebo solution , the DMSO vehicle , oral diclofenac ( ODiclo ) and the combination of TDiclo + ODiclo for relieving the signs and symptoms of knee osteoarthritis . Subjects applied study solution , 40 drops four times daily , and took one study tablet daily for 12 weeks . Co‐ primary efficacy variables were WOMAC pain and physical function and a patient overall health assessment . Secondary variables were WOMAC stiffness and patient global assessment ( PGA ) of the knee osteoarthritis . TDiclo was superior to placebo for pain ( −6.0 vs. −4.7 , P = 0.015 ) , physical function ( −15.8 vs. −12.3 , P = 0.034 ) , overall health ( −0.95 vs. −0.37 , P < 0.0001 ) , and PGA ( −1.36 vs. −1.01 , P = 0.016 ) , and was superior to DMSO vehicle for all efficacy variables . No significant difference was observed between DMSO vehicle and placebo or between TDiclo and ODiclo . The commonest adverse event associated with TDiclo was dry skin ( 18.2 % ) . Fewer digestive system and laboratory abnormalities were observed with TDiclo than with ODiclo . Addition of TDiclo to ODiclo did not increase the incidence of systemic adverse events . TDiclo in DMSO vehicle is an effective treatment option for knee osteoarthritis with efficacy similar to , but tolerability better than ODiclo . DMSO vehicle was no more efficacious than placebo Objective . To investigate the efficacy of 6 weeks of daily low-dose oral prednisolone in improving pain , mobility , and systemic low- grade inflammation in the short term and whether the effect would be sustained at 12 weeks in older adults with moderate to severe knee osteoarthritis ( OA ) . Methods . A total of 125 patients with primary knee OA were r and omized 1:1 ; 63 received 7.5 mg/day of prednisolone and 62 received placebo for 6 weeks . Outcome measures included pain reduction and improvement in function scores and systemic inflammation markers . Pain was assessed using the visual analog pain scale ( 0–100 mm ) . Secondary outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index scores , patient global assessment ( PGA ) of the severity of knee OA , and 6-min walk distance ( 6MWD ) . Serum levels of interleukin 1 ( IL-1 ) , IL-6 , tumor necrosis factor (TNF)-α , and high-sensitivity C-reactive protein ( hsCRP ) were measured . Results . There was a clinical ly relevant reduction in the intervention group compared to the placebo group for knee pain , physical function , PGA , and 6MWD at 6 weeks . The mean difference between treatment arms ( 95 % CI ) was 10.9 ( 4.8–18.0 ) , p < 0.001 ; 9.5 ( 3.7–15.4 ) , p < 0.05 ; 15.7 ( 5.3–26.1 ) , p < 0.001 ; and 86.9 ( 29.8–144.1 ) , p < 0.05 , respectively . Further , there was a clinical ly relevant reduction in the serum levels of IL-1 , IL-6 , TNF-α , and hsCRP at 6 weeks in the intervention group when compared to the placebo group . These differences remained significant at 12 weeks . The Outcome Measures in Rheumatology Clinical Trials-Osteoarthritis Research Society International responder rate was 65 % in the intervention group and 34 % in the placebo group ( p < 0.05 ) . Conclusion . Low-dose oral prednisolone had both a short-term and a longer sustained effect result ing in less knee pain , better physical function , and attenuation of systemic inflammation in older patients with knee OA ( Clinical Trials.gov identifier NCT01619163 ) |
985 | 25,304,469 | The available evidence suggests a moderate but significant association between ambulatory BP and pre clinical organ damage , mainly based on studies in nephropathy and /or diabetes . | OBJECTIVE In children , out-of-office blood pressure ( BP ) assessment ( especially ambulatory monitoring ) is regarded as indispensable for accurate hypertension diagnosis .
This article review ed the evidence on the association between out-of-office BP measurements and pre clinical organ damage indices in children . | Blood pressure can be determined more precisely with the use of 24 hours ambulatory measurement in type 1 diabetics . Nitric oxide ( NO ) has been suggested to be responsible for the vascular changes described in early diabetic nephropathy . We aim ed to investigate serum NO concentration along with ambulatory blood pressure monitoring ( ABPM ) parameters in type 1 diabetic patients and to find out whether there are correlation between serum NO level and ABPM parameters . Forty type 1 diabetic subjects and 35 controls were enrolled . Diabetic subjects were grouped as microalbuminuric ( n=16 ) and normalbuminuric ( n=24 ) . Casual and ambulatory blood pressure parameters and serum NO concentrations were measured in all study population . Microalbuminuric subjects had higher nighttime systolic blood pressure ( SBP ) , 24 hours diastolic blood pressure ( DBP ) and 24 hours mean arterial pressure ( MAP ) than controls . Both microalbuminuric and normalbuminuric subjects had also significantly higher nighttime DBP and nighttime MAP than controls . Serum NO concentrations were higher in normalbuminuric and microalbuminuric subjects than controls . Serum NO concentrations were positively correlated with daytime DBP and MAP , nighttime SBP , DBP and MAP , and 24 hours DBP and MAP in microalbuminuric subjects . Serum NO concentrations were also positively correlated with nighttime DBP in normalbuminuric subjects . Multiple linear regression analysis revealed that serum NO(2)- + NO(3)- concentrations and 24 hours DBP were independently associated with the development of microalbuminuria . Albuminuria seems to be closely associated with serum NO concentrations and ABPM parameters in type 1 DM patients . A prospect i ve follow-up study on diabetic patients with normo- and micro- albuminuria is needed to confirm the predictive values of increased NO concentrations and ABPM parameters on the development of albuminuria Abstract . Recently , an international consensus paper was published for st and ardization of home self-blood pressure ( BP ) measurement in adults . However , few data exist regarding home BP measurement in children , although it is recommended for all pediatric patients on renal replacement therapy in Germany . Therefore , a survey was performed among German-speaking pediatric nephrologists ( members of the Arbeitsgemeinschaft Pädiatrische Nephrologie ) in order to study their opinions about home blood pressure measurements . Approximately 75 % of German pediatric nephrology centers responded to the survey . More than 70 % of the interviewees prescribed a blood pressure device for all children with renal diseases and hypertension or on renal replacement therapy . For children with antihypertensive medication , 2.8 daily measurements were recommended at mean and 2.2 measurements for children without therapy . Auscultation of Korotkoff sounds and oscillometric BP measurements were used in the same percentage for home BP recordings . The upper cut of level for home blood pressure values was rated by the pediatric nephrologists and compared to reference values of casual blood pressure . There was good agreement for upper systolic BP , but as many as 40 to 50 % of the interviewees accepted upper diastolic BP values higher than the 97th percentile for casual BP . Home BP measurement was judged to be more important than office BP measurement by 64 % of the nephrologists and less important than 24 h ambulatory blood pressure monitoring by 67 % . The results of the survey showed wide discrepancies for st and ards of home BP measurement in children and adolescents , especially for the recommendations for upper diastolic BP . Before home blood pressure measurements can be recommended unrestrictedly in children and adolescents , we stress the need for st and ardization of blood pressure devices and measurement . Prospect i ve studies in children are needed to demonstrate that these st and ards facilitate better prediction of cardiovascular outcome using home BP measurements compared to office BP recordings in children Whereas the diurnal fall of BP ( dipping ) is an important prognostic marker in patients with chronic renal failure ( CRF ) , the integrity of physiologic ultradian ( i.e. , shorter than 24 h ) cardiovascular rhythms in patients with CRF is unknown . Also , the relationship between conventional dipping analysis and Fourier spectral rhythm analysis has not been examined in renal hypertension . The prevalence and dimensions of the circadian and three ultradian ( 12 , 8 , and 6 h ) cardiovascular rhythms were studied by ambulatory BP monitoring in 214 children ( aged 3 to 18 yr ) with CRF ( stage 2 to 4 chronic kidney disease ) and no antihypertensive treatment compared with 938 healthy control subjects , and the relationship of rhythm characteristics to conventional dipping parameters , renal function , proteinuria , and serum electrolytes was assessed . The CRF cohort exhibited significantly reduced amplitudes of the circadian and all ultradian cardiovascular rhythms studied ( all P < 0.01 ) . Moreover , all BP and most heart rate rhythms showed significantly delayed acrophases ( time of peak ; P < 0.01 ) . Whereas conventional BP dipping parameters ( day/night difference , day/night ratio ) and the 24-h BP amplitude were independent of renal function , the 8-h BP amplitude was positively correlated with GFR ( r = 0.3 , P = 0.01 ) and inversely correlated with the urinary protein/creatinine ratio ( r = -0.27 , P < 0.05 ) , and the 6-h BP amplitude was inversely correlated with proteinuria ( r = -0.3 , P < 0.02 ) . Children who displayed 24- or 12-h cardiovascular rhythms had significantly lower serum calcium levels than children without these rhythms . In summary , children with CRF display not only blunted circadian but also blunted ultradian cardiovascular rhythms . Ultradian but not circadian rhythms or conventional dipping parameters are quantitatively associated with renal function and proteinuria BACKGROUND Left-ventricular hypertrophy ( LVH ) is a risk factor for cardiovascular morbidity . Antihypertensive treatment with angiotensin-converting enzyme inhibitors ( ACEI ) is able to induce the regression of LVH in adults . However , there has been no study of the ability of ACEI to induce the regression of LVH in children . Our aim was to investigate the effect of ramipril on left-ventricular mass and blood pressure ( BP ) in hypertensive children . METHODS Twenty-one children ( median age , 15 years ) with renal ( 76 % ) or primary ( 24 % ) hypertension were prospect ively treated with ramipril monotherapy for 6 months . Blood pressure was evaluated using ambulatory BP monitoring , with hypertension defined as mean BP > or=95th percentile . Left-ventricular hypertrophy was defined either as left-ventricular mass index ( LVMI ) > 38.6 g/m(2.7 ) ( pediatric definition ) or as LVMI > 51.0 g/m(2.7 ) ( adult definition ) . RESULTS Nineteen children completed the study . The median LVMI decreased from 36.8 g/m(2.7 ) ( range , 18.9 to 55.8 g/m(2.7 ) ) to 32.6 g/m(2.7 ) ( range , 19.0 to 52.1 g/m(2.7 ) ; P < .05 ) after 6 months . The prevalence of LVH decreased from 42 % to 11 % using the pediatric definition ( P < .05 ) and did not change using the adult definition ( ie , it remained at 5 % ) . The median ambulatory BP decreased by 11 , 7 , 8 , and 7 mm Hg for daytime systolic , daytime diastolic , nighttime systolic , and nighttime diastolic BP ( P < .05 ) , respectively . A positive correlation was found between LVMI and nighttime systolic BP at the start of the study ( r = 0.46 , P < .05 ) . CONCLUSIONS Ramipril is an effective drug in children with hypertension , for its ability to reduce not only BP but also left-ventricular mass and induce regression of LVH Background : Hypertension is a frequent complication of end-stage renal disease and left ventricular hypertrophy ( LVH ) is common in patients with poorly controlled hypertension . The aim of this study was to evaluate hypertension in pediatric peritoneal dialysis ( PD ) patients , to compare casual and ambulatory blood pressure ( BP ) measurements and to evaluate the impact of BP parameters on LVH . Methods : The study comprised 25 PD patients ( 9 M , 16 F ; mean age 14.14 ± 3.32 years ) that have been followed in outpatient clinics . Medical records were review ed for demographic features ; casual BP measurements , ambulatory blood pressure monitoring ( ABPM ) and echocardiographic evaluation were applied to all patients . Results : The mean 24-hour and daytime systolic blood pressure ( SBP ) values were found to be higher than casual SBP ( p < 0.001 ) . Significant difference was present in the frequency of hypertension between casual SBP ( 32 % ) and the mean daytime SBP ( 56 % ) ( p < 0.05 ) . Nighttime systolic hypertension was detected in 14 ( 56 % ) and diastolic hypertension in 16 ( 64 % ) patients . Elevated daytime SBP load and DBP load were detected in 64 and 76 % of the patients , respectively . Elevated nighttime SBP load and DBP load were detected in 72 % of the patients . Seventeen ( 68 % ) patients had attenuated dipping for SBP . The mean left ventricular mass index ( LVMI ) was 52.65 ± 18.17 g/m2.7 and 13 ( 52 % ) patients had LVH . LVMI was significantly correlated with casual BP measurements and the majority of ABPM parameters . Conclusion : The majority of pediatric PD patients had BP abnormalities in which severity was most accurately assessed with ABPM . Casual BP and majority of ABPM parameters were found to be significantly correlated with LVMI . Ambulatory blood pressure monitoring should be performed in all pediatric PD patients BACKGROUND Angiotensin-converting enzyme inhibitors are the drugs of choice in renal hypertension . The efficacy and safety of ramipril in adults has been proved ; however , data on effectiveness of ramipril in children are few . The aim of the present study was to investigate the effect of ramipril on blood pressure ( BP ) and proteinuria in children with chronic kidney diseases . METHODS A total of 31 children ( median age 11.3 years , range 1.9 - 19.8 years ) with various chronic nephropathies and hypertension or proteinuria were prospect ively treated with ramipril for 6 months . Blood pressure was evaluated using ambulatory BP monitoring and hypertension was defined as mean BP equal to or greater than the 95th percentile for healthy children . Proteinuria was defined as protein excretion > or = 100 mg/m(2)/24 h. The starting dose of ramipril was 1.5 mg/m(2)/24 h once daily . In 27 children it was given as monotherapy . RESULTS The median decrease in ambulatory BP was 11 mm Hg for daytime systolic , 10 mm Hg for daytime and nighttime diastolic , and 8 mm Hg for nighttime systolic BP . Hypertension normalized in 55 % of the children . Proteinuria decreased in 84 % of the children with pathologic proteinuria ; the median decrease was 51 % . A positive correlation was found between initial proteinuria and change of proteinuria ( r = 0.95 , P < .001 ) . Glomerular filtration rate and serum potassium level did not change significantly . One child developed a cough that was believed to be related to ramipril . CONCLUSIONS Ramipril is an effective and safe drug in children with chronic kidney diseases associated with hypertension , proteinuria , or both BACKGROUND While the antihypertensive and renoprotective potency of angiotensin-converting enzyme ( ACE ) inhibitors is well-established in adults with hypertension and /or chronic renal failure , little experience exists in pediatric chronic kidney disease . METHODS As part of a prospect i ve assessment of the renoprotective efficacy of ACE inhibition and intensified blood pressure ( BP ) control , 397 children ( ages 3 to 18 years ) with chronic renal failure [ CRF ; glomerular filtration rate ( GFR ) 11 to 80 mL/min/1.73 m2 ] and elevated or high-normal BP received ramipril ( 6 mg/m2 ) following a 6-month run-in period including a two-month washout of any previous ACE inhibitors . Drug efficacy was assessed by two monthly office BP and proteinuria assessment s , and by ambulatory BP monitoring at start and after 6 months of treatment . RESULTS In the 352 patients completing six months of treatment , 24-hour mean arterial pressure ( MAP ) had decreased by a mean of 11.5 mm Hg ( -2.2 SDS ) in initially hypertensive subjects , but only by 4.4 mm Hg ( -0.8 SDS ) in patients with initially normal BP . A linear correlation was found between MAP at baseline and the change of MAP during treatment ( r= 0.51 ; P < 0.0001 ) . The antihypertensive response was independent of changes in concomitant antihypertensive medication or underlying renal disease . BP was reduced with equal efficacy during day- and nighttime . Urinary protein excretion was reduced by 50 % on average , with similar relative efficacy in patients with hypo/dysplastic nephropathies and glomerulopathies . The magnitude of proteinuria reduction depended on baseline proteinuria ( r= 0.32 , P < 0.0001 ) , and was correlated with the antihypertensive efficacy of the drug ( r= 0.22 , P < 0.001 ) . The incidence of rapid rises in serum creatinine and progression to end-stage CRF during treatment did not differ from the pretreatment observation period . Mean serum potassium increased by 0.3 mmol/L. Ramipril was discontinued in three patients due to symptomatic hypotension or hyperkalemia . Hemoglobin levels decreased by 0.6 g/dL in the first two treatment months and remained stable thereafter . CONCLUSION Ramipril appears to be an effective and safe antihypertensive and antiproteinuric agent in children with CRF-associated hypertension . The BP lowering and antiproteinuric effects are greatest in severely hypertensive and proteinuric children Masked hypertension , an elevated daytime ambulatory blood pressure in the presence of a normal office blood pressure , confers an increased cardiovascular risk to adults . We investigated the prevalence , persistence , and clinical significance of masked hypertension in children and adolescents . We enrolled 592 youths ( 6 to 18 years old ) . Youths with masked hypertension ( n=34 ) and a r and om sample of the normotensive participants ( n=200 ) were followed-up . In a nested case-control study , we compared echocardiographic left ventricular mass among cases with persistent masked hypertension and normotensive controls . At baseline , mean age was 10.2 years ; 535 youths were normotensive on office and daytime ambulatory blood pressure measurement ( 90.4 % ) , and 45 had masked hypertension ( 7.6 % ) . Compared with normotensive controls , participants with masked hypertension had a higher ambulatory pulse rate , were more obese , and were 2.5-times more likely to have a parental history of hypertension . Among 34 patients with masked hypertension ( median follow-up 37 months ) , 18 became normotensive , 13 had persistent masked hypertension , and 3 had sustained hypertension . Patients with persistent masked hypertension ( n=17 ) or who progressed from masked to sustained hypertension ( n=3 ) had a higher left ventricular mass index ( 34.9 versus 29.6 g/m2.7 ; P=0.023 ) and a higher percentage with left ventricular mass index above the 95th percentile ( 30 % versus 0 % ; P=0.014 ) than normotensive controls . In children and adolescents , masked hypertension is a precursor of sustained hypertension and left ventricular hypertrophy . This condition warrants follow-up and , once it becomes persistent , is an indication for blood pressure-lowering treatment Diabetes mellitus ( DM ) is now considered as the major cause of end-stage kidney failure , and hypertension ( HTN ) is one of the main determinants of progression of renal disease . The aim of this study was to assess the role of blood pressure ( BP ) by ambulatory blood pressure monitoring ( ABPM ) in children and adolescents with type-1 DM and its correlation with micro-albuminuria ( MA ) and diabetic control . Eighty-one patients with type-1 DM ( mean age 13 ± 4 years ) , whose duration of DM was at least two years , were enrolled in this study . The prevalence of HTN based on ABPM was 28.4 % , while by casual method it was 32.1 % . The pattern of HTN was as follows : mean systolic HTN 27.2 % , mean diastolic HTN 11.2 % , daytime systolic HTN 17.3 % , daytime diastolic HTN 6.2 % , night systolic HTN 30.9 % , and night diastolic HTN 29.7 % . The systolic and diastolic BP loads were 33.4 and 27.2 % , respectively . About 70.4 % of the patients were non-dippers , 12.4 % had masked HTN , and 3.7 % had white coat HTN . The pre-valence of MA was 34.6 % and that of abnormal HbA 1 c was 82.7 % . There was no correlation between HTN and both MA and HbA 1 c ; also , no correlation was found between the duration of diabetes and HbA 1 c. Moreover , no significant correlation was found between the duration of diabetes and MA ( P = 0.080 ) . Despite the high prevalence of abnormal BP profile among diabetic children , prospect i ve longitudinal studies considering the other major risk factors , particularly genetic factors , which have an impact on the progression to diabetic nephropathy , are recommended Abstract . The purpose of this study was to identify hypertension in children and adolescents in an early stage of autosomal dominant polycystic kidney disease ( ADPKD ) by the application of ambulatory blood pressure monitoring ( ABPM ) over 24 h ; 32 children and adolescents ( mean age 12.3±4.7 years ) were examined . The diagnosis was based on family history and ultrasound examination . In 21 children ADPKD was confirmed by molecular genetic analysis . At the time of the study , 45 % patients were asymptomatic and all had glomerular filtration rates ( GFRs ) ≥65 ml/min per 1.73 m2 . By ABPM , 11 patients ( 34 % ) were defined as hypertensive ( systolic or diastolic blood pressure > 95th percentile ) , including 4 with an exclusive nocturnal hypertension . Of 7 patients with daytime hypertension , 4 had normal blood pressure by casual measurements . The nocturnal dip in blood pressure was reduced in 2 patients . Blood pressure correlated with renal size , but not with GFR , concentrating capacity , proteinuria , and plasma renin activity . The study reveals an early trend for increased blood pressure in children with ADPKD , requiring close supervision BACKGROUND Hypertension and left ventricular hypertrophy ( LVH ) are possible complications in pediatric patients after renal transplantation . METHODS We performed left ventricular echocardiography , 24-hour ambulatory blood pressure monitoring ( 24-hr ABPM ) , and treadmill tests in 28 pediatric renal transplant patients ( mean age 16.1 + /- 3.7 ; time since transplantation 36 + /- 23 months ) . Left ventricular mass ( LVM ) was indexed for height 2.7 . RESULTS LVH was found in 82 % of the patients . Seven of these patients were normotensive by 24-hour ABPM , but five patients showed a hypertensive systolic BP response during the treadmill test . LVM/height 2.7 correlated significantly with the mean 24-hour systolic BP ( P = 0.002 ) and with the maximal exercise systolic BP ( P = 0.002 ) . CONCLUSION LVH is frequent in pediatric renal transplant patients . More information is needed with respect to the risk for LVH , including data from 24-hour ABPM and treadmill testing Abstract Inhibition of the angiotensin-converting enzyme ( ACE ) exerts a renoprotective effect in adult patients with chronic kidney disease . We evaluated prospect ively changes in blood pressure ( BP ) , protein excretion and renal function after administration of the long-acting ACE inhibitor ramipril as monotherapy during 6 months in 14 moderately hypertensive children aged 5–18 years with various nephropathies . Four patients initially had a decreased glomerular filtration rate ( GFR below 60 ml/min/1.73 m2 ) . BP was evaluated by ambulatory 24-h monitoring . After 2 weeks of treatment by oral ramipril ( 1.5 mg/m2 once daily ) , mean values of systolic and diastolic 24-h ambulatory BP fell by more than 5 mmHg in nine patients . In eight patients the dose was doubled . At the end of the study systolic BP was below the 95th percentile in 9 and diastolic BP in 13 patients . The initially reduced nocturnal dip increased significantly . Of 11 patients with an increased albumin excretion ( median 1.3 g/g creatinine ) , 6 responded to ramipril by a median reduction of 78 % ( range 24–83 % ) , whilst in 5 albuminuria increased ( median + 19 % ) . GFR was well preserved and no other adverse effects from the drug were noted . The study demonstrates that ramipril is an efficacious antihypertensive agent in children with renal hypertension . It is well tolerated , even in mild renal insufficiency . In addition , the drug has a persistent antiproteinuric action in about half of the patients contributing to conserve renal function |
986 | 26,529,613 | No increase in the incidence of total cancer events but an increase in the incidence of thrombus was found to be associated with HT .
Conclusions : HT is associated with a reduced risk of total , hip , and vertebral fractures , with a possible attenuation of this protection effect after it is stopped or when it is begun after 60 years .
However , there may be an increase in the incidence of thrombus formation associated with HT | Objective : The aim of this study was to investigate the association between hormone therapy ( HT ) use and the development of bone fractures . | OBJECTIVE To determine the effects of four doses of a 7-day transdermal 17beta-estradiol ( E2 ) delivery system , including 0.025 mg/day , on bone loss in postmenopausal women . METHODS This was a multicenter , double-masked , r and omized , placebo-controlled study of the effects of transdermal E2 at doses of 0.025 , 0.05 , 0.06 , and 0.1 mg/day for the prevention of postmenopausal osteoporosis . Efficacy was evaluated from bone mineral density of lumbar vertebrae L2-L4 , radius , proximal femur , and total hip measured with dual-energy x-ray absorptiometry . Serum osteocalcin and urinary pyridinoline and deoxypyridinoline concentrations were measured . RESULTS At 24 months , E2 doses of 0.025 , 0.05 , 0.06 , and 0.1 mg/day result ed in mean increases in bone mineral density of the lumbar spine of 2.37 % , 4.09 % , 3.28 % , and 4.70 % , respectively , and increased bone mineral density of the total hip by 0.26 % , 2.85 % , 3.05 % , and 2.03 % , respectively . All increases were statistically significantly greater than placebo , which decreased bone mineral density by 2.49 % at the spine and 2.04 % at the hip . Consistent and significant improvements in biochemical markers of bone turnover also were noted at various intervals in all treatment groups . The most frequent adverse events were local reactions from the transdermal drug-delivery system , effects of estrogen , and menopausal symptoms . CONCLUSION Transdermal E2 at doses of 0.025 , 0.05 , 0.06 , and 0.1 mg/day effectively prevented bone loss in postmenopausal women A 10-year , double-blind prospect i ve study was undertaken to evaluate the effects of estrogen replacement therapy . The sample population consisted of 84 pairs of r and omly chosen postmenopausal patients who were matched for age and diagnosis . One half of the patients received conjugated estrogens and cyclic progesterone , while the other half received placebo . Estrogen-treated patients whose therapy started within 3 years of menopause showed improvement or no increase in osteoporosis . Control patients demonstrate an increase in their osteoporosis Postmenopausal hormone replacement therapy is associated with a reduction in the incidence of coronary heart disease . However , inconclusive results have been reported with respect to the risk of stroke , and recent studies consistently showed an increased risk of venous thromboembolism in postmenopausal women using oral estrogen . There are surprisingly few interventional studies to assess the true effects of estrogen-progestin regimens on blood coagulation and fibrinolysis , and the impact of the route of estrogen administration on hemostasis has not been well documented . Therefore , we investigated the effects of oral and transdermal estradiol/progesterone replacement therapy on hemostatic variables . Forty-five healthy postmenopausal women , aged 45 to 64 years , were assigned r and omly to one of the three following groups : cyclic oral or transdermal estradiol , both combined with progesterone , or no hormonal treatment . Hemostatic variables were assayed at baseline and after a 6-month period . Pairwise differences in the mean change between the three groups were compared using nonparametric tests . Oral but not transdermal estradiol regimen significantly increased the mean value of prothrombin activation peptide ( F1 + 2 ) and decreased mean antithrombin activity compared with no treatment . Differences in fragment F1 + 2 levels between active treatments were significant . The oral estrogen group was associated with a significant decrease in both mean tissue-type plasminogen ( t-PA ) concentration and plasminogen activator inhibitor ( PAI-1 ) activity and a significant rise in global fibrinolytic capacity ( GFC ) compared with the two other groups . A transdermal estrogen regimen had no significant effect on PAI-1 , t-PA , and GFC levels . There were no significant changes in mean values of fibrinogen , factor VII , von Willebr and factor , protein C , fibrin D-dimer , and plasminogen between and within the three groups . We conclude that oral estrogen/progesterone replacement therapy may result in coagulation activation and increased fibrinolytic potential , whereas opposed transdermal estrogen appears without any substantial effects on hemostasis . Whereas these results may account for an increased risk of venous thromboembolism in users of oral postmenopausal estrogen , they emphasize the potential importance of the route of estrogen administration in prescribing hormone replacement therapy to postmenopausal women , especially to those at high risk of thrombotic disease CONTEXT Therapy with individual antiresorptive agents has been shown to be effective for prevention and treatment of postmenopausal osteoporosis , but whether combination antiresorptive therapy with hormones and bisphosphonates is safe or efficacious or how these agents compare in elderly women is unknown . OBJECTIVE To determine whether hormone replacement and the bisphosphonate alendronate sodium in combination are efficacious and safe , and how they compare with monotherapy in community-dwelling elderly women . DESIGN R and omized , double-blind , placebo-controlled , clinical trial . SETTING AND PARTICIPANTS Five hundred seventy-three community-dwelling women age 65 years or older were screened : 485 completed screening and 373 ( aged 65 to 90 years ) were r and omized following a 3-month , open-label , run-in phase with hormone replacement and alendronate placebo . The trial was conducted at a single academic US medical center from January 1996 to May 2001 . INTERVENTIONS Participants were r and omly assigned in a 2 x 2 factorial design to receive hormone replacement ( conjugated equine estrogen , 0.625 mg/d , with or without medroxyprogesterone , 2.5 mg/d ) and alendronate , 10 mg daily , both agents , or neither . All participants received calcium and vitamin D supplements . MAIN OUTCOME MEASURES Annualized change in bone mineral density of the hip and spine and occurrence of adverse events . RESULTS Bone mineral density at 3 years was significantly greater at all femoral and vertebral sites in women treated with combination therapy than with monotherapy , with mean ( SD ) increases of 5.9 % ( 3.8 ) at the total hip , 10.4 % ( 5.4 ) at the posteroanterior lumbar spine , and 11.8 % ( 6.8 ) at the lateral lumbar spine . Mean ( SD ) increases in bone mass at the hip in women treated with alendronate alone were significantly greater than in those treated with hormone replacement therapy alone ( 4.2 % [ 3.8 ] vs 3.0 % [ 4.9 ] ; P<.05 , respectively ) , and alendronate result ed in more responders to therapy . All therapies were well tolerated and participant retention was 90 % at 3 years . CONCLUSIONS Combination therapy with hormone replacement and alendronate was efficacious and well tolerated in this cohort . Alendronate was superior to hormone replacement , and combination therapy was superior to either therapy alone . Combination therapy may represent an option for women with more severe disease or for those who have failed to achieve an adequate response to monotherapy BACKGROUND Long-term treatment of patients with asymptomatic primary hyperparathyroidism remains controversial , but the presence of osteoporosis is regarded as an indication for parathyroidectomy . Hormone replacement therapy ( HRT ) is a possible alternative therapy in osteopenic postmenopausal women with the disorder , and results of short-term studies suggest a beneficial effect on bone mass comparable to that achieved by parathyroidectomy . Longer-term data are required to further assess the efficacy of this treatment in chronic stable primary hyperparathyroidism . METHODS We report the results of the extension from 2 to 4 years of a r and omized , placebo-controlled trial of HRT in postmenopausal women with primary hyperparathyroidism . Of 23 postmenopausal women with primary hyperparathyroidism , 11 received active HRT with conjugated equine estrogen , 0.625 mg/d , and medroxyprogesterone acetate , 5 mg/d , and 12 received placebo . Bone mineral density was measured throughout the skeleton at 6-month intervals using dual-energy x-ray absorptiometry in these women and in 50 normocalcemic age-matched control subjects . None of the 23 patients withdrew during the extension period . RESULTS Changes in bone mineral density were more positive in those taking HRT than placebo , with the between-group differences at 4 years being 4.6 % in the total body , 7.5 % in the lumbar spine , 7.4 % in the femoral neck , 8.2 % in the femoral trochanter , 6.8 % in the legs , and 7.0 % in the forearm ( P<.01 ) . At skeletal sites composed predominantly of cortical bone , there was a progressive divergence of the 2 groups . Biochemical markers of bone turnover remained lower throughout the study in women taking HRT . When rates of bone loss were compared between the placebo group and healthy women of comparable age , bone loss tended to be more marked throughout the skeleton in women with hyperparathyroidism , but only in the total body and its legs subregion was this difference significant . CONCLUSIONS Hormone replacement therapy is efficacious in the long-term management of osteopenia in postmenopausal women with primary hyperparathyroidism and thus represents an important new therapeutic option for asymptomatic patients who do not have other indications for surgery . Bone loss seems to be accelerated in untreated primary hyperparathyroidism BACKGROUND We conducted a 3-year , double-blind , r and omized , placebo-controlled study to determine whether the positive effects of hormone/estrogen replacement therapy ( H/ERT ) on postcranial bone density are accompanied by similar positive effects on oral bone mass . METHODS A total of 135 postmenopausal women ( aged 41 - 70 years ) with no evidence of moderate or severe periodontal disease were r and omized to receive daily oral conjugated estrogen ( Premarin ; 0.625 mg ) alone or in combination with medroxyprogesterone acetate ( Prempro ; 0.625 and 2.5 mg , respectively ) or placebo . All subjects received calcium carbonate ( 1000 mg/d ) and cholecalciferol ( 400 [ corrected ] IU/d ) supplements . The primary efficacy end points were the changes in alveolar crest height and alveolar bone density . Alveolar crest height was measured on bite-wing radiographs , and changes in alveolar bone mass were assessed by means of digital-subtraction radiography . Postcranial bone density was measured in the lumbar spine and left proximal femur by means of dual-energy x-ray absorptiometry . RESULTS Hormone/estrogen replacement therapy significantly increased alveolar bone mass compared with placebo ( + 1.84 % vs + 0.95 % [ P = .04 ] ) , and tended to improve alveolar crest height ( + 4.83 % vs + 3.46 % [ P = .34 ] ) . Bone mineral density of the proximal femur significantly increased in the H/ERT compared with the placebo group ( total proximal femur , + 3.59 % vs + 0.22 % [ P = .001 ] ; neck , + 2.05 % vs -0.34 % [ P = .02 ] ; trochanter , + 3.49 % vs + 0.08 % [ P<.001 ] ) , but not the lumbar spine ( + 1.01 % vs + 0.17 % [ P = .39 ] ) . Changes in alveolar bone mass correlated with bone density changes in the total femur ( r = 0.28 [ P = .02 ] ) and femoral trochanter ( r = 0.25 [ P = .04 ] ) in the H/ERT but not in the placebo group . CONCLUSIONS Postcranial and oral bone mass were increased in postmenopausal women receiving H/ERT . Improvement in oral bone health constitutes an additional benefit of H/ERT OBJECTIVE To determine the relative risk for sustaining a first hip fracture after hormone replacement therapy . DESIGN Prospect i ve population -based cohort study with an average observation period of 5.7 years . SETTING A prescription-based cohort in the Uppsala health care region in Sweden . PARTICIPANTS The cohort ( 23 246 women ) comprised virtually all women of 35 years of age and older who received noncontraceptive estrogens from April 1977 through March 1980 . Comparisons were made with women in the background population . MEASUREMENTS Follow-up through 1983 was done with regard to hospital admissions for a first cervical or trochanteric hip fracture . The observed number of cases was compared with that expected on the basis of person-years of observation in the cohort and incidence rates in the background population . Analyses were made in exposure categories , based solely on prescription data . MAIN RESULTS During 133 022 person-years of observation , 163 cases of first hip fracture occurred , compared with the 205.5 expected , yielding an overall relative risk of 0.79 ( 95 % CI , 0.68 to 0.93 ) . The greatest protective effect ( relative risk , 0.37 ; CI , 0.13 to 0.79 ) was found against trochanteric fracture among women receiving potent estrogens who were under 60 years of age at cohort entry . This group also had the highest proportion of treatments with combinations of estrogens and progestogen ( 41 % ) . Treatment with less potent estrogens , mainly estriols , had no protective effect . Data indicated that the baseline risk for hip fracture was not lower in the cohort women than in the background population . CONCLUSIONS Treatment with potent estrogens , both alone and possibly when combined with progestogens , reduces the risk for both cervical and trochanteric hip fractures within the first decade after menopause We examined whether estradiol and norethindrone hormone therapy ( HT ) prevented decline in delayed verbal recall in older women with normal to mildly impaired memory functioning . This was a 2-year , r and omized , double-blind , placebo-controlled trial of 142 women aged 61 - 87 , r and omly assigned to receive 1 mg 17-beta estradiol daily and 0.35 mg norethindrone 3 days/week or daily placebo for 2 years . The primary outcome was short-delay verbal recall of the California Verbal Learning Test ( CVLT ) . To look for differences in response to HT by baseline short-delay recall , we examined the primary outcome in participants grouped according to whether their baseline scores were below average for the age group or greater than or equal to this score and according to whether they met criteria for Mild Cognitive Impairment ( MCI ) or not . 133 women completed 1 year of the trial and 128 completed 2 years . Prespecified covariates in all repeated measures analyses of covariance ( RANCOVA ) included age , education , APOE epsilon4 , and prior HT use . RANCOVA showed no overall significant treatment effects at year 1 or year 2 . After testing for an interaction , which was significant ( p=0.02 ) , we found that women in the HT group who scored at or above the average showed significantly less decline than the placebo group in short-delay verbal recall after 1 year , p=0.007 and 2 years , p=0.01 . No treatment effects were found in women below the average in either year . When grouped according to whether the participant met criteria for MCI , the interaction between treatment group and MCI subgroup was not significant . These results suggest that benefits of estrogen exposure may be limited to those with average to above average scores on the delayed verbal recall . HT dose and formulation may have contributed to these beneficial outcomes . Replication is warranted before recommendations can be made in the clinical setting Objective To assess the long term risks and benefits of hormone replacement therapy ( combined hormone therapy versus placebo , and oestrogen alone versus combined hormone therapy ) . Design Multicentre , r and omised , placebo controlled , double blind trial . Setting General practice s in UK ( 384 ) , Australia ( 91 ) , and New Zeal and ( 24 ) . Participants Postmenopausal women aged 50 - 69 years at r and omisation . At early closure of the trial , 56 583 had been screened , 8980 entered run-in , and 5692 ( 26 % of target of 22 300 ) started treatment . Interventions Oestrogen only therapy ( conjugated equine oestrogens 0.625 mg orally daily ) or combined hormone therapy ( conjugated equine oestrogens plus medroxyprogesterone acetate 2.5/5.0 mg orally daily ) . Ten years of treatment planned . Main outcome measures Primary outcomes : major cardiovascular disease , osteoporotic fractures , and breast cancer . Secondary outcomes : other cancers , death from all causes , venous thromboembolism , cerebrovascular disease , dementia , and quality of life . Results The trial was prematurely closed during recruitment , after a median follow-up of 11.9 months ( interquartile range 7.1 - 19.6 , total 6498 women years ) in those enrolled , after the publication of early results from the women 's health initiative study . The mean age of r and omised women was 62.8 ( SD 4.8 ) years . When combined hormone therapy ( n=2196 ) was compared with placebo ( n=2189 ) , there was a significant increase in the number of major cardiovascular events ( 7 v 0 , P=0.016 ) and venous thromboembolisms ( 22 v 3 , hazard ratio 7.36 ( 95 % CI 2.20 to 24.60 ) ) . There were no statistically significant differences in numbers of breast or other cancers ( 22 v 25 , hazard ratio 0.88 ( 0.49 to 1.56 ) ) , cerebrovascular events ( 14 v 19 , 0.73 ( 0.37 to 1.46 ) ) , fractures ( 40 v 58 , 0.69 ( 0.46 to 1.03 ) ) , and overall deaths ( 8 v 5 , 1.60 ( 0.52 to 4.89 ) ) . Comparison of combined hormone therapy ( n=815 ) versus oestrogen therapy ( n=826 ) outcomes revealed no significant differences . Conclusions Hormone replacement therapy increases cardiovascular and thromboembolic risk when started many years after the menopause . The results are consistent with the findings of the women 's health initiative study and secondary prevention studies . Research is needed to assess the long term risks and benefits of starting hormone replacement therapy near the menopause , when the effect may be different . Trial registration Current Controlled Trials IS RCT N BACKGROUND Results of observational studies suggest that hormone replacement therapy ( HRT ) could reduce the risk of coronary heart disease ( CHD ) , but those of r and omised trials do not indicate a lower risk in women who use oestrogen plus progestagen . The aim of this study was to ascertain whether or not unopposed oestrogen reduces the risk of further cardiac events in postmenopausal women who survive a first myocardial infa rct ion . METHODS The study was a r and omised , blinded , placebo controlled , secondary prevention trial of postmenopausal women , age 50 - 69 years ( n=1017 ) who had survived a first myocardial infa rct ion . Individuals were recruited from 35 hospitals in Engl and and Wales . Women received either one tablet of oestradiol valerate ( 2 mg ; n=513 ) or placebo ( n=504 ) , daily for 2 years . Primary outcomes were reinfa rct ion or cardiac death , and all-cause mortality . Analyses were by intention-to-treat . Secondary outcomes were uterine bleeding , endometrial cancer , stroke or other embolic events , and fractures . FINDINGS Frequency of reinfa rct ion or cardiac death did not differ between treatment groups at 24 months ( rate ratio 0.99 , 95 % CI 0.70 - 1.41 , p=0.97 ) . Similarly , the reduction in all-cause mortality between those who took oestrogen and those on placebo was not significant ( 0.79 , 0.50 - 1.27 , p=0.34 ) . The relative risk of any death ( 0.56 , 0.23 - 1.33 ) and cardiac death ( 0.33 , 0.11 - 1.01 ) was lowest at 3 months post-recruitment . INTERPRETATION Oestradiol valerate does not reduce the overall risk of further cardiac events in postmenopausal women who have survived a myocardial infa rct ion Objective —Activated protein C ( APC ) resistance not related to the factor V Leiden mutation is a risk factor for venous thrombosis . Oral estrogen replacement therapy ( ERT ) has been reported to induce APC resistance . Little is known about the effect of transdermal estrogen . Methods and Results —We enrolled 196 postmenopausal women who were r and omly allocated to receive either 1 mg 17&bgr;-estradiol orally ( n=63 ) or 50 & mgr;g 17&bgr;-estradiol transdermally per day ( n=68 ) , both associated with 100 mg progesterone daily or placebo ( n=65 ) for 6 months . An activated partial thromboplastin time (APTT)–based test and the effect of APC on thrombin potential ( ETP ) were used . Oral ERT induced an ETP-based APC resistance compared with both placebo ( P = 0.006 ) and transdermal ERT ( P < 0.001 ) , but there was no significant effect of transdermal ERT compared with placebo ( P = 0.191 ) . There was no significant effect of ERT on the APTT-based APC sensitivity ratio . Prothrombin fragment 1 + 2 plasma levels were significantly higher after 6 months of treatment in women allocated to oral ERT compared with those on placebo and transdermal ERT and were positively and significantly correlated with changes in ETP-based APC sensitivity ratio . Conclusions —Our data show that oral , unlike transdermal , estrogen induces APC resistance and activates blood coagulation . These results emphasize the importance of the route of estrogen administration OBJECTIVE To determine the relation between estrogen replacement therapy and fractures . DESIGN Prospect i ve cohort study . SETTING Four clinical centers in Baltimore County , Maryl and ; Minneapolis , Minnesota ; Portl and , Oregon ; and the Monongahela Valley , Pennsylvania . PARTICIPANTS 9704 ambulatory , nonblack women 65 years of age or older . MEASUREMENTS Estrogen use , medical history , and anthropometric data were obtained by question naire , interview , and examination . Appendicular bone mass was measured by single-photon absorptiometry . Incident fractures were vali date d by radiographic report . RESULTS After adjustment for potential confounders , current estrogen use was associated with a decrease in the risk for wrist fractures ( relative risk [ RR ] , 0.39 ; 95 % CI , 0.24 to 0.64 ) and for all nonspinal fractures ( RR , 0.66 ; CI , 0.54 to 0.80 ) when compared with no estrogen use . Results were similar for women using unopposed estrogen or estrogen plus progestin , for women younger or older than 75 years of age , and for current smokers or nonsmokers . The effect of estrogen remained after adjustment was made for appendicular bone mass . The relative risk for hip fracture tended to be lower among current users ( RR , 0.60 ; CI , 0.36 to 1.02 ) than among never-users . Estrogen was most effective in preventing hip fracture among those older than 75 years . Current users who started estrogen within 5 years of menopause had a decreased risk for hip fractures ( RR , 0.29 ; CI , 0.09 to 0.92 ) , wrist fractures ( RR , 0.29 ; CI , 0.13 to 0.68 ) , and all nonspinal fractures ( RR , 0.50 ; CI , 0.36 to 0.70 ) when compared with women who had never used estrogen . Previous use of estrogen for more than 10 years or use begun soon after menopause had no substantial effect on the risk for fractures . CONCLUSIONS Current use of estrogen appears to decrease the risk for fracture in older women . These results suggest that for protection against fractures , estrogen should be initiated soon after menopause and continued indefinitely The value of oestrogen therapy in the prevention of osteoporosis after oophorectomy was assessed in 114 middle-aged women who participated in a double-blind controlled trial of mestranol in an average daily dose of 23 mug . The skeletal response to treatment was measured by a photon absorption technique . Where treatment was started within two months of operation subsequent bone mineral loss was prevented . Treatment started three years after oophorectomy caused a highly significant increase in bone mineral content . When treatment was delayed for six years mestranol failed to prevent subsequent bone mineral loss with age . These effects occurred independently of the associated humoral changes in calcium and phosphorus homoeostasis . Mestranol in this dosage appeared to be relatively safe , but it is too early to evaluate the long-term hazards of such therapy BACKGROUND Previous studies demonstrate that postmenopausal women who use estrogen are somewhat protected from bone loss and fractures compared with nonusers , but the extent to which estrogen users remain at risk for osteoporosis and fractures is uncertain . OBJECTIVE To determine long-term probabilities for incident fractures among postmenopausal estrogen users . METHODS We examined data from the Study of Osteoporotic Fractures , a prospect i ve cohort study with 10 years of follow-up ( 1986 - 1999 ) . This cohort includes 8816 women 65 years and older from community setting s in 4 areas of the United States . MAIN OUTCOME MEASURES Hip , wrist , vertebral , and nonvertebral fractures . RESULTS At baseline , using criteria developed by the World Health Organization , 40 % of continuous estrogen users were osteopenic and 13 % were osteoporotic at the hip or spine . Although women currently using estrogen lost less bone density than past users or those who never used estrogen , all user groups on average lost bone from the hip and calcaneus . During 10 years of observation , the adjusted probability of nonvertebral fractures was 19.6 % for continuous estrogen users , similar to current partial users and lower than past users and those who never used estrogen ( P<.05 ) . These comparisons were similar for hip , wrist , and vertebral fractures . CONCLUSIONS Although estrogen use is associated with reduced prevalence of low bone density , less bone loss , and lower probabilities for fractures , osteoporosis and fractures are common in older women who used estrogen continuously since menopause . Estrogen users should be considered in strategies design ed to detect , prevent , and treat osteoporosis BACKGROUND Hormone replacement therapy ( HRT ) , the mainstay of osteoporosis prevention , is limited because of dose-related risks , side effects , and patient acceptance . The bone-sparing efficacy and tolerability of the lowest available doses of HRT have not been adequately studied in elderly women . OBJECTIVE To determine the bone-sparing effect of continuous low-dose HRT in elderly women . DESIGN R and omized , double-blind , placebo-controlled trial . SETTING University osteoporosis research and clinical center . PATIENTS 128 healthy white women ( age > 65 years ) with low bone mass recruited by word of mouth and by local advertisement . The principal eligibility criterion was spinal bone mineral density of 0.90 g/cm2 or less . INTERVENTION Continuous therapy with conjugated equine estrogen , 0.3 mg/d , and medroxyprogesterone , 2.5 mg/d , or matching placebo . Sufficient calcium supplementation was given to bring all calcium intakes above 1000 mg/d in both groups ; supplemental oral 25-hydroxyvitamin D was given to maintain serum 25-hydroxyvitamin D levels of at least 75 nmol/L in both groups . MEASUREMENTS Bone mineral density of the spine , hip , total body , and forearm ; serum total alkaline phosphatase and serum osteocalcin levels at 6-month intervals ; and 24-hour urine creatinine and hydroxyproline excretion at baseline , 12 months , and 42 months . RESULTS During 3.5 years of observation , spinal bone mineral density increased by 3.5 % ( P < 0.001 ) in an intention-to-treat analysis and by 5.2 % among patients with greater than 90 % adherence to therapy . Significant increases were seen in total-body and forearm bone density ( P < 0.01 ) . Symptoms related to HRT ( breast tenderness , spotting , pelvic discomfort , and mood changes ) were mild and short-lived . CONCLUSIONS Continuous low-dose HRT with conjugated equine estrogen and oral medroxyprogesterone combined with adequate calcium and vitamin D provides a bone-sparing effect that is similar or superior to that provided by other , higher-dose HRT regimens in elderly women . This combination is well tolerated by most patients OBJECTIVES At present the Women 's Health Initiative trial is the only reported r and omised controlled trial study ing the effects of hormone therapy among healthy postmenopausal women . The Women 's Health Initiative reports have been criticized for lacking in generalisability , due to the characteristics of the trial population . We aim ed to compare the health effects of oral continuous combined hormone therapy with a placebo and non-treatment among healthy Estonian women . METHODS Eligible women were r and omised into a blind group of hormone therapy versus placebo and into a non-blind group of open label hormone therapy versus non-treatment . One thous and seven hundred and seventy-eight postmenopausal women aged 50 - 64 at the time of sampling were recruited in 1999 - 2001 at three clinical centers in Estonia . Participants received conjugated equine oestrogens , 0.625 mg/d , plus medroxyprogesterone acetate , 2.5mg/d , or conjugated equine oestrogens , 0.625 mg/d , plus medroxyprogesterone acetate , 5mg/d , if less than 3 years had passed since menopause at recruitment , or matched placebo or non-treatment . Trial treatment was stopped gradually from 1 January 2004 to 31 May 2004 . RESULTS After a follow-up period from 2.0 to 5.0 years the combined hazard ratio , stratified by blinding and adjusted for age at recruitment and former oral contraceptive use was 1.12 ( 95 % confidence interval [ CI ] : 0.90 - 1.40 ) for coronary heart disease , 1.24 ( 95 % CI : 0.85 - 1.82 ) for cerebrovascular disease , 1.36 ( 95 % CI : 0.73 - 2.52 ) for total cancer , and 0.61 ( 95 % CI : 0.42 to 0.89 ) for bone fractures . CONCLUSIONS The results from the Estonian Postmenopausal Hormone Therapy r and omised trial are consistent with the Women 's Health Initiative findings OBJECTIVES We investigated the incidence of new non-vertebral fractures during HRT or low-dose vitamin ( Vit ) D3 supplementation in a 5-year prospect i ve trial . METHODS A total of 464 early postmenopausal women , ( a subgroup of the Kuopio Osteoporosis Study , n = 13100 ) were r and omized to four groups : ( 1 ) HRT , a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate ; ( 2 ) Vit D ( 300 IU/day and 100 IU/day during the fifth year ) ; ( 3 ) HRT + Vit D ; and ( 4 ) placebo . Lumbar ( L2 - 4 ) and femoral neck bone mineral densities ( BMD ) were determined by dual X-ray absorptiometry ( DXA ) at baseline , after 2.5 and 5 years of treatment . All new symptomatic non-vertebral , radiographically defined fractures were recorded . RESULTS Altogether , 368 women ( 79 % ) completed the 5 year treatment . In all , 32 women had 39 non-vertebral fractures during a mean of 4.3 year follow-up ( HRT 4 , Vit D 10 , HRT + Vit D 8 and placebo 17 ) . The reduction in the incidence of new non-verterbral fractures was significant in women with HRT alone ( P = 0.032 ) when adjusted by baseline BMD and previous fractures ; observed also with the intention-to-treat principle ( P = 0.048 ) . When the HRT groups were pooled , HRT showed a significantly lower incidence of new non-vertebral fractures ( P = 0.042 ) than women receiving placebo and also after adjusting as above ( P = 0.016 ) ; both in valid-case and in the intention-to-treat analysis . In the Vit D group , the fracture incidence was non-significantly decreased ( P = 0.229 ) in comparison with the placebo group . The estimated risk of new non-vertebral fractures among women treated with HRT alone was 0.29 ( 95 % CI , 0.10 - 0.90 ) and with Vit D 0.47 ( 95 % CI , 0.20 - 1.14 ) and with HRT + Vit D 0.44 ( 95 % CI , 0.17 - 1.15 ) , in comparison with the placebo group ( adjusted by femoral BMD and previous fractures ) . CONCLUSIONS This study is the first prospect i ve trial confirming the beneficial effect of HRT on prevention of peripheral fractures in non-osteoporotic postmenopausal women . The effect of low-dose Vit D remains to be proved CONTEXT Several reports from small clinical trials have suggested that estrogen replacement therapy may be useful for the treatment of Alzheimer disease ( AD ) in women . OBJECTIVE To determine whether estrogen replacement therapy affects global , cognitive , or functional decline in women with mild to moderate AD . DESIGN The Alzheimer 's Disease Cooperative Study , a r and omized , double-blind , placebo-controlled clinical trial conducted between October 1995 and January 1999 . SETTING Thirty-two study sites in the United States . PARTICIPANTS A total of 120 women with mild to moderate AD and a Mini-Mental State Examination score between 12 and 28 who had had a hysterectomy . INTERVENTIONS Participants were r and omized to estrogen , 0.625 mg/d ( n = 42 ) , or 1.25 mg/d ( n = 39 ) , or to identically appearing placebo ( n = 39 ) . One subject withdrew after r and omization but before receiving medication ; 97 subjects completed the trial . MAIN OUTCOME MEASURES The primary outcome measure was change on the Clinical Global Impression of Change ( CGIC ) 7-point scale , analyzed by intent to treat ; secondary outcome measures included other global measures as well as measures of mood , specific cognitive domains ( memory , attention , and language ) , motor function , and activities of daily living ; compared by the combined estrogen groups vs the placebo group at 2 , 6 , 12 , and 15 months of follow-up . RESULTS The CGIC score for estrogen vs placebo was 5.1 vs 5.0 ( P = .43 ) ; 80 % of participants taking estrogen vs 74 % of participants taking placebo worsened ( P = .48 ) . Secondary outcome measures also showed no significant differences , with the exception of the Clinical Dementia Rating Scale , which suggested worsening among patients taking estrogen ( mean posttreatment change in score for estrogen , 0.5 vs 0.2 for placebo ; P = .01 ) . CONCLUSIONS Estrogen replacement therapy for 1 year did not slow disease progression nor did it improve global , cognitive , or functional outcomes in women with mild to moderate AD . The study does not support the role of estrogen for the treatment of this disease . The potential role of estrogen in the prevention of AD , however , requires further research Abstract : The effects of 17β-estradiol ( E2 ) 1 mg combined with low doses of norethisterone acetate ( NETA ) on postmenopausal bone loss and turnover were investigated in a 2-year , r and omized , double-masked , placebo-controlled trial . A total of 135 postmenopausal women with a lumbar spine bone mineral density ( BMD ) T-score between −2 and + 2 were r and omized to daily treatment with an oral tablet of either placebo , E2 1 mg/NETA 0.25 mg , or E2 1 mg/NETA 0.5 mg . Significant ( p<0.001 ) increases in BMD at the lumbar spine ( L1–4 ) were observed with E2 1 mg/NETA 0.25 mg ( 5.2 % ) and E2 1 mg/NETA 0.5 mg ( 5.4 % ) compared with placebo ( −0.9 % ) . The total hip BMD increased significantly in the E2 1 mg/NETA 0.25 mg ( 3.1 % ) and E2 1 mg/NETA 0.5 mg groups ( 3.3 % ) compared with placebo . At the femoral trochanter , the increase in BMD in the E2 1 mg/NETA 0.5 mg group ( 6.3 % ) was significantly different from the placebo group ( 0.8 % ) , while that in the E2 1 mg/NETA 0.25 mg group ( 3.3 % ) was not . No statistical differences were found between the active groups and placebo for the change in BMD at the femoral neck . Significant increases in BMD at the distal radius and total body were found for both E2 1 mg/NETA 0.25 mg ( 0.9 % and 2.5 % , respectively ) and E2 1 mg/NETA 0.5 mg ( 2.1 % and 3.0 % , respectively ) compared with placebo ( −0.7 % and 0.4 % , respectively ) . At the end of the treatment , urinary pyridinoline type I collagen C-telopeptide had decreased by 65 % and 60 % in the E2 1 mg/NETA 0.25 mg and E2 1 mg/NETA 0.5 mg groups , respectively , while the mean serum concentrations of osteocalcin had decreased by 39 % and 34 % , bone-specific alkaline phosphatase by 32 % and 29 % , and C-terminal propeptide of type I collagen by 21 % and 19 % had decreased by 34 - 39 % , 29 - 32 % , and 19 - 21 % in the E2 1 mg/NETA 0.25 mg and E2 1 mg/NETA 0.25 mg groups , respectively . In conclusion , combinations of E2 1 mg and NETA 0.25 or 0.5 mg prevent bone loss in postmenopausal women at the lumbar spine , hip , distal radius and total body , and normalize bone turnover OBJECTIVE To assess the effects of hormone therapy on bone mineral density ( BMD ) in the spine and hip of postmenopausal women . DESIGN A 3-year , multicenter , r and omized , double-blinded , placebo-controlled clinical trial . PARTICIPANTS A total of 875 healthy women aged 45 to 64 years recruited at 7 clinical centers . INTERVENTIONS Treatments were ( 1 ) placebo ; ( 2 ) conjugated equine estrogens ( CEE ) , 0.625 mg/d ; ( 3 ) CEE , 0.625 mg/d plus medroxyprogesterone acetate ( MPA ) , 10 mg/d for 12 d/mo ; ( 4 ) CEE , 0.625 mg/d plus MPA , 2.5 mg/d daily ; or ( 5 ) CEE , 0.625 mg/d plus micronized progesterone ( MP ) , 200 mg/d for 12 d/mo . MAIN OUTCOME MEASURES Bone mineral density at baseline , 12 months , and 36 months . RESULTS Participants assigned to the placebo group lost an average of 1.8 % of spine BMD and 1.7 % of hip BMD by the 36-month visit , while those assigned to active regimens gained BMD at both sites , ranging from 3.5 % to 5.0 % mean total increases in spinal BMD and a mean total increase of 1.7 % of BMD in the hip . Changes in BMD for women assigned to active regimens were significantly greater than those assigned to placebo . Women assigned to CEE plus continuous MPA had significantly greater increases in spinal BMD ( increase of 5 % ) than those assigned to the other 3 active regimens ( average increase , 3.8 % ) . Findings were similar among those adhering to assigned therapy , although , among adherent participants , there were no significant differences in BMD changes among the 4 active treatment groups . Older women , women with low initial BMD , and those with no previous hormone use gained significantly more bone than younger women , women with higher initial BMD , and those who had used hormones previously . CONCLUSIONS Postmenopausal women assigned to placebo demonstrated decreased BMD at the spine and hip , whereas women assigned to estrogen therapy increased BMD during a 36-month period . These findings demonstrate that estrogen replacement therapy increases BMD at clinical ly important sites BACKGROUND Heart disease is a major cause of illness and death in women . To underst and better the role of estrogen in the treatment and prevention of heart disease , more information is needed about its effects on coronary atherosclerosis and the extent to which concomitant progestin therapy may modify these effects . METHODS We r and omly assigned a total of 309 women with angiographically verified coronary disease to receive 0.625 mg of conjugated estrogen per day , 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate per day , or placebo . The women were followed for a mean ( + /-SD ) of 3.2+/-0.6 years . Base-line and follow-up coronary angiograms were analyzed by quantitative coronary angiography . RESULTS Estrogen and estrogen plus medroxyprogesterone acetate produced significant reductions in low-density lipoprotein cholesterol levels ( 9.4 percent and 16.5 percent , respectively ) and significant increases in high-density lipoprotein cholesterol levels ( 18.8 percent and 14.2 percent , respectively ) ; however , neither treatment altered the progression of coronary atherosclerosis . After adjustment for measurements at base line , the mean ( + /-SE ) minimal coronary-artery diameters at follow-up were 1.87+/-0.02 mm , 1.84+/-0.02 mm , and 1.87+/-0.02 mm in women assigned to estrogen , estrogen plus medroxyprogesterone acetate , and placebo , respectively . The differences between the values for the two active-treatment groups and the value for the placebo group were not significant . Analyses of several secondary angiographic outcomes and subgroups of women produced similar results . The rates of clinical cardiovascular events were also similar among the treatment groups . CONCLUSIONS Neither estrogen alone nor estrogen plus medroxyprogesterone acetate affected the progression of coronary atherosclerosis in women with established disease . These results suggest that such women should not use estrogen replacement with an expectation of cardiovascular benefit Sodium fluoride stimulates bone formation and has been used to treat osteoporosis for decades despite debate about the antifracture efficacy . Hormone replacement therapy ( HRT ) results in only modest increases in bone mineral density ( BMD ) . However , for women with low bone mass , the ideal therapy should not only inhibit bone resorption but simultaneously stimulate bone formation to increase bone mass above the fracture threshold . We thus performed a r and omized , double-blind , placebo-controlled intervention study to prospect ively investigate the effect of a low dose of fluoride , in combination with HRT , on BMD and biochemical markers of bone turnover . One hundred healthy postmenopausal women ( 60 - 70 yr old ) were thus r and omly assigned to : 1 ) HRT [ transdermal 17beta-estradiol , releasing 50 microg/day ; plus oral norethisterone acetate ( NETA ) , 1 mg/day ] ; or 2 ) oral monofluorophosphate ( MFP ; equivalent to fluoride , 20 mg/day ) ; or 3 ) HRT+MFP ; or 4 ) placebo , for 96 weeks . All participants received a calcium supplement of 1000 mg/day . Sixty-eight women completed the study . We found a pronounced , linear increase in spinal BMD during treatment with HRT+MFP [ 11.8 % ( 1.7 % SEM ) ] , which was significantly greater than the increase in the HRT group [ 4.0 % ( 0.5 % per yr ) ; P < 0.05 ] . MFP produced a smaller increase [ 2.4 % ( 0.6 % per yr ) ] , whereas there was no change in the placebo group [ 0.0 % ( 0.5 % SEM ) ] . Similar changes were found at the other skeletal sites ( distal forearm , hip , and total body ) . Markers of bone formation showed a fall in the HRT group , which was significantly more pronounced than in the combined HRT+MFP group . A nonsignificant increase was found in the MFP group , whereas the placebo group showed a decrease caused by calcium treatment . The marker of bone resorption decreased significantly more in the HRT and the HRT+MFP groups than in the placebo group but tended to increase in the MFP group . In conclusion , this study shows , by use of biochemical markers of bone turnover , that bone resorption and formation may be dissociated , as a result of actions of two compounds with diverging effects on bone turnover . Furthermore , the synergistic effects of relatively low doses of the compounds suggested statistically and clinical ly significant increases in trabecular and probably also cortical bone . Adverse effects were relatively rare and mild Hormone replacement therapy ( HRT ) is often prescribed for a few years to suppress menopausal symptoms . Although its long-term use of HRT for the primary prevention of osteoporosis is not currently recommended , the long-term skeletal benefits of the limited therapy are of great interest . To determine whether administration of HRT for 2 - 3 years in the early postmenopausal years provides long-term benefits , such as prevention of bone loss and osteoporotic fractures , we studied a group of 347 healthy postmenopausal women with normal bone mass who had earlier completed one of four placebo-controlled HRT trials and who were reexamined 5 , 11 , or 15 years after stopping HRT . Of these women , 263 received either HRT or placebo for 2 - 3 years with no further bone-sparing treatment until follow-up , and the remaining 84 women reported either prolonged or current use of HRT at reexamination . Bone mineral density ( BMD ) at the spine ( L1-L4 ) and bone mineral content ( BMC ) in the forearm were measured at baseline , the end of the trials , and follow-up . At follow-up , we assessed the radiological presence of vertebral fracture and collected information on the new incidence of nonvertebral fractures . Compared with that of the placebo-treated women , the BMD and BMC of HRT-treated women continued to show significantly higher values ( > 5 % ) even many years after stopping HRT . After stopping treatment , the rate of bone loss returned to normal postmenopausal rates . The preservation of bone mass in the HRT group was accompanied by a significantly reduced risk of all osteoporotic fractures as compared with the placebo group [ OR = 0.48 ( 95 % CI , 0.26 - 0.88 ) ] . ' Fast losers ' on placebo had more than a 4-fold higher risk of fractures than had the women on limited HRT with a normal rate of bone loss after withdrawal . In conclusion , limited HRT administered in the early postmenopausal years offers long-lasting benefits for the prevention of postmenopausal bone loss and osteoporotic fracture Objective : Although the route of estrogen administration is known to be an important determinant of the thrombotic risk among postmenopausal women using hormone therapy , recent data have shown that norpregnane derivatives but not micronized progesterone increase venous thromboembolism risk among transdermal estrogens users . However , the differential effects of progesterone and norpregnanes on hemostasis have not yet been investigated . Methods : We set up a cross-sectional study among healthy postmenopausal women aged 45 to 70 years . The impact of activated protein C ( APC ) on endogenous thrombin potential was investigated in the plasma sample s of 108 women who did not use any hormone therapy ( n = 40 ) or who were treated with transdermal estrogens combined with micronized progesterone ( n = 30 ) or norpregnane derivatives ( n = 38 ) . Results : After exclusion of women with factor V Leiden and /or G20210A prothrombin gene mutations , there was no significant change in APC sensitivity among women who used transdermal estrogens combined with micronized progesterone compared with nonusers . Women using transdermal estrogens combined with norpregnanes were less sensitive to APC than were nonusers ( P = 0.003 ) or users of transdermal estrogens combined with micronized progesterone ( P = 0.004 ) . In addition , prothrombin fragment 1 + 2 concentration was higher in users of transdermal estrogens plus norpregnanes than in nonusers ( P = 0.004 ) . Other hemostatic parameters did not vary significantly across the different subgroups . Conclusions : Transdermal estrogens combined with norpregnanes may induce APC resistance and activate blood coagulation . These results provide a biological support to epidemiological data regarding the potential thrombogenic effects of norpregnanes . However , these findings need to be confirmed in a r and omized trial PURPOSE Hormone replacement therapy ( HRT ) with estrogen and treatment with bisphosphonates have been shown to increase bone mineral density ( BMD ) in postmenopausal women . This 4-year prospect i ve r and omized study was carried out to assess the effectiveness of the combined HRT plus etidronate on BMD in postmenopausal women with established osteoporosis . PATIENTS AND METHODS Seventy-two postmenopausal women ( mean age 64.9+/-0.5 years ) attending metabolic bone disease outpatient clinics with established osteoporosis were r and omly allocated into one of four treatment groups and monitored for 4 years . All patients enrolled in this study including the control group ( n=18 ) received 1.0 g elemental calcium and 400 units vitamin D per day . The HRT group ( n=18 ) received cyclical estrogen and progesterone ; the etidronate group ( n=17 ) received intermittent cyclical etidronate ; and the combined therapy group ( n=19 ) received both HRT and etidronate . BMD was measured in the lumbar spine and the hip before treatment and at 2 and 4 years after treatment . Changes in height were recorded , and the occurrence of new vertebral fractures were documented in comparison with the baseline radiographic evaluation . In 40 patients ( 10 patients per group ) , analysis of bone histomorphometry was carried out after 4 years of treatment . RESULTS In patients who received the combined therapy , BMD increased in the lumbar spine by 10.4 % ( P < 0.001 ) and in the hip by 7.0 % ( P < 0.001 ) at 4 years . For patients treated with ICE , these increases were 7.3 % ( P < 0.001 ) and 0.9 % ( P < 0.05 ) , and with HRT , the increases were 7.0 % ( P < 0.001 ) and 4.8 % ( P < 0.01 ) in the vertebrae and femora , respectively . The group treated with calcium and vitamin D lost 2.5 % ( P < 0.05 ) and 4.4 % ( P < 0.01 ) of BMD in the vertebrae and femora , respectively , after 4 years . Patients who received combined therapy had significantly higher BMD in both the vertebrae and in the femora ( P < 0.05 ) in comparison with patients who were treated with HRT or etidronate alone after 4 years . In comparison with patients in the control group , there was a trend toward a lower rate of new vertebral fractures in the treatment groups . Height loss was significantly less in all three active treatment groups ( HRT [ P < 0.001 ] , etidronate [ P < 0.02 ] , and combined therapy group [ P < 0.0001 ] ) , in comparison with the control group . The combined therapy group did not have a significant height loss , in comparison with the HRT ( P < 0.02 ) and the etidronate ( P < 0.001 ) groups . None of the patients had histomorphometric evidence of osteomalacia . CONCLUSION This 4-year r and omized study showed an additive effect of etidronate and HRT on hip and spine BMD in postmenopausal women with established osteoporosis Based on data from 153 early postmenopausal women who completed a double-blind , r and omized 3 year study of grade d hormone replacement therapy ( HRT ) doses or placebo , we investigated the value of bone markers to predict prevention of bone loss . Absolute values of serum and urinary CrossLaps ( S-CTX and U-CTX ) after 2 weeks of treatment were significantly correlated to 3 year bone mass response ( r = -0 . 28/-0.35 ; p < 0.001 ) . These associations were fully expressed at 6 months ( r = -0.61/-0.64 ; p < 0.001 ) . Receiver operating characteristic analyses revealed that the predictive capacity of one measurement of a resorption marker after 6 months ' treatment performed similarly as assessment of hip bone mass over 3 years in predicting preservation of spinal bone mass over 3 years . Comparable results were obtained using percent change from baseline in resorption markers at both 6 and 12 months , whereas for formation markers percent change was superior to absolute value at 6 months but not at 12 months . Values of accuracy for S-CTX for a cutoff of 1881 pmol/L at 6 months were 85.2 % ( sensitivity ) , 74.3 % ( specificity ) , 90.5 % ( positive predictive value ) , and 63.4 % ( negative predictive value ) ; U-CTX performed similarly , whereas the values for the formation markers were slightly lower . A cutoff for S-CTX of 1245 pmol/L eliminated false-positive individuals ( those who had a decrease below the cutoff but lost bone ) . In the false-negative group , which was composed of individuals whose S-CTX did not decrease below the cutoff but had preserved bone mass , S-CTX was significantly associated with spinal bone mass response ( r = -0 . 41 ; p < 0.01 ) , indicating these women had been treated with a dose that was not at its optimum for their individual bone turnover . For this cutoff , the values were 49.5 % ( sensitivity ) , 97.1 % ( specificity ) , 98 % ( positive predictive value ) , and 40 % ( negative predictive value ) . In conclusion , early bone marker measurements predict long-term preservation of bone mass during HRT . Resorption markers seem superior to formation markers , which reflects that the primary effect of HRT is on bone resorption . A strategy with two cutoff levels may optimize the use of bone markers to predict bone mass response . Whether resorption markers can be used to guide individualized treatment remains to be investigated OBJECTIVES To study the fracture reducing potential of hormonal replacement therapy ( HRT ) in recent postmenopausal women in a primary preventive scenario . METHODS Prospect i ve controlled comprehensive cohort trial : 2016 healthy women aged 45 - 58 years , from three to 24 months past last menstrual bleeding were recruited from a r and om sample of the background population . Mean age was 50 . 8+/-2.8 years , and the number of person years followed was 9335.3 . There were two main study arms : a r and omised arm ( r and omised to HRT ; n=502 , or not ; n=504 ) and a non-r and omised arm ( on HRT ; n=221 , or not ; n=789 by own choice ) . First line HRT was oral sequential oestradiol/norethisterone in women with intact uterus and oral continuous oestradiol in hysterectomised women . RESULTS After five years , a total of 156 fractures were sustained by 140 women . There were 51 forearm fractures in 51 women . By intention-to-treat analysis ( n=2016 ) , overall fracture risk was borderline statistically significantly reduced ( RR=0.73 , 95 % CI : 0.50 - 1.05 ) , and forearm fracture risk was significantly reduced ( RR=0.45 , 95 % CI : 0.22 - 0.90 ) with HRT . Restricting the analysis to women who had adhered to their initial allocation of either HRT ( n=395 ) or no HRT ( n=977 ) showed a significant reduction in both the overall fracture risk ( RR=0.61 , 95 % CI : 0.39 - 0.97 ) and the risk of forearm fractures ( RR=0.24 , 95 % CI : 0.09 - 0.69 ) . Compliance with HRT was 65 % after five years . CONCLUSIONS It is possible to reduce the number of forearm fractures and possibly the total number of fractures in recent postmenopausal women by use of HRT as primary prevention PURPOSE To determine if estrogen plus progestin reduces the incidence of fractures or height loss in postmenopausal women with coronary disease . SUBJECTS AND METHODS We enrolled 2,763 postmenopausal women with coronary disease and with an intact uterus into the Heart Estrogen/progestin Replacement Study , a r and omized double-blind , placebo-controlled secondary prevention trial of cardiovascular disease . Radiographically documented clinical fractures were a prespecified secondary endpoint . Height loss was used as a surrogate for vertebral fractures . The average age of the women was 66.7 + /- 6.7 years , and fewer than 15 % of the women had osteoporosis based on their bone density . Women were r and omly assigned to either 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate in 1 tablet daily ( n = 1,380 ) or placebo ( n = 1,383 ) . Follow-up averaged 4.1 years ; 82 % of those assigned to hormone treatment were taking it at the end of 1 year , and 64 % at the end of the study . RESULTS During 10,554 person years of follow-up , 286 women experienced a fracture : 138 in the treatment group ( 26.3 per 1,000 person years ) and 148 in the placebo group ( 28.0 per 1,000 person years ) ; relative hazard , 0.94 ; 95 % confidence interval 0.8 to 1.2 , P = 0.61 ) . These included 58 wrist fractures ( 1.01 ; 0.6 to 1.7 ) ; 27 hip fractures ( 1.09 ; 0.5 to 2.3 ) ; 32 spine fractures ( 0.69 ; 0.3 to 1.4 ) , and 192 other fractures ( 0.91 ; 0.7 to 1.2 ) . There was no difference in average height loss between the treatment and placebo groups or in the percent of women who lost more than 2 cm in height : 10.6 % in the treatment group and 12.1 % in the placebo group . CONCLUSIONS There was no evidence of a reduction in the incidence of fractures or rate of height loss in older women not selected for osteoporosis . R and omized studies are needed to clarify the effect of hormone replacement therapy on fracture risk among women with and without osteoporosis OBJECTIVE To determine the relative risk of hip fracture associated with postmenopausal hormone replacement therapy including the effect of duration and recency of treatment , the addition of progestins , route of administration , and dose . DESIGN Population based case-control study . SETTING Six counties in Sweden . SUBJECTS 1327 women aged 50 - 81 years with hip fracture and 3262 r and omly selected controls . MAIN OUTCOME MEASURE Use of hormone replacement therapy . RESULTS Compared with women who had never used hormone replacement therapy , current users had an odds ratio of 0.35 ( 95 % confidence interval 0.24 to 0.53 ) for hip fracture and former users had an odds ratio of 0.76 ( 0.57 to 1.01 ) . For every year of therapy , the overall risk decreased by 6 % ( 3 % to 9 % ) : 4 % ( 1 % to 8 % ) for regimens without progestin and 11 % ( 6 % to 16 % ) for those with progestin . Last use between one and five years previously , with a duration of use more than five years , was associated with an odds ratio of 0.27 ( 0.08 to 0.94 ) . After five years without hormone replacement therapy the protective effect was substantially diminished ( -7 % to 48 % ) . With current use , an initiation of therapy nine or more years after the menopause gave equally strong reduction in risk for hip fracture as an earlier start . Oestrogen treatment with skin patches gave similar risk estimates as oral regimens . CONCLUSIONS Recent use of hormone replacement therapy is required for optimum fracture protection , but therapy can be started several years after the menopause . The protective effect increases with duration of use , and an oestrogen-sparing effect is achieved when progestins are included in the regimen Objective To determine the lowest effective dose of an estradiol ( E2 ) matrix-type transdermal delivery system ( EMTDS ; Alora ) for preventing bone loss in postmenopausal women . Design This double-blind , double-dummy , r and omized , placebo-controlled , multicenter study enrolled 355 nonosteoporotic postmenopausal women who had been hysterectomized with or without oophorectomy at least 12 months earlier . Participants were r and omly assigned to one of three doses of the EMTDS ( 0.025 , 0.05 , or 0.075 mg/day ) or placebo administered twice weekly . Lumbar bone mineral density ( LBMD ) was measured by dual-energy x-ray absorptiometry at screening and after 1 and 2 years of treatment . Safety was assessed at regularly scheduled visits . Results EMTDS provided statistically significant and clinical ly meaningful changes in LBMD relative to placebo . At 2 years , LBMD declined from baseline by 0.59 % in the placebo group , but it increased from baseline by 1.65 % ( p = 0.0065 ) , 4.08 % ( p = 0.0001 ) , and 4.82 % ( p = 0.0001 ) in the EMTDS 0.025 , 0.05 , and 0.075 mg/day groups , respectively . The corresponding responder rates ( defined as no change or increase in LBMD at endpoint ) were 39.7 % for placebo , 59.6 % , 79.3 % , and 83.9 % in the EMTDS 0.025 , 0.05 , and 0.075 mg/day groups , respectively . Mean serum E2 concentrations were proportional to the dose of the E2 transdermal system and did not accumulate over the course of the study . Adverse events were generally comparable across treatment groups , with the majority being mild or moderate in severity and unrelated to study medication . Mammogram findings and other safety assessment s were also comparable across groups and did not reveal any safety concerns with 2-y transdermal E2 treatment . Conclusions The EMTDS ( Alora ) administered twice weekly improves lumbar bone mineral density in healthy postmenopausal women , with the benefit of treatment evident by 1 year . The lowest effective dose is 0.025 mg/day BACKGROUND Prospect i ve studies have shown that doses equivalent to conjugated equine estrogens of 0.625 mg/d or higher are needed to produce a significant increase in bone mineral density of the lumbar spine . OBJECTIVES To determine the effects of unopposed esterified estrogens on bone mineral density , lipid levels , and endometrial tissue structure , and to relate these effects to changes in plasma estradiol levels . METHODS Four hundred six postmenopausal women were given calcium , 1000 mg/d , and r and omly assigned to receive continuous esterified estrogens ( 0.3 , 0.625 , or 1.25 mg/d ) or placebo for 24 months . Bone mineral density measurements and endometrial and laboratory assessment s were conducted every 6 months ; plasma estradiol concentrations were measured after 12 , 18 , and 24 months . RESULTS All doses of esterified estrogens produced significant increases in bone mineral density of the lumbar spine compared with baseline and with placebo at 6 , 12 , 18 , and 24 months . Mean plasma estradiol levels increased with esterified estrogens dose , and individual subject bone mineral density changes appeared related to plasma estradiol concentrations . Clinical ly relevant rates of endometrial hyperplasia were noted only in the groups receiving 0.625 and 1.25 mg of esterified estrogens daily . Lipid changes were dose related and apparent in all groups . CONCLUSIONS Esterified estrogens at doses from 0.3 to 1.25 mg/d , administered unopposed by progestin , produce a continuum of positive changes on bone and lipids . Plasma estradiol concentrations increased with esterified estrogens dose and were related to positive bone mineral densities . The 0.3-mg dose result ed in positive bone and lipid changes without inducing endometrial hyperplasia CONTEXT In the Women 's Health Initiative trial of estrogen-plus-progestin therapy , women assigned to active treatment had fewer fractures . OBJECTIVE To test the hypothesis that the relative risk reduction of estrogen plus progestin on fractures differs according to risk factors for fractures . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial ( September 1993-July 2002 ) in which 16 608 postmenopausal women aged 50 to 79 years with an intact uterus at baseline were recruited at 40 US clinical centers and followed up for an average of 5.6 years . INTERVENTION Women were r and omly assigned to receive conjugated equine estrogen , 0.625 mg/d , plus medroxyprogesterone acetate , 2.5 mg/d , in 1 tablet ( n = 8506 ) or placebo ( n = 8102 ) . MAIN OUTCOME MEASURES All confirmed osteoporotic fracture events that occurred from enrollment to discontinuation of the trial ( July 7 , 2002 ) ; bone mineral density ( BMD ) , measured in a subset of women ( n = 1024 ) at baseline and years 1 and 3 ; and a global index , developed to summarize the balance of risks and benefits to test whether the risk-benefit profile differed across tertiles of fracture risk . RESULTS Seven hundred thirty-three women ( 8.6 % ) in the estrogen-plus-progestin group and 896 women ( 11.1 % ) in the placebo group experienced a fracture ( hazard ratio [ HR ] , 0.76 ; 95 % confidence interval [ CI ] , 0.69 - 0.83 ) . The effect did not differ in women stratified by age , body mass index , smoking status , history of falls , personal and family history of fracture , total calcium intake , past use of hormone therapy , BMD , or summary fracture risk score . Total hip BMD increased 3.7 % after 3 years of treatment with estrogen plus progestin compared with 0.14 % in the placebo group ( P<.001 ) . The HR for the global index was similar across tertiles of the fracture risk scale ( lowest fracture risk tertile , HR , 1.20 ; 95 % CI , 0.93 - 1.58 ; middle tertile , HR , 1.23 ; 95 % CI , 1.04 - 1.46 ; highest tertile , HR , 1.03 ; 95 % CI , 0.88 - 1.24 ) ( P for interaction = .54 ) . CONCLUSIONS This study demonstrates that estrogen plus progestin increases BMD and reduces the risk of fracture in healthy postmenopausal women . The decreased risk of fracture attributed to estrogen plus progestin appeared to be present in all subgroups of women examined . When considering the effects of hormone therapy on other important disease outcomes in a global model , there was no net benefit , even in women considered to be at high risk of fracture Objective The purpose of this r and omised double‐blind placebo‐controlled study over two years followed by a six year open controlled extension phase was to investigate the effects of hormonal replacement therapy ( HRT ) both continuous combined HRT and sequential HRT ) versus no treatment on lumbar spine bone mineral density ( L‐BMD ) and distal forearm bone mineral content ( F‐ BMC ) . Further , bone mineral density of the proximal femur , lateral spine , and distal forearm was studied after eight years |
987 | 24,434,188 | CONCLUSIONS Treatment effects of convective dialysis are unreliable due to limitations in trial methods and reporting .
Convective dialysis may reduce cardiovascular but not all-cause mortality , and effects on nonfatal cardiovascular events and hospitalization are inconclusive | BACKGROUND Convective dialysis therapies ( hemofiltration or hemodiafiltration ) are associated with lower mortality compared to hemodialysis in observational studies .
A previous meta- analysis of r and omized trials comparing convective modalities with hemodialysis in 2006 was inconclusive due to insufficient data .
Additional r and omized trials recently have reported conflicting results . | There is increasing evidence that the biochemical and cellular phenomena induced by blood/ membrane/dialysate interactions contribute to dialysis-related intradialytic and long-term complications . However , there is a lack of large , prospect i ve , r and omized trials comparing biocompatible and bioincompatible membranes , and convective and diffusive treatment modalities . The primary aim of this prospect i ve , r and omized trial was to evaluate whether the use of polysulfone membrane with bicarbonate dialysate offers any advantage ( in terms of treatment tolerance , nutritional parameters and pre-treatment beta-microglobulin levels ) over a traditional membrane ( Cuprophan ) . A secondary aim was to assess whether the use of more sophisticated methods consisting of a biocompatible synthetic membrane with different hydraulic permeability at different ultrafiltration rate ( high-flux hemodialysis and hemodiafiltration ) offers any further advantages . Seventy-one Centers were involved and stratified according to the availability of only the first two or all four of the following techniques : Cuprophan hemodialysis ( Cu-HD ) , low-flux polysulfone hemodialysis ( LfPS-HD ) , high-flux polysulfone high-flux hemodialysis ( HfPS-HD ) , and high-flux polysulfone hemodiafiltration ( HfPS-HDF ) . The 380 eligible patients were r and omized to one of the two or four treatments ( 132 to Cu-HD , 147 to LfPS-HD , 51 to HfPS-HD and 50 to HfPS-HDF ) . The follow-up was 24 months . No statistical difference was observed in the algebraic sum of the end points between bicarbonate dialysis with Cuprophan or with low-flux polysulfone , or among the four dialysis methods under evaluation . There was a significant decrease in pre-dialysis plasma beta 2-microglobulin levels in high-flux dialysis of 9.04 + /- 10.46 mg/liter ( 23 % ) and in hemodiafiltration of 6.35 + /- 12.28 mg/liter ( 16 % ) , both using high-flux polysulfone membrane in comparison with Cuprophan and low-flux polysulfone membranes ( P = 0.032 ) . The significant decrease in pre-dialysis plasma beta 2-microglobulin levels could have a clinical impact when one considers that beta 2-microglobulin accumulation and amyloidosis are important long-term dialysis-related complications BACKGROUND Accumulation of larger molecular weight uraemic toxins molecules may have a negative effect on the cardiovascular and nutritional state of dialysis patients and influence uraemic symptomatology . Their clearance can be enhanced by the use of haemofiltration ( HF ) . METHODS The effects of low-flux haemodialysis ( HD ) ( ultrapure dialysate ; polyamide membranes ) and pre-dilution on-line HF ( 1:1 blood/substitution ratio ; target filtration volume : 1.2 times body weight ) on cardiovascular and nutritional parameters , interdialytic levels of uraemic toxins and quality of life ( QOL ; Laupacis question naire ) were assessed during 1 year follow-up . Forty patients were r and omized . RESULTS After 1 year , 27 patients were eligible for analysis ( HF : 13 patients ; HD : 14 patients ) . Left ventricular mass index did not change in the HF patients ( 127+/-33 -- > 131+/-36 g/m(2 ) after 12 months ) or in the HD group ( 135+/-34 -- > 138+/-32 g/m(2 ) ) . Also , there were no changes in pulse wave velocity , and 48 h systolic and diastolic blood pressures . Lean body mass , assessed by dual-energy X-ray absorptiometry , increased in the HF group ( 44.8+/-8.9 -- > 46.2+/-9.6 kg ; P<0.05 ) , but not in the HD group ( 49.4+/-9.2 -- > 50.6+/-8.8 kg ) , although differences between groups were not significant . Insulin-like growth factor-1 levels remained stable in the HF patients , but decreased in the HD group ( P<0.05 between groups ) . QOL for physical symptoms improved in the HF group ( 4.2+/-1.2 -- > 5.0+/-1.1 ; P<0.05 within the HF group and P = 0.06 between groups ) , but not in the HD group ( 4.0+/-1.0 -- > 4.4+/-1.4 ) . beta2-microglobulin , complement factor D and homocysteine decreased significantly in the HF but not in the HD group , whereas l-ADMA , leptin and advanced glycation end-products-related fluorescence did not change . CONCLUSIONS No changes in cardiovascular parameters were observed during pre-dilution on-line HF compared with low-flux HD . Treatment with on-line HF result ed in marked changes in the uraemic toxicity profile , an improvement in physical well-being and a small improvement in nutritional state Some of the morbidity associated with chronic hemodialysis is thought to result from retention of large molecular weight solutes that are poorly removed by diffusion in conventional hemodialysis . Hemodiafiltration combines convective and diffusive solute removal in a single therapy . The hypothesis that hemodiafiltration provides better solute removal than high-flux hemodialysis was tested in a prospect i ve , r and omized clinical trial . Patients were r and omized to either on-line postdilution hemodiafiltration or high-flux hemodialysis . The groups did not differ in body size , treatment time , blood flow rate , or net fluid removal . The filtration volume in hemodiafiltration was 21 + /-1 L. Therapy prescriptions were unchanged for a 12-mo study period . Removal of both small ( urea and creatinine ) and large ( ss(2)-microglobulin and complement factor D ) solutes was significantly greater for hemodiafiltration than for high-flux hemodialysis . The increased urea and creatinine removal did not result in lower pretreatment serum concentrations in the hemodiafiltration group . Pretreatment plasma beta(2)-microglobulin concentrations decreased with time ( P < 0.001 ) ; however , the decrease was similar for both therapies ( P = 0.317 ) . Pretreatment plasma complement factor D concentrations also decreased with time ( P<0.001 ) , and the decrease was significantly greater with hemodiafiltration than with high-flux hemodialysis ( P = 0.010 ) . The conclusion is that on-line hemodiafiltration provides superior solute removal to high-flux hemodialysis over a wide molecular weight range . The improved removal may not result in lower pretreatment plasma concentrations , however , possibly because of limitations in mass transfer rates within the body In patients with ESRD , the effects of online hemodiafiltration on all-cause mortality and cardiovascular events are unclear . In this prospect i ve study , we r and omly assigned 714 chronic hemodialysis patients to online postdilution hemodiafiltration ( n=358 ) or to continue low-flux hemodialysis ( n=356 ) . The primary outcome measure was all-cause mortality . The main secondary endpoint was a composite of major cardiovascular events , including death from cardiovascular causes , nonfatal myocardial infa rct ion , nonfatal stroke , therapeutic coronary intervention , therapeutic carotid intervention , vascular intervention , or amputation . After a mean 3.0 years of follow-up ( range , 0.4 - 6.6 years ) , we did not detect a significant difference between treatment groups with regard to all-cause mortality ( 121 versus 127 deaths per 1000 person-years in the online hemodiafiltration and low-flux hemodialysis groups , respectively ; hazard ratio , 0.95 ; 95 % confidence interval , 0.75 - 1.20 ) . The incidences of cardiovascular events were 127 and 116 per 1000 person-years , respectively ( hazard ratio , 1.07 ; 95 % confidence interval , 0.83 - 1.39 ) . Receiving high-volume hemodiafiltration during the trial associated with lower all-cause mortality , a finding that persisted after adjusting for potential confounders and dialysis facility . In conclusion , this trial did not detect a beneficial effect of hemodiafiltration on all-cause mortality and cardiovascular events compared with low-flux hemodialysis . On-treatment analysis suggests the possibility of a survival benefit among patients who receive high-volume hemodiafiltration , although this subgroup finding requires confirmation BACKGROUND Morbidity and mortality rates in diabetic patients on regular dialysis treatment ( RDT ) are higher than in non-diabetic-subjects on RDT . Moreover , diabetic patients experience an intradialitic morbidity unacceptably higher than in patients with other causes of terminal renal failure . The aim of the present investigation was to compare st and ard bicarbonate haemodialysis ( BHD ) with acetate-free biofiltration ( AFB ) in a group of 41 diabetic patients stable on dialysis treatment for 25 + /- 22 months . METHODS Twenty-four type II and 17 type I diabetic patients , all requiring insulin therapy , were included and were followed for 1 year in a 6-month cross-over r and omized study for both methods . The analysis was carried out on dialysis symptoms , interdialysis symptoms , and nutritional status , and the multivariate analysis of variance for repeated measures on the same subjects in the two techniques was used . RESULTS AFB significantly reduced dialytic and extradialytic symptoms ( P=0.003 and 0.001 respectively ) . Cardiovascular collapses decreased by 43 % , and other dialysis symptoms showed a similar trend ( -35 % ) . The interdialysis symptoms decreased by 28 % and were accompanied by an increase in subjective wellbeing ( 39 % ) when patients were switched from traditional haemodialysis to AFB . Acid base control was better with AFB ( P=0.01 ) , both at the beginning and during the session . Slightly significant differences were also obtained for Kt/V ( AFB 1.48 + /- 0.29 vs BHD 1.38 + /- 0.30 ) , while no significant difference was noted with respect to sodium mass balance , nutritional status , calorie-protein intake , nPCR , blood glucose profile , and insulin requirements . The number of hospital admissions and the mortality rate , which were much lower during the AFB than the BHD period , were not analysed statistically . CONCLUSIONS AFB allows better control of some metabolic aspects , reduces intra- and extradialysis symptoms , and improves patient quality of life . Whether the long-term prognosis can be improved by AFB remains to be established with further studies Chronic inflammation contributes to the pathogenesis of several complications of hemodialysis therapy . It is thought that backfiltration of bacteria-derived contaminations during dialysis may induce a chronic inflammatory state . High-sensitivity C-reactive protein ( hs-CRP ) is one of the tools which can take a hold on such a chronic inflammatory condition . We examined the effect of ultrapure dialysate which contributes to chronic inflammation with hs-CRP and tried to reduce endotoxin ( ET ) levels at the end of the dialysate from 70 EU/l to < 1.0 EU/l ( ultrapure dialysate ) . Other dialysis conditions , except ET level , were fixed . We investigated the hs-CRP of 23 patients receiving regular dialysis before the use of ultrapure dialysate and 1 year after use of it prospect ively . The data showed a significant decrease in the median value of the hs-CRP from 0.16 to 0.07 mg/dl ( p < 0.05 ) . The value of serum β2-microglobulin decreased from 33.2 to 28.4 mg/dl ( p < 0.01 ) and the hemoglobin level increased from 10.0 to 11.0 g/dl ( p < 0.05 ) . These results indicate that even a dialysate containing 70 EU/l of ET level may induce a chronic inflammatory state . hs-CRP is a very useful marker of chronic inflammation and the use of ultrapure dialysate is necessary to improve a chronic inflammatory state . The targeted ET level at the end of the dialysate should be set at ≤1.0 EU/l Background : Controlled r and omised studies to prove improved cardiovascular stability and improved anaemia management during on-line haemodiafiltration ( oHDF ) are scarce . Methods : 70 patients were treated with both haemodialysis ( HD ) and oHDF in a cross-over design during 2 × 24 weeks at a dialysis dose of eKt/V≧1.2 . Patients r and omised into group A started on HD and switched over to oHDF , whereas patients in group B began with oHDF and were treated with HD afterwards . Intradialytic morbid events ( IME ) , such as symptomatic hypotension or muscle cramps , were noted in case of appearance . Blood parameters reflecting anaemic status , phosphate status , lipid metabolism , oxidative stress , and accumulation of advanced glycation end products were recorded either monthly or at the end of each study phase . Results : The mean incidence of IME was 0.15 IME per treatment , and there was no statistical difference between oHDF and HD . A higher haematocrit ( oHDF 31.5 % vs. HD 30.5 % , p < 0.01 ) at a lower erythropoietin dose ( oHDF 4,913 vs. HD 5,492 IU/week , p = 0.02 ) was found during oHDF , when the sequence of HD and oHDF had not been taken into account . For the study groups , the results were less distinct : in group A , a higher haematocrit ( HD 30.4 % vs. oHDF 32.0 % , p < 0.01 ) at a comparable erythropoietin dose ( HD 5,421 vs. oHDF 5,187 IU/week , ns ) was observed during oHDF , whereas in group B an identical haematocrit ( oHDF 30.8 % vs. HD 30.7 % , ns ) was achieved at a reduced erythropoietin dose ( oHDF 4,622 vs. HD 5,568 IU/week , p < 0.01 ) . During oHDF , lower levels of free and protein-bound pentosidine and of serum phosphate were found . Conclusion : In contrast to other studies , no benefit regarding cardiovascular stability for oHDF was found , but oHDF could well offer a potential benefit regarding anaemia correction , inflammation , oxidative stress , lipid profiles , and calcium-phosphate product Background / Aims : Data from studies comparing the effect of hemodiafiltration ( HDF ) and conventional hemodialysis ( HD ) on clinical ly important outcomes are insufficient to support superiority of HDF . None of these studies has been participant-blinded . Methods : We performed a prospect i ve , r and omized , and patient-blinded cross-over study . Twenty patients on chronic HD received either HD for 2 months followed by post-dilution HDF for 2 months or in opposite order . A range of clinical parameters , as well as markers of inflammation , oxidative stress and iron metabolism was measured . Results : The two treatments were similar with respect to dialysis-related complications , quality of life , and the biomarkers of oxidative stress and inflammation . Compared to HD , 25-hepcidin and β2-microglobulin were 38 and 32 % , respectively , lower after 60 days of HDF ( p < 0.001 and p < 0.01 , respectively ) . The consumption of ESA ( erythropoietin-stimulating agent ) and LMWH ( low-molecular-weight heparin ) was significantly higher with HDF . Conclusion : In short term , HDF is not superior to HD regarding dialysis-related complications . The higher ESA consumption observed with HDF can be explained by blood clotting in tubing and dialyzers , as more anticoagulation was needed with post-dilution HDF . In a longer perspective , lowering serum hepcidin levels may improve pathological iron homeostasis BACKGROUND The residual uraemic syndrome that is inadequately cleared by diffusion is thought to contribute to the poor outcome of maintenance dialysis patients . Haemodiafiltration combines diffusion and convection in a single therapy , conferring theoretical benefits over haemodialysis . However , only few r and omised comparisons have been carried out . METHODS The prospect i ve crossover clinical evaluation of high-flux ultrapure haemodialysis and online haemodiafiltration included 76 clinical ly stable patients on low-flux conventional bicarbonate buffered haemodialysis . They were r and omized to high-flux haemodialysis or online haemodiafiltration ( 24 months ) and switched to the alternative treatment ( 24 months ) . RESULTS Removal of urea ( Kt/V ) and phosphate was significantly greater for online haemodiafiltration than for haemodialysis . Both high-flux haemodialysis and haemodiafiltration were associated with sustained reductions of pretreatment beta 2 microglobulin levels , however , the decrease was greater with haemodiafiltration . Both modes of renal replacement therapy significantly improved nutritional status and the haematopoietic response to rHu EPO . Under unmatched conditions ( sodium and energy balance ) haemodiafiltration was associated with a lower number of hypotensive episodes and partial improvement of quality of life . The incidence of death was low in both groups and did not differ among the two modes of renal replacement therapy . CONCLUSION Online haemodiafiltration is a safe , effective and well tolerated therapy for end-stage renal disease patients even in the long run . Whether the dismal mortality rates of unselected end-stage renal disease patients can be changed by online haemodiafiltration remains to be shown in large scale long-term trials Background Convective dialysis modalities ( haemofiltration ( HF ) , haemodiafiltration ( HDF ) , and acetate-free biofiltration ( AFB ) ) removed excess body fluid across the dialysis membrane with positive pressure and accumulated middle- and larger-size accumulated solutes more efficiently than haemodialysis ( HD ) . This increased larger solute removal combined with use of ultra-pure dialysis fluid in convective dialysis is hypothesised to reduce the frequency and severity of symptoms during dialysis as well as improve clinical outcomes . Convective dialysis therapies ( HDF and HF ) are associated with lower mortality compared to diffusive therapy ( HD ) in observational studies . This is an up date of a review first published in 2006 . Objectives To compare convective ( HF , HDF , or AFB ) with diffusive ( HD ) dialysis modalities on clinical outcomes ( mortality , major cardiovascular events , hospitalisation and treatment-related adverse events ) in men and women with end-stage kidney disease ( ESKD ) . Search methods We search ed the Cochrane Renal Group 's Specialised Register ( to 18 February 2015 ) through contact with a Trials ' Search Co-ordinator using search terms relevant to this review . Selection criteria We included r and omised controlled trials comparing convective therapy ( HF , HDF , AFB ) with another convective therapy or diffusive therapy ( HD ) for treatment of ESKD . Data collection and analysis Two independent authors identified studies , extracted data and assessed study risk of bias . We summarised treatment effects using the r and om effects model . We reported results as a risk ratio ( RR ) for dichotomous outcomes and mean difference ( MD ) for continuous data together with 95 % confidence intervals ( CI ) . We assessed for heterogeneity using the Chi2 test and explored the amount of variation in treatment estimates beyond that expected by chance using the I2 statistic . Main results Twenty studies comprising 667 participants were included in the 2006 review . In that review , there was insufficient evidence of treatment effects on major clinical outcomes to draw clinical ly meaningful conclusions . Search ing to February 2015 identified 40 eligible studies comprising 3483 participants overall . In total , 35 studies ( 4039 participants ) compared HF , HDF or AFB with HD , three studies ( 54 participants ) compared AFB with HDF , and three studies ( 129 participants ) compared HDF with HF . Risks of bias in all studies were generally high result ing in low confidence in estimated treatment effects . Convective dialysis had no significant effect on all-cause mortality ( 11 studies , 3396 participants : RR 0.87 , 95 % CI 0.72 to 1.05 ; I2 = 34 % ) , but significantly reduced cardiovascular mortality ( 6 studies , 2889 participants : RR 0.75 , 95 % CI 0.61 to 0.92 ; I2 = 0 % ) . One study reported no significant effect on rates of nonfatal cardiovascular events ( 714 participants : RR 1.14 , 95 % CI 0.86 to 1.50 ) and two studies showed no significant difference in hospitalisation ( 2 studies , 1688 participants : RR 1.23 , 95 % CI 0.93 to 1.63 ; I2 = 0 % ) . One study reported rates of hypotension during dialysis were significantly reduced with convective therapy ( 906 participants : RR 0.72 , 95 % CI 0.66 to 0.80 ) . Adverse events were not systematic ally evaluated in most studies and data for health-related quality of life were sparse . Convective therapies significantly reduced predialysis levels of B2 microglobulin ( 12 studies , 1813 participants : MD -5.55 mg/dL , 95 % CI -9.11 to -1.98 ; I2 = 94 % ) and increased dialysis dose ( Kt/V urea ) ( 14 studies , 2022 participants : MD 0.07 , 95 % CI -0.00 to 0.14 ; I2 = 90 % ) compared to diffusive therapy , but results across studies were very heterogeneous . Sensitivity analyses limited to studies comparing HDF with HD showed very similar results . Directly comparative data for differing types of convective dialysis were insufficient to draw conclusions . Studies had important risks of bias leading to low confidence in the summary estimates and were generally limited to patients who had adequate dialysis vascular access . Authors ' conclusions Convective dialysis may reduce cardiovascular but not all-cause mortality and effects on nonfatal cardiovascular events and hospitalisation are inconclusive . However , any treatment benefits of convective dialysis on all patient outcomes including cardiovascular death are unreliable due to limitations in study methods and reporting . Future studies which assess treatment effects of convection dose on patient outcomes including mortality and cardiovascular events would be informative Using acetate as a buffer during hemodialysis is recognized to predispose to intradialytic hypotension ; however , bicarbonate-based dialysis is not acetate free . Paired hemodiafiltration ( PHF ) is a novel online acetate-free technique . We investigated whether PHF is capable of abrogating the changes in systemic hemodynamics and troponin T ( cTnT ) seen with conventional hemodialysis . Twelve patients entered a r and omized crossover study . Blood pressure ( BP ) and a full range of hemodynamic variables were measured throughout PHF and st and ard dialysis using continuous pulse wave analysis . We also measured predialysis cTnT in 54 stable and unstable dialysis patients . BP was lower during PHF but without increased instability . Stoke volume and cardiac output declined progressively during both treatments but to a much lesser extent during PHF ( p = 0.003 , p < 0.0001 respectively ) , whereas peripheral resistance rose to a larger degree during hemodialysis ( p < 0.0001 ) . cTnT levels were lower before PHF as compared with hemodialysis ( p = 0.023 ) , with levels falling after PHF and rising after hemodialysis ( p < 0.0001 ) . In the supplementary patient group , predialysis median serum cTnT was higher in the unstable patients ( p = 0.0001 ) . This study demonstrates that PHF ( without exposure to acetate ) is associated with less deterioration in systemic hemodynamics , maintenance of BP , and less suppression of myocardial contractility as compared with bicarbonate dialysis Efficient removal of total body burden beta 2-Microglobulin ( beta 2-M ) in uremia is a continuing challenge , as dialysis-related amyloidosis represents a major complication of chronic renal replacement therapy . To investigate long-term beta 2-M removal we studied 3 groups of stable end-staged renal failure patients over a period of 4 years ; we compared low flux ( cuprophane ) hemodialysis ( n = 12 ) , high flux ( polysulfone ) hemodialysis ( n = 12 ) and hemofiltration using high flux polysulfone ( n = 8) . In contrast to the cuprophane membrane , the polysulfone membrane eliminated considerable amounts of beta 2-M. This was associated with a sustained reduction of predialysis serum beta 2-M-levels ( by 20 % ) . Compared with high flux hemodialysis , hemofiltration provided a 50 % higher elimination of beta 2-M. Thus , our long-term evaluation of beta 2-M removal suggests that hemofiltration rather than hemodialysis may be the treatment of choice for delaying the incidence of dialysis-related amyloidosis INTRODUCTION The dialytic management of hyper-phosphoremia , which is inadequate because of insufficient intra-dialytic removal of phosphate ( P ) , is further limited by PDR-P , i.e. the significant increase in serum P levels during the early postdialytic period . Patients and methods . To investigate the effects of enhanced P removal by haemodiafiltration on the inter-dialytic phosphoremia , we studied 12 uremic patients that were switched , with cross-over r and omised modality , to a single session of st and ard hemodialysis ( HD ) and hemodiafiltration ( HDF ) ( Acute Study ) . Blood sample s were obtained before the treatment , at the end ( T0 ) , after 30 , 60 , 90 and 120 minutes , and at 24 , 48 and 68 hours . During both dialytic treatments the whole effluent dialysate was collected to evaluate the intradialytic removal of P. Thereafter , patients were r and omised to receive either HD or HDF for three months , in the presence of constantly similar Kt/V , food intake and dose of phosphate binder ( Chronic Study ) . RESULTS Acute Study . Compared to HD , P removal in HDF was about 44 % greater in the presence of identical predialytic P levels ( 6.0+/-0.2 and 5.9+/-0.4 mg/dl ) and Kt/V ( 1.35+/-0.06 and 1.34+/-0.05 ) ; however , the inter-dialytic decline of serum P levels did not differ ( -50+/-3 % versus -42+/-3 % , p=0.098 ) . In HDF , PDR-P was faster ( 30 min versus 90 min ) and better ( at T120 : + 69+/-6 % versus + 31+/-4 % , p<0.001 ) . The higher P levels were maintained throughout the inter-dialytic period whereas Ca x P changed in parallel . Chronic Study . During the three months , pre-dialytic serum P diminished in HDF ( from 5.8+/-0.2 to 4.4+/-0.3 mg/dl , p<0.05 ) , while it remained unchanged in HD . A similar pattern of changes was detected in Ca x P. CONCLUSIONS Enhancement of P removal , acutely amplifies the extent of PDR-P , but allows better control of Ca-P homeostasis in the medium term . This effect is likely to be dependent on the enhanced mobilisation of phosphate from a deep compartment Retrospective studies suggest that online hemodiafiltration ( OL-HDF ) may reduce the risk of mortality compared with st and ard hemodialysis in patients with ESRD . We conducted a multicenter , open-label , r and omized controlled trial in which we assigned 906 chronic hemodialysis patients either to continue hemodialysis ( n=450 ) or to switch to high-efficiency postdilution OL-HDF ( n=456 ) . The primary outcome was all-cause mortality , and secondary outcomes included cardiovascular mortality , all-cause hospitalization , treatment tolerability , and laboratory data . Compared with patients who continued on hemodialysis , those assigned to OL-HDF had a 30 % lower risk of all-cause mortality ( hazard ratio [ HR ] , 0.70 ; 95 % confidence interval [ 95 % CI ] , 0.53 - 0.92 ; P=0.01 ) , a 33 % lower risk of cardiovascular mortality ( HR , 0.67 ; 95 % CI , 0.44 - 1.02 ; P=0.06 ) , and a 55 % lower risk of infection-related mortality ( HR , 0.45 ; 95 % CI , 0.21 - 0.96 ; P=0.03 ) . The estimated number needed to treat suggested that switching eight patients from hemodialysis to OL-HDF may prevent one annual death . The incidence rates of dialysis sessions complicated by hypotension and of all-cause hospitalization were lower in patients assigned to OL-HDF . In conclusion , high-efficiency postdilution OL-HDF reduces all-cause mortality compared with conventional hemodialysis BACKGROUND Activation of polymorphonuclear neutrophils ( PMNs ) and monocytes has been described during hemodialysis ( HD ) , which results in the release of reactive oxygen species and cytokines . Acetate-free biofiltration ( AFB ) has been shown to cause less monocyte activation and cytokine release than bicarbonate HD ( BHD ) . No data are available to date on the effect of AFB on PMN activation . METHODS We studied ex vivo superoxide anion release by PMNs isolated from nine patients treated in r and om order with AFB or BHD ( three sessions each ) . Plasma interleukin-1beta ( IL-1beta ) levels and the nitric oxide ( NO ) synthetic pathway also were evaluated . A polyacrylonitrile ( AN69 ; Hospal , Bologna , Italy ) dialyzer was used for both treatments . Fourteen healthy volunteers were used as controls . Blood sample s were drawn predialysis and 5 and 15 minutes after starting dialysis to obtain plasma and PMNs . RESULTS Neither ex vivo superoxide anion release nor blood PMN count was affected by AFB . Conversely , a peak in superoxide anion production associated with a decrease in PMN count was observed at 5 minutes during BHD . Results of superoxide anion production by control PMNs exposed in vitro to AFB or bicarbonate dialysis bath or Hank 's balanced salt solution supplemented with bicarbonate or acetate indicated that BHD-induced PMN activation could be attributed to the amount of bicarbonate present in the dialysis bath . IL-1beta plasma levels did not change during dialysis with AFB and were numerically higher at 5 and 15 minutes with respect to predialysis values during BHD . Uremic plasma obtained during either AFB or BHD induced greater NO synthesis by human umbilical vein endothelial cells than control plasma . CONCLUSION AFB , unlike BHD , does not cause PMN and monocyte activation , which could have a positive impact on dialysis-associated cardiovascular disease of dialyzed patients BACKGROUND AND AIM Acetate free biofiltration ( AFB ) provides a well-tolerated and efficient renal replacement therapy . Replacement of most of the acetate by bicarbonate in st and ard hemodialysis has result ed in a decrease in intradialytic hypotensive episodes . This has been attributed to a decrease in the acetate-induced impairment of myocardial contractility . The aim of the present study was to investigate whether the total absence of acetate in AFB would further enhance dialysis stability and improve cardiovascular status . PATIENTS AND METHODS In a long-term , r and omized trial we included 11 patients on AFB and 9 patients on bicarbonate hemodialysis ( HD ) for one year . Patients were matched for age , sex and urea reduction rate , but not for the presence of hypertension or cardiovascular history . During each dialysis session blood pressure was measured automatically and the presence of significant hypotension was recorded . Antihypertensive medication was registered every three months . Before and at the end of the study M-mode echocardiography was performed and left ventricular mass index ( LVMi ) was calculated . Every six months serum lipids were measured . RESULTS At baseline , mean arterial pressure ( MAP ) before and after dialysis , the percentage of hypotensive dialyses , LVMi and serum lipids did not differ between AFB and HD . Pre-dialysis MAP decreased in AFB ( from 112.5 to 107 mmHg ) and increased in HD ( from 101.7 to 105.3 mmHg ; p = 0.01 , HD versus AFB ) . Postdialysis MAP remained stable in both groups ( AFB 91.6 mmHg at 0 months and 90.6 mmHg at 12 months , for HD respectively 83.9 and 86.5 mmHg , NS ) . The percentage of hypotensive dialyses did not differ significantly between the groups during the study . LVMi decreased in AFB from 195.4 to 162.1 gr/m2 and increased in HD patients from 153.8 to 182.5 gr/m2 ( p = 0.03 HD versus AFB ) . The number of antihypertensive medications per patient did not differ between groups . Serum lipids remained unchanged during the trial . CONCLUSION In conclusion , AFB provided better control of pre-dialysis MAP compared to HD , and stable postdialysis MAP . The percentage of dialysis sessions with hypotension did not differ . LVMi decreased significantly in AFB , but rose in HD Introduction About ten years ago it was discovered that changes in filter design which increase passive filtration improved dialysis efficiency . Later , these modified membranes showed similar intradialytic efficiency when used in on-line hemodiafiltration or in bicarbonate dialysis , called internal hemodiafiltration . Aim and Methods On the basis of these previous results , we studied the long-term effects of internal hemodiafiltration , in comparison with low-flux bicarbonate dialysis . The pre-dialysis beta2-microglobulin level was chosen as the primary outcome variable . A prospect i ve multicenter study with a cross-over scheme , 2 treatments and 3 periods , was design ed . Twenty-four patients , followed in two dialysis centers , were enrolled . Many other parameters were measured every month at the first dialysis session of the week . The intra-dialytic removal of urea , beta2-microglobulin and homocysteine was also calculated . Results The removal of uremic toxins was significantly higher in internal hemodiafiltration than in low-flux bicarbonate dialysis . The pre-dialysis value of urea , phosphorus , beta2-microglobulin and homocysteine was lower during internal hemodiafiltration as compared with low-flux bicarbonate dialysis . The mean pre-dialysis value of hemoglobin was significantly higher during internal hemodiafiltration than low-flux bicarbonate dialysis , with a trend towards a significantly lower consumption of erythropoiesis stimulating agents during internal hemodiafiltration as compared with low-flux bicarbonate dialysis . Conclusions Long-term treatment with internal hemodiafiltration improves the removal of small molecules and stops the continuous increase of middle molecules as seen in low-flux bicarbonate dialysis . Internal hemodiafiltration may substitute low-flux bicarbonate dialysis , but we need new prospect i ve studies about long-term hard end-points Symptomatic intradialytic hypotension is a common complication of hemodialysis ( HD ) . The application of convective therapies to the outpatient setting may improve outcomes , including intradialytic hypotension . In this multicenter , open-label , r and omized controlled study , we r and omly assigned 146 long-term dialysis patients to HD ( n = 70 ) , online predilution hemofiltration ( HF ; n = 36 ) , or online predilution hemodiafiltration ( HDF ; n = 40 ) . The primary end point was the frequency of intradialytic symptomatic hypotension ( ISH ) . Compared with the run-in period , the frequency of sessions with ISH during the evaluation period increased for HD ( 7.1 to 7.9 % ) and decreased for both HF ( 9.8 to 8.0 % ) and HDF ( 10.6 to 5.2 % ) ( P < 0.001 ) . Mean predialysis systolic BP increased by 4.2 mmHg among those who were assigned to HDF compared with decreases of 0.6 and 1.8 mmHg among those who were assigned to HD and HF , respectively ( P = 0.038 ) . Multivariate logistic regression demonstrated significant risk reductions in ISH for both HF ( odds ratio 0.69 ; 95 % confidence interval 0.51 to 0.92 ) and HDF ( odds ratio 0.46 , 95 % confidence interval 0.33 to 0.63 ) . There was a trend toward higher dropout for those who were assigned to HF ( P = 0.107 ) . In conclusion , compared with conventional HD , convective therapies ( HDF and HF ) reduce ISH in long-term dialysis patients Background : Intradialytic hypotension ( IH ) is a common complication of bicarbonate hemodialysis ( BD ) and contributes to the intolerance of dialysis and the high cardiovascular morbidity and mortality among dialysis patients , the risk of which can be contained by convective therapies . Aims / Methods : To assess whether acetate-free biofiltration ( AFB ) , a hemodiafiltration technique found to improve intradialytic cardiovascular stability in short-term studies , can influence long-term IH rates , predialysis systolic blood pressure ( SBP ) , cardiovascular morbidity and mortality by comparison with BD , we analyzed data from a r and omized controlled trial enrolling 371 new-to-dialysis patients , 194 on BD and 177 on AFB . Results : During a 3-year follow-up , AFB carried a significantly lower risk of IH ( incidence rate ratio 0.60 ( 95 % CI 0.53–0.68 ) , p < 0.0001 ) . SBP dropped on AFB ( p = 0.01 ) , while it did not change on BD . Cardiovascular morbidity and mortality were similar between AFB and BD . Conclusion : AFB carries a lower long-term IH rate and reduces SBP by comparison with BD Background / Aims : In spite of the better efficiency of on-line hemodiafiltration ( HDF ) compared with conventional hemodialysis ( HD ) , it is relatively expensive . The aim of this study was to assess the advantages in the biochemical , hemodynamic and clinical effects in uremic patients treated with on-line HDF and with different frequencies of combination high-flux HD . Methods : One hundred eleven patients were divided into four groups receiving different frequencies of on-line HDF ( thrice , twice , once per week ) and high-flux HD . Results : Hemodynamic parameters including maximum drop of systolic blood pressure , episodes of symptomatic hypotension and mean saline infusion volumes during dialysis were reduced when frequencies of on-line HDF were increased . Significant improvements in urea kinetic were observed when frequencies of on-line HDF were increased . On-line HDF significantly reduced the amount of erythropoietin needed and improved intra- and inter-dialysis symptoms , physical well-being , menstruation and skin pigmentation when frequency of HDF is increased to three time per week . Conclusion : On-line HDF offers a better cardiovascular stability and clinical improvement . Thrice weekly on-line HDF offers a significant benefit when compared with lower frequencies of HDF per week and high-flux HD Nine patients on regular dialysis were studied , in a cross-over format comparing hemodialysis ( HD ) and hemofiltration ( HF ) , to identify potential mechanisms of the disparate hemodynamic responses . Dialysis and substitution fluid composition ( high sodium , acetate ) , treatment time , fluid loss rate , and membrane type ( AN 69 ) were matched . Cardiac output was determined by changes in thoracic electrical bioimpedance . Cardiac output remained stable during HF but increased during HD ( p < 0.001 , HD vs. HF ) , despite a parallel reduction in stroke volume . The heart rate response was significantly greater during HD relative to HF ( p < 0.01 ) . Systemic vascular resistance remained stable during HF but decreased significantly during HD ( p < 0.05 ) . Although there was a modest fall during HD , the difference in blood pressure at the end of treatment between HD and HF was not significant . Comparable increases in body temperature were observed during both treatments . Plasma catecholamines increased in parallel during HD and HF and following orthostatic stimulation at the end of treatment , and extracorporeal catecholamine clearances were similar . The values for serum sodium , total CO2 , anion gap , potassium , and hematocrit at the end of treatment were similar , whereas total serum calcium was significantly greater following HD . There were no significant differences in indices of myocardial contractility or central blood volume . These results suggest that the disparate hemodynamic responses to fluid and solute removal during HD and HF can be dissociated from changes in osmolality or venous tone , membrane bioincompatibility , thermal stress , or differences in acetate delivery or catecholamine release . The explanation for the disparate hemodynamic responses between these two treatment modalities remains unclear . A role for an as yet unidentified vasodilatory substance generated during dialysate exposure , or convectively removed during hemofiltration , remain intriguing possibilities BACKGROUND The accumulation of beta2-microglobulin ( beta2-M ) in long-term dialysis patients may lead to dialysis amyloidosis . In this respect , the removal with different modes of on-line haemodiafiltration ( HDF ) of beta2-M was studied . Long-term clinical observations in patients with more than 10 years of dialysis , treated mainly with biocompatible and highly permeable membranes and in the last years with on-line HDF are also reported . METHODS In the first part of this report , the reduction ratios and clearances of beta2-M , blood urea nitrogen , creatinine and phosphorus ( P ) of on-line HDF with 40 to 120 ml/min replacement fluid are compared with bicarbonate haemodialysis ( HD ) . In the second part , we investigated 16 patients with more than 10 years of dialysis treatment . The prevalence of dialysis amyloidosis and the mean values for serum albumin , serum total cholesterol , HDL and LDL cholesterol and parathyroid hormone are reported , as well as the mean dose of erythropoietin . RESULTS In the first part with on-line HDF , starting from HDF 60 ml/min a significantly higher beta2-M reduction ratio and clearance vs HD is noted . In HDF100 ( i.e. with 241 replacement volume per 4-h treatment ) vs HD , a beta2-M reduction ratio of 72.7 % vs 49.7 % ( P= 0.0000 ) and a beta2-M clearance of 116.8 vs 63.8 ml/min ( P=0.0000 ) was obtained . Comparing HDF120 with HDF100 , there is a significantly higher beta2-M clearance with the former ( P<0.005 ) , although the beta2-M reduction ratio was not significantly better . In the HDF120 session the amount of beta2-M in the total dialysate was 292 mg per session . If one adds the known 17 % adsorption on the polysulfone membrane , a total of 341.6 mg beta2-M per session is removed , which adds up to 1024.8 mg a week . Concerning the small molecules , our results with HDF100 also show a higher creatinine and especially P clearance vs HD . In the second part with 16 patients with more than 10 years of dialysis treatment ( mean 14 years 1 month ) , the mean time on HDF amounted to 39.5 % of the total treatment time . In four patients only biocompatible and highly permeable membranes were used , AN69 and mainly polysulfone , and in four other patients these membranes were used for more than 95 % of the treatment time . Therefore , it is not surprising that the prevalence of carpal tunnel syndrome was only 12.5 % in the patients after 10 years of dialysis . Twenty-five percent of these patients met the criteria for diagnosis of beta2-M bone-amyloidosis , proposed by van Ypersele de Strihou et al. , but without a retrospective X-ray analysis . The mean predialysis beta2-M value was 29.6 mg/l . The mean values for serum albumin , serum total cholesterol , HDL and LDL cholesterol were within normal limits . For the parathyroid hormone a mean of 287.5 pg/ml was found . Subtotal parathyroidectomy was performed in five patients . The mean dose of 43 U erythropoietin/kg per session is comparable with those reported in the literature . Conclusions . Like Canaud , in our renal unit , treatment with on-line HDF with a highly permeable and biocompatible membrane has proven to be an efficient , well-tolerated and safe technique . Furthermore it leads to a low prevalence of dialysis amyloidosis and a superior P clearance . However , continuous attention must be paid to an on-line sterile and apyrogenic dialysate . Although on-line HDF is undoubtedly a more optimal approach of chronic dialytic treatment , it also carries a higher cost , which is currently evaluated to be nearly US$ 11 per session BACKGROUND Increased oxidative stress ( OxSt ) as well as inflammation are risk factors for cardiovascular events and determinant of cardiovascular disease which remains the most common cause of excess morbidity and mortality for end-stage renal disease ESRD patients . Haemodiafiltration with on-line regeneration of ultrafiltrate ( HFR ) has been shown to have a positive impact on markers of inflammation while its effect on OxSt is not known . METHODS This study evaluates in haemodialysis patients the effect of HFR on the plasma level of oxidized LDL ( OxLDL ) , a marker of OxSt , and mononuclear cell gene and protein expression of OxSt-related proteins such as p22phox ( subunit of NAD(P)H oxidase ) , PAI-1 ( induced by OxSt and atherothrombogenetic ) and haeme-oxygenase-1 ( HO-1 ) ( induced by OxSt ) . Fourteen patients were r and omized into two groups in a crossover design , treated for 6 month periods with HFR ( SG8 Plus-Bellco , Mir and ola , Italy ) or low-flux bicarbonate dialysis ( HD ) using a polysulphone dialyser 1.8 m2 . Blood sample s were collected at the beginning of the study , after 6 months ( crossover ) and after 12 months . RESULTS ANOVA analysis of the data performed to rule out any crossover effect in either sequence was not significant and thus data from both sequences were combined and then analysed further statistically . HFR reduced mRNA production and protein expression of p22phox and PAI-1 compared with HD ( -9+/-5 vs 2+/-6 Delta% , P<0.0001 and -15+/-20 vs 3+/-17 Delta% , P<0.05 for p22phox ; -19+/-6 vs -5+/-5 Delta% , P<0.0001 and -24+/-12 vs 9+/-15 Delta% , P<0.0001 for PAI-1 ) . HO-1 was unchanged ( -12+/-8 vs -10+/-8 Delta% and -21+/-12 vs -14+/-8 Delta% ) while plasma OxLDL was reduced ( -14+/-19 vs 1+/-14 Delta% , P<0.01 ) . CONCLUSIONS The results of our study indicate that HFR treatment , compared with st and ard dialysis , has a lower impact on OxSt . Given , the strong relationship between OxSt and inflammation and their impact on the long-term cardiovascular complications in end-stage renal disease patients , HFR might have a more beneficial impact in reducing the risk of atherosclerotic cardiovascular disease in dialysis patients BACKGROUND Current methods of renal replacement therapy lead only to an insignificant removal of larger , potentially toxic , substances , which are excreted by healthy kidneys . On-line preparation of substituate from dialysate and the use of high-flux membranes allow substantial convective removal of such substances . A modified on-line haemodiafiltration method with the use of a large membrane surface and a high convective part was chosen to test whether the elimination of larger substances , such as low-molecular-mass proteins , has a clinical impact . METHODS In a prospect i ve , controlled study over 24 months , 44 unselected chronic dialysis patients were r and omized to undergo either low-flux haemodialysis ( HD ; n = 21 ) or haemodiafiltration ( HDF ; n = 23 ) . To eliminate confounding factors , low-molecular efficacy was matched ( Kt/V 1.8 ) , and the same membrane material ( polysulfone ) , ultrapure dialysate and the same treatment duration ( 4.5 h ) were applied to each group . RESULTS Morbidity , mortality , blood pressure , dialysis-associated hypotensive episodes , haematocrit and erythropoietin dose did not differ between the groups . The same was true for body weight and , accordingly , bioimpedance values , clinical hydration score , skinfold thickness , plasma albumin , prealbumin and transferrin . beta2-Microglobulin in the plasma did not change in the HD group and varied between 32 and 43 mg/l throughout the 2 years . In HDF , beta2 microglobulin decreased from similar values to 18 mg/l predialysis ( P<0.01 ) in the first 6 months of HDF treatment and then remained constant during the remaining 18 months . CONCLUSION In the absence of any clinical marker of uraemic toxicity the removal of larger molecules over the time-span of 2 years during HDF had no clinical implication compared with extremely ( and for routine practice unrealistically ) well-dialysed patients with low-flux HD . In the absence of any side-effects of on-line HDF and supposing that plasma beta2-microglobulin is a marker of morbidity , on-line HDF ensures an excellent dialysis quality which apparently takes time to translate into measurable clinical sequelae Atherosclerotic complications have a significant effect on mortality in patients undergoing hemodialysis ( HD ) therapy . However , anti-atherosclerotic and cardioprotective effects of on-line hemodiafiltration ( HDF ) remain to be eluci date d. We prospect ively compared the anti-atherosclerotic and cardioprotective effects in two r and omly divided groups , i.e. on-line HDF group ( n = 13 ) and conventional HD group ( n = 9 ) for 1 year . Surrogate markers were brachial-ankle pulse wave velocity ( baPWV ) , intima-media thickness ( IMT ) of carotid artery as an atherosclerosis marker , and cardiac functional surrogate markers included left ventricular mass index ( LVMI ) , ejection fraction ( EF ) , and LV diastolic capacity represented as E/A and deceleration time ( DT ) . LVMI in on-line HDF patients showed significant regression after 1 year of treatment ( 131.9 ± 25.8 to 116.5 ± 24.7 g/m(2 ) , P = 0.03 ) , while LVMI in HD patients did not show any significant change ( 148.0 ± 47.1 to 142.3 ± 35.5 g/m(2 ) ) . Levels of baPWV in HD patients showed a significant increase ( 11.4 % ) from basal levels , while on-line HDF groups showed no significant increase . Furthermore , HD patients showed significant worsening of LV diastolic capacity ( E/A : from 0.87 ± 0.12 to 0.79 ± 0.08 , P = 0.03 ) , while it was not shown in on-line HDF patients . Ejection fraction and IMT did not show any significant change in both groups . Serum albumin , C-reactive protein , β2 microglobulin , blood pressure , and anti-hypertensive drug use did not change in both groups . On-line HDF showed a significant improvement in LVMI and prevented a significant worsening of baPWV or LV diastolic capacity compared with patients on conventional HD therapy The effect of acetate dialysis ( AD ) , bicarbonate dialysis ( BD ) , and acetate-free biofiltration ( AFB ) on nitric oxide ( NO ) synthesis and the implication s for dialysis hypotension was studied . The finding that uremic plasma is a potent inducer of NO synthesis by endothelial cells in vitro suggested that the cardiovascular instability of dialysis patients might result from excessive NO formation . Cardiovascular instability is more frequent in patients undergoing AD than BD . To see whether these differences were attributable to NO , we studied the NO synthetic pathway ex vivo in patients undergoing different dialysis procedures . Five patients were treated , in a r and om order , with AD , BD , and AFB , a technique using a buffer-free dialysate and postdilution of a sterile bicarbonate solution . Each type of dialysis was used for 1 week , comprising three dialysis sessions . A polyacrylonitrile dialyzer was used for all three methods . Before and after the third dialysis , plasma was collected , added to [3H]L-arginine , and incubated with human umbilical vein endothelial cells ( HUVECs ) for 24 hours . NO synthesis was evaluated as [3H]L-citrulline formation . Plasma concentrations of interleukin-1beta ( IL-1beta ) , a potent inducer of inducible NO synthase ( iNOS ) in endothelial cells , were also measured . Plasma collected from patients after AD stimulated endothelial NO synthesis more than plasma from the same patients before the dialysis session ( pre-AD , 0.173+/-0.028 nmol/10(5 ) cells v post-AD , 0.280+/-0.093 nmol/10(5 ) cells ; P < 0.05 ) . A slight , although not significant , increase was also observed when HUVECs were incubated with plasma drawn after BD ( pre-BD , 0.151+/-0.014 nmol/10(5 ) cells ; post-BD , 0.230+/-0.055 nmol/10(5 ) cells ) . AFB did not aggravate the stimulatory effect of uremic plasma on endothelial NO synthesis ( pre-AFB , 0.184+/-0.038 nmol/10(5 ) cells ; post-AFB , 0.189+/-0.040 nmol/10(5 ) cells ) . Plasma IL-1beta was greater ( P < 0.01 ) after AD than after BD and AFB ( post-AD , 0.234+/-0.028 pg/mL ; post-BD , 0.124+/-0.019 pg/mL ; post-AFB , 0.120+/-0.013 pg/mL ) . With AD , there was a greater intradialytic decrease in systolic blood pressure than with BD or AFB . Weight and blood volume loss and sodium balance were similar in AD , BD , and AFB . These data were consistent with the possibility that NO and cytokines , released in excessive amounts during AD , may contribute to hemodynamic instability BACKGROUND Given the paucity of prospect i ve r and omized controlled trials assessing comparative performances of different dialysis techniques , we compared on-line high-flux hemofiltration ( HF ) with ultrapure low-flux hemodialysis ( HD ) , assessing survival and morbidity in patients with end-stage renal disease ( ESRD ) . STUDY DESIGN An investigator-driven , prospect i ve , multicenter , 3-year-follow-up , central ly r and omized study with no blinding and based on the intention-to-treat principle . SETTING & PARTICIPANTS Prevalent patients with ESRD ( age , 16 to 80 years ; vintage > 6 months ) receiving renal replacement therapy at 20 Italian dialysis centers . INTERVENTIONS Patients were central ly r and omly assigned to HD ( n = 32 ) or HF ( n = 32 ) . OUTCOMES & MEASUREMENTS All-cause mortality , hospitalization rate for any cause , prevalence of dialysis hypotension , st and ard biochemical indexes , and nutritional status . Analyses were performed using the multivariate analysis of variance and Cox proportional hazard method . RESULTS There was significant improvement in survival with HF compared with HD ( 78 % , HF versus 57 % , HD ) at 3 years of follow-up after allowing for the effects of age ( P = 0.05 ) . End-of-treatment Kt/V was significantly higher with HD ( 1.42 + /- 0.06 versus 1.07 + /- 0.06 with HF ) , whereas beta(2)-microglobulin levels remained constant in HD patients ( 33.90 + /- 2.94 mg/dL at baseline and 36.90 + /- 5.06 mg/dL at 3 years ) , but decreased significantly in HF patients ( 30.02 + /- 3.54 mg/dL at baseline versus 23.9 + /- 1.77 mg/dL ; P < 0.05 ) . The number of hospitalization events for each patient was not significantly different ( 2.36 + /- 0.41 versus 1.94 + /- 0.33 events ) , whereas length of stay proved to be significantly shorter in HF patients compared with HD patients ( P < 0.001 ) . End-of-treatment body mass index decreased in HD patients , but increased in HF patients . Throughout the study period , the difference in trends of intradialytic acute hypotension was statistically significant , with a clear decrease in HF ( P = 0.03 ) . LIMITATIONS This is a small preliminary intervention study with a high dropout rate and problematic generalizability . CONCLUSION On-line HF may improve survival independent of Kt/V in patients with ESRD , with a significant decrease in plasma beta(2)-microglobulin levels and increased body mass index . A larger study is required to confirm these results BACKGROUND It is the prevailing view that convective dialysis techniques stabilize blood pressure . The aim of this study was to compare the hemodynamics of high-dose predilution hemodiafiltration ( HDF ) and low-flux hemodialysis ( HD ) , under matched conditions and using high calcium-ion concentration in the replacement/dialysis fluid . METHODS 13 stable hemodialysis patients were investigated in a r and omized crossover , blinded controlled trial . The patients were allocated to one session of predilution HDF ( substitution fluid 1.20 1/kg BW ) and one session of HD at 4.5 hours . At the start of the dialysis the patient 's core temperature was " locked " by an automatic feedback system regulating the dialysate temperature , thereby patient 's temperature was kept stable throughout the whole treatment . The Ca ion concentration in the substitution/dialysis fluid was 1.75 mM. Cardiac output was measured hourly by the ultrasound velocity dilution method . RESULTS Within treatments comparisons revealed that both treatments displayed stable mean blood pressure and equally reduced cardiac output . HDF showed decreased stroke volume and increased total peripheral resistance . The pulse rate decreased significantly only during HD . Arterial temperature was kept constant during both treatments . Ultrafiltration volume , cardiopulmonary recirculation , relative blood volume , Kt/V and total energy transfer were matched for HD and HDF . The overall between treatments comparisons revealed no significant differences . CONCLUSIONS We have shown that during matched conditions and high calcium concentrations , the hemodynamic profiles of high dose predilution HDF and lowflux HD were similar . Both modalities showed stable mean blood pressure profiles . An acute circulatory benefit of convective solute removal over diffusive , could not be demonstrated Background : Hemodiafiltration with online preparation of the substitution [ online high-flux hemodiafiltration ( OHDF ) ] and hemodiafiltration with prepared bags of substitution ( HDF ) are important , recently widely used renal replacement therapies in patients with end-stage renal disease . However , there is little information on the comparative impacts of these modalities versus conventional low-flux hemodialysis ( HD ) on the quality of life ( QoL ) of HD patients . This study investigates the effect of dialysis modality on QoL in chronic HD patients . Methods : In this prospect i ve , r and omized , cross-over , open label study , 24 patients were enrolled . Their age were 62 ± 13.34 years ( mean ± SD ) , with the duration of dialysis of 31 ± 23.28 months ( mean ± SD ) . Five of the patients were women . QoL was measured by the Short-Form Health Survey with 36 questions ( SF-36 ) and subscale scores were calculated . Each patient received HD , OHDF , and HDF for 3 months , with the dialysis modality subsequently being altered . They completed the question naire of QoL at the end of each period . Results : There were statistical significant differences in QoL for the total SF-36 [ 36.1 ( 26.7–45.7 ) and 40.7 ( 30.2–62.8 ) ] , for classic low-flux HD and high-flux hemodiafiltration , for bodily pain [ 45 ( 26.9–66.9 ) and 55 ( 35.6–87.5 ) ] , and for role limitations due to emotional functioning [ 0 ( 0–33.3 ) and 33.3 ( 0–100 ) ] , respectively . The scores did not differ significantly between the two types of hemodiafiltration . Conclusions : Our study indicates that QoL differs significantly among patients receiving low-flux HD and high-flux hemodiafiltration , on total SF-36 , bodily pain , and role limitations due to emotional functioning . Convective modalities may offer better QoL than diffusive HD BACKGROUND AND OBJECTIVES Theoretical advantages exist of online hemodiafiltration ( HDF ) over high-flux hemodialysis ( HD ) , but outcome data are scarce . Our objective was to compare outcomes between these modalities . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS We studied 858 incident patients in our incremental high-flux HD and online HDF program during an 18-yr period . We compared outcomes , including survival , in those who were treated predominantly with HDF ( > 50 % sessions ) and those with high-flux HD . Survival comparisons used a Cox model taking into account the time-varying proportion of time spent on HDF . All data were prospect ively collected . RESULTS A total of 152,043 sessions were delivered as HDF and 291,222 as high-flux HD . A total of 232 ( 27 % ) patients were treated predominantly with HDF and 626 ( 73 % ) with high-flux HD . Total Kt/V , serum albumin , erythropoietin resistance index , and BP were similar in both groups up to 5 yr after HD initiation . Intradialytic hypotension was less frequent in the predominant HDF group . Predominant HDF treatment was associated with a reduced risk for death after correction for confounding variables . In a second Cox model , proportion of time spent on HDF predicted survival , such that patients who were treated solely by HDF would have a hazard for death of 0.66 compared with those who solely used high-flux HD . CONCLUSIONS We found no benefits of HDF over high-flux HD with respect to anemia management , nutrition , mineral metabolism , and BP control . The mortality benefit associated with HDF requires confirmation in large r and omized , controlled trials . These data may contribute to their design BACKGROUND The discussion about the pathogenesis of renal anaemia , whether it is primarily due to relative erythropoietin ( Epo ) deficiency or to uraemic inhibition of erythropoiesis , is still open . Although it has so far not been possible to identify or isolate a substance retained in uraemia with a suppressive action directed specifically against red-cell production , dialysis therapy can improve the effect of both residual endogenous Epo and exogenous rHuEpo . To what extent the mode and /or the dose of dialysis influence Epo efficacy is as yet poorly understood . METHODS This study was performed as a single-centre trial . The protocol included a run-in period of 4 months followed by a prospect i ve cross-over study including 6 months each of acetate-free biofiltration ( AFB ) with a high-flux biocompatible membrane and st and ard bicarbonate dialysis ( BD ) with a low-flux cellulosic membrane in a r and om sequence . AFB is a haemodiafiltration technique based on a continuous post-dilution infusion of a sterile isotonic bicarbonate solution . At the start of the run-in period ( and for the entire length of the study ) , rHuEpo administration was withdrawn ; patients whose haemoglobin ( Hb ) levels dropped at a level < 8.0 g/dl at one single monthly check , had to be withdrawn from the study . A blood sample was collected every month for the blood gas analysis and for the determination of blood urea nitrogen , serum creatinine , sodium , potassium , calcium , phosphorus , Hb , erythrocyte , reticulocyte , leukocyte and thrombocyte cell counts , mean globular volume and haematocrit . An equilibrated single pool Kt/V(urea)>1.2 was m and atory in both treatment modalities . Serum iron , total iron-binding capacity , and ferritin were checked every 3 months . RESULTS Twenty-three of 137 haemodialysis patients were considered eligible for the trial on the basis of the entry criteria . Of these , 15 volunteered and only 10 completed the study . No significant differences in the haematological indices , in the biochemical parameters assessing body iron stores , or in i.v . iron dosage was observed when comparing AFB with BD treatments . The equilibrated single pool Kt/V(urea ) was always > 1.2 and in no case was a significant difference observed when comparing AFB with BD treatments . Treatment time was significantly different between the two treatments ( 262+/-2 min in BD and 249+/-1 in AFB , P<0.0001 ) . Neither pre- nor post-dialysis systolic and diastolic blood pressures , pre-dialysis serum bicarbonate and pH , pre-dialysis serum sodium , potassium , calcium , or phosphorus were significantly different when comparing the two treatment modalities . All 10 patients completed the 1-year follow-up without any major side-effects . CONCLUSIONS Our study did not show any improvement of anaemia when treating a highly selected patient group , in the absence of any Epo therapy , with AFB compared with st and ard BD . Even though these conclusions can not be extended in toto to the entire dialysis population , in which there is a large proportion of Epo-treated patients with Hb levels around 11 g/dl , we may nevertheless conclude that when patients are well selected , adequately dialysed , and not iron- and /or vitamin-depleted , the effect of a haemodiafiltration technique with a high-flux biocompatible membrane is less than might be expected from the results of uncontrolled studies BACKGROUND Middle molecules ( MMs ) and protein-bound solutes are poorly removed by conventional hemodialysis ( HD ) . Hemodiafiltration ( HDF ) combines convection and diffusion in a single therapy and has been shown to be superior for the elimination of several small and larger retention molecules . Information on the elimination of protein-bound solutes during convective strategies is scarce . The primary aim of this r and omized crossover study is to evaluate the influence of internal filtration , postdilution HDF , and predilution HDF on removal of the protein-bound solute p-cresol . METHODS Fourteen stable patients on regular thrice-weekly medium-flux HD therapy were assigned to 5 treatment periods of 2 weeks each for : HD with HF80(S ) ; HD with FX80 ; postdilution HDF , 20 L , with FX80 ; predilution HDF , 20 L , with FX80 ; and predilution HDF , 60 L , with FX80 ( all dialyzers from Fresenius Medical Care , Bad Homburg , Germany ) . RESULTS As for the water-soluble solutes , elimination of p-cresol was better during HDF and increased with greater filtration volumes . Removal of beta2-microglobulin ( beta2 m ) also was enhanced during HDF . However , the positive effect of convection was offset when high predilution substitution volumes were applied , probably as a result of dilution . Within each dialytic approach , removal of the MM beta2 m and the protein-bound solute p-cresol was significantly less than that of the water-soluble molecules urea nitrogen and creatinine . CONCLUSION Our data indicate that convection can provide superior protein-bound solute removal compared with high-flux HD . Our findings also suggest that better elimination of the unbound fraction is the most plausible underlying mechanism CONTEXT Patients with chronic kidney disease ( CKD ) experience increased rates of hospitalization and death . Depressive disorders are associated with morbidity and mortality . Whether depression contributes to poor outcomes in patients with CKD not receiving dialysis is unknown . OBJECTIVE To determine whether the presence of a current major depressive episode ( MDE ) is associated with poorer outcomes in patients with CKD . DESIGN , SETTING , AND PATIENTS Prospect i ve cohort study of 267 consecutively recruited out patients with CKD ( stages 2 - 5 and who were not receiving dialysis ) at a VA medical center between May 2005 and November 2006 and followed up for 1 year . An MDE was diagnosed by blinded personnel using the Diagnostic and Statistical Manual of Mental Disorders ( Fourth Edition ) criteria . MAIN OUTCOME MEASURES The primary outcome was event-free survival defined as the composite of death , dialysis initiation , or hospitalization . Secondary outcomes included each of these events assessed separately . RESULTS Among 267 patients , 56 had a current MDE ( 21 % ) and 211 did not ( 79 % ) . There were 127 composite events , 116 hospitalizations , 38 dialysis initiations , and 18 deaths . Events occurred more often in patients with an MDE compared with those without an MDE ( 61 % vs 44 % , respectively , P = .03 ) . Four patients with missing date s of hospitalization were excluded from survival analyses . The mean ( SD ) time to the composite event was 206.5 ( 19.8 ) days ( 95 % CI , 167.7 - 245.3 days ) for those with an MDE compared with 273.3 ( 8.5 ) days ( 95 % CI , 256.6 - 290.0 days ) for those without an MDE ( P = .003 ) . The adjusted hazard ratio ( HR ) for the composite event for patients with an MDE was 1.86 ( 95 % CI , 1.23 - 2.84 ) . An MDE at baseline independently predicted progression to dialysis ( HR , 3.51 ; 95 % CI , 1.77 - 6.97 ) and hospitalization ( HR , 1.90 ; 95 % CI , 1.23 - 2.95 ) . CONCLUSION The presence of an MDE was associated with an increased risk of poor outcomes in CKD patients who were not receiving dialysis , independent of comorbidities and kidney disease severity Introduction : Left ventricular hypertrophy ( LVH ) is present in a majority of hemodialysis ( HD ) patients and is among the strongest risk factors for cardiovascular events and mortality . Hemofiltration ( HF ) , a purely convective dialysis treatment , has been associated with enhanced hemodynamic stability compared with HD , possibly as a result of a more physiologic removal of fluid and solutes . Methods : In a r and omized controlled study conducted at ten dialysis centers in Sweden and Denmark , incident patients ( HD <3 months ) without clinical signs or history of cardiovascular disease were r and omized to treatment with either online , predilution HF or low-flux HD . The primary endpoint was change in left ventricular mass index ( LVMI ) , as measured by two-dimensional M-mode and Doppler echocardiography . Results : The analyses included 34 patients ( 18 HF , 16 HD ) followed for up to 2 years . At baseline , 65 % of the patients had LVH , but LVMI did not differ between the study groups . In the HF group , LVMI decreased by 22 ± 48 g/m2 during a mean treatment time of 19 ± 7 months , while in the HD group the decrease was 15 ± 57 g/m2 during 16 ± 7 months . As analyzed by MANOVA ( mixed model ) , the difference in LVMI over the whole period was statistically significant ( p = 0.03 ) with a more favorable outcome in HF . Blood pressure and other study variables did not differ between the groups , but at baseline and throughout the study , HF patients required heavier antihypertensive treatment . Conclusions : In incident dialysis patients , long-term predilution HF , a purely convective dialysis treatment , is associated with a significantly more favorable development of LVMI compared with regular low-flux HD . Considering the predictive strength of LVMI as a risk factor , the quantitative difference between the treatments is of clinical importance |
988 | 19,301,219 | At a professional level , it appears that contemporary dancers demonstrate higher maximal oxygen uptake and higher scores in muscular endurance than ballet dancers .
However , contemporary dance students are equally fit compared to their ballet counterparts and their body composition is also very similar .
Further research is needed in order to confirm preliminary data , which suggest that the implementation of additional fitness training is beneficial for contemporary dance students to achieve a better performance outcome | It has been suggested that dancers are less fit compared to other athletes .
However , the majority of studies make their arguments based on data deriving mainly from ballet .
Therefore , the aim of the current review was to investigate : a ) aerobic and anaerobic fitness , muscular strength and body composition characteristics in contemporary dancers of different levels , and b ) whether supplementary exercise interventions , in addition to normal dance training , further improves contemporary dance performance . | The purpose of the present study was to assess the effects of a 12-week aerobic and muscular strength training program on selected dance performance and fitness-related parameters in modern dance students . The sample consisted of 32 men and women ( age 19 ± 2.2 years ) who were r and omly assigned into exercise ( n = 19 ) and control ( n = 13 ) groups . Anthropometric and flexibility assessment s , treadmill ergometry , strength measurements , and —on a separate day — a dance technique test were conducted pre and postexercise training in both groups . After the end of the program , the exercise group revealed significant increases in dance ( p > 0.02 ) , & OV0312;O2max ( p > 0.04 ) , flexibility ( p > 0.01 ) , and leg strength ( p > 0.001 ) tests compared to controls . It is concluded that in modern dance students ( a ) a 3-month aerobic and strength training program has positive effects on selected dance performance and fitness-related parameters , ( b ) aerobic capacity and leg strength improvements do not hinder dance performance as studied herein , and ( c ) the dance-only approach does not provide enough scope for physical fitness enhancements PURPOSE The aim of this study was to generate and vali date a prediction equation for estimating the body composition in dancers using the bioelectrical impedance analysis ( BIA ) as a method of assessment . METHODS The fat-free mass ( FFM ) of 42 young female professional dance students was estimated by four different methods : dual x-ray absorptiometry ( DXA ) , BIA , simple anthropometry , and skinfold thickness ; DXA was used as a criterion method . RESULTS The dancers ' FFM was 42.6 kg ( SD : 3.3 ) and , on the average , body fat represented the 19.4 % ( SD : 4.3 ) of their body weight . Two dancer-specific BIA equations for the prediction of FFM ( E(BIA ) ) were developed by multiple regression analysis using weight , height , resistance index , and triceps as predictor variables ( E(BIA ) and E(BIA-TRICEPS ) ) . The validity of these equations as well as of those previously reported was assessed in two r and omly selected subgroups of the initial study group , as described by the Bl and -Altman analysis . The bias and the limits of agreement of the equations developed in the present study were lower than those result ing from the application of the previously used equations of Segal et al. and Hergenroeder et al. It was also found that , when vali date d against DXA , skinfolds measurements did not accurately predict body fatness in this group of young females . CONCLUSION The new equations allow for an accurate routine assessment of body composition in young female dancers by using the method of BIA . Further studies are needed for the cross-validation of the equations in various groups of dancers OBJECTIVES To compare the hip and ankle range of motion and hip muscle strength in 8 - 11 year old novice female ballet dancers and controls . METHODS Subjects were 77 dancers and 49 controls ( mean ( SD ) age 9.6 ( 0.8 ) and 9.6 ( 0.7 ) years respectively ) . Supine right active hip external rotation ( ER ) and internal rotation ( IR ) were measured using an inclinometer . A turnout protractor was used to assess st and ing active turnout range . The measure of ER achieved from below the hip during turnout ( non-hip ER ) was calculated by subtracting hip ER range from turnout range , and hip ER : IR was derived by dividing ER range by IR range . Range of right weight bearing ankle dorsiflexion was measured in a st and ing lunge using two methods : the distance from the foot to the wall ( in centimetres ) and the angle of the shank to the vertical via an inclinometer ( in degrees ) . Right calf muscle range was measured in weight bearing using an inclinometer . A manual muscle tester was used to assess right isometric hip flexor , internal rotator , external rotator , abductor , and adductor strength . RESULTS Dancers had less ER ( p<0.05 ) and IR ( p<0.01 ) range than controls but greater ER : IR ( p<0.01 ) . Although there was no difference in turnout between groups , the dancers had greater non-hip ER . Dancers had greater range of ankle dorsiflexion than controls , measured in both centimetres ( p<0.01 ) and degrees ( p<0.05 ) , but similar calf muscle range . After controlling for body weight , controls had stronger hip muscles than dancers except for hip abductor strength which was similar . Regression analyses disclosed a moderate relation between turnout and hip ER ( r = 0.40 ) . There were no significant correlations between range of motion and training years and weekly training hours . CONCLUSIONS Longitudinal follow up will assist in determining whether or not hip and ankle range in young dancers is genetically fixed and unable to be improved with further balletic training This study evaluated the body composition ( underwater weighing ) and cardiorespiratory function ( VO(2)max and O(2)debt max measured by the treadmill exercise test ) in 12 members of the women 's volleyball team ( mean age 17.4 years ) and 11 members of the women 's basketball team ( mean age 17.6 years ) that won the championship in the Japan Inter-high School Meeting . We also examined differences in the physical abilities between the members of the top teams of different events . The following results were obtained . ( 1 ) The mean values of the height and body weight were 168.7+/-5.89 cm and 59.7+/-5.73 kg in the volleyball players and 166.5+/-7.87 cm and 58.8+/-6.85 kg in the basketball players . ( 2 ) The mean % Fat was 18.4+/-3.29 % in the volleyball players and 15.7+/-5.05 % in the basketball players , and was similar to the reported values in elite adult players . ( 3 ) The mean VO(2)max was 2.78+/-0.32 L x min(-1 ) ( 46.5+/-2.90 ml x kg(-1 ) x min(-1 ) ) in the volleyball players and 3.32+/-0.31 L x min(-1 ) ( 56.7+/-4.17 ml x kg(-1 ) x min(-1 ) ) in the basketball players , and was similar to the reported values in elite adult players . ( 4 ) The mean O(2)debt max was 6.18+/-1.15 L ( 103.2+/-12.40 ml x kg(-1 ) ) in the volleyball players and 7.92+/-1.80 L ( 134.3+/-23.24 ml x kg(-1 ) ) in the basketball players . These values were 2.6 times and 3.3 times as high as the average values in high school students in general . ( 5 ) No significant difference was observed in any measured item of the physique , skinfold thickness , or body composition between the volleyball players and basketball players . ( 6 ) The VO(2)max and O(2)debt max were 22 % and 28 % higher in the basketball players than in the volleyball players . From these results , the female volleyball players and basketball players evaluated in this study had the physical abilities needed to win the championship in the Japan Inter-high School Meets , i.e. a large FFM and excellent aerobic and anaerobic work capacities . Also , basketball appears to require higher aerobic and anaerobic work capacities than volleyball & NA ; Wyon , M.A. , A. Grant , E. Redding , A. Head , and N.C.C. Sharp . Oxygen uptake during modern dance class , rehearsal , and performance . J. Strength Cond . Res . 18(3):646–649 . 2004.—The aim of the present study was to examine whether the workload , expressed in oxygen uptake and heart rate , during dance class and rehearsal prepared the dancer for performance . Previous research on the dem and s of class and performance has been affected by equipment limitations and could only provide limited insight into the physiological dem and s placed on the dancer . The present study noted that dance performance had significantly greater mean oxygen uptake and heart rate than noted in both class and rehearsal ( p < 0.05 ) . Further analysis noted that , during class and rehearsal , heart rates were rarely within the aerobic training zone ( 60–90%HRmax , where HRmax is the maximum heart rate ) . Dance performance placed a greater dem and on the aerobic and anaerobic glycolytic energy systems than seen during class and rehearsal , which placed a greater emphasis on the adenosine triphosphate‐creatine phosphate system . Practical implication s suggest the need to supplement training within dance companies to overcome this deficit in training dem and BACKGROUND Carried out to investigate cardiovascular and metabolic response during various gymnastic routines [ Pommel Horse ( PH ) , Roman Ring ( RR ) , Parallel Bar ( PB ) , Horizontal Bar ( HB ) and Floor Exercise ( FE ) ] . METHODS EXPERIMENTAL DESIGN comparative and r and omized . SETTING General purpose , applicable on gymnastics training . Participants . Five male volunteers drawn from students attending sports coaching course in gymnastics at NIB , Patiala . A mixed population from all over India who had competitive experience of 6 to 10 years . INTERVENTIONS no interventions . MEASURES presence of heart rate overshooting , high lactate levels and individual characteristics of the gymnastics routines . RESULTS In all the routines peak HR was much lower than maximum heart rate ( HRmax ) of the gymnasts . Mean HR was lowest in first set and highest in the final ( 3rd set ) on all the apparatuses . Highest mean HR was recorded in HB followed by FE , RR , PB and PH respectively . After both first and third sets blood lactic acid ( La ) was highest in FE followed by RR , PB , HB and PH . La levels following the first set were 7.11 , 6.77 , 6.23 , 5.97 and 5.18 mM/l , respectively . Third set values were 10.54 , 10.16 , 8.95 , 8.74 and 8.04 mM/l . CONCLUSIONS ( a ) Cardiovascular load in various gymnastic routines is considerably less than maximal running ; ( b ) HR overshoot is common at the end of all the men 's gymnastic routines ; training evaluation or performance evaluation in gymnastics through heart rate should consider this fact to avoid any misinterpretation ; ( c ) PH is physiologically least dem and ing among the five while FE and RR are most stressful ; ( d ) repetition of gymnastic exercise routines with short rest pause may lead the gymnast to reach nearer to his lactate tolerance ; ( e ) gymnastics activity is dominated by anaerobic metabolism |
989 | 18,596,421 | Bilateral subthalamic nucleus stimulation is effective in the treatment of PD .
Further refinements in patient selection and surgical technique may lessen the incidence of complications associated with this procedure | OBJECTIVE To evaluate the benefits and adverse effects of bilateral subthalamic nucleus stimulation in the treatment of Parkinson 's disease ( PD ) by systematic ally review ing the published literature . | Abstract Preliminary reports in patients with Parkinson 's disease ( PD ) showed that subthalamic nucleus ( STN ) stimulation was able to reverse parkinsoniam state . Since 1998 we evaluated the safety and the efficacy of STN stimulation in 7 patients affected by advanced PD . All patients were included using CAPIT protocol . Motor functions and quality of life were evaluated , before and after surgery , with UPDRS and PDQ38 , respectively . At the 6-month follow-up , the off medication/on stimulation UPDRS motor score improved by 50.6 % and the on medication/on stimulation by 20.3 % . Motor fluctuations were reduced by 57.2 % and dyskinesias by 73.5 % . The total D-dopa equivalent daily dose was reduced by 40.7 % . PDQ38 ameliorated by 49.9 % . We did not observe any perioperatory complication and only mild and tolerable side effects after stimulation A series of 24 consecutive PD patients were prospect ively studied prior to and within 6 months postoperatively for mood , motor , and cognitive status to investigate the effects on mood of subthalamic deep brain stimulation ( DBS ) in PD . In six patients ( 25 % ) , mood state worsened significantly , and three were transiently suicidal despite clear motor improvement . Caregivers and patients should be educated about the potential impact of this neurosurgical procedure on mood OBJECTIVE To evaluate the effects of bilateral deep brain stimulation in the subthalamic nucleus for symptomatic relief of advanced idiopathic Parkinson 's disease . DESIGN Prospect i ve cohort study . SETTING Patients were assessed and received medical treatment at the Kingston Centre , Southern Health , Melbourne . Surgery took place at Melbourne Neuroscience Centre , The Royal Melbourne Hospital . Both are tertiary public institutions . SUBJECTS 14 patients with Parkinson 's disease with intact cognition and difficult to manage motor symptoms who were referred to Kingston Centre between 1996 and 2000 and were eligible for surgical intervention . INTERVENTIONS All patients were assessed both after 12 hours ' withdrawal from and while taking their levodopa medication on two occasions before surgery . Further assessment s were carried out one , three , six and 12 months after surgery . MAIN OUTCOME MEASURES The Unified Parkinson 's Disease Rating Scale motor exam and gait parameters , such as stride length and velocity , were compared at six months after surgery with neither stimulation nor medication , with stimulation only , with medication only , and with stimulation and medication . RESULTS Stimulators were explanted in one patient after intracranial haemorrhage and relocated to the thalamus in a second . Extraneous factors prevented two patients from attending at six-month follow-up . Motor performance improved significantly with stimulation alone in the 10 remaining patients . Further significant gains were seen with stimulation and medication combined , with an apparent reduction in side-effects such as dyskinesia . CONCLUSIONS Bilateral deep brain stimulation of the subthalamic nucleus significantly improves motor performance in advanced Parkinson 's disease , despite a rather high complication rate OBJECTIVES Deep brain stimulation of the basal ganglia has become a promising treatment option for patients with Parkinson 's disease who have side effects from drugs . Which is the best target — globus pallidus internus ( GPi ) or subthalamic nucleus (STN)—is still a matter of discussion . The aim of this prospect i ve study is to compare the long term effects of GPi and STN stimulation in patients with severe Parkinson 's disease . PATIENTS AND METHODS Bilateral deep brain stimulators were implanted in the GPi in six patients and in the STN in 12 patients with severe Parkinson 's disease . Presurgery and 3 , 6 , and 12 months postsurgery patients were scored according to the CAPIT protocol . RESULTS Stimulation of the STN increased best Schwab and Engl and scale score significantly from 62 before surgery to 81 at 12 months after surgery ; GPi stimulation did not have an effect on the Schwab and Engl and scale . Stimulation of the GPi reduced dyskinesias directly whereas STN stimulation seemed to reduce dyskinesias by a reduction of medication . Whereas STN stimulation increased the unified Parkinson 's disease rating scale ( UPDRS ) motor score , GPi stimulation did not have a significant effect . Fluctuations were reduced only by STN stimulation and STN stimulation suppressed tremor very effectively . CONCLUSION Stimulation of the GPi reduces medication side effects , which leads to a better drug tolerance . There was no direct improvement of bradykinesia or tremor by GPi stimulation . Stimulation of the STN ameliorated all parkinsonian symptoms . Daily drug intake was reduced by STN stimulation . The STN is the target of choice for treating patients with severe Parkinson 's disease who have side effects from drugs Background The main advantage of deep brain stimulation ( DBS ) in the treatment of PD is that the electrical setting s can be adjusted to optimize benefits and minimize adverse effects . The main objective of this study was to discover how varying these electrical parameters impacted on parkinsonian motor signs . Methods Twelve patients with PD with chronic bilateral subthalamic nucleus ( STN ) stimulation were selected . The authors evaluated the effects of a variation in the voltages , frequencies , and pulse widths on tremor , bradykinesia , and rigidity using two different paradigms : one in which the total electrical energy delivered was held constant , and one in which this was varied . Up to 26 parameter conditions were tested under double blind r and omized conditions . Results Voltages ≥3 V and frequencies ≥130 Hz led to the greatest improvement in all three parkinsonian signs . A rate of 5 Hz significantly worsened akinesia . The combination of the highest voltage with the narrowest pulse width was most effective . Conclusions This study confirms that the most beneficial effects induced by STN stimulation are obtained at high frequencies and that voltage is the most critical factor to obtain adequate alteration in STN activity . The mechanisms by which STN DBS improves parkinsonism remain speculative Abstract Bilateral deep brain stimulation is an effective treatment for most motor signs of Parkinson 's disease ( PD ) , but the effects on cognitive functions are less clear . We therefore examined the effects of bilateral deep brain stimulation on central information processing , using the event-related auditory P300 potential as an electrophysiological index of mental chronometry . Eight PD patients with bilateral stimulators within the subthalamic nuclei ( STN ) and eight age-matched controls participated . Patients were examined after overnight withdrawal of antiparkinson medication , both “ on ” and “ off ” stimulation ( in r and om sequence ) . The P300 and reaction times were recorded using an auditory oddball paradigm . P300 latencies were prolonged in PD patients off stimulation ( 440 ± 45 ms ) compared to controls ( 397 ± 16 ms ; P < 0.05 ) . STN stimulation significantly reduced clinical disease severity ( as indexed by the Unified Parkinson 's Disease Rating Scale ) and markedly improved reaction times , but did not improve the prolonged P300 latencies in PD patients ( 429 ± 36 ms ) . These results confirm that P300 latencies are prolonged in PD . Significantly , bilateral STN stimulation did not improve this electrophysiological measure of cognitive impairment , even though motor disability was markedly reduced . This suggests that some dopa-responsive features are resistant to STN stimulation , possibly due to involvement of dopaminergic deficits outside the nigrostriatal pathway , which are not influenced by outflow from the STN Abstract . Thirty patients with idiopathic Parkinson 's disease were treated with deep brain stimulation electrode in the subthalamic nucleus . After surgery , the patients ' best mean Unified Parkinson 's Disease Rating Scale ( UPDRS III ) scores ( medictionOFF-stimulatorON versus preoperative medicationOFF ) were 77±14 % at 3 months ( n=20 patients ) and 72±14 % at 12 months follow-up ( n=16 ) . The mean reduction in therapy ( expressed in levodopa dose equivalents in mg ) was 68±25 % at 12 months . Postoperative complications were rare , mostly mild , and reversible . Therapeutic success depends on a multidisciplinary team approach , meticulous patient selection , including patients ' cognitive , psychic , and behavioral status , and patient and family lifestyles CONTEXT This study was part of a large double-blind sham surgery-controlled trial design ed to determine the effectiveness of transplantation of human embryonic dopamine neurons into the brains of persons with advanced Parkinson 's disease . This portion of the study investigated the quality of life ( QOL ) of participants during the 1 year of double-blind follow-up . OBJECTIVES To determine whether QOL improved more in the transplant group than in the sham surgery group and to investigate outcomes at 1 year based on perceived treatment ( the type of surgery patients thought they received ) . DESIGN Participants were r and omly assigned to receive either the transplant or sham surgery . Reported results are from the 1-year double-blind period . SETTING Participants were recruited from across the United States and Canada . Assessment and surgery were conducted at 2 separate university medical centers . PARTICIPANTS A volunteer sample of 40 persons with idiopathic Parkinson 's disease participated in the transplant ( " parent " ) study , and 30 agreed to participate in the related QOL study : 12 received the transplant and 18 received sham surgery . INTERVENTIONS Interventions in the parent study were transplantation and sham brain surgery . Assessment s of QOL were made at baseline and 4 , 8 , and 12 months after surgery . MAIN OUTCOME MEASURES Comparison of the actual transplant and sham surgery groups and the perceived treatment groups on QOL and medical outcomes . We also investigated change over time . RESULTS There were 2 differences or changes over time in the transplant and sham surgery groups . Based on perceived treatment , or treatment patients thought they received , there were numerous differences and changes over time . In all cases , those who thought they received the transplant reported better scores . Blind ratings by medical staff showed similar results . CONCLUSIONS The placebo effect was very strong in this study , demonstrating the value of placebo-controlled surgical trials OBJECTIVE Deep brain stimulation ( DBS ) of the globus pallidus internus ( GPi ) and subthalamic nucleus ( STN ) has been reported to be effective in alleviating the symptoms of advanced Parkinson 's disease ( PD ) . Although recent studies suggest that STN stimulation may be superior to GPi stimulation , a r and omized , blinded comparison has not been reported . The present study was design ed to provide a preliminary comparison of the safety and efficacy of DBS at either site . METHODS Ten patients with idiopathic PD , L-dopa-induced dyskinesia , and response fluctuations were r and omized to implantation of bilateral GPi or STN stimulators . Neurological condition was assessed preoperatively with patients on and off L-dopa and on DBS at 10 days and 3 , 6 , and 12 months after implantation . Patients and evaluating clinicians were blinded to stimulation site throughout the study period . Complete follow-up data were analyzed for four GPi patients and five STN patients . RESULTS When off-L-dopa , both GPi and STN groups demonstrated a similar response , with approximately 40 % improvement in Unified PD Rating Scale motor scores after 12 months of DBS . Rigidity , tremor , and bradykinesia improved in both groups . In combination with L-dopa , Unified PD Rating Scale motor scores were more improved by GPi stimulation than by STN stimulation . On-L-dopa axial symptoms were clinical ly improved in the GPi but not the STN group . L-Dopa-induced dyskinesia was reduced by DBS at either site , although medication requirement was reduced only in the STN group . There were no serious intraoperative complications among patients in either group . CONCLUSION Pallidal and STN stimulation appears to be safe and efficacious for the management of advanced PD . A larger study is needed to investigate further the differences in symptom response and the interaction of L-dopa with stimulation at either site BACKGROUND Although the short-term benefits of bilateral stimulation of the subthalamic nucleus in patients with advanced Parkinson 's disease have been well documented , the long-term outcomes of the procedure are unknown . METHODS We conducted a five-year prospect i ve study of the first 49 consecutive patients whom we treated with bilateral stimulation of the subthalamic nucleus . Patients were assessed at one , three , and five years with levodopa ( on medication ) and without levodopa ( off medication ) , with use of the Unified Parkinson 's Disease Rating Scale . Seven patients did not complete the study : three died , and four were lost to follow-up . RESULTS As compared with base line , the patients ' scores at five years for motor function while off medication improved by 54 percent ( P<0.001 ) and those for activities of daily living improved by 49 percent ( P<0.001 ) . Speech was the only motor function for which off-medication scores did not improve . The scores for motor function on medication did not improve one year after surgery , except for the dyskinesia scores . On-medication akinesia , speech , postural stability , and freezing of gait worsened between year 1 and year 5 ( P<0.001 for all comparisons ) . At five years , the dose of dopaminergic treatment and the duration and severity of levodopa-induced dyskinesia were reduced , as compared with base line ( P<0.001 for each comparison ) . The average scores for cognitive performance remained unchanged , but dementia developed in three patients after three years . Mean depression scores remained unchanged . Severe adverse events included a large intracerebral hemorrhage in one patient . One patient committed suicide . CONCLUSIONS Patients with advanced Parkinson 's disease who were treated with bilateral stimulation of the subthalamic nucleus had marked improvements over five years in motor function while off medication and in dyskinesia while on medication . There was no control group , but worsening of akinesia , speech , postural stability , freezing of gait , and cognitive function between the first and the fifth year is consistent with the natural history of Parkinson 's disease Abstract We selected 14 patients with advanced idiopathic Parkinson 's disease ( PD ) and examined the clinical effects of STN DBS versus GPi DBS . Nine patients underwent bilateral STN DBS and five underwent bilateral GPi patients . All patients were followed for at least 12 months . The evaluation was performed on and off drug before surgery ; on-drug/on-DBS and off-drug/on-DBS at 1 , 2 , 6 and 12 months after stereotactic surgery . At 1 and 3 months after surgery in off-drug/on-DBS condition , both groups showed an improvement in motor score ( UPDRS II ) . Nevertheless , the results changed after long-term stimulation in the two groups . Chronic STN DBS is superior to GPi DBS in the amelioration of the clinical features and in the decrease of time spent in the off state . The efficacy in reduction of LID was comparable at 1 and 3 months after surgery , but the results were better in STN DBS after chronic stimulation . The L-dopa dose was reduced only in the STN group Motor fluctuations are a major disabling complication in the treatment of Parkinson 's disease . To investigate whether such oscillations in mobility can be attributed to changes in the synaptic levels of dopamine , we studied prospect ively patients in the early stages of Parkinson 's disease with a follow-up after at least 3 years of levodopa treatment . At baseline , 3 positron emission tomography ( PET ) scans using [11C]raclopride before and after ( 1 hour and 4 hours ) orally administered levodopa were performed on the same day for each patient . Patients who developed " wearing-off " fluctuations during the follow-up period had a different pattern of levodopa-induced changes in [11C]raclopride binding potential ( BP ) from that observed in patients who were still stable by the end of the follow-up . Thus , 1 hour post-levodopa the estimated increase in the synaptic level of dopamine was 3 times higher in fluctuators than in stable responders . By contrast , only stable responders maintained increased levels of synaptic dopamine in the PET scan performed after 4 hours . These results indicate that fluctuations in the synaptic concentration of dopamine precede clinical ly apparent " wearing-off " phenomena . The rapid increase in synaptic levels of dopamine observed in fluctuators suggests that increased dopamine turnover might play a relevant role in levodopa-related motor complications The aim of the present study was to assess the efficacy and safety of chronic subthalamic nucleus deep-brain stimulation ( STN-DBS ) in patients with Parkinson 's disease ( PD ) . 18 consecutive severely affected PD patients were included ( mean age , SD : 56.9+/-6 years ; mean disease duration : 13.5+/-4.4 years ) . All the patients were evaluated clinical ly before and 6 months after the surgical procedure using the Unified Parkinson 's Disease Rating Scale ( UPDRS ) . Additionally , a 12 months follow-up was available in 14 patients . The target coordinates were determined by ventriculography under stereotactic conditions , followed by electrophysiology and intraoperative stimulation . After surgery , continuous monopolar stimulation was applied bilaterally in 17 patients at 2.9+/-0.4 V through 1 ( n = 31 ) or 2 contacts ( n = 3 ) . One patient had bilateral bipolar stimulation . The mean frequency of stimulation was 140+/-16 Hz and pulse width 68+/-13 micros . Off medication , the UPDRS part III score ( max = 108 ) was reduced by 55 % during on stimulation ( score before surgery : 44.9+/-13.4 vs at 6 months : 20.2+/-10 ; p < 0.001 ) . In the on medication state , no difference was noted between the preoperative and the postoperative off stimulation conditions ( scores were respectively : 17.9+/-9.2 and 23+/-12.6 ) . The severity of motor fluctuations and dyskinesias assessed by UPDRS IV was reduced by 76 % at 6 months ( scores were respectively : 10.3+/-3 and 2.5+/-3 ; p < 0.001 ) . Off medication , the UPDRS II or ADL score was reduced by 52.8 % during on stimulation ( 26.9+/-6.5 preop versus 12.7+/-7 at 6 months ) . The daily dose of antiparkinsonian treatment was diminished by 65.5 % ( levodopa equivalent dose -- mg/D -- was 1045 + /- 435 before surgery and 360 + /- 377 at 6 months ; p < 0.01 ) . These results remained stable at 12 months for the 14 patients studied . Side effects comprised lower limb phlebitis ( n = 2 ) , pulmonary embolism ( n = 1 ) , depression ( n = 6 ) , dysarthria and freezing ( n = 1 ) , sialorrhea and drooling ( n = 1 ) , postural imbalance ( n = 1 ) , transient paresthesias and dyskinesias . This study confirms the great value of subthalamic nucleus stimulation in the treatment of intractable PD . Some adverse events such as depression may be taken into account in the inclusion criteria and also in the post-operative outcome The Unified Parkinson 's Disease Rating Scale ( UPDRS ) is primarily composed of an investigator-derived objective rating of motor function and a patient-derived assessment of activities of daily living ( ADL ) . Using a stringent definition of placebo effect , we examined the frequency , temporal development , and stability of improvements during placebo treatment over 6 months in a large placebo-controlled trial of deprenyl and tocopherol in early Parkinson 's disease ( DATA TOP ) . One hundred ninety-nine subjects received placebo treatment in the r and omized , multicenter , placebo-controlled DATA TOP study . We compared the baseline UPDRS motor section scores with follow-up scores at 4 , 13 , and 26 weeks . Placebo-associated improvement was defined as an improvement over baseline score in motor UPDRS of at least 50 % or a change in at least two motor items at any one visit by two or more points . Seventeen percent of the 185 subjects who qualified for analysis met the placebo response criteria . The group prevalence of response was steady ( 7 % to 10 % ) at any one visit without a marked predominance of an early study effect . Older subjects with more motor impairment at baseline were most likely to show a placebo-associated improvement . ADL scores were low throughout the study , and ADL improvements did not identify the subjects with objective ly defined placebo-associated improvement . Prominent improvements in investigator-derived objective measures of Parkinson 's disease motor impairment occur during clinical trials , including one that was not aim ed at showing improved short-term efficacy . Although the notion of placebo effect often implies patient-based perceptions , we found subjective changes to be infrequent in placebo-treated patients , suggesting that either : ( 1 ) the placebo effect was rater-driven ; ( 2 ) the ADL question naire is insensitive to transient but objective ly demonstrable motor changes ; or ( 3 ) that the objective changes , albeit major , are within the realm of natural variation in the UPDRS motor scale from visit to visit Abstract Deep brain stimulation of the subthalamic nucleus has been proved to be an effective treatment for advanced Parkinson 's disease when therapeutical strategies have failed . A correct selection of c and i date s for surgery is fundamental to obtain a good clinical effect . In this study we present our protocol of patient selection . In addition we report the data relative to the different causes of exclusion and the clinical efficacy of the electrical stimulation of the subthalamic nucleus at 3 months and 1 year follow-up OBJECT Bilateral subthalamic nucleus ( STN ) stimulation is increasingly used in patients with advanced Parkinson disease ( PD ) . This study was performed to evaluate the long-term efficacy and safety of bilateral STN stimulation in cases of PD . METHODS The authors performed a prospect i ve , open-label study in patients with PD who underwent bilateral STN stimulation . The authors compared motor scores and activities of daily living ( ADL ) scores based on the Unified PD Rating Scale ( UPDRS ) obtained before surgery while patients were in the medication-off state with scores obtained at follow-up evaluations of these patients while in the medication-off/stimulator-on state . Data contained in patient diaries were also compared . Thirty-three patients with PD were evaluated 12 months postoperatively and 19 were evaluated at a mean follow-up time of 28 months . A comparison between UPDRS scores obtained in patients in the medication-off/stimulator-on state and those obtained when patients were in the baseline medication-off state showed a 27 % improvement in ADL scores and a 28 % improvement in motor scores after surgery . There was a 57 % reduction in the use of levodopa-equivalent medication doses . The percentage of the waking day that patients were in the medication-on state increased from 38 to 72 % . Surgical complications included seizures ( three patients ) , confusion ( five patients ) , hemiballismus ( one patient ) , and visual disturbance ( one patient ) . Stimulation-related adverse effects were mild . Device-related events included nine lead replacements , seven lead revisions , six extension replacements , and 12 implantable pulse generator ( IPG ) replacements ; one IPG was cleaned and one IPG was placed in a pocket because of the presence of a shunt . CONCLUSIONS Bilateral STN simulation is associated with a significant improvement in the motor features of PD . Device-related events were common in the first 20 patients who underwent surgery , often requiring repeated surgeries Background : The clinical efficacy of chronic deep brain stimulation in the treatment of parkinsonian patients with severe levodopa-related motor adverse effects has been repeatedly shown . Bilateral subthalamic nucleus ( STN ) stimulation has been shown to present an advantage over pallidal stimulation as it induces a higher antiakinetic effect and has positive effects on all parkinsonian symptoms . The morbidity of such surgery is usually considered to be very low . However , few studies have extensively examined the effects of chronic STN stimulation on cognitive function . Objective : The aim of the present study was to assess the effects of chronic bilateral STN stimulation on performance in an extensive battery of neuropsychological tests , three months and one year after surgery . Methods : Nine patients with Parkinson 's disease were selected for STN electrodes implantation . They underwent a neuropsychological evaluation at one month before and at three months after surgery . Six of them were examined again at one year after surgery . Results : Before surgery , no patient showed cognitive decline . At three months after surgery , no modification was observed for most tasks . The information processing speed tended to improve . There was a significant reduction of the performance in a delayed free recall test and a trend toward a significant reduction of categorial word fluency . At one year after surgery , most task measures did not change . Slight impairment was observed for tasks evaluating executive function . Examination of individual results showed that some patients ( 30 % at 3 months after surgery ) showed an overall cognitive decline . Behavioural changes were also observed in 4 patients with overall cognitive decline in one of them . Conclusion : In general , STN deep brain stimulation can be considered as a significant contribution to the treatment of severe Parkinson 's disease However , in some patients it can induce overall cognitive decline or behavioural changes Abstract —Twenty-two patients with Parkinson ’s disease were treated by implanting electrodes in the subthalamic nucleus . The follow-up evaluation was conducted at one ( 22 patients ) and two years ( 9 patients ) . Significant improvement in the Unified PD Rating Scale scores was found . Tremor diminished 100 % in the on drug/on stimulation and 70 % off drug/on stimulation state . Rigidity decreased by 68 % in the on drug/on stimulation and by 52 % in off drug/on stimulation state . Subthalamic stimulation is reliable OBJECT Palliative neurosurgery has reemerged as a valid therapy for patients with advanced Parkinson disease ( PD ) that is complicated by severe motor fluctuations . Despite great enthusiasm for long-term deep brain stimulation ( DBS ) of the subthalamic nucleus ( STN ) , existing reports on this treatment are limited . The present study was design ed to investigate the safety and efficacy of bilateral stimulation of the STN for the treatment of PD . METHODS In 12 patients with severe PD , electrodes were stereotactically implanted into the STN with the assistance of electrophysiological conformation of the target location . All patients were evaluated preoperatively during both medication-off and -on conditions , as well as postoperatively at 3 , 6 , and 12 months during medication-on and -off states and stimulation-on and -off conditions . Tests included assessment s based on the Unified Parkinson 's Disease Rating Scale ( UPDRS ) and timed motor tests . The stimulation effect was significant in patients who were in the medication-off state , result ing in a 47 % improvement in the UPDRS Part III ( Motor Examination ) score at 12 months , compared with preoperative status . The benefit was stable for the duration of the follow-up period . Stimulation produced no additional benefit during the medication-on state , however , when compared with patient preoperative status . Significant improvements were made in reducing dyskinesias , fluctuations , and duration of off periods . CONCLUSIONS This study demonstrates that DBS of the STN is an effective treatment for patients with advanced , medication-refractory PD . Deep brain stimulation of the STN produced robust improvements in motor performance in these severely disabled patients while they were in the medication-off state . Serious adverse events were common in this cohort ; however , only two patients suffered permanent sequelae & NA ; In this study , research ers evaluated the effect of bilateral subthalamic nucleus stimulation on various measures of Parkinson 's disease . Assessment s were completed before and after surgery in a double‐blind fashion under the following six conditions : ( a ) on medication , ( b ) off medication , ( c ) on medication/on stimulation , ( d ) on medication/off stimulation , ( e ) off medication/on stimulation , and ( f ) off medication/off stimulation . On average , improvement was noted in all areas including the Unified Parkinson 's Disease Rating Scale , Schwab and Engl and Activities of Daily Living Scale , Modified Hoehn and Yahr Staging , and timed tests . In addition , dyskinesia duration and dyskinesia disability were reduced BACKGROUND High-frequency stimulation of the subthalamic nucleus constitutes a therapeutic advance for severely disabled patients with Parkinson disease . OBJECTIVE To evaluate the efficacy and safety of continuous bilateral high-frequency stimulation of the subthalamic nucleus in patients with Parkinson disease . DESIGN A prospect i ve study of patients with Parkinson disease treated at a university hospital . PATIENTS AND METHODS Electrodes were implanted bilaterally in the subthalamic nucleus of 23 consecutive patients with Parkinson disease who responded well to levodopa but had severe motor complications . There were 16 men and 7 women ( mean + /- SEM age , 53 + /- 2 years ) who had a mean + /- SEM disease duration of 14.7 + /- 1.0 years . Targets were determined by 3-dimensional magnetic resonance imaging , combined with intraoperative electrophysiologic recordings and stimulation . RESULTS Six months after surgery , motor disability , levodopa-induced motor fluctuations , dyskinesias , and the daily dose of levodopa equivalent decreased significantly by 67 % , 78 % , 77 % , and 61 % , respectively , compared with the preoperative state . No significant morbidity was observed , except transient depression in 4 patients . CONCLUSIONS The beneficial effects of subthalamic stimulation depend on ( 1 ) the criteria used for patient selection , ( 2 ) the precision with which the subthalamic nucleus is targeted ( dependent on the 3-dimensional magnetic resonance imaging and the intraoperative electrophysiologic and clinical assessment s ) , and ( 3 ) the long-term postoperative adjustment of stimulation variables We present the efficacy and side effects of bilateral deep brain stimulation ( DBS ) of the subthalamic nuclei ( STN ) performed with a more simplified surgical procedure than described by the Grenoble group . A consecutive series of 26 patients with advanced and levodopa-responsive Parkinson 's disease and motor complications was evaluated using the Unified Parkinson 's Disease Rating Scale ( UPDRS ) part I-VI , timed tests , and a patient diary for 2 days concerning on-off phenomenon and dyskinesias . At 3 months , evaluation of stimulation by the UPDRS motor score was performed in a double-blind manner and a significant improvement of 57 % was found . The results 12 months after surgery off medication showed significant improvement in both UPDRS motor score and activities of daily living of 64 % and , on medication , a significant reduction of 86 % in duration of dyskinesias and 83 % in duration of off-periods . Reduction in medication was less than for other groups , probably because we used smaller doses of levodopa before the operation . No serious side effects were encountered . When the patients are carefully selected and followed up , bilateral DBS of STN is a significant progress in treatment of advanced idiopathic Parkinson 's disease with levodopa-induced motor complications This gene transfer experiment is the first Parkinson 's Disease ( PD ) protocol to be su bmi tted to the Recombinant DNA Advisory Committee . The principal investigators have uniquely focused their careers on both pre- clinical work on gene transfer in the brain and clinical expertise in management and surgical treatment of patients with PD . They have extensively used rodent models of PD for proof-of-principle experiments on the utility of different vector systems . PD is an excellent target for gene therapy , because it is a complex acquired disease of unknown etiology ( apart from some rare familial cases ) yet it is characterized by a specific neuroanatomical pathology , the degeneration of dopamine neurons of the substantia nigra ( SN ) with loss of dopamine input to the striatum . This pathology results in focal changes in the function of several deep brain nuclei , which have been well-characterized in humans and animal models and which account for many of the motor symptoms of PD . Our original approaches , largely to vali date in vivo gene transfer in the brain , were design ed to facilitate dopamine transmission in the striatum using an AAV vector expressing dopamine-synthetic enzymes . Although these confirmed the safety and potential efficacy of AAV , complex patient responses to dopamine augmenting medication as well as poor results and complications of human transplant studies suggested that this would be a difficult and potentially dangerous clinical strategy using current approaches . Subsequently , we and others investigated the use of growth factors , including GDNF . These showed some encouraging effects on dopamine neuron survival and regeneration in both rodent and primate models ; however , uncertain consequences of long-term growth factor expression and question regarding timing of therapy in the disease course must be resolved before any clinical study can be contemplated . We now propose to infuse into the subthalamic nucleus ( STN ) recombinant AAV vectors expressing the two isoforms of the enzyme glutamic acid decarboxylase ( GAD-65 and GAD-67 ) , which synthesizes the major inhibitory neurotransmitter in the brain , GABA . The STN is a very small nucleus ( 140 cubic mm or 0.02 % of the total brain volume , consisting of approximately 300,000 neurons ) which is disinhibited in PD , leading to pathological excitation of its targets , the internal segment of the globus pallidus ( GPi ) and substantia nigra pars reticulata ( SNpr ) . Increased GPi/SNpr outflow is believed responsible for many of the cardinal symptoms of PD , i.e. , tremor , rigidity , bradykinesia , and gait disturbance . A large amount of data based on lesioning , electrical stimulation , and local drug infusion studies with GABA-agonists in human PD patients have reinforced this circuit model of PD and the central role of the STN . Moreover , the closest conventional surgical intervention to our proposal , deep brain stimulation ( DBS ) of the STN , has shown remarkable efficacy in even late stage PD , unlike the early failures associated with recombinant GDNF infusion or cell transplantation approaches in PD . We believe that our gene transfer strategy will not only palliate symptoms by inhibiting STN activity , as with DBS , but we also have evidence that the vector converts excitatory STN projections to inhibitory projections . This additional dampening of outflow GPi/SNpr outflow may provide an additional advantage over DBS . Moreover , of perhaps the greatest interest , our pre clinical data suggests that this strategy may also be neuroprotective , so this therapy may slow the degeneration of dopaminergic neurons . We will use both GAD isoforms since both are typically expressed in inhibitory neurons in the brain , and our data suggest that the combination of both isoforms is likely to be most beneficial . Our pre clinical data includes three model systems : ( 1 ) old , chronically lesioned parkinsonian rats in which intraSTN GAD gene transfer results not only in improvement in both drug-induced asymmetrical behavior ( apomorphine symmetrical rotations ) , but also in spontaneous behaviors . In our second model , GAD gene transfer precedes the generation of a dopamine lesion . Here GAD gene transfer showed remarkable neuroprotection . Finally , we carried out a study where GAD-65 and GAD-67 were used separately in monkeys that were resistant to MPTP lesioning and hence showed minimal symptomatology . Nevertheless GAD gene transfer showed no adverse effects and small improvements in both Parkinson rating scales and activity measures were obtained . In the proposed clinical trial , all patients will have met criteria for and will have given consent for STN DBS elective surgery . Twenty patients will all receive DBS electrodes , but in addition they will be r and omized into two groups , to receive either a solution containing rAAV-GAD , or a solution which consists just of the vector vehicle , physiological saline . Patients , care providers , and physicians will be blind as to which solution any one patient receives . All patients , regardless of group , will agree to not have the DBS activated until the completion and unblinding of the study . Patients will be assessed with a core clinical assessment program modeled on the CAPSIT , and in addition will also undergo a preop and several postop PET scans . At the conclusion of the study , if any patient with sufficient symptomatic improvement will be offered DBS removal if they so desire . Any patients with no benefit will simply have their stimulators activated , which would normally be appropriate therapy for them and which requires no additional operations . If any unforeseen symptoms occur from STN production of GABA , this might be controlled by blocking STN GABA release with DBS , or STN lesioning could be performed using the DBS electrode . Again , this treatment would not subject the patient to additional invasive brain surgery . The trial described here reflects an evolution in our thinking about the best strategy to make a positive impact in Parkinson Disease by minimizing risk and maximizing potential benefit . To our knowledge , this proposal represents the first truly blinded , completely controlled gene or cell therapy study in the brain , which still provides the patient with the same surgical procedure which they would normally receive and should not subject the patient to additional surgical procedures regardless of the success or failure of the study . This study first and foremost aims to maximally serve the safety interests of the individual patient while simultaneously serving the public interest in rigorously determining in a scientific fashion if gene therapy can be effective to any degree in treating Parkinson 's disease |
990 | 23,396,504 | However , the effect of many other strategies is less clear , including the use of video to provide trial information and interventions aim ed at recruiters .
Questions remain as to the applicability of results originating from hypothetical trials , including those relating to the use of monetary incentives , and there is a clear knowledge gap with regard to effective strategies aim ed at recruiters | OBJECTIVE To identify interventions design ed to improve recruitment to r and omised controlled trials , and to quantify their effect on trial participation . | Background A commonly reported problem with the conduct of multicentre r and omised controlled trials ( RCTs ) is that recruitment is often slower or more difficult than expected , with many trials failing to reach their planned sample size within the timescale and funding originally envisaged . The aim of this study was to explore factors that may have been associated with good and poor recruitment in a cohort of multicentre trials funded by two public bodies : the UK Medical Research Council ( MRC ) and the Health Technology Assessment ( HTA ) Programme . Methods The cohort of trials was identified from the administrative data bases held by the two funding bodies . 114 trials that recruited participants between 1994 and 2002 met the inclusion criteria . The full scientific applications and subsequent trial reports su bmi tted by the trial teams to the funders provided the principal data sources . Associations between trial characteristics and recruitment success were tested using the Chi-squared test , or Fisher 's exact test where appropriate . Results Less than a third ( 31 % ) of the trials achieved their original recruitment target and half ( 53 % ) were awarded an extension . The proportion achieving targets did not appear to improve over time . The overall start to recruitment was delayed in 47 ( 41 % ) trials and early recruitment problems were identified in 77 ( 63 % ) trials . The inter-relationship between trial features and recruitment success was complex . A variety of strategies were employed to try to increase recruitment , but their success could not be assessed . Conclusion Recruitment problems are complex and challenging . Many of the trials in the cohort experienced recruitment difficulties . Trials often required extended recruitment periods ( sometimes supported by additional funds ) . While this is of continuing concern , success in addressing the trial question may be more important than recruitment alone Objectives : To determine the effects of risk and payment on subjects ’ willingness to participate , and to examine how payment influences subjects ’ potential behaviours and risk evaluations . Methods : A 3 ( level of risk ) × 3 ( level of monetary payment ) , between subjects , completely r and omised factorial design was used . Students enrolled at one of five US pharmacy schools read a recruitment notice and informed consent form for a hypothetical study , and completed a question naire . Risk level was manipulated using recruitment notices and informed consent documents from hypothetical biomedical research projects . Payment levels were determined using the payment models evaluated by Dickert and Grady as a guide . Five dependent variables were assessed in the question naire : willingness to participate , willingness to participate with no payment , propensity to neglect to tell about restricted activities , propensity to neglect to tell about negative effects , and risk rating . Results : Monetary payment had positive effects on respondents ’ willingness to participate in research , regardless of the level of risk . However , higher monetary payments did not appear to blind respondents to the risks of a study . Payment had some influence on respondents ’ potential behaviours regarding concealing information about restricted activities . However , payment did not appear to have a significant effect on respondents ’ propensity to neglect to tell research ers about negative effects . Conclusions : Monetary payments appear to do what they are intended to do : make subjects more willing to participate in research . Concerns about payments blinding subjects to risks could not be substantiated in the present study . However , the findings do raise other concerns — notably the potential for payments to diminish the integrity of a study ’s findings . Future research is critical to make sound decisions about the payment of research subjects Background It is notoriously difficult to recruit patients to r and omised controlled trials in primary care . This is particularly true when the disease process under investigation occurs relatively infrequently and must be investigated during a brief time window . Bell 's palsy , an acute unilateral paralysis of the facial nerve is just such a relatively rare condition . In this case study we describe the organisational issues presented in setting up a large r and omised controlled trial of the management of Bell 's palsy across primary and secondary care in Scotl and and how we managed to successfully recruit and retain patients presenting in the community . Methods Where possible we used existing evidence on recruitment strategies to maximise recruitment and retention . We consider that the key issues in the success of this study were ; the fact that the research was seen as clinical ly important by the clinicians who had initial responsibility for recruitment ; employing an experienced trial co-ordinator and dedicated research ers willing to recruit participants seven days per week and to visit them at home at a time convenient to them , hence reducing missed patients and ensuring they were retained in the study ; national visibility and repeated publicity at a local level delivered by locally based principal investigators well known to their primary care community ; encouraging recruitment by payment to practice s and reducing the workload of the referring doctors by providing immediate access to specialist care ; good collaboration between primary and secondary care and basing local investigators in the otolarnygology trial centres Results Although the recruitment rate did not meet our initial expectations , enhanced retention meant that we exceeded our planned target of recruiting 550 patients within the planned time-scale . Conclusion While difficult , recruitment to and retention within multi-centre trials from primary care can be successfully achieved through the application of the best available evidence , establishing good relationships with practice s , minimising the workload of those involved in recruitment and offering enhanced care to all participants . Primary care trialists should describe their experiences of the methods used to persuade patients to participate in their trials when publishing their results OBJECTIVES To evaluate the impact of an information booklet on HIV clinical trials , Clinical Trials in HIV and AIDS : Information For People Who Are Thinking About Joining a Trial , in addition to the st and ard trial information ( SI ) on patients ' knowledge ; underst and ing and attitudes about clinical trials ; and to investigate patients ' motivations and reasons for enrolling or not enrolling in a clinical trial . METHODS Fifty HIV-1 positive patients who attended the HIV clinic at a west London hospital were r and omized to receive either SI alone ( n = 27 ) or SI and a 16 page information booklet explaining the principles and procedures of HIV clinical trials ( n = 23 ) . A self-administered question naire was used at baseline to assess past experience and attitudes to clinical trials ( 10 questions ) , knowledge and underst and ing of HIV treatments ( 8 questions ) and clinical trials ( 11 questions ) . At 2 - 6 months after r and omization , a second interviewer-administered question naire addressed the patient 's assessment of the usefulness and comprehensiveness of the information provided by the SI and information booklet , whether or not the patient had enrolled in a clinical trial and reasons for enrolling/not enrolling , knowledge of specific aspects of the trial protocol the patient was eligible to join ( 13 questions ) and general knowledge of clinical trial procedures ( repeat of 11 baseline questions ) . Changes in the attitudes and scores on knowledge and underst and ing of clinical trials were compared for the two groups . RESULTS In both groups , patient knowledge of clinical trial procedures improved significantly over the study period . The median score increased from 30 at baseline to 35/44 at follow-up ( SI only ) vs. 24 - 31/44 ( SI plus booklet ) , but this did not differ significantly between the two groups . However , knowledge of the specific trial protocol was poor [ median score 13/25 , interquartile range ( IQR ) 8 - 14 ] , and there was no difference in the scores for the two groups . The prime motivations for joining a clinical trial were to benefit personal health and to gain access to new treatments . Potential side-effects were the main concern of prospect i ve trial participants . CONCLUSIONS This small trial shows that , while the patients ' general knowledge and underst and ing of clinical trials improved over time , this was not improved by the information booklet and re collection of the details of the relevant trial protocol remained poor Background Recruitment is a major challenge for trials but there is little evidence regarding interventions to increase trial recruitment . We report three controlled trials of interventions to increase recruitment to the Txt2stop trial . Purpose To evaluate : Trial 1 . The impact on registration s of a text message regarding an online registration facility ; Trial 2 . The impact on r and omizations of sending £ 5 with a covering letter to those eligible to join the trial ; Trial 3 . The impact on r and omizations of text messages containing quotes from existing participants . Methods Single blind controlled trials with allocation concealment . Interventions : Trial 1 : A text message regarding our new online registration facility ; Trial 2 : A letter with £ 5 enclosed ; Trial 3 : A series of four text messages containing quotes from participants . The control group in each trial received st and ard Txt2stop procedures . Results Trial 1 : 3.6 % ( 17/470 ) of the intervention group and 1.1 % ( 5/467 ) of the control group registered for the trial , risk difference 2.5 % ( 95 % CI 0.6—4.5 ) . 0 % ( 0/ 470 ) of the intervention group and 0.2 % ( 1/467 ) of the control group registered successfully online , risk difference —0.2 ( 95 % CI —0.6—0.2 ) ; Trial 2 : 4.5 % ( 11/246 ) of the intervention group and 0.4 % ( 1/245 ) of the control group were r and omized into the Txt2stop trial , risk difference 4.0 % ( 95 % CI 1.4—6.7 ) ; Trial 3 : 3.5 % ( 14/405 ) of the intervention group and 0 % ( 0/406 ) of the control group were r and omized into the Txt2stop trial , risk difference 3.5 ( 95 % CI 1.7—5.2 ) . Limitations There were no baseline data available for trial 1 . Allocation of participant IDs in trials 2 and 3 were systematic . Conclusion Sending a text message about an online registration facility increased registration s to Txt2stop , but did not increase online registration s. Sending a £ 5 reimbursement for participants ’ time and sending text messages containing quotes from existing participants increased r and omizations into the Txt2stop trial . Clinical Trials 2010 ; 7 : 265—273 . BACKGROUND physical activity studies in older people often have poor recruitment . Including a question naire with the invitation would provide information about non- participants and selection bias , but could reduce recruitment . Telephone contact might encourage participation . OBJECTIVE to test the effects of different strategies for recruitment into a study of physical activity in older people . DESIGN factorial r and omised controlled trial . R and omisation by household into four groups : telephone contact plus question naire , telephone contact only , question naire only , neither . SETTING primary care , Oxfordshire , United Kingdom . PARTICIPANTS 560 patients > or = 65 years r and omly selected after exclusions . INTERVENTIONS question naire to assess health , functional ability and physical activity . Telephone contact by the research nurse a week after sending study information . MAIN OUTCOME MEASURE recruitment into physical activity study . RESULTS telephone contact increased recruitment : contact 47.9 % ( 134/280 ) , no contact 37.9 % ( 106/280 ) , difference ( adjusted for the clustering effect of household ) 10.0 % ( 95 % CI 0.2 - 19.8 ) . Question naire inclusion did not significantly reduce recruitment : no question naire 44.3 % ( 124/280 ) question naire 41.4 % ( 116/280 ) difference -2.9 % ( 95 % CI -12.7 - 7.0 ) . CONCLUSIONS telephone contact significantly increased recruitment and should be considered in studies where recruitment may be low . While inclusion of a question naire provided valuable information on non- participants and did not significantly reduce recruitment , an adverse recruitment effect could not be excluded BACKGROUND Latinas have low rates of participation in breast cancer prevention trials . We evaluated the feasibility and effectiveness of a r and omized trial of brief counseling and print material s compared to print material s alone to increase intent to participate in a breast cancer prevention trial . METHODS We enrolled 450 women Spanish-speaking women from three urban community primary care clinics . The outcome was intent , defined as might , probably , or definitely would enroll in the trial . We also examined results using a more stringent definition restricted to probably and definitely intend to participate . RESULTS The trial was feasible within these busy clinics , and 96 % of women agreed to participate . The level of breast cancer knowledge was fairly high ( 66 % correct answers ) , but underst and ing about clinical trials was lower ( 40.5 % correct answers ) . Using the less stringent criteria for intent , 72 % of women stated that they intended to enroll in the STAR trial if eligible , but rates of intent decreased to 52 % with framing that included medication side effects and 45 % if uterine cancer was mentioned ( P < 0.01 for trend ) . Using the more stringent definition , slightly fewer than half of the women indicated an interest in participating , with the same trend towards decreasing intent with increasing presentation of side effects . The intervention was only effective using the less stringent definition and if no side effects were mentioned ( 77 % intent vs. 67 % in the intervention and control groups , respectively , P = 0.03 ) . Intention was independently associated with greater worry about breast cancer and younger age , but not acculturation or knowledge . CONCLUSIONS Latina women are interested in participating in clinical trials to prevent breast cancer , although interest declines with increasing discussion of side effects . Unfortunately , brief education only increased rates of intention using the least stringent definition and when no side effects were presented in framing the question . Future work should focus on qualitative research to underst and the theoretical foundations of preventive health behaviors in this population PURPOSE Studies have documented that the majority of consent documents for medical diagnosis and treatment are written at a reading level above that of the majority of the U.S. population . This study hypothesized that use of an easy-to-read consent statement , when compared with a st and ard consent statement , will result in higher patient comprehension of the clinical treatment protocol , lower patient anxiety , higher patient satisfaction , and higher patient accrual . METHODS A r and omized controlled trial was conducted in 44 institutions that were members or affiliates of three cooperative oncology groups . Institutions were r and omly assigned to administer either an easy-to-read consent statement or the st and ard consent statement to patients being recruited to participate in selected cancer treatment trials . Telephone interviews were conducted with a total of 207 patients to assess study outcomes . RESULTS Patients in the intervention arm demonstrated significantly lower consent anxiety and higher satisfaction compared with patients in the control arm . Patient comprehension and state anxiety were not affected by the intervention . Accrual rates into the parent studies also did not differ significantly between the two study groups . CONCLUSION Clinical trial informed consent statements can be modified to be easier to read without omitting critical information . Patient anxiety and satisfaction can be affected by the consent document . The generalizability of these study results is limited by the characteristics of the patient sample . Ninety percent of the sample were white women , and the mean Rapid Estimate of Adult Literacy in Medicine score was approximately 64 , indicating a literacy level at or above the ninth grade The study purpose was to determine whether the framing of treatment information influenced patients ' reported preferences for participating in treatment decision making and for trial entry . Ninety cancer patients read either neutrally- , positively- , or negatively-framed infor mation about a chemotherapeutic treatment , then indicated their preferences for participating in the treatment decision , and whether they would participate in a clinical trial incorporating this protocol . There was no difference across information groups in preferences for partici pating in treatment decision making or willingness to enter such a clinical trial . Preference for participation in treatment decision making was significantly related to age ( t = 2.54 ; p = 0.022 ) , sex ( x2 = 3.89 ; p = 0.05 ) , and education ( t = 2.54 ; p = 0.018 ) ; trial entry preferences were unrelated to these demographic variables . These results imply that , in this clinical context , attitudes towards participation in treatment decision making may be asso ciated with characteristics of the patient , and attitudes towards trial entry may be dependent upon the clinical characteristics of a particular trial , but neither set of attitudes is influenced by the framing of protocol information . Key words : framing effect ; patients ' preferences ; quality of life ; decision making ; clinical trials . ( Med Decis Making 1995;15:4 - 12 OBJECTIVE To evaluate which of two invitation methods , e-mail or post , was most effective at recruiting general practitioners ( GPs ) to an online trial . STUDY DESIGN AND SETTING R and omized controlled trial . Participants were GPs in Scotl and , United Kingdom . RESULTS Two hundred and seventy GPs were recruited . Using e-mail did not improve recruitment ( risk difference=0.7 % [ 95 % confidence interval -2.7 % to 4.1 % ] ) . E-mail was , however , simpler to use and cheaper , costing £ 3.20 per recruit compared with £ 15.69 for postal invitations . Reminders increased recruitment by around 4 % for each reminder sent for both invitation methods . CONCLUSIONS In the Scottish context , inviting GPs to take part in an online trial by e-mail does not adversely affect recruitment and is logistically easier and cheaper than using postal invitations Only 3 % of women with breast cancer participate in cancer clinical trials nationwide . The lack of awareness about clinical trials is a significant barrier towards clinical trials participation . A study was conducted at a large urban Comprehensive Cancer Center to test ( 1 ) the effectiveness of an 18-min educational video on improving attitudes toward clinical trials and trials enrollment among new breast cancer patients seen at the Karmanos Cancer Institute , and ( 2 ) to assess racial differences in attitudes regarding clinical trials . Participants were r and omized to either the educational intervention prior to their first oncology clinic appointment or to st and ard care . A baseline and 2-week post-intervention survey to assess attitudes toward clinical trials participation was completed by participants . Of 218 subjects recruited , 196 ( 55 % white vs. 45 % African American ( AA ) ) eligible patients were included in the analysis . A small increase in therapeutic clinical trial enrollment was observed in the intervention arm but was not statistically significant ( 10.4 % vs. 6.1 % ; P = 0.277 ) . The intervention also did not result in a clear improvement in patients ’ attitudes toward clinical trials at posttest . However , a lower enrollment rate for the AA women was noted after adjusting for stage ( OR = 0.282 , P = 0.049 ) . Significantly more negative scores were noted in 3 out of the 5 baseline attitudinal scales for AA women . The educational video did not significantly increase enrollment in breast cancer clinical trials . The findings that AA women had significantly more negative attitudes toward clinical trials than white women may partially explain the racial disparity in enrollment . An educational video remains a simple and cost-effective way to educate patients . Future studies should focus on design ing a new educational video to specifically target cultural and attitudinal barriers in the AA population to more effectively change attitudes and increase trial enrollment Recruitment to cancer clinical trials needs to be improved , as does patient knowledge and underst and ing about clinical trials , in order for patients to make an informed choice about whether or not to take part . Audiovisual patient information ( AVPI ) has been shown to improve knowledge and underst and ing in various areas of practice , but there is limited information about its effect in the cancer clinical trial setting , particularly in relation to consent rates . In this study , 173 patients were r and omised to receive either the AVPI , in addition to the st and ard trial-specific written information , or the written information alone . There was no difference in clinical trial recruitment rates between the two groups with similar study entry rates : 72.1 % in the AVPI group and 75.9 % in the st and ard information group . The estimated odds ratio for refusal ( intervention/no intervention ) was 1.19 ( 95 % CI 0.55–2.58 , P=0.661 ) . Knowledge scores increased more in the AVPI group compared to the st and ard group ( P=0.0072 ) . The change in anxiety score between the arms was also statistically significant ( P=0.011 ) with anxiety improving in the intervention arm more than in the no intervention arm . Audiovisual patient information was shown to be a useful tool in improving patient knowledge and anxiety , but further work is necessary in relation to its effect on clinical trial recruitment rates BACKGROUND Failure to recruit adequate numbers of participants represents a major barrier to the completion of r and omized controlled trials in primary care and is associated with substantial opportunity costs . However , uncertainty exists regarding the relative effectiveness of different methods to promote recruitment . OBJECTIVES The purpose of this study was to estimate the proportion of strategies used to promote patient recruitment to r and omized controlled trials in primary care that are evidence based . METHODS Investigators from seven primary care-based clinical trials of dyspepsia management aim ing to recruit a total of 6070 patients participated . Following a survey of trial organization , a Delphi technique was used to reach consensus on levels of evidence on the effectiveness of interventions or organizational characteristics in influencing recruitment . The main outcome measures were the proportions of interventions or organizational characteristics for influencing patient recruitment that are based upon r and omized controlled trials , on convincing non-experimental evidence or meeting neither of these criteria . RESULTS Out of a total of 56 interventions used across the trials , 35 ( 63 % ) were judged as evidence based . Out of a total of 29 organizational characteristics possessed by the trials , five ( 17 % ) were judged as evidence based . Across the seven dyspepsia trials , the presence of ' favourable ' organizational characteristics appeared to be important contributors towards successful recruitment . CONCLUSIONS A wide range of interventions and organizational characteristics with the potential to promote recruitment were used or possessed by seven primary care trials . Many were not evidence based . Our experience suggests that organizational characteristics could be more influential in trial recruitment than the use of specific interventions . Given the costs of primary care-based trials , research ers need more rigorous evidence to inform recruitment strategies We aim ed to describe enrollment patterns in a large cohort of r and omized controlled trials ( RCTs ) and evaluate whether early recruitment predicts the ability of RCTs to reach their target enrollment . We considered all 77 efficacy RCTs initiated by the AIDS Clinical Trials Group between 1986 and 1996 ( 28,992 patients enrolled until November 1999 ) . Thirteen RCTs ( 17 % ) failed to reach half their target recruitment . Enrollment trajectories showed that the initial rate of accrual determined the subsequent rates of enrollment . The target sample size was attained by 7/8 , 11/14 , 15/35 and 4/20 of trials with very rapid , rapid , moderate and slow enrollment during the first 3 months , respectively ( P < 0.001 ) . Enrollment during the first month or two strongly correlated with subsequent accrual ( P < 0.001 ) . The patient pool , the eligibility criteria , the attractiveness of a trial and adequacy of the network of clinical sites may influence RCT enrollment . Early enrollment offers strong evidence on the feasibility of a trial and is indicative of its future pace of recruitment Background Trials frequently encounter difficulties in recruitment , but evidence on effective recruitment methods in primary care is sparse . A robust test of recruitment methods involves comparing alternative methods using a r and omized trial , ' nested ' in an ongoing ' host ' trial . There are potential scientific , logistical and ethical obstacles to such studies . Methods Telephone interviews were undertaken with four groups of stakeholders ( funders , principal investigators , trial managers and ethics committee chairs ) to explore their views on the practicality and acceptability of undertaking nested trials of recruitment methods . These semi-structured interviews were transcribed and analysed thematically . Results Twenty people were interviewed . Respondents were familiar with recruitment difficulties in primary care and recognised the case for ' nested ' studies to build an evidence base on effective recruitment strategies . However , enthusiasm for this global aim was tempered by the challenges of implementation . Challenges for host studies included increasing complexity and management burden ; compatibility between the host and nested study ; and the impact of the nested study on trial design and relationships with collaborators . For nested recruitment studies , there were concerns that host study investigators might have strong preferences , limiting the nested study investigators ' control over their research , and also concerns about sample size which might limit statistical power . Nested studies needed to be compatible with the main trial and should be planned from the outset . Good communication and adequate re sources were seen as important . Conclusions Although research on recruitment was welcomed in principle , the issue of which study had control of key decisions emerged as critical . To address this concern , it appeared important to align the interests of both host and nested studies and to reduce the burden of hosting a recruitment trial . These findings should prove useful in devising a programme of research involving nested studies of recruitment interventions The problem of generalisability in r and omised clinical trials was highlighted by studies that entered only 10 - 14 % of screened patients . To determine the magnitude and source of prer and omisation losses in clinical trials a survey was conducted of 41 trials listed in the 1979 inventory of the National Institute of Health . Two thirds of the trials maintained screening logs , but only half maintained any records of the number of patients who met the eligibility criteria but were not entered into the trial . Among 21 trials ( 51 % ) that kept data on the number of patients who were eligible but not entered , losses of eligible subjects were attributable to refusals by patients in 25 % and refusals by physicians in 29 % . Other protocol requirements accounted for the remaining losses of eligible patients . Only a few trials documented the characteristics of patients who were eligible but not entered ; in those trials the patients who were not entered were similar demographically but differed clinical ly from those enrolled . Thus minimising prer and omisation losses of eligible patients requires the use of less restrictive criteria for entering patients . Twenty four of the trials achieved 75 % or more of their recruitment goals , eight between 25 % and 74 % , and six less than 25 % . Among trials that screened less than twice their projected sample size , only three out of 13 ( 23 % ) achieved 75 % or more of their recruitment goal . By contrast , 12 out of 16 trials ( 75 % ) that screened more than twice their projected sample size achieved 75 % or more of their recruitment goal . Screening large numbers of patients appears to be a pragmatic requirement for success in achieving recruitment goals ; therefore , trials should not be criticised as lacking generalisability on that basis alone . The number and characteristics of eligible patients who were not entered , however , were documented by only a few trials ; these data are critical in the assessment of generalisability . Additionally , the number of patients with the index disease who did not meet the eligibility criteria should also be documented . Together , these two types of data characterise the population to whom the trial results may be applied BACKGROUND To evaluate the impact of an educational booklet on women 's knowledge of and willingness to participate in a r and omized clinical trial of treatment for breast cancer . MATERIAL S AND METHODS Women undergoing surgery for newly diagnosed early stage breast cancer were r and omized to receive , or not , an information booklet explaining the need for and manner in which r and omized trials are conducted . RESULTS Eighty-three women with newly diagnosed early stage breast cancer completed a question naire assessing attitudes to r and om clinical trials ( RCTs ) and were r and omized to receive usual information treatment options provided from their oncologist , or the educational booklet in addition to usual information from their oncologist ( 42 usual information , 41 booklet ) . Fewer women who received the clinical trials booklet ( 40 % versus 47 % ) would consider participating in the hypothetical clinical trial ( P = 0.6 ) . Mean knowledge scores increased for both groups ; moreover , women who did not receive the booklet showed similar improvements to women who received the booklet [ mean difference 0.09 , 95 % confidence interval ( CI ) -0.66 to 0.83 ] . In a multivariate analysis women who would consider participating in the clinical trial were more anxious [ odds ratio ( OR ) 5.9 , P = 0.02 ] had involved lymph nodes ( OR 5.8 , P = 0.02 ) and were less influenced by negative aspects of clinical trials ( OR 7.7 , P = 0.0001 ) . After adjustment for these variables women who received the educational booklet were significantly less likely to consider trial participation ( OR 0.22 , P = 0.05 ) . CONCLUSIONS Educating women about clinical trials in this manner appears ineffective in improving recruitment to RCTs . Women appear to be more influenced by their perception of risk than underst and ing . This finding has ethical implication s for communication of information about RCTs Methods of obtaining informed consent have evolved differently in Western countries without substantive information on the impact of these different practice s on the patients . A r and omised study was performed to compare two commonly adopted methods of seeking consent to r and omised treatment : an individual approach at the discretion of each doctor and a uniform policy of total disclosure of all relevant information . The impact of both consent procedures on the patient 's underst and ing and anxiety levels and on the doctor-patient relationship was assessed by means of a question naire given soon after the consent interview . Fifty seven patients were assigned at r and om to two groups : to 29 patients an individual approach to seeking consent was adopted and to 28 patients all relevant information was given . Seven patients refused consent to r and omised treatment , with slightly more refusals by patients in the total disclosure group ( 5 v 2 , p = 0.25 ) . The main effects of total disclosure of all information compared with an individual approach to seeking consent were : a better underst and ing of treatment and side effects and of research aspects of the treatments ; less willingness to agree to r and omised treatment ; and increased anxiety . No significant differences were found in patients ' perceptions of the doctor-patient relationship . A repeat question naire given three to four weeks later no longer showed significant differences between the two groups Limitations of printed , text-based , consent forms have long been documented and may be particularly problematic for persons at risk for impaired decision-making capacity , such as those with schizophrenia . We conducted a r and omized controlled comparison of the effectiveness of a multimedia vs routine consent procedure ( augmented with a 10-minute control video presentation ) as a means of enhancing comprehension among 128 middle-aged and older persons with schizophrenia and 60 healthy comparison subjects . The primary outcome measure was manifest decisional capacity ( underst and ing , appreciation , reasoning , and expression of choice ) for participation in a ( hypothetical ) clinical drug trial , as measured with the MacArthur Competence Assessment Tool for Clinical Research ( MacCAT-CR ) and the University of California San Diego ( UCSD ) Brief Assessment for Capacity to Consent ( UBACC ) . The MacCAT-CR and UBACC were administered by research assistants kept blind to consent condition . Additional assessment s included st and ardized measures of psychopathology and cognitive functioning . Relative to patients in the routine consent condition , schizophrenia patients receiving multimedia consent had significantly better scores on the UBACC and on the MacCAT-CR underst and ing and expression of choice subscales and were significantly more likely to be categorized as being capable to consent than those in the routine consent condition ( as categorized with several previously established criteria ) . Among the healthy subjects , there were few significant effects of consent condition . These findings suggest that multimedia consent procedures may be a valuable consent aid that should be considered for use when enrolling participants at risk for impaired decisional capacity , particularly for complex and /or high-risk research protocol AIMS We evaluated the effectiveness of telephoning injured patients after discharge , compared with contacting them in the clinic during the acute care visit , for screening for hazardous drinking and eliciting willingness to participate in a lifestyle intervention trial . METHODS We conducted a quasi-r and omized controlled trial among acutely injured adult patients in trauma and acute care clinics , assigning telephone and clinic screening strategies systematic ally by week . During telephone weeks , we mailed study information to patients identified from computerized records , then telephoned them . During clinic weeks , research ers recruited patients awaiting care . We screened for hazardous drinking using the AUDIT-C ( Alcohol Use Disorders Identification Test-C ) . We examined the proportion of all injured adult patients who were screened , the proportion of screened patients with hazardous drinking ( AUDIT-C score > or=4 ) , and the proportion willing to participate in a ( hypothetical ) lifestyle intervention trial . Differences were analysed with non-linear mixed models using generalized estimating equations , controlling for age , sex , and facility . Levers and barriers to screening were explored through structured interviews with research staff . RESULTS We enrolled 29 % ( 469/1,609 ) of all injured adult patients and 76 % of injured patients contacted and found to be eligible . Of screened patients , 23.1 % screened positive for hazardous drinking . Telephone and clinic contact were equally effective for screening patients ( OR = 1.05 ; 95 % CI = 0.59 - 1.87 ) , identifying hazardous drinking ( OR=0.97 ; 95 % CI = 0.54 - 1.74 ) , and eliciting willingness to participate in an intervention trial ( OR=1.49 ; 95 % CI = 0.97 - 2.30 ) . Clinic site modified results : telephone was more effective than clinic contact for screening urban patients ( OR=1.99 ; 95 % CI = 1.36 - 2.93 ) , but less effective for screening suburban patients ( OR = 0.70 ; 95 % CI = 0.69 - 0.71 ) . Barriers to clinic screening included lack of clinic staff support , time constraints , and difficulty recruiting elderly or acutely distressed patients . Barriers to telephone screening included erroneous contact information and failure to answer the telephone . CONCLUSIONS Telephone screening is a feasible and efficient method for screening moderately injured adult patients for hazardous drinking , but characteristics of the clinical site ( including personnel ) influence its effectiveness . Trauma and acute care clinics are likely to be fruitful sites for identification of patients with hazardous drinking , whether for enrollment into brief intervention trials or treatment programmes BACKGROUND Paying patients to participate in clinical trials is ethically controversial . However , there has been no empirical documentation regarding whether payment represents an undue or unjust inducement . METHODS To evaluate these questions , we described hypothetical placebo-controlled trials of a new antihypertensive drug to 126 patients with mild-to-moderate hypertension recruited from hypertension and general medicine clinics at a university hospital . Using a 3 x 3 , within-subjects design , we altered a risk to participation ( either adverse effect rate or rate of r and omization to placebo ) and the payment participants would receive ( $ 100 , $ 1000 , and $ 2000 ) and asked patients to indicate their willingness to participate ( WTP ) in each trial using a 6-point scale . RESULTS Clustered ordinal logistic regression models revealed that patients ' WTP decreased with higher risk of adverse effects ( P<.001 ) , higher risk of being assigned to placebo ( P = .02 ) , and lower payment level ( P<.001 ) . There were no significant interactions between payment level and either risk variable , suggesting that increasing payments do not alter peoples ' perceptions of risk . There was a trend toward a positive interaction between income and the influence of payment on WTP ( P = .09 ) , suggesting that payment more strongly influences WTP among wealthier people . Wealthier patients were more likely to state that payment was important in their participation decision ( 37 % vs 20 % , P = .05 ) . CONCLUSION Although higher payment motivates research participation , we found no evidence that commonly used payment levels represent undue or unjust inducements There is little rigorous evidence to underpin clinical guidelines for palliative care . However , research in palliative care is difficult , especially with dying patients . Consent is a major issue , since staff do not wish to invite dying patients to participate in trials . We , therefore , conducted a feasibility study in two units within the North West Wales NHS Trust . We explored two novel approaches to research in palliative care -cluster r and omisation and r and omised consent . All patients admitted to the two units during the study were asked for permission to use their data for research . We allocated the two units , at r and om , to use cluster r and omisation or r and omised consent for three months , and then to crossover to the other design . Of 24 patients dying during cluster-r and omised phases , 13 gave consent on admission to use their data and were , thus , eligible to enter the trial ; however , defined eligibility criteria reduced these to six active participants . Of 29 patients dying during r and omised consent phases , seven gave consent on admission to use their data ; although two were eligible for r and omisation , neither entered the trial . We judge that cluster r and omisation is the more effective design for research with dying patients . Computer simulation , based on data from 1500 dying patients on the Welsh Integrated Care Pathway , shows that crossover cluster trials need much smaller sample s than simple cluster trials . Furthermore , this study has shown that crossover cluster trials are entirely feasible . We recommend a ‘ definitive ’ trial to test the crossover design more widely OBJECTIVE To assess the efficacy , with respect to participant underst and ing of information , of a computer-based approach to communication about complex , technical issues that commonly arise when seeking informed consent for clinical research trials . DESIGN , SETTING AND PARTICIPANTS An open , r and omised controlled study of 60 patients with diabetes mellitus , aged 27 - 70 years , recruited between August 2006 and October 2007 from the Department of Diabetes and Endocrinology at the Alfred Hospital and Baker IDI Heart and Diabetes Institute , Melbourne . INTERVENTION Participants were asked to read information about a mock study via a computer-based presentation ( n = 30 ) or a conventional paper-based information statement ( n = 30 ) . The computer-based presentation contained visual aids , including diagrams , video , hyperlinks and quiz pages . MAIN OUTCOME MEASURES Underst and ing of information as assessed by quantitative and qualitative means . RESULTS Assessment scores used to measure level of underst and ing were significantly higher in the group that completed the computer-based task than the group that completed the paper-based task ( 82 % v 73 % ; P = 0.005 ) . More participants in the group that completed the computer-based task expressed interest in taking part in the mock study ( 23 v 17 participants ; P = 0.01 ) . Most participants from both groups preferred the idea of a computer-based presentation to the paper-based statement ( 21 in the computer-based task group , 18 in the paper-based task group ) . CONCLUSIONS A computer-based method of providing information may help overcome existing deficiencies in communication about clinical research , and may reduce costs and improve efficiency in recruiting participants for clinical trials The purpose of this study was to describe and compare the rates of recruitment during a r and omized clinical trial on smoking cessation in two primary care practice s. One site was a five-physician private family practice setting with about 15,000 patients . During 34 days , 576 patients were screened , of whom 22 % were smokers . Among the smokers screened , 54 % consented , 33 % refused consent , and 13 % were called in too early to consent . The other site was a six-physician academic medical practice with about 16,000 patients . During 53 days , 1,692 subjects were screened , of whom 16.2 % were smokers . Among the smokers , 19 % consented , 81 % refused consent , and none were called in early . The enrollment of smokers was 3.3 times greater in the private practice than the academic practice . At the first site , study personnel screened 26.6 subjects per day , whereas the practice receptionist screened only 13.4 subjects per day ( P less than .01 ) . A r and omized trial of having subjects read the informed consent versus having study personnel read it to them showed no differences in recruitment . The data suggest that private practice s may have greater potential for subject recruitment than academic sites , that using study personnel improves recruitment , and that having study personnel actively involved in informed consent does not improve recruitment Background : Privacy laws have recently created restrictions on how research ers can approach study participants . Method : In a r and omised trial of 152 patients , 50–74 years old , in a family practice , 60 were r and omly selected to opt-out and 92 to opt-in methods . Patients were sent an introductory letter by their doctor in two phases , opt-out before and opt-in after introduction of the new Privacy Legislation in December 2001 . Opt-out patients were contacted by research ers . Opt-in patients were contacted if patients responded by email , free telephone number or a reply-paid card . Results : Opt-in recruited fewer patients ( 47 % ; 43/92 ) after invitation compared with opt-out ( 67 % ; 40/60 ) ; ( −20 % ; [ −4 % to −36 % ] ) . No proportional difference in recruitment was found between opt-in and opt-out groups varied by age , sex or socioeconomic status . The opt-in group had significantly more people in active decision-making roles ( + 30 % ; [ 10 % to 50 % ] ; p = 0.003 ) . Non-significant trends were observed towards opt-in being less likely to include people with lower education ( −11.8 % ; [ −30 % to 6.4 % ] ; p = 0.13 ) and people who were not screened ( −19.1 % ; [ −40.1 % to 1.9 % ] ; p = 0.08 ) . Opt-in was more likely to recruit people with a family history of colorectal cancer ( + 12.7 % ; [ −2.8 % , 28.2 % ] ; p = 0.12 ) . Conclusions : The number of participants required to be approached was markedly increased in opt-in recruitment . Existing participants ( eg , screening attendees ) with a vested interest such as increased risk , and those preferring an active role in health decision making and with less education were likely to be recruited in opt-in . Research costs and generalisability are affected by implementing privacy legislation OBJECTIVE Studies investigating means of recruiting participants to r and omized controlled trials ( RCTs ) are sparse . We investigated the effects of telephone reminders as a recruitment strategy . STUDY DESIGN AND SETTING Sick-listed employees received a written invitation to participate in a study comparing st and ard treatments with a solution-focused follow-up and were r and omly allocated to an intervention or control group ( n=703 ) . Those who did not respond within 2 weeks received either ' no reminder ' ( n=242 ) or ' attempted telephone reminder ' ( n=256 ) . Outcome was enrollment to the RCT . RESULTS An intention to recruit analysis revealed no significant differences between the groups ( P=.229 ) . An intention to phone analysis among nonresponders revealed significant differences between ' no reminder ' ( recruited 4.5 % ) and ' attempted telephone reminder ' ( recruited 12.1 % ) ( P=.003 , odds ratio 2.89 , 95 % confidence interval [ CI ] 1.42 - 5.90 ) . An analysis of numbers needed to phone showed that to recruit one more person in this group of nonresponders , we needed to phone 13 persons ( 95 % CI=8 - 33 ) . CONCLUSION Systematic use of telephone calls can increase the recruitment rate among nonresponders in RCTs Abstract Objective : To investigate whether including a placebo arm in a clinical trial of hormone replacement therapy influenced women 's stated willingness to participate . Design : Quasir and omised , interview based study . Setting : 10 group practice s in the Medical Research Council 's General Practice Research Framework . Participants : 436 postmenopausal women aged 45 - 64 who had not had a hysterectomy . Main outcome measures : Stated willingness to enter a trial and reasons for the decisions made . Results : Of 218 women told about the trial without a placebo arm , 85 ( 39 % ) indicated their willingness to enter compared with 65 ( 30 % ) of the 218 women told about the trial with the placebo arm ( P=0.06 ) . Part of this difference was due to explicit reluctance to take a placebo . Altruism and personal benefit were the reasons most frequently given for wanting to take part in a trial . The reasons most frequently cited for not wanting to take part were reluctance to restart periods , not wanting to take unknown or unnecessary tablets , or not wanting to interfere with present good health . Conclusion : For preventive trials the inclusion of a placebo arm may reduce patients ' willingness to participate OBJECTIVE To test the effect of publicity on recruitment to a r and omized trial . Recruitment is often poor in trials . Publicity within recruitment packs might be an inexpensive method of increasing recruitment . We tested this in two quasi-r and omized trials . STUDY DESIGN In a primary care setting , within the context of a r and omized trial of falls prevention , we allocated participants to receive a newspaper article about the study with their information sheet . The first trial compared one newspaper article against no article ; the second compared a more favorably written article against the original . RESULTS In the first study 4,488 participants were allocated into two groups . The response rate was 102 and 97 in the intervention and control groups , respectively ( 4.55 % vs. 4.32 % , 95 % confidence interval [ CI ] : -0.98 , 1.43 ) ; the recruitment rate was 73 and 71 , respectively , the difference not being statistically significant . In the second study 2,745 were allocated into two groups with a response rate of 75 and 69 for the control and intervention groups , respectively ( 5.46 % vs. 5.03 % , 95 % CI : -1.24 , 2.09 ) ; the recruitment rate was 57 and 54 , respectively , the difference not being statistically significant . CONCLUSION These two large experiments revealed no evidence of effect of publicity on recruitment rates Timely participant recruitment remains a significant challenge for most clinical trials . We evaluated the effects on participant recruitment of communication between the central trial coordinators and the clinical sites in the setting of a large international multi-centre clinical trial . The effects of communication were determined in a single-blind r and omised controlled trial involving 167 clinical sites in 19 countries . Clinical sites were r and omised to either additional or usual communication strategies - the additional communication group received a communication package based on additional , individually-tailored feedback about recruitment , in addition to the usual correspondence from the central trial coordinators that was provided to the control group . The two study outcomes were the median time to half r and omisation target and the median total number of participants r and omised per clinical site . Eighty-five clinical centres were r and omised to receive additional communication and 82 to receive usual communication . At the conclusion of recruitment , there was no significant difference in the median number of participants r and omised per centre between the additional and usual groups ( 37.5 vs. 37.0 , p=0.68 ) . The median time to half r and omisation target was lower in the additional communication group compared to the usual group , however this difference did not achieve conventional levels of statistical significance ( 4.4 months vs. 5.8 months , p=0.08 ) . The findings suggest that the additional communication strategy may be of some incremental benefit in helping sites achieve recruitment targets sooner Background Incidence rates for many types of cancer are higher among African American men than in the general population , yet African American men are less likely to participate in cancer screening trials . This paper describes the outcomes of a r and omized trial ( the AAMEN Project ) design ed to recruit African American men aged 55–74 years to a prostate , lung and colorectal cancer screening trial . Methods The recruitment interventions address four types of barriers to clinical trial participation : sociocultural barriers , economic barriers , individual barriers and barriers inherent in study design . Subjects were r and omized to a control group or one of three increasingly intensive intervention arms , which used different combinations of mail , phone and in person church-based recruitment . Results Of the 39 432 African American men residing in the geographically defined study population ( southeastern Michigan and northern Ohio ) , 17 770 men ( 45 % ) could be contacted , and 12 400 ( 31 % of 39 432 ) were found to be eligible to participate . No statistically significant differences in age , education or income level were found among participants in the four study arms . A significantly greater enrollment yield ( 3.9 % ) was seen in the most intensive , church-based intervention arm , compared to the enrollment yields in the other two intervention arms ( 2.5 and 2.8 % ) or the control group ( 2.9 % ) ( P , 0.01 ) . Conclusions The intervention that involved the highest rate of face-to-face contact with the study participants produced the highest enrollment yield , but several strategies that were thought could improve yield had no effect . These findings , which are consistent with current literature on population -based recruitment , should facilitate the development of future recruitment efforts involving older African American men Concern has been expressed over a possible widespread belief amongst patients in trials , that a new treatment is better than the st and ard , despite the lack of evidence of such superiority . A sample of the general public ( N = 130 ) read a leaflet describing a hypothetical trial comparing two similar treatments for either arthritis or back-pain . Half read that both treatments were st and ard and generally available ; half that one was new and available only within the trial . Participants rated any preference for one or the other treatment , gave written reasons , and indicated their willingness to enter the r and omized trial . Fifteen participants subsequently talked through their answers . Most participants expressed no preference for either treatment when both were described as st and ard . When one was new more people with the arthritis ( but not the back-pain ) scenario expressed a preference ( chi2 = 5.44 , P = 0.031 ) . Importantly , this was not more likely to be for the new treatment . Rationally , those who preferred a freely available treatment were less likely to participate in the trial ( chi2 = 23.3 , P < 0.001 ) . The mere description of a trial treatment as new was insufficient to engender a preference for it over a st and ard treatment , although it may contribute to preference under certain additional circumstances This study evaluates the relationship between interviewer level of experience and the positive predictive value and cost of telephone screening of subjects for r and omized clinical trials . This is a previously uninvestigated area . Respondents to advertisements for chronic depression treatment research received brief , semi-structured telephone interviews ( N = 347 ) either by research assistants ( RAs ) or by a senior investigator ( SI ) . Those who met criteria based on the phone interview were then interviewed in person using the SCID-P. The RAs did not significantly differ from the SI in the proportion of phone screen positives who were also SCID positive or the proportion of phone screen positives who were r and omized . While the SI performed phone interviews significantly faster than the RAs , the SI 's higher salary generated a phone screening cost per r and omized subject 56 % more than that of RAs . The results suggest that trained research assistants are more cost effective than senior investigators for initial screening of depressed patients for research protocol s. Further studies are needed to determine whether the findings reported would generalize to other research setting s or patient population BACKGROUND . Valid consent for research requires comprehensive and underst and able information to be disclosed to participants . The way that information is shared varies , but regulatory bodies usually determine style . Some reports have suggested that although information may be all-inclusive , it does little to support underst and ing . OBJECTIVE . To explore the impact of various information-sharing approaches on parents ' underst and ing of a research study and the validity of their consent . METHODS . This was a r and omized , controlled trial . Parents of immature but well infants admitted to a large tertiary NICU in Edinburgh , Scotl and , were r and omly assigned within 72 hours of their infant 's admission to receive 1 of 2 information leaflets , with or without a st and ardized verbal explanation , for a hypothetical intensive care research study . The leaflets differed in length and in the amount of detail in which the study process , risks , benefits , and patient rights were described . A question naire was used to elicit underst and ing about the purpose of the research , design of the study , procedures involved , and the consent process . RESULTS . Forty-one parents participated in the study . Those who received the longer leaflet without verbal explanation gained only limited underst and ing of the purpose of the research . The procedures involved in the study were understood better by those who received the shorter leaflet . Issues relating to consent and study design were readily understood in all groups . Irrespective of documentation style , verbal explanation significantly improved underst and ing . Differences in underst and ing had little effect on whether a parent would enroll his or her infant into the study . CONCLUSIONS . Verbal explanation significantly enhances underst and ing of the research process for participants regardless of the style of written documentation . However , shorter written information may lead to better underst and ing than lengthy , more complex documentation To compare two strategies of consent requirement ( classical informed consent and r and omised consent according to Zelen ) , the Clinical Data Elaboration Centre of South Italy , within the special project Clinical Application of Oncological Research of the National Research Council of Italy ( CNR-ACRO ) invited healthy people visiting the 7th edition of the scientific exhibition " Futuro Remoto " to simulate of being ill and receiving the offer of entering a clinical trial . Within informed consent strategy patients are asked to agree to the r and omisation process , while , in the r and omised consent , r and omised treatment assignment is performed before consent requirement and patients should agree directly to the assigned therapy . Major aims of the study were ( a ) to compare the strategies in terms of refusal rate to a hypothetical clinical trial , and ( b ) to estimate whether severity of prognosis affected subjects ' decision . 3,217 visiting people participated to the simulation ; they were prevalently young , males and with a high level of school education . The study was performed in two different scenarios . In the first one , with one choice option , subject refusing consent could receive st and ard therapy only ; refusal rate was 16 % after informed consent and 13.4 % after r and omised consent ( for experimental therapy ) . In the other scenario , with two choice options , subjects refusing consent could choose the preferred therapy ; refusal rate was 20.6 % after informed consent , 48.1 % after r and omised consent ( for st and ard therapy ) and 13.4 % after r and omised consent ( for experimental therapy ) . ( ABSTRACT TRUNCATED AT 250 WORDS Purpose To provide empirical evidence on the impact of on-site initiation visits on the following outcomes : patient recruitment , quantity and quality of data su bmi tted to the trial coordinating office , and patients ' follow-up time . Patients and methods This method ological study was performed as part of a r and omized trial comparing two combination chemotherapies for adjuvant treatment of breast cancer . Centers participating to the trial were r and omized to either receive systematic on-site visits ( Visited group ) , or not ( Non-visited group ) . Results The study was terminated after two years , while the main r and omized trial continued . Of the 135 centers that had expressed an interest in the trial , only 69 r and omized at least one patient ( 35/68 in the Visited group , 34/67 in the Nonvisited group ) . Almost two-thirds of the patients were entered by 17 centers ( 10 in the Visited group , seven in the Non-visited group ) that accrued more than 10 patients each . None of the prespecified outcomes favored the group of centers su bmi tted to on-site initiation visits ( ie , mean number of queries par patient : 6.1 ± 9.7 versus 5.4 ± 6.4 , respectively for the Visited and Non-visited groups ) . Spontaneous transmittal of case report forms , although required by protocol , was low in both r and omized groups ( mean number of pages per patient : 1.5 ± 2.0 versus 2.1 ± 2.3 , respectively ) , with investigators su bmi tting about one-third of the expected forms on time ( 29 % and 39 % , respectively ) . Limitations This study could not evaluate the impact of repeated on-site visits on clinical outcomes . Conclusion Systematic on-site initiation visits did not contribute significantly to this clinical trial Objective To compare the efficiency and ease of use of internet data capture compared with conventional paper based data recording in the conduct of a clinical trial . Design Multicentre , cluster r and omized clinical trial . Setting General practice in the UK . Main outcome measures Timings for study l and marks , queries , data entry and monitoring time ; Investigator Question naire Results . Results The internet-derived data base was ready for release 33 days after the last patient visit compared with 48 days for the paper-derived data base , despite much higher numbers of patients in the internet group . The mean times from visit to data entry were 10.2 ( SD 18.9 ) days and 95.4 ( SD 44.6 ) days respectively ( P , 0.01 ) . The mean times from a visit to a query being resolved were 121.4 ( SD 58.3 ) days and 182.1 ( SD 58.9 ) days respectively ( P , 0.01 ) . The post- study responses from investigators were positive . Seventy-one percent of centressaid they would prefer to use the internet rather than paper CRFs for future studies . Conclusions There were efficiency gains seen with the use of an internet-based system when compared with a paper-based system in terms data entry , query resolution and the time to the release of the data base . The investigators'response to the internet system was generally favourable although on average investigators reported increased time spent on the study . Further efficiency might be gained with improved programming , increased investigator familiarity with the internet system , and with newly adapted working practice s for sponsors ' monitors and data base personnel BACKGROUND Little is known about the effects of investigators ' financial disclosures on potential research participants . METHODS We conducted a vignette trial in which 470 participants in a telephone survey were r and omly assigned to receive a simulated informed consent document that contained 1 of 2 financial disclosures ( per capita payments to the research institution or equity ownership by the investigator ) or no disclosure . The main outcome measures were trust in medical research and willingness to participate in a hypothetical clinical trial . RESULTS Participants in the equity group reported less willingness to participate than participants in the per capita payments group ( P = .01 ) and the no disclosure group ( P = .03 ) . Trust in the investigator was highest in the per capita payments group and lowest in the equity group ( P < .001 ) . Trust among participants who received no disclosure was also greater than trust among participants in the equity group ( P = .04 ) but did not differ significantly from trust among participants in the per capita payments group ( P = .15 ) . Participants in the equity group made 3 times as many negative comments as participants in the per capita payments group ; and 10 participants in the equity group spontaneously said they would not participate in the hypothetical trial because of the financial interest , compared with only 1 such participant from the other groups . CONCLUSIONS Although investigators ' financial disclosures in research do not substantially affect willingness to participate , potential research participants are more troubled by equity interests than by per capita payments This study examined the use of lay advocates ( i.e. , women enrolled in a study who advocate to others ) to improve recruitment among Hispanic women in the Arizona recruitment sites for a large-scale , national prevention study , the Women 's Health Initiative ( WHI ) . We examined whether trained , Hispanic lay advocates ( called Embajadoras ) brought more women into the study than a matched group of Hispanic and Anglo enrollees in the WHI who were supplied with brochures . Fifty-six Hispanic participants in the WHI were r and omized to receive training or no training on advocacy , and continued to meet quarterly for 18 months . Also , 42 Anglo women were assigned to control . All groups received brochures to use for advocating the WHI . The number of women referred and enrolled was tracked as well as other factors expected to influence outcomes . Embajadoras were more successful at referral and enrollment than untrained Hispanic women and more successful at enrollment than untrained Anglo controls . Embajadoras were also found to distribute significantly more brochures than control groups . Therefore , a culturally aligned training program to encourage current Hispanic participants in a clinical trial to advocate the study to others may be an effective way to boost referrals and enrollments . Other potential influences on enrollment or referral success could not be determined due to the small sample size . Further study is needed to examine the best methods to encourage enrollment for women referred to the study Objective To identify the advantages and disadvantages of using a partially r and omised patient preference design rather than a conventional r and omised controlled design when evaluating alternative managements for heavy menstrual bleeding Informed consent has been indirectly studied only in setting s that do not replicate the actual consent process . We design ed a sham study and r and omly allocated adult ambulatory patients to receive one of two consent forms : Consent A ( n = 52 ) described a r and omized trial of usual treatment vs a new medication that " may work twice as fast as the usual treatment " ; or Consent B ( n = 48 ) that described a r and omized trial of a new medication that " may work half as fast as the usual treatment " . Patients r and omized to Consent A were more likely to consent than those r and omized to Consent B ( consent rate A = 67 % , consent rate B = 42 % , p less than 0.01 ) . Among patients who cited quantitative information , the difference in consent rate was even more marked ( 95 % vs 36 % , p less than 0.001 ) ; patients who did not cite quantitative information had equivalent consent rates . Patients who perceived minimal or severe symptoms had lower consent rates than those with mid-range symptom scores ( chi 2(2 ) = 8.35 , p = 0.015 ) . Patients who recognize quantitative information will use it to make informed consent decisions We evaluate the impact of a videotape specially produced to supplement written information about preventive HIV vaccine trials . One hundred eighty-six injection drug users were r and omly assigned to an education session in which either : ( a ) a pamphlet was review ed before a brief discussion period or ( b ) the videotape was watched prior to review ing the pamphlet and participating in the discussion . The relationship among retention of information , trust in government , and willingness to participate in a vaccine trial was tested before the presentation of information , immediately after , and 1 month later . Results indicate that both methods produced significant increases in knowledge immediately after information presentation , but only the video-supplemented group retained the information 1 month later . Subjects receiving the video supplement also showed a significant increase in trust at the first posttest period , but this increase was not maintained 1 month later . Regardless of group assignment or evaluation point , willingness to participate was not associated with knowledge but was associated with trust in government Introduction : Only 3 to 5 % of new adult cancer patients participate in clinical trials nationwide . The lack of knowledge and awareness about clinical trials is a significant barrier to clinical trials participation . A r and omized trial was conducted to test the effect of an educational video on positively changing patients ’ knowledge and attitudes regarding clinical trials and thereby increasing enrollment rates . Methods : Lung cancer patients were r and omized to viewing either an 18-minute video about clinical trials before first clinic appointment or to st and ard care . Participants completed a baseline and 2-week postintervention survey to assess their knowledge and attitudes toward trials participation . Fisher ’s exact test tests , t tests , and regression were used to compare patient characteristics and outcomes between arms . Results : Of 145 subjects r and omized , 126 ( 63/arm ) satisfied all inclusion criteria and were included in the analysis . A linear regression showed that the video intervention was significantly associated with patients ’ self-assessed likelihood to enroll score measured at 2-week follow-up ( p = 0.019 ) . Although statistically insignificant , enrollment rates were found to be higher in the intervention arm for therapeutic trials alone ( 17.5 % versus 11.1 % ) and for therapeutic and nontherapeutic trials combined ( 25.4 % versus 15.9 % ) . Conclusions : The brief educational video seems to be effective in positively changing lung cancer patients ’ attitudes about participation in clinical trials . Higher enrollment rates were also observed in the intervention group but the differences did not reach statistical significance . These findings suggest a potential impact of the educational video on clinical trial enrollment ; however , larger studies are needed to confirm these findings The study objective was to assess the relative effects of 2 approaches to teaching about a clinical trial , in terms of patients ' satisfaction , information underst and ing , and whether or not they would enter such a trial . One hundred patients receiving radiation therapy for a variety of cancer diagnoses were r and omized to receive information about a hypothetical trial , either by audio tape or interactive computer program . A day later , information underst and ing was assessed . One week later , method satisfaction and whether respondents would enter such a trial were assessed . There were no differences in underst and ing or satisfaction . Members of the computer program group tended to report a more positive attitude towards trial entry ( chi 2 = 4.0 ; 1 df ; P = 0.05 ) . Overall , refusers tended to be women with higher underst and ing scores . The results suggest that teaching with interactive components might not adversely affect trial accrual . Further work involving an actual trial entry decision is merited ; the sex of the respondent should be controlled in design ing this future work The study objective was to evaluate the effect of a patient information video during the informed consent process of a perinatal trial . Ninety women , between 19 and 33 weeks gestation , were r and omised to receive written information about this perinatal trial and watch an information video or to receive written information only . Participants completed a question naire immediately after entry and 2 - 4 weeks later assessing knowledge of ; feelings about the worth of ; and willingness for future participation in the perinatal trial . When initially asked , more women who watched the video thought they would consent to the study ( chi 2 = 6.3 ; df = 1 ; P = 0.01 ) . No differences in knowledge about the perinatal trial were found initially , but 2 - 4 weeks later more knowledge had been retained by women who had watched the video ( chi 2 = 6.7 ; df = 1 ; P = 0.01 ) . These results suggest that a patient information video combined with an information sheet may result in greater participation in a research trial and may increase women 's knowledge of a specific health problem and related research trial We tested the hypothesis that the risk or discomfort associated with a clinical trial influence patients ' decisions to participate . Simultaneously , we evaluated factors likely to influence patients ' decisions such as underst and ing of the risk and discomfort associated with the study , patient age , educational level , and psychological status . With IRB approval , participants , who believed they were being asked to participate in a real trial , were presented one of three sham protocol s : no risk or pain ( Control , n = 48 ) , pain but no risk ( Pain , n = 51 ) , or risk but no pain ( Risk , n = 51 ) . Patients were debriefed at the end of the interview . Our major outcome measures were ( a ) underst and ing risk or pain associated with the proposed studies , ( b ) the extent to which patients felt pressured to participate , and ( c ) willingness to participate . Whereas underst and ing was similar in all groups ( Control , 68 % ; Pain , 67 % ; and Risk , 72 % ) , willingness to participate differed significantly ( Control , 64 % ; Pain , 35 % ; Risk , 26 % ; P < 0.001 ) . Patients who understood the level of risk or pain associated with the protocol s were twice as likely to participate than those who did not ( 49 % versus 24 % ; P = 0.003 ) . Nine percent agreed to participate in the risky or painful protocol s without underst and ing the risks involved . Patients who felt pressured did not agree to participate . Thus , the consent process protected patients , although for unexpected reasons . Underst and ing was poor , but patients who did not underst and the risks or pain involved or who felt pressured rarely consented . Consequently , relatively few patients unknowingly agreed to participate in risky or painful studies BACKGROUND The st and ard process of obtaining informed consent sometimes prevents physicians or patients from participating in clinical trials , partly because they are concerned about eventual treatment allocation or the physician is concerned the patient might harbor some uncertainty about the best treatment . Alternative r and omization methods have been advocated that may address these and other concerns . METHODS After institutional ethics committee gave its approval , the authors interviewed 770 patients before operation and asked them to consider enrolling in a mock anesthesia trial . Patients were allocated r and omly to one of five methods of r and omization and consent : one-sided informed consent ( the most common approach ) , prer and omized consent to experimental treatment , prer and omized consent to st and ard treatment , one-sided physician-modified informed consent , or one-sided patient-modified informed consent . Recruitment rates were compared and sociodemographic and perioperative predictors of recruitment were identified . RESULTS The r and omization method did not result in any significant difference in recruitment rates : one-sided informed consent , 55.6 % ; prer and omized consent to experimental treatment , 53.3 % ; prer and omized consent to st and ard treatment , 53 % ; one-sided physician-modified informed consent , 60.7 % ; and one-sided patient-modified informed consent , 56.7 % ( P = 0.66 ) . Multivariate predictors of recruitment were patient age > 45 yr ( odds ratio , 1.44 ; 95 % confidence interval [ CI ] , 1.08 to 1.93 ) , English-speaking at home ( 1.49 ; 1.0 to 2.21 ) , and male research er-male patient interaction ( 1.37 ; 1.20 to 1.57 ) . CONCLUSIONS No evidence emerged that alternative r and omization and consent design s result ed in increased recruitment rates compared with simple one-sided informed consent for a sham anesthesia trial in patients awaiting elective surgery . Older , male patients were more likely to provide consent Background In r and omized trials there may be no overriding reason whether or not to have a placebo control . Purpose We assessed the effects of an open trial design ( no placebo and people know what tablets they are given ) compared with a blinded , placebo-controlled design on recruitment , compliance and retention within a r and omized trial of secondary osteoporotic fracture prevention . Methods We undertook a r and omized controlled comparison nested within a placebo-controlled trial of nutritional supplementation amongst people aged 70 years or over who had previously sustained a fracture , recruited in a UK teaching hospital . R and omization was 2 : 1 in favour of the blinded , placebo-controlled trial design . Results From 180 eligible participants r and omized to receive information based on the open trial design , 134 ( 74.4 % ) consented to take part , compared with 233 ( 65.1 % ) of 358 people r and omized to the blinded , placebo-controlled design ( difference 9.4 % , 95 % confidence interval 1.3–17.4 % ) . Reluctance to take a placebo and the desire to know tablet allocation were reasons given for not taking part in the blinded , placebo-controlled design . There was no significant difference in tablet compliance . Open trial participants were more likely to remain in the trial for one year ( difference 13.9 % , 95 % confidence interval 3.1–24.6 % ) , mainly reflecting the high retention of the open trial no tablet group compared to the open trial tablet group ( difference 23.6 % , 95 % confidence interval 11.9–35.2 % ) . The odds ratio for reporting an adverse event in the open trial compared to the blinded , placebo-controlled design was 0.64 ( 95 % confidence interval 0.28–1.49 ) , and for reporting a fracture was 0.81 ( 0.36–1.85 ) . Conclusions We conclude that using an open trial design may enhance participant recruitment and retention and thus improve generalizability and statistical power , but withdrawal rates may differ between the study allocations and may threaten the internal validity of the trial AIMS We compared the effect of three different modes of question naire administration on screening for hazardous drinking and acquiescence to trial participation . METHODS A quasi-r and omized controlled trial among injured patients seen in acute care clinics compared self-administered paper- and -pencil , self-administered electronic , and orally-administered interview question naires . Outcomes included positive AUDIT-C screens for hazardous drinking , willingness to participate in a ( hypothetical ) lifestyle intervention trial , and recruitment success . Differences were analyzed with nonlinear mixed models , controlling for age , sex , and facility . Structured interviews with staff explored levers and barriers to screening . RESULTS Of the 370 participants , 22.7 % scored > or = 4 and 7.8 % > or = 6 on the AUDIT-C. Electronic question naires were more likely than paper question naires to identify an AUDIT-C > or = 6 ( OR = 1.96 ; 95 % CI 1.10 - 3.48 ) , but not > or = 4 ( OR = 0.83 ; 95 % CI 0.43 - 1.62 ) . Oral question naires were as likely as paper question naires to identify an AUDIT-C > or = 4 ( OR = 1.00 ; 95 % CI 0.40 - 2.51 ) or > or = 6 ( OR = 1.94 ; 95 % CI 0.83 - 4.50 ) . Electronic and oral question naires were more likely to elicit acquiescence to trial participation ( OR = 1.59 ; 95 % CI 1.23 - 2.07 , and OR = 1.66 ; 95 % CI 1.22 - 2.26 , respectively ) . Oral question naires created problems with confidentiality , privacy , and disruption of patient flow , and reduced recruitment success ( OR = 0.51 ; 95 % CI 0.42 - 0.62 ) . CONCLUSIONS Among acutely injured patients in clinics who consented to screening , nearly one-fourth reported hazardous drinking . Compared to paper question naires , electronic screening produced less social desirability bias and greater acquiescence to trial participation . Oral question naires produced greater acquiescence , but barriers to use adversely affected recruitment . Electronic question naires may be preferable for screening for hazardous drinking and recruitment into intervention trials in acute care clinics PURPOSE To compare the effect of blind design ( active drug and placebo ) and nonblind design ( active drug and no treatment ) on recruitment . SETTING A primary prevention trial with postmenopausal hormone therapy in Estonia . METHODS Women who were eligible and willing to participate on the basis of the question naire survey were r and omized into blind and nonblind groups . Recruitment rates are based on record keeping , and reasons for participating were requested in the first-year follow-up . RESULTS The recruitment was 30 % higher in the nonblind group : of the 4,295 women invited , 37 % ( 95 % confidence interval CI=35 - 39 % ) in the blind group and 48 % ( 95 % CI=46 - 49 % ) in the nonblind group were recruited . In both groups , once r and omized , most of the losses were women who did not attend the first clinical examination : 49 % ( blind ; 95 % CI=47 - 51 % ) and 40 % ( nonblind ; 95 % CI=38 - 42 % ) . The rest were found ineligible or lost their interest during clinical examinations . The reasons for joining the trial were relatively similar in the two groups . CONCLUSIONS Blinding decreased women 's interest in joining a long-term preventive trial . Women 's reasons for joining the trial were not influenced by blinding PURPOSE To design and test a geriatric educational intervention to improve accrual of cancer patients age 65 years and older to cooperative group-sponsored treatment trials . METHODS Main member institutions of the Cancer and Leukemia Group B ( CALGB ) and its affiliates were r and omly assigned to receive st and ard information ( n = 73 ) or educational intervention ( n = 53 ) . St and ard information included CALGB Web site access and periodic notification about existing trials . The geriatric educational intervention included st and ard information plus : ( 1 ) an educational seminar ; ( 2 ) educational material s ; ( 3 ) a list of available protocol s for use on charts ; ( 4 ) a monthly e-mail and mail reminders for 1 year ; and ( 5 ) a case discussion seminar . The main outcome was percentage of accrual of older persons to phase II and III treatment protocol s after study initiation compared with baseline . RESULTS There were 3,032 patients entered onto trials in the baseline year , and 2,160 and 1,239 during the 2 years postintervention , respectively . Overall percentage of accrual of older patients was 37 % at baseline , and 33 % and 31 % during the first and second years after intervention . There was no improvement in accrual in the intervention versus control arm : 36 % v 32 % in the first year and 31 % v 31 % in the second year . CONCLUSION Accrual of older patients was not increased by this intervention . Reasons for lack of effect include low intervention intensity , high baseline accrual rates , and closure of several high-accruing protocol s during the study . More intense and multifaceted approaches will be needed to change physician ( and patient ) behavior and to increase accrual of older persons to clinical trials Few publications have examined maximising recruitment to r and omised controlled trials in primary care . Mass mailings have been used as a recruitment strategy , 1 - 3 but have had low response rates . Short messages in mass mailings have acheived better recruitment rates than longer messages.4 Within a primary care injury prevention trial we assessed response and recruitment rates to the trial using mass mailing , comparing an invitation to participate with and without a home safety question naire . We considered that sending a question naire may reduce the recruitment rate because of the time and effort needed for completion4 or because questions on safety behaviours and previous injury may be perceived as intrusive ; alternatively we considered that the question naire may raise awareness of risk of injury and through this might increase the recruitment rate.5 The study population comprised the first 2397 families |
991 | 28,379,501 | CV events did not decrease over time .
Comparing shorter studies ( < 52 weeks ) to longer ones did not reveal any statistical differences .
However , in long-term studies with febuxostat vs allopurinol , results were nearly significant , with more CVE occurring with febuxostat treatment .
Conclusion RCT data do not suggest differences in CV events among ULTs in gout .
Trials had few events despite high-risk patients being enrolled and may have been too short to show CV reduction by controlling inflammatory attacks and lowering uric acid | Objectives To determine if urate-lowering treatment ( ULT ) in gout can reduce cardiovascular ( CV ) outcomes . | OBJECTIVE The use of colchicine to prevent acute gout flares during initiation of allopurinol therapy is widely practice d despite lack of proven benefit . We investigated if colchicine administration during initiation of allopurinol for chronic gouty arthritis reduces the frequency and /or severity of acute gout flares . METHODS Patients starting allopurinol for crystal-proven chronic gouty arthritis were r and omized to receive colchicine 0.6 mg po bid or placebo in a r and omized , prospect i ve , double blind , placebo controlled trial . Subjects were followed for evidence of acute gout flares and remained on study drug for 3 months beyond attaining a serum urate concentration < 6.5 mg/dl . Treatment arms were analyzed regarding frequency of flares , likelihood of any flare or multiple flares , severity of flares on the visual analog scale ( VAS ) , and length of flares in days . RESULTS Forty-three subjects were studied . Subjects treated with colchicine experienced fewer total flares ( 0.52 vs 2.91 , p = 0.008 ) , fewer flares from 0 to 3 months ( 0.57 vs 1.91 , p = 0.022 ) , fewer flares 3 - 6 months ( 0 vs 1.05 , p = 0.033 ) , less severe flares as reported on VAS ( 3.64 vs 5.08 , p = 0.018 ) , and fewer recurrent gout flares ( p = 0.001 ) . Colchicine was well tolerated . CONCLUSION Colchicine prophylaxis during initiation of allopurinol for chronic gouty arthritis reduces the frequency and severity of acute flares , and reduces the likelihood of recurrent flares . Treating patients with colchicine during initiation of allopurinol therapy for 6 months is supported by our data Background — Although gout and hyperuricemia are related to several conditions that are associated with reduced survival , no prospect i ve data are available on the independent impact of gout on mortality . Furthermore , although many studies have suggested that hyperuricemia is associated with cardiovascular disease ( CVD ) , limited data are available on the impact of gout on CVD . Methods and Results — Over a 12-year period , we prospect ively examined the relation between a history of gout and the risk of death and myocardial infa rct ion in 51 297 male participants of the Health Professionals Follow-Up Study . During the 12 years of follow-up , we documented 5825 deaths from all causes , which included 2132 deaths from CVD and 1576 deaths from coronary heart disease ( CHD ) . Compared with men without history of gout and CHD at baseline , the multivariate relative risks among men with history of gout were 1.28 ( 95 % confidence interval [ CI ] , 1.15 to 1.41 ) for total mortality , 1.38 ( 95 % CI , 1.15 to 1.66 ) for CVD deaths , and 1.55 ( 95 % CI , 1.24 to 1.93 ) for fatal CHD . The corresponding relative risks among men with preexisting CHD were 1.25 ( 95 % CI , 1.09 to 1.45 ) , 1.26 ( 95 % CI , 1.07 to 1.50 ) , and 1.24 ( 95 % CI , 1.04 to 1.49 ) , respectively . In addition , men with gout had a higher risk of nonfatal myocardial infa rct ion than men without gout ( multivariate relative risk , 1.59 ; 95 % CI , 1.04 to 2.41 ) . Conclusions — These prospect i ve data indicate that men with gout have a higher risk of death from all causes . Among men without preexisting CHD , the increased mortality risk is primarily a result of an elevated risk of CVD death , particularly from CHD Objectives : To investigate the efficacy and tolerability of allopurinol as the first-choice antihyperuricaemic treatment for gout , and compare the efficacy and tolerability of benzbromarone and probenecid as second-choice treatment . Methods : Prospect i ve , multicentre , open-label , two-stage r and omised controlled trial in gout patients with normal renal function . Enrolled patients were given 300 mg allopurinol for 2 months ( stage 1 ) . Those patients who could not tolerate allopurinol or who did not attain the target serum urate concentration ( sUr ) ⩽0.30 mmol/l ( 5.0 mg/dl ) , which was defined as successful , were r and omised to benzbromarone 200 mg/day or probenecid 2 g/day for another 2 months ( stage 2 ) . Results : 96 patients were enrolled in stage 1 . 82 patients ( 85 % ) were eligible for the analysis at the end of stage 1 : there was a mean ( SD ) decrease in sUr concentration of 35 (11)% from baseline ; 20 patients ( 24 % ) attained target sUr ⩽0.30 mmol/l ; and 9 patients ( 11 % ) stopped allopurinol because of adverse drug reactions . 62 patients were enrolled in stage 2 . 27 patients received benzbromarone ( 3 patients not eligible for analysis ) and 35 received probenecid ( 4 patients not eligible for analysis ) . Treatment with benzbromarone was successful in 22/24 patients ( 92 % ) and with probenecid in 20/31 patients ( 65 % ) ( p = 0.03 compared with benzbromarone ) . Compared with baseline values , there was a mean ( SD ) decrease of sUr concentration of 64 (9)% with benzbromarone and 50 (7)% with probenecid ( p<0.001 ) . Conclusion : This study showed that allopurinol 300 mg/day has a poor efficacy and tolerability profile when used to attain a biochemical predefined target level of sUr ⩽0.30 mmol/l , following 2 months of treatment . In stage 2 , benzbromarone 200 mg/day was more effective and better tolerated than probenecid 2 g/day . Trial registration number : IS RCT N21473387 Aim Assess influences of demographics and co-morbidities of gout patients with or without diabetes on safety and efficacy of urate-lowering agents . Methods Post-hoc analysis of 312 diabetic and 1957 non-diabetic gout patients [ baseline serum urate levels ( sUA ) ≥8.0 mg/dl ] enrolled in a 6-month r and omized controlled trial comparing urate-lowering efficacy ( ULE ) and safety of daily xanthine oxidase inhibitors ( XOIs ) febuxostat ( 40 mg or 80 mg ) and allopurinol ( 200 mg or 300 mg ) . We compared baseline demographic , gout and co-morbid characteristics , ULE , and safety of XOI treatment in diabetic and non-diabetic gout patients . ULE was measured by the proportion of diabetic and non-diabetic patients in each treatment group achieving final visit sUA < 6.0 mg/dl . Safety was monitored throughout the trial . Results Diabetic gout patients were older , more frequently female , and had longer gout duration . Co-morbidities were more frequent among diabetic patients : cardiovascular disease ; impaired renal function ; hyperlipidemia ; and obesity ( body mass index > 30 kg/m2 ) ( p < 0.001 for all comparisons ) . Febuxostat 80 mg ULE exceeded that of febuxostat 40 mg or allopurinol ( p < 0.050 ) at all levels of renal function , achieving sUA goal range in the majority of diabetic and non-diabetic patients . Diabetics and non-diabetics reported self-limiting diarrhoea and URIs as the most common adverse events . Conclusions Despite higher co-morbidity rates in diabetic patients , febuxostat and allopurinol were safe in both groups at the doses tested . Febuxostat 80 mg achieved sUA < 6.0 mg/dl more often than febuxostat 40 mg or allopurinol at commonly prescribed doses Introduction The purpose of this study was to compare urate-lowering ( UL ) efficacy and safety of daily febuxostat and allopurinol in subjects with gout and serum urate ( sUA ) ≥ 8.0 mg/dL in a six-month trial . Methods Subjects ( n = 2,269 ) were r and omized to febuxostat 40 mg or 80 mg , or allopurinol 300 mg ( 200 mg in moderate renal impairment ) . Endpoints included the proportion of all subjects with sUA < 6.0 mg/dL and the proportion of subjects with mild/moderate renal impairment and sUA < 6.0 mg/dL. Safety assessment s included blinded adjudication of each cardiovascular ( CV ) adverse event ( AE ) and death . Results Comorbidities included : renal impairment ( 65 % ) ; obesity ( 64 % ) ; hyperlipidemia ( 42 % ) ; and hypertension ( 53 % ) . In febuxostat 40 mg , febuxostat 80 mg , and allopurinol groups , primary endpoint was achieved in 45 % , 67 % , and 42 % , respectively . Febuxostat 40 mg UL was statistically non-inferior to allopurinol , but febuxostat 80 mg was superior to both ( P < 0.001 ) . Achievement of target sUA in subjects with renal impairment was also superior with febuxostat 80 mg ( 72 % ; P < 0.001 ) compared with febuxostat 40 mg ( 50 % ) or allopurinol ( 42 % ) , but febuxostat 40 mg showed greater efficacy than allopurinol ( P = 0.021 ) . Rates of AEs did not differ across treatment groups . Adjudicated ( APTC ) CV event rates were 0.0 % for febuxostat 40 mg and 0.4 % for both febuxostat 80 mg and allopurinol . One death occurred in each febuxostat group and three in the allopurinol group . Conclusions Urate-lowering efficacy of febuxostat 80 mg exceeded that of febuxostat 40 mg and allopurinol ( 300/200 mg ) , which were comparable . In subjects with mild/moderate renal impairment , both febuxostat doses were more efficacious than allopurinol and equally safe . At the doses tested , safety of febuxostat and allopurinol was comparable . Clinical Trial Registration Introduction Gout affects 2.5 % of the UK 's adult population and is now the most common type of inflammatory arthritis . The long-term management of gout requires reduction of serum urate levels and this is most often achieved with use of xanthine oxidase inhibitors , such as allopurinol . Febuxostat is the first new xanthine oxidase inhibitor since allopurinol and was licensed for use in 2008 . The European Medicines Agency requested a postlicensing cardiovascular safety study of febuxostat versus allopurinol , which has been named the Febuxostat versus Allopurinol Streamlined trial ( FAST ) . Methods and analysis FAST is a cardiovascular safety study using the prospect i ve , r and omised , open , blinded endpoint design . FAST is recruiting in the UK and Denmark . Recruited patients are aged over 60 years , prescribed allopurinol for symptomatic hyperuricaemia and have at least one additional cardiovascular risk factor . After an allopurinol lead-in phase where the dose of allopurinol is optimised to achieve European League against Rheumatism ( EULAR ) urate targets ( serum urate < 357 µmol/L ) , patients are r and omised to either continue optimal dose allopurinol or to use febuxostat . Patients are followed-up for an average of 3 years . The primary endpoint is first occurrence of the Anti-Platelet Trialists ’ Collaboration ( APTC ) cardiovascular endpoint of non-fatal myocardial infa rct ion , non-fatal stroke or cardiovascular death . Secondary endpoints are all cause mortality and hospitalisations for heart failure , unstable , new or worsening angina , coronary or cerebral revascularisation , transient ischaemic attack , non-fatal cardiac arrest , venous and peripheral arterial vascular thrombotic event and arrhythmia with no evidence of ischaemia . The primary analysis is a non-inferiority analysis with a non-inferiority upper limit for the HR for the primary outcome of 1.3 . Ethics and dissemination FAST ( IS RCT N72443728 ) has ethical approval in the UK and Denmark , and results will be published in a peer review ed journal . Trial Registration number FAST is registered in the EU Clinical Trials Register ( EUDRACT No : 2011 - 001883 - 23 ) and International St and ard R and omised Controlled Trial Number Register ( IS RCT N No : IS RCT N72443728 ) CONTEXT Patients with chronic disabling gout refractory to conventional urate-lowering therapy need timely treatment to control disease manifestations related to tissue urate crystal deposition . Pegloticase , monomethoxypoly(ethylene glycol)-conjugated mammalian recombinant uricase , was developed to fulfill this need . OBJECTIVE To assess the efficacy and tolerability of pegloticase in managing refractory chronic gout . DESIGN , SETTING , AND PATIENTS Two replicate , r and omized , double-blind , placebo-controlled trials ( C0405 and C0406 ) were conducted between June 2006 and October 2007 at 56 rheumatology practice s in the United States , Canada , and Mexico in patients with severe gout , allopurinol intolerance or refractoriness , and serum uric acid concentration of 8.0 mg/dL or greater . A total of 225 patients participated : 109 in trial C0405 and 116 in trial C0406 . INTERVENTION Twelve biweekly intravenous infusions containing either pegloticase 8 mg at each infusion ( biweekly treatment group ) , pegloticase alternating with placebo at successive infusions ( monthly treatment group ) , or placebo ( placebo group ) . MAIN OUTCOME MEASURE Primary end point was plasma uric acid levels of less than 6.0 mg/dL in months 3 and 6 . RESULTS In trial C0405 the primary end point was reached in 20 of 43 patients in the biweekly group ( 47 % ; 95 % CI , 31%-62 % ) , 8 of 41 patients in the monthly group ( 20 % ; 95 % CI , 9%-35 % ) , and in 0 patients treated with placebo ( 0/20 ; 95 % CI , 0%-17 % ; P < .001 and < .04 for comparisons between biweekly and monthly groups vs placebo , respectively ) . Among patients treated with pegloticase in trial C0406 , 16 of 42 in the biweekly group ( 38 % ; 95 % CI , 24%-54 % ) and 21 of 43 in the monthly group ( 49 % ; 95 % CI , 33%-65 % ) achieved the primary end point ; no placebo-treated patients reached the primary end point ( 0/23 ; 95 % CI , 0%-15 % ; P = .001 and < .001 , respectively ) . When data in the 2 trials were pooled , the primary end point was achieved in 36 of 85 patients in the biweekly group ( 42 % ; 95 % CI , 32%-54 % ) , 29 of 84 patients in the monthly group ( 35 % ; 95 % CI , 24%-46 % ) , and 0 of 43 patients in the placebo group ( 0 % ; 95 % CI , 0%-8 % ; P < .001 for each comparison ) . Seven deaths ( 4 in patients receiving pegloticase and 3 in the placebo group ) occurred between r and omization and closure of the study data base ( February 15 , 2008 ) . CONCLUSION Among patients with chronic gout , elevated serum uric acid level , and allopurinol intolerance or refractoriness , the use of pegloticase 8 mg either every 2 weeks or every 4 weeks for 6 months result ed in lower uric acid levels compared with placebo . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00325195 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 long-term safety ( up to 3 years ) of treatment with pegloticase in patients with refractory chronic gout . Methods This open-label extension ( OLE ) study was conducted at 46 sites in the USA , Canada and Mexico . Patients completing either of two replicate r and omised placebo-controlled 6-month trials received pegloticase 8 mg every 2 weeks ( biweekly ) or every 4 weeks ( monthly ) . Safety was evaluated as the primary outcome , with special interest in gout flares and infusion-related reactions ( IRs ) . Secondary outcomes included urate-lowering and clinical efficacy . Results Patients ( n=149 ) received a mean±SD of 28±18 pegloticase infusions and were followed for a mean of 25±11 months . Gout flares and IRs were the most frequently reported adverse events ; these were least common in patients with a sustained urate-lowering response to treatment and those receiving biweekly treatment . In 10 of the 11 patients with a serious IR , the event occurred when uric acid exceeded 6 mg/dl . Plasma and serum uric acid levels remained < 6 mg/dl in most r and omised controlled trial ( RCT ) -defined pegloticase responders throughout the OLE study and were accompanied by sustained and progressive improvements in tophus resolution and flare incidence . Conclusions The safety profile of long-term pegloticase treatment was consistent with that observed during 6 months of RCT treatment ; no new safety signals were identified . Improvements in clinical status , in the form of flare and tophus reduction initiated during RCT pegloticase treatment in patients maintaining goal range urate-lowering responses were sustained or advanced during up to 2.5 years of additional treatment Introduction Two replicate r and omized , placebo-controlled six-month trials ( RCTs ) and an open-label treatment extension ( OLE ) comprised the pegloticase development program in patients with gout refractory to conventional therapy . In the RCTs , approximately 40 % of patients treated with the approved dose saw complete response ( CR ) of at least one tophus . Here we describe the temporal course of tophus resolution , total tophus burden in patients with multiple tophi , tophus size at baseline , and the relationship between tophus response and urate-lowering efficacy . Methods Baseline subcutaneous tophi were analyzed quantitatively using computer-assisted digital images in patients receiving pegloticase ( 8 mg biweekly or monthly ) or placebo in the RCTs , and pegloticase in the OLE . Tophus response , a secondary endpoint in the trials , was evaluated two ways . Overall tophus CR was the proportion of patients achieving a best response of CR ( without any new/enlarging tophi ) and target tophus complete response ( TT-CR ) was the proportion of all tophi with CR . Results Among 212 patients r and omized in the RCTs , 155 ( 73 % ) had ≥1 tophus and 547 visible tophi were recorded at baseline . Overall tophus CR was recorded in 45 % of patients in the biweekly group ( P = 0.002 versus placebo ) , 26 % in the monthly group , and 8 % in the placebo group after six months of RCT therapy . TT-CR rates at six months were 28 % , 19 % , and 2 % of tophi , respectively . Patients meeting the primary endpoint of sustained urate-lowering response to therapy ( responders ) were more likely than nonresponders to have an overall tophus CR at six months ( 54 % vs 20 % , respectively and 8 % with placebo).Both overall tophus CR and TT-CRs increased with treatment duration in the OLE , reaching 70 % ( 39/56 ) of patients and 55 % ( 132/238 ) of target tophi after one year of treatment in patients receiving pegloticase during both the RCTs and OLE . At that time point , more tophi had resolved in responders ( 102/145 or 70 % of tophi ) than nonresponders ( 30/93 ; 32 % ) . Conclusions Pegloticase reduced tophus burden in patients with refractory tophaceous gout , especially those achieving sustained urate-lowering . Complete resolution of tophi occurred in some patients by 13 weeks and in others with longer-term therapy . Trial registration sNCT00325195 , Background The incidence of gout rises with increasing age . Management of elderly ( ≥65 years ) gout patients can be challenging due to high rates of comorbidities , such as renal impairment and cardiovascular disease , and concomitant medication use . However , there is little data specifically addressing the efficacy and safety of available urate-lowering therapies ( ULT ) in the elderly . The objective of this post hoc analysis was to examine the efficacy and safety of ULT with febuxostat or allopurinol in a subset of elderly subjects enrolled in the CONFIRMS trial . Methods Hyperuricemic ( serum urate [ sUA ] levels ≥ 8.0 mg/dL ) gout subjects were enrolled in the 6-month , double-blind , r and omized , comparative CONFIRMS trial and r and omized , 1:1:1 , to receive febuxostat , 40 mg or 80 mg , or allopurinol ( 200 mg or 300 mg based on renal function ) once daily . Flare prophylaxis was provided throughout the study duration . Study endpoints were the percent of elderly subjects with sUA < 6.0 mg/dL at the final visit , overall and by renal function status , percent change in sUA from baseline to final visit , flare rates , and rates of adverse events ( AEs ) . Results Of 2,269 subjects enrolled , 374 were elderly . Febuxostat 80 mg was significantly more efficacious ( 82.0 % ) than febuxostat 40 mg ( 61.7 % ; p < 0.001 ) or allopurinol ( 47.3 % ; p < 0.001 ) for achieving the primary efficacy endpoint . Febuxostat 40 mg was also superior to allopurinol in this population ( p = 0.029 ) . In subjects with mild-to-moderate renal impairment , significantly greater ULT efficacy was observed with febuxostat 40 mg ( 61.6 % ; p = 0.028 ) and febuxostat 80 mg ( 82.5 % ; p < 0.001 ) compared to allopurinol 200/300 mg ( 46.9 % ) . Compared to allopurinol 200/300 mg , the mean percent change in sUA from baseline was significantly greater for both febuxostat 80 mg ( p < 0.001 ) and febuxostat 40 mg ( p = 0.011 ) groups . Flare rates declined steadily in all treatment groups . Rates of AEs were low and comparable across treatments . Conclusions These data suggest that either dose of febuxostat is superior to commonly prescribed fixed doses of allopurinol ( 200/300 mg ) in subjects ≥65 years of age with high rates of renal dysfunction . In addition , in this high-risk population , ULT with either drug was well tolerated . Trial registration clinical trials.gov Background African Americans are twice as likely as Caucasians to develop gout , but they are less likely to be treated with urate-lowering therapy ( ULT ) . Furthermore , African Americans typically present with more comorbidities associated with gout , such as hypertension , obesity , and renal impairment . We determined the efficacy and safety of ULT with febuxostat or allopurinol in African American subjects with gout and associated comorbidities and in comparison to Caucasian gout subjects . Methods This is a secondary analysis of the 6-month Phase 3 CONFIRMS trial . Eligible gouty subjects with baseline serum urate ( sUA ) ≥ 8.0 mg/dL were r and omized 1:1:1 to receive febuxostat 40 mg , febuxostat 80 mg , or allopurinol ( 300 mg or 200 mg depending on renal function ) daily . All subjects received gout flare prophylaxis . Primary efficacy endpoint was the proportion of subjects in each treatment group with sUA < 6.0 mg/dL at the final visit . Additional endpoints included the proportion of subjects with mild or with moderate renal impairment who achieved a target sUA < 6.0 mg/dL at final visit . Adverse events ( AEs ) were recorded throughout the study . Results Of the 2,269 subjects enrolled , 10.0 % were African American and 82.1 % were Caucasian . African American subjects were mostly male ( 89.5 % ) , obese ( BMI ≥ 30 kg/m2 ; 67.1 % ) , with mean baseline sUA of 9.8 mg/dL and mean duration of gout of 10.4 years . The proportions of African American subjects with a baseline history of diabetes , renal impairment , or cardiovascular disease were significantly higher compared to Caucasians ( p < 0.001 ) . ULT with febuxostat 80 mg was superior to both febuxostat 40 mg ( p < 0.001 ) and allopurinol ( p = 0.004 ) . Febuxostat 40 mg was comparable in efficacy to allopurinol . Significantly more African American subjects with mild or moderate renal impairment achieved sUA < 6.0 mg/dL in the febuxostat 80 group than in either the febuxostat 40 mg or allopurinol group ( p < 0.05 ) . Efficacy rates in all treatment groups regardless of renal function were comparable between African American and Caucasian subjects , as were AE rates . Conclusions In African American subjects with significant comorbidities , febuxostat 80 mg is significantly more efficacious than either febuxostat 40 mg or allopurinol 200/300 mg . Febuxostat was well tolerated in this African American population .Please see related article : http://www.biomed central .com/1741 - In 2003 , the uricosuric drug benzbromarone was withdrawn from the market . The first alternative drug of choice was the xanthine oxidase inhibitor allopurinol . The purpose was to ( 1 ) investigate the efficacy of allopurinol ( st and ard dosage ) compared with previous treatment with benzbromarone ; and ( 2 ) investigate the combination therapy allopurinol – probenecid as an effective alternative treatment compared with previous benzbromarone treatment . A prospect i ve , open study was carried out in a cohort of 51 gout patients who discontinued benzbromarone therapy because of market withdrawal . Patients were given 200–300 mg allopurinol ( stage 1 ) . When allopurinol failed to attain the target serum urate ( sUr ) levels ≤0.30 mmol/l , probenecid 1,000 mg/day was added ( stage 2 ) . Treatment with benzbromarone monotherapy ( range : 100–200 mg/day ; mean 138 mg/day ) result ed in 92 % of patients reaching target levels sUr ≤ 0.30 mmol/l with a decrease of 61[11]% compared to baseline . In stage 1 , 32 patients completed treatment with allopurinol monotherapy ( range 200–300 mg/day ; mean 256 mg/day ) , which result ed in 25 % of patients attaining sUr target levels . Decrease in sUr levels was 36[11]% , which was significantly less compared to treatment with benzbromarone ( p < 0.001 ) . In stage 2 , 14 patients received allopurinol – probenecid combination therapy , which result ed in 86 % of patients attaining target sUr levels ( after failure on allopurinol monotherapy ) , which was comparable to previous treatment with benzbromarone ( p = 0.81 ) . Decrease in sUr levels was 53[9]% ( CI 95 % : 48–58 % ) , which was a non-significant difference compared to previous treatment with benzbromarone ( p = 0.23 ) . Benzbromarone is a very effective antihyperuricemic drug with 91 % success in attainment of target sUr levels ≤0.30 mmol/l . Allopurinol 200–300 mg/day was shown to be a less potent alternative for most selected patients to attain target sUr levels ( 13 % success ) . In patients failing on allopurinol monotherapy , the addition of probenecid proves to be an effective treatment strategy for attaining sUr target levels ( 86 % success ) Objective . To examine ( 1 ) the risk of death from cardiovascular disease ( CVD ) and from all causes in patients with gout who do not undergo urate-lowering therapy ( ULT ) , and ( 2 ) the effect of ULT on mortality risk in patients with gout . Methods . In this prospect i ve case-matched cohort study , 40,623 Taiwanese individuals aged ≥ 17 years were followed for 6.5 years . Mortality rate was compared between 1189 patients with gout who did not receive ULT and reference subjects ( no gout , no ULT ) matched for age , sex , and the index date of gout diagnosis ( 1:3 patients with gout/reference subjects ) , and between 764 patients with gout who received ULT and 764 patients with gout who did not receive ULT matched 1-to-1 based on their propensity score and the index date of ULT prescription . Cox proportional hazard modeling was used to estimate the respective risk of CVD ( International Classification of Diseases , 9th ed . code 390–459 ) and all-cause mortality . Results . After adjustment , patients with gout not treated with ULT had an increased risk of CVD mortality ( HR 2.43 , 95 % CI 1.33–4.45 ) and all-cause mortality ( 1.45 , 1.05–2.00 ) relative to the matched reference subjects ( no gout , no ULT ) . Patients with gout treated with ULT had a lower risk of CVD ( 0.29 , 0.11–0.80 ) and all-cause mortality ( 0.47 , 0.29–0.79 ) relative to patients with gout not treated with ULT . This survival benefit persisted for users of either allopurinol or benzbromarone . Conclusion . Patients with gout who received ULT had significantly better survival rates than those who did not . Thus , undertreatment of gout has serious negative consequences OBJECTIVES To study the efficacy of allopurinol and benzbromarone to reduce serum urate concentrations in patients with primary chronic gout . METHODS Prospect i ve , parallel , open study of 86 consecutive male patients with primary chronic gout . Forty nine patients ( 26 normal excretors and 23 under excretors ) were given allopurinol 300 mg/day and 37 under excretors benzbromarone 100 mg/day . After achieving steady plasma urate concentrations with such doses , treatment was then adjusted to obtain optimal plasmatic urate concentrations ( under 6 mg/dl ) . RESULTS Patients receiving allopurinol 300 mg/day showed a mean reduction of plasmatic urate of 2.75 mg/dl ( from 8.60 to 5.85 mg/dl ) and 3.34 mg/dl ( from 9.10 to 5.76 mg/dl ) in normal excretors and under excretors respectively . Patients receiving benzbromarone 100 mg/day achieved a reduction of plasmatic urate of 5.04 mg/dl ( from 8.58 to 3.54 mg/dl ) . Fifty three per cent of patients receiving allopurinol and 100 % receiving benzbromarone achieved optimal plasma urate concentrations at such doses . The patients with poor results with allopurinol 300 mg/day achieved a proper plasma urate concentration with allopurinol 450 to 600 mg/day , the mean final dose being 372 mg/day . Renal fuction improved and no case of renal lithiasis was observed among benzbromarone treated patients , whose mean final dose was 76 mg/day . CONCLUSION Benzbromarone is very effective to control plasma urate concentrations at doses ranging from 50 to 100 mg/day . Uricosuric treatment is a suitable approach to the treatment of patients with gout who show underexcretion of urate Treatment of gout and hyperuricemia can be difficult in patients with chronic renal failure . At present , there is no study available comparing the efficacy of the most widely used agent , allopurinol , and the uricosuric benzbromarone for the control of hyperuricemia in patients with renal insufficiency . We describe an open , r and omized , actively controlled , comparative trial in patients with clearance of creatinine from 20 to 80 mL/ min/1.73 m(2 ) . Patients were r and omized to take benzbromarone ( 100 - 200 mg/day ) or allopurinol ( 100 - 300 mg/day ) . Outcome variables were the following : reduction of serum urate ( Sur ) , Sur & tl ; 6 mg/dL ( 357 micromol/L ) , reduction of gouty bouts and reduction of tophi . During 9 - 24 months of follow-up 36 patients were studied . The reduction of Sur was higher with benzbromarone , and only 1 of 17 patients taking benzbromarone did not achieve Sur < 6 mg/dL versus 7 of 19 taking allopurinol . Patients who did not reach optimal Sur levels with allopurinol were more frequently taking diuretics and showed lower fractional excretion of urate and higher initial Sur levels than patients with proper control of Sur . Seven patients with suboptimal control of serum urate were changed to benzbromarone 100 mg/day , which showed efficacy similar in those who were initially r and omized to benzbromarone . A reduction of gouty bouts and size of tophi was observed after proper control of Sur . Allopurinol is effective in controlling hyperuricemia , but patients with higher initial Sur levels or taking concomitant diuretic therapy are less prone to reach therapeutic goals .Benzbromarone is useful for the control of hyperuricemia in patients with renal insufficiency even with concomitant diuretic administration ; patients benefited include those who previously had no improvement by taking allopurinol OBJECTIVE To assess the short-term urate-lowering effect of fenofibrate in men on long-term allopurinol therapy for hyperuricaemia and gout . METHODS Ten male patients ( 38 - 74 yr ) with a history of chronic tophaceous or recurrent acute gout with hyperuricaemia and on established allopurinol at 300 - 900 mg/day for > or =3 months were studied in an open-crossover study of fenofibrate therapy . Allopurinol at the established dose was continued throughout the study . Clinical and biochemical assessment s ( serum urate and creatinine , 24-h urinary excretion of urate and creatinine , liver function tests , creatine kinase and fasting serum lipids ) were undertaken at : ( i ) baseline , ( ii ) after 3 weeks of once-daily therapy with micronized fenofibrate ( Lipantil Micro ) at 200 mg and ( iii ) 3 weeks after fenofibrate was withdrawn . RESULTS Fenofibrate was associated with a 19 % reduction in serum urate after 3 weeks of treatment ( mean+/-S.E. 0.37+/-0.04 vs 0.30+/-0.02 mM/l ; P=0.004 ) . The effect was reversed after a 3-week fenofibrate withdrawal period ( 0.30+/-0.02 vs 0.38+/-0.03 mM/l ) . There was a rise in uric acid clearance with fenofibrate treatment of 36 % ( 7.2+/-0.9 vs 11.4+/-1.6 ml/min , normal range 6 - 11 ; P=0.006 ) without a significant change in creatinine clearance . Both total cholesterol and serum triglycerides were also reduced . No patient developed acute gout whilst taking fenofibrate . CONCLUSIONS Fenofibrate has a rapid and reversible urate-lowering effect in patients with hyperuricaemia and gout on established allopurinol prophylaxis . Fenofibrate may be a potential new treatment for hyperuricaemia and the prevention of gout , particularly in patients with coexisting hyperlipidaemia or those resistant to conventional therapy for hyperuricaemia BACKGROUND Allopurinol has been widely used for the treatment of hyperuricemia , however , it may be associated with various adverse effects . Febuxostat has been identified as a potentially safe and efficacious alternative . OBJECTIVES A multicenter study with r and omized , placebo-controlled , double-blind , parallel , intergroup comparison was carried out to evaluate the dose-response relationship , efficacy , and safety of febuxostat in 202 patients with hyperuricemia ( including patients with gout ) in Japan . METHODS The subjects were treated with febuxostat at fixed maintenance doses ( 20 - 80 mg/d ) or a placebo for 16 weeks . The percentage of patients achieving serum uric acid levels 6.0 mg/dL or less and the percent change in serum uric acid levels after 16 weeks of treatment were evaluated . RESULTS The percentage of patients achieving serum uric acid levels 6.0 mg/dL or less at 16 weeks was 87.8 % in the 80-mg/d dose group , 83.3 % in the 60-mg/d group , 82.9 % in the 40-mg/d group , 46.5 % in the 20-mg/d group , and 2.6 % in the placebo group ( P < 0.001 , Mantel-Haenszel test ) . A statistically significant dose-response relationship was found . The percent change in serum uric acid levels after 16 weeks of treatment differed significantly between each febuxostat dose group and the placebo group and increased in a dose-dependent manner above 40 mg/d . No deaths , events posing a clinical problem , or serious adverse reactions attributable to febuxostat were noted . Similar results were obtained regardless of gout history . CONCLUSIONS Febuxostat can safely reduce serum uric acid levels to 6.0 mg/dL or less in 80 % or more of patients with hyperuricemia ( including gout ) at doses of 40 mg/d or higher Comprehensive safety evaluation of new drugs for noncardiac indications is needed in the area of cardiovascular ( CV ) outcomes , particularly in population s with high CV risk such as gout . Febuxostat is a potent nonpurine selective inhibitor of xanthine oxidase approved for the treatment of gout . Long-term CV safety of febuxostat is being established in a r and omized , allopurinol-controlled clinical study in patients with gout who have increased CV risk using an analytical approach that provides 90 % power to meet a noninferiority margin of 1.3 for the hazard ratio ( HR ) ( febuxostat relative to allopurinol ) . The primary CV end point for this trial is a composite of CV death , nonfatal myocardial infa rct ion , nonfatal stroke , and unstable angina requiring urgent coronary revascularization . Approximately 7,500 men and women with gout and CV disease are being recruited and will be followed up for up to 5 years postr and omization . The statistical plan for the trial uses a design that evaluates the HR of febuxostat to allopurinol based on the primary CV composite end point when there are a maximum of 624 CV events . Interim analyses will be conducted when approximately 25 % , 50 % , and 75 % of events have occurred . At each analysis , if the upper 1-sided confidence limit of the HR is < 1.3 , the study will be stopped , and the noninferiority of febuxostat relative to allopurinol with regard to CV risk will be declared . The CARES trial will define the CV safety profile of febuxostat and allopurinol in gout patients at high risk for CV events To compare the characteristics of female versus male gout patients and assess urate‐lowering efficacy and safety of febuxostat or allopurinol treatment in women with gout BACKGROUND Hyperuricemia is associated with reduced survival among patients with heart failure ( HF ) , but the effect of gout on HF outcomes is unknown . A recent r and omized trial suggested that allopurinol may reduce adverse outcomes among patients with hyperuricemia and HF . Our objective was to determine whether gout and allopurinol use are associated with HF outcomes . METHODS Time-matched , nested case-control analysis of a retrospective cohort of patients with HF who were 66 years or older using health care data bases in Quebec , Canada . The primary outcome measure was a composite measure of HF readmission and all-cause mortality . The secondary outcome measure was all-cause mortality . Rate ratios were calculated using conditional logistic regression and adjusted for known prognostic factors . RESULTS Of the 25,090 patients in this cohort , 14,327 experienced the primary outcome . Both a remote history of gout and an acute episode of gout ( within 60 days of the event date ) were associated with an increased risk of HF readmission or death ( adjusted rate ratio , 1.63 ; 95 % confidence interval , 1.48 - 1.80 ; P<.001 and 2.06 ; 1.39 - 3.06 ; P<.001 , respectively ) . Continuous allopurinol use ( > 30 days of continuous use ) was not associated with the primary outcome among the overall population with HF ( adjusted rate ratio , 1.02 ; 95 % confidence interval , 0.95 - 1.10 ; P=.55 ) but was associated with reduced HF readmissions or death ( 0.69 ; 0.60 - 0.79 ; P<.001 ) and all-cause mortality ( 0.74 ; 0.61 - 0.90 ; P<.001 ) among patients with a history of gout . CONCLUSIONS Patients with HF and a history of gout represent a high-risk population . Among such patients , the use of allopurinol is associated with improved outcomes BACKGROUND Hyperuricemia has been linked to cardiovascular and renal diseases , possibly through the generation of reactive oxygen species ( ROS ) and subsequent endothelial dysfunction . The enzymatic effect of xanthine oxidase is the production of ROS and uric acid . Studies have shown that inhibiting xanthine oxidase with allopurinol can reverse endothelial dysfunction . Furthermore , rat studies have shown that hyperuricemia-induced hypertension and vascular disease is at least partially reversed by the supplementation of the nitric oxide synthase ( NOS ) substrate , L-arginine . Therefore , we hypothesized that uric acid induces endothelial dysfunction by inhibiting nitric oxide production . METHODS Hyperuricemia was induced in male Sprague-Dawley rats with an uricase inhibitor , oxonic acid , by gavage ; control rats received vehicle . Allopurinol was placed in drinking water to block hyperuricemia . Rats were r and omly divided into four groups : ( 1 ) control , ( 2 ) allopurinol only , ( 3 ) oxonic acid only , and ( 4 ) oxonic acid + allopurinol . Rats were sacrificed at 1 and 7 days , and their serum analyzed for serum uric acid and nitrites/nitrates concentrations . The effect of uric acid on nitric oxide production was also determined in bovine aortic endothelial cells . RESULTS Oxonic acid induced mild hyperuricemia at both 1 and 7 days ( P < 0.05 ) . Allopurinol reversed the hyperuricemia at 7 days ( P < .001 ) . Serum nitrites and nitrates ( NO(X ) ) were reduced in hyperuricemic rats at both 1 and 7 days ( P < .001 ) . Allopurinol slightly reversed the decrease in NO(X ) at 1 day and completely at 7 days ( P < .001 ) . There was a direct linear correlation between serum uric acid and NO(X ) ( R(2)= 0.56 ) and a trend toward higher systolic blood pressure in hyperuricemic rats ( P= NS ) . Uric acid was also found to inhibit both basal and vascular endothelial growth factor (VEGF)-induced nitric oxide production in bovine aortic endothelial cells . CONCLUSION Hyperuricemic rats have a decrease in serum nitric oxide which is reversed by lowering uric acid levels . Soluble uric acid also impairs nitric oxide generation in cultured endothelial cells . Thus , hyperuricemia induces endothelial dysfunction ; this may provide insight into a pathogenic mechanism by which uric acid may induce hypertension and vascular disease OBJECTIVE Gout affects approximately 1 - 2 % of the American population . Current options for treating hyperuricemia in chronic gout are limited . The purpose of this study was to assess the safety and efficacy of febuxostat , a nonpurine selective inhibitor of xanthine oxidase , in establishing normal serum urate ( sUA ) concentrations in gout patients with hyperuricemia ( > or=8.0 mg/dl ) . METHODS We conducted a phase II , r and omized , double-blind , placebo-controlled trial in 153 patients ( ages 23 - 80 years ) . Subjects received febuxostat ( 40 mg , 80 mg , 120 mg ) or placebo once daily for 28 days and colchicine prophylaxis for 14 days prior to and 14 days after r and omization . The primary end point was the proportion of subjects with sUA levels < 6.0 mg/dl on day 28 . RESULTS Greater proportions of febuxostat-treated patients than placebo-treated patients achieved an sUA level < 6.0 mg/dl at each visit ( P < 0.001 for each comparison ) . The targeted sUA level was attained on day 28 in 0 % of those taking placebo and in 56 % of those taking 40 mg , 76 % taking 80 mg , and 94 % taking 120 mg of febuxostat . The mean sUA reduction from baseline to day 28 was 2 % in the placebo group and 37 % in the 40-mg , 44 % in the 80-mg , and 59 % in the 120-mg febuxostat groups . Gout flares occurred with similar frequency in the placebo ( 37 % ) and 40-mg febuxostat ( 35 % ) groups and with increased frequency in the higher dosage febuxostat groups ( 43 % taking 80 mg ; 55 % taking 120 mg ) . During colchicine prophylaxis , gout flares occurred less frequently ( 8 - 13 % ) . Incidences of treatment-related adverse events were similar in the febuxostat and placebo groups . CONCLUSION Treatment with febuxostat result ed in a significant reduction of sUA levels at all dosages . Febuxostat therapy was safe and well tolerated BACKGROUND The Losartan Intervention For Endpoint reduction in hypertension ( LIFE ) study demonstrated the superiority of a losartan-based regimen over atenolol-based regimen for reduction of cardiovascular ( CV ) morbidity and mortality . It has been suggested that the LIFE study results may be related to the effects of losartan on serum uric acid ( SUA ) . SUA has been proposed as an independent risk factor for CV morbidity and death . METHODS Cox regression analysis was used to assess relationship of SUA and treatment regimens with the LIFE primary composite outcome ( CV death , fatal or nonfatal myocardial infa rct ion , fatal or nonfatal stroke ) . RESULTS Baseline SUA was significantly associated with increased CV events [ hazard ratio ( HR ) 1.024 ( 95 % CI 1.017 - 1.032 ) per 10 micromol/L , P < 0.0001 ] in the entire study population . The association was significant in women [ HR = 1.025 ( 1.013 - 1.037 ) , P < 0.0001 ] , but not in men [ HR = 1.009 ( 0.998 - 1.019 ) , P= 0.108 ] . After adjustment for Framingham risk score ( FRS ) , SUA was no longer significant in the entire study population [ HR = 1.006 ( 0.998 - 1.014 ) , P= 0.122 ] or in men [ HR = 1.006 ( 0.995 - 1.017 ) , P= 0.291 ] , but was significant in women [ HR = 1.013 ( 1 - 1.025 ) , P= 0.0457 ] . The baseline-to-end-of- study increase in SUA ( st and ard deviation , SD ) was greater ( P < 0.0001 ) in atenolol-treated subjects ( 44.4 + /- 72.5 micromol/L ) than in losartan-treated subjects ( 17.0 + /- 69.8 micromol/L ) . SUA as a time-varying covariate was strongly associated with events ( P < 0.0001 ) in the entire population . The contribution of SUA to the treatment effect of losartan on the primary composite end point was 29 % ( 14%-107 % ) , P= 0.004 . The association between time-varying SUA and increased CV risk tended to be stronger in women ( P < 0.0001 ) than in men ( P= 0.0658 ) , although the gender- outcome interaction was not significant ( P= 0.079 ) . CONCLUSION The increase in SUA over 4.8 years in the LIFE study was attenuated by losartan compared with atenolol treatment , appearing to explain 29 % of the treatment effect on the primary composite end point . The association between SUA and events was stronger in women than in men with or without adjustment of FRS Objective . To determine longterm urate-lowering efficacy and clinical benefits and safety of therapy with febuxostat or allopurinol in subjects with gout . Methods . Subjects ( n = 1086 ) in this open-label extension study were assigned to fixed-dose daily urate-lowering treatment ( ULT ) with febuxostat ( 80 mg or 120 mg ) or allopurinol ( 300 mg ) . ULT reassignment was permitted during months 1 to 6 to achieve serum urate ( SUA ) concentrations between 3.0 and < 6.0 mg/dl . Flares requiring treatment , tophus size , safety , and SUA levels were monitored during up to 40 months of ULT maintenance . Results . After 1 month initial treatment , > 80 % of subjects receiving either febuxostat dose , but only 46 % of subjects receiving allopurinol , achieved SUA < 6.0 mg/dl . After ULT reassignment , > 80 % of all remaining subjects maintained the primary efficacy endpoint of SUA < 6.0 mg/dl at each visit . More subjects initially r and omized to allopurinol required ULT reassignment to achieve SUA < 6.0 mg/dl compared with subjects receiving febuxostat . Maintenance of SUA < 6.0 mg/dl result ed in progressive reduction to nearly 0 in proportion of subjects requiring gout flare treatment . Baseline tophus resolution was achieved by 46 % , 36 % , and 29 % of subjects maintained on febuxostat 80 mg , febuxostat 120 mg , and allopurinol , respectively . Overall adverse event rates ( including cardiovascular adverse event rates ) , adjusted for 10-fold greater febuxostat than allopurinol exposure , did not differ significantly among treatment groups . Conclusion . Durable maintenance of goal range SUA level with either dose of febuxostat or in smaller numbers of subjects with allopurinol result ed in near elimination of gout flares and improved tophus status over time . Registered as NCT00175019 OBJECTIVE Streamlining the initiation of allopurinol could result in a cost benefit for a common medical problem and obviate the perception that no treatment is required once acute attacks have resolved . Our objective was to test the hypothesis that there is no difference in patient daily pain or subsequent attacks with early versus delayed initiation of allopurinol for an acute gout attack . METHODS A total of 57 men with crystal-proven gout were r and omized to allopurinol 300 mg daily or matching placebo for 10 days . All subjects received indomethacin 50 mg 3 times per day for 10 days , a prophylactic dose of colchicine 0.6 mg 2 times per day for 90 days , and open-label allopurinol starting at day 11 . Primary outcome measures were pain on visual analogue scale ( VAS ) for the primary joint on days 1 to 10 and self-reported flares in any joint through day 30 . RESULTS On the basis of 51 evaluable subjects ( allopurinol in 26 , placebo in 25 ) , mean daily VAS pain scores did not differ significantly between study groups at any point between days 1 and 10 . Initial VAS pain scores for allopurinol and placebo arms were 6.72 versus 6.28 ( P=.37 ) , declining to 0.18 versus 0.27 ( P=.54 ) at day 10 , with neither group consistently having more daily pain . Subsequent flares occurred in 2 subjects taking allopurinol and 3 subjects taking placebo ( P=.60 ) . Although urate levels decreased rapidly in the allopurinol group ( from 7.8 mg/dL at baseline to 5.9 mg/dL at day 3 ) , sedimentation rates and C-reactive protein levels did not differ between groups at any point . CONCLUSIONS Allopurinol initiation during an acute gout attack caused no significant difference in daily pain , recurrent flares , or inflammatory markers OBJECTIVE To compare the urate-lowering efficacy and safety of febuxostat , allopurinol , and placebo in a large group of subjects with hyperuricemia and gout , including persons with impaired renal function . METHODS Subjects ( n = 1,072 ) with hyperuricemia ( serum urate level > or = 8.0 mg/dl ) and gout with normal or impaired ( serum creatinine level > 1.5 to < or = 2.0 mg/dl ) renal function were r and omized to receive once-daily febuxostat ( 80 mg , 120 mg , or 240 mg ) , allopurinol ( 300 or 100 mg , based on renal function ) , or placebo for 28 weeks . RESULTS Significantly ( P < or = 0.05 ) higher percentages of subjects treated with febuxostat 80 mg ( 48 % ) , 120 mg ( 65 % ) , and 240 mg ( 69 % ) attained the primary end point of last 3 monthly serum urate levels < 6.0 mg/dl compared with allopurinol ( 22 % ) and placebo ( 0 % ) . A significantly ( P < 0.05 ) higher percentage of subjects with impaired renal function treated with febuxostat 80 mg ( 4 [ 44 % ] of 9 ) , 120 mg ( 5 [ 45 % ] of 11 ) , and 240 mg ( 3 [ 60 % ] of 5 ) achieved the primary end point compared with those treated with 100 mg of allopurinol ( 0 [ 0 % ] of 10 ) . Proportions of subjects experiencing any adverse event or serious adverse event were similar across groups , although diarrhea and dizziness were more frequent in the febuxostat 240 mg group . The primary reasons for withdrawal were similar across groups except for gout flares , which were more frequent with febuxostat than with allopurinol . CONCLUSION At all doses studied , febuxostat more effectively lowered and maintained serum urate levels < 6.0 mg/dl than did allopurinol ( 300 or 100 mg ) or placebo in subjects with hyperuricemia and gout , including those with mild to moderately impaired renal function OBJECTIVES The aim of this study was to evaluate the effect of high-dose allopurinol on vascular oxidative stress ( OS ) and endothelial function in subjects with stable coronary artery disease ( CAD ) . BACKGROUND Allopurinol , a xanthine oxidase inhibitor , prolongs the time to chest pain during exercise in angina . We sought to ascertain whether allopurinol also improves endothelial dysfunction in optimally treated CAD patients , because such an effect might be of value to reduce future cardiovascular mortality . The mechanism of the anti-ischemic effect of allopurinol could be related to its reducing xanthine oxidase-induced OS , and our second aim was to see whether allopurinol really does reduce vascular tissue OS in CAD patients . METHODS A r and omized , double-blind , placebo-controlled , crossover study was conducted in 80 patients with CAD , comparing allopurinol ( 600 mg/day ) with placebo . Endothelial function was assessed by forearm venous occlusion plethysmography , flow-mediated dilation , and pulse wave analysis . Vascular OS was assessed by intra-arterial co-infusion of vitamin C and acetylcholine . RESULTS Compared with placebo , allopurinol significantly improved endothelium-dependent vasodilation , by both forearm venous occlusion plethysmography ( 93 ± 67 % vs. 145 ± 106 % , p = 0.006 ) and flow-mediated dilation ( 4.2 ± 1.8 % vs. 5.4 ± 1.7 % , p < 0.001 ) . Vascular oxidative stress was completely abolished by allopurinol . Central augmentation index improved significantly with allopurinol ( 2.6 ± 7.0 % , p < 0.001 ) but not with placebo . CONCLUSIONS Our study demonstrates that , in optimally treated CAD patients , high-dose allopurinol profoundly reduces vascular tissue OS and improves 3 different measures of vascular/endothelial dysfunction . The former effect on OS might underpin the anti-ischemic effect of allopurinol in CAD . Both effects ( on OS and endothelial dysfunction ) increase the likelihood that high-dose allopurinol might reduce future cardiovascular mortality in CAD , over and above existing optimum therapy . ( Exploring the therapeutic potential of xanthine oxidase inhibitor allopurinol in angina ; IS RCT N15253766 ) BACKGROUND Allopurinol has been widely used for the treatment of hyperuricemia , however , it may be associated with various adverse effects . Febuxostat has been identified as a potentially safe and efficacious alternative . OBJECTIVES Febuxostat was administered to patients with hyperuricemia including gout in Japan to compare its efficacy and safety with those of allopurinol . METHODS The starting dose of febuxostat and allopurinol was 10 and 100 mg/d , respectively , and was increased to the fixed maintenance dose of 40 or 60 mg/d for febuxostat and 300 mg/d for allopurinol for 16 weeks . RESULTS : The percent change in the serum uric acid level at 16 weeks compared with the baseline serum uric acid level was -42.96 % ± 13.33 % and -52.47 % ± 9.79 % for the febuxostat 40- and 60-mg/d groups , respectively , and -36.55 % ± 18.59 % for the allopurinol group , indicating that the hypouricemic effects of febuxostat increased in a dose-dependent manner and equaled to or surpassed those of allopurinol ( P = 0.0239 , 2- sample t test ) . The percentage of patients with serum uric acid levels of 6.0 mg/dL or less at 16 weeks was 88.9 % and 100 % for the febuxostat 40- and 60-mg/d groups , respectively , and 68.8 % for the allopurinol group , showing higher achievements for the febuxostat groups compared with the allopurinol group . All adverse drug reactions were mild to moderate in severity , and there were no severe symptoms or reactions leading to drug discontinuation . CONCLUSIONS These results suggest that febuxostat is safe at doses of 40 and 60 mg/d and has equal or greater efficacy than 300 mg/d allopurinol Objective . Hyperuricemia of gout can arise due to either overproduction or underexcretion of uric acid . Not all available urate-lowering therapies are equally effective and safe for use in patients with renal disease . The objective of this post-hoc analysis was to determine the effectiveness of the xanthine oxidase inhibitor febuxostat in reducing serum urate ( sUA ) levels in gouty patients who were either overproducers or underexcretors . Methods . Gouty subjects 18 to 85 years of age with sUA ≥ 8.0 mg/dl at baseline were enrolled in a Phase 2 , 28-day , multicenter , r and omized , double-blind , placebo-controlled trial and r and omized to receive febuxostat 40 mg , 80 mg , or 120 mg daily , or placebo . The primary efficacy endpoint was the proportion of subjects with sUA < 6.0 mg/dl at Day 28 . Secondary efficacy endpoints included percentage reductions in sUA and urinary uric acid ( uUA ) from baseline to Day 28 . Results . Of the 153 subjects , 118 ( 77 % ) were underexcretors ( uUA ≤ 800 mg/24 h ) and 32 ( 21 % ) were overproducers ( uUA > 800 mg/24 h ) ; baseline uUA data were missing for 3 subjects . Treatment with febuxostat led to the majority of subjects achieving sUA < 6.0 mg/dl at Day 28 . Treatment with any dose of febuxostat led to significantly greater percentage reductions in uUA than that observed in the placebo group , for both underexcretors and overproducers . Conclusion . Febuxostat is a highly efficacious urate-lowering therapy in patients with gout regardless of overproduction or underexcretion status |
992 | 29,439,949 | Conclusion This review suggests that patients with FAIS may demonstrate hip biomechanical impairments during walking and squatting , with minimal literature available to comment on other tasks .
Clinical relevance The information presented in the review provides insight into the biomechanical differences associated with FAIS ; however , the between-group differences were small to moderate . | Objective ( 1 ) Identify differences in hip and pelvic biomechanics in patients with femoroacetabular impingement syndrome ( FAIS ) compared with controls during everyday activities ( eg , walking , squatting ) ; and ( 2 ) evaluate the effects of interventions on hip and pelvic biomechanics during everyday activities . | BACKGROUND Femoroacetabular impingement is a common hip pathology result ing in pain and impaired physical function . However , very little is known about gait differences between those with and without femoroacetabular impingement . Thus , the purpose of this study was to compare three-dimensional gait kinematics and kinetics between those with femoroacetabular impingement and a healthy , pain-free control group . METHODS Three-dimensional gait analysis was conducted on 30 individuals with symptomatic femoroacetabular impingement scheduled for surgery and 30 pain-free controls . Spatiotemporal and peak hip kinematics and joint moments were compared between the two groups . Ensemble averages were also calculated for kinematic and kinetic profiles across the gait cycle in all three planes of movement for visual inspection . FINDINGS Participants with femoroacetabular impingement walked slower and with significantly smaller cadences than those in the control group . Kinematically , the impingement group exhibited significantly less peak hip extension , adduction and internal rotation during stance , with effect sizes ranging from 0.48 ( adduction ) to 1.00 ( internal rotation ) . Finally , those with FAI exhibited significantly less peak external hip flexion ( effect size=0.52 ) and external rotation ( effect size=0.85 ) moments than the control group . INTERPRETATION Individuals with femoroacetabular impingement exhibit differences in gait kinematics in all planes of motion compared to those with without FAI . These findings support the need for focused neuromuscular reconditioning across all movement directions in this patient group OBJECTIVE To determine if compensatory actions take place at the pelvis and other joints of the affected lower limb in subjects who were in an early stage of hip osteoarthritis ( OA ) . DESIGN Nonr and omized , case-control study . SETTING A gait laboratory . PARTICIPANTS Seventeen patients with OA of the hip ( clinical group ) matched with 17 healthy elderly subjects ( non clinical group ) . INTERVENTIONS Video data obtained while subjects walked a 10-meter walkway twice and stepped across a forceplate . MAIN OUTCOME MEASURES Four phasic and temporal gait parameters ( walking speed , stance phase relative duration , stride length , cadence ) 10 pelvic ( pelvic tilt , obliquity , rotation at push-off maximum range of motion for all 3 ) and hip ( 3 hip angles at push-off , maximum hip flexion ) kinematic parameters , 3 hip moments , and twenty-seven 3-dimensional peak muscle powers ( labeled by joint , peak power , plane ) developed in the lower limb joints during the gait cycle . RESULTS Subjects in the clinical group were characterized by a 12.4 % slower walking speed . The pelvis was more upwardly tilted ( 2.5 times ) at push-off in the clinical group than in the non clinical group . Obliquity , measured in the frontal plane , revealed that the pelvis dropped more ( 2.4 times ) on the unsupported limb of the clinical group at push-off . In the sagittal plane , subjects in the clinical group absorbed less energy in their second hip peak power for decelerating the thigh extension and generated less hip pull ( third hip peak power ) than the non clinical group by 34 % and 29 % , respectively . In the sagittal plane , the clinical group had 57 % lower second knee peak power to straighten the joint shortly after heel strike , and 43 % less knee absorption ( third peak power ) at push-off . During the push-off phase , the clinical group developed more than twice their third peak knee power in the frontal plane and 5 times more their third peak knee power in the transversal plane than the peak knee power of the non clinical group in an attempt to control knee adduction and to facilitate body-weight transfer by an internal rotation . At the end of the swing phase , the fourth peak power in the sagittal plane showed the absorption power required to decelerate the leg ; it was reduced by 35 % in the clinical group , representing a strategy to increase walking speed by lengthening the stride length . CONCLUSIONS Even at an early stage of hip OA , joint degeneration was compensated by an increase in pelvis motion and muscle power generation or absorption modifications in other lower limb joints Objective To determine the association between cam impingement , which is hip incongruity by a non-spherical femoral head and development of osteoarthritis . Methods A nationwide prospect i ve cohort study of 1002 early symptomatic osteoarthritis patients ( CHECK ) , of which st and ardised anteroposterior pelvic radiographs were obtained at baseline and at 2 and 5 years follow-up . Asphericity of the femoral head was measured by the α angle . Clinical ly , decreased internal hip rotation ( ≤20 ° ) is suggestive of cam impingement . The strength of association between those parameters at baseline and development of incident osteoarthritis ( K&L grade 2 ) or end-stage osteoarthritis ( K&L grade s 3 , 4 , or total hip replacement ) within 5 years was expressed in OR using generalised estimating equations . Results At baseline , 76 % of the included hips had no radiographic signs of osteoarthritis and 24 % doubtful osteoarthritis . Within 5 years , 2.76 % developed end-stage osteoarthritis . A moderate ( α angle > 60 ° ) and severe ( α angle > 83 ° ) cam-type deformity result ed in adjusted OR of 3.67 ( 95 % CI 1.68 to 8.01 ) and 9.66 ( 95 % CI 4.72 to 19.78 ) , respectively , for end-stage osteoarthritis . The combination of severe cam-type deformity and decreased internal rotation at baseline result ed in an even more pronounced adjusted OR , and in a positive predictive value of 52.6 % for end-stage osteoarthritis . For incident osteoarthritis , only a moderate cam-type deformity was predictive OR=2.42 ( 95 % CI 1.15 to 5.06 ) . Conclusions Individuals with both severe cam-type deformity and reduced internal rotation are strongly predisposed to fast progression to end-stage osteoarthritis . As cam impingement might be a modifiable risk factor , early recognition of this condition is important Gluteus minimus is believed to consist of two structurally and functionally unique segments ( anterior and posterior ) ; however there is a lack of electromyography ( EMG ) research that attempts to verify current theoretical knowledge of this muscle . The purpose of this study was therefore to evaluate the function of gluteus minimus during gait , and to determine whether anterior and posterior segments are functionally independent . Bipolar fine wire intramuscular EMG electrodes were inserted into anterior and posterior gluteus minimus segments of fifteen healthy volunteers ( 9 males ) according to previously verified guidelines . Participants completed a series of four walking trials , followed by maximum voluntary isometric contractions in five different positions . Temporal and amplitude variables for each segment were compared across the gait cycle with independent t-tests . The relative contribution of each segment to the maximum resisted trials was compared with Mann-Whitney U tests ( α = 0.05 ) . Anterior and posterior segments were contracting at different relative intensities for three of the five maximum resisted trials ( effect size = 0.39 to 0.62 , P < 0.037 ) . The posterior segment was larger in EMG amplitude ( peak and average ) during the first 20 % of the gait cycle ( effect size = 0.96 to 1.03 , P < 0.02 ) , while the anterior segment peaked later in the stance phase ( effect size = 0.83 , P = 0.034 ) . Gluteus minimus is therefore composed of functionally independent segments . These results build on contemporary theoretical knowledge and may signify hip stabilising roles for each segment across different phases of the gait cycle OBJECTIVE To investigate the differences in hip movement patterns during different daily and athletic activities in persons with cam-type femoroacetabular impingement ( FAI ) with and without cartilage lesions compared with control subjects in a preliminary study . DESIGN Controlled laboratory study using a cross-sectional design . SETTING Research institution with a tertiary care medical center . PARTICIPANTS Fifteen subjects [ M : F , 13:2 ; age , 31.6 ± 9.7 years ( range , 22 - 52 years ) ; body mass index , 24.9 ± 4.6 ( range , 18.8 - 38.4 ) ; FAI : control , 7:8 ] . METHODS All subjects had 3-Tesla magnetic resonance imaging of the hip and also underwent 3-dimensional motion capture during walking , deep-squat , and drop-l and ing tasks . Experienced radiologists grade d cartilage lesions on clinical magnetic resonance images . OUTCOMES Peak kinematic and kinetic variables were compared between subjects who did and did not have FAI , and subjects who had FAI and cartilage lesions were compared with subjects who did not have cartilage lesions . RESULTS Subjects who had FAI demonstrated no significant differences for walking or drop l and ing compared with control subjects . However , during the deep-squat task , subjects with FAI adducted more and had a greater internal rotation moment . Subjects who had cartilage lesions in the presence of a cam lesion demonstrated ( 1 ) no difference for walking ; ( 2 ) greater adduction , greater internal rotation moment , and lower transverse plane range of motion during the deep-squat task ; and ( 3 ) greater adduction and lower internal rotation during the drop-l and ing task compared with subjects who did not have cartilage lesions . CONCLUSIONS We observed differences in movement patterns between subjects who had FAI compared with control subjects . However , the differences were more pronounced between subjects with FAI who had cartilage lesions compared with subjects who did not have cartilage lesions . These findings highlight the importance of underst and ing the complex interplay between bony morphologic features , cartilage lesions , and movement patterns in persons with cam-type FAI |
993 | 29,028,651 | Results Compared with open vein harvest , it is reasonable to perform endoscopic vein harvest of saphenous vein to reduce wound-related complications , postoperative length of stay , and outpatient wound management re sources and to increase patient satisfaction ( class I , level A ) .
Based on the quality of the conduit and major adverse cardiac events as well as 6-month angiographic patency , endoscopic vein harvest was noninferior to open harvest .
Conclusions Based on the consensus statements , the consensus panel recommends ( class I , level B ) that endoscopic saphenous vein and radial artery harvesting should be the st and ard of care for patients who require these conduits for coronary revascularization | Objective The purpose of this consensus conference was to develop and up date evidence -informed consensus statements and recommendations on harvesting saphenous vein and radial artery via an open as compared with endoscopic technique by systematic ally review ing and performing a meta- analysis of r and omized and nonr and omized clinical trials . | Objective : Interleukin-10 ( IL-10 ) is an anti-inflammatory cytokine that suppresses lymphocyte functions , regulates production of proinflammatory cytokines , and suppresses nitric oxide production by activated macrophages . We examined IL-10 expression and its value as a surrogate index for nitric oxide ( NO ) production in endothelial cultures obtained from saphenous vein sample s. Methods : Using 2 different techniques ( the open and endoscopic ) , we harvested sample s of human saphenous veins from 90 r and omly selected patients undergoing coronary artery bypass surgery ( CABG ) . Endothelial cells collected from the vein sample s retrieved through both techniques were cultured for 72 hours . Using a solid phase enzyme linked-immuno-sorbent assay ( ELISA ) , we analyzed pre- and postoperative sera , in addition to the supernatants from the cultures , for IL-10 . Results : Mean preoperative levels of IL-10 ( 0.09 ± 0.04 pg/mL ) did not differ significantly from that for postoperative sera ( 0.14 ± 0.17 pg/mL ) ( P = 0.54 ) . Mean IL-10 levels for endothelial cell culture supernatants did not differ significantly between the endoscopic ( 0.32 ± 0.39 pg/mL ) and the open method ( 0.46 ± 0.80 pg/mL ) ( P = 0.30 ) . Conclusion : Our findings indicate that endoscopic and open saphenectomies are technically comparable with respect to their effects on IL-10 release during saphenous vein harvesting for CABG . We recommend the endoscopic method for its low morbidity and earlier hospital discharge BACKGROUND Levels of the cytokines Interleukin-1 ( IL-1 ) , IL-2 , and IL-10 are sensitive to the traumatic effect of saphenous vein harvesting . Their levels are compared between the endoscopic and traditional open techniques of harvesting . METHODS Sample s of human saphenous veins were harvested from 90 r and omly selected patients undergoing coronary artery bypass surgery ( CABG ) , using the open or endoscopic techniques . Endothelial cells collected from the vein sample s retrieved through both techniques were cultured for 72 hours . Pre and postoperative sera , in addition to the supernatants from the cultures , were analyzed for IL-1 , IL-2 , and IL-10 using ELISA . RESULTS Mean preoperative concentrations of IL-1 , Il-2 , and IL-10 were 0.11+/- 0.04 , 0.09 + /- 0.04 , and 0.09 + /- 0.04 pg/ml , respectively . Corresponding values for postoperative sera were 0.13 + /- 0.08 , 0.12 + /- 0.10 , 0.14 + /- 0.17 pg/ml , respectively . The differences between pre and postoperative means for each cytokine were not statistically significant ( p = 0.13 , 0.18 , 0.05 , respectively ) . Mean IL-1 , IL-2 , and IL-10 concentrations for endothelial cell culture supernatants did not differ significantly between the endoscopic ( 0.17 + /- 0.11 , 0.11 + /- 0.05 , and 0.32 + /- 0.40 pg/ml , respectively ) and the open method ( 0.19 + /- 0.16 , 0.11 + /- 0.05 , and 0.46 + /- 0.80 pg/ml , respectively ) ( p = 0.48 , 0.81 , 0.30 , respectively ) . CONCLUSION Since endoscopic and open saphenectomies are technically comparable with respect to their effects on IL-1 , Il-2 , and IL-10 levels , we recommend the endoscopic method for its lower morbidity and the potential for earlier hospital discharge OBJECTIVE Preparation of the great saphenous vein for coronary artery bypass grafts is usually performed through one or many cutaneous incisions . A technique of endoscopic harvesting is now available . An aim of the study was to compare both methods , prospect ively . METHODS Sixty coronary artery bypass grafting patients were r and omly assigned to two groups according to saphenous vein harvesting technique : 30 patients to group 1 -- open harvesting technique ( OHT ) and 30 patients to group 2 -- endoscopic harvesting technique ( EHT ) . The results were assessed on the basis of ( 1 ) clinical outcome ( hematomas , inflammations ) , ( 2 ) length of the cutaneous incisions compared to length of the segment of vein harvested , ( 3 ) time of harvesting , ( 4 ) postoperative pain . RESULTS Both groups were comparable in terms of : age , sex , diabetes , peripheral artery disease , site of harvesting , number of anastomoses , and length of the vein harvested . Both the length of the cutaneous incisions and the postoperative pain were decreased in the EHT group . Harvesting time was increased in the OHT group . CONCLUSIONS Endoscopic saphenous vein harvesting allows improved aesthetic aspect , less postoperative discomfort , with an increased time in harvesting in the beginning BACKGROUND Minimally invasive techniques to harvest the saphenous vein for coronary artery bypass grafting continue to improve and evolve . Smaller cutaneous incisions have been shown to decrease postoperative discomfort and improve healing . We describe a technique involving carbon dioxide insufflation and endoscopic dissection to allow easier and atraumatic dissection . METHODS The VasoView endoscope system ( Origin Medsystems , Inc ) was used to harvest the saphenous vein for coronary artery bypass grafting in 27 patients . This group was compared with 24 patients having traditional saphenous vein harvesting . Wounds were examined for complications daily . Pain and postoperative mobility were quantified independently by physical therapists . RESULTS Comparison of patients in the two groups revealed greater edema in the legs with traditional harvesting . Patients with endoscopic removal also had less pain and increased mobility postoperatively . On average , minimally invasive harvesting allowed patients to ambulate to a predischarge goal of 300 ft 2 days earlier . CONCLUSIONS Minimally invasive harvesting of the saphenous vein by insufflation techniques is safe , effective , and atraumatic to the conduit . Discomfort is minimized , promoting earlier and improved ambulation Background In coronary artery bypass grafting surgery , arterial conduits are preferred because of more favourable long-term patency and outcome . Anyway the greater saphenous vein continues to be the most commonly used bypass conduit . Minimally invasive endoscopic saphenous vein harvesting is increasingly being investigated in order to reduce the morbidity associated with conventional open vein harvesting , includes postoperative leg wound complications , pain and patient satisfaction . However , to date the short and the long-term benefits of the endoscopic technique remain controversial . This study provides an interesting opportunity to address this gap in the literature . Methods / Design Endoscopic Saphenous harvesting with an Open CO2System trial includes two parallel vein harvesting arms in coronary artery bypass grafting surgery . It is an interventional , single centre , prospect i ve , r and omized , safety/efficacy , cost/effectiveness study , in adult patients with elective planned and first isolated coronary artery disease . A simple size of 100 patients for each arm will be required to achieve 80 % statistical power , with a significant level of 0.05 , for detecting most of the formulated hypotheses . A six-weeks leg wound complications rate was assumed to be 20 % in the conventional arm and less of 4 % in the endoscopic arm . Previously quoted studies suggest a first-year vein-graft failure rate of about 20 % with an annual occlusion rate of 1 % to 2 % in the first six years , with practically no difference between the endoscopic and conventional approaches . Similarly , the results on event-free survival rates for the two arms have barely a 2 - 3 % gap . Assuming a 10 % drop-out rate and a 5 % cross-over rate , the goal is to enrol 230 patients from a single Italian cardiac surgery centre . Discussion The goal of this prospect i ve r and omized trial is to compare and to test improvement in wound healing , quality of life , safety/efficacy , cost-effectiveness , short and long-term outcomes and vein-graft patency after endoscopic open CO2 harvesting system versus conventional vein harvesting . The expected results are of high clinical relevance and will show the safety/efficacy or non-inferiority of one treatment approach in terms of vein harvesting for coronary artery bypass grafting surgery . Trial registration www . clinical Trials.gov NCT01121341 UNLABELLED Conventional conduit harvesting used for coronary artery bypass graft for many decades but there has been some wound complication problem . Endoscopic conduit harvesting is a minimal invasive surgery for reduced wounds complication . The authors aim ed to compare the result between two techniques . MATERIAL AND METHOD Prospect i ve enroll of 100 patients for elective coronary artery bypass graft surgery . Divided in 2 groups . The first groups was a convention conduit harvesting ( C groups ) and the second groups was endoscopic conduit harvesting ( E groups ) . The endoscopic conduit harvesting performed using the Maquet Vasoview system under CO2 inflation assisted . RESULTS Endoscopic conduit harvesting was successful 94 % . Harvest time C group 32.4 mins E group 48.9 mins , ET CO2 C group 40.3 , E group 50.9 , Wounds infection C group 6 % E group O , wounds echymosis C group 6 % E group 44 % . CONCLUSION Endoscopic conduit harvesting showed better results with conventional conduit harvesting in wounds with serious complications but they need more harvest time and risk of CO2 embolism . However a long term graft patency needs more investigation Classical excision of saphenous vein grafts requires a continuous incision on the leg or the thigh or both . To minimise the trauma due to this method , an endoscopic method has been recently developed . The aim of this paper was to assess the benefits of this new method compared with the classical technique . One hundred and twenty patients requiring aorto-coronary grafts were included in this prospect i ve study and divided into two groups according to the method of saphenous vein harvesting . Group A comprised 60 patients who underwent the classical method os saphenous vein harvesting and Group B 60 patients who benefited from the endoscopic method . No difference was observed between the two groups with respect to mean age , sex ratio , history of diabetes and obliterative arterial disease of the lower limbs . Parsonnet index number of bypass grafts and length of vein excised . The length of the skin wound in group A was 30.8 + /- 8.5 cm compared with only 4.1 + /- 1 cm in Group B ( p = 0.006 ) but the harvesting time was longer by endoscopy ( 55.7 + /- 23.7 minutes : 72.5 + /- 22.6 minutes for the first 10 patients , 48.5 + /- 24.7 minutes for the last 50 patients ) compared with the classical technique ( 39.8 + /- 6.6 minutes : p = 0.001 ) . Moreover , patients who underwent videosurgery had less operative pain ( 8 % versus 15 % ) ( p = 0.001 ) . The number of infectious complications was slightly lower in Group B ( 3.3 % , 2/60 , versus 10 % , 6/60 ) , ( NS ) . The authors conclude that harvesting of the saphenous vein by videosurgery reduces postoperative pain and gives a more aesthetic result but with a slightly longer operative time at the beginning of the experience Background Saphenous vein remains the most common conduit for coronary artery bypass grafting with increasing uptake of minimally invasive harvesting techniques . While Endoscopic Vein Harvest ( EVH ) has been demonstrated to improve early morbidity compared to Open Vein Harvest ( OVH ) , recent literature suggests that this may be at the expense of graft patency at one year and survival at three years . Methods We undertook a retrospective single-centre , single-surgeon , case-control study of EVH ( n = 89 ) and OVH ( n = 182 ) . The primary endpoint was death with secondary endpoints including acute coronary syndrome , revascularisation or other major adverse cardiac events . Freedom from angina , wound complications and self-rated health status were also assessed . Where repeat angiography had been performed , this was review ed . Results Both groups were well matched demographically and for peri-operative characteristics . All cause mortality was 2/89 ( 2 % ) and 11/182 ( 6 % ) in the EVH and OVH groups respectively . This was shown by Cox Log-Rank analysis to be non-significant ( p = 0.65 ) , even if adjusting for inpatient mortality ( p = 0.74 ) . There was no difference in the rates of freedom from angina ( p = 1.00 ) , re-admission ( p = 0.78 ) or need for further anti-anginals ( p = 1.00 ) . There was a significant reduction in the incidence of leg wound infections and complications in the endoscopic group ( EVH : 7 % ; OVH : 28 % ; p = 0.0008 ) and the skew of high patient self-rated health scores in the EVH group ( 61 % compared to 52 % in the open group ) approached statistical significance ( p = 0.06 ) . Conclusions While aware of the limitations of this small retrospective study , we are heartened by the preliminary results and consider our data to be justification for continuing to provide patients the opportunity to have minimally invasive conduit harvest in our centre . More robust evidence is still required to eluci date the implication s of endoscopic techniques on conduit patency and patient outcome , but until the results of a large , prospect i ve and r and omised trial are available , we believe we can confidently offer our patients the option and benefits of EVH OBJECTIVE Conventional open saphenous vein harvest ( OVH ) for coronary artery bypass graft surgery is often associated with significant pain and morbidity . This study aims to determine whether endoscopic saphenous vein harvest ( EVH ) reduces leg wound morbidity and improves patient satisfaction as compared to OVH in Asian population . METHODS Between March 2005 and June 2006 , 120 patients who underwent isolated CABG were prospect ively r and omized into EVH ( n = 60 ) and OVH ( n = 60 ) groups . VirtuoSaph ( Terumo Cardiovascular Corp. , Ann Arbor , MI , USA ) harvesting system was used for EVH . We analyzed leg wound complications ( ASEPSIS score ) , postoperative pain , satisfaction , and clinical outcomes . Fisher 's exact test and Mann-Whitney U test were used for categorical and continuous variables analysis respectively . RESULTS Six patients in the EVH group required conversion to open technique . Both groups had matched demographic characteristics and risk factors . Mean numbers of grafts performed were 3.2 + /- 0.6 ( EVH n = 54 ) and 3.0 + /- 0.7 ( OVH n = 60 ) ( p = 0.03 ) . ASEPSIS scores at postoperation days three , seven , and 21 were significantly lower in the EVH group than the OVH group ( p = 0.02 , p = 0.002 and p = 0.01 , respectively ) . Wound pain scores at postoperative days three , seven , and 21 were significantly lower in the EVH group ( p = 0.000 , p = 0.001 and p = 0.000 respectively ) . Wound numbness was found in 5.7 % of the EVH group and 33.3 % of the OVH group patients ( p = 0.01 ) . [ Six patients required conversion to open technique . ] There was one hospital mortality ( OVH group ) and major postoperative complications were not significantly different between the groups . CONCLUSION EVH system is a safe and effective alternative to OVH with better wound healing , reduced postoperative pain , and wound numbness . However , the higher conversion rate to OVH in Asian patients requires further evaluation BACKGROUND The purpose of this study was to determine whether or not endoscopic vein harvest is a reliable , beneficial , and cost-effective method for saphenous vein harvest in coronary bypass surgery ( CABG ) . METHODS A total of 100 patients having primary CABG were prospect ively r and omized to either endoscopic ( EVH ; n = 47 ) or open saphenous vein harvest ( OVH ; n = 50 ) . Three patients in the EVH group required both techniques and were excluded from analysis . RESULTS The groups did not differ in preoperative characteristics , including : age , gender , left ventricular function , height , weight , percent over ideal body weight , incidence of diabetes , peripheral vascular disease , or preoperative laboratory values ( creatinine , albumin , or hematocrit ) . The EVH group had longer vein harvest and preparation times than the OVH group , while the incision length was significantly shorter . There was no difference between groups in mortality , perioperative myocardial infa rct ion , intensive care unit or postoperative length of stay , blood product utilization , or discharge laboratory measures . There was more drainage noted from leg incisions at hospital discharge in the OVH ( 34 % ) versus EVH group ( 8 % ; p = 0.001 ) , but more ecchymosis in the EVH group . Although there was a trend towards reduced leg incision pain in the EVH group , there was no statistically significant difference in pain or in the quality of life measure at any point in time . There was no difference between groups in readmission to hospital , administration of antibiotics , or incidence of leg infection . While mean hospital charges for the EVH group were approximately $ 1,500 greater than for OVH , this difference did not reach statistical significance . CONCLUSIONS EVH is a safe , reliable , and cost-neutral method for saphenous vein harvest . The best indication for EVH may be in patients who are at increased risk for wound infection and in those for whom cosmesis is a major concern Objective The aims of the study were to determine whether endoscopic harvesting of the radial artery ( RA ) reduces morbidity due to pain , infection , and disability with improvement in satisfaction and cosmesis compared to the conventional technique and ( 2 ) to compare the 6-month angiographic patency of the RA harvested conventionally and endoscopically . Methods In a prospect i ve r and omized study , 119 patients undergoing coronary artery bypass grafting using the RA were r and omized to have RA harvested either conventionally ( n = 59 ) or endoscopically ( n = 60 ) . Results Radial artery harvest time ( open wound time ) was significantly reduced in the endoscopic group ( 36.5 ± 9.4 vs 57.7 ± 9.4 minutes , P < 0.001 ) . Only one patient developed wound infection ( 1.6 % ) in the endoscopic group compared with six patients ( 10.2 % ) , P = 0.061 , in the conventional group . Although this was not statistically significant , clinical ly this was relevant in terms of reduction in postoperative morbidity . Postoperative pain in the arm incision was significantly lower in the endoscopic group at postoperative day 2 ( P < 0.001 ) and at discharge ( P < 0.001 ) and similar to the conventional open group at 6 weeks ’ follow-up ( P = 0.103 ) . Overall patient satisfaction and cosmesis were significantly better in the endoscopic group at postoperative day 2 ( P < 0.001 ) , at discharge ( P < 0.001 ) , and at 6 weeks ’ follow-up ( P < 0.001 ) . There was no difference in the arm disability postoperatively ( P = 0.505 ) between the two groups . Six-month angiographic assessment of 23 patients ( 12 endoscopic and 11 open ) revealed no difference in the patency rate ( 10/12 in endoscopic and 9/11 in open group ) . Conclusions Endoscopic RA harvesting reduced the incidence of postoperative wound infection and wound pain and improved patient satisfaction and cosmesis compared with conventional harvesting technique . There was no difference in the 6-month angiographic patency of the RA harvested conventionally and endoscopically OBJECTIVES The use of an open vein harvesting ( OVH ) technique for saphenous vein harvesting ( SVH ) is associated with wound complications and delayed patient mobilization . This has led to the development of minimally invasive vein harvesting ( MIVH ) techniques , such as st and ard bridging and endoscopic SVH ( EVH ) . This r and omized trial was established to assess immediate clinical outcome and patient satisfaction in our centre . METHODS A total of 150 consecutive patients were prospect ively r and omized into three groups . Group 1 consisted of 50 patients who underwent OVH , Group 2 consisted of 50 patients who underwent a st and ard bridging technique ( SBT ) and Group 3 consisted of 50 patients who underwent EVH . Each group was assessed for the incidence of wound infection , postoperative pain and satisfaction and the number of vein repairs using previously vali date d scoring systems . RESULTS The MIVH techniques reduced the pain at hospital ( P < 0.001 ) and at 6 weeks ( P < 0.001 ) , and improved cosmesis ( P < 0.001 ) , compared with the OVH group . Patient satisfaction was greatest in the EVH group followed by the SBT and then the OVH group . The clinical markers of inflammation were reduced with an MIVHt . There were more vein repairs in the EVH compared with the OVH ( P < 0.001 ) and the SBT ( P = 0.04 ) groups . CONCLUSIONS This study demonstrates that MIVH reduces wound morbidity . We believe that each technique has advantages and disadvantages , which should be considered during the selection of a harvesting procedure by both the patient and the surgeon AIMS The aim of this study was to compare coronary artery bypass grafting ( CABG ) using either endoscopic ( EVH ) or open harvest ( OVH ) . Leg-related morbidity and histological comparison of the veins were the outcome measures . METHODS One hundred consecutive patients scheduled for isolated CABG were r and omly divided into two goups : an EVH and OVH group . Perioperative data were recorded . Patients were examined 7 days and 1 month postoperatively for leg-related morbidity . Sample s for histological examination were taken from each harvested vein during the surgery . RESULTS Postoperative pain was statistically significantly lower in the EVH group 7 days postoperatively but the incidence of haematoma was non statistically higher in the EVH group while swelling was higher in the OVH group . Almost 40 % of all histological sample s were described as showing endothelial damage . There was significantly more endothelial damage in the EVH than the OVH group . CONCLUSIONS We confirmed the advantage of EVH in terms of leg-related morbidity as well as cosmetic effect . This method however , was associated with more acute endothelial damage of the graft . These results support concerns that endoscopic vein harvest may be connected with detrimental effects on vein endothelium which could promote a thrombogenic environment leading to a decrease in graft patency . This could be extremely important . The results suggest that further investigation of the long-term patency of vein grafts harvested endoscopically is required Background We compared wound complications between endoscopic and open great saphenous vein harvesting for coronary artery bypass surgery . Methods A total of 228 consecutive patients were prospect ively r and omized into two groups : open vein harvesting ( OVH ) , 115 patients ; and endoscopic vein harvesting ( EVH ) , 113 patients . Each group was assessed for post-operative wound complications , pain intensity , and neuropathy in the early post-surgical period . Lymphoscintigraphy of the lower limbs as well as morphological studies of vein walls using light and electron scanning microscopy were performed . Results Vein harvesting time was shorter for EVH than OVH : 31.8 ± 6.2 min and 40.3 ± 15.8 min , respectively ( p < 0.01 ) . There were fewer complications after vein harvesting in the EVH group ( 11.5 % ) than in the OVH group ( 44.4 % ) ( р = 0.001 ) . Multivariate analysis showed that diabetes mellitus was the only risk factor for post-surgical complications after OVH ( odds ratio = 3.95 % ; 95 % confidence interval 1.03–8.6 ) . Lymphoscintigraphic data in the EVH group did not demonstrate considerable disturbances in lymph drainage after surgery . In the OVH group , the accumulation of radiopharmaceutical drugs in the lymphatic nodes reduced two-fold ( р ≤ 0.001 ) . Histological evaluation of vein sample s did not show considerable damage to the vein wall in either group . Conclusions Using electron microscopy of vein fragments , this study demonstrated that EVH reduces wound complications and provides good- quality conduits Background Coronary artery bypass grafting using the radial artery has , since the 1990s , gone through a revival . Observational studies have indicated better long-term patency when using radial arteries . Therefore , radial artery might be preferred especially in younger patients where long time patency is important . During the last 10 years different endoscopic techniques to harvest the radial artery have evolved . Endoscopic radial artery harvest only requires a small incision near the wrist in contrast to open harvest , which requires an incision from the elbow to the wrist . However , it is unknown whether the endoscopic technique results in fewer complications or a graft patency comparable to open harvest . When the radial artery has been harvested , there are two ways to use the radial artery as a graft . One way is sewing it onto the aorta and another is sewing it onto the mammary artery . It is unknown which technique is the superior revascularisation technique . Methods / Design The NEO Trial is a r and omised clinical trial with a 2 × 2 factorial design . We plan to r and omise 300 participants into four intervention groups : ( 1 ) mammario-radial endoscopic group ; ( 2 ) aorto-radial endoscopic group ; ( 3 ) mammario-radial open surgery group ; and ( 4 ) aorto-radial open surgery group . The h and function will be assessed by a question naire , a clinical examination , the change in cutaneous sensibility , and the measurement of both sensory and motor nerve conduction velocity at 3 months postoperatively . All the postoperative complications will be registered , and we will evaluate muscular function , scar appearance , vascular supply to the h and , and the graft patency including the patency of the central radial artery anastomosis . A patency evaluation by multi-slice computer tomography will be done at one year postoperatively . We expect the nerve conduction studies and the st and ardised neurological examinations to be able to discriminate differences in h and function comparing endoscopic to open harvest of the radial artery . The trial also aims to show if there is any patency difference between mammario-radial compared to aorto-radial revascularisation techniques but this objective is exploratory . Trial registration Clinical Trials.gov identifier : NCT01848886.Danish Ethics committee number : H-3 - 2012 - 116.Danish Data Protection Agency : 2007 - 58 - 0015/jr.n:30–0838 OBJECTIVE Endoscopic saphenectomy is associated with a decreased incidence of wound complications without an increase in histologic trauma or endothelial dysfunction in published reports . Concern remains about the patency of saphenous vein grafts harvested endoscopically and the development of early intimal hyperplasia . The purpose of this study was to compare early quantitative coronary analysis of saphenous vein grafts used for coronary artery bypass grafting harvested with the open versus endoscopic techniques . METHODS Forty patients undergoing primary coronary artery bypass grafting surgery with at least 1 saphenous vein graft were r and omized preoperatively to open versus endoscopic saphenectomy with bipolar cauterization of side branches . Quantitative coronary angiography was performed a mean of 3 months ( range , 1 - 9 months ) after the operation . RESULTS There was no statistically significant difference in the patency rates of internal thoracic artery grafts between the open and endoscopic groups and no statistically significant difference in the patency rates of saphenous vein grafts between both groups ( 85.2 % vs 84.4 % , P = .991 ) . Quantitative coronary angiography showed no difference in graft stenosis ( > or=50 % of the internal diameter of the graft ) in the body of the saphenous vein grafts in the open versus endoscopic saphenectomy groups ( 3.7 % vs 0 % , P = .280 ) . CONCLUSION Angiographic appearance and patency rates of saphenous vein grafts harvested with the endoscopic technique are similar to those of saphenous vein grafts harvested with the open technique . These results support the use of endoscopic saphenectomy because of the known lower incidence of wound and infectious complications and superior functional results The R and omized Endo‐vein Graft Prospect i ve ( REGROUP ) trial ( Clinical Trials.gov NCT01850082 ) is a r and omized , intent‐to‐treat , 2‐arm , parallel‐ design , multicenter study funded by the Cooperative Studies Program ( CSP No. 588 ) of the US Department of Veterans Affairs . Cardiac surgeons at 16 Veterans Affairs ( VA ) medical centers with technical expertise in performing both endoscopic vein harvesting ( EVH ) and open vein harvesting ( OVH ) were recruited as the REGROUP surgeon participants . Subjects requiring elective or urgent coronary artery bypass grafting using cardiopulmonary bypass with use of ≥1 saphenous vein graft will be screened for enrollment using pre‐established inclusion /exclusion criteria . Enrolled subjects ( planned N = 1150 ) will be r and omized to 1 of the 2 arms ( EVH or OVH ) after an experienced vein harvester has been assigned . The primary outcomes measure is the rate of major adverse cardiac events ( MACE ) , including death , myocardial infa rct ion , or revascularization . Subject assessment s will be performed at multiple times , including at baseline , intraoperatively , postoperatively , and at discharge ( or 30 days after surgery , if still hospitalized ) . Assessment of leg‐wound complications will be completed at 6 weeks after surgery . Telephone follow‐ups will occur at 3‐month intervals after surgery until the participating sites are decommissioned after the trial 's completion ( approximately 4.5 years after the full study startup ) . To assess long‐term outcomes , central ized follow‐up of MACE for 2 additional years will be central ly performed using VA and non‐VA clinical and administrative data bases . The primary MACE outcome will be compared between the 2 arms , EVH and OVH , at the end of the trial duration OBJECTIVES Our objectives were ( 1 ) to determine whether minimally invasive endoscopic harvesting of the saphenous vein reduces morbidity due to postoperative wound infection and pain with improved cosmetic results and mobilization as compared with the conventional technique and ( 2 ) to compare the histologic properties of the saphenous veins harvested conventionally and endoscopically . METHODS One hundred forty-four patients undergoing coronary artery bypass grafting were r and omized to have vein harvesting performed by either the conventional ( n = 72 ) or an endoscopic ( n = 72 ) minimally invasive technique . RESULTS Vein harvest time ( open leg wound time ) was significantly reduced in the endoscopic group ( 27.6 vs 64.4 minutes ; P < .0001 ) . The rate of leg wound infection was significantly reduced in the endoscopic group ( 4.3 % ) as compared with the conventional group ( 24.6 % ) , a relative risk reduction of 83 % ( 95 % confidence interval : 36%-129 % ; P = .0006 ) . The majority of infections ( 84.2 % ) occurred after hospital discharge . Postoperative leg pain , mobilization , and overall patient satisfaction were also significantly improved in the endoscopic group . Double blinded histologic assessment of harvested vein ( n = 28 ) showed no evidence of any clinical ly important significant damage to the specimens in either group . CONCLUSIONS In this prospect i ve r and omized trial , endoscopic harvesting of the saphenous vein significantly reduced postoperative leg wound complications , including infection , and improved patient satisfaction as compared with the conventional harvesting technique . There were no significant histologic differences between the conventional and endoscopically harvested saphenous veins BACKGROUND A short saphenous vein segment is commonly used as a conduit for coronary artery bypass grafting , and clinicians must decide whether to obtain it by performing open ( OVH ) or endoscopic vein harvest ( EVH ) . We conducted a health economic evaluation , using data on re source usage collected alongside a r and omized controlled trial , to investigate whether EVH is cost-effective compared with OVH . METHODS Analyses were performed in accordance with international guidelines for health economic evaluations . We constructed 3 cost-levels as the current literature is inconclusive as to which re source consumptions differ significantly between harvesting methods . Outcomes were measured as purulent infections avoided in the cost-effectiveness analysis and for the cost-utility analysis we estimated quality -adjusted life-years gained . Results were presented as incremental cost-effectiveness ratios : ie , the extra cost of obtaining one extra quality -adjusted life-year and the extra cost of avoiding one purulent infection . To h and le uncertainties , we performed bias corrected bootstrap analyses on 5,000 re sample s and constructed cost-effectiveness acceptability curves . RESULTS The incremental cost-effectiveness ratio was $ 79,391/ quality -adjusted life-year and $ 1,970/purulent infection avoided when costs and outcomes within 35 days postoperatively were compared . Within 35 days postoperatively , EVH was less than 1 % cost-effective at a willingness-to-pay threshold of $ 50,000/ quality -adjusted life-year . CONCLUSIONS The EVH was not cost-effective within 35 days postoperatively . Future studies should investigate long-term cost effectiveness BACKGROUND Conventional saphenous vein harvest is associated with numerous complications , which may be reduced by minimally invasive vein-harvesting techniques . The integrity of the venous endothelium must be guaranteed before using new saphenous vein harvesting techniques . This short-term study compared the clinical outcome of two minimally invasive techniques with the conventional technique , and compared morphology as documented by light and electron microscopy . METHODS Ninety-two patients were prospect ively r and omized into three groups . Two different minimally invasive techniques of greater saphenous vein harvesting were used in sixty-two patients . One used a video-assisted dissector ( group A , n = 31 ) , and one used a light-coupled retractor ( group B , n = 31 ) . Thirty patients were treated by the conventional technique ( group C ) . RESULTS Incision lengths were 7.6+/-2.1 cm in group A and 9.3+/-3.2 cm in group B , as compared with 38.9+/-8.7 cm in the conventional group . Harvesting time was prolonged by a mean of 26 % when using a minimally invasive technique . Conversion rate to the open technique was 3 of 31 ( 9.3 % ) in group A and 2 of 31 ( 6.2 % ) in group B. No wound complications were noted in group A , but one wound inflammation was seen in group B ; only a mild hematoma was seen in both groups . Edge necrosis , wound separation and inflammation were noted in the conventional group . Light and electron microscopy revealed no significant denudation of the endothelial layer in groups A and B as compared with group C. CONCLUSIONS These data show an excellent postoperative result when using the minimally invasive technique as compared with the conventional group . The safety of the technique is demonstrated by the preservation of endothelial integrity BACKGROUND Endoscopic radial artery harvest provides better cosmetic result without compromising the quality of the graft . We sought to compare postoperative harvesting site neurologic and vascular outcome . METHODS From 10/2002 until 10/2004 , 50 patients were r and omized to have their radial artery harvested for coronary bypass either endoscopically ( group A , n = 25 ) or conventionally ( group B , n = 25 ) . Radial arteries were preoperatively evaluated by Doppler echocardiography . Neurologic and functional status was assessed by a self reporting question naire with a semiquantitative ( 1 - 5 ) scale . Vascular status of the forearm was assessed by control echocardiography . RESULTS At an average follow-up of 37 + /- 7 months , patients undergoing endoscopic radial artery harvesting had less overall neurologic complications ( 11 versus 17 patients , P = .023 ) and they were less severe ( 0.8 + /- 1.1 versus 2.2 + /- 1.2 ; P < .001 ) . Ulnar flow increase was similar among the groups : 13.1 + /- 5.43 cm/s in group A versus 15.9 + /- 4.9 cm/s in group B ( P = .147 ) as well as ulnar artery diameter increase 0.29 + /- 0.16 mm in group A versus 0.29 + /- 0.26 cm in group B ( P = .914 ) . CONCLUSION Endoscopic radial artery is safe and does not compromise graft quality or forearm and h and circulation postoperatively . Along with providing a better cosmetic result , endoscopic artery harvesting reduces postoperative harvesting site pain and neurologic complications BACKGROUND Endoscopic harvesting of the greater saphenous vein is increasingly used during cardiac surgery to improve patient satisfaction and reduce the wound complications associated with traditional open techniques . Although histologic studies suggest no significant difference in vein quality between these two techniques , long-term follow-up is lacking to address whether graft patency and event-free survival are influenced by the harvest method . METHODS A total of 112 isolated coronary artery bypass patients were prospect ively r and omized to have veins harvested using either an endoscopic ( n = 54 ) or traditional ( n = 58 ) technique . Groups were demographically similar with regard to preoperative risk stratification and coronary procedures performed . Event-free survival ( freedom from death , myocardial infa rct ion , or recurrent angina ) and use of outpatient re sources for resolution of wound complications were determined . Follow-up was 100 % at 5 years . RESULTS Five-year actual event-free survival was similar in patients with endoscopic versus traditionally harvested v e ins ( 75 % versus 74 % , P = .85 ) . The number of outpatient office visits required to manage each wound complication to complete resolution was significantly less following endoscopic versus traditional vein harvest ( 1.5 versus 6 visits , P = .001 ) . CONCLUSIONS Wound complication management following endoscopic versus traditional vein harvest requires less re source utilization . Five-year follow-up of a prospect i ve r and omized trial demonstrates that use of endosco pic versus traditionally harvested saphenous veins does not influence event-free survival BACKGROUND Healthy unaltered vascular endothelium in graft material is a prerequisite for a successful CABG operation . Damage done to the endothelium during vein harvest is responsible for an early graft occlusion rate of 20 % in the first year after operation . Minimally invasive vein harvesting is regarded to minimize the damage done to the Endothelium . We compared minimally invasive vein harvesting with conventional vein harvesting and studied the influence of a continuous perfusion of the veins with patient autologous blood on their endothelial integrity . METHODS 80 patients were r and omly split into 4 groups : Group 1 : Conventional vein harvest and storage of the vein in a crystalloid solution before usage . Group 2 : Endoscopic vein harvest and storage in cristallloid solution . Group 3 : Conventional harvest under continuous perfusion of the vein with 100 ml blood via the heart lung machine . Group 4 : Endoscopic vein harvest under continuous perfusion . Immediately prior to the first peripheral anastomosis a sample was taken from each graft and evaluated by scanning electron microscopy . The endothelial integrity was rated in 5 categories ( from " completely confluent endothelium " ( 1 ) to " no endothelium " ( 5 ) ) . RESULTS Group 1 : 2.7+/-1.13 Group 2 : 2.2+/-1.06 Group 3 : 1.6+/-0.68 Group 4 : 1.6+/-0.69 CONCLUSION In regard to the endothelial integrity endoscopic vein harvesting is superior to conventional vein harvest . If the grafts are harvested while continuously perfused with blood there is no more difference between the groups . Considering the well known additional benefits such as reduction in wound healing disorders endoscopic vein harvesting appears to be the preferable technique Minimally invasive vein harvesting is associated with better leg wound healing and a lower incidence of wound infections . We analyzed our experience in 2 prospect ively enrolled groups of non-r and omized patients undergoing elective coronary artery bypass grafting . Group 1 was 81 patients who had endoscopic vein harvesting ; group 2 was 80 who had conventional open vein harvesting . The time taken for endoscopic harvest ( skin incision to skin closure ) was significantly less than that for open harvest ( 51.07 vs 75.94 min ) . The number of cases to reach a plateau on the learning curve for endoscopic vein harvest was 20 for 2 lengths of vein and 35 for 3 lengths of vein . Significantly more suture repairs per vein were required in group 1 ( 1.32 ) than group 2 ( 0.38 ) . The incidence of wound infection was 1.2 % in group 1 vs 8.8 % in group 2 . Endoscopic vein harvesting is not difficult to learn and it should be preferred over open vein harvest , given its benefits in wound healing BACKGROUND Vein-graft harvesting with the use of endoscopy ( endoscopic harvesting ) is a technique that is widely used to reduce postoperative wound complications after coronary-artery bypass grafting ( CABG ) , but the long-term effects on the rate of vein-graft failure and on clinical outcomes are unknown . METHODS We studied the outcomes in patients who underwent endoscopic harvesting ( 1753 patients ) as compared with those who underwent graft harvesting under direct vision , termed open harvesting ( 1247 patients ) , in a secondary analysis of 3000 patients undergoing CABG . The method of graft harvesting was determined by the surgeon . Vein-graft failure was defined as stenosis of at least 75 % of the diameter of the graft on angiography 12 to 18 months after surgery ( data were available in an angiographic subgroup of 1817 patients and 4290 grafts ) . Clinical outcomes included death , myocardial infa rct ion , and repeat revascularization . Generalized estimating equations were used to adjust for baseline covariates associated with vein-graft failure and to account for the potential correlation between grafts within a patient . Cox proportional-hazards modeling was used to assess long-term clinical outcomes . RESULTS The baseline characteristics were similar between patients who underwent endoscopic harvesting and those who underwent open harvesting . Patients who underwent endoscopic harvesting had higher rates of vein-graft failure at 12 to 18 months than patients who underwent open harvesting ( 46.7 % vs. 38.0 % , P<0.001 ) . At 3 years , endoscopic harvesting was also associated with higher rates of death , myocardial infa rct ion , or repeat revascularization ( 20.2 % vs. 17.4 % ; adjusted hazard ratio , 1.22 ; 95 % confidence interval [ CI ] , 1.01 to 1.47 ; P=0.04 ) , death or myocardial infa rct ion ( 9.3 % vs. 7.6 % ; adjusted hazard ratio , 1.38 ; 95 % CI , 1.07 to 1.77 ; P=0.01 ) , and death ( 7.4 % vs. 5.8 % ; adjusted hazard ratio , 1.52 ; 95 % CI , 1.13 to 2.04 ; P=0.005 ) . CONCLUSIONS Endoscopic vein-graft harvesting is independently associated with vein-graft failure and adverse clinical outcomes . R and omized clinical trials are needed to further evaluate the safety and effectiveness of this harvesting technique BACKGROUND Radial arteries are being used more often for coronary artery bypass grafting . A minimally invasive technique was devised for harvesting vessels and compared with the traditional harvesting technique . METHODS In a prospect i ve study of 200 consecutive patients undergoing coronary artery bypass grafting , 100 patients had traditional open radial artery harvesting and 100 underwent endoscopic radial artery harvesting . All patients had a preoperative modified Allen 's test with Doppler imaging . The traditional technique involved a longitudinal incision over the radial aspect of the arm from the wrist to the antecubital fossa . The radial artery was dissected subfascially and removed . The endoscopic technique involved a 3-cm incision over the radial aspect of the arm . A vessel loop was placed around the artery and carbon dioxide was insufflated into the wound . The radial artery was dissected to the brachial artery and ligated with an Endo-loop ligature . The branches were divided with bipolar electrocautery and ligated with clips . Patients were evaluated for postoperative pain , bleeding , neuralgias , infection , and any adverse events . A p value of less than 0.05 was considered significant . RESULTS All 200 radial arteries were successfully harvested and used as grafts . Patients who had undergone endoscopic radial artery harvesting had significantly fewer major complications than patients who underwent the open technique : hematomas ( five versus no complications ) or wound infections requiring antibiotics ( seven versus one complication ) . The occurrence of major neuralgias that restricted function were also significantly lower postoperatively and 1 , 3 , and 6 months later ( ten versus one , eight versus one , five versus zero , and one versus zero , respectively ) . CONCLUSIONS Endoscopic radial artery harvesting results in good cosmetic results , useable grafts , and minimal neuralgias . Endoscopic radial artery harvesting is better than traditional open radial artery harvesting BACKGROUND Conventional open long saphenous vein harvest ( OVH ) is often associated with significant wound pain and serious morbidity in some patients with a result ant extended treatment period . Endoscopic vein harvest ( EVH ) in theory should alleviate wound pain , be less predisposed towards leg wound infection and lead to greater patient satisfaction . This study aims to compare the two techniques on this basis and determine whether EVH is a viable technique within normal operative time . METHODS During September and December 2000 , 60 saphenous vein harvests were prospect ively r and omised to EVH ( n=30 ) and OVH ( n=30 ) ; all performed by one surgeon with the Clearglide(r ) endoscopic vein harvest system ( Ethicon Inc ) . End points were impaired wound healing ( ASEPSIS score ) and postoperative pain ( Visual analogue scale ) and operative variables . Statistical analysis done using Fisher s exact test and Mann-Whitney U test as appropriate . RESULTS The groups were well matched demographically . Patients in the EVH group had significantly lower ASEPSIS scores ( p<0.001 ) and postoperative pain ( p<0.001 ) . The vein was harvested at 0.96cm/min ( 0.43 - 1.5+/-0.33 ) in the OVH group compared to 0.81cm/min ( 0.41 - 1.13+/-0.19 ) in the EVH group ( p=0.09 ) . The new procedure did not prolong the overall operative time ( p=0.53 ) . Two patients needed to be converted to open technique . There was no difference found in the vein quality by histological analysis . CONCLUSIONS These data clearly demonstrate that endoscopic vein harvest results in significantly reduced post-operative pain , better impaired wound healing , allows earlier ambulation and does not prolong the operative time significantly with no compromise in vein quality AIM comparative assessment of endoscopic and open exposure of the great saphenous vein during the operation of coronary artery bypass grafting . MATERIAL AND METHODS a total of 228 patients with endured coronary artery bypass graft operation were r and omized depending on the method of exposing the great saphenous vein ( GSV ) - an open method of vein exposure ( OVE ) - 115 patients and endoscopic vein exposure ( EVE ) - 113 patients . The evaluated parameters included healing of the postoperative wounds , postoperative oedema , pain intensity , and neuropathies in the early postoperative period . We performed lymphoscintigraphy of the lower limbs , as well as morphological examination of the venous wall by means of light and electron scanning microscopy . RESULTS the duration of vein exposure was less in the EVE group than in the OVE group , amounting to 31.8 ± 6.2 min and 40.3 ± 15.8 min , respectively ( p<0.01 ) . Complications after GSV isolation were encountered considerably less often in the EVE group ( 11.5 % ) as compared to 44.4 % in the OVE ( p=0.001 ) . According to the results of the multivariate analysis , diabetes mellitus was the only risk factor for postoperative complications in OVE . According the findings of lymphoscintigraphy the EVE group had no significant impairments of lymph outflow after the operation , whereas during OVE , accumulation of radiopaque material in the lymph nodes decreased twofold ( p ≤ 0.001 ) . Histological assessment of the sample d vein specimens showed no considerable lesions of the venous wall in the examined groups . CONCLUSION the obtained findings confirm high efficacy of using EVE during operations of CABG , lower traumaticity of this method with a conduit of good quality , which was proven based on electron microscopy of the vein fragments BACKGROUND The longest incision used in surgery is the st and ard incision for harvesting the greater saphenous vein for arterial grafting . This long incision is associated with significant pain and morbidity . We present a comparative study between two relatively less invasive techniques : the st and ard bridge technique ( BT ) and the endoscopic saphenous vein harvest ( ESVH ) . PATIENTS AND METHODS This is a prospect i ve , nonr and omized , case-matched study of contemporaneous minimally invasive saphenous vein harvest in patients undergoing multiple vessel coronary artery bypass grafting ( CABG ) . Data points include operative time , total wound length , length of vein harvested , intraoperative complications , conversions to open , injury to the graft , postoperative complications and hospital length of stay . Follow-up continued for 8 weeks postdischarge . RESULTS Within a 10-month period ( July 1996 to May 1997 ) , 60 saphenous vein harvests were performed , with 29 by BT and 31 by ESVH . Patient demographics were well matched , except for a larger number of patients with peripheral vascular disease in the ESVH group . ESVH only required 2.3 incisions versus 5 for the BT ( P = 0.000001 ) , whereas ESVH produced on average longer veins of 53.9 cm versus 47.7 cm for BT ( P = 0.05 ) . Harvest times were comparable in the two groups . However , mean vein preparation times , incision closure times , and total vein operative times for the BT were , respectively , 18.5 minutes , 35.1 minutes , and 94 minutes versus significantly less times of 11.3 minutes ( P = 0.009 ) , 10.6 minutes ( P = 0.000001 ) , and 73 minutes ( P = 0.0001 ) , respectively , for ESVH . The early , minor wound complication rate was 32 % for the ESVH group versus 3 % for the BT group ( P = 0.0048 ) . However , excluding small wound hematomas , the wound complication rate in the ESVH group fell to 13 % . Graft quality was acceptable in both groups . CONCLUSIONS ESVH was demonstrated to be a useful procedure to harvest saphenous veins for CABG surgery . The ESVH technique allowed the harvesting of a longer vein , via shorter and fewer incisions and in less time . However , for maximum operating room efficiency with the new technology , staff education is essential . There was a greater incidence of minor wound complications in the ESVH group ; however , the majority of these ESVH complications were small wound hematomas , which did not occur as surgeon experience with the technique increased BACKGROUND Endoscopic vein harvest ( EVH ) has been promoted as a possible solution to the wound complications , incisional pain , and prolonged convalesce associated with open vein harvesting ( OVH ) . The purpose of this study was to objective ly compare the two techniques . METHODS One hundred patients were prospect ively r and omized to EVH or OVH . Primary outcomes were wound complications , pain ( Medical Outcomes Study Pain Survey ) , and general health ( SF-12 ) . Secondary outcomes were operative times and patient preferences . Patients were assessed at hospital discharge , 3 , and 6 weeks postdischarge . RESULTS No significant differences were detected in the primary outcomes : leg infection ( p = 0.75 ) , incisional pain ( p = 0.74 ) , physical health ( p = 0.84 ) , mental health ( p = 0.47 ) , and postoperative length of stay ( p = 0.74 ) . However , patient preference for EVH was highly significant ( p < 0.01 ) . CONCLUSIONS EVH does not demonstrate significant differences compared with OVH . This , coupled with higher operating room costs , should limit its use until clinical benefit is shown . However , strong patient preference and dem and for EVH overshadow equivocal clinical outcomes BACKGROUND Saphenous vein harvested with a traditional longitudinal technique often results in leg wound complications . An alternative endoscopic harvest technique may decrease these complications . METHODS One hundred twelve patients scheduled for elective coronary artery bypass grafting were prospect ively r and omized to have vein harvested using either an endoscopic ( group A , n = 54 ) or traditional technique ( group B , n = 58 ) . Groups A and B , respectively , were similar with regard to length of vein harvested ( 41 + /- 8 cm versus 40 + /- 14 cm ) , bypasses done ( 4.1 + /- 1.1 versus 4.2 + /- 1.4 ) , age , preoperative risk stratification , and risks for wound complication ( diabetes , sex , obesity , preoperative anemia , hypoalbuminemia , and peripheral vascular disease ) . RESULTS Leg wound complications were significantly ( p < or = 0.02 ) reduced in group A ( 4 % [ 2 of 51 ] versus 19 % [ 11 of 58 ] ) . Univariate analysis identified traditional incision ( p < or = 0.02 ) and diabetes ( p < or = 0.05 ) as wound complication risk factors . Multiple logistic regression analysis identified only the traditional harvest technique as a risk factor for leg wound complications with no significant interaction between harvest technique and any preoperative risk factor ( p < or = 0.03 ) . Harvest rate ( 0.9 + /- 0.4 cm/min versus 1.2 + /- 0.5 cm/min ) was slower for group A ( p < or = 0.02 ) and conversion from endoscopic to a traditional harvest occurred in 5.6 % ( 3 of 54 ) of patients . CONCLUSIONS In a prospect i ve , r and omized trial , saphenous vein harvested endoscopically was associated with fewer wound complications than the traditional longitudinal method Objective Endoscopic vein harvesting ( EVH ) is increasingly used as an alternative to open vein harvesting ( OVH ) for coronary artery bypass graft ( CABG ) surgery . Concerns about the safety of EVH with regard to midterm clinical outcomes following CABG have been raised . The objective of this study was to assess the impact of EVH on short-term and midterm clinical outcomes following CABG . Design This was a retrospective analysis of prospect ively collected multi-centre data . A propensity score was developed for EVH and used to match patients who underwent EVH to those who underwent OVH . Setting Blackpool Victoria Hospital , Plymouth Derriford Hospital and the University Hospital of South Manchester were the main study setting s. Patients There were 4709 consecutive patients who underwent isolated CABG using EVH or OVH between January 2008 and July 2010 . Main outcome measures The main outcome measure was a combined end point of death , repeat revascularisation or myocardial infa rct ion . Secondary outcome measures included in-hospital morbidity , in-hospital mortality and midterm mortality . Results Compared to OVH , EVH was not associated with an increased risk of the main outcome measure at a median follow-up of 22 months ( HR 1.15 ; 95 % CI 0.76 to 1.74 ) . EVH was also not associated with an increased risk of in-hospital morbidity , in-hospital mortality ( 0.9 % vs 1.1 % , p=0.71 ) or midterm mortality ( HR 1.04 ; 95 % CI 0.65 to 1.66 ) . Conclusions This multi-centre study demonstrates that at a median follow-up of 22 months , EVH was not associated with adverse short-term or midterm clinical outcomes . However , before the safety of EVH can be clearly determined , further analyses of long-term clinical outcomes are required BACKGROUND Leg wound complications after saphenectomy are frequent after coronary bypass operations and have a detrimental effect on postoperative quality of life and treatment cost . To reduce morbidity , we evaluated a new technique of video-assisted vein harvest . METHODS Between March 1996 and October 1996 , 50 patients had video-assisted saphenectomy ( VAS ) and 40 patients had the st and ard open technique ( control group ) . An additional 13 patients had both procedures ( hybrid group ) . Level of pain , edema , and wound complications were evaluated at discharge and at 2 , 4 , and 6 weeks postoperatively . RESULTS The mean operating time for VAS patients was slightly higher than for control ( 60.6+/-24.7 minutes versus 53.2+/-21.1 minutes ; p > 0.05 ) . The average incision length in VAS patients was 13.8+/-8.8 cm for an average of 3.3 grafts per patient . Three VAS procedures were aborted , two because of time constraints , and one because of bleeding , and a segment of vein was lost to injury . The VAS group had considerably less early postoperative pain than the control group ( 1.7+/-1.2 versus 4.1+/-1.4 [ 1 = mild , 10 = severe ] ; p < 0.005 ) and edema was similar for both groups . Patients in the hybrid group reported less pain in the VAS-operated leg . Serious wound infection occurred in 4 patients , with 2 patients in the control group requiring reoperation for drainage and flap reconstruction . CONCLUSIONS Based on this initial experience , VAS harvesting , although initially more time consuming , is a rapidly mastered technique , results in shorter overall incision length , and is associated with considerably less postoperative pain than the st and ard open technique BACKGROUND Utilization of bridging vein harvesting ( BVH ) of saphenous vein grafts ( SVG ) for coronary artery bypass grafting ( CABG ) results in large wounds with great potential for pain and infection . Endoscopic vein harvesting ( EVH ) may significantly reduce the morbidity associated with SVG harvesting . METHODS A prospect i ve data base of 200 matched patients receiving EVH and BVH was compared . The patients all underwent CABG done over a period of 4 months ( April to August 2000 ) . Patients were excluded if they had prior vein harvesting . RESULTS The EVH and BVH group included 100 patients each with similar demographics . The patients in the EVH group had significantly fewer wound complications , mean days to ambulation , and total length of stay ( P < 0.05 ) . There was no difference in harvest time or vein injuries . CONCLUSION Endoscopic vein harvesting results in significantly fewer wound complications , decrease in days to ambulation , and the total length of stay . EVH is superior to BVH in patients undergoing CABG INTRODUCTION Saphenous vein is routinely harvested using one or a few long continuous skin incisions . This method is associated with typical healing complications such as oedemas , pain , necrosis , what often restricts proper rehabilitation . An alternative minimally invasive techniques may decrease these complications . MATERIAL AND METHODS This prospect i ve r and omised trial compared outcomes associated with saphenous vein harvested using three minimally invasive techniques versus a traditional longitudinal incision . RESULTS In the less invasive group we observed statistically significant improvement in all estimated parameters of wound healing , oedemas and pain . We present also costs analysis between the groups . CONCLUSIONS We conclude that less invasive techniques of saphenous vein harvesting may be alternatively introduced in coronary bypass surgery OBJECTIVE The influence of endoscopic harvesting techniques on the prevalence of leg-wound complications after coronary artery bypass grafting remains to be defined for patients at high risk for the development of wound infections . METHODS Among 1473 patients undergoing coronary artery bypass grafting who had the saphenous vein harvested by either a continuous incision or skip incisions leaving intact skin bridges , we determined the prevalence of wound infections to be 9.6 % . The following variables were entered into logistic regression analysis to identify significant risk factors that might be predictive of wound infection : diabetes , peripheral vascular disease , obesity , renal failure , steroid use , age , sex , and type of closure . We then prospect ively r and omized 132 patients found to be at high risk of wound infection to either endoscopic vein harvesting or a continuous open incision . RESULTS Univariate analysis showed female sex ( P = .04 ) , diabetes ( P < .001 ) , and obesity ( P < .001 ) to be predictors of wound infection . In a multivariate model diabetes ( P = .02 ) and obesity ( P = .001 ) were independent predictors . In patients at high risk , the prevalence of wound infection was 4.5 % for the endoscopic group versus 20 % for the open group ( P = .01 ) . Vein procurement time was greater in the endoscopic group ( 65 minutes vs 32 minutes , P < .001 ) , as was the number of vein repairs required ( 2.5 vs 0.6 , P < .001 ) . CONCLUSION The use of endoscopic vein harvesting decreases the prevalence of postoperative leg-wound infections in high-risk patients with diabetes and obesity . Whether this translates into an economic benefit that justifies the additional cost of that technology requires further analysis The aim of the study was to compare three different methods of radial artery harvesting with regard to postoperative complications and perioperative stress of the patient . A total of 60 patients admitted for coronary artery bypass surgery were r and omized into three groups . Each patient underwent extraction of radial artery , all performed by a single surgeon . The radial artery was harvested by one of the following three techniques : classical technique ( 20 patients ) , mini-invasive technique ( 20 ) , and endoscopic technique ( 20 ) . The time required for the graft harvest was greater in the group where the endoscopic technique was used ( 52.6 ± 11.3 min ) than with the mini-invasive ( 41.5 ± 7.3 min ) or the classical ( 27.8 ± 4.6 min ) technique . Postoperative blood loss into drains was higher where the classical technique was used ( 35.5 ± 9.4 ml ) as compared to the mini-invasive ( 20 ± 5 ml ) or the endoscopic ( 10 ± 7.3 ml ) technique . There was no significant difference among the groups in the rate of local neurological complications , contusion of wound edge , edema of the extremity , or wound infection rate . We observed no case of ischemia of the extremity , and a single case of postoperative myocardial ischemia in the group where the classical technique was used . From a clinical point of view , the mini-invasive and the endoscopic approach are comparable , but the latter is more expensive . Both mini-invasive and endoscopic techniques prolong the operation , reduce perioperative blood loss , and require additional training time In a retrospective post hoc analysis of the previously published PREVENT IV trial , Lopes et al1 found significantly higher rates of mortality , myocardial infa rct ion , or repeat revascularization 3 years after primary coronary artery bypass grafting when an endoscopic approach was compared with an open approach for harvesting the vein graft . These are important findings , but this study should be considered in the context of all available evidence in the field of technology assessment . Multiple r and omized trials of patients who are prognostically similar at baseline have demonstrated that endoscopic vein-graft harvesting ( EVH ) significantly reduces perioperative complications and need for surgical reintervention , all without adverse effects on graft failure , survival , or major coronary adverse events in the near term.2 In our recent meta- analysis ( 13 r and omized ; 23 nonr and omized ) in 36 trials of 9632 patients undergoing saphenous vein harvest,2 the risk of wound complications was significantly reduced by EVH compared with open vein-graft harvesting ( OVH ) ( OVH ; Odds Ratio [ OR ] 0.31 , 95 % CI 0.23–0.41 ; Fig. 1 ) . Similarly , the risk of wound infections was significantly reduced ( OR 0.23 , 95 % CI 0.20–0.53 ; P 0.0001 ) . Need for surgical wound intervention was also significantly reduced ( OR 0.16 , 95 % CI 0.08–0.29 ; Fig. 2 ) . The incidence of pain ( 23.1 % versus 6.7 % ) , neuralgia ( 24.3 % versus 7.1 % ) , and patient satisfaction ( 49 % versus 75 % ) was significantly improved with EVH compared with OVH . Postoperative myocardial infa rct ion , stroke , reintervention for ischemia or angina recurrence , and mortality were similar between patients having OVH or EVH . ( Table 1 ) Although time to harvest the vein was significantly increased ( weighted mean differences [ WMD ] 15.26 minutes , 95 % CI 0.01–30.51 ) , overall operative times were similar , hospital length of stay was reduced ( WMD 0.85 days , 95 % CI 1.55 to 0.15 ) , and readmissions were reduced ( OR 0.53 , 95 % CI 0.29–0.98).2,3 One r and omized trial of 110 patients using clinical event free survival at 5-years as a surrogate marker for graft failure reported no difference between groups ( 75 % vs. 74%)4 Indeed , pooled analysis of all observational and r and omized trials of shortto midterm follow-up showed no difference in survival ( Fig. 3).2 The difference in conclusions by Lopes et al,1 suggesting that EVH has a negative impact on graft patency in contrast to the meta-analyses of all comparative studies , 2 highlights the risk of focusing only on one single retrospective post hoc analysis , which have important prognostic differences between groups unaccounted for.5 In particular , there was no accounting for the proportion of patients undergoing on-pump versus off-pump bypass in the analysis by Lopes et al1 In another publication comparing off-pump and on-pump coronary artery bypass grafting from the same data set , BACKGROUND The greater saphenous vein is a common conduit for coronary revascularizations . Traditional vein harvesting uses long incision(s ) that can lead to significant morbidities . A minimally invasive technique has been developed that allows the harvest of much of the saphenous vein with one incision and fewer morbidities . METHODS Our technique and outcomes on 110 patients with minimally invasive harvest ( endoscopic vein harvesting ) is presented . Comparisons are made with an equivalent retrospective group within the same hospital and to a smaller ( n = 28 ) prospect i ve group at other hospitals . RESULTS Endoscopic vein harvesting has evolved to one above-knee incision of 3 cm length that allows for the harvest of 35 cm of vein . Harvest times were longer for endoscopic vein harvesting , showed a learning curve , and appeared to reach a baseline of 35 minutes . Incision closure times were less for the endoscopic vein harvesting group . Total skin to skin operating times for the entire cardiovascular procedure did not differ between the groups . In relatively homogeneous population s , leg infection rates did not differ , but other leg morbidities were less for the patients who underwent endoscopic vein harvesting . Hospital readmissions for leg wound care were low in both groups although the number of office visits required for leg care was higher for patients undergoing traditional vein harvesting . Pain perception by the patients was much less for the endoscopic vein harvesting and remained lower for up to 4 weeks . CONCLUSIONS Although endoscopic vein harvesting is a relatively new procedure , it is safe , effective , and less painful for the patient and carries fewer morbidities BACKGROUND Most of the grafts used in coronary bypass surgery are still venous grafts . The preferred vein for bypass surgery is the long saphenous vein . Severe wound complications caused by saphenous vein harvesting occur in 1 % to 3 % of cases . Minor complications that do not need surgical revision occur in up to 43 % of cases . We developed an endoscopic harvesting technique using non-disposable instruments to reduce wound complications caused by vein harvesting . METHOD In a retrospective study , the occurrence of wound complications , haematoma , postoperative pain , ambulation , sensory disturbances and patient satisfaction were studied ( n = 182 ) . Patients who had either endoscopically harvested ( n = 91 ) or conventionally harvested ( n = 91 ) saphenous vein grafts were review ed . RESULTS Results were collected for 173 patients . The overall prevalence of wound complications was 18.7 % . The incidence of wound healing complications could be reduced significantly ( p = 0.015 ) from 15.3 % to 3.4 % using the endoscopic technique . In the endoscopic group , postoperative ambulation was significantly ( p = 0.002 ) easier , patient satisfaction was significantly ( p = 0.007 ) higher , and postoperative leg swelling ( p = 0.003 ) and haematoma ( p = 0.004 ) could be reduced significantly . The occurrence of postoperative pain and sensory disturbances did not differ significantly . COMMENT We conclude that the used endoscopic vein harvesting is a safe and cost effective method that can significantly reduce wound complications . An ongoing prospect i ve study should establish our demonstrated data Abstract Objectives . Endoscopic vein harvest has gained widespread use in coronary artery bypass surgery . However , potential negative mid- and long-term effects following endoscopic vein harvest have been described . We aim ed to compare long-term clinical outcomes following endoscopic and open vein graft harvesting . Design . This study was a clinical follow-up with additional computed tomographic coronary angiography among 126 first-time bypass patients originally included in a r and omized study comparing early leg wound complications and cosmetic results . Deceased patients were retrospectively followed up . Results . Follow-up was complete , but information on clinical endpoints was not available in all patients . A total of 111 patients were alive at follow-up . Median observation time was 6.3 ( range : 0.2–9.1 ) years including three in-hospital deaths . Vein graft failure was significantly higher in the endoscopic vein harvest ( EVH ) group ( 13 of 31 ; 42 % ) compared with the open vein harvest ( OVH ) group ( 2 of 32 , 6 % ) ( P = 0.001 ) . However , this difference was not reflected by differences in recurrence of angina ( P = 0.44 ) , myocardial infa rct ion ( P = 0.11 ) , and all-cause mortality ( P = 0.15 ) . Conclusions . Using a median follow-up time of 6.3 years significantly more vein graft failures were identified following EVH compared with OVH without any differences in long-term clinical outcomes . Trial registration : Clinical Trials.gov identifier : NCT01480726 BACKGROUND The radial artery 's propensity for vasospasm and vulnerability to surgical trauma are well known . A less invasive endoscopic method to harvest the radial artery was recently introduced , but its effect on radial artery integrity is unknown . METHODS To compare the effects of harvest method on radial artery function , we prospect ively r and omized 54 patients undergoing coronary artery bypass grafting with the radial artery into 3 groups on the basis of harvest techniques : endoscopic , conventional with cautery , and conventional with harmonic scalpel . We assessed endothelium-dependent and endothelium-independent relaxation of radial artery segments to sequential doses of acetylcholine and nitroglycerin , respectively , using st and ard organ-chamber methodology . Vasospasm was assessed as the vasoconstrictor response to the thromboxane analog U46619 . We assessed endothelial integrity using light and electron microscopy and by rating intercellular adhesion molecule 1 , vascular cell adhesion molecule 1 , and P-selectin expression by means of immunohistochemistry on a semiquantitative 0- to 3-point scale . Harvest procedures were performed by a single surgeon , and data analyses were blinded to the harvesting method . RESULTS Maximal relaxation-contraction responses to acetylcholine , nitroglycerin , and U46619 and effective drug concentration yielding 50 % response were similar in the 3 groups . Adhesion molecule expression and histologic changes , as assessed by means of light and electron microscopy , were similar in the 3 groups . CONCLUSIONS Endoscopic harvest does not alter radial artery vasoreactivity or endothelial integrity compared with conventional harvest techniques . Because the endoscopic technique is less invasive , it might prove to be the technique of choice to harvest the radial artery BACKGROUND Endoscopic saphenous vein harvest ( EVH ) decreases leg wound infections and improves cosmesis after coronary artery bypass grafting ( CABG ) . Recent data , however , suggest that EVH may be associated with reduced graft patency rates . The objective of this study is to assess the effect of EVH on short-term and midterm outcomes after CABG . METHODS Data were prospect ively collected on all first-time isolated CABG and combined valve/CABG with saphenous vein graft between 1998 and 2007 at a single center . Patients having traditional " open " vein harvest ( OVH ) were compared with patients having EVH . Multivariate models were used to examine the risk-adjusted impact of EVH on postoperative leg infection , composite in-hospital adverse events , and individual and composite midterm adverse events . RESULTS The study included 5,825 patients , of whom 2,004 ( 34.4 % ) had EVH . Patients having EVH were more likely to have ejection fraction less than 50 % ( 32.0 % versus 29.3 % , p = 0.04 ) , recent myocardial infa rct ion ( 24.2 % versus 18.3 % , p < 0.0001 ) , and left main disease ( 26.0 % versus 22.1 % , p = 0.0009 ) . Median follow-up was 2.6 years . After risk adjustment , EVH was associated with reduced rates of leg infection ( odds ratio 0.48 , p = 0.003 ) but had no association with either in-hospital ( odds ratio 0.93 , p = 0.56 ) or midterm adverse outcomes ( hazard ratio 0.93 , p = 0.22 ) . Endoscopic saphenous vein harvest was associated with reduced readmission to hospital for unstable angina ( odds ratio 0.74 , p = 0.01 ) . CONCLUSIONS Endoscopic saphenous vein harvest is associated with a lower rate of leg infection and is not an independent predictor of in-hospital or midterm adverse outcomes . Endoscopic saphenous vein harvest is a safe alternative to OVH for patients undergoing CABG with saphenous vein OBJECTIVE In the R and omized On/Off Bypass ( ROOBY ) Trial , the efficacy of on-pump versus off-pump coronary artery bypass grafting was evaluated . This ROOBY Trial planned sub analysis compared the effects on postbypass patient clinical outcomes and graft patency of endoscopic vein harvesting and open vein harvesting . METHODS From April 2003 to April 2007 , the technique used for saphenous vein graft harvesting was recorded in 1471 cases . Of these , 894 patients ( 341 endoscopic harvest and 553 open harvest ) also underwent coronary angiography 1 year after coronary artery bypass grafting . Univariate and multivariable analyses were used to compare patient outcomes in the endoscopic and open groups . RESULTS Preoperative patient characteristics were statistically similar between the endoscopic and open groups . Endoscopic vein harvest was used in 38 % of the cases . There were no significant differences in both short-term and 1-year composite outcomes between the endoscopic and open groups . For patients with 1-year catheterization follow-up ( n=894 ) , the saphenous vein graft patency rate for the endoscopic group was lower than that in the open harvest group ( 74.5 % vs 85.2 % , P<.0001 ) , and the repeat revascularization rate was significantly higher ( 6.7 % vs 3.4 % , P<.05 ) . Multivariable regression documented no interaction effect between endoscopic approach and off-pump treatment . CONCLUSIONS In the ROOBY Trial , endoscopic vein harvest was associated with lower 1-year saphenous vein graft patency and higher 1-year revascularization rates , independent of the use of off-pump or on-pump cardiac surgical approach The purpose of this study was to evaluate and compare the benefits of endoscopic saphenous vein harvesting ( EVH ) with the traditional incision technique ( TIT ) for coronary artery bypass grafting ( CABG ) in respect to the technical procedure and clinical outcome . In a prospect i ve nonr and omized , case-matched study the greater saphenous vein was harvested for CABG in 22 patients using the endoscopic technique and in 18 patients with the traditional method . Comparisons were made for the operating time , length of incision and vein harvested , graft quality , postoperative complications , and pain assessment . Patient demographics were well matched . EVH required smaller incisions than did the TIT ( 10.5 ± 6.6 vs. 31.2 ± 7.8 cm , respectively ; p < 0.0001 ) . Harvest time and vein quality were comparable in the two groups . Total vein operating time was shorter following the endoscopic technique ( 60 ± 24 vs. 100 ± 35 minutes , respectively ; p < 0.0001 ) . EVH had fewer complications ( NS ) , and postoperative pain was significantly less ( p= 0.0034 ) . The major advantages of endoscopic vein harvesting are a significant reduction of postoperative pain and strikingly better cosmetic results . Wound complications seem to be less frequent BACKGROUND The saphenous vein is an established conduit for coronary revascularization . Disadvantages of traditional harvest technique are significant pain and morbidity . We compared the endoscopic harvest technique with the traditional method . METHOD 140 coronary artery bypass graft ( CABG ) patients were r and omized into 2 groups : endoscopic vein harvesting ( EVH ; n = 80 ) and traditional open vein harvesting ( OVH ; n = 60 ) . Analysis included preoperative risk factors for wound complication , harvesting time , graft injury , and intraoperative and postoperative complications . Patient follow-up lasted 3 months . RESULTS The preoperative risk profiles of the groups were comparable . In the EVH group , 5 patients ( 7.1 % ) had to be switched to the open technique . EVH time was 45 + /- 6.2 min vs. 31.1 + /- 6.5 min . Two patients ( 2.5 % ) had to be revised because of bleeding complication vs. 6 ( 10 % ) in the OVH group . No local infections or wound complications were observed in the EVH group vs. 11 ( 18 % ) cases in the OVH group . Two OVH cases ( 3.6 % ) were readmitted for wound debridement . All EVH patients reported less pain and were completely satisfied by the cosmetic results . CONCLUSION EVH is a safe and efficient technique for CABG . Morbidity was significantly lower , with reduced pain and better cosmetic results . EVH time was significantly longer compared to the traditional harvesting technique BACKGROUND The radial artery ( RA ) is a commonly used arterial conduit in coronary artery bypass grafting ( CABG ) . Traditional open-vessel harvest often leads to postoperative wound complications and cosmetic problems . Endoscopic RA harvesting ( ERAH ) has been widely used to prevent these problems . The purpose of this study was to assess these problems and graft patency in the first 50 patients who underwent ERAH . METHODS Between February 2006 and October 2007 , 50 patients underwent ERAH with the VasoView system ( Boston Scientific ) . These patients were compared with 50 patients who underwent the traditional open technique . RESULTS The mean age was 62.8 years in both groups . All RAs were successfully harvested . No conversion was made from ERAH to the traditional open technique . The mean harvesting time ( forearm ischemic time ) was 27.4 + or - 6.5 minutes , and the mean length of the RA in the ERAH group was 18.5 cm . Neither wound complications , such as wound infection and skin necrosis , nor severe neurologic complications were recorded . The patency rate was 95.9 % ( 95/99 ) in the ERAH group and 94 % ( 94/100 ) in the open group . CONCLUSION ERAH can be performed safely , and the early results are satisfactory . Endoscopic vessel harvesting is therefore recommended as the technique of choice for RA harvesting OBJECTIVES In the postoperative course after conventional open removal of the greater saphenous vein , wound healing disturbances are common and often painful . Therefore the primary goal of this investigation was to prove the safety and practicability of this new less invasive technique for saphenous vein harvesting and the effect on complications and morbidity . METHODS The study comprised 103 coronary artery bypass grafting ( CABG ) patients with an endoscopic approach to harvest the saphenous vein ( MIVH ) . We used the VasoView II system developed by Origin , and compared the intraoperative procedure time and the clinical results with 105 equivalent patients in which a conventional open technique was used . RESULTS In 101 patients endoscopic vein harvesting was successful ; a conversion into open technique was necessary in two patients . On average 2.6 vein segments could be harvested in the endogroup versus 2.9 segments in the opengroup . The mean procedure time was 13.2 min per segment in the endogroup compared to 12.2 min per segment in the opengroup . Relevant hematoma were found in 29 patients ( 27.6 % ) of the opengroup , whereas only nine patients ( 8.7 % ) of the endogroup revealed severe hematoma . Infection was apparent in nine patients ( 8.5 % ) after conventional vein harvesting . Two infections were found after endoscopic intervention . CONCLUSIONS Endoscopic saphenous vein harvesting as part of a less invasive concept in cardiac surgery is a safe and after the learning curve , fast alternative to harvest the saphenous graft . The cosmetic result is excellent and the complication rate seems to be lower . It must be noted however , that the cost effectiveness of the method has to be proved and that further histological and functional studies are needed in order to check the intimal structure of the vein Objective This purpose of this consensus statement was to compare endoscopic vascular graft harvesting ( EVH ) with conventional open vascular harvesting ( OVH ) in adults undergoing coronary artery bypass grafting ( CABG ) surgery and to determine which result ed in improved clinical and re source outcomes . Methods Before the consensus conference , the consensus panel review ed the best available evidence , whereby systematic review s , r and omized trials , and nonr and omized trials were considered in descending order of importance . Evidence -based statements were created , and consensus processes were used to determine the ensuing statements . The AHA/ACC system was used to label the level of evidence and class of recommendation . Results The consensus panel agreed upon the following statements : 1 . EVH is recommended to reduce wound related complications when compared with OVH ( Class I , Level A ) . 2 . Based on quality of conduit harvested , either endoscopic or open vein harvest technique may be used ( Class IIa ; Level B ) . 3 . Based on major adverse cardiac events and angiographic patency at 6 months , either endoscopic or open vein harvest technique may be used ( Class IIa ; Level A ) . 4 . EVH is recommended for vein harvesting to improve patient satisfaction and postoperative pain when compared with OVH in CABG surgery ( Class I , Level A ) . 5 . EVH is recommended for vein harvesting to reduce postoperative length of stay and outpatient wound management re sources ( Class I , Level A ) . Conclusions Given these evidence -based statements , the consensus panel stated that EVH should be the st and ard of care for patients who require saphenous vein grafts for coronary revascularization ( Class I , Level B ) . Future research should address long-term safety , cost-effectiveness , and endoarterial harvest OBJECTIVE Residual clot str and s within the excised saphenous vein are an increasingly recognized sequela of endoscopic vein harvest . We hypothesized that endoscopic visualization facilitated by sealed carbon dioxide insufflation causes stagnation of blood within the saphenous vein . In the absence of prior heparin administration , this stasis provokes clot formation . METHODS Forty consecutive patients having coronary artery bypass grafting underwent endoscopic vein harvest using sealed ( Guidant VasoView , n = 30 ; Guidant Corp , Minneapolis , Minn ) or open ( Data scope ClearGlide , n = 10 ; Data scope Corp , Montvale , NJ ) carbon dioxide insufflation followed by ex vivo assessment of intraluminal saphenous vein clot via optical coherence tomography . In the sealed carbon dioxide insufflation groups , clot formation was compared with ( preheparinized , n = 20 ) and without ( control , n = 10 ) heparin administration before endoscopic vein harvest , either at a fixed dose or titrated to an activated clotting time greater than 300 seconds . Risk factors for clot formation were assessed . RESULTS Residual saphenous vein clot was a universal finding in control veins ( sealed carbon dioxide insufflation endoscopic vein harvest without preheparinization ) . At either dose used , heparin given before endoscopic vein harvest significantly decreased saphenous vein clot burden . A similar reduction in clot was observed when using open carbon dioxide insufflation endoscopic vein harvest without preheparinization . Intraoperative blood loss and blood product requirements were similar in all groups . Patient age and preoperative maximum amplitude of the thrombelastography tracing showed a linear correlation with saphenous vein clot volume . CONCLUSION By enabling the quantification of this issue as never before possible , optical coherence tomography screening revealed that intraluminal saphenous vein clot is frequently found after endoscopic vein harvest . Systemic heparinization before harvest or an open carbon dioxide endoscopic vein harvest system are benign changes in practice that can significantly lessen this complication OBJECTIVE We aim ed to investigate the initial experience of endoscopic vein harvesting ( EVH ) for coronary artery bypass grafting ( CABG ) in Chinese patients . METHODS Forty patients scheduled for isolated CABG were prospect ively r and omized into an EVH group ( n = 20 ) and an open vein harvesting ( OVH ) group ( n = 20 ) . Clinical data were collected , and all of the vein grafts were assessed by macroscopic appearance , histologic quality ( endothelial integrity ) , and functional characteristics of endothelial nitric oxide synthase . RESULTS The 2 groups were similar with respect to hospital mortality ( EVH group , 0 ; OVH group , 1 ; P = 1 ) . There were no postoperative myocardial infa rct ions in either group and no deaths or re interventions in either group during the follow-up period . Harvesting times in the 2 groups were similar ( EVH , 12.15 ± 2.32 min ; OVH , 12.55 ± 2.11 min ; P = .571 ) . Three patients in the EVH group were converted to a partly open or skin-bridge technique . Electrocautery at least 2 mm distal to the origin of the side branch was the safety margin . CONCLUSIONS The use of EVH in Chinese patients was not related to adverse events and may be safely used for CABG procedures . Preoperative duplex mapping , systemic heparinization before harvesting , minimal surgical manipulation , and sectioning of side branches at least 2 mm distal to the origin may help improve the quality of vein grafts harvested with EVH and maximize the benefit of this less-invasive technique BACKGROUND Although long saphenous vein remains the most commonly used conduit in coronary revascularization , traditional open vein harvest ( OVH ) may lead to significantly impaired wound healing and postoperative pain . Endoscopic vein harvest ( EVH ) attempts to reduce this morbidity and improve patient satisfaction with no compromise in outcome . METHODS From September 2000 to November 2001 , 108 saphenous vein harvests were prospect ively r and omly assigned to EVH ( n = 52 ) or OVH ( n = 56 ) ; EVH was performed with the Clearglide endoscopic vein harvest system ( Cardiovations ) by a single surgeon . Endpoints included impaired wound healing ( ASEPSIS score ) , operative and harvest time , vein quality ( including histology ) , outcome and postoperative pain ( Visual Analog Scale ) . Follow-up was as long as 3 years . RESULTS The groups were well matched demographically . Endoscopic vein harvest was quicker to perform if sufficient vein for two grafts was needed ( p < 0.01 ) . Wound healing was significantly impaired ( ASEPSIS score ) in the OVH group compared with the EVH group ( p < 0.01 ) . The new procedure did not prolong the overall operative time ( p = 0.77 ) . Postoperative pain was less ( p < 0.01 ) in the EVH group . Stepwise multiple regression showed age , diabetes , peripheral vascular disease , total operative time , type of procedure , length of incision , and number of vein grafts to be predictive of impaired wound healing . More late interventions were needed in the OVH group for wound-related morbidity . CONCLUSIONS These data demonstrate that endoscopic vein harvest results in fewer cases of impaired wound healing and reduced postoperative pain , and it does not prolong the operative time significantly nor compromise the vein quality . Furthermore , it is quicker to perform if two grafts are needed , and it reduces late interventions BACKGROUND Wound complications associated with long incisions used to harvest the greater saphenous vein are well documented . Recent reports suggest that techniques of endoscopic vein harvest may result in decreased wound complications . A prospect i ve , nonr and omized study was developed to compare outcomes of open versus endoscopic vein harvest procedures . METHODS There were 106 patients in the open vein harvest group , and 154 patients in the endoscopic vein harvest group . Patient characteristics and demographics were similar in both groups . Wound complications identified were dehiscence , drainage for greater than 2 weeks postoperatively , cellulitis , hematoma , and seroma/lymphocele . RESULTS Wound complications were significantly less in the endoscopic vein harvest group ( 9 of 133 , 6.8 % ) versus the open vein harvest group ( 26 of 92 , 28.3 % ) , p less than 0.001 . By multivariable analysis with logistic regression , the open vein harvest technique was the only risk factor for postoperative leg wound complication ( relative risk 4.0 ) . CONCLUSIONS Endoscopic vein harvest offered improved patient outcomes in terms of wound healing compared with the open vein harvest technique BACKGROUND Numbers of intercellular and vascular cell adhesion molecules ( ICAM and VCAM ) and major lig and s on endothelial cells for adherence of activated polymorphnuclear leukocytes , macrophages , and lymphoid cells increase in many inflammatory disorders and after trauma to different tissues . METHODS Sample s of human saphenous veins were harvested from 90 r and omly selected patients who underwent coronary artery bypass graft ( CABG ) surgery , utilizing two different techniques ( open and endoscopic ) . Endothelial cells were collected from the vein sample s and cultured for 72 hours . Pre- and postoperative sera , in addition to the supernatants from the cultures , were analyzed for ICAM-1 and VCAM-1 using enzyme-linked immunosorbent assay . RESULTS Mean preoperative levels of ICAM-1 and VCAM-1 ( 0.95 + /- 0.58 ng/mL and 1.81 + /- 1.03 ng/mL , respectively ) did not differ significantly from that of postoperative sera ( 0.98 + /- 0.451 ng/mL and 1.74 + /- 1.05 ng/mL , respectively ) ( p = 0.77 and p = 0.73 , respectively ) . Mean ICAM-1 and VCAM-1 levels in endothelial cell culture supernatants did not differ significantly between the endoscopic ( 0.16 + /- 0.05 ng/mL and 0.23 + /- 0.10 ng/mL , respectively ) and the open method ( 0.18 + /- 0.08 ng/mL and 0.30 + /- 0.27 ng/mL , respectively ) ( p = 0.19 and 0.13 , respectively ) . CONCLUSION Our findings indicate that endoscopic and open saphenectomies are technically comparable in their effects on ICAM-1 and VCAM-1 synthesis during saphenous vein harvesting for CABG . We recommend the endoscopic method for its low morbidity and earlier hospital discharge OBJECTIVE Endoscopic saphenous vein harvesting ( EVH ) for coronary artery bypass grafting ( CABG ) has been developed to reduce leg wound morbidity and improve patient satisfaction . Choosing between EVH of a short vein segment from the thigh and open venous harvesting ( OVH ) of a short segment from the calf represents a clinical dilemma as EVH is easiest to perform from the thigh and OVH is easiest to perform from the calf . The purpose of this study was to investigate whether leg wound morbidity was reduced after EVH of a short vein segment from the thigh compared with OVH from the calf . Secondly we investigated whether EVH would reduce length of hospital stay and improve cosmetic results . METHODS From April 2004 to June 2007 , 132 patients undergoing elective isolated CABG were r and omized to have a short segment of saphenous vein harvested either by the EVH or OVH technique . Clinical follow-up was scheduled at day 5 and at 1 month . Primary end-points included wound morbidity . Secondary end-points included harvest time , length of hospital stay , cosmetic results and need for additional wound care after discharge . RESULTS The groups were preoperative similar . Three patients in the OVH group were excluded from the study as it became apparent that it was necessary to extend the incision beyond the knee . Harvest time was longer for the EVH group , but these patients suffered from significantly fewer cases of infectious and non-infective wound complications , with a substantial reduction in the need for post-discharge leg wound care . The purulent infection rates in the EVH and OVH groups were 0 % and 11 % , respectively . The overall leg wound morbidity rates regarding cellulitis , purulent infection , dehiscence and skin necrosis were 3 % and 27 % in the EVH and OVH groups , respectively ( p<0.001 ) . The length of hospital stay was similar . The conversion rate from EVH to OVH was 14 % . The EVH group experienced less pain and better cosmetic results . CONCLUSIONS EVH of a short vein segment from the thigh results in less wound morbidity and better cosmetic results compared with OVH of a short vein segment from the calf |
994 | 28,367,128 | Overall , the studies provided indirect evidence that α-AR activity may play an important role in aberrant regulation of cognition , arousal , and valence systems associated with MDD and schizophrenia .
Characterization of the NE pathway in patients may provide clinicians with information for more personalized therapy of these heterogeneous diseases .
Current clinical studies do not provide direct evidence to support the role of NE α-ARs in the pathophysiology of MDD and schizophrenia and in the treatment response of patients with these diseases , in particular with relation to specific valence systems . | Norepinephrine ( NE ) is recognized as having a key role in the pathophysiology of major depressive disorder ( MDD ) and schizophrenia , although its distinct actions via α-adrenergic receptors ( α-ARs ) are not well defined .
We performed a systematic review examining the roles of NE and α-ARs in MDD and schizophrenia . | BACKGROUND Cognitive deficits form core features in schizophrenia . Several studies have shown improvements in prefrontal cognitive function by α 2 -agonists in schizophrenia . In the present study , it was investigated whether clonidine ( an α 2 -adrenoceptor agonist ) could normalize sensorimotor gating deficits in schizophrenia . METHODS In a double blind , placebo controlled , r and omized , yet balanced , cross-over experiment , 20 male schizophrenia patients on stable medication were assessed in an auditory prepulse inhibition ( PPI ) , sensitization , and habituation of the startle reflex paradigm on 5 occasions : once after oral administration of placebo and after a single dose of 25 , 50 , 75 , and 150 µg of clonidine . Their results were compared with 20 age- and gender-matched healthy volunteers , who received no treatment . RESULTS In the placebo treatment , patients showed deficient PPI and sensitization , yet normal habituation compared with the controls . Except the highest dose , all dosages of clonidine significantly increased percentage PPI in the patients compared with placebo , to such levels that it no longer differed significantly from the healthy controls . However , none of the dosages increased sensitization or influenced habituation . CONCLUSIONS This is the first study to show that even a single low dose of clonidine added to the medical treatment of patients with schizophrenia who are clinical ly stable on their antipsychotic medication not only significantly ameliorates their PPI deficits , but also normalizes them . The results have a potentially high clinical relevance for the medical treatment of schizophrenia Adjunctive mirtazapine improved negative symptoms of schizophrenia in several studies . Recently , we found an improvement also in positive symptoms when mirtazapine was added to first generation antipsychotics ( FGAs ) in a 6 week r and omized controlled trial ( RCT ) . The short duration of that trial was its limitation . This study aim ed to explore whether longer treatment is worthwhile Major depressive disorder ( MDD ) has been associated with alterations in the noradrenergic system and impaired memory function . In turn , enhanced memory function has been associated with noradrenergic stimulation . In this study , we examined whether noradrenergic stimulation would differentially improve memory function in patients with MDD and healthy controls . In a placebo-controlled crossover study , 20 patients with MDD and 18 age- and sex-matched healthy controls received either placebo or 5 mg of yohimbine , an alpha-2-adrenoceptor antagonist that causes increased noradrenergic activity , orally before memory testing . A word list paradigm was used to test memory consolidation . Furthermore , the autobiographical memory test assessing memory retrieval and a working memory test were administered . Salivary alpha-amylase and blood pressure were measured . Yohimbine improved memory consolidation ( word list learning ) across groups ( main effect of yohimbine : p = 0.05 ) . This effect was more prominent in depressed patients compared with controls ( post hoc t-test : MDD p = 0.01 , controls p = 0.77 ) . Memory retrieval ( autobiographical memory specificity ) and working memory were not affected by yohimbine . Across groups , yohimbine administration result ed in an increase in blood pressure and alpha-amylase . In sum , these results further support the hypothesis that noradrenergic stimulation enhances memory consolidation . The mechanism by which yohimbine leads to stronger memory consolidation in depressed patients compared with healthy controls remains to be eluci date BACKGROUND Due to their favorable side-effect profile , atypical antipsychotic agents offer important therapeutic advantages in mood disorders . Ziprasidone , an atypical antipsychotic agent with strong 5-HT(1A ) agonist activity , may be particularly useful when used in conjunction with st and ard antidepressants in treatment-resistant depression . The purpose of this study is to test this hypothesis in depressed out patients who have not experienced significant clinical improvement following an adequate trial of a selective serotonin reuptake inhibitor ( SSRI ) . METHOD Twenty patients with major depressive disorder ( MDD ) who had failed to experience a clinical response to an adequate trial of an SSRI were treated with open-label ziprasidone in addition to their SSRI for 6 weeks between February 2002 and December 2002 . MDD was diagnosed with the Structured Clinical Interview for DSM-IV Axis I disorders . Clinical response was defined as a 50 % or greater decrease in depressive symptoms during the course of the trial ( baseline to endpoint ) , as measured by the HAM-D-17 total score . RESULTS Thirteen of 20 patients ( 65.0 % ) completed the trial . Using a completer analysis , 8 patients ( 61.5 % ) were classified as responders . An intent-to-treat ( ITT ) analysis result ed in 10 responders ( 50.0 % ) . The overall proportion of remitters was 5 of 13 ( 38.5 % ) using a completer analysis and 5 of 20 ( 25.0 % ) using the ITT analysis . Ziprasidone administration appeared to be safe , with no clinical ly significant QTc prolongation or severe adverse events observed in any of the study participants . CONCLUSION These results suggest a possible augmentation role for ziprasidone when used in conjunction with SSRIs in SSRI-resistant MDD BACKGROUND The comparative antidepressant effects of clozapine and other atypical antipsychotics for schizophrenia remain elusive , leading us to examine this question using the data from the Clinical Antipsychotic Trials of Intervention Effectiveness phase 2E . METHODS Ninety-nine patients who discontinued treatment with olanzapine , quetiapine , risperidone , or ziprasidone because of inadequate efficacy were r and omly assigned to open-label treatment with clozapine ( n=49 ) or double-blind treatment with another atypical antipsychotic not previously received in the trial ( olanzapine [ n=19 ] , quetiapine [ n=15 ] , or risperidone [ n=16 ] ) . The primary outcome was the Calgary Depression Scale for Schizophrenia ( CDSS ) total score . Antidepressant effects of clozapine and the other atypical antipsychotics were compared in patients with chronic schizophrenia and those with a major depressive episode ( MDE ) at baseline ( i.e. ≥6 on the CDSS ) , using mixed models . RESULTS No differences in the baseline CDSS total scores were found between the treatment groups regardless of presence of an MDE . Clozapine was more effective than quetiapine in antidepressant effects for chronic schizophrenia ( p<.01 for the whole sample and p=.01 for those with an MDE ) , and comparable to olanzapine and risperidone . CONCLUSION The present findings suggest that clozapine demonstrates superior antidepressant effects to quetiapine and comparable effects to olanzapine and risperidone in chronic schizophrenia regardless of presence of MDE . Given the indication of clozapine for treatment-resistant schizophrenia ( TRS ) and the negative impacts of depressive symptoms on clinical outcomes in schizophrenia , further research is warranted to investigate antidepressant effects of clozapine in TRS with an MDE OBJECTIVE Major depressive disorder has been linked with inflammatory processes , but it is unclear whether individual differences in levels of inflammatory biomarkers could help match patients to treatments that are most likely to be beneficial . The authors tested the hypothesis that C-reactive protein ( CRP ) , a commonly available marker of systemic inflammation , predicts differential response to escitalopram ( a serotonin reuptake inhibitor ) and nortriptyline ( a norepinephrine reuptake inhibitor ) . METHOD The hypothesis was tested in the Genome-Based Therapeutic Drugs for Depression ( GENDEP ) study , a multicenter open-label r and omized clinical trial . CRP was measured with a high-sensitivity method in serum sample s from 241 adult men and women with major depressive disorder r and omly allocated to 12-week treatment with escitalopram ( N=115 ) or nortriptyline ( N=126 ) . The primary outcome measure was the score on the Montgomery-Åsberg Depression Rating Scale ( MADRS ) , administered weekly . RESULTS CRP level at baseline differentially predicted treatment outcome with the two antidepressants ( CRP-drug interaction : β=3.27 , 95 % CI=1.65 , 4.89 ) . For patients with low levels of CRP ( < 1 mg/L ) , improvement on the MADRS score was 3 points higher with escitalopram than with nortriptyline . For patients with higher CRP levels , improvement on the MADRS score was 3 points higher with nortriptyline than with escitalopram . CRP and its interaction with medication explained more than 10 % of individual-level variance in treatment outcome . CONCLUSIONS An easily accessible peripheral blood biomarker may contribute to improvement in outcomes of major depressive disorder by personalizing treatment choice Background The Mental Health Biomarker Project ( 2010–2014 ) selected commercial biochemistry markers related to monoamine synthesis and metabolism and measures of visual and auditory processing performance . Within a case – control discovery design with exclusion criteria design ed to produce a highly characterised sample , results from 67 independently DSM IV-R-diagnosed cases of schizophrenia and schizoaffective disorder were compared with those from 67 control participants selected from a local hospital , clinic and community catchment area . Participants underwent protocol -based diagnostic-checking , functional-rating , biological sample - collection for thirty c and i date markers and sensory-processing assessment . Results Fifteen biomarkers were identified on ROC analysis . Using these biomarkers , odds ratios , adjusted for a case – control design , indicated that schizophrenia and schizoaffective disorder were highly associated with dichotic listening disorder , delayed visual processing , low visual span , delayed auditory speed of processing , low reverse digit span as a measure of auditory working memory and elevated levels of catecholamines . Other nutritional and biochemical biomarkers were identified as elevated hydroxyl pyrroline-2-one as a marker of oxidative stress , vitamin D , B6 and folate deficits with elevation of serum B12 and free serum copper to zinc ratio . When individual biomarkers were ranked by odds ratio and correlated with clinical severity , five functional domains of visual processing , auditory processing , oxidative stress , catecholamines and nutritional-biochemical variables were formed . When the strengths of their inter-domain relationships were predicted by Lowess ( non-parametric ) regression , predominant bidirectional relationships were found between visual processing and catecholamine domains . At a cellular level , the nutritional-biochemical domain exerted a pervasive influence on the auditory domain as well as on all other domains . Conclusions The findings of this biomarker research point towards a much-required advance in Psychiatry : quantification of some theoretically-underst and able , translationally-informative , treatment-relevant underpinnings of serious mental illness . This evidence reveals schizophrenia and schizoaffective disorder in a somewhat different manner , as a conglomerate of several disorders many of which are not currently being assessed-for or treated in clinical setting s. Currently available remediation techniques for these underlying conditions have potential to reduce treatment-resistance , relapse-prevention , cost burden and social stigma in these conditions . If replicated and vali date d in prospect i ve trials , such findings will improve progress-monitoring and treatment-response for schizophrenia and schizoaffective disorder No studies have compared mirtazapine with duloxetine in patients with major depressive disorder ( MDD ) . Fifty-six patients were nonr and omly assigned to a 4-week treatment with either 15 to 45 mg/day of mirtazapine ( n = 22 ) or 20 to 60 mg/day of duloxetine ( n = 34 ) . The primary efficacy measurements were the Hamilton Rating Scale for Depression ( HRSD ) and the Montgomery – Åsberg Depression 6-point Rating Scale ( MADRS ) scores . The second efficacy measurements were the response and remission rates of treatment . Tolerability assessment s were also performed . Fifty-six patients ( 43 male ; age , 43.6 years ) were recruited . There was no significant difference in the discontinuation rate between the mirtazapine and duloxetine treatment groups ( P = 0.867 ) . Both mirtazapine and duloxetine significantly improved the HRSD and MADRS scores from baseline ( P < 0.0001–0.0004 ) . While mirtazapine was superior to duloxetine in the reduction of HRSD scores ( P = 0.0421 ) , there was no significant change in MADRS scores in terms of between-group differences ( P = 0.171 ) . While more somnolence was observed with mirtazapine ( P = 0.0399 ) , more nausea was associated with duloxetine ( P = 0.0089 ) . No serious adverse events were observed for either antidepressant . Mirtazapine and duloxetine were safe and well-tolerated treatments for Japanese patients with MDD . Double-blind controlled studies are needed to further explore the efficacy and safety of mirtazapine and duloxetine in Japanese patients with MDD BACKGROUND Sensory gating deficits are among the core features of schizophrenia . Recently , we reported significantly increased sensorimotor gating following additional administration of single dosages of clonidine to the treatment of stably medicated patients with schizophrenia who , in spite of their medication , showed gating deficits . In the current study , we investigated whether this result is generalizable to filtering of sensory information as a whole , by examining clonidine 's effect on P50 suppression in the same group of patients . METHODS In a double-blind , placebo-controlled , r and omized yet balanced cross-over design , 20 male schizophrenia patients on stable medication were assessed in a psychophysiological test battery , including a sensory gating paradigm on 5 occasions : once after oral administration of placebo and after single doses of 25 , 50 , 75 , and 150 µg of clonidine . Their results were compared with 20 age-matched healthy male volunteers , who received no treatment . RESULTS Patients showed significantly reduced levels of P50 suppression in the placebo session compared with controls . All dosages of clonidine significantly diminished these deficits to such levels that they no longer differed significantly from the healthy controls ( except the highest dose ) . CONCLUSIONS This is the first study to show that even a single low dose of clonidine administered to stably medicated patients with schizophrenia not only significantly increases their levels of P50 suppression but also normalizes them . The results indicate that α2-noradrenergic agonists are capable of normalizing levels of P50 gating , which has a potentially high clinical relevance for the medical treatment of schizophrenia The treatment of schizophrenic patients who fail to respond to adequate trials of neuroleptics is a major challenge . Clozapine , an atypical antipsychotic drug , has long been of scientific interest , but its clinical development has been delayed because of an associated risk of agranulocytosis . This report describes a multicenter clinical trial to assess clozapine 's efficacy in the treatment of patients who are refractory to neuroleptics . DSM-III schizophrenics who had failed to respond to at least three different neuroleptics underwent a prospect i ve , single-blind trial of haloperidol ( mean dosage , 61 + /- 14 mg/d ) for six weeks . Patients whose condition remained unimproved were then r and omly assigned , in a double-blind manner , to clozapine ( up to 900 mg/d ) or chlorpromazine ( up to 1800 mg/d ) for six weeks . Two hundred sixty-eight patients were entered in the double-blind comparison . When a priori criteria were used , 30 % of the clozapine-treated patients were categorized as responders compared with 4 % of chlorpromazine-treated patients . Clozapine produced significantly greater improvement on the Brief Psychiatric Rating Scale , Clinical Global Impression Scale , and Nurses ' Observation Scale for Inpatient Evaluation ; this improvement included " negative " as well as positive symptom areas . Although no cases of agranulocytosis occurred during this relatively brief study , in our view , the apparently increased comparative risk requires that the use of clozapine be limited to selected treatment-resistant patients The development of therapeutic strategies to effectively treat negative symptoms remains one of the primary goals in the treatment of schizophrenia . Mirtazapine is the first of a new class of dual action compounds , the noradrenergic and specific serotonergic antidepressants ( NaSSa ) , whose activity is related to the enhancement of noradrenergic and serotonergic transmission by a presynaptic & agr;2 antagonism and postsynaptic 5-HT2 and 5-HT3 antagonism , respectively . This study was a 8-week double-blind , r and omized , placebo-controlled trial of 30 mg adjunctive mirtazapine to clozapine therapy in 24 patients with DSM-IV schizophrenia . The main finding at the end of the trial was a significant reduction on the Scale for the Assessment of Negative Symptoms ( SANS ) total scores in the mirtazapine group compared to placebo ( P<0.01 ) with a significant improvement on the SANS subscales avolition/apathy and anhedonia/asociality . The Brief Psychiatric Rating Scale total score at week 8 showed superiority of mirtazapine over placebo . These findings suggest a potential role for mirtazapine as an augmentation strategy in the treatment of negative symptoms of schizophrenia Previously , we found an anxiolytic effect of ziprasidone augmentation to escitalopram ( compared with placebo augmentation ) in patients with depression in an 8-week , r and omized , double-blind , parallel-group , placebo-controlled trial . Here , we carried out a post-hoc analysis , comparing changes in the Hamilton Depression and Anxiety Rating Scales between patients with anxious depression versus nonanxious depression , using a moderator analysis . Hamilton Depression Rating Scales total change scores from baseline and endpoint were not significantly different ( interaction term P=0.91 ) in patients with anxious depression on ziprasidone augmentation ( n=19 ; −9.1±4.9 ) or placebo ( n=19 ; −6.1±8.9 ) versus patients without anxious depression on ziprasidone ( n=52 ; −5.5±6.7 ) or placebo ( n=49 ; −2.3±4.5 ) . There was a trend toward statistical significance ( interaction term P=0.1 ) in favor of patients without anxious depression for a difference in Hamilton Anxiety Rating Scale total change scores from baseline to endpoint [ patients with anxious depression on ziprasidone augmentation ( n=19 ; −2.7±5.3 ) or placebo ( n=19 ; −3.3±5.8 ) versus patients without anxious depression on ziprasidone ( n=51 ; −3.9±6.6 ) or placebo ( n=44 ; −0.9±4.7 ) ] . Ziprasidone augmentation was equally efficacious in treating depression in patients with versus without anxious depression . However , the observed anxiolytic effect for patients with higher anxiety was not clinical ly significant UNLABELLED Atypical antipsychotics ( AP ) have high affinity for many neurotransmitter receptors . Among these receptors , APs are antagonist at α-adrenergic and β-adrenergic receptors , and this pharmacological property has been postulated to be involved in the mechanism of action of these drugs with respect to both clinical response and adverse effects . OBJECTIVE We tested the hypotheses that AP-induced weight gain is associated with genetic variation in adrenergic receptors and pathway enzymes . We analyzed nine genetic polymorphisms across seven adrenergic genes ( ADRA1A , ADRA2A , ADRA2C , ADRB3 , DBH , MAOA and COMT ) . METHODS One hundred thirty-nine patients with schizophrenia were prospect ively assessed for AP-induced weight gain . The HelixTree software ( Golden Helix , Bozeman , MT , USA ) was employed to detect differences in genotypic distribution between weight gainer and non-weight gainer groups . Furthermore , for the dopamine β-hydroxylase haplotype , we were able to obtain both the molecular and the statistical phases , analyzing the phenotype considering both phases . RESULTS Weight gain was not associated with any adrenergic gene . CONCLUSIONS Our results suggest that genetic polymorphisms in the adrenergic system may not play a major role in AP-induced weight gain ; however , adrenergic 2A receptor gene that produced previously the most consistent associations with this phenotype showed a significant interaction with the monoamine oxidase A in weight gainers It has been reported that mirtazapine would be helpful for treating negative symptoms in schizophrenia . Nevertheless , the results are contradictory so far . This study was design ed to investigate the effect of mirtazapine added to risperidone as augmentation therapy in patients with chronic schizophrenia and prominent negative symptoms in a double-blind and r and omized clinical trial . Eligible participants in the study were 40 patients with chronic schizophrenia with ages ranging from 19 to 49 years . All patients were in patients and were in the active phase of the illness , and met DSM-IV-TR criteria for schizophrenia . Patients were allocated in a r and om fashion 20 to risperidone 6 mg/day plus mirtazapine 30 mg/day and 20 to risperidone 6 mg/day plus placebo . The principal measure of the outcome was Positive and Negative Syndrome Scale ( PANSS ) . The mirtazapine group had significantly greater improvement in the negative symptoms and PANSS total scores over the eight-week trial . Therapy with 30 mg/day of mirtazapine was well tolerated and no clinical ly important side effects were observed . The present study indicates mirtazapine as a potential combination treatment strategy for chronic schizophrenia particularly for negative symptoms Quetiapine , originally developed as an antipsychotic , demonstrates efficacy in clinical studies of schizophrenia , bipolar mania and depression , major depressive disorder and generalized anxiety disorder . This broad spectrum of efficacy was not predicted from the pre clinical pharmacology of quetiapine . Binding studies in vitro show that quetiapine and its major active human metabolite , norquetiapine , have moderate to high affinity for dopamine D2 and serotonin 5-HT2A receptors , while norquetiapine alone has high affinity for the norepinephrine transporter ( NET ) . This positron emission tomography ( PET ) study measured NET occupancy in human subjects treated with extended-release quetiapine ( quetiapine XR ) at doses relevant in the treatment of depression . PET measurements using the specific NET radiolig and (S , S)-[(18)F]FMeNER-D2 were performed before and after quetiapine XR treatment at 150 and 300 mg/d for 6 - 8 d in nine healthy males ( aged 21 - 33 yr ) . Regions of interest were defined for the thalamus , using the cau date as reference region . NET occupancy was calculated using a target : reference region ratio method . Plasma concentrations of quetiapine and norquetiapine were monitored during PET measurements . Following quetiapine XR treatment , the mean NET occupancy in the thalamus was 19 and 35 % , respectively , at quetiapine XR doses of 150 and 300 mg/d . The estimated plasma concentration of norquetiapine corresponding to 50 % NET occupancy was 161 ng/ml . This is the first demonstration of NET occupancy by an antipsychotic in the human brain . NET inhibition is accepted as a mechanism of antidepressant activity . NET occupancy may therefore contribute to the broad spectrum of efficacy of quetiapine Both stress-system activation and melancholic depression are characterized by fear , constricted affect , stereotyped thinking , and similar changes in autonomic and neuroendocrine function . Because norepinephrine ( NE ) and corticotropin-releasing hormone ( CRH ) can produce these physiological and behavioral changes , we measured the cerebrospinal fluid ( CSF ) levels each hour for 30 consecutive hours in controls and in patients with melancholic depression . Plasma adrenocorticotropic hormone ( ACTH ) and cortisol levels were obtained every 30 min . Depressed patients had significantly higher CSF NE and plasma cortisol levels that were increased around the clock . Diurnal variations in CSF NE and plasma cortisol levels were virtually superimposable and positively correlated with each other in both patients and controls . Despite their hypercortisolism , depressed patients had normal levels of plasma ACTH and CSF CRH . However , plasma ACTH and CSF CRH levels in depressed patients were inappropriately high , considering the degree of their hypercortisolism . In contrast to the significant negative correlation between plasma cortisol and CSF CRH levels seen in controls , patients with depression showed no statistical relationship between these parameters . These data indicate that persistent stress-system dysfunction in melancholic depression is independent of the conscious stress of the disorder . These data also suggest mutually reinforcing bidirectional links between a central hypernoradrenergic state and the hyperfunctioning of specific central CRH pathways that each are driven and sustained by hypercortisolism . We postulate that alpha-noradrenergic blockade , CRH antagonists , and treatment with antiglucocorticoids may act at different loci , alone or in combination , in the treatment of major depression with melancholic features 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 OBJECTIVE The authors sought to test the efficacy of adjunctive ziprasidone in adults with nonpsychotic unipolar major depression experiencing persistent symptoms after 8 weeks of open-label treatment with escitalopram . METHOD This was an 8-week , r and omized , double-blind , parallel-group , placebo-controlled trial conducted at three academic medical centers . Participants were 139 out patients with persistent symptoms of major depression after an 8-week open-label trial of escitalopram ( phase 1 ) , r and omly assigned in a 1:1 ratio to receive adjunctive ziprasidone ( escitalopram plus ziprasidone , N=71 ) or adjunctive placebo ( escitalopram plus placebo , N=68 ) , with 8 weekly follow-up assessment s. The primary outcome measure was clinical response , defined as a reduction of at least 50 % in score on the 17-item Hamilton Depression Rating Scale ( HAM-D ) . The Hamilton Anxiety Rating scale ( HAM-A ) and Visual Analog Scale for Pain were defined a priori as key secondary outcome measures . RESULTS Rates of clinical response ( 35.2 % compared with 20.5 % ) and mean improvement in HAM-D total scores ( -6.4 [ SD=6.4 ] compared with -3.3 [ SD=6.2 ] ) were significantly greater for the escitalopram plus ziprasidone group . Several secondary measures of antidepressant efficacy also favored adjunctive ziprasidone . The escitalopram plus ziprasidone group also showed significantly greater improvement on HAM-A score but not on Visual Analog Scale for Pain score . Ten ( 14 % ) patients in the escitalopram plus ziprasidone group discontinued treatment because of intolerance , compared with none in the escitalopram plus placebo group . CONCLUSIONS Ziprasidone as an adjunct to escitalopram demonstrated antidepressant efficacy in adult patients with major depressive disorder experiencing persistent symptoms after 8 weeks of open-label treatment with escitalopram Several neuroimaging studies have reported ' hypofrontality ' in depressed patients performing a cognitive challenge compared to control subjects . Hypofrontality in depression is likely associated with an impaired behavioral performance . It is unclear whether this impaired performance is the consequence or the cause of hypofrontality . Consequently , we proposed to compare the cerebral activity of depressed patients and healthy subjects while controlling for the level of performance . Ten individuals meeting DSM-IV criteria for Major Depression and 10 healthy controls were tested with a verbal version of the n-back task during fMRI scanning . The working memory load was manipulated across the experiment ( 1,2,3-back ) to increase the cognitive dem and s. fMRI data were acquired on a 1.5-T GE scanner and analyzed using SPM99 software . We did not find any difference between groups in both performance and reaction times for each level of complexity of the n-back task . Depressed patients and control subjects showed bilateral activation of the lateral prefrontal cortex , anterior cingulate and parietal cortex . Activation of these regions was modulated by the complexity of the task . Within this n-back neural network , depressed patients showed greater activation of the lateral prefrontal cortex and the anterior cingulate compared to healthy subjects . This study provides evidence that depressed patients need greater activation within the same neural network to maintain a similar level of performance as controls during a working memory task . Our findings suggest that depression may impair the cognitive capacity of depressed patients by recruiting more brain re sources than controls during cognitive control OBJECTIVE Clozapine is an atypical neuroleptic with superior efficacy in severely ill , treatment-resistant in patients with schizophrenia . To determine if clozapine 's differential efficacy generalizes to less ill , out patients population s , the authors examined the effects of clozapine on positive and negative symptoms in out patients with schizophrenia . METHOD Out patients with schizophrenia who had histories of partial response to conventional neuroleptics and who had not responded to a prospect i ve 6-week trial of fluphenazine participated in a 10-week , double-blind , parallel-groups comparison of clozapine and haloperidol . Thirteen men and six women were given clozapine , and 15 men and five women were given haloperidol . Clinical response rates were determined and effects on primary versus secondary negative symptoms were addressed . Doses of clozapine and haloperidol at the end of the 10-week trial were 410.5 mg/day ( SD = 45.8 ) and 24.8 mg/day ( SD = 5.5 ) , respectively . RESULTS Clozapine was superior to haloperidol for treating positive symptoms . In addition , eight of the patients given clozapine and only one of the patients given haloperidol fulfilled clinical responder criteria . Clozapine was also superior to haloperidol for treating negative symptoms , although these effects were relatively minor . Negative symptoms were significantly affected in the subgroup of patients with nondeficit schizophrenia but not in the subgroup with deficit schizophrenia . Overall , clozapine was well tolerated . CONCLUSIONS Clozapine has superior efficacy for treating positive symptoms in partially responsive out patients with chronic schizophrenia , suggesting that it has utility for a broad spectrum of patients with schizophrenia beyond the most severely ill OBJECTIVE To determine whether single-nucleotide polymorphisms ( SNPs ) in c and i date genes are associated with response to olanzapine-fluoxetine combination . METHOD A post hoc analysis of a priori-selected SNPs used data from a clinical trial ( date s : April 2002-July 2005 ) of olanzapine-fluoxetine combination , fluoxetine , and olanzapine in patients with major depressive disorder ( DSM-IV criteria ) and with nonresponse to pre study antidepressant treatment and nonresponse to fluoxetine treatment during the study . Patients received open-label treatment with fluoxetine for 8 weeks ( 2 weeks , 25 mg/d ; then 6 weeks , 50 mg/d ) , at the end of which nonresponders ( < 25 % decline in the 17-item Hamilton Depression Rating Scale score ) were r and omized to receive double-blind , monotherapy treatment with olanzapine-fluoxetine combination ( 6/50 - 18/50 mg/d , n = 71 ) , fluoxetine ( 50 mg/d , n = 78 ) , or olanzapine ( 6 - 18 mg/d , n = 56 ) for 8 weeks . Statistical significance was assessed at P < .05 . The primary efficacy measure for within- study treatment was improvement on the Montgomery-Asberg Depression Rating Scale ( MADRS ) . RESULTS Rs36024 , an intronic SNP in the norepinephrine transporter ( SLC6A2 ) , as well as 3 SNPs in melanocortin 3 receptor ( MC3R ) and 2 SNPs in tryptophan hydroxylase 2 ( TPH2 ) , were associated with MADRS-defined response to treatment with olanzapine-fluoxetine combination ( adjusted Li-Nyholt P < .05 ) . Except for 1 SNP in TPH2 , identified SNPs were not significantly associated with response to continued-fluoxetine or olanzapine treatments . CONCLUSIONS Our findings further support the hypothesis that the synergistic effect of olanzapine and fluoxetine on prefrontal cortical levels of norepinephrine and dopamine might be an underlying mechanism for the efficacy of olanzapine-fluoxetine combination in the treatment of treatment-resistant depression and , if replicated , may form a basis on which response to olanzapine-fluoxetine combination versus continued fluoxetine can be predicted based on variants in SLC6A2 . TRIAL REGISTRATION Parent study registered at Clinical Trials.gov identifier : NCT00035321 OBJECTIVE To assess the efficacy , tolerability , and safety of brexpiprazole as adjunctive therapy to antidepressant treatments ( ADTs ) in adults with major depressive disorder ( as defined by DSM-IV-TR criteria ) and inadequate response to ADTs . METHOD Patients with historical inadequate response to 1 - 3 ADTs were enrolled . All patients entered a prospect i ve 8-week phase on physician-determined , open-label ADT . Those with inadequate response were r and omized to ADT + brexpiprazole 2 mg/d or ADT + placebo for 6 weeks . The study was conducted between July 2011 and May 2013 . The primary efficacy end point was change from baseline to week 6 in Montgomery-Asberg Depression Rating Scale ( MADRS ) total score . The key secondary end point was change from baseline to week 6 in Sheehan Disability Scale ( SDS ) mean score . The efficacy population comprised all patients who had ≥ 1 dose of study drug in the double-blind phase and both baseline and ≥ 1 postr and omization MADRS scores . The efficacy population per final protocol included patients from the efficacy population who met amended r and omization criteria of inadequate response throughout prospect i ve treatment . RESULTS Brexpiprazole ( n = 175 ) reduced mean MADRS total score versus placebo ( n = 178 ) at week 6 in the efficacy population per final protocol ( -8.36 vs -5.15 , P = .0002 ) . Brexpiprazole improved SDS mean score versus placebo ( -1.35 vs -0.89 , P = .0349 ) . The most common treatment-related adverse events were weight gain ( brexpiprazole , 8.0 % ; placebo , 3.1 % ) and akathisia ( 7.4 % vs 1.0 % ) . CONCLUSIONS Adjunctive brexpiprazole therapy demonstrated efficacy and was well tolerated in patients with major depressive disorder and inadequate response to ADTs . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01360645 The authors conducted a double-blind study evaluating the cortisol response to 75 mg of desipramine ( DMI ) , administered intramuscularly to 20 patients with major depressive disorder ( MDD ) and 20 age- and sex-matched normal control subjects . A blunted placebo-corrected cortisol response to DMI was found in MDD patients in comparison with the normal control subjects . Since the behavioral/side effect and pharmacokinetic profiles of DMI were similar for patients with MDD and normal control subjects , these findings suggest that patients with MDD have an underlying biological insensitivity of the hypothalamic-pituitary-adrenal axis to DMI . It is hypothesized that these findings are consistent with a norepinephrine deficit , an alpha 1-adrenergic receptor insensitivity , or both . Further use of DMI as a neuroendocrine probe for the noradrenergic system is indicated |
995 | 24,817,895 | Most trials indicated that LTRA are not superior to placebo or antihistamine therapy , while combination therapy of LTRA and antihistamines appear to be more efficacious compared to antihistamine alone .
The side effect profile and tolerability of this group of drugs is acceptable .
The use of LTRA as monotherapy can not be recommended .
LTRA are effective add-on therapy to anti-histamines , and their use in patients responding poorly to antihistamines is justifiable . | A significant proportion of patients with chronic urticaria respond inadequately to first line treatment with antihistamines .
Leukotreine receptor antagonists ( LTRA ) are also used for chronic urticaria , although firm recommendations on their use are lacking .
We performed a systematic review of r and omised trials to determine the role of LTRA in treatment of chronic urticaria . | BACKGROUND Because leukotrienes have potent local effects on cutaneous vasculature , leukotriene antagonists might be effective in the treatment of chronic urticaria . OBJECTIVE A double-blinded , placebo-controlled trial comparing cetirizine 10 mg daily in combination with zafirlukast 20 mg twice a day versus cetirizine 10 mg daily and placebo was conducted to determine whether subjects with chronic urticaria benefit from add-on therapy with a leukotriene-modifying agent . METHODS Patients 12 years or older with a history of chronic urticaria ( more than 6 weeks in duration ) required diary documentation of 6 or more hives on at least 2 days/week and a suboptimal response to H(1)-antagonist therapy for enrollment . At baseline , all subjects were skin tested to autologous serum to assess for the potential presence of FcepsilonRI or IgE autoantibodies . Subjects meeting the initial entry criteria were treated with cetirizine 10 mg a day and placebo twice daily for 1 week . Those patients with persistent hives were r and omized to receive cetirizine 10 mg daily and zafirlukast 20 mg twice a day or cetirizine 10 mg daily and placebo . At each successive weekly visit , physician and patient treatment effectiveness score ( TES ) and visual analog scale ( VAS ) ratings were recorded . Statistical analysis used generalizing estimating equations to compare the effect of combination therapy versus monotherapy on TES and VAS ratings . Results were adjusted for baseline rating , recruiting center , and autologous serum skin test ( ASST ) . A separate analysis evaluated patients with positive ASST results receiving combination therapy versus monotherapy . RESULTS Combination therapy with zafirlukast demonstrated a modest but significantly greater improvement compared with cetirizine monotherapy in physician and patient recorded VAS ratings at visit 4 and across treatment visits 4 through 6 ( P < .05 unless stated otherwise ) . Subjects with ASST positive results receiving combination therapy as compared with subjects with negative ASST results exhibited a significant improvement in patient recorded VAS ratings across visits 4 through 6 . Subgroup analysis of subjects with ASST positive results receiving combination therapy versus monotherapy showed improvement in physician recorded TES at visit 5 , physician recorded VAS at visits 4 and 5 and across visits 4 through 6 , as well as for patient recorded VAS at visit 5 . There were no significant results for patients with ASST negative results . CONCLUSION The results of this study indicate that only patients with autoimmune ( ASST positive ) chronic urticaria refractory to H(1)-antagonist monotherapy might benefit from the addition of the leukotriene D(4)-receptor antagonist zafirlukast to their treatment regimen . These results also suggest that routine screening of patients with chronic urticaria with the ASST might be useful in formulating therapeutic algorithms in the management of chronic urticaria BACKGROUND Antihistamines ( AH ) alleviate pruritus and decrease the incidence of hives in patients with chronic idiopathic urticaria ( CU ) . However , some patients do not respond completely to this therapy . We hypothesized that some of them might benefit from the addition of leukotriene receptor antagonists ( LA ) . METHODS We screened patients diagnosed and treated for CU and selected those that had symptoms despite antihistamine treatment . In a double-blind crossover study , patients took the leukotriene antagonist montelukast ( 10 mg per day ) or placebo . Efficacy was assessed by a symptom score . RESULTS In a group of 22 patients , the symptom score was not significantly different between periods using montelukast ( 48.8 ; 0 - 214 ) or placebo ( 68.5 ; 0 - 230 ) . However in the subgroup of five patients with the most severe urticaria , defined as patients with symptom scores in the upper quartile at inclusion in the study , montelukast ( 41 ; 11 214 ) was superior to placebo ( 95.5 ; 48 230 ; p < 0.05 ) , but only when using an in-house symptom score question naire and not when using a vali date d urticaria activity score question naire . CONCLUSIONS We showed that in patients with antihistamine-resistant CU the addition of montelukast significantly diminished symptoms in only a small minority of patients . However , response to add-on montelukast was seen in the subgroup of patients with particularly severe disease . To confirm this observation , a study with a larger group of patients is warranted Background Chronic urticaria ( CU ) is a common skin condition . It is frequently a disabling disease due to the persistency of clinical symptoms , the unpredictable course and negative influence on the quality of life Background : Chronic idiopathic urticaria ( CIU ) is often difficult to treat . Although histamine-releasing activity is detectable for up to 50 % of CIU patients , antihistamine therapy provides only a limited response . Objective : This study aim ed to assess the clinical efficacy of combined leukotriene receptor antagonist ( LRA ) and H1 antihistamine , H1 and H2 antihistamine , and two H1 antihistamines as a synergistic therapeutic regimen for treating CIU compared with a matched placebo modality . Methods : A total of 120 newly diagnosed adult patients were evaluated . Patients were single blinded and r and omly assigned to one of four medication groups that received the following regimens for 4 weeks : Group A , combination of sedating H1 antihistamine and non-sedating H1 antihistamine ; Group B , combination of H1 antihistamine and H2 antihistamine ; Group C , combination of H1 antihistamine and LRA ; and Group D , matched placebo medication . The primary measure of treatment efficacy was the daily urticaria activity score ( UAS ) of ‘ wheal and itch ’ . A positive therapeutic response was defined as a reduction to < 25 % of baseline weekly UAS , while a relapse was a return to > 75 % of baseline weekly UAS . Results : In all , 107 patients completed the trial medication . At the end of 4 weeks , the UAS score as a response to treatment was 23.3 % for Group A , 63.3 % for Group B , 53.3 % for Group C , and no real change for the placebo treatment group . Conclusions : The combination of LRA and H1 receptor antagonist is promising for CIU treatment and is reasonably well tolerated by patients . The combination of H1- and H2-receptor antagonists provided the greatest treatment efficacy by the measures used in this small study BACKGROUND H 1 -receptor antagonists are considered to be particularly effective in reducing pruritus , and they are therefore recommended as first-line treatment in patients with chronic idiopathic urticaria ( CIU ) . Recently , antileukotriene receptors have been used in patients with CIU , either administered as monotherapy or combined with H 1 -receptor antagonists . OBJECTIVE We compared the clinical efficacy of 5 mg of desloratadine administered once daily either as monotherapy or combined with a leukotriene antagonist , 10 mg of montelukast daily , and 10 mg of montelukast administered daily as monotherapy for the treatment of patients affected by CIU with placebo . METHODS One hundred sixty patients aged 18 to 69 years ( mean + /- SD , 43.9 + /- 13.4 years ) with a history of moderate CIU were selected . A r and omized , double-blind , double-dummy , placebo-controlled , parallel-group study design was used . Patients were treated with 5 mg of desloratadine once daily ( n = 40 ) , 10 mg of montelukast once daily ( n = 40 ) , 5 mg of desloratadine ( n = 40 ) in the morning plus montelukast in the evening , or matched placebo ( n = 40 ) . Assessment of treatment efficacy was based on scores of daily cutaneous symptoms evaluated reflectively and instantaneously . RESULTS Only the group treated with desloratadine as monotherapy or as combined therapy concluded the whole study . Twenty-seven of the 40 patients in the montelukast group and 35 of the 40 patients in the placebo group discontinued the treatment . As reflective evaluation , all groups showed significant differences compared with the placebo group in terms of total symptom score , number of hives , and size of largest hive . In addition to the pruritus , only the groups treated with desloratadine as monotherapy or combined therapy showed significant differences compared with those receiving placebo , whereas there were no differences between the montelukast and placebo groups . Finally , no differences were found between the desloratadine group and the desloratadine plus montelukast group . The instantaneous evaluation demonstrated similar results regarding the desloratadine group and the desloratadine plus montelukast group versus the placebo group , whereas there were no significant differences between the group treated with montelukast alone and the placebo group for pruritus and size of largest hive . No differences were found between the group treated with desloratadine alone and the desloratadine plus montelukast group . CONCLUSIONS The results of this comparative study demonstrate that desloratadine is highly effective for the treatment of patients affected by CIU . In addition , the regular combined therapy of desloratadine plus montelukast does not seem to offer a substantial advantage with respect to desloratadine as monotherapy in patients affected by moderate CIU BACKGROUND Chronic idiopathic urticaria ( CIU ) might be refractory to st and ard therapies . For the patients with severe unremitting CIU who have failed to benefit from conventional therapy with antihistamines , other effective and safe therapeutic modalities are required . OBJECTIVE A r and omized , single-blind , placebo-controlled crossover study was conducted to evaluate the efficacy and safety of the new selective leukotriene antagonist montelukast sodium in the treatment of refractory CIU . METHODS Thirty patients with refractory CIU were enrolled in the trial . After informed consent was obtained , patients were r and omly assigned to 2 groups . The patients in group A received 10 mg/d montelukast and a nonsedating H(1 ) antihistamine ( cetirizine ) when needed for 6 weeks . After a 2-week washout period , they received placebo for 6 weeks and the same H(1 ) antihistamine as needed . Group B received the treatment vice versa . Improvement was monitored by using the self-estimated urticaria activity score , which is the sum of the wheal number score and the itch severity score , and the antihistamine counts used in each study period . RESULTS More significant decreases occurred in urticaria activity scores with montelukast therapy compared with those with placebo therapy ( P < .001 ) . H(1 ) antihistamine use was also significantly less frequent during the montelukast period ( P < .001 ) . There were no significant side effects with montelukast therapy . CONCLUSION The present study results suggest that montelukast might be an effective and safe therapeutic agent in the treatment of refractory CIU Background Leukotriene receptor antagonists have shown some efficacy in the treatment of asthma . Injection of LTC4 , LTD4 and LTE4 into the skin leads to a weal‐ and ‐flare reaction , suggesting an involvement of leukotrienes in the pathogenesis of urticaria . Indeed , various reports have indicated a beneficial effect for leukotriene receptor antagonists in patients with chronic urticaria Background The cause and pathogenesis of chronic urticaria are still poorly understood . IgE‐independent reactions , are common in adult patients with chronic urticaria , who have daily spontaneous occurrence of weals . H1‐receptor antagonists ( antihistamines ) are the major class of therapeutic agents used in the management of urticaria and angioedema . Nevertheless , chronic urticaria is often difficult to treat and may not be controlled by antihistamines alone . It has been postulated that mediators other than histamine , such as kinins , prostagl and in and leukotrienes , may be responsible for some of the symptoms in urticaria which are not controlled by antihistamines . In this study , which was r and omized double‐blind , placebo‐controlled , we compare the clinical efficacy and safety of montelukast ( MT ) 10 mg given once a day and cetirizine ( CET ) 10 mg given once a day with placebo ( PLA ) , in the treatment of patients with chronic urticaria who have positive challenge to acetylsalicylic acid ( ASA ) and /or food additives |
996 | 19,546,410 | Our study suggests that targeting hemoglobin levels in excess of 12.0 g/dL leads to small and not clinical ly meaningful improvements in HQOL .
This , in addition to significant safety concerns , suggests that targeting treatment to hemoglobin levels that are in the range of 9.0 to 12.0 g/dL is preferred | BACKGROUND Treatment of anemia in chronic kidney disease ( CKD ) with erythropoietin-stimulating agents ( ESAs ) is commonplace .
The optimal hemoglobin treatment target has not been established .
A clearer underst and ing of the health-related quality of life ( HQOL ) impact of hemoglobin target levels is needed . | In recent years quality of life instruments have been featured as primary outcomes in many r and omized trials . One of the challenges facing the investigator using such measures is determining the significance of any differences observed , and communicating that significance to clinicians who will be applying the trial results . We have developed an approach to elucidating the significance of changes in score in quality of life instruments by comparing them to global ratings of change . Using this approach we have established a plausible range within which the minimal clinical ly important difference ( MCID ) falls . In three studies in which instruments measuring dyspnea , fatigue , and emotional function in patients with chronic heart and lung disease were applied the MCID was represented by mean change in score of approximately 0.5 per item , when responses were presented on a seven point Likert scale . Furthermore , we have established ranges for changes in question naire scores that correspond to moderate and large changes in the domains of interest . This information will be useful in interpreting question naire scores , both in individuals and in groups of patients participating in controlled trials , and in the planning of new trials BACKGROUND Patients with diabetes and anemia are at high risk of cardiovascular disease . The Anemia CORrection in Diabetes ( ACORD ) Study aim ed to investigate the effect of anemia correction on cardiac structure , function , and outcomes in patients with diabetes with anemia and early diabetic nephropathy . METHODS One hundred seventy-two patients with type 1 or 2 diabetes mellitus , mild to moderate anemia , and stage 1 to 3 chronic kidney disease were r and omly assigned to attain a target hemoglobin ( Hb ) level of either 13 to 15 g/dL ( 130 to 150 g/L ; group 1 ) or 10.5 to 11.5 g/dL ( 105 to 115 g/L ; group 2 ) . The primary end point was change in left ventricular mass index ( LVMI ) . Secondary end points included echocardiographic variables , renal function , quality of life , and safety . RESULTS Median Hb level and LVMI were similar in groups 1 and 2 ( Hb , 11.9 and 11.7 g/dL [ 119 and 117 g/L ] ; LVMI , 113.5 and 112.3 g/m(2 ) , respectively ) . At study end , Hb levels were 13.5 g/dL ( 135 g/L ) in group 1 and 12.1 g/dL ( 121 g/L ) in group 2 ( P < 0.001 ) . No significant differences were observed in median LVMI at month 15 between study groups ( group 1 , 112.3 g/m(2 ) ; group 2 , 116.5 g/m(2 ) ) . Multivariate analysis showed a nonsignificant decrease in LVMI ( P = 0.15 ) in group 1 versus group 2 . Anemia correction had no effect on the rate of decrease in creatinine clearance , but result ed in significantly improved quality of life in group 1 ( P = 0.04 ) . There were no clinical ly relevant differences in adverse events between study groups . CONCLUSION In patients with diabetes with mild to moderate anemia and moderate left ventricular hypertrophy , correction to an Hb target level of 13 to 15 g/dL ( 130 to 150 g/L ) does not decrease LVMI . However , normalization of Hb level prevented an additional increase in left ventricular hypertrophy , was safe , and improved quality of life BACKGROUND This r and omized clinical trial is design ed to assess whether the prevention and /or correction of anemia , by immediate versus delayed treatment with erythropoietin alfa in patients with chronic kidney disease , would delay left ventricular ( LV ) growth . Study design and sample size calculations were based on previously published Canadian data . METHODS One hundred seventy-two patients were r and omly assigned . The treatment group received therapy with erythropoietin alfa subcutaneously to maintain or achieve hemoglobin ( Hgb ) level targets of 12.0 to 14.0 g/dL ( 120 to 140 g/L ) . The control/delayed treatment group had Hgb levels of 9.0 + /- 0.5 g/dL ( 90 + /- 5 g/L ) before therapy was started : target level was 9.0 to 10.5 g/dL ( 90 to 105 g/L ) . Optimal blood pressure and parathyroid hormone , calcium , and phosphate level targets were prescribed ; all patients were iron replete . The primary end point is LV growth at 24 months . RESULTS One hundred fifty-two patients were eligible for the intention-to-treat analysis : mean age was 57 years , 30 % were women , 38 % had diabetes , and median glomerular filtration rate was 29 mL/min ( 0.48 mL/s ; range , 12 to 55 mL/min [ 0.20 to 0.92 mL/s ] ) . Blood pressure and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use were similar in the control/delayed treatment and treatment groups at baseline . Erythropoietin therapy was administered to 77 of 78 patients in the treatment group , with a median final dose of 2,000 IU/wk . Sixteen patients in the control/delayed treatment group were administered erythropoietin at a median final dose of 3,000 IU/wk . There was no statistically significant difference between groups for the primary outcome of mean change in LV mass index ( LVMI ) from baseline to 24 months , which was 5.21 + /- 30.3 g/m2 in the control/delayed treatment group versus 0.37 + /- 25.0 g/m2 in the treatment group . Absolute mean difference between groups was 4.85 g/m2 ( 95 % confidence interval , -4.0 to 13.7 ; P = 0.28 ) . Mean Hgb level was greater in the treatment group throughout the study and at study end was 12.75 g/dL ( 127.5 g/L in treatment group versus 11.46 g/dL [ 114.6 g/L ] in control/delayed treatment group ; P = 0.0001 ) . LV growth occurred in 20.1 % in the treatment group versus 31 % in the control/delayed treatment group ( P = 0.136 ) . In patients with a stable Hgb level , mean LVMI did not change ( -0.25 + /- 26.7 g/m2 ) , but it increased in those with decreasing Hgb levels ( 19.3 + /- 28.2 g/m2 ; P = 0.002 ) . CONCLUSION This trial describes disparity between observational and r and omized controlled trial data : observed and r and omly assigned Hgb level and LVMI are not linked ; thus , there is strong evidence that the association between Hgb level and LVMI likely is not causal . Large r and omized controlled trials with unselected patients , using morbidity and mortality as outcomes , are needed The investigators evaluated the impact of recombinant human erythropoietin ( r-HuEPO ) therapy on health-related quality of life ( HRQL ) in predialysis chronic renal disease patients with anemia . Eighty-three patients were entered into a r and omized , parallel-group , open-label clinical trial with follow-up evaluations over 48 weeks . Forty-three patients were assigned to r-HuEPO treatment , and 40 patients were assigned to an untreated control group . Hematocrit levels were measured at baseline and monthly . HRQL was assessed at baseline and at weeks 16 , 32 , and 48 . The HRQL assessment included measures of physical function , energy , role function , health distress , cognitive function , social function , home management , sexual dysfunction , depression , and life satisfaction . Significant improvements in hematocrit levels were observed in the r-HuEPO-treated group ( P < 0.0001 ) , and no changes were seen in the untreated group . Correction of anemia ( hematocrit > or = 36 ) occurred in 79 % of r-HuEPO-treated patients and 0 % of control patients . Significant improvements in assessment s of energy ( P < 0.05 ) , physical function ( P < 0.05 ) , home management ( P < 0.05 ) , social activity ( P < 0.05 ) , and cognitive function ( P < 0.05 ) were found for the r-HuEPO-treated group . No changes were observed in the control group , except for a decrease in physical function ( P < 0.05 ) . Between-group differences favoring the r-HuEPO-treated group were found for energy ( P < 0.05 ) and physical functioning ( P < 0.05 ) . In patients receiving r-HuEPO , significant improvements were seen in hemotocrit levels , and these increases result ed in improvements in HRQL BACKGROUND This study is design ed to assess the effect of early and complete correction of anemia by using recombinant human erythropoietin ( epoetin ) alfa on the progression of chronic kidney disease ( CKD ) . METHODS Patients were r and omly assigned to achieve high ( 13 to 15 g/dL [ 130 to 150 g/L ] ) or low ( 11 to 12 g/dL [ 110 to 120 g/L ] ) hemoglobin-level targets during 4 months of stabilization , followed by 36 months of maintenance . Glomerular filtration rate ( GFR ) decrease was measured by using iohexol clearance . Quality of life , nutrition , and safety also were monitored . RESULTS Because of labeling changes for subcutaneous administration of epoetin alfa ( Eprex ; Johnson and Johnson , Schaffhausen , Switzerl and ) , the study was terminated prematurely . There were 195 patients enrolled in each group ; 108 high-hemoglobin and 133 low-hemoglobin patients entered the maintenance phase . Mean maintenance duration was 7.4 months for the high-hemoglobin group and 8.3 months for the low-hemoglobin group . GFR decrease was numerically , but not statistically significantly , lower with the high-hemoglobin group ( 0.058 versus 0.081 mL/min/1.73 m2/mo [ < 0.01 mL/s/1.73 m2/mo ] ) . Physical quality -of-life measures showed trends ( Role-Physical , P = 0.055 ; Physical Function , P = 0.083 ) or statistically significant improvement ( Vitality , P = 0.042 ) with high hemoglobin levels at the end of the stabilization phase . Adverse events were similar between groups . Cardiovascular adverse events occurred in 25 % of the high-hemoglobin and 18 % of the low-hemoglobin patients ( P = 0.137 ) . Neither epoetin dosage nor hemoglobin level was associated with cardiovascular adverse events or death . CONCLUSION These data suggest that normalization of hemoglobin levels in patients with CKD is safe . Longer duration studies are needed to clarify efficacy benefits with high hemoglobin levels BACKGROUND Partial correction of renal anaemia with erythropoietin improves quality of life ( QoL ) . We aim ed to examine if normalization of haemoglobin with epoetin alfa in pre-dialysis and dialysis patients further improves QoL and is safe . METHODS 416 Sc and inavian patients with renal anaemia [ pre-dialysis , haemodialysis ( HD ) and peritoneal dialysis patients ] were r and omized to reach a normal haemoglobin of 135 - 160 g/l ( n=216 ) or a subnormal haemoglobin of 90 - 120 g/l ( n=200 ) with or without epoetin alfa . Study duration was 48 - 76 weeks . QoL was measured using Kidney Disease Question naires in 253 Swedish dialysis patients . Safety was examined in all patients . RESULTS QoL improved , measured as a decrease in physical symptoms ( P=0.02 ) , fatigue ( P=0.05 ) , depression ( P=0.01 ) and frustration ( P=0.05 ) in the Swedish dialysis patients when haemoglobin was normalized . In pre-dialysis patients , diastolic blood pressure was higher in the normal compared with the subnormal haemoglobin group after 48 weeks . However , the progression rate of chronic renal failure was comparable . In the normal haemoglobin group ( N-Hb ) , 51 % had at least one serious adverse event compared with 49 % in the subnormal haemoglobin group ( S-Hb ) ( P=0.32 ) . The incidence of thrombovascular events and vascular access thrombosis in HD patients did not differ . The mortality rate was 13.4 % in the N-Hb group and 13.5 % in the S-Hb group ( P=0.98 ) . Mortality decreased with increasing mean haemoglobin in both groups . CONCLUSIONS Normalization of haemoglobin improved QoL in the subgroup of dialysis patients , appears to be safe and can be considered in many patients with end-stage renal disease BACKGROUND In patients with end-stage renal disease , anemia develops as a result of erythropoietin deficiency , and recombinant human erythropoietin ( epoetin ) is prescribed to correct the anemia partially . We examined the risks and benefits of normalizing the hematocrit in patients with cardiac disease who were undergoing hemodialysis . METHODS We studied 1233 patients with clinical evidence of congestive heart failure or ischemic heart disease who were undergoing hemodialysis : 618 patients were assigned to receive increasing doses of epoetin to achieve and maintain a hematocrit of 42 percent , and 615 were assigned to receive doses of epoetin sufficient to maintain a hematocrit of 30 percent throughout the study . The median duration of treatment was 14 months . The primary end point was the length of time to death or a first nonfatal myocardial infa rct ion . RESULTS After 29 months , there were 183 deaths and 19 first nonfatal myocardial infa rct ions among the patients in the normal-hematocrit group and 150 deaths and 14 nonfatal myocardial infa rct ions among those in the low-hematocrit group ( risk ratio for the normal-hematocrit group as compared with the low-hematocrit group , 1.3 ; 95 percent confidence interval , 0.9 to 1.9 ) . Although the difference in event-free survival between the two groups did not reach the prespecified statistical stopping boundary , the study was halted . The causes of death in the two groups were similar . The mortality rates decreased with increasing hematocrit values in both groups . The patients in the normal-hematocrit group had a decline in the adequacy of dialysis and received intravenous iron dextran more often than those in the low-hematocrit group . CONCLUSIONS In patients with clinical ly evident congestive heart failure or ischemic heart disease who are receiving hemodialysis , administration of epoetin to raise their hematocrit to 42 percent is not recommended BACKGROUND Erythropoietin is known to improve outcomes in patients with anemia from chronic renal disease . However , there is uncertainty about the optimal timing of initiation of erythropoietin treatment in predialysis patients with non-severe anemia . METHODS We conducted a r and omized controlled trial of early versus deferred initiation of erythropoietin in nondiabetic predialysis patients with serum creatinine 2 to 6 mg/dL and hemoglobin 9 to 11.6 g/dL. The early treatment arm was immediately started on 50 U/kg/wk of erythropoietin alpha with appropriate titration aim ing for hemoglobin of > or = 13 g/dL. The deferred treatment arm would start erythropoietin only when hemoglobin decreased to < 9 g/dL. The primary end point was a composite of doubling of creatinine , renal replacement , or death . RESULTS Eighty-eight patients were r and omized ( early treatment N= 45 , deferred treatment N= 43 ) and followed for a median of 22.5 months . During follow-up , 13 versus 23 patients reached the primary end point in the two arms , respectively ( log-rank P= 0.0078 ) . The relative hazard for reaching an end point was 0.42 ( P= 0.012 ) . Adjusting for baseline serum creatinine , the adjusted relative hazard was 0.37 ( P= 0.004 ) , while the risk increased 2.23-fold ( P < 0.001 ) per 1 mg/dL higher creatinine at baseline . The benefit was similar regardless of the baseline hemoglobin and proteinuria . No patients had any severe adverse events . CONCLUSION Early initiation of erythropoietin in predialysis patients with non-severe anemia significantly slows the progression of renal disease and delays the initiation of renal replacement therapy It is not known whether prevention of anemia among patients with chronic kidney disease would affect the development or progression of left ventricular ( LV ) hypertrophy . A r and omized controlled trial was performed with 155 patients with chronic kidney disease ( creatinine clearance , 15 to 50 ml/min ) , with entry hemoglobin concentrations ( [ Hb ] ) of 110 to 120 g/L ( female patients ) or 110 to 130 g/L ( male patients ) . Patients were monitored for 2 yr or until they required dialysis ; the patients were r and omized to receive epoetin alpha as necessary to maintain [ Hb ] between 120 and 130 g/L ( group A ) or between 90 and 100 g/L ( group B ) . [ Hb ] increased for group A ( from 112 + /- 9 to 121 + /- 14 g/L , mean + /- SD ) and decreased for group B ( from 112 + /- 8 to 108 + /- 13 g/L ) ( P < 0.001 , group A versus group B ) . On an intent-to-treat analysis , the changes in LV mass index for the groups during the 2-yr period were not significantly different ( 2.5 + /- 20 g/m(2 ) for group A versus 4.5 + /- 20 g/m(2 ) for group B , P = NS ) . There was no significant difference between the groups in 2-yr mean unadjusted systolic BP ( 141 + /- 14 versus 138 + /- 13 mmHg ) or diastolic BP ( 80 + /- 6 versus 79 + /- 7 mmHg ) . The decline in renal function in 2 yr , as assessed with nuclear estimations of GFR , also did not differ significantly between the groups ( 8 + /- 9 versus 6 + /- 8 ml/min per 1.73 m(2 ) ) . In conclusion , maintenance of [ Hb ] above 120 g/L , compared with 90 to 100 g/L , had similar effects on the LV mass index and did not clearly affect the development or progression of LV hypertrophy . The maintenance of [ Hb ] above 100 g/L for many patients in group B might have been attributable to the relative preservation of renal function BACKGROUND Hemoglobin levels below 10 g/dL lead to left ventricular ( LV ) hypertrophy , LV dilation , a lower quality of life , higher cardiac morbidity , and a higher mortality rate in end-stage renal disease . The benefits and risks of normalizing hemoglobin levels in hemodialysis patients without symptomatic cardiac disease are unknown . METHODS One hundred forty-six hemodialysis patients with either concentric LV hypertrophy or LV dilation were r and omly assigned to receive doses of epoetin alpha design ed to achieve hemoglobin levels of 10 or 13.5 g/dL. The study duration was 48 weeks . The primary outcomes were the change in LV mass index in those with concentric LV hypertrophy and the change in cavity volume index in those with LV dilation . RESULTS In patients with concentric LV hypertrophy , the changes in LV mass index were similar in the normal and low target hemoglobin groups . The changes in cavity volume index were similar in both targets in the LV dilation group . Treatment-received analysis of the concentric LV hypertrophy group showed no correlation between the change in mass index and a correlation between the change in LV volume index and mean hemoglobin level achieved ( 8 mL/m2 per 1 g/dL hemoglobin decrement , P = 0.009 ) . Mean hemoglobin levels and the changes in LV mass and cavity volume index were not correlated in patients with LV dilation . Normalization of hemoglobin led to improvements in fatigue ( P = 0.009 ) , depression ( P = 0.02 ) , and relationships ( P = 0.004 ) . CONCLUSIONS Normalization of hemoglobin does not lead to regression of established concentric LV hypertrophy or LV dilation . It may , however , prevent the development of LV dilation , and it leads to improved quality of life BACKGROUND The effects of the dose of dialysis and the level of flux of the dialyzer membrane on mortality and morbidity among patients undergoing maintenance hemodialysis are uncertain . METHODS We undertook a r and omized clinical trial in 1846 patients undergoing thrice-weekly dialysis , using a two-by-two factorial design to assign patients r and omly to a st and ard or high dose of dialysis and to a low-flux or high-flux dialyzer . RESULTS In the st and ard-dose group , the mean ( + /-SD ) urea-reduction ratio was 66.3+/-2.5 percent , the single-pool Kt/V was 1.32+/-0.09 , and the equilibrated Kt/V was 1.16+/-0.08 ; in the high-dose group , the values were 75.2+/-2.5 percent , 1.71+/-0.11 , and 1.53+/-0.09 , respectively . Flux , estimated on the basis of beta2-microglobulin clearance , was 3+/-7 ml per minute in the low-flux group and 34+/-11 ml per minute in the high-flux group . The primary outcome , death from any cause , was not significantly influenced by the dose or flux assignment : the relative risk of death in the high-dose group as compared with the st and ard-dose group was 0.96 ( 95 percent confidence interval , 0.84 to 1.10 ; P=0.53 ) , and the relative risk of death in the high-flux group as compared with the low-flux group was 0.92 ( 95 percent confidence interval , 0.81 to 1.05 ; P=0.23 ) . The main secondary outcomes ( first hospitalization for cardiac causes or death from any cause , first hospitalization for infection or death from any cause , first 15 percent decrease in the serum albumin level or death from any cause , and all hospitalizations not related to vascular access ) also did not differ significantly between either the dose groups or the flux groups . Possible benefits of the dose or flux interventions were suggested in two of seven prespecified subgroups of patients . CONCLUSIONS Patients undergoing hemodialysis thrice weekly appear to have no major benefit from a higher dialysis dose than that recommended by current U.S. guidelines or from the use of a high-flux membrane It is unclear whether physiologic hemoglobin targets lead to cardiac benefit in incident hemodialysis patients without symptomatic heart disease and left ventricular dilation . In this r and omized , double-blind study , lower ( 9.5 to 11.5 g/dl ) and higher ( 13.5 to 14.5 g/dl ) hemoglobin targets were generated with epoetin alpha over 24 wk and maintained for an additional 72 wk . Major eligibility criteria included recent hemodialysis initiation and absence of symptomatic cardiac disease and left ventricular dilation . The primary outcome measure was left ventricular volume index ( LVVI ) . The study enrolled 596 patients . Mean age , duration of dialysis therapy , baseline predialysis hemoglobin , and LVVI were 50.8 yr , 0.8 yr , 11.0 g/dl , and 69 ml/m2 , respectively ; 18 % had diabetic nephropathy . Mean hemoglobin levels in the higher and lower target groups were 13.3 and 10.9 g/dl , respectively , at 24 wk . Percentage changes in LVVI between baseline and last value were similar ( 7.6 % in the higher and 8.3 % in the lower target group ) as were the changes in left ventricular mass index ( 16.8 versus 14.2 % ) . For the secondary outcomes , the only between-group difference was an improved SF-36 Vitality score in the higher versus the lower target group ( 1.21 versus -2.31 ; P = 0.036 ) . Overall adverse event rates were similar in both target groups ; higher ( P < 0.05 ) rates of skeletal pain , surgery , and dizziness were seen in the lower target group , and headache and cerebrovascular events were seen in the higher target group . Normalization of hemoglobin in incident hemodialysis patients does not have a beneficial effect on cardiac structure , compared with partial correction Background . It is generally agreed that r and omized controlled trials should be powered to detect small but clinical ly significant treatment effects . Toward these ends , minimal important difference ( MID ) was proposed as a benchmark for design ing trials and for interpreting health-related quality -of-life instrument scores . MID was defined in 1989 as “ the smallest difference in score in the domain of interest which patients perceive as beneficial and which would m and ate , in the absence of troubling side effects and excessive cost , a change in the patient ’s management . ” Objective . 1 ) To exp and the idea of minimal clinical ly important difference so as to take into account harms as well as benefits . 2 ) To propose concepts and methods with which to do so . Summary . The authors define sufficiently important difference ( SID ) as the smallest amount of patient-valued benefit that an intervention would require to justify associated costs , risks , and other harms . As a means toward estimation of SID , the authors propose benefit-harm tradeoff methods , in which domains of benefit and harm are systematic ally traded off against each other and assessed in relation to the global decision of whether a treatment choice is worthwhile . Specific SID estimates can be used to power and interpret clinical trials or to inform health services research and /or public health policy . This article briefly describes the evolution of the important difference concept and outlines similarities and differences between MID and SID Elevated serum phosphorus and calcium are associated with arterial calcification and mortality in dialysis patients . Unlike calcium-based binders , sevelamer attenuates arterial calcification but it is unknown whether sevelamer affects mortality or morbidity . In a multicenter , r and omized , open-label , parallel design trial we compared sevelamer and calcium-based binders on all-cause and cause-specific mortality ( cardiovascular , infection , and other ) in prevalent hemodialysis patients . A total of 2103 patients were initially r and omized to treatment and 1068 patients completed the study . All-cause mortality rates and cause-specific mortality rates were not significantly different . There was a significant age interaction on the treatment effect . Only in patients over 65 years of age was there a significant effect of sevelamer in lowering the mortality rate . There was a suggestion that sevelamer was associated with lower overall , but not cardiovascular-linked , mortality in older patients . We suggest that further research is needed to confirm these findings The Clinical Practice Guideline ( CPG ) and Clinical Practice Recommendations ( CPRs ) are design ed to provide information and assist decision-making . They are not intended to define a st and ard of care , and should not be construed as one . Neither should they be interpreted as prescribing an exclusive course of management . Variations in practice will inevitably and appropriately occur when clinicians take into account the needs of individual patients , available re sources , and limitations unique to an institution or type of practice . Every health-care professional making use of the CPG and CPRs is responsible for evaluating the appropriateness of applying them in the setting of any particular clinical situation . The National Kidney Foundation ( NKF ) makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal , professional , or business interest of a member of the Work Group . Specifically , all members of the Work Group are required to complete , sign , and su bmi t a Conflict of Interest : Disclosure and Attestation form showing all such relationships that might be perceived as real or potential conflicts of interest . All affiliations are published in their entirety at the end of this document in the Work Group members ' biographical sketch and are on file at the NKF . FIGURES Figure 1 . R and omized controlled trials comparing lower with higher Hb target levels … … … . 11 Figure 2 . Relative mortality risk for assignment to higher Hb treatment targets in patients with non-dialysis CKD ( Stages 1 - 5 ) … …… …… …… …… …… …… …… …… …… 13 Figure 3 . Relative risk of adverse cardiovascular events for assignment to higher Hb treatment target in patients with non-dialysis CKD ( Stage 1 - 5 ) …… …… …… …… .. 13 Figure 4 . Relative mortality risk for assignment to higher Hb treatment target in CKD patients undergoing dialysis …… …… …… …… …… …… …… …… …… …… …… 14 Figure 5 . Relative risk of adverse cardiovascular events for assignment to higher Hb treatment target in CKD patients undergoing dialysis … … … … … … … … … … … … . 2 3 The Hb target is the intended aim of ESA therapy for the individual CKD patient . In clinical 4 practice , achieved Hb results vary considerably from the Hb target . 5 6 7 2.1.1 In the opinion of the work group , selection of the Hb target and selection of the Hb 8 level at which ESA therapy is initiated in the individual patient should include 9 consideration of potential benefits ( including improvement in quality of life and 10 avoidance of transfusion ) and potential harms ( including the risk of life-threatening 11 adverse events ) . ( Clinical Practice RECOMMENDATION ) 12 BACKGROUND Whether correction of anemia in patients with stage 3 or 4 chronic kidney disease improves cardiovascular outcomes is not established . METHODS We r and omly assigned 603 patients with an estimated glomerular filtration rate ( GFR ) of 15.0 to 35.0 ml per minute per 1.73 m2 of body-surface area and mild-to-moderate anemia ( hemoglobin level , 11.0 to 12.5 g per deciliter ) to a target hemoglobin value in the normal range ( 13.0 to 15.0 g per deciliter , group 1 ) or the subnormal range ( 10.5 to 11.5 g per deciliter , group 2 ) . Subcutaneous erythropoietin ( epoetin beta ) was initiated at r and omization ( group 1 ) or only after the hemoglobin level fell below 10.5 g per deciliter ( group 2 ) . The primary end point was a composite of eight cardiovascular events ; secondary end points included left ventricular mass index , quality -of-life scores , and the progression of chronic kidney disease . RESULTS During the 3-year study , complete correction of anemia did not affect the likelihood of a first cardiovascular event ( 58 events in group 1 vs. 47 events in group 2 ; hazard ratio , 0.78 ; 95 % confidence interval , 0.53 to 1.14 ; P=0.20 ) . Left ventricular mass index remained stable in both groups . The mean estimated GFR was 24.9 ml per minute in group 1 and 24.2 ml per minute in group 2 at baseline and decreased by 3.6 and 3.1 ml per minute per year , respectively ( P=0.40 ) . Dialysis was required in more patients in group 1 than in group 2 ( 127 vs. 111 , P=0.03 ) . General health and physical function improved significantly ( P=0.003 and P<0.001 , respectively , in group 1 , as compared with group 2 ) . There was no significant difference in the combined incidence of adverse events between the two groups , but hypertensive episodes and headaches were more prevalent in group 1 . CONCLUSIONS In patients with chronic kidney disease , early complete correction of anemia does not reduce the risk of cardiovascular events . ( Clinical Trials.gov number , NCT00321919 [ Clinical Trials.gov ] . ) |
997 | 19,359,999 | There is strong evidence that the use of insoles does not prevent back pain .
There is limited evidence that insoles alleviate back pain or adversely shift the pain to the lower extremities .
CONCLUSION There is strong evidence that insoles are not effective for the prevention of back pain . | SUMMARY OF BACKGROUND DATA There is lack of theoretical and clinical knowledge of the use of insoles for prevention or treatment of back pain . | 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 Study Design . R and omized controlled trial . Objectives . To determine if the use of custom shoe orthoses can lessen the incidence of weight bearing-induced back pain . Summary of Background Data . The scientific basis for the use of orthoses to prevent back pain is based principally on studies that show that shoe orthoses can attenuate the shock wave generated at heel strike . The repetitive impulsive loading that occurs because of this shock wave can cause wear of the mechanical structures of the back . Previous r and omized studies showed mixed results in preventing back pain , were not blinded , and used orthoses for only short periods of time . Methods . A total of 404 eligible new infantry recruits without a history of prior back pain were r and omly assigned to received either custom soft , semirigid biomechanical , or simple shoe inserts without supportive or shock absorbing qualities . Recruits were review ed biweekly by an orthopaedist for back signs and symptoms during the course of 14 weeks of basic training Results . The overall incidence of back pain was 14 % . By intention-to treat and per- protocol analyses , there was no statistically significant difference between the incidence of either subjective or objective back pain among the 3 treatment groups . Significantly more recruits who received soft custom orthoses finished training in their assigned orthoses ( 67.5 % ) than those who received semirigid biomechanical orthoses ( 45.5 % ) or simple shoe inserts ( 48.6 % ) , P = 0.001 . Conclusions . The results of this study do not support the use of orthoses , either custom soft or semirigid biomechanical , as prophylactic treatment for weight bearing-induced back pain . Custom soft orthoses had a higher utilization rate than the semirigid biomechanical or simple shoe inserts . The pretraining physical fitness and sports participation of recruits were not related to the incidence of weight bearing-induced back pain & NA ; Pain intensity is frequently measured on an 11‐point pain intensity numerical rating scale ( PI‐NRS ) , where 0=no pain and 10=worst possible pain . However , it is difficult to interpret the clinical importance of changes from baseline on this scale ( such as a 1‐ or 2‐point change ) . To date , there are no data driven estimates for clinical ly important differences in pain intensity scales used for chronic pain studies . We have estimated a clinical ly important difference on this scale by relating it to global assessment s of change in multiple studies of chronic pain . Data on 2724 subjects from 10 recently completed placebo‐controlled clinical trials of pregabalin in diabetic neuropathy , postherpetic neuralgia , chronic low back pain , fibromyalgia , and osteoarthritis were used . The studies had similar design s and measurement instruments , including the PI‐NRS , collected in a daily diary , and the st and ard seven‐point patient global impression of change ( PGIC ) , collected at the endpoint . The changes in the PI‐NRS from baseline to the endpoint were compared to the PGIC for each subject . Categories of ‘ much improved ’ and ‘ very much improved ’ were used as determinants of a clinical ly important difference and the relationship to the PI‐NRS was explored using graphs , box plots , and sensitivity/specificity analyses . A consistent relationship between the change in PI‐NRS and the PGIC was demonstrated regardless of study , disease type , age , sex , study result , or treatment group . On average , a reduction of approximately two points or a reduction of approximately 30 % in the PI‐NRS represented a clinical ly important difference . The relationship between percent change and the PGIC was also consistent regardless of baseline pain , while higher baseline scores required larger raw changes to represent a clinical ly important difference . The application of these results to future studies may provide a st and ard definition of clinical ly important improvement in clinical trials of chronic pain therapies . Use of a st and ard outcome across chronic pain studies would greatly enhance the comparability , validity , and clinical applicability of these studies The prevalence and incidence of low back pain in general society is high . Workers whose job involves walking long distances have an even higher tendency to suffer from low back pain . A positive effect of insoles in reducing low back pain was found in professional sports players . This was not examined on people whose job involves walking long distances . In this double blind prospect i ve study we examined the effectiveness of insoles constructed in a computerized method to placebo insoles in 58 employees whose work entailed extensive walking and who suffered from low back pain . The evaluation was performed by the MILLION question naire , which is considered as a valid question naire for evaluation of low back pain . We calculated the differences of the pain intensity before and after the intervention , in the employees using the insoles manufactured by computer in comparison to the users of the placebo insoles . In each group , the analysis was performed in comparison to the baseline . A total of 81 % of the employees preferred the real insoles as effective and comfortable in comparison to 19 % of the users of the placebo insoles ( P<0.05 ) . The results of this study indicate a substantial improvement in the low back pain after the use of the true insoles . The average pain intensity according to the MILLION question naire before the use of the insoles was 5.46 . However , after the use of the real insoles and the placebo insoles , the average pain intensity decreased to 3.96 and 5.11 , respectively . The difference of the average pain intensity at the start of the study and after the use of the real insoles was significant : −1.49 ( P=0.0001 ) , whereas this difference after the use of the placebo insoles was not significant : −0.31 ( P=0.1189 ) . The reported severity of pain also decreased significantly : a level 5 pain and above was reported by 77 % of the subjects at the start of the study . After the use of the real insoles only 37.9 % of the subjects reported a similar degree of pain severity , and 50 % of the subjects did so after the use of the placebo insoles ( P < 0.05 ) . We did not find a link between low back pain and other variables such as gender , age , number of offspring , work seniority , smoking , previous use of insoles and previous medication . This study demonstrates that the low back pain decreased significantly after the use of real insoles compared to placebo ones Sedentary individuals , particularly new military recruits , who start a physical training program have a substantial risk of developing an overuse injury of the lower limb . In this study we investigated the effect of neoprene insoles on the incidence of overuse injuries during 9 weeks of basic military training . The experimental group consisted of 237 r and omly selected new recruits , while 1151 recruits were the control group . Insoles were given to the experimental group and compliance was monitored . A panel of doctors documented and classi fied all injuries occurring during the 9 week period . A total of 54 ( 22.8 % ) and 237 ( 31.9 % ) injuries were reported in the experimental and control groups , re spectively . In both groups , the majority of injuries were overuse ( experimental group , 90.7 % ; control group , 86.4 % ) . The mean weekly incidence of total overuse injuries and tibial stress syndrome was significantly lower ( P < 0.05 ) in the experimental group . The mean incidence of stress fractures was lower in the experimental group but not significantly so ( 0.05 < P < 0.1 ) . This study shows that the incidence of total overuse injuries and tibial stress syndrome during 9 weeks of basic military training can be reduced by wearing insoles The purpose of this study was to assess the effect of viscoelastic shoe inserts on pain in nursing students . Students ( N = 100 ) were r and omly assigned to control and viscoelastic groups . The viscoelastic group used viscoelastic insoles in their work shoes for five weeks . A pain question naire was used to measure location and intensity of post-work pain . The question naire was administered as a pre-test and after five weeks . Post-test comparisons between groups indicated significant differences which were not present at pre-test . The viscoelastic group reported a significant peripheral shift in pain location from back to lower extremity ; the viscoelastic group also showed significant changes in duration of post-work pain and frequency of pain during the workday . The clinical efficacy of viscoelastic shoe inserts for modifying weight bearing-induced back pain is supported . Further clinical research into the therapeutic and prophylactic value of shock-attenuating shoe inserts for healthy as well as patient population s is advocated |
998 | 26,646,017 | Compared to other antiarrhythmics ( four studies , 839 participants ) amiodarone appeared to increase the risk of SCD ( RR 1.40 ; 95 % CI 0.56 to 3.52 ; very low quality of evidence ) , but there was no effect in all-cause mortality ( RR 1.03 ; 95 % CI 0.75 to 1.42 ; low quality evidence ) .Amiodarone was associated with an increase in pulmonary and thyroid adverse events .
AUTHORS ' CONCLUSIONS There is low to moderate quality evidence that amiodarone reduces SCD , cardiac and all-cause mortality when compared to placebo or no intervention for primary prevention , and its effects are superior to other antiarrhythmics . | BACKGROUND Sudden cardiac death ( SCD ) is one of the main causes of cardiac death .
There are two main strategies to prevent it : managing cardiovascular risk factors and reducing the risk of ventricular arrhythmias .
Implantable cardiac defibrillators ( ICDs ) constitute the st and ard therapy for both primary and secondary prevention ; however , they are not widely available in setting s with limited re sources .
The antiarrhythmic amiodarone has been proposed as an alternative to ICD .
OBJECTIVES To evaluate the effectiveness of amiodarone for primary or secondary prevention in SCD compared with placebo or no intervention or any other antiarrhythmic drugs in participants at high risk ( primary prevention ) or who have recovered from a cardiac arrest or a syncope due to Ventricular Tachycardia/Ventricular Fibrillation , or VT/VF ( secondary prevention ) . | BACKGROUND We conducted a prospect i ve , multicenter , r and omized comparison of implantable cardioverter-defibrillator ( ICD ) versus antiarrhythmic drug therapy in survivors of cardiac arrest secondary to documented ventricular arrhythmias . METHODS AND RESULTS From 1987 , eligible patients were r and omized to an ICD , amiodarone , propafenone , or metoprolol ( ICD versus antiarrhythmic agents r and omization ratio 1:3 ) . Assignment to propafenone was discontinued in March 1992 , after an interim analysis conducted in 58 patients showed a 61 % higher all-cause mortality rate than in 61 ICD patients during a follow-up of 11.3 months . The study continued to recruit 288 patients in the remaining 3 study groups ; of these , 99 were assigned to ICDs , 92 to amiodarone , and 97 to metoprolol . The primary end point was all-cause mortality . The study was terminated in March 1998 , when all patients had concluded a minimum 2-year follow-up . Over a mean follow-up of 57+/-34 months , the crude death rates were 36.4 % ( 95 % CI 26.9 % to 46.6 % ) in the ICD and 44.4 % ( 95 % CI 37.2 % to 51.8 % ) in the amiodarone/metoprolol arm . Overall survival was higher , though not significantly , in patients assigned to ICD than in those assigned to drug therapy ( 1-sided P=0.081 , hazard ratio 0.766 , [ 97.5 % CI upper bound 1.112 ] ) . In ICD patients , the percent reductions in all-cause mortality were 41.9 % , 39.3 % , 28 . 4 % , 27.7 % , 22.8 % , 11.4 % , 9.1 % , 10.6 % , and 24.7 % at years 1 to 9 of follow-up . CONCLUSIONS During long-term follow-up of cardiac arrest survivors , therapy with an ICD is associated with a 23 % ( nonsignificant ) reduction of all-cause mortality rates when compared with treatment with amiodarone/metoprolol . The benefit of ICD therapy is more evident during the first 5 years after the index event Background Carvedilol therapy has been reported to be more effective than other beta-blockers in patients with chronic heart failure ( CHF ) . Amiodarone is an anti-arrhythmic medicine that has also been reported to be effective in patients with CHF . But the usefulness of combined therapy with carvedilol and amiodarone has not been reported . Methods We compared 15 patients ( M/F=3/12 , age=57±8 y ) with dilated cardiomyopathy ( DCM ) receiving carvedilol and amiodarone with 15 patients ( M/F=3/12 , age=61±9 y ) receiving carvedilol alone . Patients were studied before and after 1 year of treatment ( 1Y ) . NYHA class and exercise capacity based on the specific-activity-scale ( SAS ) , were assessed . Cardiac sympathetic nerve activity was estimated using total defect score ( TDS ) , H/M ratio and washout rate ( WR ) of 123I-MIBG imaging . Cardiac function was evaluated using 99mTc-MIBI QGS . Results Combined , therapy improved several parameters much more than carvedilol alone ( p<0.05 ) including delta-TDS ( 15.0±8.6 vs. 7.6±7.2 ) and delta- WR ( 15.9±11.0 % vs. 7.3±10.0 % ) for 123I-MIBG imaging , delta-LVEF ( 26.1±11.4 % vs. 15.5±13.8 % ) , delta-endsystolic volume ( 100±63.8 ml vs. 58.9±47.3 ml ) , 1Y NYHA class ( 1.5±0.5 vs. 1.9±0.5 ) , 1Y SAS ( 7.3±0.7 Mets vs. 6.2±1.0 Mets ) , and delta-SAS ( 3.4±0.8 Mets vs. 2.6±1.1 Mets ) . Conclusion Combined therapy with carvedilol and amiodarone is more effective in improving cardiac symptoms , exercise capacity , cardiac function and cardiac sympathetic nerve activity in patients with DCM Background In the Basel Antiarrhythmic Study of Infa rct Survival trial , low-dose amiodarone improved 1-year survival in patients with asymptomatic complex ventricular arrhythmias persisting 2 weeks after myocardial infa rct ion . To assess whether this beneficial effect persisted despite discontinuation of amiodarone after 1 year , the long-term outcomes of all patients of the amiodarone-treated group ( initially n=98 ) and those of the control group ( n=114 ) were assessed . Methods and Results After a mean follow-up of 72 ( 55–125 ) months , information on 96 % of patients ( 203 of 212 ) was obtained regarding survival or cause of death . The probability of death after 84 months according to actuarial life-table analysis ( Kaplan-Meier ) was 30%1 for the amiodarone-treated patients and 45 % for control patients . For the total follow-up , mortality remained significantly lower in the amiodarone group versus the control group regarding all deaths ( p=0.03 ) as well as cardiac death ( p=0.047 ) . This mortality reduction was entirely due to the first-year amiodarone effect , since there was no significant mortality difference between groups when considering survival after discontinuation of amiodarone only . Conclusion These data suggest that the beneficial effect of amiodarone on survival in this high-risk group of patients persists for several years . In addition , the results stress the importance of early treatment after myocardial infa rct ion , whereas the rate of sudden death and all cardiac death is low ( 1.6 % and 4.1 % per year , respectively ) during late follow-up and therefore may not warrant further therapy Background — Corresponding with a continuing decline in the prevalence of sudden cardiac arrest cases presenting with ventricular fibrillation ( VF ) , there has been a significant rise in the prevalence of pulseless electrical activity ( PEA ) . Given significantly lower survival from PEA versus VF , we comprehensively investigated PEA correlates by incorporating first-responder data with lifetime clinical history information . Methods and Results — In the Portl and , Ore , metropolitan area ( population ≈1 million ) , cases of out-of-hospital sudden cardiac arrest who underwent attempted resuscitation were identified prospect ively ( 2002–2007 ) . Those presenting with PEA versus VF and asystole were compared with & khgr;2 tests , ANOVA , and logistic regression . A total of 1277 cases aged ≥18 years underwent resuscitation by first responders ( mean age , 65±16 years ; 67 % male ) . Presenting arrhythmia was VF in 48 % , PEA in 25 % , and asystole/other in the remainder . Compared with VF cases , PEA cases were older ( mean age , 68 versus 63 years ; P=0.0002 ) , more likely to be female ( 37 % versus 26 % ; P=0.0008 ) , and less likely to survive to hospital discharge ( 6 % versus 25 % ; P<0.0001 ) . A history of syncope was strongly associated with PEA ( odds ratio , 2.6 ; confidence interval , 1.3 to 5.3 ) after adjustment for age , gender , response time , and arrest circumstances . Black race was also independently associated with PEA ( odds ratio , 2.6 ; confidence interval , 1.3 to 5.4 ) . Pulmonary disease and female gender were significant factors associated with PEA ( P for interaction=0.04 ) . In a subgroup analysis of resting ECGs ( n=391 ) , there were no differences in cardiac clinical history or prevalence of cardiac conduction system disease ( PEA , 31.6 % versus VF , 32.2 % ; P=0.48 ) . Conclusions — PEA cases had a significantly higher prevalence of syncope in their lifetime , with other correlates , including black race , that were distinct from VF cases . Potential mechanistic links between syncope and future manifestation with PEA warrant further exploration Objective : To study the therapeutic effects of low-dose amiodarone and Betaloc on hypertrophic cardiomyopathy complicated by malignant ventricular arrhythmias . Methods : Eighty-two such patients were selected and divided into a treatment group and a control group by the r and om number method ( n=41 ) , which were administered with low-dose amiodarone plus Betaloc and individual Betaloc respectively . Results : The treatment group had a significantly higher overall effective rate ( 85.4 % ) than the control group ( 65.9 % ) did . Based on the New York Heart Association 's classification of cardiovascular disease , the treatment group mainly comprised Class III and IV patients before treatment , which were significantly relieved after treatment ( P<0.05 ) . The heart rate was evidently decreased from ( 119.99±18.91 ) bpm to ( 80.98±12.34 ) bpm , and the incidences of premature ventricular contraction and tachycardia were significantly reduced ( P<0.05 ) . The longest QT intervals after and before treatment were ( 421±32 ) ms and ( 411±35 ) ms respectively . The shortest QT interval after treatment [ ( 350±36 ) ms ] was significantly longer than that before [ ( 307±31 ) ms ] . The QT dispersion before treatment [ ( 96±29 ) ms ] was significantly higher that after [ ( 64±17 ) ms ] ( P<0.05 ) . Six out of eighty two patients in the treatment group succumbed to adverse reactions ( 14.63 % ) . Conclusion : Hypertrophic cardiomyopathy complicated with malignant ventricular arrhythmias can be well treated with low-dose amiodarone and Betaloc , with mitigated symptoms , improved prognosis and few adverse reactions OBJECTIVES The purpose of this multicenter r and omized trial was to compare total mortality during therapy with amiodarone or an implantable cardioverter-defibrillator ( ICD ) in patients with nonischemic dilated cardiomyopathy ( NIDCM ) and nonsustained ventricular tachycardia ( NSVT ) . BACKGROUND Whether an ICD reduces mortality more than amiodarone in patients with NIDCM and NSVT is unknown . METHODS One hundred three patients with NIDCM , left ventricular ejection fraction < or = 0.35 , and asymptomatic NSVT were r and omized to receive either amiodarone or an ICD . The primary end point was total mortality . Secondary end points included arrhythmia-free survival , quality of life , and costs . RESULTS The study was stopped when the prospect i ve stopping rule for futility was reached . The percent of patients surviving at one year ( 90 % vs. 96 % ) and three years ( 88 % vs. 87 % ) in the amiodarone and ICD groups , respectively , were not statistically different ( p = 0.8 ) . Quality of life was also similar with each therapy ( p = NS ) . There was a trend with amiodarone , as compared to the ICD , towards improved arrhythmia-free survival ( p = 0.1 ) and lower costs during the first year of therapy ( $ 8,879 US dollars vs. $ 22,039 US dollars , p = 0.1 ) . CONCLUSIONS Mortality and quality of life in patients with NIDCM and NSVT treated with amiodarone or an ICD are not statistically different . There is a trend towards a more beneficial cost profile and improved arrhythmia-free survival with amiodarone therapy Background —Sudden cardiac death ( SCD ) is a leading cause of death in the United States , but the relative public health burden is unknown . We estimated the burden of premature death from SCD and compared it with other diseases . Methods and Results —Analyses were based on the following data sources ( using most recent sources that provided appropriately stratified data ): ( 1 ) leading causes of death among men and women from 2009 US death certificate reporting ; ( 2 ) individual cancer mortality rates from 2008 death certificate reporting from the Centers for Disease Control and Prevention ’s National Program of Cancer Registries ; ( 3 ) county , state , and national population data for 2009 from the US Census Bureau ; and ( 4 ) SCD rates from the Oregon Sudden Unexpected Death Study ( SUDS ) population -based surveillance study of SCD between 2002 and 2004 . Cases were identified from multiple sources in a prospect ively design ed surveillance program . Incidence , counts , and years of potential life lost for SCD and other major diseases were compared . The age-adjusted national incidence of SCD was 60 per 100 000 population ( 95 % confidence interval , 54–66 per 100 000 ) . The burden of premature death for men ( 2.04 million years of potential life lost ; 95 % uncertainty interval , 1.86–2.23 million ) and women ( 1.29 million years of potential life lost ; 95 % uncertainty interval , 1.13–1.45 million ) was greater for SCD than for all individual cancers and most other leading causes of death . Conclusions —The societal burden of SCD is high relative to other major causes of death . Accordingly , improved national surveillance with the goal of optimizing and monitoring SCD prevention and treatment should be a high priority The Cardiac Arrest in Seattle : Conventional Versus Amiodarone Drug Evaluation ( CASCADE ) study evaluated antiarrhythmic drug therapy in patients who had survived an episode of out-of-hospital ventricular fibrillation ( VF ) and who were thought to be at high risk for recurrence of VF . Therapy with empiric amiodarone was compared to therapy with other antiarrhythmic agents , guided by electrophysiologic testing and /or Holter recording . The study evaluated the endpoints of ( 1 ) cardiac death , ( 2 ) cardiac arrest from ventricular fibrillation with resuscitation , and ( 3 ) complete syncope followed by a shock from an automatic implanted defibrillator that restored consciousness . The study comprised 228 patients , 113 treated with amiodarone and 115 treated with conventional antiarrhythmic drug therapy . Most patients had coronary artery disease with a prior myocardial infa rct ion , and one half of the population had a history of congestive heart failure . The mean left ventricular ejection fraction was 35 % . Survival was better in patients treated with amiodarone than in patients treated with other antiarrhythmic agents . Patients treated with amiodarone were less likely to receive a shock from an implanted defibrillator , and syncope followed by a shock from a defibrillator was less common in patients treated with amiodarone . However , overall mortality was high , and side effects of therapy were common . Patients treated with amiodarone , even at the low doses used in this study , were still at risk for thyroid dysfunction ( both hyperthyroidism and hypothyroidism ) and for pulmonary toxicity Sudden cardiac death is a common cause of mortality in patients with congestive heart failure . To determine if low-dose amiodarone could reduce sudden death among these patients , a prospect i ve , placebo-controlled , double-blind pilot trial was conducted . One hundred one patients with ejection fractions less than 30 % , New York Heart Association class III or IV symptoms , and frequent but asymptomatic spontaneous ventricular ectopy ( Lown class II to V ) were r and omly assigned to treatment with low-dose amiodarone ( 400 mg/day for 4 weeks and then 200 mg/day ) or placebo . Mean follow-up was 357 days ( range 4 to 1009 days ) . Side effects were infrequent and there was no difference in the incidence of side effects between the treatment groups . The frequency of spontaneous ventricular ectopy in the group receiving amiodarone fell from 4992 + /- 1240 beats/24 hours at baseline to 1135 + /- 494 beats/24 hours after 1 month of treatment ( p = 0.02 ) and remained low after 6 months , while there was no change in ventricular ectopy among the patients receiving placebo . Despite the reduction in ectopy , there was no improvement in mortality or decrease in the incidence of sudden death . One-year mortality by Kaplan-Meier analysis was 28 % in the group receiving amiodarone and 19 % in the group receiving placebo ( p = NS ) . One-year mortality in patients with greater than 75 % reduction in ventricular ectopy after 1 month of treatment was 31 % versus 17 % in patients with less than or equal to 75 % ectopic suppression ( p = NS ) . ( ABSTRACT TRUNCATED AT 250 WORDS A r and omized trial was conducted to assess the efficacy of amiodarone versus metoprolol or no antiarrhythmic treatment to suppress asymptomatic ectopic activity and improve survival in patients who have had myocardial infa rct ion with a left ventricular ejection fraction of 20 to 45 % and > or = 3 ventricular premature complexes per hour ( pairs or runs ) . Patients ( n = 368 ) were r and omly assigned to receive amiodarone 200 mg/day ( n = 115 ) 10 to 60 days after the acute episode , and metoprolol 100 to 200 mg/day ( n = 130 ) or no antiarrhythmic therapy ( n = 123 ) . After a median follow-up of 2.8 years , mortality in the amiodarone-treated patients ( 3.5 + /- 2 % SEM ) did not differ significantly from that of untreated control subjects ( 7.7 + /- 2.5 % , p = 0.19 ) , but was lower than that in the metoprolol group ( 15.4 + /- 3.5 % , p = 0.006 ) . Patients treated with metoprolol had twice the mortality seen in control subjects , even though the differences were not statistically significant . Holter studies performed at 1 , 6 and 12 months showed that both amiodarone and metoprolol were equally effective in reducing heart rate , whereas only amiodarone significantly reduced ectopic activity ( p < 0.0001 ) . Thus , long-term treatment with amiodarone was clearly safe in patients with an ejection fraction of 20 to 45 % , was effective in suppressing arrhythmias , and was associated with a lower mortality than metoprolol ; corroboration is required in a larger trial AIMS The prevalence of diabetes mellitus in industrialized countries is rapidly increasing , and diabetes is suspected to carry a particular high risk for sudden cardiac death ( SCD ) . METHODS AND RESULTS We conducted a population -based case-control study at Group Health Cooperative . Cases ( n=2040 ) experienced out-of-hospital cardiac arrest due to heart disease between 1980 and 1994 . Controls ( n=3800 ) were a stratified r and om sample of enrollees . Diabetes status was classified into four exclusive groups : ( i ) no diabetes , ( ii ) borderline , ( iii ) diabetes without microvascular disease ( retinopathy or proteinuria ) , and ( iv ) diabetes with microvascular disease . When compared with no diabetes , we observed progressively higher risk of SCD associated with borderline diabetes [ Odds ratio (OR)=1.24 ( 0.98 - 1.57 ) ] , diabetes without microvascular disease [ OR=1.73 ( 1.28 - 2.34 ) ] , and diabetes with microvascular disease [ OR=2.66 ( 1.84 - 3.85 ) ] , after adjustment for potential confounders ( P-value for trend < 0.001 ) . Higher glucose levels were also associated with the risk of SCD both in the absence and in the presence of microvascular disease . However , subjects with microvascular complications but with glucose level < 7.7 mmol/L were not at significant increased risk of SCD . CONCLUSION These results emphasize the role of diabetes as a strong risk factor for SCD and outline the importance of glucose level at every stage of diabetes severity BACKGROUND Asymptomatic ventricular arrhythmias in patients with congestive heart failure are associated with increased rates of overall mortality and sudden death . Amiodarone is now used widely to prevent ventricular tachycardia and fibrillation . We conducted a trial to determine whether amiodarone can reduce overall mortality in patients with congestive heart failure and asymptomatic ventricular arrhythmias . METHODS We used a double-blind , placebo-controlled protocol in which 674 patients with symptoms of congestive heart failure , cardiac enlargement , 10 or more premature ventricular contractions per hour , and a left ventricular ejection fraction of 40 percent or less were r and omly assigned to receive amiodarone ( 336 patients ) or placebo ( 338 patients ) . The primary end point was overall mortality , and the median follow-up was 45 months ( range , 0 to 54 ) . RESULTS There was no significant difference in overall mortality between the two treatment groups ( P = 0.6 ) . The two-year actuarial survival rate was 69.4 percent ( 95 percent confidence interval , 64.2 to 74.6 ) for the patients in the amiodarone group and 70.8 percent ( 95 percent confidence interval , 65.7 to 75.9 ) for those in the placebo group . At two years , the rate of sudden death was 15 percent in the amiodarone group and 19 percent in the placebo group ( P = 0.43 ) . There was a trend toward a reduction in overall mortality among the patients with nonischemic cardiomyopathy who received amiodarone ( P = 0.07 ) . Amiodarone was significantly more effective in suppressing ventricular arrhythmias and increased the left ventricular ejection fraction by 42 percent at two years . CONCLUSIONS Although amiodarone was effective in suppressing ventricular arrhythmias and improving ventricular function , it did not reduce the incidence of sudden death or prolong survival among patients with heart failure , except for a trend toward reduced mortality among those with nonischemic cardiomyopathy BACKGROUND Implantable cardioverter-defibrillators ( ICDs ) are the most effective therapy in reducing the mortality of patients with life-threatening ventricular tachyarrhythmias . However , the ICD can not prevent the recurrence of tachycarida attacks and that limits the clinical usefulness of them . The Nippon ICD Plus Pharmachologic Option Necessity ( NIPPON ) trial was design ed as the first prospect i ve r and omized study to test the hypothesis whether amiodarone could improve the patient 's clinical outcome by reducing the amount of ICD therapy in the Japanese patient population . METHODS AND RESULTS Approximately 400 patients with organic heart disease and spontaneous episode(s ) of sustained ventricular tachycardia/fibrillation ( VT/VF ) will be r and omly assigned to one of 2 groups ; the amiodarone group and non-amiodarone group . Both groups of patients will be followed at least for 24 months . The end-point committee will adjudicate events in a blinded fashion . The primary end-points of this study are determination of the appropriate therapy from the ICD and alteration of the assigned treatment because of its harmful effects and /or frequent ICD therapies . CONCLUSION The NIPPON study is expected to confirm our underst and ing of the prognostic and therapeutic usefulness of adjuvant amiodarone therapy for patients with an ICD and with a history of sustained VT/VF BACKGROUND Patients surviving ventricular fibrillation ( VF ) or sustained ventricular tachycardia ( VT ) are at a high risk of death due to a recurrence of arrhythmia . The implantable cardioverter defibrillator ( ICD ) terminates VT or VF , but it is not known whether this device prolongs life in these patients compared with medical therapy with amiodarone . METHODS AND RESULTS A total of 659 patients with resuscitated VF or VT or with unmonitored syncope were r and omly assigned to treatment with the ICD or with amiodarone . The primary outcome measure was all-cause mortality , and the secondary outcome was arrhythmic death . A total of 328 patients were r and omized to receive an ICD . A thoracotomy was done in 33 , no ICD was implanted in 18 , and the rest had a nonthoracotomy ICD . All 331 patients r and omized to amiodarone received it initially . At 5 years , 85.4 % of patients assigned to amiodarone were still receiving it at a mean dose of 255 mg/day , 28.1 % of ICD patients were also receiving amiodarone , and 21.4 % of amiodarone patients had received an ICD . A nonsignificant reduction in the risk of death was observed with the ICD , from 10.2 % per year to 8.3 % per year ( 19.7 % relative risk reduction ; 95 % confidence interval , -7.7 % to 40 % ; P=0.142 ) . A nonsignificant reduction in the risk of arrhythmic death was observed , from 4.5 % per year to 3.0 % per year ( 32.8 % relative risk reduction ; 95 % confidence interval , -7.2 % to 57.8 % ; P=0.094 ) . CONCLUSIONS A 20 % relative risk reduction occurred in all-cause mortality and a 33 % reduction occurred in arrhythmic mortality with ICD therapy compared with amiodarone ; this reduction did not reach statistical significance Background — Many patients with implanted cardioverter defibrillators ( ICDs ) receive adjunctive antiarrhythmic drug therapy , most commonly amiodarone or sotalol . The effects of these drugs on defibrillation energy requirements have not been previously assessed in a r and omized controlled trial . Methods and Results — The Optimal Pharmacological Therapy in Cardioverter Defibrillator Patients ( OPTIC ) trial was a r and omized clinical trial evaluating the efficacy of amiodarone plus β-blocker and sotalol versus β-blocker alone for reduction of ICD shocks . Within OPTIC , a prospect ively design ed sub study evaluated the effects of the 3 treatment arms on defibrillation energy requirements . Defibrillation thresholds ( DFTs ) were measured ( binary step-down protocol ) at baseline and again after 8 to 12 weeks of therapy in 94 patients , of whom 29 were r and omized to receive β-blocker therapy ( control group ) , 35 to amiodarone plus β-blocker , and 30 to sotalol . In the control group , the mean DFT decreased from 8.77±5.15 J at baseline to 7.13±3.43 J ( P=0.027 ) ; in the amiodarone group , DFT increased from 8.53±4.29 to 9.82±5.84 J ( P=0.091 ) . In the sotalol group , DFT decreased from 8.09±4.81 to 7.20±5.30 J ( P=0.21 ) . DFT changes in the β-blocker and the amiodarone group were significantly different ( P=0.006 ) . In all patients , adequate safety margins for defibrillation were maintained . No clinical variable predicted baseline DFT or changes in DFT on therapy . Conclusion — Although amiodarone increased DFT , the effect size with modern ICD systems is very small . Therefore , DFT re assessment after the institution of antiarrhythmic drug therapy with amiodarone or sotalol is not routinely required AIM To compare the efficacy of sotalol versus amiodarone for long-term treatment of ventricular tachyarrhythmias . METHODS Patients ( n=75 ) with spontaneous , sustained ventricular tachyarrhythmias secondary to remote myocardial infa rct ion were studied . After intravenous electrophysiological testing , both sotalol and amiodarone were predicted to be ineffective in 50 ( 67 % ) patients . Five patients were excluded . Forty-five patients were r and omized to receive sotalol ( n=22 ) or amiodarone ( n=23 ) for maintenance therapy . The primary outcome variable was the time to first recurrence of sustained ventricular tachyarrhythmia . RESULTS At 36 months . 75 % of those allocated sotalol remained free of ventricular tachyarrhythmia compared with 38 % of those allocated amiodarone ( P=0.05 ) . On multivariate analysis the risk of recurrence of ventricular tachyarrhythmia for patients on amiodarone was 5.9 times higher ( P=0.008 ) than that for patients on sotalol . CONCLUSION Sotalol is superior to amiodarone for long-term treatment of ventricular tachyarrhythmia secondary to coronary artery disease when both drugs have been predicted to be ineffective at intravenous electrophysiological testing . R and omized trials in larger numbers of patients with ventricular tachyarrhythmia need to be performed comparing the two agents directly BACKGROUND Sudden death from cardiac causes remains a leading cause of death among patients with congestive heart failure ( CHF ) . Treatment with amiodarone or an implantable cardioverter-defibrillator ( ICD ) has been proposed to improve the prognosis in such patients . METHODS We r and omly assigned 2521 patients with New York Heart Association ( NYHA ) class II or III CHF and a left ventricular ejection fraction ( LVEF ) of 35 percent or less to conventional therapy for CHF plus placebo ( 847 patients ) , conventional therapy plus amiodarone ( 845 patients ) , or conventional therapy plus a conservatively programmed , shock-only , single-lead ICD ( 829 patients ) . Placebo and amiodarone were administered in a double-blind fashion . The primary end point was death from any cause . RESULTS The median LVEF in patients was 25 percent ; 70 percent were in NYHA class II , and 30 percent were in class III CHF . The cause of CHF was ischemic in 52 percent and nonischemic in 48 percent . The median follow-up was 45.5 months . There were 244 deaths ( 29 percent ) in the placebo group , 240 ( 28 percent ) in the amiodarone group , and 182 ( 22 percent ) in the ICD group . As compared with placebo , amiodarone was associated with a similar risk of death ( hazard ratio , 1.06 ; 97.5 percent confidence interval , 0.86 to 1.30 ; P=0.53 ) and ICD therapy was associated with a decreased risk of death of 23 percent ( 0.77 ; 97.5 percent confidence interval , 0.62 to 0.96 ; P=0.007 ) and an absolute decrease in mortality of 7.2 percentage points after five years in the overall population . Results did not vary according to either ischemic or nonischemic causes of CHF , but they did vary according to the NYHA class . CONCLUSIONS In patients with NYHA class II or III CHF and LVEF of 35 percent or less , amiodarone has no favorable effect on survival , whereas single-lead , shock-only ICD therapy reduces overall mortality by 23 percent BACKGROUND Left ventricular dysfunction after myocardial infa rct ion is associated with an increased risk of death . Other studies have suggested that a potassium-channel blocker might reduce this risk with minimal adverse effects . We investigated whether d-sotalol , a pure potassium-channel blocker with no clinical ly significant beta-blocking activity , could reduce all-cause mortality in these high-risk patients . METHODS Patients with a left ventricular ejection fraction of 40 % or less and either a recent ( 6 - 42 days ) myocardial infa rct ion or symptomatic heart failure with a remote ( > 42 days ) myocardial infa rct ion were r and omly assigned d-sotalol ( 100 mg increased to 200 mg twice daily , if tolerated ) or matching placebo twice daily . FINDINGS After 3121 of the planned 6400 patients had been recruited , the trial was stopped . Among 1549 patients assigned d-sotalol , there were 78 deaths ( 5.0 % ) compared with 48 deaths ( 3.1 % ) among the 1572 patients assigned placebo ( relative risk 1.65 [ 95 % CI 1.15 - 2.36 ] , p = 0.006 ) . Presumed arrhythmic deaths ( relative risk 1.77 [ 1.15 - 2.74 ] , p = 0.008 ) accounted for the increased mortality . The effect was greater in patients with a left ventricular ejection fraction of 31 - 40 % than in those with lower ( < or= 30 % ) ejection fractions ( relative risk 4.0 vs 1.2 , p = 0.007 ) . INTERPRETATION Among the 1549 patients evaluated , administration of d-sotalol was associated with increased mortality , which was presumed primarily to be due to arrhythmias . The prophylactic use of a specific potassium-channel blocker does not reduce mortality , and may be associated with increased mortality in high-risk patients after myocardial infa rct ion BACKGROUND Patients who survive life-threatening ventricular arrhythmias are at risk for recurrent arrhythmias . They can be treated with either an implantable cardioverter-defibrillator or antiarrhythmic drugs , but the relative efficacy of these two treatment strategies is unknown . METHODS To address this issue , we conducted a r and omized comparison of these two treatment strategies in patients who had been resuscitated from near-fatal ventricular fibrillation or who had undergone cardioversion from sustained ventricular tachycardia . Patients with ventricular tachycardia also had either syncope or other serious cardiac symptoms , along with a left ventricular ejection fraction of 0.40 or less . One group of patients was treated with implantation of a cardioverter-defibrillator ; the other received class III antiarrhythmic drugs , primarily amiodarone at empirically determined doses . Fifty-six clinical centers screened all patients who presented with ventricular tachycardia or ventricular fibrillation during a period of nearly four years . Of 1016 patients ( 45 percent of whom had ventricular fibrillation , and 55 percent ventricular tachycardia ) , 507 were r and omly assigned to treatment with implantable cardioverter-defibrillators and 509 to antiarrhythmic-drug therapy . The primary end point was overall mortality . RESULTS Follow-up was complete for 1013 patients ( 99.7 percent ) . Overall survival was greater with the implantable defibrillator , with unadjusted estimates of 89.3 percent , as compared with 82.3 percent in the antiarrhythmic-drug group at one year , 81.6 percent versus 74.7 percent at two years , and 75.4 percent versus 64.1 percent at three years ( P<0.02 ) . The corresponding reductions in mortality ( with 95 percent confidence limits ) with the implantable defibrillator were 39+/-20 percent , 27+/-21 percent , and 31+/-21 percent CONCLUSIONS Among survivors of ventricular fibrillation or sustained ventricular tachycardia causing severe symptoms , the implantable cardioverter-defibrillator is superior to antiarrhythmic drugs for increasing overall survival Sudden cardiac death is a common cause of mortality in patients with congestive heart failure . Asymptomatic ventricular arrhythmia has been attributed as the cause for increased overall mortality in such patients . We conducted a prospect i ve r and omised single-blind placebo-controlled trial with low-dose amiodarone to assess its efficacy in reducing mortality in severe congestive heart failure and its effect on exercise tolerance , left ventricular systolic function and ventricular ectopic activity . Patients were r and omised to receive amiodarone ( n = 36 ) 400 mg/day orally for one month followed by a maintenance dose of 200 mg/day , or to a st and ard treatment ( n = 40 ) according to intention-to-treat principle . There were 10 cardiac deaths in the amiodarone-treated group and 16 in the control group . Significant improvement was noted in exercise time in the treadmill test ( modified Bruce Protocol ) among patients in the amiodarone-treated group while no such statistical difference was detectable in the placebo group . Side-effects in the amiodarone group included asymptomatic rise in hepatic enzymes ( three-fold ) in 6 percent and proarrhythmia in 3 percent of patients . Nausea was reported in one patient and rash in one . Though low-dose amiodarone proved to be an effective antiarrhythmic agent , it failed to live up to the expectation of improving sudden cardiac death in patients with severe chronic heart failure and asymptomatic ventricular ectopy Implantable cardioverter-defibrillators ( ICDs ) are being used increasingly for treatment of malignant ventricular tachyarrhythmias . However , ICD discharge is associated with significant morbidity . Antiarrhythmic therapy could reduce the frequency of ICD discharge , but its effect is uncertain . Thus , the effect of antiarrhythmic therapy was evaluated in a r and omized trial . Thirty-four patients ( 32 men and 2 women , average age 60 years ) who received an ICD for sustained ventricular tachycardia or fibrillation were entered in the trial and r and omized to the best " drug " therapy ( group 1 ; n = 17 ) or no therapy ( group 2 ; n = 17 ) . After the first ICD discharge , patients were to be crossed over to the alternative treatment arm . Twenty-nine patients had coronary artery disease . The induced arrhythmia was ventricular tachycardia in 33 patients and ventricular fibrillation in 1 . Ejection fraction averaged 39 % . The 2 groups were well balanced , without differences in demographic variables . In group 1 , class I therapy was given to 9 patients and class III to 9 . Beta blockade was used in a similar number of patients in groups 1 and 2 ( n = 8 and 6 , respectively ) . Time to the first shock or the end of follow-up averaged 143 days ( range 1 to 609 ) . During follow-up , 21 patients had a first ICD discharge event ( 11 in group 1 , and 10 in group 2 ; p = 0.72 ) . Event-free survival in each group was assessed by the Kaplan-Meier method , using the intention-to-treat approach . Overall median time to the first event was 134 days . Time to the first event did not differ between groups ( p = 0.66 ; log-rank test ) . ( ABSTRACT TRUNCATED AT 250 WORDS The efficiency of prophylactic antiarrhythmic treatment with amiodarone in reducing 1-year mortality in patients with reduced left ventricular ejection fraction ( < 35 % ) and asymptomatic ventricular arrhythmias ( Lown classes 2 and 4 ) was investigated in a prospect i ve , multicenter , r and omized , controlled study . Among 127 patients who entered the study , 61 were assigned to no antiarrhythmic therapy ( control group [ CG ] and 66 to amiodarone treatment ( amiodarone group [ AG ] ) . Amiodarone was administered at a dosage of 800 mg/day for 2 weeks followed by 400 mg/day thereafter . A 12-month follow-up was completed for 106 patients ( 57 in the AG and 49 in the CG ) . Amiodarone reduced the overall mortality rate , which was 10.5 % in the AG versus 28.6 % in the CG ( odds ratio [ OR ] 0.29 ; 95 % confidence interval [ CI ] 0.10 to 0.84 ; log-rank test 0.02 ) and sudden death rate , which was 7.0 % in the AG versus 20.4 % in the CG ( OR 0.29 ; 95 % CI 0.08 to 1.00 ; log-rank test 0.04 ) . Side effects were rare , and in only three patients did amiodarone treatment have to be discontinued The Cardiac Arrest in Seattle , Conventional Versus Amiodarone Drug Evaluation ( CASCADE ) study evaluated antiarrhythmic drug therapy in high-risk survivors of out-of-hospital ventricular fibrillation . Antiarrhythmic drug therapy for 228 patients was r and omized to amiodarone or conventional antiarrhythmic drugs . Additional therapy with an implantable cardioverter-defibrillator was provided to 105 of these patients . Clinical predictors of shocks were evaluated for the 88 patients with coronary artery disease ( amiodarone 46 , conventional 42 ) , treated with an implantable cardioverter-defibrillator . Survival free of all shocks at 2 years was 77 % for patients taking amiodarone and 42 % for those receiving conventional therapy ( p = 0.014 ) . Two-year survival free of syncopal shocks was 98 % for amiodarone-treated patients and 81 % for those receiving conventional agents ( p = 0.01 ) . Multiple clinical factors were evaluated by Cox analysis for potential clinical predictors of shocks . The independent clinical predictors of shocks were low ejection fraction ( p = 0.002 ) , female gender ( p = 0.007 ) and conventional antiarrhythmic drug therapy ( p = 0.015 ) . The only independent predictor of a shock associated with syncope was conventional antiarrhythmic drug therapy ( p = 0.035 ) . Patients treated with amiodarone receive fewer shocks than patients treated with conventional drug therapy In the BASIS study , an improvement in 1 year survival of patients with asymptomatic complex ventricular arrhythmias with low-dose amiodarone was shown in comparison with an untreated control group . To assess whether this beneficial effect would last for a longer follow-up despite discontinuation of amiodarone therapy after one year , we assessed long-term survival and mode of death in the 91 survivors of the first year in the amiodarone treatment group and the 99 survivors in the control group by phone calls to private physicians , patients and hospitals . During a median follow-up of 72 ( 55 - 125 ) months , 184/193 patients ( 95 % ) could be reached . Causes of death during the follow-up were sudden ( 6 vs 14 ) , non-sudden cardiac ( 8 vs 9 ) , non cardiac ( 5 vs 9 ) and unknown ( 7 vs 6 ) in patients initially treated with amiodarone versus the control group respectively . The probability of death after 84 months was 30 % in the amiodarone group and 45 % in the control group , and was significantly lower in amiodarone treated patients with respect to all deaths ( p = 0.024 ) as well as cardiac deaths ( p = 0.027 ) . This mortality reduction was only due to amiodarone treatment during the first year after the index infa rct ion , whereas the survival curves did not differ significantly during the late follow-up . Thus , the risk of cardiac death is low after the first year after myocardial infa rct ion and may not justify continued antiarrhythmic therapy in patients with initially complex asymptomatic ventricular arrhythmias Background Among survivors of acute myocardial infa rct ion , frequent and repetitive ventricular premature depolarizations ( VPDs ) detected on ambulatory monitoring contribute independently to the risk of all-cause mortality and sudden death . Apart from the P-blockers , no antiarrhythmic drug has been reliably demonstrated to reduce mortality among patients with VPDs . A pilot study was undertaken to gather data to aid in the design of a multicenter trial of amiodarone for the reduction of mortality from cardiac arrhythmias in such patients . Methods and Results Seventy-seven patients with acute myocardial infa rct ion within the previous 6–30 days and 10 or more VPDs/hr or one or more runs of ventricular tachycardia on 24-hour electrocardiographic recording were r and omized in a double-blind fashion in a 2:1 amiodarone-to-placebo ratio . The loading dose was 10 mg/kg/day for 3 weeks . The maintenance dose was 300–400 mg/day with reductions at 4-month intervals in response to VPD suppression , excessive plasma levels , or toxicity . VPD suppression at 1 week and 2 weeks was 63 % and 85 % , respectively , on amiodarone and 17 % and 27 % , respectively , on placebo . Apart from thyroid-stimulating hormone elevation and skin reactions , no side effects occurred more frequently with amiodarone . The study drug was stopped for side effects or noncompliance in 35 % of amiodarone patients and 34 % of placebo patients . Patients were followed for a maximum of 2 years ( mean , 20 months ) . Arrhythmic death or resuscitated ventricular fibrillation Occurred in two of 48 amiodarone patients ( 6 % ) and four of 29 placebo patients ( 14 % ) , whereas the rates of all-cause mortality were five of 48 ( 10 % ) and six of 29 ( 21 % ) , respectively . Conclusions Amiodarone , in moderate loading and maintenance dosages with adjustments in response to plasma levels , VPD suppression , and side effects , results in effective VPD suppression and acceptable levels of toxicity BACKGROUND Arrhythmias cause much morbidity and mortality after myocardial infa rct ion , but in previous trials , antiarrhythmic drug therapy has not been convincingly effective . Dofetilide , a new class III agent , was investigated for effects on all-cause mortality and morbidity in patients with left-ventricular dysfunction after myocardial infa rct ion . METHODS In 37 Danish coronary-care units , 1510 patients with severe left-ventricular dysfunction ( wall motion index < or = 1.2 , corresponding to ejection fraction < or = 0.35 ) were enrolled in a r and omised , double-blind study comparing dofetilide ( n=749 ) with placebo ( n=761 ) . The primary endpoint was all-cause mortality . Secondary endpoints included cardiac and arrhythmic mortality and total arrhythmic deaths . Analyses were by intention to treat . FINDINGS No significant differences were found between the dofetilide and placebo groups in all-cause mortality ( 230 [ 31 % ] vs 243 [ 32 % ] ) , cardiac mortality ( 191 [ 26 % ] vs 212 [ 28 % ] ) , or total arrhythmic deaths ( 129 [ 17 % ] vs 140 [ 18 % ] ) . Atrial fibrillation or flutter was present in 8 % of the patients at study entry . In these patients , dofetilide was significantly better than placebo at restoring sinus rhythm ( 25 of 59 vs seven of 56 ; p=0.002 ) . There were seven cases of torsade de pointes ventricular tachycardia , all in the dofetilide group . INTERPRETATION In patients with severe left-ventricular dysfunction and recent myocardial infa rct ion , treatment with dofetilide did not affect all-cause mortality , cardiac mortality , or total arrhythmic deaths . Dofetilide was effective in treating atrial fibrillation or flutter in this population BACKGROUND Ventricular arrhythmias are a major cause of death after myocardial infa rct ion , especially in patients with poor left-ventricular function . Previous attempts to identify and suppress arrhythmias with various antiarrhythmic drugs failed to reduce or actually increase mortality . Amiodarone is a powerful antiarrhythmic drug with several potentially beneficial actions , and has shown benefit in several small-scale studies . We postulated that this drug might reduce mortality in patients at high risk of death after myocardial infa rct ion because of impaired ventricular function , irrespective of whether they had ventricular arrhythmias . METHODS The European Myocardial Infa rct Amiodarone Trial ( EMIAT ) was a r and omised double-blind placebo-controlled trial to assess whether amiodarone reduced all-cause mortality ( primary endpoint ) and cardiac mortality and arrhythmic death ( secondary endpoints ) in survivors of myocardial infa rct ion with a left-ventricular ejection fraction ( LVEF ) of 40 % or less . Intention-to-treat and on-treatment analyses were done . FINDINGS EMIAT enrolled 1486 patients ( 743 in the amiodarone group , 743 in the placebo group ) . Median follow-up was 21 months . All-cause mortality ( 103 deaths in the amiodarone group , 102 in the placebo group ) and cardiac mortality did not differ between the two groups . However , in the amiodarone group , there was a 35 % risk reduction ( 95 % CI 0 - 58 , p = 0.05 ) in arrhythmic deaths . INTERPRETATION Our findings do not support the systematic prophylactic use of amiodarone in all patients with depressed left-ventricular function after myocardial infa rct ion . However , the lack of proarrhythmia and the reduction in arrhythmic death support the use of amiodarone in patients for whom antiarrhythmic therapy is indicated Amiodarone in doses of 200 to 400 mg/day has shown promise in secondary prevention trials for reducing mortality in patients surviving myocardial infa rct ion who have complex ventricular ectopy or nonsustained ventricular tachycardia , or both . In an attempt to explore the lowest dose of amiodarone with antiarrhythmic and hemodynamic activity , we studied 48 patients ( mean age 53 + /- 11 years , ejection fraction 23 + /- 9 % , clinical heart failure in 85 % ) with nonsustained ventricular tachycardia . This was a 3-month , r and omized , parallel , double-blind pilot study comparing placebo ( n = 16 ) with amiodarone 50 mg/day ( n = 15 ) and 100 mg/day ( n = 17 ) . Patients r and omized to amiodarone received a mean loading dose of 422 mg/day for the first study week . At the end of the 12 weeks , amiodarone ( 100 mg ) significantly reduced ventricular premature complexes ( 177 + /- 64 to 98 + /- 38/hour ) , couplets ( 8 + /- 3 to 4 + /- 2/hour ) , and runs of nonsustained ventricular tachycardia ( 13 + /- 7 to 3 + /- 2/day ) , all p < 0.01 versus baseline . In addition , 10 of 14 patients taking 100 mg/day had total suppression of nonsustained ventricular tachycardia compared with 4 of 15 taking placebo , p = 0.021 . Left ventricular ejection fraction improved by > or = 7 % ( absolute ) in 11 of 29 patients taking amiodarone as compared with only 1 of 15 placebo patients ( p = 0.02 ) . In these 11 patients with the greatest measurable hemodynamic improvement , amiodarone significantly increased ejection fraction ( 21 + /- 7 % to 33 + /- 11 % , p < 0.01 ) , stroke volume index ( 28 + /- 9 to 40 + /- 7 ml/m2 , p < 0.01 ) and decreased end-systolic volume index ( 116 + /- 48 to 92 + /- 44 ml/m2 , p < 0.01 ) . ( ABSTRACT TRUNCATED AT 250 WORDS A r and omized , placebo-controlled study examined the effect of amiodarone on the incidence of ventricular arrhythmias after acute myocardial infa rct ion ( AMI ) . Two hundred patients with AMI were r and omized to receive amiodarone , 200 mg every 8 hours for 1 month , followed by 200 mg/day , or placebo , starting 48 hours after the onset of chest pain . Twenty-four-hour Holter monitoring was performed on day 1 , repeated after 8 days and subsequently at 3-month intervals . One hundred seventy-two patients were followed for 6 to 42 months and monitor data were available at 6 to 9 months in 129 patients . Amiodarone was well tolerated , with no serious side effects ; 12 patients were withdrawn from therapy . At 6 to 9 months more than 1 ventricular premature complex per hour was present in 3 of the 59 amiodarone-treated patients ( 5 % ) and 24 of the 70 placebo-treated patients ( 34 % ) ( p less than 0.02 ) . Complex arrhythmias ( multifocal , early cycle , repetitive , bigeminy , trigeminy or ventricular tachycardia ) were present in 5 of 59 of the amiodarone-treated patients ( 8 % ) and 20 of 70 placebo-treated patients ( 28 % ) ( p less than 0.005 ) . Sixteen patients in the amiodarone group and 11 in the placebo group died ( difference not significant ) . Thus , amiodarone can reduce the frequency and complexity of ventricular arrhythmias after AMI , but it is unlikely that this will result in a substantial beneficial effect on post-AMI mortality risk BACKGROUND Although sudden cardiac death ( SCD ) is relatively common , contemporary data on its incidence are lacking . OBJECTIVE The purpose of this study was to investigate the current incidence of SCD and its trend over the past 2 decades in a general middle-aged and elderly population . METHODS This study was performed within the Rotterdam Study , a prospect i ve population -based cohort study of persons aged 45 years and older . Age-st and ardized incidence rates of SCD were calculated . To study trends in incidence , we compared 2 subcohorts within the total study population , 1 followed from 1990 - 2000 and the other from 2001 - 2010 . RESULTS From 1990 - 2010 , 5512 of 14,628 participants died , of whom 583 ( 4.0 % ) were classified as SCD . The overall incidence was 4.2 per 1000 person-years . The incidence was higher in men ( 5.2 per 1000 person-years ) than in women ( 3.6 per 1000 person-years ) . Age-adjusted hazard ratio ( HR ) 1.84 ( 95 % confidence [ CI ] 1.56 - 2.17 ) and risk of SCD increased with age ( HR 1.10 per year ; 95 % CI 1.09 - 1.11 ) . The incidence rate from 1990 - 2000 was 4.7 per 1000 person-years vs 2.1 per 1000 person-years from 2001 - 2010 ( age- and sex-adjusted HR of SCD 0.60 , 95 % CI 0.44 - 0.80 ) . To check for cohort effects , we also analyzed the incidence of total mortality and found an age- and sex-adjusted HR of total mortality of 0.82 ( 95 % CI 0.75 - 0.90 ) for the second compared to the first subcohort , which was significantly higher than the decline in SCD incidence . CONCLUSION We found an incidence of SCD of 4.2 per 1000 person-years . The incidence decreased from 1990 - 2010 , a period during which the diagnosis and treatment of heart disease greatly improved In severe heart failure many deaths are sudden and are presumed to be due to ventricular arrhythmias . The GESICA trial evaluated the effect of low-dose amiodarone on two-year mortality in patients with severe heart failure . Our prospect i ve multicentre trial included 516 patients on optimal st and ard treatment for heart failure . Patients were r and omised to 300 mg/day amiodarone ( 260 ) or to st and ard treatment ( 256 ) . Intention-to-treat analysis showed 87 deaths in the amiodarone group ( 33.5 % ) compared with 106 in the control group ( 41.4 % ) ( risk reduction 28 % ; 95 % CI 4%-45 % ; log rank test p = 0.024 ) . There were reductions in both sudden death ( risk reduction 27 % ; p = 0.16 ) and death due to progressive heart failure ( risk reduction 23 % ; p = 0.16 ) . Fewer patients in the amiodarone group died or were admitted to hospital due to worsening heart failure ( 119 versus 149 in the control group ; risk reduction 31 % ; 95 % CI 13 - 46 % ; p = 0.0024 ) . The decrease in mortality and hospital admission was present in all subgroups examined and independent of the presence of non-sustained ventricular tachycardia . Side-effects were reported in 17 patients ( 6.1 % ) ; amiodarone was withdrawn in 12 . Low-dose amiodarone proved to be an effective and reliable treatment , reducing mortality and hospital admission in patients with severe heart failure independently of the presence of complex ventricular arrhythmias OBJECTIVES The goal of this study was to evaluate the effect of amiodarone on mortality , ventricular arrhythmias and clinical complications in high risk postinfa rct ion patients . BACKGROUND No therapy has been shown to reduce sudden death in patients ineligible to receive beta-adrenergic blocking agents after myocardial infa rct ion . METHODS Patients who were not eligible to receive beta-blockers were r and omized to receive amiodarone ( n = 305 ) or placebo ( n = 308 ) for 1 year . RESULTS There were 21 deaths in the amiodarone group compared with 33 in the placebo group ( odds ratio 0.62 , 95 % confidence interval [ CI ] 0.35 to 1.08 , p = 0.095 ) . There were two noncardiac deaths in the amiodarone group and none in the placebo group ; thus , the difference in cardiac mortality ( 19 vs. 33 , respectively ) was statistically significant ( odds ratio 0.55 , 95 % CI 0.32 to 0.99 , p = 0.048 ) . There was a significant decrease in Lown class 4 ventricular arrhythmias ( 7.5 % vs. 19.7 % , respectively , p < 0.001 ) . Adverse effects developed in 30 % of amiodarone-treated patients and 10 % of placebo-treated patients . Pulmonary toxicity , which was mild and reversible , occurred in only one patient in the amiodarone group but in no patient in the placebo group . CONCLUSIONS This trial demonstrated a significant reduction in cardiac mortality and ventricular arrhythmias with amiodarone treatment . However , given the wide confidence intervals and borderline statistical significance of our trial , larger trials are needed to confirm or refute this view UNLABELLED ICDs can affect a patient 's perceived quality -of-life ( QOL ) . This article describes the QOL in patients who participated in The CABG Patch Trial . This trial evaluated the potential benefit of empiric ICD implantation in patients with an increased risk of arrhythmic cardiac death as determined by reduced ejection fraction ( < 0.36 ) and an abnormal signal-averaged ECG . Patients were r and omized to control ( no ICD ) or treatment ( ICD ) limbs . QOL was measured using the SF-36 and other measures among 490 ( 68 % ) of 719 patients available at 6-month follow-up . Analysis was performed on 228 control patients ( those without ICDs ) and 262 patients with ICDs . RESULTS Six months after having CABG surgery , patients in the ICD group had lower levels of psychological well-being than those in the control group . In addition , compared to controls , patients whose ICDs had delivered therapy reported feeling less healthy , had reduced physical and emotional role functioning , and had lower levels of psychological well-being . CONCLUSION Strategies aim ed at easing patients ' adjustment to ICDs should be developed and tested for efficacy in the setting of ICD prophylaxis OBJECTIVES We sought to determine the annual incidence of sudden cardiac death ( SCD ) in the general population using a prospect i ve approach . To assess the validity of retrospective surveillance , a simultaneous comparison was made with a death certificate-based method of determining SCD incidence . BACKGROUND Accurate surveillance and characterization of SCD in the general population is likely to significantly facilitate current and future community-based preventive and therapeutic interventions . METHODS We performed a prospect i ve evaluation of SCD among all residents of Multnomah County , Oregon ( population 660,486 ) using multiple sources of surveillance . A comprehensive analysis of circumstances of death , medical records , and available autopsy data was performed . Comparisons were made with a retrospective , death certificate-based determination of SCD incidence using International Classification of Diseases-Version 10 codes and location of death . RESULTS Between February 1 , 2002 , and January 31 , 2003 , 353 residents suffered SCD ( incidence 53 of 100,000 ; median age 69 years , 57 % male ) accounting for 5.6 % of overall mortality . Of these , 75 cases ( 21 % ) were identified using sources other than first responders . Resuscitation was attempted in 237 cases ( 67 % ) and successful ( survival to hospital discharge ) in 28 ( 8 % ) . The retrospective death certificate-based review yielded 1,007 cases ( incidence 153 of 100,000 ; median age 81 years , 51 % male ) , and the positive predictive value of this methodology was 19 % . CONCLUSIONS Sudden cardiac death accounts for 5.6 % of annual mortality , and prospect i ve evaluation in the general population appears to be feasible . The use of multiple sources of ascertainment and information significantly enhances phenotyping of SCD cases . Retrospective death certificate-based surveillance results in significant overestimation of SCD incidence OBJECTIVES The objective of this study was to examine prospect ively the incidence , predisposing cardiovascular conditions , and risk factors for sudden death in women compared with men . METHODS AND RESULT The study design was a prospect i ve general population examination of a cohort of 2873 women for development of sudden coronary death in relation to antecedent overt coronary heart disease ( CHD ) , cardiac failure , and risk factors for coronary heart disease . Participants were women aged 30 to 62 years participating in the Framingham Study , receiving routine biennial examinations for risk factors and cardiovascular conditions . Among women monitored over a period of 38 years , there were 750 initial coronary events , of which 94 ( 12 % ) were sudden cardiac deaths . Of the 292 CHD fatalities in women , 32 % were sudden cardiac deaths and 37 % of the women had a history of prior CHD . Sudden death incidence in women logged behind that in men by > 10 years . However , above age 75 years , 17 % of all CHD events in women were sudden deaths . Sudden death risk in women with CHD was half as high as in men if they had CHD . In both sexes , a myocardial infa rct ion conferred twice the risk of angina . Cardiac failure escalated sudden death risk of women 5-fold but was only one fourth that of men with failure or CHD . Ventricular ectopy increased sudden death risk only in women without prior overt CHD . Except for diabetes , CHD risk factors imposed a lower sudden death risk in women than men . However , even in women , sudden death risk increased over a 17-fold range in relation to their burden of CHD risk factors . CONCLUSIONS Sudden death is a prominent feature of CHD in women as well as men , particularly in advanced age . A higher fraction of sudden deaths in women than men is unexpected occurring in the absence of prior overt CHD . It is subject to the same risk factors and as predictable in women as in men . However , at any level of multivariate risk , women are less vulnerable to sudden death than men CONTEXT Implantable cardioverter defibrillator ( ICD ) therapy is effective but is associated with high-voltage shocks that are painful . OBJECTIVE To determine whether amiodarone plus beta-blocker or sotalol are better than beta-blocker alone for prevention of ICD shocks . DESIGN , SETTING , AND PATIENTS A r and omized controlled trial with blinded adjudication of events of 412 patients from 39 outpatient ICD clinical centers located in Canada , Germany , United States , Engl and , Sweden , and Austria , conducted from January 13 , 2001 , to September 28 , 2004 . Patients were eligible if they had received an ICD within 21 days for inducible or spontaneously occurring ventricular tachycardia or fibrillation . INTERVENTION Patients were r and omized to treatment for 1 year with amiodarone plus beta-blocker , sotalol alone , or beta-blocker alone . MAIN OUTCOME MEASURE Primary outcome was ICD shock for any reason . RESULTS Shocks occurred in 41 patients ( 38.5 % ) assigned to beta-blocker alone , 26 ( 24.3 % ) assigned to sotalol , and 12 ( 10.3 % ) assigned to amiodarone plus beta-blocker . A reduction in the risk of shock was observed with use of either amiodarone plus beta-blocker or sotalol vs beta-blocker alone ( hazard ratio [ HR ] , 0.44 ; 95 % confidence interval [ CI ] , 0.28 - 0.68 ; P<.001 ) . Amiodarone plus beta-blocker significantly reduced the risk of shock compared with beta-blocker alone ( HR , 0.27 ; 95 % CI , 0.14 - 0.52 ; P<.001 ) and sotalol ( HR , 0.43 ; 95 % CI , 0.22 - 0.85 ; P = .02 ) . There was a trend for sotalol to reduce shocks compared with beta-blocker alone ( HR , 0.61 ; 95 % CI , 0.37 - 1.01 ; P = .055 ) . The rates of study drug discontinuation at 1 year were 18.2 % for amiodarone , 23.5 % for sotalol , and 5.3 % for beta-blocker alone . Adverse pulmonary and thyroid events and symptomatic bradycardia were more common among patients r and omized to amiodarone . CONCLUSIONS Despite use of advanced ICD technology and treatment with a beta-blocker , shocks occur commonly in the first year after ICD implant . Amiodarone plus beta-blocker is effective for preventing these shocks and is more effective than sotalol but has an increased risk of drug-related adverse effects . Clinical Trials Registration Clinical Trials.gov Identifier : NCT00257959 BACKGROUND Survivors of acute myocardial infa rct ion with frequent or repetitive ventricular premature depolarisations ( VPDs ) have higher mortality 1 - 2 years after the event than those without VPDs . Although there is no therapy of proven efficacy for such patients , previous studies of amiodarone have been encouraging . CAMIAT was a r and omised double-blind placebo-controlled trial design ed to assess the effect of amiodarone on the risk of resuscitated ventricular fibrillation or arrhythmic death among survivors of myocardial infa rct ion with frequent or repetitive VPDs ( > or = 10 VPDs per h or > or = 1 run of ventricular tachycardia ) . METHODS Patients from 36 Canadian hospitals were r and omly assigned amiodarone or placebo ; a loading dose of 10 mg/kg daily for 2 weeks , a maintenance dose of 300 - 400 mg daily for 3.5 months , 200 - 300 mg daily for 4 months , and 200 mg for 5 - 7 days per week for 16 months . Patients were followed up for 2 years . The primary outcome was the composite of resuscitated ventricular fibrillation or arrhythmic death . FINDINGS We recruited 1202 patients ( 606 in the amiodarone group and 596 in the placebo group ) . The mean follow-up was 1.79 years ( SD 0.44 ) . In the efficacy analysis , resuscitated ventricular fibrillation or arrhythmic death occurred in 39 ( 6.9 % ) [ corrected ] patients in the placebo group and in 25 ( 4.5 % ) [ corrected ] in the amiodarone group ( relative-risk reduction 48.5 % [ 95 % CI 4.5 to 72.2 ] , p = 0.016 ) . In the intention-to-treat analysis , primary outcome events occurred in 24 ( 6.9 % ) patients in the placebo group and in 15 ( 4.5 % ) in the amiodarone group ( 38.2 % [ 95 % CI -2.1 to 62.6 ] , p = 0.029 ) . The absolute-risk reductions were greatest among patients with congestive heart failure or a history of myocardial infa rct ion . INTERPRETATION Amiodarone reduces the incidence of ventricular fibrillation or arrhythmic death among survivors of acute myocardial infa rct ion with frequent or repetitive VPDs . Treatment decisions for individual survivors should require an assessment of their baseline risk factors and judgments based on the synthesis of our findings with those of related trials AIMS MAVERIC was a r and omised clinical trial design ed to test the possibility of prospect ively identifying patients who would benefit most from the implantable cardioverter-defibrillator ( ICD ) by electrophysiology ( EP ) study in the context of secondary prevention of sudden cardiac death ( SCD ) through comparing EP-guided interventions ( anti-arrhythmic drugs , coronary revascularization , and ICD ) against empirical amiodarone therapy . METHODS Two hundred and fourteen survivors of sustained ventricular tachycardia ( VT ) , ventricular fibrillation ( VF ) or SCD were r and omized to either treatment strategy , pre-stratified for haemodynamic status at index event , and followed up for a median of 5 years . RESULTS Of the 106 amiodarone arm patients , 89 ( 84 % ) received the drug and 5 ( 5 % ) received an ICD after crossing over . Of the 108 EP arm patients , 31 ( 29 % ) received an ICD , 46 ( 43 % ) received anti-arrhythmic drugs only ( mainly amiodarone or sotalol ) and 18 ( 17 % ) received coronary revascularization but no ICD . No significant differences in survival or arrhythmia recurrence existed between the two treatment arms after 6 years . However , ICD recipients had a lower mortality than non-ICD recipients , regardless of allocated treatment ( hazard ratio=0.54 , p=0.0391 ) . CONCLUSIONS Prospect i ve selection of patients to receive the ICD by EP study did not improve survival compared with empirical amiodarone therapy among survivors of VT , VF or SCD , whereas ICD implantation improved survival regardless of allocated treatment . On this basis , routine EP study has no role in the management of such patients , who should be offered empirical ICD therapy according to the results of other secondary prevention ICD trials The purpose of this prospect i ve r and omized trial was to compare the efficacy of propranolol and amiodarone in suppressing ventricular arrhythmias during the first 6 months following myocardial infa rct ion ( MI ) . 97 patients were treated with either amiodarone ( n = 48 ) or propranolol ( n = 49 ) starting on the 9th day following MI . Holter monitoring was carried out on four occasions : on D7 , D21 , D90 and D180 . There was no statistical difference in the incidence of ' major ' arrhythmias ( an average of at least 10 ventricular premature complexes ( VPCs ) h-1 , multiform or paired VPCs or runs ) between the two groups on D7 . A significant difference in favour of amiodarone became apparent at D180 ( P = 0.04 ) . Patients were also classified according to whether treatment failed or was successful . ' Success ' was recorded when arrhythmias remained minor or became minor ( less than 10 uniform VPCs h-1 ) and ' failure ' when arrhythmias remained major or became major , or when patients were withdrawn because of side-effects , or lost to follow-up . The difference remained in favour of amiodarone ( P = 0.03 at D21 ; P = 0.05 at D90 ; P = 0.06 at D180 ) . Evaluation of the percentage reduction in the number of VPCs at D21 , D90 or D180 compared with D7 showed superiority of amiodarone at D90 ( P less than 0.01 ) and D180 ( P less than 0.04 ) . In this study , the overall effect of amiodarone on ventricular arrhythmias following MI was shown to be superior to that of propranolol The Cardiac Arrest in Seattle : Conventional Versus Amiodarone Drug Evaluation ( CASCADE ) study evaluated antiarrhythmic drug treatment of survivors of out-of-hospital ventricular fibrillation ( VF ) not associated with a Q-wave myocardial infa rct ion who were at especially high risk of recurrence of VF . Therapy was r and omized to empiric treatment with amiodarone versus treatment with other antiarrhythmic drugs guided by electrophysiologic testing , Holter recording , or both ( conventional therapy ) . The primary end points of the study were cardiac mortality , resuscitated cardiac arrest due to documented VF , or complete syncope followed by a shock from an implanted automatic defibrillator . Two hundred twenty-eight patients were enrolled in the study , and baseline characteristics were similar in the patients treated with amiodarone and with conventional therapy . Two hundred two patients ( 89 % ) were men with an average age of 62 years . Coronary artery disease was the most common underlying condition ( 188 of 228 , 82 % ) , and in coronary patients , 153 of 188 ( 81 % ) had experienced a prior myocardial infa rct ion before the index VF event . Mean left ventricular ejection fraction was 0.35 , and 102 patients ( 45 % ) had a prior history of congestive heart failure . Survival free of cardiac death , resuscitated VF , or syncopal defibrillator shock for the entire population was 75 % at 2 years ( amiodarone , 82 % ; conventional , 69 % ) , 59 % at 4 years ( amiodarone , 66 % ; conventional , 52 % ) , and 46 % at 6 years ( amiodarone , 53 % ; conventional , 40 % ) ; p = 0.007 . The survival free of cardiac death and sustained ventricular arrhythmias was 65 % at 2 years ( amiodarone , 78 % ; conventional , 52 % ) , 43 % at 4 years ( amiodarone , 52 % ; conventional , 36 % ) , and 30 % at 6 years ( amiodarone , 41 % ; conventional , 20 % ) ; p < 0.001 BACKGROUND Uncertainty persists about the safety and efficacy of amiodarone for the management of heart failure . METHODS AND RESULTS We r and omized 3029 patients with chronic heart failure to receive carvedilol or metoprolol and followed patients for a median of 58 months . One hundred fifty-five of 1466 patients in New York Heart Association ( NYHA ) Class II and 209 of 1563 in Class III or IV received amiodarone at baseline . Persistence with amiodarone treatment was high and 66 % received amiodarone after 4 years . During follow-up , 38.7 % and 58.9 % of patients receiving amiodarone in NYHA Classes II and III + IV died versus 26.2 % and 43.3 % not receiving amiodarone ( P < .001 ) . This difference was maintained in multivariable analysis ( hazard ratio [ HR ] 1.5 , 95 % confidence interval [ CI ] 1.2 - 1.7 , P < .001 ) . The difference was explained by an increased risk of death due to circulatory failure ( HR 2.4 , CI 1.9 - 3.1 , P < .001 ) in patients receiving amiodarone . Sudden death was not different ( HR 1.07 , CI 0.8 - 1.4 , P = .7 ) . The increased risk was similar across NYHA classes with HR of 1.60 ( CI 1.2 - 2.1 , P < .001 ) in NYHA Class II versus 1.58 ( CI 1.3 - 1.9 , P < .001 ) in Classes III + IV . CONCLUSIONS Treatment with amiodarone was associated with an increased risk of death from circulatory failure independent of functional class In a prospect i ve and parallel , r and omized study , the long-term stability of epicardial defibrillation threshold was evaluated in 22 patients , using a patch-patch lead configuration at the time of implantation and generator replacement . The concomitant antiarrhythmic drug treatment consisted of either mexiletine ( 720 mg/day ) or amiodarone ( 400 mg/day ) and was administered to patients in a r and omized and parallel manner . During a mean follow-up of 24 + /- 6 months , the defibrillation threshold increased significantly from 14.3 + /- 2.8 to 17.9 + /- 5.3 J ( p < 0.05 ) for the entire patient group . The increase in the chronic defibrillation threshold was due to a marked increase in defibrillation energy needs in the subgroup of patients receiving amiodarone . Whereas no significant change in the defibrillation threshold was documented in the subgroup of patients receiving mexiletine , the mean defibrillation threshold increased from 14.1 + /- 3.0 to 20.9 + /- 5.4 J ( p < 0.001 ) in those receiving amiodarone . In all patients with increased defibrillation thresholds , reevaluation showed a reduction in the defibrillation threshold after discontinuation of antiarrhythmic drug therapy . The only variable associated with an increase in the chronic defibrillation threshold was amiodarone treatment . These findings suggest that the defibrillation threshold should be measured at each generator replacement and in case of a change in antiarrhythmic drug treatment . In particular , if amiodarone treatment is initiated , it is recommended that the defibrillation threshold should be reevaluated to ensure an adequate margin of safety In view of the high risk of sudden cardiac death and the prognostic importance of complex ventricular ectopic activity , the effects of prophylactic antiarrhythmic treatment were investigated prospect ively in patients with persisting asymptomatic complex arrhythmias after myocardial infa rct ion . End points were total mortality and arrhythmic events ( sudden death , sustained ventricular tachycardia and ventricular fibrillation ) . Of 1,220 consecutively screened survivors of myocardial infa rct ion , 312 had Lown class 3 or 4b arrhythmia on 24 h electrocardiographic recordings before hospital discharge and consented to the study . They were r and omized to individualized antiarrhythmic treatment ( Group 1 , n = 100 ) , treatment with low dose amiodarone , 200 mg/day ( Group 2 , n = 98 ) or no antiarrhythmic therapy ( Group 3 [ control group ] , n = 114 ) . During the 1 year follow-up period , 10 patients in Group 1 died , as did 5 in Group 2 and 15 in Group 3 . On the basis of an intention to treat analysis , the probability of survival of patients given amiodarone was significantly greater than that of control patients ( p less than 0.05 ) . In addition , arrhythmic events were significantly reduced by amiodarone ( p less than 0.01 ) . These effects were less marked and not significant for individually treated patients ( Group 1 ) . These findings suggest that low dose amiodarone decreases mortality in the 1st year after myocardial infa rct ion in patients at high risk of sudden death The effects of amiodarone in a low dosage ( 200 mg every 8 h for 2 weeks , then 200 mg/day ) was assessed in a double-blind placebo-controlled trial in 34 patients with a history of severe congestive heart failure but no sustained ventricular arrhythmia . Left ventricular ejection fraction , treadmill exercise tolerance and 48 h electrocardiographic monitoring were assessed before and repeatedly after beginning amiodarone or placebo therapy over 6 months , and side effects were monitored . In patients receiving amiodarone , the ejection fraction increased significantly from 19 + /- 7 to 29 + /- 15 % at 6 months ( p less than 0.01 from baseline ) , but not significantly in 14 placebo-treated patients ( 18 + /- 5 to 22 + /- 9 % ) . Exercise tolerance increased significantly in amiodarone-treated patients ( median 433 s to 907 s , p less than 0.05 ) , but not significantly in placebo-treated patients ( 757 to 918 s ) . Nonsustained ventricular tachycardia was present in 88 % of amiodarone-treated patients before , but in only 21 % of patients after 6 months of treatment ( p = 0.06 ) ; it was seen in 43 % of placebo-treated patients at baseline and in 50 % after 6 months . Fifty percent of amiodarone-treated patients had side effects ( principally nausea ) and the drug was withdrawn in 28 % of cases ; no life-threatening effects were seen . Low dose amiodarone appears to have a multifaceted potential to produce benefits in arrhythmia control , exercise tolerance and ventricular function in patients with a history of severe congestive heart failure , but better control of side effects ( principally nausea ) appears essential . Effects on mortality could not be determined from this study ; such assessment requires a larger cohort of patients Cardiovascular disease , and the incidence of sudden cardiac death ( SCD ) , will increase significantly in low- and middle-income countries ( LMIC ) . Thus , SCD threatens to become a global public health problem . We present a summary of the current research that has investigated the epidemiology of SCD in LMIC . Few studies of SCD in LMIC exist , and they are of variable method ological quality . Risk factors for SCD are described , taking into account recent global burden of disease and risk factor statistics . We describe 1 proposal for a community-based , prospect i ve , multiple- source methodology for SCD monitoring and surveillance that can be implemented in LMIC . Further research into the epidemiology of SCD in LMIC , using st and ardized methodology , would allow investigators and policy makers to determine the regions , communities , and individuals most at need for SCD prevention . Focusing on SCD and its prevention in LMIC should be a priority for the global health community To determine whether the beneficial effect of low-dose amiodarone on survival in patients with complex ventricular arrhythmias after myocardial infa rct ion was dependent on left ventricular ( LV ) function , results of the Basel Antiarrhythmic Study of Infa rct Survival were analyzed . Two hundred twelve patients after acute myocardial infa rct ion with asymptomatic complex arrhythmias were r and omly assigned to receive amiodarone 200 mg/day or to a control group and followed up for 1 year . Results of mortality and arrhythmic events were related to baseline radionuclide LV ejection fraction . With preserved ( greater than or equal to 40 % ) LV ejection fraction , there was a significantly lower 1-year cardiac mortality in patients treated with amiodarone ( 1 of 68 or 1.5 % ) versus control subjects ( 5 of 56 or 8.9 % ; p less than 0.03 ) . This was not the case for patients with LV ejection fraction less than 40 % . Similarly , arrhythmic events were significantly reduced only in patients with preserved LV function . These results suggest an interaction between the effects of amiodarone on survival and LV dysfunction in patients after acute myocardial infa rct ion . Because of 2 other small studies with similar results , this finding may be of clinical relevance and should be addressed in ongoing and future research with this drug BACKGROUND Although trials of amiodarone therapy in patients with congestive heart failure have produced discordant results with regard to effects on survival , most studies have reported a significant rise in left ventricular ejection fraction during long-term therapy . In the present study , we determined whether this increase in ejection fraction is associated with an improvement in the symptoms and /or physical findings of heart failure or a reduction in the number of hospitalizations for heart failure . METHODS AND RESULTS In the Department of Veterans Affairs cooperative study of amiodarone in congestive heart failure , 674 patients with New York Heart Association class II through IV symptoms and ejection fractions of < or = 40 % were treated with amiodarone or placebo for a median of 45 months in a r and omized , double-blind , placebo-controlled protocol . Clinical assessment s and radionuclide ejection fraction were performed at baseline and after 6 , 12 , and 24 months . Compared with the placebo group , ejection fraction increased more in the amiodarone group at each time point ( 8.1 + /- 10.2 % [ mean + /- SD ] versus 2.6 + /- 7.9 % at 6 months , 8.0 + /- 10.9 % versus 2.7 + /- 8.0 % at 12 months , and 8.8 + /- 10.1 % versus 1.9 + /- 9.4 % after 24 months , all P < .001 ) . However , this difference was not associated with greater clinical improvement , lesser diuretic requirements , or fewer hospitalizations for heart failure ( 11.1 % for amiodarone and 13.6 % for placebo group ; overall relative risk in the amiodarone group , 0.81 [ 95 % CI , 0.56 to 1.10 ] , P = .18 ) . Of note is the trend toward a reduction in the combined end point of hospitalizations and cardiac deaths ( relative risk , 0.82 [ CI , 0.65 to 1.03 ] , P = .08 ) , which was significant in patients with nonischemic etiology ( relative risk , 0.56 [ CI , 0.36 to 0.87 ] , P = .01 ) and absent in the ischemic group ( relative risk , 0.95 ) . CONCLUSIONS Although amiodarone therapy result ed in a substantial increase in left ventricular ejection fraction in patients with congestive heart failure , this was not associated with clinical benefit in the population as a whole . The substantial reduction in the combined end point of cardiac death plus hospitalizations for heart failure in the nonischemic group suggests possible benefit in these patients Background The purpose of this study was to eluci date whether the reduction of mortality with amiodarone after myocardial infa rct ion depended on ejection fraction . Methods The data from the Polish Amiodarone Trial were analysed retrospectively . Patients with acute myocardial infa rct ion and contraindications to betablockers| were r and omized on days 5–7 after admission to receive amiodarone ( n = 305 ) or placebo ( n = 308 ) . Short and long-term ( 46 months ) mortality were analysed companng the groups with impaired ( ejection fraction < 40 % ) and preserved ( ejection fraction ≥40 % ) left ventncular function . A subset of patients ( n = 523 ) with available echocardiograms were subjected to this analysis . Results Long-term and sudden cardiac mortality were significantly reduced with amiodarone in the group of patients with ejection fraction ≥40 % ( amiodarone versus placebo , respectively : 9.1 versus 16.5 % , P<0.05 ; 3.4 versus 8.2 , P<0.05 ) . No beneficial effect of amiodarone was observed in the group with low ejection fraction ( cardiac and sudden cardiac mortality : amiodarone versus placebo , 20.8 versus 19.3 % and 7.8 versus 5.7 % respectively ) . One-year mortality also revealed a favourable trend only in amiodarone-allocated patients with ejection fraction ≥40 % . Conclusion Amiodarone decreased long-term and sudden cardiac mortality after myocardial infa rct ion only in patients with preserved left ventricular function . No benefit was observed in patients with decreased ejection fraction Background — Celivarone is a new antiarrhythmic agent developed for the treatment of ventricular arrhythmias . This study investigated the efficacy and safety of celivarone in preventing implantable cardioverter-defibrillator ( ICD ) interventions or death . Methods and Results — Celivarone ( 50 , 100 , or 300 mg/d ) was assessed compared with placebo in this r and omized , double-blind , placebo-controlled , parallel-group study . Amiodarone ( 200 mg/d after loading dose of 600 mg/d for 10 days ) was used as a calibrator . A total of 486 patients with a left ventricular ejection fraction ⩽40 % and at least 1 ICD intervention for ventricular tachycardia or ventricular fibrillation in the previous month or ICD implantation in the previous month for documented ventricular tachycardia/ventricular fibrillation were r and omized . Median treatment duration was 9 months . The primary efficacy end point was occurrence of ventricular tachycardia/ventricular fibrillation – triggered ICD interventions ( shocks or antitachycardia pacing ) or sudden death . The proportion of patients experiencing an appropriate ICD intervention or sudden death was 61.5 % in the placebo group ; 67.0 % , 58.8 % , and 54.9 % in the celivarone 50- , 100- , and 300-mg groups , respectively ; and 45.3 % in the amiodarone group . Hazard ratios versus placebo for the primary end point ranged from 0.860 for celivarone 300 mg to 1.199 for celivarone 50 mg . None of the comparisons versus placebo were statistically significant . Celivarone had an acceptable safety profile . Conclusions — Celivarone was not effective for the prevention of ICD interventions or sudden death . Clinical Trial Registration — http://www . clinical trials.gov . Unique identifier : NCT00993382 BACKGROUND Amiodarone 's role as a cause of toxic optic neuropathy is based on case reports . Annual frequency estimates of 0.36 % to 2.0 % , which have been made without reference to the dose or duration of treatment , are 12 to 200 times higher than those for idiopathic nonarteritic anterior ischemic neuropathy . The object of this study was to determine the incidence , dose , and time until onset of bilateral vision loss from amiodarone as a secondary end point in an investigation of amiodarone 's role in preventing sudden death . METHODS R and omized subjects received body weight-determined doses of closed-label amiodarone ( n = 837 ) or placebo ( n = 832 ) in a prospect i ve double-masked manner . Closed-label amiodarone subjects were followed , unless death occurred , for a minimum of 27 months . Median follow-up in survivors was 45.5 months . The end point was removal from the study because of bilateral vision loss . RESULTS No subject was removed from the study because of bilateral vision loss . Subjects receiving continuous amiodarone for 4 to > 60 months at daily doses of > 2.0 mg/kg ( n = 696 ) , > 3.0 mg/kg ( n = 559 ) , or > 4.0 mg/kg ( n = 219 ) had maximum possible ( 95 % confidence ) annual incidences of bilateral toxic vision loss of 0.23 % , 0.29 % , or 0.74 % , respectively . The maximum possible annual incidence rate of bilateral vision loss from amiodarone in all 837 subjects ( median age 60 years ) receiving a mean daily dose of 3.7 mg/kg ( 300 mg ) was 0.13 % . CONCLUSIONS At the doses commonly used clinical ly , bilateral vision loss from amiodarone toxic optic neuropathy occurs infrequently , if at all BACKGROUND Atrial fibrillation occurs frequently in patients with congestive heart failure and commonly results in clinical deterioration and hospitalization . Sinus rhythm may be maintained with antiarrhythmic drugs , but some of these drugs increase the risk of death . METHODS We studied 1518 patients with symptomatic congestive heart failure and severe left ventricular dysfunction at 34 Danish hospitals . We r and omly assigned 762 patients to receive dofetilide , a novel class III antiarrhythmic agent , and 756 to receive placebo in a double-blind study . Treatment was initiated in the hospital and included three days of cardiac monitoring and dose adjustment . The primary end point was death from any cause . RESULTS During a median follow-up of 18 months , 311 patients in the dofetilide group ( 41 percent ) and 317 patients in the placebo group ( 42 percent ) died ( hazard ratio , 0.95 ; 95 percent confidence interval , 0.81 to 1.11 ) . Treatment with dofetilide significantly reduced the risk of hospitalization for worsening congestive heart failure ( risk ratio , 0.75 ; 95 percent confidence interval , 0.63 to 0.89 ) . Dofetilide was effective in converting atrial fibrillation to sinus rhythm . After one month , 22 of 190 patients with atrial fibrillation at base line ( 12 percent ) had sinus rhythm restored with dofetilide , as compared with only 3 of 201 patients ( 1 percent ) given placebo . Once sinus rhythm was restored , dofetilide was significantly more effective than placebo in maintaining sinus rhythm ( hazard ratio for the recurrence of atrial fibrillation , 0.35 ; 95 percent confidence interval , 0.22 to 0.57 ; P<0.001 ) . There were 25 cases of torsade de pointes in the dofetilide group ( 3.3 percent ) as compared with none in the placebo group . CONCLUSIONS In patients with congestive heart failure and reduced left ventricular function , dofetilide was effective in converting atrial fibrillation , preventing its recurrence , and reducing the risk of hospitalization for worsening heart failure . Dofetilide had no effect on mortality BACKGROUND Implantable cardioverter-defibrillator ( ICD ) therapy significantly prolongs life in patients at increased risk for sudden death from depressed left ventricular function . However , whether this increased longevity is accompanied by deterioration in the quality of life is unclear . METHODS In a r and omized trial , we compared ICD therapy or amiodarone with state-of-the-art medical therapy alone in 2521 patients who had stable heart failure with depressed left ventricular function . We prospect ively measured quality of life at baseline and at months 3 , 12 , and 30 ; data collection was 93 to 98 % complete . The Duke Activity Status Index ( which measures cardiac physical functioning ) and the Medical Outcomes Study 36-Item Short-Form Mental Health Inventory 5 ( which measures psychological well-being ) were prespecified primary outcomes . Multiple additional quality -of-life outcomes were also examined . RESULTS Psychological well-being in the ICD group , as compared with medical therapy alone , was significantly improved at 3 months ( P=0.01 ) and at 12 months ( P=0.003 ) but not at 30 months . No clinical ly or statistically significant differences in physical functioning among the study groups were observed . Additional quality -of-life measures were improved in the ICD group at 3 months , 12 months , or both , but there was no significant difference at 30 months . ICD shocks in the month preceding a scheduled assessment were associated with a decreased quality of life in multiple domains . The use of amiodarone had no significant effects on the primary quality -of-life outcomes . CONCLUSIONS In a large primary -prevention population with moderately symptomatic heart failure , single-lead ICD therapy was not associated with any detectable adverse quality -of-life effects during 30 months of follow-up Long-term beta blockade for perhaps a year or so following discharge after an MI is now of proven value , and for many such patients mortality reductions of about 25 % can be achieved . No important differences are clearly apparent among the benefits of different beta blockers , although some are more convenient than others ( or have slightly fewer side effects ) , and it appears that those with appreciable intrinsic sympathomimetic activity may confer less benefit . If monitored , the side effects of long-term therapy are not a major problem , as when they occur they are easily reversible by changing the beta blocker or by discontinuation of treatment . By contrast , although very early IV short-term beta blockade can definitely limit infa rct size , more reliable information about the effects of such treatment on mortality will not be available until a large trial ( ISIS ) reports later this year , with data on some thous and s of patients entered within less than 4 hours of the onset of pain . Our aim has been not only to review the 65-odd r and omized beta blocker trials but also to demonstrate that when many r and omized trials have all applied one general approach to treatment , it is often not appropriate to base inference on individual trial results . Although there will usually be important differences from one trial to another ( in eligibility , treatment , end-point assessment , and so on ) , physicians who wish to decide whether to adopt a particular treatment policy should try to make their decision in the light of an overview of all these related r and omized trials and not just a few particular trial results . Although most trials are too small to be individually reliable , this defect of size may be rectified by an overview of many trials , as long as appropriate statistical methods are used . Fortunately , robust statistical methods exist -- based on direct , unweighted summation of one O-E value from each trial -- that are simple for physicians to use and underst and yet provide full statistical sensitivity . These methods allow combination of information from different trials while avoiding the unjustified direct comparison of patients in one trial with patients in another . ( Moreover , they can be extended of such data that there is no real need for the introduction of any more complex statistical methods that might be more difficult for physicians to trust . ) Their robustness , sensitivity , and avoidance of unnecessary complexity make these particular methods an important tool in trial overviews |
999 | 15,106,233 | In general , the quality of reporting was poor , and many review s did not report adverse effects systematic ally .
The treatment response in the bright light group was better than in the control treatment group , but did not reach statistical significance .
Treatment REVIEW ERS ' CONCLUSIONS For patients suffering from non-seasonal depression , bright light therapy offers modest though promising antidepressive efficacy , especially when administered during the first week of treatment , in the morning , and as an adjunctive treatment to sleep deprivation responders . | BACKGROUND Efficacy of light therapy for non-seasonal depression has been studied without any consensus on its efficacy .
OBJECTIVES To evaluate clinical effects of bright light therapy in comparison to the inactive placebo treatment for non-seasonal depression . | The influence of diurnal variations of mood ( DVM ) and sleep disturbances on treatment response was investigated in 42 patients with major depressive disorder ( not SAD ) under the treatment of either bright white light ( 2,500 lx ) or dim red light ( 50 lx ) . We found only a slight influence in certain subscales of DVM and no influence of sleep disturbances . These results are discussed under a clinical point of view and with respect to phase shift theories of depressive disorders In a group of 17 patients with non-SAD depressive disorders we compared the response of bipolar spectrum versus unipolar patients to treatment with light therapy . The main hypothesis was that bipolar spectrum depressed patients would preferentially respond to bright light therapy as compared to unipolar depressed patients . All patients were treated with either 400 or 2500 lux phototherapy for 2 h on seven consecutive days . All outcome measures , which included the SIGH-SAD , CGI , and the Anxiety and Depressive Factors of the SCL-90 , showed significant improvement in the bipolar vs. the unipolar spectrum patients . Unexpected this occurred regardless of the intensity of the light . These changes were judged to be quite clinical ly significant . All patients showing response were noted to have maintained their response at a 3-month follow-up Patients with recurrent winter depression and its subsyndromal form have been reported to benefit from bright full-spectrum light ( phototherapy ) . In order to determine whether this treatment ( 2 h in the morning ) during winter is effective in a r and om sample of the general population we investigated the responses of 20 subjects with varying degrees of winter difficulties . A control group ( n = 20 ) matched for the degree of seasonality , age , and sex was treated with dim light . Individuals were selected from a larger survey sample of the Montgomery County population ( MD , U.S.A. ) and were comparable to the latter in their degree of winter difficulties . Enhancement of environmental light does not , on the basis of the present study , appear to be indicated for the public at large , but rather for a subgroup of individuals with histories of winter difficulties Light therapy ( LT ) is regarded as the treatment of choice for seasonal affective disorder ( SAD ) . In nonseasonal depression the results of light therapy are nonconclusive . Sleep deprivation ( SD ) , however , is effective in 50 - 60 % of the patients with major depression . The predictive value of Total Sleep Deprivation ( TSD ) for the treatment outcome of antidepressiva has been already examined . Purpose of the present study was to test whether light therapy is more beneficial in TSD responders than in TSD nonresponders . 40 in patients with major depressive disorder completed one night of TSD . Twenty TSD responders and 20 TSD nonresponders were r and omly assigned to 14 days of bright light therapy ( 2500 lux , 7 - 9 a.m. ) or 14 days of dim light therapy ( red light 50 lux , 7 - 9 a.m. ) . Manova with repeated measurements revealed a significant difference in the course of depression over the time between TSD responders and nonresponders , but no significant difference between bright and dim light . Questions of placebo effect , of SAD and of personality variables as predictors of response to SD and LT are being discussed Phototherapy is regularly used in the treatment of seasonal affective disorder . There is evidence that it is also useful in the treatment of non‐seasonal depression , but relevant controlled experiments are difficult to design . In this study we r and omly assigned depressed in‐ patients to high and low levels of artificial light , the high levels exceeding those most commonly used in earlier reported trials . Both unipolar and bipolar depressions responded when phototherapy was used as an adjunct to pharmacotherapy , and mood improvement was related to the intensity of illumination , that is , patients treated with high levels of illumination improved significantly more than those who received low levels ( P < 0.02 ) . Our findings suggest that light therapy is generally applicable to depressive illnesses , and that the light intensities commonly used are suboptimal The data of the Berlin light therapy study were systematic ally reinvestigated for side-effects of light therapy as described in the literature . Forty-two patients with major depressive disorder ( RDC ) , who also met the criteria of ICD-9 ( 296.1 and 296.3 ) , were included . Patients were either given bright white-light treatment ( 2,500 lux ) or dim red-light treatment ( 50 lux ) from 7.20 a.m. to 9.20 a.m. every morning for a period of seven days . The study did not reveal any differences in side-effects between the two treatments . The results are discussed in relation to the two different treatment conditions The effects of two non-drug treatments ( physical exercise and bright light ) on mood , body weight and oxygen consumption were compared in age-matched groups of female subjects with winter depression , non-seasonal depression or without depression . It was found that oxygen consumption in the pre-treatment condition was similar in non-depressed subjects ( n=18 ) and depressed non-seasonals ( n=18 ) , while comparatively lower values were obtained in winter depression ( n=27 ) . Neither mood nor metabolic parameters changed significantly in the group of nine untreated winter depressives . One week of physical exercise ( 1-h pedaling on a bicycle ergometer between 13.00 and 14.00 h ) increased oxygen consumption in the group of nine winter depressives and lowered oxygen consumption in nine-subject groups of depressed and non-depressed non-seasonals . One week of bright light treatment ( 2-h exposure to 2500 lux between 14.00 and 16.00 h ) increased oxygen consumption in nine winter depressives and nine non-depressed subjects , while no significant change in oxygen consumption was found in nine subjects with non-seasonal depression . Weight loss was observed in the groups treated with physical exercise and in the group of light-treated winter depressives . Winter depression responded equally well to exercising and light , while a significant therapeutic difference in favor of exercising was found in non-seasonal depression . Overall , the results of the study suggest that energy-regulating systems are implicated in the antidepressant action of the non-drug treatments The clinical usefulness of total sleep deprivation ( TSD ) in the treatment of bipolar depression is hampered by a high-rate short-term relapse . Previous literature has suggested that both long-term lithium treatment and light therapy could successfully prevent relapse . We r and omized 115 bipolar depressed in patients to receive three cycles of TSD , alone or in combination with morning light exposure , given at an intensity of 150 or 2500 lux . Forty-nine patients were undergoing long-term treatment with lithium salts ( at least 6 months ) , while 66 patients were taking no psychotropic medication . Mood was self-rated by the Visual Analogue Scale three times a day during treatment . The results showed that both light therapy and ongoing lithium treatment significantly enhanced the effects of TSD on the perceived mood , with no additional benefit when the two treatments were combined . Subjective sleepiness during TSD , as rated by the self-administered Stanford Sleepiness Scale , was significantly reduced by light exposure , and was correlated with the outcome . This study confirms the possibility of obtaining a sustained antidepressant response to TSD in bipolar patients In previous research , the therapeutic effect of bright white light for so so-called seasonal affective disorder was clearly confirmed . The aim of the present study was to evaluate possible beneficial effects of bright white light in non-seasonal depression . 30 patients fulfilling RDC- criteria for major depressive disorder were r and omly assigned to a 7 day exposure from 7.20 to 9.20 a.m. The degree of illness was ascertained both objective ly with observer rating scales ( Hamilton Depression Scale , AMDP-system ) and through self-rating scales ( Complaint List and Depression Scale by von Zerssen ) . No difference was noted between bright light and dim light though a significant reduction of depressive symptomatology was observed for all patients during the treatment . These results were consistent for both observer rating and self-rating . In conclusion , bright white light has no superior effect as compared to dim light exposure in non-seasonal depression INTRODUCTION The aim of a double-blind study was to assess the efficacy of bright light therapy and /or imipramine in the treatment of in patients suffering with recurrent non-seasonal major depressive disorder . METHOD 34 in- patients with DSM-III-R diagnosis of major depressive disorder , recurrent type , were r and omly allocated into 3 treatment groups . After 4-day washout period with baseline assessment they underwent 3 weeks of different types of treatment : a ) Group A : bright light therapy ( 5000 lux from 6 - 8 a.m. ) and imipramine 150 mg/day . b ) Group B : bright light therapy ( 5000 lux from 6 - 8 a.m. ) and imipramine-like placebo . c ) Group C : dim red light ( 500 lux from 6 - 8 a.m. ) and imipramine 150 mg/day . Outcome measures included weekly Hamilton Psychiatric Rating Scale for Depression , Clinical Global Impression Scale , Montgomery and Asberg Psychiatric Rating Scale for Depression and Beck Depression Inventory . RESULTS Patients of all three groups improved significantly . The improvement of the patients of group B treated with bright light therapy plus placebo was superior to the other two groups , but not significantly . CONCLUSION Bright light therapy can be effective in the treatment of non-seasonal major depressive disorder Light therapy ( bright or dim light ) was given at different times ( morning or evening ) to 27 unmedicated patients with nonseasonal depression ( according to DSM-III-R criteria ) and 16 normal volunteers . Circadian rhythms in body temperature were measured before and after light therapy . Bright light significantly improved clinical symptoms of depression , as measured by the Hamilton Rating Scale for Depression ( HRSD ) , independent of the time of phototherapy . Dim light therapy had no effect on HRSD scores . Circadian rhythms of body temperatures in patients with affective disorder were more sensitive to the entraining effects of bright light than those of normal subjects , but these effects were not related to clinical improvement . Bright light exposure has an antidepressant effect on patients with nonseasonal depression , but the effect is unlikely to be mediated via the same circadian system that regulates body temperature OBJECTIVE About 5 % of pregnant women meet criteria for major depression . No pharmacotherapy is specifically approved for antepartum depression ; novel treatment approaches may be welcome . The authors explored the use of morning bright light therapy for antepartum depression . METHOD An open trial of bright light therapy in an A-B-A design was conducted for 3 - 5 weeks in 16 pregnant patients with major depression . The Hamilton Depression Rating Scale , Seasonal Affective Disorders Version , was administered to assess changes in mood . A follow-up question naire was used to assess outcome after delivery . RESULTS After 3 weeks of treatment , mean depression ratings improved by 49 % . Benefits were seen through 5 weeks of treatment . There was no evidence of adverse effects of light therapy on pregnancy . CONCLUSIONS These data provide evidence that morning light therapy has an antidepressant effect during pregnancy . A r and omized controlled trial is warranted to test this alternative to medication Inpatient studies have suggested that bright light therapy can be used to sustain the antidepressant effects of wake therapy ( sleep deprivation ) . In an outpatient trial , a half night of home wake treatment was followed by 1 week of light treatment . All subjects had Major Depressive Disorders according to DSM-IV criteria and were receiving concomitant antidepressant medication . Subjects were r and omly assigned to receive either 10,000 lux bright white light for 30 min between 6 and 9 AM or dim red ( placebo ) light at a comparable time . Seven subjects completed treatment with bright white light and six completed treatment with placebo . On the Hamilton Depression Rating Scale ( HDRS17 , SIGH-SAD-SR version ) , the group receiving bright light improved 27 % in 1 week ( P=0.002 ) . The group receiving placebo did not improve , except for one outlier . The benefit of bright light was significant compared to placebo with removal of the outlier ( P<0.025 ) Antidepressant and energizing effects of bright light exposure ( phototherapy ) have been widely reported to occur in patients with seasonal affective disorder . We have attempted to evaluate whether other segments of the population might benefit from phototherapy , most notably individuals with subsyndromal seasonal affective disorder , as well as healthy individuals with no winter difficulties ( controls ) . We have studied 20 subjects in each of these two categories and have found that bright artificial light did not alter mood and behavior in controls . In contrast , individuals with subsyndromal seasonal affective disorder responded favorably to treatment with bright environmental light . A dose of 5 hours of bright light exposure , divided between morning and evening , was more effective than 2 hours of exposure . This finding may have practical implication s for establishing optimal environmental lighting conditions for those individuals whose winter difficulties do not meet criteria for seasonal affective disorder BACKGROUND Using bright light for treating major depressive disorders which are not seasonal needs re assessment . METHODS Clinical trials of light treatment for nonseasonal major depressive disorders were compared with selected trials of light treatment of winter depression and with antidepressant clinical drug trials . RESULTS Light treatment of nonseasonal depression produces net benefits in the range of 12 - 35 % , often within 1 week . CONCLUSIONS Light 's value for nonseasonal and seasonal depression are comparable . Light appears to produce faster antidepressant benefits than psychopharmacologic treatment . LIMITATIONS Direct r and omizing comparisons between light and medications for nonseasonal depression are not available . CLINICAL RELEVANCE Bright light can be combined with st and ard therapies for treating nonseasonal depressions and appears synergistic Serum concentrations of thyroxine ( T4 ) , triiodothyronine ( T3 ) , and thyrotropine were measured in 34 patients with nonseasonal affective disorders before and after 1 week of light treatment . Nineteen of these patients received bright white light ( 2500 lx ) and 15 dim red light ( 50 lx ) for 2 hours daily in the mornings over a 1-week period . Slight but significant reductions in the rating scores for the depressive symptomatology were found for both the bright- and dim-light groups , but there were no significant differences between the two groups . The improvement is thus most likely a placebo effect . Surprisingly , the small changes in the severity of the depressive symptoms in the group as a whole were significantly correlated to the changes in the serum levels of T4 during the weeks of bright- and dim-light treatment , respectively . The more a patient improved , the further his or her T4 level fell and vice versa . The fluctuations in the concentrations of T4 during light treatment were significantly greater in the depressed patients than in a group of 12 healthy controls who also received bright or dim light , whereas the changes in T3 were significantly smaller than those of the healthy controls . The pronounced fluctuations in T4 levels were probably not secondary to changes in mood . Rather , they are likely to reflect changes in tissue ( intracellular ) metabolism of T4 , which may be involved in the mechanisms underlying the fluctuations in mood in these patients The present study was design ed to investigate the clinical efficacy of trimipramine with adjunct sleep deprivation ( SD ) or bright light ( BL ) and to evaluate psychometric and neurobiological variables that might be of predictive value for treatment response . We used ( 1 ) the combined dexamethasone-corticotropin releasing hormone test ( DEX-CRH test ) to characterize alterations of the hypothalamic-pituitary-adrenal ( HPA ) system ; ( 2 ) polysomnography to evaluate sleep disturbances ; and ( 3 ) a st and ardized test battery to assess cognitive psychomotor functions after study initiation and after 5 weeks of treatment . The overall response rate ( > or = 50 % decrease in score on Hamilton Rating Scale for Depression [ HRS ] ) was 55 % ( N = 42 ) . The response rate in the group with trimipramine monotherapy ( N = 14 ) was 79 % , whereas in the groups with adjunct SD ( N = 14 ) and BL ( N = 14 ) , respectively , it was only 43 % . All three groups showed significant improvement at the end of the third week of treatment . Neither of the adjunct treatments hastened the onset of antidepressant action as measured by HRS . A significantly higher proportion of nonresponders than responders ( p < .05 ) had HPA dysregulation , disturbed rapid eye movement ( REM ) sleep ( REM latency , REM% first third of night ) and decreased non-REM sleep ( % stage 2 ) . The non-responders showed significantly more corticotropin ( ACTH ) secretion after CRH stimulation in the DEX-CRH test than the responders and a less rapid normalization of the neuroendocrine dysregulation ( cortisol secretion ) ( p < .01 ) . In addition , REM latency was significantly shorter in the BL group than in the monotherapy group and estimated duration of illness significantly longer in the SD group than in the monotherapy group . REM latency , percentage of REM sleep during the first third of the total sleep period , percentage of non-REM sleep stage 2 and ACTH release after a DEX-CRH challenge predicted response across all three treatment groups . The neurobiological symptoms were unevenly distributed , among the three groups , thus creating heterogeneity in these measures . This heterogeneity may have contributed to the different treatment response rates as defined by psychopathology ( HRS ) . In contrast , the neuropsychological tests and some of the sleep-EEG investigations revealed different response patterns for different groups : The onset of improvement in simple cognitive functions and in sleep continuity was earlier in the adjunct treatment groups . This study underlines the need for a multidimensional approach including use of neurobiological and neuropsychological measures to identify the therapeutic profiles of different treatment strategies and predictors of outcome ABSTRACT The purpose of this study was to test the efficacy of a tri-modal intervention ( LEVITY ) to improve women 's mood . This eight-week r and omized experiment with a placebo-control group targeted women with symptoms of mild to moderate depression . Women in the intervention group were instructed to take a brisk 20-minute outdoor walk at target heart rate of 60 % of maximum heart rate , to increase light exposure throughout the day and to take a specific vitamin regimen . Women in the control group took a daily placebo vitamin . The sample consisted of 112 women ages 19–78 who reported mild to moderate depressive symptoms . They were in otherwise good health and were not currently taking any mood-altering medication . Pre- and post-intervention assessment utilized five measures of mood : Center for Epidemiology Studies Depression Scale , Profile of Mood States , Depression-Happiness Scale , Rosenberg Self-Esteem Scale , and the General Well-Being Schedule . Analysis of covariance indicated that the intervention was effective in improving women 's overall mood , self-esteem , and general sense of well-being and in decreasing symptoms on two measures of depression . Of particular note , the data from all five outcome measures supported the efficacy of the intervention . In addition , a high level of adherence to the intervention protocol was observed with two-thirds of the women reporting 100 % adherence . Study implication s suggest that this type of intervention may provide an effective , clinical ly manageable therapy for mild-to-moderately depressed women who prefer a self-directed approach or who have difficulties with the cost or side-effects of medication or psychotherapy We investigated the effectiveness of two brief psychotherapies , interpersonal psychotherapy and cognitive behavior therapy , for the treatment of out patients with major depression disorder diagnosed by Research Diagnostic Criteria . Two hundred fifty patients were r and omly assigned to one of four 16-week treatment conditions : interpersonal psychotherapy , cognitive behavior therapy , imipramine hydrochloride plus clinical management ( as a st and ard reference treatment ) , and placebo plus clinical management . Patients in all treatments showed significant reduction in depressive symptoms and improvement in functioning over the course of treatment . There was a consistent ordering of treatments at termination , with imipramine plus clinical management generally doing best , placebo plus clinical management worst , and the two psychotherapies in between but generally closer to imipramine plus clinical management . In analyses carried out on the total sample s without regard to initial severity of illness ( the primary analyses ) , there was no evidence of greater effectiveness of one of the psychotherapies as compared with the other and no evidence that either of the psychotherapies was significantly less effective than the st and ard reference treatment , imipramine plus clinical management . Comparing each of the psychotherapies with the placebo plus clinical management condition , there was limited evidence of the specific effectiveness of interpersonal psychotherapy and none for cognitive behavior therapy . Superior recovery rates were found for both interpersonal psychotherapy and imipramine plus clinical management , as compared with placebo plus clinical management . On mean scores , however , there were few significant differences in effectiveness among the four treatments in the primary analyses . Secondary analyses , in which patients were dichotomized on initial level of severity of depressive symptoms and impairment of functioning , helped to explain the relative lack of significant findings in the primary analyses . Significant differences among treatments were present only for the subgroup of patients who were more severely depressed and functionally impaired ; here , there was some evidence of the effectiveness of interpersonal psychotherapy with these patients and strong evidence of the effectiveness of imipramine plus clinical management . In contrast , there were no significant differences among treatments , including placebo plus clinical management , for the less severely depressed and functionally impaired patients Circadian profiles of melatonin in serum and serotonin in blood were assessed before and after 7 days of artificial light treatment in 30 patients with non-seasonal depression and 12 healthy subjects . Patients and volunteers were allocated at r and om to either dim ( 50 lux ) or bright light ( 2,500 lux ) for 2 hours daily . The study has not been completed yet . Preliminary findings are presented here . Light treatment modifies marginally the circadian melatonin profiles of depressed patients and healthy subjects ; however , it augments blood serotonin throughout the day . This increase is seen in all patients and healthy subjects after bright as well as dim light . These results suggest that the influence of light is more pronounced on serotonin than melatonin metabolism BACKGROUND An important parallel exists between patients with seasonal affective disorder and institutionalized older adults . Many older patients , as a result of global physical decline and immobility , are confined to their rooms , experiencing little natural sunlight . Thus , institutionalized older adults are at risk for chronic light deprivation . Testing the hypothesis that chronic light deprivation might be responsible , at least in part , for some depression among institutionalized older adults , the aim of this study was to investigate the efficacy of morning bright light treatment on depression among older adults residing in a long-term care facility . METHODS In a placebo controlled , crossover design , participants ( N = 10 , six women and four men ; M age = 83.8 ) received each of the following : ( i ) 1 week ( 5 days ) of 10,000 lux ( therapeutic dose ) ; ( ii ) 1 week ( 5 days ) of 300 lux ( placebo ) ; or 1 week of no treatment ( control ) . Each week of light treatment was 5 consecutive days , 30 minutes daily , with a wash-out period consisting of 1 week between conditions . RESULTS Geriatric Depression Scale ( GDS ) scores at baseline during all treatment conditions were positively correlated ( r = .81 , p < .01 ) with months of institutionalization , where participants with higher GDS scores experienced more time institutionalized . Scores on the GDS remained unchanged during the placebo and control conditions , but depression scores decreased significantly during the 10,000 lux treatment ( pretest GDS M = 15 vs posttest GDS M = 11 , p < .01 ) . After the 10,000 lux treatment , 50 % of the participants no longer scored in the depressed range . Improvement during the 10,000 lux condition was positively correlated ( r = .62 , p < .05 ) to baseline GDS scores , where participants with higher GDS scores experienced greater improvement following the 10,000 lux treatment . CONCLUSIONS The results of the present study suggest that bright light treatment may be effective among institutionalized older adults , providing nonpharmacological intervention in the treatment of depression . Furthermore , the length of institutionalization may play an important role in determining the efficacy of bright light treatment for older adults in the nursing-home setting BACKGROUND Bright artificial light improves non-seasonal depression . Preliminary observations suggest that sunlight could share this effect . METHODS Length of hospitalization was recorded for a sample of 415 unipolar and 187 bipolar depressed in patients , assigned to rooms with eastern ( E ) or western ( W ) windows . RESULTS Bipolar in patients in E rooms ( exposed to direct sunlight in the morning ) had a mean 3.67-day shorter hospital stay than patients in W rooms . No effect was found in unipolar in patients . CONCLUSIONS Natural sunlight can be an underestimated and uncontrolled light therapy for bipolar depression . LIMITATIONS This is a naturalistic retrospective observation , which needs to be confirmed by prospect i ve studies Nine patients with rapid cycling bipolar disorder were treated with a total of 13 trials of bright light therapy in the morning ( n = 5 ) , evening ( n = 3 ) , or midday ( n = 5 ) . In each instance , the patient 's mood ratings during 3 months of light therapy ( added to a stable medication regimen ) were compared to his or her mood ratings during 3 months on the same medication but without light treatment . Of the 3 light therapy schedules , only midday lights appeared to have beneficial clinical effects , improving mood ratings in 3 patients . In contrast , the morning light therapy trial was terminated prematurely in 3 patients because of clinical instability . Light treatment was better tolerated if patients discontinued it on days when they were hypomanic . The clinical and theoretical implication s of these preliminary findings are discussed Partial sleep deprivation ( PSD ) results in a pronounced decrease of depressive symptoms in the majority of patients with major depressive disorder . Generally this acute antidepressant effect is not stable , relapse usually occurs after one night of recovery sleep . We therefore studied whether light therapy , beginning in the morning after PSD , is able to prevent the relapse after sleep deprivation , using a controlled , balanced , parallel design . All patients received an antidepressant medication , which was kept constant before and during the study period . Fourteen of 20 patients ( 70 % ) showed a reduction of at least 40 % in the Hamilton Depression Rating Scale ( HDRS ) in the morning after PSD and were classified as PSD responders . Responders as well as nonresponders were r and omly assigned to receive either bright light ( BL/3000 lux ) or dim light ( DL/100 lux ) therapy during the following 6 days after PSD . In the responder group BL therapy prevented significantly ( p = 0.005 ) the relapse after the next night of sleep and prolonged significantly ( p = 0.011 ) the antidepressant effects of PSD up to 7 days . In contrast , patients in the DL condition relapsed after the recovery night and showed no further improvement of the depressive syndrome after 1 week of DL therapy . PSD nonresponders did not benefit from light treatment . These findings indicate that BL therapy might be efficacious to prevent relapse after PSD BACKGROUND Selective serotonin reuptake inhibitors are effective in approximately 70 % of patients with a major depressive episode , but therapeutic changes usually require 2 weeks of administration to become clinical ly relevant . Adjunct light therapy has been proposed to hasten the effects of drug treatment . The purpose of the present study was to evaluate the effect of morning light therapy or placebo combined with citalopram in the treatment of patients affected by a major depressive episode without psychotic features . METHOD Thirty in patients ( DSM-IV major depressive disorder [ N = 21 ] and bipolar disorder [ N = 9 ] ) were treated with citalopram , 40 mg , and r and omized in a 3:2 manner to receive 30 minutes of 400 lux green light treatment in the morning or placebo ( exposure to a deactivated negative ion generator ) during the first 2 weeks of drug treatment . Timing of light therapy was individually defined to obtain a 2-hour phase advance to morning light . Outcome was measured with the Hamilton Rating Scale for Depression and the Zung Self-Rating Depression Scale every week , and with a Visual Analogue Scale 3 times a day during the first week . RESULTS All outcome measures showed significantly ( p < .05 ) better mood improvement in light-treated patients , result ing in faster responses to antidepressant treatment . CONCLUSION The combination of citalopram and light treatment was more effective than citalopram and placebo in the treatment of major depression . With an optimized timing of administration , low-intensity light treatment significantly hastened and potentiated the effect of citalopram , thus providing the clinical psychiatrists with an augmenting strategy that was found effective and devoid of side effects Psychotropic drug-free hospitalized veterans with nonseasonal major depressive disorders or depressed forms of bipolar disorder were treated with light for 1 week . Twenty-five patients were r and omly assigned to bright white light treatment ( 2000 - 3000 lux ) , and 26 patients were r and omized to dim red light placebo control treatment . Unlike those treated with dim red light , those treated with bright white light showed declines in three measures of depression during treatment . Partial relapse appeared within 2 days . A global depression score showed a statistically significant ( p = 0.02 ) difference favoring bright white light treatment . Two bright-light-treated patients became mildly hypomanic , but side effects were mild . Improvement was not correlated with patient expectations ; indeed , patients expected somewhat greater benefit from the placebo . Patients treated in summer responded as well as those treated in winter . Baseline electroencephalogram ( EEG ) sleep stage data ( e.g. , rapid eye movement ; REM latency ) did not predict treatment responses . These 1-week treatment results suggest that bright light might produce benefits for patients with nonseasonal depression . Bright light should not be recommended for routine clinical application before additional assessment s with longer treatment duration s are done In this study , the effect of bright white light ( 2500 lux ) and dim light ( 50 lux ) were assessed in 30 patients with non-seasonal major depressive disorder r and omly assigned to either procedure . Patients met RDC for major depressive disorder and ICD-9 criteria ( 296.1 and 296.3 ) . During a 7-day period , the patients were exposed to bright white light ( 2500 lux ) or dim light ( 50 lux ) from 7.00 to 9.00 h daily . The severity of depression was assessed with observer scales ( AMDP system , Hamilton depression scale , CGI ) and through self-evaluation by self-rating scales ( depression scale and list of complaints by von Zerssen ) . No difference was noted between bright light therapy and dim light , though a significant reduction of depressive symptomatology was observed for all patients during the study . These findings are discussed from a clinical point of view The assumption that depressed patients who are assigned to placebo in antidepressant clinical trials are exposed to substantial morbidity and mortality has not been based on research data . Because of worldwide concern about placebo use and the implication s of our earlier findings of no increased suicide risk in placebo-treated patients , we conducted a replication study in a new patient sample . We assessed suicide risk and symptom reduction among placebo-treated patients participating in antidepressant clinical trials for two recently approved antidepressants , venlafaxine ER and citalopram , which were unavailable during our previous study . Among 23,201 participant patients , 32 committed suicide and 172 attempted suicide . Rates of suicide and attempted suicide did not differ significantly among the placebo- and drug-treated groups . Based on patient exposure years , annual rates of suicide and attempted suicide were 0.5 and 6.7 % with placebo , 0.9 % with active comparator ( rates for attempted suicide are unavailable ) , and 0.6 and 6.3 % with investigational antidepressants . Symptom reduction was 47.9 % with investigational drugs ( n = 1172 ) , 47.5 % with active comparators ( n = 161 ) , and 35.5 % with placebo ( n = 606 ) . These data may inform discussion s about the use of placebo in antidepressant clinical trials Prior analyses from the National Institute of Mental Health Treatment of Depression Collaborative Research Program indicated that patients ' expectancies of treatment effectiveness ( S. M. Sotsky et al. , 1991 ) and the quality of the therapeutic alliance ( J. L. Krupnick et al. , 1996 ) predicted clinical improvement . These data were reanalyzed to examine the hypothesis that the link between treatment expectancies and outcome would be mediated by patients ' contribution to the alliance . Among 151 patients who completed treatment , this hypothesis was supported , suggesting that patients who expect treatment to be effective tend to engage more constructively in session , which helps bring about symptom reduction . Therapists ' expectancies for patient improvement also predicted outcome , although this association was not mediated by the alliance . None of the expectancy scales interacted with alliance ratings in the prediction of clinical improvement |
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